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Hydrogel coils improve outcomes in medium-sized intracranial aneurysms
HOUSTON – Hydrogel coils significantly outperformed bare platinum coils in treating patients with medium-sized intracranial aneurysms, reducing the incidence of adverse outcomes by about 9% in an open-label, randomized trial.
Compared against the platinum coils, the self-expandable, hydrophilic coils scored significantly better on a composite endpoint of aneurysm recurrence at 18 months, re-treatment by 18 months, serious morbidity that prevented angiographic follow-up, and death, Christian Taschner, MD, said at the International Stroke Conference sponsored by the America Heart Association.
These are the company’s second-generation products, said Dr. Taschner, a neuroradiologist at University Hospital Freiburg (Germany). The initial hydrogel-coated coils were not well received because they were too stiff, he said in an interview.
The 18-month study comprised 513 patients and was conducted in 15 centers in France and 7 in Germany. Patients with medium-sized aneurysms (4-12 mm) were randomized to coiling with either the hydrogel coils or bare platinum coils and followed for 18 months. The cohort was stratified by rupture status in the analysis.
Angiographic images of the aneurysm were obtained before treatment, immediately after treatment, at 6 months, and at 18 months. All images were reviewed by an independent laboratory that was blinded to the treatment.
In addition to the primary composite outcome, the study assessed secondary endpoints of modified Rankin Scale (mRS) score at 18 months and coil packing density.
The final analysis included 484 patients. They were a mean of 52 years old, and about 70% were women. The aneurysms were ruptured at baseline in about 43% of cases. The mean aneurysm size was 7 mm, and the mean neck size, 3.5 mm. The dome-to-neck ratio was less than 1.5 in about a third of the group. Most lesions (89%) had anterior circulation.
Most patients needed some kind of adjunctive endovascular-assisting device during the procedure. These included balloon remodeling, which was necessary in about 50% of cases to help keep the coils from extruding into the parent vessel, and stents in 22%.
Intraoperative adverse events were uncommon in both groups. They were numerically, but not significantly, less common in the hydrogel group. These included thromboembolism (8 vs. 12), intraoperative rupture (3 vs. 7), parent vessel occlusion (1 vs. 3), and vessel perforation (one in each group). There were no vessel dissections.
By 18 months, 20% of the hydrogel group and 29% of the platinum coil group had experienced the composite primary endpoint. The 9% absolute difference was statistically significant. It was largely driven by the subcomponents of major recurrence (12% vs. 18%) and re-treatment (3% vs. 6%).
An mRS of 3-5 was used as the proxy for patients whose clinical status prevented them from having angiographic follow-up. That endpoint occurred in three patients in the hydrogel group but in none of the platinum coil group. Dr. Taschner said that difference was not statistically significant.
In an analysis that stratified by baseline rupture status and by aneurysm size, the hydrogel coils were largely superior to bare platinum. However, the hydrogel coils were not significantly more effective than the platinum coils for aneurysms 10 mm or larger, Dr. Taschner noted.
There was no significant difference in the secondary endpoint of mRS at 18 months. Most patients (85% vs. 86%) did well, with an mRS of 0. Scores of 1-2 were seen in 9% of each group. An mRS of 3-5 occurred in 3% of the hydrogel group and 1% of the platinum coil group. There were 17 deaths: 7 in the hydrogel group and 10 in the platinum coil group (3% vs. 4%). This was not a significant difference.
Patients whose aneurysms were unruptured at baseline did significantly better than did those with ruptured lesions, although the mRS scores did not vary significantly between treatment groups. Among those with intact lesions, 90% of the hydrogel and 94% of the platinum coil group achieved an mRS of 0, and 2% of each group died. Among those with ruptured lesions at baseline, 78% of the hydrogel group and 75% of the platinum coil group achieved an mRS of 0. Five patients in the hydrogel group and seven in the platinum coil group died.
On the technical outcome of coil volume, hydrogel did somewhat better (0.041 cm3 vs. 0.038 cm3). The mean packing density was significantly higher (39% vs. 31%).
Dr. Taschner said the study provides good support for using the hydrogel coils in medium-sized aneurysms, and that other recent data reaffirm this.
“A recent trial in Canada and the U.S. looked at hydrogel coils in aneurysms 12 mm or larger, with broad necks, and it failed to show a benefit of the hydrogel coils.”
Additionally, a study published in January found that hydrogel coils were no better than platinum coils in 250 patients with large or recurrent aneurysms (AJNR Am J Neuroradiol. 2017 Jan 12. doi: 10.3174/ajnr.A5101).
“I myself would use them in medium-sized aneurysms with an unfavorable dome-to-neck ratio, and in those that have a broad neck. In those instances, I do think that hydrogel coils have their place. I wouldn’t use them in really large aneurysms. I don’t think they are well suited for that. In those cases, I would probably use platinum coils in combination with a flow diverter. That really provides very stable aneurysm occlusion with acceptable complication rates.”
Dr. Taschner said that he received research support from MicroVention during the study.
[email protected]
On Twitter @alz_gal
HOUSTON – Hydrogel coils significantly outperformed bare platinum coils in treating patients with medium-sized intracranial aneurysms, reducing the incidence of adverse outcomes by about 9% in an open-label, randomized trial.
Compared against the platinum coils, the self-expandable, hydrophilic coils scored significantly better on a composite endpoint of aneurysm recurrence at 18 months, re-treatment by 18 months, serious morbidity that prevented angiographic follow-up, and death, Christian Taschner, MD, said at the International Stroke Conference sponsored by the America Heart Association.
These are the company’s second-generation products, said Dr. Taschner, a neuroradiologist at University Hospital Freiburg (Germany). The initial hydrogel-coated coils were not well received because they were too stiff, he said in an interview.
The 18-month study comprised 513 patients and was conducted in 15 centers in France and 7 in Germany. Patients with medium-sized aneurysms (4-12 mm) were randomized to coiling with either the hydrogel coils or bare platinum coils and followed for 18 months. The cohort was stratified by rupture status in the analysis.
Angiographic images of the aneurysm were obtained before treatment, immediately after treatment, at 6 months, and at 18 months. All images were reviewed by an independent laboratory that was blinded to the treatment.
In addition to the primary composite outcome, the study assessed secondary endpoints of modified Rankin Scale (mRS) score at 18 months and coil packing density.
The final analysis included 484 patients. They were a mean of 52 years old, and about 70% were women. The aneurysms were ruptured at baseline in about 43% of cases. The mean aneurysm size was 7 mm, and the mean neck size, 3.5 mm. The dome-to-neck ratio was less than 1.5 in about a third of the group. Most lesions (89%) had anterior circulation.
Most patients needed some kind of adjunctive endovascular-assisting device during the procedure. These included balloon remodeling, which was necessary in about 50% of cases to help keep the coils from extruding into the parent vessel, and stents in 22%.
Intraoperative adverse events were uncommon in both groups. They were numerically, but not significantly, less common in the hydrogel group. These included thromboembolism (8 vs. 12), intraoperative rupture (3 vs. 7), parent vessel occlusion (1 vs. 3), and vessel perforation (one in each group). There were no vessel dissections.
By 18 months, 20% of the hydrogel group and 29% of the platinum coil group had experienced the composite primary endpoint. The 9% absolute difference was statistically significant. It was largely driven by the subcomponents of major recurrence (12% vs. 18%) and re-treatment (3% vs. 6%).
An mRS of 3-5 was used as the proxy for patients whose clinical status prevented them from having angiographic follow-up. That endpoint occurred in three patients in the hydrogel group but in none of the platinum coil group. Dr. Taschner said that difference was not statistically significant.
In an analysis that stratified by baseline rupture status and by aneurysm size, the hydrogel coils were largely superior to bare platinum. However, the hydrogel coils were not significantly more effective than the platinum coils for aneurysms 10 mm or larger, Dr. Taschner noted.
There was no significant difference in the secondary endpoint of mRS at 18 months. Most patients (85% vs. 86%) did well, with an mRS of 0. Scores of 1-2 were seen in 9% of each group. An mRS of 3-5 occurred in 3% of the hydrogel group and 1% of the platinum coil group. There were 17 deaths: 7 in the hydrogel group and 10 in the platinum coil group (3% vs. 4%). This was not a significant difference.
Patients whose aneurysms were unruptured at baseline did significantly better than did those with ruptured lesions, although the mRS scores did not vary significantly between treatment groups. Among those with intact lesions, 90% of the hydrogel and 94% of the platinum coil group achieved an mRS of 0, and 2% of each group died. Among those with ruptured lesions at baseline, 78% of the hydrogel group and 75% of the platinum coil group achieved an mRS of 0. Five patients in the hydrogel group and seven in the platinum coil group died.
On the technical outcome of coil volume, hydrogel did somewhat better (0.041 cm3 vs. 0.038 cm3). The mean packing density was significantly higher (39% vs. 31%).
Dr. Taschner said the study provides good support for using the hydrogel coils in medium-sized aneurysms, and that other recent data reaffirm this.
“A recent trial in Canada and the U.S. looked at hydrogel coils in aneurysms 12 mm or larger, with broad necks, and it failed to show a benefit of the hydrogel coils.”
Additionally, a study published in January found that hydrogel coils were no better than platinum coils in 250 patients with large or recurrent aneurysms (AJNR Am J Neuroradiol. 2017 Jan 12. doi: 10.3174/ajnr.A5101).
“I myself would use them in medium-sized aneurysms with an unfavorable dome-to-neck ratio, and in those that have a broad neck. In those instances, I do think that hydrogel coils have their place. I wouldn’t use them in really large aneurysms. I don’t think they are well suited for that. In those cases, I would probably use platinum coils in combination with a flow diverter. That really provides very stable aneurysm occlusion with acceptable complication rates.”
Dr. Taschner said that he received research support from MicroVention during the study.
[email protected]
On Twitter @alz_gal
HOUSTON – Hydrogel coils significantly outperformed bare platinum coils in treating patients with medium-sized intracranial aneurysms, reducing the incidence of adverse outcomes by about 9% in an open-label, randomized trial.
Compared against the platinum coils, the self-expandable, hydrophilic coils scored significantly better on a composite endpoint of aneurysm recurrence at 18 months, re-treatment by 18 months, serious morbidity that prevented angiographic follow-up, and death, Christian Taschner, MD, said at the International Stroke Conference sponsored by the America Heart Association.
These are the company’s second-generation products, said Dr. Taschner, a neuroradiologist at University Hospital Freiburg (Germany). The initial hydrogel-coated coils were not well received because they were too stiff, he said in an interview.
The 18-month study comprised 513 patients and was conducted in 15 centers in France and 7 in Germany. Patients with medium-sized aneurysms (4-12 mm) were randomized to coiling with either the hydrogel coils or bare platinum coils and followed for 18 months. The cohort was stratified by rupture status in the analysis.
Angiographic images of the aneurysm were obtained before treatment, immediately after treatment, at 6 months, and at 18 months. All images were reviewed by an independent laboratory that was blinded to the treatment.
In addition to the primary composite outcome, the study assessed secondary endpoints of modified Rankin Scale (mRS) score at 18 months and coil packing density.
The final analysis included 484 patients. They were a mean of 52 years old, and about 70% were women. The aneurysms were ruptured at baseline in about 43% of cases. The mean aneurysm size was 7 mm, and the mean neck size, 3.5 mm. The dome-to-neck ratio was less than 1.5 in about a third of the group. Most lesions (89%) had anterior circulation.
Most patients needed some kind of adjunctive endovascular-assisting device during the procedure. These included balloon remodeling, which was necessary in about 50% of cases to help keep the coils from extruding into the parent vessel, and stents in 22%.
Intraoperative adverse events were uncommon in both groups. They were numerically, but not significantly, less common in the hydrogel group. These included thromboembolism (8 vs. 12), intraoperative rupture (3 vs. 7), parent vessel occlusion (1 vs. 3), and vessel perforation (one in each group). There were no vessel dissections.
By 18 months, 20% of the hydrogel group and 29% of the platinum coil group had experienced the composite primary endpoint. The 9% absolute difference was statistically significant. It was largely driven by the subcomponents of major recurrence (12% vs. 18%) and re-treatment (3% vs. 6%).
An mRS of 3-5 was used as the proxy for patients whose clinical status prevented them from having angiographic follow-up. That endpoint occurred in three patients in the hydrogel group but in none of the platinum coil group. Dr. Taschner said that difference was not statistically significant.
In an analysis that stratified by baseline rupture status and by aneurysm size, the hydrogel coils were largely superior to bare platinum. However, the hydrogel coils were not significantly more effective than the platinum coils for aneurysms 10 mm or larger, Dr. Taschner noted.
There was no significant difference in the secondary endpoint of mRS at 18 months. Most patients (85% vs. 86%) did well, with an mRS of 0. Scores of 1-2 were seen in 9% of each group. An mRS of 3-5 occurred in 3% of the hydrogel group and 1% of the platinum coil group. There were 17 deaths: 7 in the hydrogel group and 10 in the platinum coil group (3% vs. 4%). This was not a significant difference.
Patients whose aneurysms were unruptured at baseline did significantly better than did those with ruptured lesions, although the mRS scores did not vary significantly between treatment groups. Among those with intact lesions, 90% of the hydrogel and 94% of the platinum coil group achieved an mRS of 0, and 2% of each group died. Among those with ruptured lesions at baseline, 78% of the hydrogel group and 75% of the platinum coil group achieved an mRS of 0. Five patients in the hydrogel group and seven in the platinum coil group died.
On the technical outcome of coil volume, hydrogel did somewhat better (0.041 cm3 vs. 0.038 cm3). The mean packing density was significantly higher (39% vs. 31%).
Dr. Taschner said the study provides good support for using the hydrogel coils in medium-sized aneurysms, and that other recent data reaffirm this.
“A recent trial in Canada and the U.S. looked at hydrogel coils in aneurysms 12 mm or larger, with broad necks, and it failed to show a benefit of the hydrogel coils.”
Additionally, a study published in January found that hydrogel coils were no better than platinum coils in 250 patients with large or recurrent aneurysms (AJNR Am J Neuroradiol. 2017 Jan 12. doi: 10.3174/ajnr.A5101).
“I myself would use them in medium-sized aneurysms with an unfavorable dome-to-neck ratio, and in those that have a broad neck. In those instances, I do think that hydrogel coils have their place. I wouldn’t use them in really large aneurysms. I don’t think they are well suited for that. In those cases, I would probably use platinum coils in combination with a flow diverter. That really provides very stable aneurysm occlusion with acceptable complication rates.”
Dr. Taschner said that he received research support from MicroVention during the study.
[email protected]
On Twitter @alz_gal
AT THE INTERNATIONAL STROKE CONFERENCE
Key clinical point:
Major finding: Compared with bare-metal coils, hydrogel coils reduced by 9% the incidence of a composite primary outcome of recurrence, re-treatment, morbidity, and death.
Data source: An 18-month, open-label, randomized study of 513 patients.
Disclosures: MicroVention sponsored the study. Dr. Taschner said that he received research support from the company during the study.
Spotlight shifts to active treatment for concussions
The prevailing notion that concussions should be managed solely or primarily with prescribed cognitive and physical rest is shifting.
Experts in concussion management are increasingly in agreement that concussion is a much more heterogeneous injury than previously believed, and that “active” approaches targeting specific symptoms and impairments can be initiated early and may improve recovery for patients who have concussions from sports as well as from falls, motor vehicle accidents, or other accidents.
Evidence for such active approaches to rehabilitation – including vestibular, vision, and behavioral therapies, and submaximal aerobic training – is deemed “preliminary” by experts and comes from small, mostly single-center studies.
“There’s emerging evidence that strict or prolonged rest is not good, and there’s emerging consensus that we need to start looking at concussion subtypes” and then target treatments to those clinical profiles, he said. “We’re at the cusp of dramatic changes [in management].”
An article published recently in Neurosurgery and coauthored by several dozen concussion experts details 16 “statements of agreement” on targeted evaluation and active management. The experts – from neuropsychology, sports medicine, neurology and neurosurgery, athletic training, and other fields – convened in Pittsburgh in late 2015 at the invitation of Michael W. Collins, PhD, and his colleagues at the University of Pittsburgh Medical Center (UPMC), where the Sports Medicine Concussion Program was established in 2000 (Neurosurgery. 2016 Dec;79[6]:912-29).
Thus far, guidelines and statements on concussion in sport have advised a rest-based approach to management that’s dependent on the spontaneous resolution of symptoms. In some documents, rest is recommended until patients are asymptomatic. Other statements mention the possibility of symptom-based approaches after initial rest, but offer little if any guidance.
The theory of prescribed rest has been twofold, driven both by concern about re-injury in sport and by the belief that cognitive and physical activity can exacerbate symptoms and concussion-associated impairments, thus prolonging recovery, the Pittsburgh paper says.
However, “avoiding contact during the vulnerable period after concussion and prescribed rest represent two separate strategies,” the experts wrote. Avoiding contact “is always recommended to avoid further head impacts,” they say, but monitored activity does not appear to worsen injury.
Recent research suggests, moreover, that prolonged physical and cognitive rest – not activity – is associated with increased symptoms and delayed recovery. And strict rest – avoidance of nearly all brain stimulation – is “not empirically supported ... and may have unintended adverse effects,” the experts wrote.
Physicians and others “have to avoid treating concussion as a punishment,” said Dr. Halstead of St. Louis Children’s Hospital in Chesterfield, Mo., who coauthored a recent editorial entitled “Rethinking Cognitive Rest” (Br J Sports Med. 2017;51:147).
“It’s been taken to the extreme. When we talk about not texting or not going out or not doing anything physically active until you’re without symptoms ... students can develop symptoms of depression and anxiety that then just complicate the injury altogether,” he said.
Physicians also need to dig beneath symptom checklists and perform multidomain assessments to better understand root contributors of symptoms that, without active treatment, can persist for weeks upon weeks in some patients. “There could be neck injuries, sleep issues, vestibular issues, oculomotor issues” and different types of headache, Dr. Halstead said. “If we can identify these things, we can actually be doing rehabilitation to fix these injuries.”
At UPMC’s Sports Medicine Concussion Program, concussions are generally categorized into six clinical profiles – vestibular, ocular-motor, cognitive/fatigue, posttraumatic migraine, cervical, and anxiety/mood. The profiles are not mutually exclusive, but each drives particular rehabilitation recommendations. Clinicians at other concussion programs and centers are similarly attempting to classify concussions.
“We still need to come to agreement as to what exactly the clinical profiles are,” said UPMC’s Dr. Collins, who directs the concussion program and is the lead author of the Neurosurgery paper. “But I think the big concept to come out of our meeting is that we now agree there are different profiles and that we have to match treatment.”
Additional research is needed to determine and validate concussion clinical profiles, to identify biomarkers to assess recovery and determine the effectiveness of treatments, and to determine the best timing of specific active treatments, he and his coauthors said.
Applying individualized and active treatments after concussion is consistent with approaches taken for other injuries and conditions, noted Dr. Hainline, who attended both the UPMC conference and the 5th International Conference on Concussion in Sport.
“It’s rare that prolonged rest is the answer. Look at stroke – you don’t have patients resting indefinitely. You have to get their nervous systems re-engaged,” he said.
“If you keep [concussion] patients with predominantly vestibular symptoms at rest [for example], the vestibular symptoms can become more centralized, and that then becomes the behavior of the nervous system,” he said. “Another example is convergence insufficiencies – if you keep resting [the vision system] and don’t rehabilitate it,” symptoms perpetuate.
Prolonged rest also may lead to deconditioning that lowers tolerance for physical activity. Randomized clinical trials are needed to compare the benefits of physical rest with those of more physically active treatments, but “emerging clinical research” suggests that exposing patients to supervised low-level physical activity (for example, submaximal aerobic training) after an initial period of rest is “not only safe but effective,” the Pittsburgh conference paper says.
The Pittsburgh conference paper “rang a bell with me,” Dr. Wergin said. “Rest is still important, but prolonged rest may not be best for all patients, and maybe it’s possible to do some interventions. We need to stay tuned as we get more of an evidence base.”
The conference – coined the TEAM (for targeted evaluation and active management) Approaches to Treating Concussion Meeting – was attended by staff from the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Defense, and the National Football League (NFL) and other sporting organizations, Dr. Collins said. It was sponsored by UPMC and the NFL. Coauthors reported numerous disclosures, including various advising and consulting roles with the NFL.
The prevailing notion that concussions should be managed solely or primarily with prescribed cognitive and physical rest is shifting.
Experts in concussion management are increasingly in agreement that concussion is a much more heterogeneous injury than previously believed, and that “active” approaches targeting specific symptoms and impairments can be initiated early and may improve recovery for patients who have concussions from sports as well as from falls, motor vehicle accidents, or other accidents.
Evidence for such active approaches to rehabilitation – including vestibular, vision, and behavioral therapies, and submaximal aerobic training – is deemed “preliminary” by experts and comes from small, mostly single-center studies.
“There’s emerging evidence that strict or prolonged rest is not good, and there’s emerging consensus that we need to start looking at concussion subtypes” and then target treatments to those clinical profiles, he said. “We’re at the cusp of dramatic changes [in management].”
An article published recently in Neurosurgery and coauthored by several dozen concussion experts details 16 “statements of agreement” on targeted evaluation and active management. The experts – from neuropsychology, sports medicine, neurology and neurosurgery, athletic training, and other fields – convened in Pittsburgh in late 2015 at the invitation of Michael W. Collins, PhD, and his colleagues at the University of Pittsburgh Medical Center (UPMC), where the Sports Medicine Concussion Program was established in 2000 (Neurosurgery. 2016 Dec;79[6]:912-29).
Thus far, guidelines and statements on concussion in sport have advised a rest-based approach to management that’s dependent on the spontaneous resolution of symptoms. In some documents, rest is recommended until patients are asymptomatic. Other statements mention the possibility of symptom-based approaches after initial rest, but offer little if any guidance.
The theory of prescribed rest has been twofold, driven both by concern about re-injury in sport and by the belief that cognitive and physical activity can exacerbate symptoms and concussion-associated impairments, thus prolonging recovery, the Pittsburgh paper says.
However, “avoiding contact during the vulnerable period after concussion and prescribed rest represent two separate strategies,” the experts wrote. Avoiding contact “is always recommended to avoid further head impacts,” they say, but monitored activity does not appear to worsen injury.
Recent research suggests, moreover, that prolonged physical and cognitive rest – not activity – is associated with increased symptoms and delayed recovery. And strict rest – avoidance of nearly all brain stimulation – is “not empirically supported ... and may have unintended adverse effects,” the experts wrote.
Physicians and others “have to avoid treating concussion as a punishment,” said Dr. Halstead of St. Louis Children’s Hospital in Chesterfield, Mo., who coauthored a recent editorial entitled “Rethinking Cognitive Rest” (Br J Sports Med. 2017;51:147).
“It’s been taken to the extreme. When we talk about not texting or not going out or not doing anything physically active until you’re without symptoms ... students can develop symptoms of depression and anxiety that then just complicate the injury altogether,” he said.
Physicians also need to dig beneath symptom checklists and perform multidomain assessments to better understand root contributors of symptoms that, without active treatment, can persist for weeks upon weeks in some patients. “There could be neck injuries, sleep issues, vestibular issues, oculomotor issues” and different types of headache, Dr. Halstead said. “If we can identify these things, we can actually be doing rehabilitation to fix these injuries.”
At UPMC’s Sports Medicine Concussion Program, concussions are generally categorized into six clinical profiles – vestibular, ocular-motor, cognitive/fatigue, posttraumatic migraine, cervical, and anxiety/mood. The profiles are not mutually exclusive, but each drives particular rehabilitation recommendations. Clinicians at other concussion programs and centers are similarly attempting to classify concussions.
“We still need to come to agreement as to what exactly the clinical profiles are,” said UPMC’s Dr. Collins, who directs the concussion program and is the lead author of the Neurosurgery paper. “But I think the big concept to come out of our meeting is that we now agree there are different profiles and that we have to match treatment.”
Additional research is needed to determine and validate concussion clinical profiles, to identify biomarkers to assess recovery and determine the effectiveness of treatments, and to determine the best timing of specific active treatments, he and his coauthors said.
Applying individualized and active treatments after concussion is consistent with approaches taken for other injuries and conditions, noted Dr. Hainline, who attended both the UPMC conference and the 5th International Conference on Concussion in Sport.
“It’s rare that prolonged rest is the answer. Look at stroke – you don’t have patients resting indefinitely. You have to get their nervous systems re-engaged,” he said.
“If you keep [concussion] patients with predominantly vestibular symptoms at rest [for example], the vestibular symptoms can become more centralized, and that then becomes the behavior of the nervous system,” he said. “Another example is convergence insufficiencies – if you keep resting [the vision system] and don’t rehabilitate it,” symptoms perpetuate.
Prolonged rest also may lead to deconditioning that lowers tolerance for physical activity. Randomized clinical trials are needed to compare the benefits of physical rest with those of more physically active treatments, but “emerging clinical research” suggests that exposing patients to supervised low-level physical activity (for example, submaximal aerobic training) after an initial period of rest is “not only safe but effective,” the Pittsburgh conference paper says.
The Pittsburgh conference paper “rang a bell with me,” Dr. Wergin said. “Rest is still important, but prolonged rest may not be best for all patients, and maybe it’s possible to do some interventions. We need to stay tuned as we get more of an evidence base.”
The conference – coined the TEAM (for targeted evaluation and active management) Approaches to Treating Concussion Meeting – was attended by staff from the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Defense, and the National Football League (NFL) and other sporting organizations, Dr. Collins said. It was sponsored by UPMC and the NFL. Coauthors reported numerous disclosures, including various advising and consulting roles with the NFL.
The prevailing notion that concussions should be managed solely or primarily with prescribed cognitive and physical rest is shifting.
Experts in concussion management are increasingly in agreement that concussion is a much more heterogeneous injury than previously believed, and that “active” approaches targeting specific symptoms and impairments can be initiated early and may improve recovery for patients who have concussions from sports as well as from falls, motor vehicle accidents, or other accidents.
Evidence for such active approaches to rehabilitation – including vestibular, vision, and behavioral therapies, and submaximal aerobic training – is deemed “preliminary” by experts and comes from small, mostly single-center studies.
“There’s emerging evidence that strict or prolonged rest is not good, and there’s emerging consensus that we need to start looking at concussion subtypes” and then target treatments to those clinical profiles, he said. “We’re at the cusp of dramatic changes [in management].”
An article published recently in Neurosurgery and coauthored by several dozen concussion experts details 16 “statements of agreement” on targeted evaluation and active management. The experts – from neuropsychology, sports medicine, neurology and neurosurgery, athletic training, and other fields – convened in Pittsburgh in late 2015 at the invitation of Michael W. Collins, PhD, and his colleagues at the University of Pittsburgh Medical Center (UPMC), where the Sports Medicine Concussion Program was established in 2000 (Neurosurgery. 2016 Dec;79[6]:912-29).
Thus far, guidelines and statements on concussion in sport have advised a rest-based approach to management that’s dependent on the spontaneous resolution of symptoms. In some documents, rest is recommended until patients are asymptomatic. Other statements mention the possibility of symptom-based approaches after initial rest, but offer little if any guidance.
The theory of prescribed rest has been twofold, driven both by concern about re-injury in sport and by the belief that cognitive and physical activity can exacerbate symptoms and concussion-associated impairments, thus prolonging recovery, the Pittsburgh paper says.
However, “avoiding contact during the vulnerable period after concussion and prescribed rest represent two separate strategies,” the experts wrote. Avoiding contact “is always recommended to avoid further head impacts,” they say, but monitored activity does not appear to worsen injury.
Recent research suggests, moreover, that prolonged physical and cognitive rest – not activity – is associated with increased symptoms and delayed recovery. And strict rest – avoidance of nearly all brain stimulation – is “not empirically supported ... and may have unintended adverse effects,” the experts wrote.
Physicians and others “have to avoid treating concussion as a punishment,” said Dr. Halstead of St. Louis Children’s Hospital in Chesterfield, Mo., who coauthored a recent editorial entitled “Rethinking Cognitive Rest” (Br J Sports Med. 2017;51:147).
“It’s been taken to the extreme. When we talk about not texting or not going out or not doing anything physically active until you’re without symptoms ... students can develop symptoms of depression and anxiety that then just complicate the injury altogether,” he said.
Physicians also need to dig beneath symptom checklists and perform multidomain assessments to better understand root contributors of symptoms that, without active treatment, can persist for weeks upon weeks in some patients. “There could be neck injuries, sleep issues, vestibular issues, oculomotor issues” and different types of headache, Dr. Halstead said. “If we can identify these things, we can actually be doing rehabilitation to fix these injuries.”
At UPMC’s Sports Medicine Concussion Program, concussions are generally categorized into six clinical profiles – vestibular, ocular-motor, cognitive/fatigue, posttraumatic migraine, cervical, and anxiety/mood. The profiles are not mutually exclusive, but each drives particular rehabilitation recommendations. Clinicians at other concussion programs and centers are similarly attempting to classify concussions.
“We still need to come to agreement as to what exactly the clinical profiles are,” said UPMC’s Dr. Collins, who directs the concussion program and is the lead author of the Neurosurgery paper. “But I think the big concept to come out of our meeting is that we now agree there are different profiles and that we have to match treatment.”
Additional research is needed to determine and validate concussion clinical profiles, to identify biomarkers to assess recovery and determine the effectiveness of treatments, and to determine the best timing of specific active treatments, he and his coauthors said.
Applying individualized and active treatments after concussion is consistent with approaches taken for other injuries and conditions, noted Dr. Hainline, who attended both the UPMC conference and the 5th International Conference on Concussion in Sport.
“It’s rare that prolonged rest is the answer. Look at stroke – you don’t have patients resting indefinitely. You have to get their nervous systems re-engaged,” he said.
“If you keep [concussion] patients with predominantly vestibular symptoms at rest [for example], the vestibular symptoms can become more centralized, and that then becomes the behavior of the nervous system,” he said. “Another example is convergence insufficiencies – if you keep resting [the vision system] and don’t rehabilitate it,” symptoms perpetuate.
Prolonged rest also may lead to deconditioning that lowers tolerance for physical activity. Randomized clinical trials are needed to compare the benefits of physical rest with those of more physically active treatments, but “emerging clinical research” suggests that exposing patients to supervised low-level physical activity (for example, submaximal aerobic training) after an initial period of rest is “not only safe but effective,” the Pittsburgh conference paper says.
The Pittsburgh conference paper “rang a bell with me,” Dr. Wergin said. “Rest is still important, but prolonged rest may not be best for all patients, and maybe it’s possible to do some interventions. We need to stay tuned as we get more of an evidence base.”
The conference – coined the TEAM (for targeted evaluation and active management) Approaches to Treating Concussion Meeting – was attended by staff from the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Defense, and the National Football League (NFL) and other sporting organizations, Dr. Collins said. It was sponsored by UPMC and the NFL. Coauthors reported numerous disclosures, including various advising and consulting roles with the NFL.
VIDEO: Clot aspiration equals retrieval for ischemic stroke
HOUSTON – Intracerebral clot aspiration was as safe and effective as stent retriever thrombectomy for restoring cerebral blood flow in a French multicenter, randomized trial with 381 acute ischemic stroke patients.
This study is the “first direct comparison of aspiration versus stent retrieval” as the initial strategy for clot removal in acute ischemic stroke, and it “opens the door to add a new tool” for clot removal, Bertrand Lapergue, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The new results “are the first to show that aspiration first is as good as a stent retriever, but we need to also see the results from COMPASS,” a U.S. multicenter trial that is in the process of making the same comparison, commented Ricardo A. Hanel, MD, a vascular neurosurgeon at Baptist Health in Jacksonville, Fla. The COMPASS Trial: a Direct Aspiration First Pass Technique has now enrolled about two-thirds of its target patient number, and until the study is complete the role of direct aspiration for clot removal in stroke remains investigational for U.S. practice, said Dr. Hanel, a COMPASS investigator.
The aspiration catheter tested in ASTER is marketed by Penumbra and has already received Food and Drug Administration approval for revascularization of ischemic stroke patients. U.S. use of aspiration for treating acute ischemic stroke, however, has remained limited because there is no clear evidence of the method’s efficacy. Dr. Hanel said that he occasionally uses aspiration as an adjunct to clot removal with a stent retriever.
ASTER’s primary endpoint was the percentage of patients who achieved thrombolysis in cerebral infarction (TICI) 2b or 3 flow at the end of treatment, which occurred in 85% of patients treated with aspiration first and in 83% of those treated by clot removal first, a difference that was not statistically significant, Dr. Lapergue reported. The rate of patients who achieved either TICI 2b or 3 flow after the initial strategy only was 63% with aspiration and 68% with clot removal, also a nonsignificant difference. The two strategies also showed no significant difference for any measured safety parameter. The results showed a trend toward more vasospasm with clot removal – a 6% rate, versus 3% with clot aspiration – but this did not reach statistical significance.
Results from additional analyses of the clinical outcomes of patients in the trial and of cost efficacy will be reported later in 2017, Dr. Lapergue said.
ASTER received an unrestricted research grant from Penumbra, a company that markets clot removal aspiration catheters. Dr. Lapergue had no personal disclosures. Dr. Hanel has been a consultant to and received grant support from Medtronic. He has received research grants from MicroVention and has an ownership interest in InNeuroCo.
[email protected]
On Twitter @mitchelzoler
ASTER is an important trial. It shows for the first time that an aspiration device is probably as safe and reasonable for opening an acute occlusion in a large cerebral artery as is a stent retriever.
ASTER, however, was done entirely in a French population, making it uncertain whether the results are applicable to other populations. For example, U.S. acute ischemic stroke patients, especially African Americans and Hispanics, generally have more intracerebral atherostenotic disease than do patients from European countries, while French patients tend to have more embolic disease. Will aspiration be as effective in U.S. patients with atherostenotic blockages? I would love to see this study repeated in a U.S. population of ischemic stroke patients, and that is now happening in the COMPASS trial. It would be helpful to know if there are selected U.S. patients who might be better treated using either aspiration or a stent retriever first.
Although aspiration catheters have already received Food and Drug Administration approval for clot removal in acute ischemic stroke patients, many U.S. interventionalists have moved to deploying stent retrievers based on the very positive results reported with these devices about 2 years ago. For the moment, stent retrievers remain the most prominent devices to open large vessel occlusions.
Ralph L. Sacco, MD, is professor and chairman of neurology at the University of Miami. He had no relevant disclosures. He made these comments in a video interview and during a press conference.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ASTER is an important trial. It shows for the first time that an aspiration device is probably as safe and reasonable for opening an acute occlusion in a large cerebral artery as is a stent retriever.
ASTER, however, was done entirely in a French population, making it uncertain whether the results are applicable to other populations. For example, U.S. acute ischemic stroke patients, especially African Americans and Hispanics, generally have more intracerebral atherostenotic disease than do patients from European countries, while French patients tend to have more embolic disease. Will aspiration be as effective in U.S. patients with atherostenotic blockages? I would love to see this study repeated in a U.S. population of ischemic stroke patients, and that is now happening in the COMPASS trial. It would be helpful to know if there are selected U.S. patients who might be better treated using either aspiration or a stent retriever first.
Although aspiration catheters have already received Food and Drug Administration approval for clot removal in acute ischemic stroke patients, many U.S. interventionalists have moved to deploying stent retrievers based on the very positive results reported with these devices about 2 years ago. For the moment, stent retrievers remain the most prominent devices to open large vessel occlusions.
Ralph L. Sacco, MD, is professor and chairman of neurology at the University of Miami. He had no relevant disclosures. He made these comments in a video interview and during a press conference.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ASTER is an important trial. It shows for the first time that an aspiration device is probably as safe and reasonable for opening an acute occlusion in a large cerebral artery as is a stent retriever.
ASTER, however, was done entirely in a French population, making it uncertain whether the results are applicable to other populations. For example, U.S. acute ischemic stroke patients, especially African Americans and Hispanics, generally have more intracerebral atherostenotic disease than do patients from European countries, while French patients tend to have more embolic disease. Will aspiration be as effective in U.S. patients with atherostenotic blockages? I would love to see this study repeated in a U.S. population of ischemic stroke patients, and that is now happening in the COMPASS trial. It would be helpful to know if there are selected U.S. patients who might be better treated using either aspiration or a stent retriever first.
Although aspiration catheters have already received Food and Drug Administration approval for clot removal in acute ischemic stroke patients, many U.S. interventionalists have moved to deploying stent retrievers based on the very positive results reported with these devices about 2 years ago. For the moment, stent retrievers remain the most prominent devices to open large vessel occlusions.
Ralph L. Sacco, MD, is professor and chairman of neurology at the University of Miami. He had no relevant disclosures. He made these comments in a video interview and during a press conference.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
HOUSTON – Intracerebral clot aspiration was as safe and effective as stent retriever thrombectomy for restoring cerebral blood flow in a French multicenter, randomized trial with 381 acute ischemic stroke patients.
This study is the “first direct comparison of aspiration versus stent retrieval” as the initial strategy for clot removal in acute ischemic stroke, and it “opens the door to add a new tool” for clot removal, Bertrand Lapergue, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The new results “are the first to show that aspiration first is as good as a stent retriever, but we need to also see the results from COMPASS,” a U.S. multicenter trial that is in the process of making the same comparison, commented Ricardo A. Hanel, MD, a vascular neurosurgeon at Baptist Health in Jacksonville, Fla. The COMPASS Trial: a Direct Aspiration First Pass Technique has now enrolled about two-thirds of its target patient number, and until the study is complete the role of direct aspiration for clot removal in stroke remains investigational for U.S. practice, said Dr. Hanel, a COMPASS investigator.
The aspiration catheter tested in ASTER is marketed by Penumbra and has already received Food and Drug Administration approval for revascularization of ischemic stroke patients. U.S. use of aspiration for treating acute ischemic stroke, however, has remained limited because there is no clear evidence of the method’s efficacy. Dr. Hanel said that he occasionally uses aspiration as an adjunct to clot removal with a stent retriever.
ASTER’s primary endpoint was the percentage of patients who achieved thrombolysis in cerebral infarction (TICI) 2b or 3 flow at the end of treatment, which occurred in 85% of patients treated with aspiration first and in 83% of those treated by clot removal first, a difference that was not statistically significant, Dr. Lapergue reported. The rate of patients who achieved either TICI 2b or 3 flow after the initial strategy only was 63% with aspiration and 68% with clot removal, also a nonsignificant difference. The two strategies also showed no significant difference for any measured safety parameter. The results showed a trend toward more vasospasm with clot removal – a 6% rate, versus 3% with clot aspiration – but this did not reach statistical significance.
Results from additional analyses of the clinical outcomes of patients in the trial and of cost efficacy will be reported later in 2017, Dr. Lapergue said.
ASTER received an unrestricted research grant from Penumbra, a company that markets clot removal aspiration catheters. Dr. Lapergue had no personal disclosures. Dr. Hanel has been a consultant to and received grant support from Medtronic. He has received research grants from MicroVention and has an ownership interest in InNeuroCo.
[email protected]
On Twitter @mitchelzoler
HOUSTON – Intracerebral clot aspiration was as safe and effective as stent retriever thrombectomy for restoring cerebral blood flow in a French multicenter, randomized trial with 381 acute ischemic stroke patients.
This study is the “first direct comparison of aspiration versus stent retrieval” as the initial strategy for clot removal in acute ischemic stroke, and it “opens the door to add a new tool” for clot removal, Bertrand Lapergue, MD, said at the International Stroke Conference sponsored by the American Heart Association.
The new results “are the first to show that aspiration first is as good as a stent retriever, but we need to also see the results from COMPASS,” a U.S. multicenter trial that is in the process of making the same comparison, commented Ricardo A. Hanel, MD, a vascular neurosurgeon at Baptist Health in Jacksonville, Fla. The COMPASS Trial: a Direct Aspiration First Pass Technique has now enrolled about two-thirds of its target patient number, and until the study is complete the role of direct aspiration for clot removal in stroke remains investigational for U.S. practice, said Dr. Hanel, a COMPASS investigator.
The aspiration catheter tested in ASTER is marketed by Penumbra and has already received Food and Drug Administration approval for revascularization of ischemic stroke patients. U.S. use of aspiration for treating acute ischemic stroke, however, has remained limited because there is no clear evidence of the method’s efficacy. Dr. Hanel said that he occasionally uses aspiration as an adjunct to clot removal with a stent retriever.
ASTER’s primary endpoint was the percentage of patients who achieved thrombolysis in cerebral infarction (TICI) 2b or 3 flow at the end of treatment, which occurred in 85% of patients treated with aspiration first and in 83% of those treated by clot removal first, a difference that was not statistically significant, Dr. Lapergue reported. The rate of patients who achieved either TICI 2b or 3 flow after the initial strategy only was 63% with aspiration and 68% with clot removal, also a nonsignificant difference. The two strategies also showed no significant difference for any measured safety parameter. The results showed a trend toward more vasospasm with clot removal – a 6% rate, versus 3% with clot aspiration – but this did not reach statistical significance.
Results from additional analyses of the clinical outcomes of patients in the trial and of cost efficacy will be reported later in 2017, Dr. Lapergue said.
ASTER received an unrestricted research grant from Penumbra, a company that markets clot removal aspiration catheters. Dr. Lapergue had no personal disclosures. Dr. Hanel has been a consultant to and received grant support from Medtronic. He has received research grants from MicroVention and has an ownership interest in InNeuroCo.
[email protected]
On Twitter @mitchelzoler
AT THE INTERNATIONAL STROKE CONFERENCE
Key clinical point:
Major finding: Recanalization occurred in 85% of patients treated with aspiration first and 83% treated with clot removal first.
Data source: ASTER, a multicenter, randomized French trial with 381 patients.
Disclosures: ASTER received an unrestricted research grant from Penumbra, a company that markets clot removal aspiration catheters. Dr. Lapergue had no personal disclosures. Dr. Hanel has been a consultant to and received grant support from Medtronic. He has received research grants from MicroVention and has an ownership interest in InNeuroCo.
Mesh cylinder effective for small to medium wide-necked aneurysms
HOUSTON – An expandable mesh cylinder that is approved to treat large, wide-necked carotid aneurysms has now proved successful in treating small lesions of the internal carotid or vertebral artery up to 12 mm in diameter.
The Pipeline Embolization Device (PED, Medtronic) completely occluded 84% of such lesions without significant stenosis or retreatment within 1 year in the PREMIER trial, Ricardo Hanel, MD, PhD, said at the International Stroke Conference sponsored by the American Heart Association.
Overall morbidity and mortality in the year-long trial was very low (2.2%). However, within the first year, three patients had a major stroke in brain regions supplied by the treated artery; one of these was related to device deployment and was fatal, said Dr. Hanel, director of the Baptist Neurological Institute, Jacksonville, Fla.
Counseling patients with these lesions is not easy, Dr. Hanel said. Treatment decisions must take into account not only the patient’s current clinical status and comorbidities, but family history and personal preference. In fact, patient preference was the largest driver of treatment (63%) in the PREMIER study.
In an interview, Dr. Hanel illustrated the importance of individualized decision making. A middle-aged female had been monitored for a small aneurysm for 7 years. When the patient was 6 years old, her mother died during an open operation to treat an aneurysm.
“We had tried to treat this patient with coiling [when the lesion was first detected], but it was unsuccessful,” Dr. Hanel said. “And since her mother had died during surgery, she did not want to go for an open approach. Now, 6 years later, we have the technology to cure her with a single device, and the odds of [recurrence over 10 years] are virtually zero. It is a very personal decision, and we take a lot of factors under consideration before we decide to expose the patient to the risks of this treatment.”
The PED is a flexible 75% cobalt-chromium/25% platinum-tungsten mesh with a braided configuration. It is advanced slightly beyond the aneurysm neck and then deployed. As it opens, it partially occludes the lesion, immediately decreasing the amount of blood entering the sac. Within a month, vascular remodeling is well underway; as endothelium grows throughout the mesh, blood flow into the aneurysm is gradually cut off. Eventually the aneurysmal sac recedes, and the normal vascular architecture is restored.
“Within 4 weeks you can’t see the metal at all,” Dr. Hanel said. “It’s covered by a thin layer of endothelial cells. This device allows the patient’s body to heal and close the aneurysm, and we don’t have to deal with the reoccurrence problem we have with stent coils. The pipeline treats the entire circumference of the vessel.”
The PED is used in combination with dual-antiplatelet therapy (DAP, aspirin/clopidogrel). Dr. Hanel initiates DAP 7 days before the procedure and continues it for 3 months. At that time, clopidogrel may be discontinued. “I advise my patients to then take a baby aspirin every day for the rest of their lives,” and they are regularly monitored, he said. “Aspirin seems to protect against the formation and rupture of aneurysms.”
PREMIER followed 141 patients with unruptured, wide-necked small aneurysms of the internal carotid (up to the terminus) or the vertebral artery segment up to and including the posterior inferior cerebellar artery. The primary efficacy endpoint was complete aneurysm occlusion and absence of significant parent artery stenosis at 1 year. The secondary endpoint was successful device deployment.
The primary safety endpoint was major stroke in the territory supplied by the treated artery or neurologic death at 1 year. There were two secondary safety endpoints: major stroke or neurologic death within 30 days, attributable to procedural complications, and intracerebral hemorrhage more than 30 days later.
The patients were largely female (88%) with a mean age of 55 years. They were asymptomatic with a mean modified Rankin Scale score of 0.2 and National Institutes of Health Stroke Scale score of 0.1. Nearly half of the patients had hypertension, and 38% had hyperlipidemia. About 28% were current smokers, and another 16% had a history of smoking.
The patients’ mean maximal aneurysm diameter was 4.6 mm, with a mean neck width of 3.7 mm. The majority of lesions (84%) were less than 7 mm in diameter, but they ranged up to 12 mm.
Internal carotid artery aneurysms comprised 95% of all in the study; 5% were in the vertebral artery. Most involved the side wall (84%), while the remainder involved a side branch (12%) or were fusiform (4%).
There was only one unsuccessful initial deployment, resulting in a 99.3% deployment success rate. The mean procedure time was 78 minutes. While most patients received just one PED, 10 received multiple devices. The PED completely covered the entire neck of the lesion in 97%. There were no intraoperative aneurysm ruptures and no intraoperative deaths.
At 1 year after implantation, 84% of the aneurysms were completely occluded, with the aneurysmal sac eliminated in 92%. A residual aneurysm remained in 11 patients (8%), and a residual neck in 8 patients (6%). Two patients (1.4%) had arterial stenosis of more than 50%. Three patients (2.2%) required retreatment.
There were three major strokes in the region supplied by the target artery in three patients.
The fatal stroke occurred in a patient who had an aneurysm on the right ophthalmic carotid segment. The first device failed to deploy correctly and was removed. A second device was implanted. The next day the patient developed a facial droop, slurred speech, and a headache. She experienced a distal intraparenchymal hemorrhage and underwent hemicraniotomy, but did not survive.
The second stroke occurred in a patient who needed two devices to occlude a lesion in the left ophthalmic segment of the carotid. The patient developed an intraparenchymal hemorrhage on postoperative day 15. The stroke resolved with sequelae and the clopidogrel dose was increased.
The third stroke was associated with treatment of a right communicating segment aneurysm. The patient stopped taking the recommended DAP and experienced an acute ischemic stroke 169 days after the procedure. This stroke also resolved with sequelae.
Based on the results of PREMIER, Medtronic will pursue Food and Drug Administration approval of the PED for small to medium wide-necked aneurysms, Dr. Hanel noted.
Medtronic sponsored the study. Dr. Hanel is an adviser to the company and has received research funds from it.
[email protected]
On Twitter @alz_gal
HOUSTON – An expandable mesh cylinder that is approved to treat large, wide-necked carotid aneurysms has now proved successful in treating small lesions of the internal carotid or vertebral artery up to 12 mm in diameter.
The Pipeline Embolization Device (PED, Medtronic) completely occluded 84% of such lesions without significant stenosis or retreatment within 1 year in the PREMIER trial, Ricardo Hanel, MD, PhD, said at the International Stroke Conference sponsored by the American Heart Association.
Overall morbidity and mortality in the year-long trial was very low (2.2%). However, within the first year, three patients had a major stroke in brain regions supplied by the treated artery; one of these was related to device deployment and was fatal, said Dr. Hanel, director of the Baptist Neurological Institute, Jacksonville, Fla.
Counseling patients with these lesions is not easy, Dr. Hanel said. Treatment decisions must take into account not only the patient’s current clinical status and comorbidities, but family history and personal preference. In fact, patient preference was the largest driver of treatment (63%) in the PREMIER study.
In an interview, Dr. Hanel illustrated the importance of individualized decision making. A middle-aged female had been monitored for a small aneurysm for 7 years. When the patient was 6 years old, her mother died during an open operation to treat an aneurysm.
“We had tried to treat this patient with coiling [when the lesion was first detected], but it was unsuccessful,” Dr. Hanel said. “And since her mother had died during surgery, she did not want to go for an open approach. Now, 6 years later, we have the technology to cure her with a single device, and the odds of [recurrence over 10 years] are virtually zero. It is a very personal decision, and we take a lot of factors under consideration before we decide to expose the patient to the risks of this treatment.”
The PED is a flexible 75% cobalt-chromium/25% platinum-tungsten mesh with a braided configuration. It is advanced slightly beyond the aneurysm neck and then deployed. As it opens, it partially occludes the lesion, immediately decreasing the amount of blood entering the sac. Within a month, vascular remodeling is well underway; as endothelium grows throughout the mesh, blood flow into the aneurysm is gradually cut off. Eventually the aneurysmal sac recedes, and the normal vascular architecture is restored.
“Within 4 weeks you can’t see the metal at all,” Dr. Hanel said. “It’s covered by a thin layer of endothelial cells. This device allows the patient’s body to heal and close the aneurysm, and we don’t have to deal with the reoccurrence problem we have with stent coils. The pipeline treats the entire circumference of the vessel.”
The PED is used in combination with dual-antiplatelet therapy (DAP, aspirin/clopidogrel). Dr. Hanel initiates DAP 7 days before the procedure and continues it for 3 months. At that time, clopidogrel may be discontinued. “I advise my patients to then take a baby aspirin every day for the rest of their lives,” and they are regularly monitored, he said. “Aspirin seems to protect against the formation and rupture of aneurysms.”
PREMIER followed 141 patients with unruptured, wide-necked small aneurysms of the internal carotid (up to the terminus) or the vertebral artery segment up to and including the posterior inferior cerebellar artery. The primary efficacy endpoint was complete aneurysm occlusion and absence of significant parent artery stenosis at 1 year. The secondary endpoint was successful device deployment.
The primary safety endpoint was major stroke in the territory supplied by the treated artery or neurologic death at 1 year. There were two secondary safety endpoints: major stroke or neurologic death within 30 days, attributable to procedural complications, and intracerebral hemorrhage more than 30 days later.
The patients were largely female (88%) with a mean age of 55 years. They were asymptomatic with a mean modified Rankin Scale score of 0.2 and National Institutes of Health Stroke Scale score of 0.1. Nearly half of the patients had hypertension, and 38% had hyperlipidemia. About 28% were current smokers, and another 16% had a history of smoking.
The patients’ mean maximal aneurysm diameter was 4.6 mm, with a mean neck width of 3.7 mm. The majority of lesions (84%) were less than 7 mm in diameter, but they ranged up to 12 mm.
Internal carotid artery aneurysms comprised 95% of all in the study; 5% were in the vertebral artery. Most involved the side wall (84%), while the remainder involved a side branch (12%) or were fusiform (4%).
There was only one unsuccessful initial deployment, resulting in a 99.3% deployment success rate. The mean procedure time was 78 minutes. While most patients received just one PED, 10 received multiple devices. The PED completely covered the entire neck of the lesion in 97%. There were no intraoperative aneurysm ruptures and no intraoperative deaths.
At 1 year after implantation, 84% of the aneurysms were completely occluded, with the aneurysmal sac eliminated in 92%. A residual aneurysm remained in 11 patients (8%), and a residual neck in 8 patients (6%). Two patients (1.4%) had arterial stenosis of more than 50%. Three patients (2.2%) required retreatment.
There were three major strokes in the region supplied by the target artery in three patients.
The fatal stroke occurred in a patient who had an aneurysm on the right ophthalmic carotid segment. The first device failed to deploy correctly and was removed. A second device was implanted. The next day the patient developed a facial droop, slurred speech, and a headache. She experienced a distal intraparenchymal hemorrhage and underwent hemicraniotomy, but did not survive.
The second stroke occurred in a patient who needed two devices to occlude a lesion in the left ophthalmic segment of the carotid. The patient developed an intraparenchymal hemorrhage on postoperative day 15. The stroke resolved with sequelae and the clopidogrel dose was increased.
The third stroke was associated with treatment of a right communicating segment aneurysm. The patient stopped taking the recommended DAP and experienced an acute ischemic stroke 169 days after the procedure. This stroke also resolved with sequelae.
Based on the results of PREMIER, Medtronic will pursue Food and Drug Administration approval of the PED for small to medium wide-necked aneurysms, Dr. Hanel noted.
Medtronic sponsored the study. Dr. Hanel is an adviser to the company and has received research funds from it.
[email protected]
On Twitter @alz_gal
HOUSTON – An expandable mesh cylinder that is approved to treat large, wide-necked carotid aneurysms has now proved successful in treating small lesions of the internal carotid or vertebral artery up to 12 mm in diameter.
The Pipeline Embolization Device (PED, Medtronic) completely occluded 84% of such lesions without significant stenosis or retreatment within 1 year in the PREMIER trial, Ricardo Hanel, MD, PhD, said at the International Stroke Conference sponsored by the American Heart Association.
Overall morbidity and mortality in the year-long trial was very low (2.2%). However, within the first year, three patients had a major stroke in brain regions supplied by the treated artery; one of these was related to device deployment and was fatal, said Dr. Hanel, director of the Baptist Neurological Institute, Jacksonville, Fla.
Counseling patients with these lesions is not easy, Dr. Hanel said. Treatment decisions must take into account not only the patient’s current clinical status and comorbidities, but family history and personal preference. In fact, patient preference was the largest driver of treatment (63%) in the PREMIER study.
In an interview, Dr. Hanel illustrated the importance of individualized decision making. A middle-aged female had been monitored for a small aneurysm for 7 years. When the patient was 6 years old, her mother died during an open operation to treat an aneurysm.
“We had tried to treat this patient with coiling [when the lesion was first detected], but it was unsuccessful,” Dr. Hanel said. “And since her mother had died during surgery, she did not want to go for an open approach. Now, 6 years later, we have the technology to cure her with a single device, and the odds of [recurrence over 10 years] are virtually zero. It is a very personal decision, and we take a lot of factors under consideration before we decide to expose the patient to the risks of this treatment.”
The PED is a flexible 75% cobalt-chromium/25% platinum-tungsten mesh with a braided configuration. It is advanced slightly beyond the aneurysm neck and then deployed. As it opens, it partially occludes the lesion, immediately decreasing the amount of blood entering the sac. Within a month, vascular remodeling is well underway; as endothelium grows throughout the mesh, blood flow into the aneurysm is gradually cut off. Eventually the aneurysmal sac recedes, and the normal vascular architecture is restored.
“Within 4 weeks you can’t see the metal at all,” Dr. Hanel said. “It’s covered by a thin layer of endothelial cells. This device allows the patient’s body to heal and close the aneurysm, and we don’t have to deal with the reoccurrence problem we have with stent coils. The pipeline treats the entire circumference of the vessel.”
The PED is used in combination with dual-antiplatelet therapy (DAP, aspirin/clopidogrel). Dr. Hanel initiates DAP 7 days before the procedure and continues it for 3 months. At that time, clopidogrel may be discontinued. “I advise my patients to then take a baby aspirin every day for the rest of their lives,” and they are regularly monitored, he said. “Aspirin seems to protect against the formation and rupture of aneurysms.”
PREMIER followed 141 patients with unruptured, wide-necked small aneurysms of the internal carotid (up to the terminus) or the vertebral artery segment up to and including the posterior inferior cerebellar artery. The primary efficacy endpoint was complete aneurysm occlusion and absence of significant parent artery stenosis at 1 year. The secondary endpoint was successful device deployment.
The primary safety endpoint was major stroke in the territory supplied by the treated artery or neurologic death at 1 year. There were two secondary safety endpoints: major stroke or neurologic death within 30 days, attributable to procedural complications, and intracerebral hemorrhage more than 30 days later.
The patients were largely female (88%) with a mean age of 55 years. They were asymptomatic with a mean modified Rankin Scale score of 0.2 and National Institutes of Health Stroke Scale score of 0.1. Nearly half of the patients had hypertension, and 38% had hyperlipidemia. About 28% were current smokers, and another 16% had a history of smoking.
The patients’ mean maximal aneurysm diameter was 4.6 mm, with a mean neck width of 3.7 mm. The majority of lesions (84%) were less than 7 mm in diameter, but they ranged up to 12 mm.
Internal carotid artery aneurysms comprised 95% of all in the study; 5% were in the vertebral artery. Most involved the side wall (84%), while the remainder involved a side branch (12%) or were fusiform (4%).
There was only one unsuccessful initial deployment, resulting in a 99.3% deployment success rate. The mean procedure time was 78 minutes. While most patients received just one PED, 10 received multiple devices. The PED completely covered the entire neck of the lesion in 97%. There were no intraoperative aneurysm ruptures and no intraoperative deaths.
At 1 year after implantation, 84% of the aneurysms were completely occluded, with the aneurysmal sac eliminated in 92%. A residual aneurysm remained in 11 patients (8%), and a residual neck in 8 patients (6%). Two patients (1.4%) had arterial stenosis of more than 50%. Three patients (2.2%) required retreatment.
There were three major strokes in the region supplied by the target artery in three patients.
The fatal stroke occurred in a patient who had an aneurysm on the right ophthalmic carotid segment. The first device failed to deploy correctly and was removed. A second device was implanted. The next day the patient developed a facial droop, slurred speech, and a headache. She experienced a distal intraparenchymal hemorrhage and underwent hemicraniotomy, but did not survive.
The second stroke occurred in a patient who needed two devices to occlude a lesion in the left ophthalmic segment of the carotid. The patient developed an intraparenchymal hemorrhage on postoperative day 15. The stroke resolved with sequelae and the clopidogrel dose was increased.
The third stroke was associated with treatment of a right communicating segment aneurysm. The patient stopped taking the recommended DAP and experienced an acute ischemic stroke 169 days after the procedure. This stroke also resolved with sequelae.
Based on the results of PREMIER, Medtronic will pursue Food and Drug Administration approval of the PED for small to medium wide-necked aneurysms, Dr. Hanel noted.
Medtronic sponsored the study. Dr. Hanel is an adviser to the company and has received research funds from it.
[email protected]
On Twitter @alz_gal
AT THE INTERNATIONAL STROKE CONFERENCE
Key clinical point:
Major finding: The PED completely occluded 84% of aneurysms of the internal carotid or vertebral artery up to 12 mm in diameter at 1 year.
Data source: PREMIER investigators prospectively evaluated the PED in 141 patients.
Disclosures: Medtronic sponsored the study. Dr. Hanel is an adviser to the company and has received research funds from it.
New and Noteworthy Information—March 2017
Serum levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were unable to distinguish between patients with mild traumatic brain injury (mTBI) and patients with orthopedic trauma, according to a study published online ahead of print January 27 in the Journal of Neurotrauma. The results cast doubt on the value of these proposed biomarkers in diagnosing mTBI, the researchers said. Serum UCH-L1 and GFAP were longitudinally measured in 73 patients with acute orthopedic injury and in 93 patients with CT-negative mTBI when they arrived at the hospital and one, two, three, and seven days after admission, as well as at a follow-up visit between three and 10 months after injury. Levels of GFAP were higher in patients with orthopedic trauma than in patients with mTBI on arrival, but subsequent levels did not differ between groups. Levels of UCH-L1 did not significantly differ between the groups.
High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation without maintenance therapy is effective for inducing long-term sustained remission of active relapsing-remitting multiple sclerosis at five years, according to a study published online ahead of print February 1 in Neurology. Twenty-five participants were evaluated for transplant, and 24 participants underwent high-dose immunosuppressive therapy and hematopoietic cell transplantation. Median follow-up was 62 months. Event-free survival (ie, survival without disability progression, relapse, or new lesions on MRI) was 69.2%. Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3%, 86.9%, and 86.3%, respectively. Adverse events were consistent with toxic effects associated with high-dose immunosuppressive therapy and hematopoietic cell transplantation, including cytopenia and infection. Neurologic disability improved among participants who survived and completed the study, with a median change in Expanded Disability Status Scale score of -0.5.
Estimated glomerular filtration rate on admission is an important predictor of poststroke short-term outcomes, according to a cohort study published in the February issue of Stroke. Investigators analyzed data from 232,236 patients with ischemic stroke in Get With The Guidelines-Stroke. Patients were age 65 or older. In all, 11.8% of patients died during hospitalization or were discharged to hospice, and 38.6% were discharged home. Renal dysfunction was independently associated with an increased risk of in-hospital mortality that was highest among those with an estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 without dialysis (odds ratio, 2.52). In addition, receiving dialysis and having an estimated glomerular filtration rate of less than 29 mL/min/1.73 m2 were associated with lower odds of being discharged home.
Habitual sleep duration in monozygotic twins may be associated with distinct patterns of differential gene expression and pathway enrichment that affect immune response, according to a study published in the January issue of Sleep. Investigators selected 11 healthy monozygotic twin pairs (82% female; mean age, 42.7) based on subjective sleep duration discordance and then monitored participants' habitual sleep duration with two weeks of wrist actigraphy. Peripheral blood leukocyte RNA from fasting blood samples was obtained on the final day of actigraphic measurement and hybridized to Illumina humanHT-12 microarrays. The mean 24-hour sleep duration of the total sample was 439.2 minutes. Mean within-pair sleep duration difference per 24 hours was 64.4 minutes. The researchers observed distinctive pathway enrichment based on sleep duration differences. Habitual short sleep was associated with upregulation of genes involved in transcription, ribosome, translation, and oxidative phosphorylation. Genes that were downregulated with short sleep were highly enriched in immunoinfammatory pathways, as well as developmental programs, coagulation cascade, and cell adhesion.
A brain-computer interface that can decipher the thoughts of people who are unable to communicate may help people with completely locked-in syndrome, according to a study published January 31 in PLOS Biology. Researchers studied a brain-computer interface in four patients with advanced amyotrophic lateral sclerosis and completely locked-in syndrome. Patients responded to "yes" or "no" questions by thinking their answers. The noninvasive brain-computer interface assessed changes in frontocentral cortical oxygenation, measured using functional near-infrared spectroscopy, to determine patients' answers. Patients communicated with an above-chance-level correct response rate over 70%. EEG oscillations and electrooculographic signals did not exceed the chance-level threshold for correct communication.
Using a new noninvasive fMRI method, physicians may be able to predict who is more likely to continue experiencing symptoms months or years after concussion, according to a study published online ahead of print January 13 in the Journal of Neurotrauma. Investigators recruited 75 patients with mild traumatic brain injury (mTBI) and 47 healthy subjects as part of the prospective, multicenter Transforming Research and Clinical Knowledge in TBI pilot study. Researchers compared the functional connectivity of the resting-state networks between patients and controls, and group differences in the interactions between resting-state networks. They assessed patients' cognitive and behavioral performance at six months post injury. Spatial maps of resting-state networks involved in behavioral and cognitive processes differed between patients with mTBI and healthy controls, and these differences were predictive of patients' outcomes at six months post injury.
Among patients with Alzheimer's disease, lifelong bilingualism correlates with functional modulations in crucial neural networks, suggesting neural reserve and compensatory mechanisms, according to a study published online ahead of print January 30 in the Proceedings of the National Academy of Sciences. Eighty-five patients with Alzheimer's disease (45 German-Italian bilingual speakers and 40 monolingual speakers) matched for disease duration were included in this study. Bilingual individuals were on average five years older than people who did not speak another language. Consistent with models of cognitive reserve, cerebral hypometabolism was more severe in the group of bilingual individuals with Alzheimer's disease. Metabolic connectivity analyses supported a neuroprotective effect of bilingualism by showing increased connectivity in the executive control and the default mode networks in bilingual patients, compared with monolingual patients.
The Huntington's Disease Society of America (HDSA), in conjunction with the FDA, conducted two surveys to gather the perspectives of patients with Huntington's disease and juvenile Huntington's disease and their caregivers. Findings from the surveys were published online ahead of print January 24 in the Journal of Huntington's Disease. One survey covered disease symptoms that matter most to people with Huntington's disease, and the other covered current approaches to treatment. The surveys received a total of 3,631 responses. "The frequency and impact of symptoms appear to be felt more by caregivers than individuals with Huntington's Disease, especially when it comes to loss of abilities," said lead investigator George J. Yohrling, PhD, Senior Director of Mission and Scientific Affairs for the HDSA. "There was also a large difference in the perception of symptom frequency between caregivers and individuals with Huntington's disease."
Intentional and unintentional head impacts are independently associated with moderate to severe CNS symptoms in adult amateur soccer players, according to a study published online ahead of print February 1 in Neurology. Soccer players completed an online questionnaire about how often they played soccer during the previous two weeks, how many times they had unintentional head impacts, how many times they headed the ball, and the frequency and severity of CNS symptoms. A total of 222 players completed 470 questionnaires. Heading-related symptoms were reported in 20% of the questionnaires. Heading in the highest quartile was significantly associated with CNS symptoms when controlling for unintentional head impacts. People with unintentional head impacts were at increased risk for CNS symptoms when controlling for heading.
Meditation or music listening may significantly enhance subjective memory function and objective cognitive performance in adults with subjective cognitive decline, according to a study published February 3 in the Journal of Alzheimer's Disease. A total of 60 participants with subjective cognitive decline were randomized to a Kirtan Kriya meditation program or a music listening program. The researchers asked participants to practice 12 minutes each day for three months, then at their discretion for the ensuing three months. At baseline, three months, and six months, researchers measured memory and cognitive functioning. Fifty-three participants completed the study. Both groups showed marked and significant improvements at three months in memory and cognitive performance. At six months, overall gains were maintained or improved, with effect sizes ranging from medium to large.
Yoga and aerobic exercise interventions do not significantly reduce objectively measured sleep disturbances among midlife women who are experiencing hot flashes, according to a study published January 15 in the Journal of Clinical Sleep Medicine. Researchers conducted secondary analyses of a randomized controlled trial in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health network. In the trial, 186 late transition and postmenopausal women ages 40 to 62 with hot flashes were randomized to 12 weeks of yoga, supervised aerobic exercise, or usual activity. Changes in the actigraphic sleep outcomes from baseline to weeks 11 to 12 were small and did not differ between groups. An exploratory analysis suggested that women with poor self-reported sleep quality at baseline potentially had improved sleep stability following yoga.
Longitudinal data provide strong evidence of cognitive aging in midlife women, with substantial within-woman declines in processing speed and memory, according to a study published January 3 in PLoS One. Researchers used data from 2,124 participants from the Study of Women's Health Across the Nation. Participants completed annual tests of processing speed, verbal episodic memory, and working memory. Average age at baseline was 54. There were 7,185 cognitive assessments with a median follow-up time of 6.5 years. In mixed effects regression, adjusted for practice effects, retention, menopause symptoms, and covariates, scores on two of four cognition tests declined. Mean decline in cognitive speed was 0.28 per year or 4.9% in 10 years, and mean decline in verbal episodic memory (delayed testing) was 0.02 per year or 2% in 10 years.
The FDA has approved Emflaza (deflazacort) for the treatment of Duchenne muscular dystrophy in patients age 5 and older. The corticosteroid is available in an immediate-release tablet formulation (6 mg, 18 mg, 30 mg, and 36 mg) as well as an oral suspension formulation (22.75 mg/mL). In a multicenter, randomized, double-blind, placebo-controlled study of 196 male pediatric patients, patients who received deflazacort had improved muscle strength at 12 weeks, compared with patients who received placebo. Through the 52-week study, an overall stability in average muscle strength was maintained in patients who received deflazacort. Results on several timed measures of patient function (eg, time to stand from supine, time to climb four stairs, and time to walk or run 30 feet) also numerically favored deflazacort 0.9 mg/kg/day at week 12. Marathon Pharmaceuticals, headquartered in Northbrook, Illinois, markets Emflaza.
—Kimberly Williams
Serum levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were unable to distinguish between patients with mild traumatic brain injury (mTBI) and patients with orthopedic trauma, according to a study published online ahead of print January 27 in the Journal of Neurotrauma. The results cast doubt on the value of these proposed biomarkers in diagnosing mTBI, the researchers said. Serum UCH-L1 and GFAP were longitudinally measured in 73 patients with acute orthopedic injury and in 93 patients with CT-negative mTBI when they arrived at the hospital and one, two, three, and seven days after admission, as well as at a follow-up visit between three and 10 months after injury. Levels of GFAP were higher in patients with orthopedic trauma than in patients with mTBI on arrival, but subsequent levels did not differ between groups. Levels of UCH-L1 did not significantly differ between the groups.
High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation without maintenance therapy is effective for inducing long-term sustained remission of active relapsing-remitting multiple sclerosis at five years, according to a study published online ahead of print February 1 in Neurology. Twenty-five participants were evaluated for transplant, and 24 participants underwent high-dose immunosuppressive therapy and hematopoietic cell transplantation. Median follow-up was 62 months. Event-free survival (ie, survival without disability progression, relapse, or new lesions on MRI) was 69.2%. Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3%, 86.9%, and 86.3%, respectively. Adverse events were consistent with toxic effects associated with high-dose immunosuppressive therapy and hematopoietic cell transplantation, including cytopenia and infection. Neurologic disability improved among participants who survived and completed the study, with a median change in Expanded Disability Status Scale score of -0.5.
Estimated glomerular filtration rate on admission is an important predictor of poststroke short-term outcomes, according to a cohort study published in the February issue of Stroke. Investigators analyzed data from 232,236 patients with ischemic stroke in Get With The Guidelines-Stroke. Patients were age 65 or older. In all, 11.8% of patients died during hospitalization or were discharged to hospice, and 38.6% were discharged home. Renal dysfunction was independently associated with an increased risk of in-hospital mortality that was highest among those with an estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 without dialysis (odds ratio, 2.52). In addition, receiving dialysis and having an estimated glomerular filtration rate of less than 29 mL/min/1.73 m2 were associated with lower odds of being discharged home.
Habitual sleep duration in monozygotic twins may be associated with distinct patterns of differential gene expression and pathway enrichment that affect immune response, according to a study published in the January issue of Sleep. Investigators selected 11 healthy monozygotic twin pairs (82% female; mean age, 42.7) based on subjective sleep duration discordance and then monitored participants' habitual sleep duration with two weeks of wrist actigraphy. Peripheral blood leukocyte RNA from fasting blood samples was obtained on the final day of actigraphic measurement and hybridized to Illumina humanHT-12 microarrays. The mean 24-hour sleep duration of the total sample was 439.2 minutes. Mean within-pair sleep duration difference per 24 hours was 64.4 minutes. The researchers observed distinctive pathway enrichment based on sleep duration differences. Habitual short sleep was associated with upregulation of genes involved in transcription, ribosome, translation, and oxidative phosphorylation. Genes that were downregulated with short sleep were highly enriched in immunoinfammatory pathways, as well as developmental programs, coagulation cascade, and cell adhesion.
A brain-computer interface that can decipher the thoughts of people who are unable to communicate may help people with completely locked-in syndrome, according to a study published January 31 in PLOS Biology. Researchers studied a brain-computer interface in four patients with advanced amyotrophic lateral sclerosis and completely locked-in syndrome. Patients responded to "yes" or "no" questions by thinking their answers. The noninvasive brain-computer interface assessed changes in frontocentral cortical oxygenation, measured using functional near-infrared spectroscopy, to determine patients' answers. Patients communicated with an above-chance-level correct response rate over 70%. EEG oscillations and electrooculographic signals did not exceed the chance-level threshold for correct communication.
Using a new noninvasive fMRI method, physicians may be able to predict who is more likely to continue experiencing symptoms months or years after concussion, according to a study published online ahead of print January 13 in the Journal of Neurotrauma. Investigators recruited 75 patients with mild traumatic brain injury (mTBI) and 47 healthy subjects as part of the prospective, multicenter Transforming Research and Clinical Knowledge in TBI pilot study. Researchers compared the functional connectivity of the resting-state networks between patients and controls, and group differences in the interactions between resting-state networks. They assessed patients' cognitive and behavioral performance at six months post injury. Spatial maps of resting-state networks involved in behavioral and cognitive processes differed between patients with mTBI and healthy controls, and these differences were predictive of patients' outcomes at six months post injury.
Among patients with Alzheimer's disease, lifelong bilingualism correlates with functional modulations in crucial neural networks, suggesting neural reserve and compensatory mechanisms, according to a study published online ahead of print January 30 in the Proceedings of the National Academy of Sciences. Eighty-five patients with Alzheimer's disease (45 German-Italian bilingual speakers and 40 monolingual speakers) matched for disease duration were included in this study. Bilingual individuals were on average five years older than people who did not speak another language. Consistent with models of cognitive reserve, cerebral hypometabolism was more severe in the group of bilingual individuals with Alzheimer's disease. Metabolic connectivity analyses supported a neuroprotective effect of bilingualism by showing increased connectivity in the executive control and the default mode networks in bilingual patients, compared with monolingual patients.
The Huntington's Disease Society of America (HDSA), in conjunction with the FDA, conducted two surveys to gather the perspectives of patients with Huntington's disease and juvenile Huntington's disease and their caregivers. Findings from the surveys were published online ahead of print January 24 in the Journal of Huntington's Disease. One survey covered disease symptoms that matter most to people with Huntington's disease, and the other covered current approaches to treatment. The surveys received a total of 3,631 responses. "The frequency and impact of symptoms appear to be felt more by caregivers than individuals with Huntington's Disease, especially when it comes to loss of abilities," said lead investigator George J. Yohrling, PhD, Senior Director of Mission and Scientific Affairs for the HDSA. "There was also a large difference in the perception of symptom frequency between caregivers and individuals with Huntington's disease."
Intentional and unintentional head impacts are independently associated with moderate to severe CNS symptoms in adult amateur soccer players, according to a study published online ahead of print February 1 in Neurology. Soccer players completed an online questionnaire about how often they played soccer during the previous two weeks, how many times they had unintentional head impacts, how many times they headed the ball, and the frequency and severity of CNS symptoms. A total of 222 players completed 470 questionnaires. Heading-related symptoms were reported in 20% of the questionnaires. Heading in the highest quartile was significantly associated with CNS symptoms when controlling for unintentional head impacts. People with unintentional head impacts were at increased risk for CNS symptoms when controlling for heading.
Meditation or music listening may significantly enhance subjective memory function and objective cognitive performance in adults with subjective cognitive decline, according to a study published February 3 in the Journal of Alzheimer's Disease. A total of 60 participants with subjective cognitive decline were randomized to a Kirtan Kriya meditation program or a music listening program. The researchers asked participants to practice 12 minutes each day for three months, then at their discretion for the ensuing three months. At baseline, three months, and six months, researchers measured memory and cognitive functioning. Fifty-three participants completed the study. Both groups showed marked and significant improvements at three months in memory and cognitive performance. At six months, overall gains were maintained or improved, with effect sizes ranging from medium to large.
Yoga and aerobic exercise interventions do not significantly reduce objectively measured sleep disturbances among midlife women who are experiencing hot flashes, according to a study published January 15 in the Journal of Clinical Sleep Medicine. Researchers conducted secondary analyses of a randomized controlled trial in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health network. In the trial, 186 late transition and postmenopausal women ages 40 to 62 with hot flashes were randomized to 12 weeks of yoga, supervised aerobic exercise, or usual activity. Changes in the actigraphic sleep outcomes from baseline to weeks 11 to 12 were small and did not differ between groups. An exploratory analysis suggested that women with poor self-reported sleep quality at baseline potentially had improved sleep stability following yoga.
Longitudinal data provide strong evidence of cognitive aging in midlife women, with substantial within-woman declines in processing speed and memory, according to a study published January 3 in PLoS One. Researchers used data from 2,124 participants from the Study of Women's Health Across the Nation. Participants completed annual tests of processing speed, verbal episodic memory, and working memory. Average age at baseline was 54. There were 7,185 cognitive assessments with a median follow-up time of 6.5 years. In mixed effects regression, adjusted for practice effects, retention, menopause symptoms, and covariates, scores on two of four cognition tests declined. Mean decline in cognitive speed was 0.28 per year or 4.9% in 10 years, and mean decline in verbal episodic memory (delayed testing) was 0.02 per year or 2% in 10 years.
The FDA has approved Emflaza (deflazacort) for the treatment of Duchenne muscular dystrophy in patients age 5 and older. The corticosteroid is available in an immediate-release tablet formulation (6 mg, 18 mg, 30 mg, and 36 mg) as well as an oral suspension formulation (22.75 mg/mL). In a multicenter, randomized, double-blind, placebo-controlled study of 196 male pediatric patients, patients who received deflazacort had improved muscle strength at 12 weeks, compared with patients who received placebo. Through the 52-week study, an overall stability in average muscle strength was maintained in patients who received deflazacort. Results on several timed measures of patient function (eg, time to stand from supine, time to climb four stairs, and time to walk or run 30 feet) also numerically favored deflazacort 0.9 mg/kg/day at week 12. Marathon Pharmaceuticals, headquartered in Northbrook, Illinois, markets Emflaza.
—Kimberly Williams
Serum levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were unable to distinguish between patients with mild traumatic brain injury (mTBI) and patients with orthopedic trauma, according to a study published online ahead of print January 27 in the Journal of Neurotrauma. The results cast doubt on the value of these proposed biomarkers in diagnosing mTBI, the researchers said. Serum UCH-L1 and GFAP were longitudinally measured in 73 patients with acute orthopedic injury and in 93 patients with CT-negative mTBI when they arrived at the hospital and one, two, three, and seven days after admission, as well as at a follow-up visit between three and 10 months after injury. Levels of GFAP were higher in patients with orthopedic trauma than in patients with mTBI on arrival, but subsequent levels did not differ between groups. Levels of UCH-L1 did not significantly differ between the groups.
High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation without maintenance therapy is effective for inducing long-term sustained remission of active relapsing-remitting multiple sclerosis at five years, according to a study published online ahead of print February 1 in Neurology. Twenty-five participants were evaluated for transplant, and 24 participants underwent high-dose immunosuppressive therapy and hematopoietic cell transplantation. Median follow-up was 62 months. Event-free survival (ie, survival without disability progression, relapse, or new lesions on MRI) was 69.2%. Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3%, 86.9%, and 86.3%, respectively. Adverse events were consistent with toxic effects associated with high-dose immunosuppressive therapy and hematopoietic cell transplantation, including cytopenia and infection. Neurologic disability improved among participants who survived and completed the study, with a median change in Expanded Disability Status Scale score of -0.5.
Estimated glomerular filtration rate on admission is an important predictor of poststroke short-term outcomes, according to a cohort study published in the February issue of Stroke. Investigators analyzed data from 232,236 patients with ischemic stroke in Get With The Guidelines-Stroke. Patients were age 65 or older. In all, 11.8% of patients died during hospitalization or were discharged to hospice, and 38.6% were discharged home. Renal dysfunction was independently associated with an increased risk of in-hospital mortality that was highest among those with an estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 without dialysis (odds ratio, 2.52). In addition, receiving dialysis and having an estimated glomerular filtration rate of less than 29 mL/min/1.73 m2 were associated with lower odds of being discharged home.
Habitual sleep duration in monozygotic twins may be associated with distinct patterns of differential gene expression and pathway enrichment that affect immune response, according to a study published in the January issue of Sleep. Investigators selected 11 healthy monozygotic twin pairs (82% female; mean age, 42.7) based on subjective sleep duration discordance and then monitored participants' habitual sleep duration with two weeks of wrist actigraphy. Peripheral blood leukocyte RNA from fasting blood samples was obtained on the final day of actigraphic measurement and hybridized to Illumina humanHT-12 microarrays. The mean 24-hour sleep duration of the total sample was 439.2 minutes. Mean within-pair sleep duration difference per 24 hours was 64.4 minutes. The researchers observed distinctive pathway enrichment based on sleep duration differences. Habitual short sleep was associated with upregulation of genes involved in transcription, ribosome, translation, and oxidative phosphorylation. Genes that were downregulated with short sleep were highly enriched in immunoinfammatory pathways, as well as developmental programs, coagulation cascade, and cell adhesion.
A brain-computer interface that can decipher the thoughts of people who are unable to communicate may help people with completely locked-in syndrome, according to a study published January 31 in PLOS Biology. Researchers studied a brain-computer interface in four patients with advanced amyotrophic lateral sclerosis and completely locked-in syndrome. Patients responded to "yes" or "no" questions by thinking their answers. The noninvasive brain-computer interface assessed changes in frontocentral cortical oxygenation, measured using functional near-infrared spectroscopy, to determine patients' answers. Patients communicated with an above-chance-level correct response rate over 70%. EEG oscillations and electrooculographic signals did not exceed the chance-level threshold for correct communication.
Using a new noninvasive fMRI method, physicians may be able to predict who is more likely to continue experiencing symptoms months or years after concussion, according to a study published online ahead of print January 13 in the Journal of Neurotrauma. Investigators recruited 75 patients with mild traumatic brain injury (mTBI) and 47 healthy subjects as part of the prospective, multicenter Transforming Research and Clinical Knowledge in TBI pilot study. Researchers compared the functional connectivity of the resting-state networks between patients and controls, and group differences in the interactions between resting-state networks. They assessed patients' cognitive and behavioral performance at six months post injury. Spatial maps of resting-state networks involved in behavioral and cognitive processes differed between patients with mTBI and healthy controls, and these differences were predictive of patients' outcomes at six months post injury.
Among patients with Alzheimer's disease, lifelong bilingualism correlates with functional modulations in crucial neural networks, suggesting neural reserve and compensatory mechanisms, according to a study published online ahead of print January 30 in the Proceedings of the National Academy of Sciences. Eighty-five patients with Alzheimer's disease (45 German-Italian bilingual speakers and 40 monolingual speakers) matched for disease duration were included in this study. Bilingual individuals were on average five years older than people who did not speak another language. Consistent with models of cognitive reserve, cerebral hypometabolism was more severe in the group of bilingual individuals with Alzheimer's disease. Metabolic connectivity analyses supported a neuroprotective effect of bilingualism by showing increased connectivity in the executive control and the default mode networks in bilingual patients, compared with monolingual patients.
The Huntington's Disease Society of America (HDSA), in conjunction with the FDA, conducted two surveys to gather the perspectives of patients with Huntington's disease and juvenile Huntington's disease and their caregivers. Findings from the surveys were published online ahead of print January 24 in the Journal of Huntington's Disease. One survey covered disease symptoms that matter most to people with Huntington's disease, and the other covered current approaches to treatment. The surveys received a total of 3,631 responses. "The frequency and impact of symptoms appear to be felt more by caregivers than individuals with Huntington's Disease, especially when it comes to loss of abilities," said lead investigator George J. Yohrling, PhD, Senior Director of Mission and Scientific Affairs for the HDSA. "There was also a large difference in the perception of symptom frequency between caregivers and individuals with Huntington's disease."
Intentional and unintentional head impacts are independently associated with moderate to severe CNS symptoms in adult amateur soccer players, according to a study published online ahead of print February 1 in Neurology. Soccer players completed an online questionnaire about how often they played soccer during the previous two weeks, how many times they had unintentional head impacts, how many times they headed the ball, and the frequency and severity of CNS symptoms. A total of 222 players completed 470 questionnaires. Heading-related symptoms were reported in 20% of the questionnaires. Heading in the highest quartile was significantly associated with CNS symptoms when controlling for unintentional head impacts. People with unintentional head impacts were at increased risk for CNS symptoms when controlling for heading.
Meditation or music listening may significantly enhance subjective memory function and objective cognitive performance in adults with subjective cognitive decline, according to a study published February 3 in the Journal of Alzheimer's Disease. A total of 60 participants with subjective cognitive decline were randomized to a Kirtan Kriya meditation program or a music listening program. The researchers asked participants to practice 12 minutes each day for three months, then at their discretion for the ensuing three months. At baseline, three months, and six months, researchers measured memory and cognitive functioning. Fifty-three participants completed the study. Both groups showed marked and significant improvements at three months in memory and cognitive performance. At six months, overall gains were maintained or improved, with effect sizes ranging from medium to large.
Yoga and aerobic exercise interventions do not significantly reduce objectively measured sleep disturbances among midlife women who are experiencing hot flashes, according to a study published January 15 in the Journal of Clinical Sleep Medicine. Researchers conducted secondary analyses of a randomized controlled trial in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health network. In the trial, 186 late transition and postmenopausal women ages 40 to 62 with hot flashes were randomized to 12 weeks of yoga, supervised aerobic exercise, or usual activity. Changes in the actigraphic sleep outcomes from baseline to weeks 11 to 12 were small and did not differ between groups. An exploratory analysis suggested that women with poor self-reported sleep quality at baseline potentially had improved sleep stability following yoga.
Longitudinal data provide strong evidence of cognitive aging in midlife women, with substantial within-woman declines in processing speed and memory, according to a study published January 3 in PLoS One. Researchers used data from 2,124 participants from the Study of Women's Health Across the Nation. Participants completed annual tests of processing speed, verbal episodic memory, and working memory. Average age at baseline was 54. There were 7,185 cognitive assessments with a median follow-up time of 6.5 years. In mixed effects regression, adjusted for practice effects, retention, menopause symptoms, and covariates, scores on two of four cognition tests declined. Mean decline in cognitive speed was 0.28 per year or 4.9% in 10 years, and mean decline in verbal episodic memory (delayed testing) was 0.02 per year or 2% in 10 years.
The FDA has approved Emflaza (deflazacort) for the treatment of Duchenne muscular dystrophy in patients age 5 and older. The corticosteroid is available in an immediate-release tablet formulation (6 mg, 18 mg, 30 mg, and 36 mg) as well as an oral suspension formulation (22.75 mg/mL). In a multicenter, randomized, double-blind, placebo-controlled study of 196 male pediatric patients, patients who received deflazacort had improved muscle strength at 12 weeks, compared with patients who received placebo. Through the 52-week study, an overall stability in average muscle strength was maintained in patients who received deflazacort. Results on several timed measures of patient function (eg, time to stand from supine, time to climb four stairs, and time to walk or run 30 feet) also numerically favored deflazacort 0.9 mg/kg/day at week 12. Marathon Pharmaceuticals, headquartered in Northbrook, Illinois, markets Emflaza.
—Kimberly Williams
New and Noteworthy Information—February 2017
Concussions may accelerate Alzheimer's disease-related brain atrophy and cognitive decline in people who are at genetic risk for the condition, according to a study published online ahead of print January 11 in Brain. A total of 160 Iraq and Afghanistan war veterans between the ages of 19 and 58, were included in this study. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness. The findings highlight the importance of documenting head injuries, as they may interact with genetic risk to produce negative long-term health consequences, according to the authors.
During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibit abnormal glucose regulation, according to a study published online ahead of print November 14 in Sleep. In all, 686 women with a singleton pregnancy attended a clinic visit at 26 to 28 weeks of gestation, as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index. Two hundred ninety-six women had poor sleep quality, and 77 women were categorized as short sleepers. One hundred thirty-one women were diagnosed with gestational diabetes mellitus. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of gestational diabetes mellitus.
Heightened activity in the amygdala is associated with a greater risk of heart disease and stroke, according to a study published online ahead of print January 12 in Lancet. Investigators followed 293 people age 30 or older without known cardiovascular disease or active cancer disorders, who underwent PET/CT scans between January 1, 2005, and December 31, 2008. Twenty-two people had a cardiovascular disease event during mean follow-up of 3.7 years. Amygdalar activity was associated with increased bone-marrow activity, arterial inflammation, and risk of cardiovascular disease events. In a cross-sectional study of 13 patients who underwent psychometric analysis, amygdalar activity was significantly associated with arterial inflammation, and perceived stress was associated with amygdalar activity, arterial inflammation, and C-reactive protein.
Developing hypertension at an older age may protect against dementia, according to a study published online January 16 in Alzheimer's & Dementia. The study included participants from a population-based longitudinal study of people age 90 and older (The 90+ Study) who were survivors of the Leisure World Cohort Study. Researchers estimated hypertension onset age using patient-reported information. A total of 559 participants without dementia were followed every six months for up to 10 years. Two hundred twenty-four participants developed dementia during follow-up. Compared with participants without hypertension, participants whose hypertension onset age was between 80 and 89 had a lower dementia risk, and participants with an onset age of 90 and older had the lowest risk.
Living close to heavy traffic is associated with a higher incidence of dementia, but not Parkinson's disease or multiple sclerosis, according to a study published online ahead of print January 4 in Lancet. Researchers assembled two population-based cohorts that included adults who resided in Ontario, Canada. Between 2001 and 2012, researchers identified 243,611 incident cases of dementia, 31,577 cases of Parkinson's disease, and 9,247 cases of multiple sclerosis. Dementia risk decreased as people lived farther away from a main road. Overall, there was a 7% higher risk of dementia among people living within 50 meters of a main road, a 4% higher risk at 50 to 100 meters, and a 2% higher risk at 101 to 200 meters. There was no increase in risk in those living more than 200 meters away.
The US Preventive Services Task Force (USPSTF) recommends that all women who are planning to become or capable of becoming pregnant take a daily supplement containing 0.4 mg to 0.8 mg of folic acid, according to a recommendation statement published in the January 10 issue of JAMA. In 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation. The USPSTF evaluated one randomized clinical trial, two cohort studies, eight case-control studies, and two publications from the previous USPSTF review. The task force found no new substantial evidence about the benefits and harms of folic acid supplementation. The USPSTF reaffirmed its 2009 recommendation.
Low serum 25-hydroxyvitamin D (25[OH]D] concentration is associated with markedly higher risk of frequent headache in men, according to a study published January 3 in Scientific Reports. The study consisted of 2,601 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Cross-sectional associations with prevalence of self-reported frequent headache were estimated with adjusted odds ratios. Participants' average serum 25(OH)D concentration was 43.4 nmol/L. A total of 250 men reported frequent (ie, weekly or daily) headache. The average serum 25(OH)D concentration among those with frequent headache was 38.3 nmol/L and 43.9 nmol/L among those without frequent headache, after adjustment for age and year and month of blood draw. After multivariable adjustments, those in the lowest versus the highest serum 25(OH)D quartile had 113% higher odds for frequent headache.
Moderate postlunch napping is associated with better cognition in Chinese older adults, according to a cross-sectional study published online ahead of print December 20, 2016, in the Journal of the American Geriatrics Society. A total of 2,974 people age 65 and older from the China Health and Retirement Longitudinal Study were included in this study. Investigators conducted interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial abilities. Patients reported their postlunch napping habits. Postlunch napping was reported in 57.7% of participants (mean duration, 63 minutes). Cognitive function was significantly associated with napping. Moderate nappers had better overall cognition than nonnappers or extended nappers. Nonnappers also had significantly poorer cognition than short nappers.
Physical exercise may be effective in the prevention of dementia, according to a study published in the January issue of the Journal of Alzheimer's Disease. Researchers assessed the interactive relationship of APOE genotype and physical exercise on dementia risk over a five-year period in 1,646 older adults from the Canadian Study of Health and Aging who were dementia-free at baseline. Physical exercise moderated the relationship between genotype and dementia. For APOE ε4 noncarriers, the odds of developing dementia were higher in nonexercisers than in exercisers (odds ratio, 1.98). For APOE ε4 carriers, the odds of developing dementia were not significantly different between nonexercisers and exercisers. "Given that most individuals are not at genetic risk, physical exercise may be an effective prevention strategy," the researchers concluded.
Lower adherence to a Mediterranean-type diet is predictive of total brain atrophy over a three-year period, according to a study published online ahead of print January 4 in Neurology. Researchers focused on total brain volume, gray matter volume, and cortical thickness. Investigators gathered information on the eating habits of 967 Scottish people at age 70. In regression models adjusting for relevant demographic and physical health indicators, lower adherence to the Mediterranean-type diet was associated with greater three-year reduction in total brain volume. Cross-sectional associations between Mediterranean-type diet and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume.
Children who sustain concussions have a 35% smaller neural response to pitch on average, according to a study published online ahead of print December 22, 2016, in Scientific Reports. Researchers studied 40 children with concussion and a control group. Children with concussion exhibited a signature neural profile. Children had worse representation of the fundamental frequency and smaller, more sluggish neural responses. As the children recovered from their head injuries, their ability to process pitch returned to normal. Neural processing of sound correctly identified 90% of concussion cases and cleared 95% of control cases, suggesting this approach has practical potential as a scalable biologic marker for sports-related concussion and other mild traumatic brain injuries.
People who are homeless sleep less and are more likely to have insomnia and daytime fatigue than people in the general population, according to a study published online ahead of print December 27, 2016, in JAMA Internal Medicine. Investigators analyzed survey responses from 3,453 people who were homeless (2,068 men; mean age, 39.8) and compared them with responses from individuals in the general population. Homeless people reported significantly shorter total sleep time than the general population (6 h 31 min vs 7 h 9 min). Eight percent reported less than four hours of total sleep time over the past 24 hours, compared with 3% of the general population. Homeless women were twice as likely as men to report that they slept less than four hours. Furthermore, insomnia was reported by 41% of homeless people, compared with 19% of controls.
—Kimberly Williams
Concussions may accelerate Alzheimer's disease-related brain atrophy and cognitive decline in people who are at genetic risk for the condition, according to a study published online ahead of print January 11 in Brain. A total of 160 Iraq and Afghanistan war veterans between the ages of 19 and 58, were included in this study. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness. The findings highlight the importance of documenting head injuries, as they may interact with genetic risk to produce negative long-term health consequences, according to the authors.
During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibit abnormal glucose regulation, according to a study published online ahead of print November 14 in Sleep. In all, 686 women with a singleton pregnancy attended a clinic visit at 26 to 28 weeks of gestation, as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index. Two hundred ninety-six women had poor sleep quality, and 77 women were categorized as short sleepers. One hundred thirty-one women were diagnosed with gestational diabetes mellitus. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of gestational diabetes mellitus.
Heightened activity in the amygdala is associated with a greater risk of heart disease and stroke, according to a study published online ahead of print January 12 in Lancet. Investigators followed 293 people age 30 or older without known cardiovascular disease or active cancer disorders, who underwent PET/CT scans between January 1, 2005, and December 31, 2008. Twenty-two people had a cardiovascular disease event during mean follow-up of 3.7 years. Amygdalar activity was associated with increased bone-marrow activity, arterial inflammation, and risk of cardiovascular disease events. In a cross-sectional study of 13 patients who underwent psychometric analysis, amygdalar activity was significantly associated with arterial inflammation, and perceived stress was associated with amygdalar activity, arterial inflammation, and C-reactive protein.
Developing hypertension at an older age may protect against dementia, according to a study published online January 16 in Alzheimer's & Dementia. The study included participants from a population-based longitudinal study of people age 90 and older (The 90+ Study) who were survivors of the Leisure World Cohort Study. Researchers estimated hypertension onset age using patient-reported information. A total of 559 participants without dementia were followed every six months for up to 10 years. Two hundred twenty-four participants developed dementia during follow-up. Compared with participants without hypertension, participants whose hypertension onset age was between 80 and 89 had a lower dementia risk, and participants with an onset age of 90 and older had the lowest risk.
Living close to heavy traffic is associated with a higher incidence of dementia, but not Parkinson's disease or multiple sclerosis, according to a study published online ahead of print January 4 in Lancet. Researchers assembled two population-based cohorts that included adults who resided in Ontario, Canada. Between 2001 and 2012, researchers identified 243,611 incident cases of dementia, 31,577 cases of Parkinson's disease, and 9,247 cases of multiple sclerosis. Dementia risk decreased as people lived farther away from a main road. Overall, there was a 7% higher risk of dementia among people living within 50 meters of a main road, a 4% higher risk at 50 to 100 meters, and a 2% higher risk at 101 to 200 meters. There was no increase in risk in those living more than 200 meters away.
The US Preventive Services Task Force (USPSTF) recommends that all women who are planning to become or capable of becoming pregnant take a daily supplement containing 0.4 mg to 0.8 mg of folic acid, according to a recommendation statement published in the January 10 issue of JAMA. In 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation. The USPSTF evaluated one randomized clinical trial, two cohort studies, eight case-control studies, and two publications from the previous USPSTF review. The task force found no new substantial evidence about the benefits and harms of folic acid supplementation. The USPSTF reaffirmed its 2009 recommendation.
Low serum 25-hydroxyvitamin D (25[OH]D] concentration is associated with markedly higher risk of frequent headache in men, according to a study published January 3 in Scientific Reports. The study consisted of 2,601 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Cross-sectional associations with prevalence of self-reported frequent headache were estimated with adjusted odds ratios. Participants' average serum 25(OH)D concentration was 43.4 nmol/L. A total of 250 men reported frequent (ie, weekly or daily) headache. The average serum 25(OH)D concentration among those with frequent headache was 38.3 nmol/L and 43.9 nmol/L among those without frequent headache, after adjustment for age and year and month of blood draw. After multivariable adjustments, those in the lowest versus the highest serum 25(OH)D quartile had 113% higher odds for frequent headache.
Moderate postlunch napping is associated with better cognition in Chinese older adults, according to a cross-sectional study published online ahead of print December 20, 2016, in the Journal of the American Geriatrics Society. A total of 2,974 people age 65 and older from the China Health and Retirement Longitudinal Study were included in this study. Investigators conducted interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial abilities. Patients reported their postlunch napping habits. Postlunch napping was reported in 57.7% of participants (mean duration, 63 minutes). Cognitive function was significantly associated with napping. Moderate nappers had better overall cognition than nonnappers or extended nappers. Nonnappers also had significantly poorer cognition than short nappers.
Physical exercise may be effective in the prevention of dementia, according to a study published in the January issue of the Journal of Alzheimer's Disease. Researchers assessed the interactive relationship of APOE genotype and physical exercise on dementia risk over a five-year period in 1,646 older adults from the Canadian Study of Health and Aging who were dementia-free at baseline. Physical exercise moderated the relationship between genotype and dementia. For APOE ε4 noncarriers, the odds of developing dementia were higher in nonexercisers than in exercisers (odds ratio, 1.98). For APOE ε4 carriers, the odds of developing dementia were not significantly different between nonexercisers and exercisers. "Given that most individuals are not at genetic risk, physical exercise may be an effective prevention strategy," the researchers concluded.
Lower adherence to a Mediterranean-type diet is predictive of total brain atrophy over a three-year period, according to a study published online ahead of print January 4 in Neurology. Researchers focused on total brain volume, gray matter volume, and cortical thickness. Investigators gathered information on the eating habits of 967 Scottish people at age 70. In regression models adjusting for relevant demographic and physical health indicators, lower adherence to the Mediterranean-type diet was associated with greater three-year reduction in total brain volume. Cross-sectional associations between Mediterranean-type diet and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume.
Children who sustain concussions have a 35% smaller neural response to pitch on average, according to a study published online ahead of print December 22, 2016, in Scientific Reports. Researchers studied 40 children with concussion and a control group. Children with concussion exhibited a signature neural profile. Children had worse representation of the fundamental frequency and smaller, more sluggish neural responses. As the children recovered from their head injuries, their ability to process pitch returned to normal. Neural processing of sound correctly identified 90% of concussion cases and cleared 95% of control cases, suggesting this approach has practical potential as a scalable biologic marker for sports-related concussion and other mild traumatic brain injuries.
People who are homeless sleep less and are more likely to have insomnia and daytime fatigue than people in the general population, according to a study published online ahead of print December 27, 2016, in JAMA Internal Medicine. Investigators analyzed survey responses from 3,453 people who were homeless (2,068 men; mean age, 39.8) and compared them with responses from individuals in the general population. Homeless people reported significantly shorter total sleep time than the general population (6 h 31 min vs 7 h 9 min). Eight percent reported less than four hours of total sleep time over the past 24 hours, compared with 3% of the general population. Homeless women were twice as likely as men to report that they slept less than four hours. Furthermore, insomnia was reported by 41% of homeless people, compared with 19% of controls.
—Kimberly Williams
Concussions may accelerate Alzheimer's disease-related brain atrophy and cognitive decline in people who are at genetic risk for the condition, according to a study published online ahead of print January 11 in Brain. A total of 160 Iraq and Afghanistan war veterans between the ages of 19 and 58, were included in this study. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness. The findings highlight the importance of documenting head injuries, as they may interact with genetic risk to produce negative long-term health consequences, according to the authors.
During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibit abnormal glucose regulation, according to a study published online ahead of print November 14 in Sleep. In all, 686 women with a singleton pregnancy attended a clinic visit at 26 to 28 weeks of gestation, as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index. Two hundred ninety-six women had poor sleep quality, and 77 women were categorized as short sleepers. One hundred thirty-one women were diagnosed with gestational diabetes mellitus. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of gestational diabetes mellitus.
Heightened activity in the amygdala is associated with a greater risk of heart disease and stroke, according to a study published online ahead of print January 12 in Lancet. Investigators followed 293 people age 30 or older without known cardiovascular disease or active cancer disorders, who underwent PET/CT scans between January 1, 2005, and December 31, 2008. Twenty-two people had a cardiovascular disease event during mean follow-up of 3.7 years. Amygdalar activity was associated with increased bone-marrow activity, arterial inflammation, and risk of cardiovascular disease events. In a cross-sectional study of 13 patients who underwent psychometric analysis, amygdalar activity was significantly associated with arterial inflammation, and perceived stress was associated with amygdalar activity, arterial inflammation, and C-reactive protein.
Developing hypertension at an older age may protect against dementia, according to a study published online January 16 in Alzheimer's & Dementia. The study included participants from a population-based longitudinal study of people age 90 and older (The 90+ Study) who were survivors of the Leisure World Cohort Study. Researchers estimated hypertension onset age using patient-reported information. A total of 559 participants without dementia were followed every six months for up to 10 years. Two hundred twenty-four participants developed dementia during follow-up. Compared with participants without hypertension, participants whose hypertension onset age was between 80 and 89 had a lower dementia risk, and participants with an onset age of 90 and older had the lowest risk.
Living close to heavy traffic is associated with a higher incidence of dementia, but not Parkinson's disease or multiple sclerosis, according to a study published online ahead of print January 4 in Lancet. Researchers assembled two population-based cohorts that included adults who resided in Ontario, Canada. Between 2001 and 2012, researchers identified 243,611 incident cases of dementia, 31,577 cases of Parkinson's disease, and 9,247 cases of multiple sclerosis. Dementia risk decreased as people lived farther away from a main road. Overall, there was a 7% higher risk of dementia among people living within 50 meters of a main road, a 4% higher risk at 50 to 100 meters, and a 2% higher risk at 101 to 200 meters. There was no increase in risk in those living more than 200 meters away.
The US Preventive Services Task Force (USPSTF) recommends that all women who are planning to become or capable of becoming pregnant take a daily supplement containing 0.4 mg to 0.8 mg of folic acid, according to a recommendation statement published in the January 10 issue of JAMA. In 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation. The USPSTF evaluated one randomized clinical trial, two cohort studies, eight case-control studies, and two publications from the previous USPSTF review. The task force found no new substantial evidence about the benefits and harms of folic acid supplementation. The USPSTF reaffirmed its 2009 recommendation.
Low serum 25-hydroxyvitamin D (25[OH]D] concentration is associated with markedly higher risk of frequent headache in men, according to a study published January 3 in Scientific Reports. The study consisted of 2,601 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Cross-sectional associations with prevalence of self-reported frequent headache were estimated with adjusted odds ratios. Participants' average serum 25(OH)D concentration was 43.4 nmol/L. A total of 250 men reported frequent (ie, weekly or daily) headache. The average serum 25(OH)D concentration among those with frequent headache was 38.3 nmol/L and 43.9 nmol/L among those without frequent headache, after adjustment for age and year and month of blood draw. After multivariable adjustments, those in the lowest versus the highest serum 25(OH)D quartile had 113% higher odds for frequent headache.
Moderate postlunch napping is associated with better cognition in Chinese older adults, according to a cross-sectional study published online ahead of print December 20, 2016, in the Journal of the American Geriatrics Society. A total of 2,974 people age 65 and older from the China Health and Retirement Longitudinal Study were included in this study. Investigators conducted interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial abilities. Patients reported their postlunch napping habits. Postlunch napping was reported in 57.7% of participants (mean duration, 63 minutes). Cognitive function was significantly associated with napping. Moderate nappers had better overall cognition than nonnappers or extended nappers. Nonnappers also had significantly poorer cognition than short nappers.
Physical exercise may be effective in the prevention of dementia, according to a study published in the January issue of the Journal of Alzheimer's Disease. Researchers assessed the interactive relationship of APOE genotype and physical exercise on dementia risk over a five-year period in 1,646 older adults from the Canadian Study of Health and Aging who were dementia-free at baseline. Physical exercise moderated the relationship between genotype and dementia. For APOE ε4 noncarriers, the odds of developing dementia were higher in nonexercisers than in exercisers (odds ratio, 1.98). For APOE ε4 carriers, the odds of developing dementia were not significantly different between nonexercisers and exercisers. "Given that most individuals are not at genetic risk, physical exercise may be an effective prevention strategy," the researchers concluded.
Lower adherence to a Mediterranean-type diet is predictive of total brain atrophy over a three-year period, according to a study published online ahead of print January 4 in Neurology. Researchers focused on total brain volume, gray matter volume, and cortical thickness. Investigators gathered information on the eating habits of 967 Scottish people at age 70. In regression models adjusting for relevant demographic and physical health indicators, lower adherence to the Mediterranean-type diet was associated with greater three-year reduction in total brain volume. Cross-sectional associations between Mediterranean-type diet and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume.
Children who sustain concussions have a 35% smaller neural response to pitch on average, according to a study published online ahead of print December 22, 2016, in Scientific Reports. Researchers studied 40 children with concussion and a control group. Children with concussion exhibited a signature neural profile. Children had worse representation of the fundamental frequency and smaller, more sluggish neural responses. As the children recovered from their head injuries, their ability to process pitch returned to normal. Neural processing of sound correctly identified 90% of concussion cases and cleared 95% of control cases, suggesting this approach has practical potential as a scalable biologic marker for sports-related concussion and other mild traumatic brain injuries.
People who are homeless sleep less and are more likely to have insomnia and daytime fatigue than people in the general population, according to a study published online ahead of print December 27, 2016, in JAMA Internal Medicine. Investigators analyzed survey responses from 3,453 people who were homeless (2,068 men; mean age, 39.8) and compared them with responses from individuals in the general population. Homeless people reported significantly shorter total sleep time than the general population (6 h 31 min vs 7 h 9 min). Eight percent reported less than four hours of total sleep time over the past 24 hours, compared with 3% of the general population. Homeless women were twice as likely as men to report that they slept less than four hours. Furthermore, insomnia was reported by 41% of homeless people, compared with 19% of controls.
—Kimberly Williams
Radiosurgery found not superior to open surgery for temporal lobe epilepsy
HOUSTON – Despite enrollment difficulties that limited the study, a recently completed randomized trial comparing radiosurgery with open lobectomy to treat temporal lobe epilepsy offers some guidance for patients and their physicians.
Radiosurgery’s noninferiority to open lobectomy couldn’t be shown from the ROSE (Radiosurgery or Open Surgery for Epilepsy) trial, but language deficits were similar – and quite small – by 3 years after either procedure. Expected visual field deficits were similar in each procedure as well. However, since the trial didn’t reach its target enrollment, several primary outcome measures could not be fully assessed.
On the face of it, radiosurgery has significant appeal. Although open resective surgery is effective, there’s still some risk of infection and blood loss, and neuropsychological changes as well as other focal neurologic deficits are seen. Still, the study saw many challenges, but the largest, according to the investigators, was in recruitment. “Patients like to choose,” said Nicholas M. Barbaro, MD, chair of the department of neurosurgery at Indiana University, Indianapolis. Dr. Barbaro, one of several ROSE coinvestigators who presented the study findings at the annual meeting of the American Epilepsy Society, noted that if patients felt that lobectomy was the best choice, then there would be no incentive to enter a trial where they might be randomized to radiosurgery. Also, he said, some patients might be reluctant to be irradiated, fearing short-term or long-term toxicity.
Trial hypotheses and protocols
The ROSE trial aimed to show that stereotactic radiosurgery (SRS) would not be inferior to anterior temporal lobectomy (ATL) in achieving a seizure-free state by months 25-36 post procedure. The lag to response after radiosurgery is about 1 year; seizure freedom, defined as 12 consecutive months with no seizures, was assessed from months 25 to 36 of the study for the primary outcome of seizure freedom.
Investigators also hypothesized that fewer SRS patients would have significant reductions in measures of language function; further, they predicted that patients in both treatment arms would experience improvements in quality of life (QOL), and that QOL would improve as seizure freedom increased. Finally, the trial sought to show that SRS was cost effective, compared with ATL, with the marginal cost-utility ratio dropping below $50,000 per quality-adjusted life-year (QALY).
Patients in the ATL arm received a standard “Spencer” ATL, with adequacy of resection assessed by MRI performed 3 months after surgery. An inadequate resection would have been classified as an adverse event, but all ATL patients had an adequate resection by study criteria, and all those whose histopathology was available (n = 20) had some hippocampal sclerosis.
Patients in the SRS arm had the amygdala and anterior 2 cm of the hippocampus, as well as the adjacent parahippocampal gyrus, irradiated. This resulted in a total treatment volume ranging from 5.5 to 7.5 cc. Patients received 4 Gy to the 50% isodose line, and treatment could involve an unlimited number of isocenters. The brain stem could receive no more than 10 Gy and the optic nerve and chiasm no more than 8 Gy. All treatment plans were cleared by the ROSE steering committee. The SRS patients had some variation in dose and volumes treated, but all were within the approved limits of the study.
Trial outcomes
As expected, the surgery arm achieved rapid seizure remission, while the SRS arm saw a steady increase in seizure-free numbers beginning at about 12 months after surgery. During study months 25-36, 78% of the ATL arm and 52% of the SRS arm were seizure free. “The null hypothesis of inferiority of SRS was not rejected,” said Mark Quigg, MD, professor of neurology at the University of Virginia, Charlottesville.
Most patients in both groups had no or minimal changes in verbal memory, with no significant differences between the groups at 36 months after treatment.
QOL measures improved rapidly for those who received open surgery, and more slowly for those in the radiosurgery arm, a pattern “consistent with the known association between improved seizure control and quality of life,” said John Langfitt, PhD, a neuropsychologist and professor of neurology and psychiatry at the University of Rochester (N.Y.). However, the study was underpowered to show noninferiority of SRS for QOL measures at 36 months.
“There was a preliminary trend toward reduced health care use over time in the open surgery arm,” said Dr. Langfitt, again noting that the earlier seizure control achieved in surgery reduced health care utilization for that group sooner than for the SRS group. “The power may be limited by sample size and the tendency of utilization to be highly skewed,” he said.
Also as expected, the ATL arm saw early surgery-related adverse events such as scalp wound infections, subdural hematomas, and deep vein thromboses. These were infrequent overall. In contrast, the SRS group saw more cerebral edema–related adverse events during months 9-18, with headaches, new neurologic deficits, and transient seizure exacerbation.
All but three patients received postoperative visual field testing. Of the patients receiving SRS, 34% (10 of 29) had an upper superior quadrant visual field defect, as did 42% (11 of 26) of patients in the ATL arm.
Since the primary treating surgeon and neurologist could not be blinded as to study arm, another neurologist who was blinded was responsible for assessing the outcome measures, and also could identify adverse events. The trial’s steering committee was also blinded to ongoing outcomes.
Pilot study results
A pilot study had previously found that SRS was comparable to the efficacy that had been seen in larger, prospective trials of open surgery, with about two-thirds of patients seizure free at 36 months. Although most patients experienced brief exacerbation of auras or complex partial seizures after radiosurgery, visual field defects were similar to those experienced by patients undergoing standard ATL. Overall, neuropsychological outcomes for those undergoing SRS in the pilot were good, with a low incidence of declines in language and verbal memory function of the dominant hemisphere, and no short-term affective changes were seen. SRS patients who were seizure free after the procedure experienced a significant improvement in QOL.
The promising pilot results contrasted with the limited findings of the ROSE study. In regard to seizure freedom in ROSE, said Dr. Quigg, “The data appear to show that radiosurgery is inferior to ATL, but the low power of the study means that we cannot conclude this with sufficient confidence. Nor can we conclude that the two treatments are noninferior.”
The study was partially funded by Elekta, the manufacturer of the Gamma Knife radiosurgery device used in the study. Dr. Barbaro reported no other disclosures. Dr. Langfitt reported being a consultant for Monteris. Dr. Quigg reported being an investigator for several antiepileptic drug trials sponsored by pharmaceutical companies.
[email protected]
On Twitter @karioakes
HOUSTON – Despite enrollment difficulties that limited the study, a recently completed randomized trial comparing radiosurgery with open lobectomy to treat temporal lobe epilepsy offers some guidance for patients and their physicians.
Radiosurgery’s noninferiority to open lobectomy couldn’t be shown from the ROSE (Radiosurgery or Open Surgery for Epilepsy) trial, but language deficits were similar – and quite small – by 3 years after either procedure. Expected visual field deficits were similar in each procedure as well. However, since the trial didn’t reach its target enrollment, several primary outcome measures could not be fully assessed.
On the face of it, radiosurgery has significant appeal. Although open resective surgery is effective, there’s still some risk of infection and blood loss, and neuropsychological changes as well as other focal neurologic deficits are seen. Still, the study saw many challenges, but the largest, according to the investigators, was in recruitment. “Patients like to choose,” said Nicholas M. Barbaro, MD, chair of the department of neurosurgery at Indiana University, Indianapolis. Dr. Barbaro, one of several ROSE coinvestigators who presented the study findings at the annual meeting of the American Epilepsy Society, noted that if patients felt that lobectomy was the best choice, then there would be no incentive to enter a trial where they might be randomized to radiosurgery. Also, he said, some patients might be reluctant to be irradiated, fearing short-term or long-term toxicity.
Trial hypotheses and protocols
The ROSE trial aimed to show that stereotactic radiosurgery (SRS) would not be inferior to anterior temporal lobectomy (ATL) in achieving a seizure-free state by months 25-36 post procedure. The lag to response after radiosurgery is about 1 year; seizure freedom, defined as 12 consecutive months with no seizures, was assessed from months 25 to 36 of the study for the primary outcome of seizure freedom.
Investigators also hypothesized that fewer SRS patients would have significant reductions in measures of language function; further, they predicted that patients in both treatment arms would experience improvements in quality of life (QOL), and that QOL would improve as seizure freedom increased. Finally, the trial sought to show that SRS was cost effective, compared with ATL, with the marginal cost-utility ratio dropping below $50,000 per quality-adjusted life-year (QALY).
Patients in the ATL arm received a standard “Spencer” ATL, with adequacy of resection assessed by MRI performed 3 months after surgery. An inadequate resection would have been classified as an adverse event, but all ATL patients had an adequate resection by study criteria, and all those whose histopathology was available (n = 20) had some hippocampal sclerosis.
Patients in the SRS arm had the amygdala and anterior 2 cm of the hippocampus, as well as the adjacent parahippocampal gyrus, irradiated. This resulted in a total treatment volume ranging from 5.5 to 7.5 cc. Patients received 4 Gy to the 50% isodose line, and treatment could involve an unlimited number of isocenters. The brain stem could receive no more than 10 Gy and the optic nerve and chiasm no more than 8 Gy. All treatment plans were cleared by the ROSE steering committee. The SRS patients had some variation in dose and volumes treated, but all were within the approved limits of the study.
Trial outcomes
As expected, the surgery arm achieved rapid seizure remission, while the SRS arm saw a steady increase in seizure-free numbers beginning at about 12 months after surgery. During study months 25-36, 78% of the ATL arm and 52% of the SRS arm were seizure free. “The null hypothesis of inferiority of SRS was not rejected,” said Mark Quigg, MD, professor of neurology at the University of Virginia, Charlottesville.
Most patients in both groups had no or minimal changes in verbal memory, with no significant differences between the groups at 36 months after treatment.
QOL measures improved rapidly for those who received open surgery, and more slowly for those in the radiosurgery arm, a pattern “consistent with the known association between improved seizure control and quality of life,” said John Langfitt, PhD, a neuropsychologist and professor of neurology and psychiatry at the University of Rochester (N.Y.). However, the study was underpowered to show noninferiority of SRS for QOL measures at 36 months.
“There was a preliminary trend toward reduced health care use over time in the open surgery arm,” said Dr. Langfitt, again noting that the earlier seizure control achieved in surgery reduced health care utilization for that group sooner than for the SRS group. “The power may be limited by sample size and the tendency of utilization to be highly skewed,” he said.
Also as expected, the ATL arm saw early surgery-related adverse events such as scalp wound infections, subdural hematomas, and deep vein thromboses. These were infrequent overall. In contrast, the SRS group saw more cerebral edema–related adverse events during months 9-18, with headaches, new neurologic deficits, and transient seizure exacerbation.
All but three patients received postoperative visual field testing. Of the patients receiving SRS, 34% (10 of 29) had an upper superior quadrant visual field defect, as did 42% (11 of 26) of patients in the ATL arm.
Since the primary treating surgeon and neurologist could not be blinded as to study arm, another neurologist who was blinded was responsible for assessing the outcome measures, and also could identify adverse events. The trial’s steering committee was also blinded to ongoing outcomes.
Pilot study results
A pilot study had previously found that SRS was comparable to the efficacy that had been seen in larger, prospective trials of open surgery, with about two-thirds of patients seizure free at 36 months. Although most patients experienced brief exacerbation of auras or complex partial seizures after radiosurgery, visual field defects were similar to those experienced by patients undergoing standard ATL. Overall, neuropsychological outcomes for those undergoing SRS in the pilot were good, with a low incidence of declines in language and verbal memory function of the dominant hemisphere, and no short-term affective changes were seen. SRS patients who were seizure free after the procedure experienced a significant improvement in QOL.
The promising pilot results contrasted with the limited findings of the ROSE study. In regard to seizure freedom in ROSE, said Dr. Quigg, “The data appear to show that radiosurgery is inferior to ATL, but the low power of the study means that we cannot conclude this with sufficient confidence. Nor can we conclude that the two treatments are noninferior.”
The study was partially funded by Elekta, the manufacturer of the Gamma Knife radiosurgery device used in the study. Dr. Barbaro reported no other disclosures. Dr. Langfitt reported being a consultant for Monteris. Dr. Quigg reported being an investigator for several antiepileptic drug trials sponsored by pharmaceutical companies.
[email protected]
On Twitter @karioakes
HOUSTON – Despite enrollment difficulties that limited the study, a recently completed randomized trial comparing radiosurgery with open lobectomy to treat temporal lobe epilepsy offers some guidance for patients and their physicians.
Radiosurgery’s noninferiority to open lobectomy couldn’t be shown from the ROSE (Radiosurgery or Open Surgery for Epilepsy) trial, but language deficits were similar – and quite small – by 3 years after either procedure. Expected visual field deficits were similar in each procedure as well. However, since the trial didn’t reach its target enrollment, several primary outcome measures could not be fully assessed.
On the face of it, radiosurgery has significant appeal. Although open resective surgery is effective, there’s still some risk of infection and blood loss, and neuropsychological changes as well as other focal neurologic deficits are seen. Still, the study saw many challenges, but the largest, according to the investigators, was in recruitment. “Patients like to choose,” said Nicholas M. Barbaro, MD, chair of the department of neurosurgery at Indiana University, Indianapolis. Dr. Barbaro, one of several ROSE coinvestigators who presented the study findings at the annual meeting of the American Epilepsy Society, noted that if patients felt that lobectomy was the best choice, then there would be no incentive to enter a trial where they might be randomized to radiosurgery. Also, he said, some patients might be reluctant to be irradiated, fearing short-term or long-term toxicity.
Trial hypotheses and protocols
The ROSE trial aimed to show that stereotactic radiosurgery (SRS) would not be inferior to anterior temporal lobectomy (ATL) in achieving a seizure-free state by months 25-36 post procedure. The lag to response after radiosurgery is about 1 year; seizure freedom, defined as 12 consecutive months with no seizures, was assessed from months 25 to 36 of the study for the primary outcome of seizure freedom.
Investigators also hypothesized that fewer SRS patients would have significant reductions in measures of language function; further, they predicted that patients in both treatment arms would experience improvements in quality of life (QOL), and that QOL would improve as seizure freedom increased. Finally, the trial sought to show that SRS was cost effective, compared with ATL, with the marginal cost-utility ratio dropping below $50,000 per quality-adjusted life-year (QALY).
Patients in the ATL arm received a standard “Spencer” ATL, with adequacy of resection assessed by MRI performed 3 months after surgery. An inadequate resection would have been classified as an adverse event, but all ATL patients had an adequate resection by study criteria, and all those whose histopathology was available (n = 20) had some hippocampal sclerosis.
Patients in the SRS arm had the amygdala and anterior 2 cm of the hippocampus, as well as the adjacent parahippocampal gyrus, irradiated. This resulted in a total treatment volume ranging from 5.5 to 7.5 cc. Patients received 4 Gy to the 50% isodose line, and treatment could involve an unlimited number of isocenters. The brain stem could receive no more than 10 Gy and the optic nerve and chiasm no more than 8 Gy. All treatment plans were cleared by the ROSE steering committee. The SRS patients had some variation in dose and volumes treated, but all were within the approved limits of the study.
Trial outcomes
As expected, the surgery arm achieved rapid seizure remission, while the SRS arm saw a steady increase in seizure-free numbers beginning at about 12 months after surgery. During study months 25-36, 78% of the ATL arm and 52% of the SRS arm were seizure free. “The null hypothesis of inferiority of SRS was not rejected,” said Mark Quigg, MD, professor of neurology at the University of Virginia, Charlottesville.
Most patients in both groups had no or minimal changes in verbal memory, with no significant differences between the groups at 36 months after treatment.
QOL measures improved rapidly for those who received open surgery, and more slowly for those in the radiosurgery arm, a pattern “consistent with the known association between improved seizure control and quality of life,” said John Langfitt, PhD, a neuropsychologist and professor of neurology and psychiatry at the University of Rochester (N.Y.). However, the study was underpowered to show noninferiority of SRS for QOL measures at 36 months.
“There was a preliminary trend toward reduced health care use over time in the open surgery arm,” said Dr. Langfitt, again noting that the earlier seizure control achieved in surgery reduced health care utilization for that group sooner than for the SRS group. “The power may be limited by sample size and the tendency of utilization to be highly skewed,” he said.
Also as expected, the ATL arm saw early surgery-related adverse events such as scalp wound infections, subdural hematomas, and deep vein thromboses. These were infrequent overall. In contrast, the SRS group saw more cerebral edema–related adverse events during months 9-18, with headaches, new neurologic deficits, and transient seizure exacerbation.
All but three patients received postoperative visual field testing. Of the patients receiving SRS, 34% (10 of 29) had an upper superior quadrant visual field defect, as did 42% (11 of 26) of patients in the ATL arm.
Since the primary treating surgeon and neurologist could not be blinded as to study arm, another neurologist who was blinded was responsible for assessing the outcome measures, and also could identify adverse events. The trial’s steering committee was also blinded to ongoing outcomes.
Pilot study results
A pilot study had previously found that SRS was comparable to the efficacy that had been seen in larger, prospective trials of open surgery, with about two-thirds of patients seizure free at 36 months. Although most patients experienced brief exacerbation of auras or complex partial seizures after radiosurgery, visual field defects were similar to those experienced by patients undergoing standard ATL. Overall, neuropsychological outcomes for those undergoing SRS in the pilot were good, with a low incidence of declines in language and verbal memory function of the dominant hemisphere, and no short-term affective changes were seen. SRS patients who were seizure free after the procedure experienced a significant improvement in QOL.
The promising pilot results contrasted with the limited findings of the ROSE study. In regard to seizure freedom in ROSE, said Dr. Quigg, “The data appear to show that radiosurgery is inferior to ATL, but the low power of the study means that we cannot conclude this with sufficient confidence. Nor can we conclude that the two treatments are noninferior.”
The study was partially funded by Elekta, the manufacturer of the Gamma Knife radiosurgery device used in the study. Dr. Barbaro reported no other disclosures. Dr. Langfitt reported being a consultant for Monteris. Dr. Quigg reported being an investigator for several antiepileptic drug trials sponsored by pharmaceutical companies.
[email protected]
On Twitter @karioakes
AT AES 2016
Key clinical point:
Major finding: During study months 25-36, 78% of the ATL arm and 52% of the SRS arm were seizure free.
Data source: Trial of 58 patients with temporal lobe epilepsy randomized to receive ATL or SRS.
Disclosures: The study was partially funded by Elekta, the manufacturer of the Gamma Knife radiosurgery device used in the study. Several of the presenting ROSE steering committee members reported financial relationships with pharmaceutical companies.
New and Noteworthy Information—January 2017
Students who played varsity high school football between 1956 and 1970 do not have an increased risk of neurodegenerative diseases, compared with athletes engaged in other varsity sports, according to a study published online ahead of print December 12, 2016, in Mayo Clinic Proceedings. Researchers identified 296 male varsity football players in public high schools in Rochester, Minnesota, and 190 male varsity swimmers, wrestlers, and basketball players. Using records from the Rochester Epidemiology Project, investigators ascertained the incidence of late-life neurodegenerative diseases. Football players had an increased risk of medically documented head trauma, especially if they played football for more than one year. Compared with other athletes, football players did not have an increased risk of neurodegenerative disease overall, nor an increased risk of dementia, parkinsonism, or amyotrophic lateral sclerosis.
Antipsychotic drug use is associated with a 60% increased risk of mortality among persons with Alzheimer's disease, according to a study published online ahead of print December 5, 2016, in the Journal of Alzheimer's Disease. Researchers examined data from the MEDALZ study for 70,718 people who were newly diagnosed with Alzheimer's disease in Finland from 2005 to 2011. Death, excluding death from cancer, was extracted from the Causes of Death Register. Incident antipsychotic use was compared with time without antipsychotics using Cox proportional hazard models. The absolute difference in mortality rate was 4.58 deaths per 100 person-years. The risk of mortality was increased from the first days of antipsychotic use and attenuated gradually. Antipsychotic polypharmacy was associated with an almost doubled risk of mortality, compared with monotherapy.
A disruption of structural connections in a brain network contributes to cognitive deficits in patients with Parkinson's disease, according to a study published online ahead of print December 7, 2016, in Radiology. The structural brain connectomes of 170 patients with Parkinson's disease and 41 healthy controls were obtained with deterministic diffusion-tensor tractography. Patients with Parkinson's disease and mild cognitive impairment (MCI) had global network alterations, compared with controls and patients with Parkinson's disease without MCI. Relative to controls, patients with Parkinson's disease and MCI had a large basal ganglia and frontoparietal network with decreased fractional anisotropy in the right hemisphere and a subnetwork with increased mean diffusivity involving similar regions bilaterally. Compared with patients with Parkinson's disease without MCI, people with Parkinson's disease and MCI had networks with decreased fractional anisotropy.
A proposed diagnostic algorithm for sporadic Creutzfeldt-Jakob disease combines CSF and olfactory mucosa real-time quaking-induced conversion testing to provide approximately 100% sensitivity and specificity in the clinical phase of the disease, according to a study published online ahead of print December 12, 2016, in JAMA Neurology. Among the 86 patients included in this analysis, 61 patients with sporadic Creutzfeldt-Jakob disease had positive real-time quaking-induced conversion findings using olfactory mucosa, CSF samples, or both, for an overall real-time quaking-induced conversion sensitivity of 100%. All patients with a final diagnosis of nonprion disease had negative real-time quaking-induced conversion findings, for 100% specificity. Of eight symptomatic patients with various mutations causing Creutzfeldt-Jakob disease or Gerstmann-Sträussler-Scheinker syndrome, six had positive and two had negative real-time quaking-induced conversion findings, for a sensitivity of 75%.
CSF autotaxin may be a useful biomarker of dysmetabolism for examining risk for and outcomes of Alzheimer's disease, according to research published December 1, 2016, in the Journal of Alzheimer's Disease. Investigators studied 287 participants in the Alzheimer's Disease Neuroimaging Initiative, including 86 cognitively normal participants, 135 participants with mild cognitive impairment (MCI), and 66 participants with Alzheimer's disease. Autotaxin levels were significantly higher in patients with MCI and those with Alzheimer's disease. Each point increase in log-based autotaxin corresponded to a 3.5- to 5-times higher likelihood of having MCI and Alzheimer's disease, respectively. Higher autotaxin in Alzheimer's disease predicted hypometabolism in the medial temporal lobe and prefrontal cortex, and worse performance on executive function and memory factors. Autotaxin was associated with decreased cortical thickness in prefrontal cortex areas.
Marital history is significantly associated with survival after stroke, according to a study published December 14, 2016, in the Journal of the American Heart Association. Data from a nationally representative sample of 2,351 older adults who experienced a stroke were used to examine whether and to what extent current marital status and past marital losses were associated with risks of dying after the onset of disease. Results showed that the risks of dying following a stroke were significantly higher among people who were never married, remarried, divorced, and widowed, relative to those who remained continuously married. Researchers also found that having multiple marital losses was especially detrimental to survival, regardless of current marital status and accounting for multiple socioeconomic, psychosocial, behavioral, and physiologic risk factors.
Prefrontal brain activity levels during a cognitively demanding walking condition predict falls in high-functioning senior citizens, according to a study published online ahead of print December 7, 2016, in Neurology. Researchers examined 166 people with a mean age of 75 with functional near-infrared spectroscopy during motor, cognitive, and combined motor and cognitive tasks. Incident falls were prospectively assessed during a 50-month study period. During a mean follow-up of 33.9 months, 116 falls occurred. Higher levels of prefrontal cortical activation during the dual-task walking condition predicted falls. Neither behavioral outcomes on the dual task nor brain activation patterns on the single tasks predicted falls in this high-functioning sample. The results remained robust after accounting for multiple confounders, cognitive status, slow gait, previous falls, and frailty.
Localized brain injury and repair, indicated by higher translocator protein 18 kDa signal and white matter changes, may be associated with National Football League (NFL) play, according to a study published online ahead of print November 28, 2016, in JAMA Neurology. This cross-sectional, case-control study included young active or former NFL players recruited from across the United States and 16 age-, sex-, highest educational level-, and BMI-matched control participants. Researchers used [11C]DPA-713 PET data and other imaging data from 12 active or former NFL players and 11 matched control participants. The NFL players showed higher total distribution volume in eight of 12 brain regions examined. Investigators also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players, compared with 15 control participants.
Exposure to maternal rheumatoid arthritis is associated with an increased risk of childhood epilepsy, while exposure to paternal rheumatoid arthritis is not, according to a study published December 13, 2016, in Neurology. Researchers performed a nationwide cohort study of 1,917,723 people that were born between 1977 and 2008. Compared with unexposed children, children exposed to maternal rheumatoid arthritis had an increased risk of early and late childhood epilepsy, while children exposed to maternal rheumatoid arthritis had no increased risk of epilepsy in adolescence and adulthood. Paternal rheumatoid arthritis was not associated with an overall risk of epilepsy in the offspring or at any age. Children exposed to maternal rheumatoid arthritis in utero had a more pronounced increased risk of early childhood epilepsy than children of mothers who were diagnosed with rheumatoid arthritis after childbirth.
Having surgery may be linked to developing Guillain-Barré syndrome for people with cancer or autoimmune disorders, according to a study published online ahead of print November 23, 2016, in Neurology Clinical Practice. Researchers retrospectively reviewed consecutive patients diagnosed with Guillain-Barré syndrome within eight weeks of a surgical procedure between January 1995 and June 2014. Of the 208 people treated for Guillain-Barré syndrome, 31 people developed the syndrome within eight weeks of having a surgical procedure. People who had had cancer within the previous six months were seven times more likely to develop Guillain-Barré syndrome after surgery than people who had not had cancer. People who had pre-existing autoimmune disorders were five times more likely to develop Guillain-Barré syndrome after surgery than those without autoimmune disorders.
Patients with Parkinson's disease and orthostatic hypotension have transient, posture-mediated changes in cognition, according to a study published online ahead of print November 30, 2016, in Neurology. To investigate the relation between orthostatic hypotension and posture-mediated cognitive impairment in Parkinson disease, researchers used a cross-sectional and within-group design. Participants included 18 patients with Parkinson's disease and orthostatic hypotension, 19 patients with Parkinson's disease but without orthostatic hypotension, and 18 healthy controls. Participants underwent neuropsychologic tests in the supine and upright-tilted positions. When relative performances were compared with each other, postural changes had no significant impact on participants with Parkinson's disease but without orthostatic hypotension, compared with the control group. Participants with Parkinson's disease and orthostatic hypotension, however, were more susceptible to posture-related impairment on several tests.
Low concentrations of neonatal vitamin D are associated with an increased risk of multiple sclerosis (MS), according to a study published online ahead of print November 30, 2016, in Neurology. Researchers conducted a matched case-control study. Dried blood spots samples from 521 patients with MS were identified in the Danish Newborn Screening Biobank. For every patient with MS, one to two controls with the same sex and birth date were retrieved from the Biobank. Lower levels of 25-hydroxyvitamin D in neonates were associated with an increased risk of MS. In the analysis by quintiles, MS risk was highest among individuals in the bottom quintile and lowest among those in the top quintile of 25-hydroxyvitamin D, with an odds ratio for top versus bottom of 0.53.
Children exposed to valproate in the womb are at an increased risk of having a malformation at birth, and the dose of valproate that the child is exposed to determines the level of risk, according to a study published November 7, 2016, in the Cochrane Database of Systematic Reviews. Researchers analyzed 50 studies, with 31 contributing to a meta-analysis. Children exposed to valproate were at a higher risk of malformation, compared with children born to women without epilepsy and to women with untreated epilepsy. Investigators found significantly higher rates of specific malformations associating phenobarbital exposure with cardiac malformations and valproate exposure with neural tube, cardiac, orofacial, craniofacial, skeletal, and limb malformations, compared with other antiepileptic drugs. Dose of exposure mediated the risk of malformation following valproate exposure.
—Kimberly Williams
Students who played varsity high school football between 1956 and 1970 do not have an increased risk of neurodegenerative diseases, compared with athletes engaged in other varsity sports, according to a study published online ahead of print December 12, 2016, in Mayo Clinic Proceedings. Researchers identified 296 male varsity football players in public high schools in Rochester, Minnesota, and 190 male varsity swimmers, wrestlers, and basketball players. Using records from the Rochester Epidemiology Project, investigators ascertained the incidence of late-life neurodegenerative diseases. Football players had an increased risk of medically documented head trauma, especially if they played football for more than one year. Compared with other athletes, football players did not have an increased risk of neurodegenerative disease overall, nor an increased risk of dementia, parkinsonism, or amyotrophic lateral sclerosis.
Antipsychotic drug use is associated with a 60% increased risk of mortality among persons with Alzheimer's disease, according to a study published online ahead of print December 5, 2016, in the Journal of Alzheimer's Disease. Researchers examined data from the MEDALZ study for 70,718 people who were newly diagnosed with Alzheimer's disease in Finland from 2005 to 2011. Death, excluding death from cancer, was extracted from the Causes of Death Register. Incident antipsychotic use was compared with time without antipsychotics using Cox proportional hazard models. The absolute difference in mortality rate was 4.58 deaths per 100 person-years. The risk of mortality was increased from the first days of antipsychotic use and attenuated gradually. Antipsychotic polypharmacy was associated with an almost doubled risk of mortality, compared with monotherapy.
A disruption of structural connections in a brain network contributes to cognitive deficits in patients with Parkinson's disease, according to a study published online ahead of print December 7, 2016, in Radiology. The structural brain connectomes of 170 patients with Parkinson's disease and 41 healthy controls were obtained with deterministic diffusion-tensor tractography. Patients with Parkinson's disease and mild cognitive impairment (MCI) had global network alterations, compared with controls and patients with Parkinson's disease without MCI. Relative to controls, patients with Parkinson's disease and MCI had a large basal ganglia and frontoparietal network with decreased fractional anisotropy in the right hemisphere and a subnetwork with increased mean diffusivity involving similar regions bilaterally. Compared with patients with Parkinson's disease without MCI, people with Parkinson's disease and MCI had networks with decreased fractional anisotropy.
A proposed diagnostic algorithm for sporadic Creutzfeldt-Jakob disease combines CSF and olfactory mucosa real-time quaking-induced conversion testing to provide approximately 100% sensitivity and specificity in the clinical phase of the disease, according to a study published online ahead of print December 12, 2016, in JAMA Neurology. Among the 86 patients included in this analysis, 61 patients with sporadic Creutzfeldt-Jakob disease had positive real-time quaking-induced conversion findings using olfactory mucosa, CSF samples, or both, for an overall real-time quaking-induced conversion sensitivity of 100%. All patients with a final diagnosis of nonprion disease had negative real-time quaking-induced conversion findings, for 100% specificity. Of eight symptomatic patients with various mutations causing Creutzfeldt-Jakob disease or Gerstmann-Sträussler-Scheinker syndrome, six had positive and two had negative real-time quaking-induced conversion findings, for a sensitivity of 75%.
CSF autotaxin may be a useful biomarker of dysmetabolism for examining risk for and outcomes of Alzheimer's disease, according to research published December 1, 2016, in the Journal of Alzheimer's Disease. Investigators studied 287 participants in the Alzheimer's Disease Neuroimaging Initiative, including 86 cognitively normal participants, 135 participants with mild cognitive impairment (MCI), and 66 participants with Alzheimer's disease. Autotaxin levels were significantly higher in patients with MCI and those with Alzheimer's disease. Each point increase in log-based autotaxin corresponded to a 3.5- to 5-times higher likelihood of having MCI and Alzheimer's disease, respectively. Higher autotaxin in Alzheimer's disease predicted hypometabolism in the medial temporal lobe and prefrontal cortex, and worse performance on executive function and memory factors. Autotaxin was associated with decreased cortical thickness in prefrontal cortex areas.
Marital history is significantly associated with survival after stroke, according to a study published December 14, 2016, in the Journal of the American Heart Association. Data from a nationally representative sample of 2,351 older adults who experienced a stroke were used to examine whether and to what extent current marital status and past marital losses were associated with risks of dying after the onset of disease. Results showed that the risks of dying following a stroke were significantly higher among people who were never married, remarried, divorced, and widowed, relative to those who remained continuously married. Researchers also found that having multiple marital losses was especially detrimental to survival, regardless of current marital status and accounting for multiple socioeconomic, psychosocial, behavioral, and physiologic risk factors.
Prefrontal brain activity levels during a cognitively demanding walking condition predict falls in high-functioning senior citizens, according to a study published online ahead of print December 7, 2016, in Neurology. Researchers examined 166 people with a mean age of 75 with functional near-infrared spectroscopy during motor, cognitive, and combined motor and cognitive tasks. Incident falls were prospectively assessed during a 50-month study period. During a mean follow-up of 33.9 months, 116 falls occurred. Higher levels of prefrontal cortical activation during the dual-task walking condition predicted falls. Neither behavioral outcomes on the dual task nor brain activation patterns on the single tasks predicted falls in this high-functioning sample. The results remained robust after accounting for multiple confounders, cognitive status, slow gait, previous falls, and frailty.
Localized brain injury and repair, indicated by higher translocator protein 18 kDa signal and white matter changes, may be associated with National Football League (NFL) play, according to a study published online ahead of print November 28, 2016, in JAMA Neurology. This cross-sectional, case-control study included young active or former NFL players recruited from across the United States and 16 age-, sex-, highest educational level-, and BMI-matched control participants. Researchers used [11C]DPA-713 PET data and other imaging data from 12 active or former NFL players and 11 matched control participants. The NFL players showed higher total distribution volume in eight of 12 brain regions examined. Investigators also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players, compared with 15 control participants.
Exposure to maternal rheumatoid arthritis is associated with an increased risk of childhood epilepsy, while exposure to paternal rheumatoid arthritis is not, according to a study published December 13, 2016, in Neurology. Researchers performed a nationwide cohort study of 1,917,723 people that were born between 1977 and 2008. Compared with unexposed children, children exposed to maternal rheumatoid arthritis had an increased risk of early and late childhood epilepsy, while children exposed to maternal rheumatoid arthritis had no increased risk of epilepsy in adolescence and adulthood. Paternal rheumatoid arthritis was not associated with an overall risk of epilepsy in the offspring or at any age. Children exposed to maternal rheumatoid arthritis in utero had a more pronounced increased risk of early childhood epilepsy than children of mothers who were diagnosed with rheumatoid arthritis after childbirth.
Having surgery may be linked to developing Guillain-Barré syndrome for people with cancer or autoimmune disorders, according to a study published online ahead of print November 23, 2016, in Neurology Clinical Practice. Researchers retrospectively reviewed consecutive patients diagnosed with Guillain-Barré syndrome within eight weeks of a surgical procedure between January 1995 and June 2014. Of the 208 people treated for Guillain-Barré syndrome, 31 people developed the syndrome within eight weeks of having a surgical procedure. People who had had cancer within the previous six months were seven times more likely to develop Guillain-Barré syndrome after surgery than people who had not had cancer. People who had pre-existing autoimmune disorders were five times more likely to develop Guillain-Barré syndrome after surgery than those without autoimmune disorders.
Patients with Parkinson's disease and orthostatic hypotension have transient, posture-mediated changes in cognition, according to a study published online ahead of print November 30, 2016, in Neurology. To investigate the relation between orthostatic hypotension and posture-mediated cognitive impairment in Parkinson disease, researchers used a cross-sectional and within-group design. Participants included 18 patients with Parkinson's disease and orthostatic hypotension, 19 patients with Parkinson's disease but without orthostatic hypotension, and 18 healthy controls. Participants underwent neuropsychologic tests in the supine and upright-tilted positions. When relative performances were compared with each other, postural changes had no significant impact on participants with Parkinson's disease but without orthostatic hypotension, compared with the control group. Participants with Parkinson's disease and orthostatic hypotension, however, were more susceptible to posture-related impairment on several tests.
Low concentrations of neonatal vitamin D are associated with an increased risk of multiple sclerosis (MS), according to a study published online ahead of print November 30, 2016, in Neurology. Researchers conducted a matched case-control study. Dried blood spots samples from 521 patients with MS were identified in the Danish Newborn Screening Biobank. For every patient with MS, one to two controls with the same sex and birth date were retrieved from the Biobank. Lower levels of 25-hydroxyvitamin D in neonates were associated with an increased risk of MS. In the analysis by quintiles, MS risk was highest among individuals in the bottom quintile and lowest among those in the top quintile of 25-hydroxyvitamin D, with an odds ratio for top versus bottom of 0.53.
Children exposed to valproate in the womb are at an increased risk of having a malformation at birth, and the dose of valproate that the child is exposed to determines the level of risk, according to a study published November 7, 2016, in the Cochrane Database of Systematic Reviews. Researchers analyzed 50 studies, with 31 contributing to a meta-analysis. Children exposed to valproate were at a higher risk of malformation, compared with children born to women without epilepsy and to women with untreated epilepsy. Investigators found significantly higher rates of specific malformations associating phenobarbital exposure with cardiac malformations and valproate exposure with neural tube, cardiac, orofacial, craniofacial, skeletal, and limb malformations, compared with other antiepileptic drugs. Dose of exposure mediated the risk of malformation following valproate exposure.
—Kimberly Williams
Students who played varsity high school football between 1956 and 1970 do not have an increased risk of neurodegenerative diseases, compared with athletes engaged in other varsity sports, according to a study published online ahead of print December 12, 2016, in Mayo Clinic Proceedings. Researchers identified 296 male varsity football players in public high schools in Rochester, Minnesota, and 190 male varsity swimmers, wrestlers, and basketball players. Using records from the Rochester Epidemiology Project, investigators ascertained the incidence of late-life neurodegenerative diseases. Football players had an increased risk of medically documented head trauma, especially if they played football for more than one year. Compared with other athletes, football players did not have an increased risk of neurodegenerative disease overall, nor an increased risk of dementia, parkinsonism, or amyotrophic lateral sclerosis.
Antipsychotic drug use is associated with a 60% increased risk of mortality among persons with Alzheimer's disease, according to a study published online ahead of print December 5, 2016, in the Journal of Alzheimer's Disease. Researchers examined data from the MEDALZ study for 70,718 people who were newly diagnosed with Alzheimer's disease in Finland from 2005 to 2011. Death, excluding death from cancer, was extracted from the Causes of Death Register. Incident antipsychotic use was compared with time without antipsychotics using Cox proportional hazard models. The absolute difference in mortality rate was 4.58 deaths per 100 person-years. The risk of mortality was increased from the first days of antipsychotic use and attenuated gradually. Antipsychotic polypharmacy was associated with an almost doubled risk of mortality, compared with monotherapy.
A disruption of structural connections in a brain network contributes to cognitive deficits in patients with Parkinson's disease, according to a study published online ahead of print December 7, 2016, in Radiology. The structural brain connectomes of 170 patients with Parkinson's disease and 41 healthy controls were obtained with deterministic diffusion-tensor tractography. Patients with Parkinson's disease and mild cognitive impairment (MCI) had global network alterations, compared with controls and patients with Parkinson's disease without MCI. Relative to controls, patients with Parkinson's disease and MCI had a large basal ganglia and frontoparietal network with decreased fractional anisotropy in the right hemisphere and a subnetwork with increased mean diffusivity involving similar regions bilaterally. Compared with patients with Parkinson's disease without MCI, people with Parkinson's disease and MCI had networks with decreased fractional anisotropy.
A proposed diagnostic algorithm for sporadic Creutzfeldt-Jakob disease combines CSF and olfactory mucosa real-time quaking-induced conversion testing to provide approximately 100% sensitivity and specificity in the clinical phase of the disease, according to a study published online ahead of print December 12, 2016, in JAMA Neurology. Among the 86 patients included in this analysis, 61 patients with sporadic Creutzfeldt-Jakob disease had positive real-time quaking-induced conversion findings using olfactory mucosa, CSF samples, or both, for an overall real-time quaking-induced conversion sensitivity of 100%. All patients with a final diagnosis of nonprion disease had negative real-time quaking-induced conversion findings, for 100% specificity. Of eight symptomatic patients with various mutations causing Creutzfeldt-Jakob disease or Gerstmann-Sträussler-Scheinker syndrome, six had positive and two had negative real-time quaking-induced conversion findings, for a sensitivity of 75%.
CSF autotaxin may be a useful biomarker of dysmetabolism for examining risk for and outcomes of Alzheimer's disease, according to research published December 1, 2016, in the Journal of Alzheimer's Disease. Investigators studied 287 participants in the Alzheimer's Disease Neuroimaging Initiative, including 86 cognitively normal participants, 135 participants with mild cognitive impairment (MCI), and 66 participants with Alzheimer's disease. Autotaxin levels were significantly higher in patients with MCI and those with Alzheimer's disease. Each point increase in log-based autotaxin corresponded to a 3.5- to 5-times higher likelihood of having MCI and Alzheimer's disease, respectively. Higher autotaxin in Alzheimer's disease predicted hypometabolism in the medial temporal lobe and prefrontal cortex, and worse performance on executive function and memory factors. Autotaxin was associated with decreased cortical thickness in prefrontal cortex areas.
Marital history is significantly associated with survival after stroke, according to a study published December 14, 2016, in the Journal of the American Heart Association. Data from a nationally representative sample of 2,351 older adults who experienced a stroke were used to examine whether and to what extent current marital status and past marital losses were associated with risks of dying after the onset of disease. Results showed that the risks of dying following a stroke were significantly higher among people who were never married, remarried, divorced, and widowed, relative to those who remained continuously married. Researchers also found that having multiple marital losses was especially detrimental to survival, regardless of current marital status and accounting for multiple socioeconomic, psychosocial, behavioral, and physiologic risk factors.
Prefrontal brain activity levels during a cognitively demanding walking condition predict falls in high-functioning senior citizens, according to a study published online ahead of print December 7, 2016, in Neurology. Researchers examined 166 people with a mean age of 75 with functional near-infrared spectroscopy during motor, cognitive, and combined motor and cognitive tasks. Incident falls were prospectively assessed during a 50-month study period. During a mean follow-up of 33.9 months, 116 falls occurred. Higher levels of prefrontal cortical activation during the dual-task walking condition predicted falls. Neither behavioral outcomes on the dual task nor brain activation patterns on the single tasks predicted falls in this high-functioning sample. The results remained robust after accounting for multiple confounders, cognitive status, slow gait, previous falls, and frailty.
Localized brain injury and repair, indicated by higher translocator protein 18 kDa signal and white matter changes, may be associated with National Football League (NFL) play, according to a study published online ahead of print November 28, 2016, in JAMA Neurology. This cross-sectional, case-control study included young active or former NFL players recruited from across the United States and 16 age-, sex-, highest educational level-, and BMI-matched control participants. Researchers used [11C]DPA-713 PET data and other imaging data from 12 active or former NFL players and 11 matched control participants. The NFL players showed higher total distribution volume in eight of 12 brain regions examined. Investigators also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players, compared with 15 control participants.
Exposure to maternal rheumatoid arthritis is associated with an increased risk of childhood epilepsy, while exposure to paternal rheumatoid arthritis is not, according to a study published December 13, 2016, in Neurology. Researchers performed a nationwide cohort study of 1,917,723 people that were born between 1977 and 2008. Compared with unexposed children, children exposed to maternal rheumatoid arthritis had an increased risk of early and late childhood epilepsy, while children exposed to maternal rheumatoid arthritis had no increased risk of epilepsy in adolescence and adulthood. Paternal rheumatoid arthritis was not associated with an overall risk of epilepsy in the offspring or at any age. Children exposed to maternal rheumatoid arthritis in utero had a more pronounced increased risk of early childhood epilepsy than children of mothers who were diagnosed with rheumatoid arthritis after childbirth.
Having surgery may be linked to developing Guillain-Barré syndrome for people with cancer or autoimmune disorders, according to a study published online ahead of print November 23, 2016, in Neurology Clinical Practice. Researchers retrospectively reviewed consecutive patients diagnosed with Guillain-Barré syndrome within eight weeks of a surgical procedure between January 1995 and June 2014. Of the 208 people treated for Guillain-Barré syndrome, 31 people developed the syndrome within eight weeks of having a surgical procedure. People who had had cancer within the previous six months were seven times more likely to develop Guillain-Barré syndrome after surgery than people who had not had cancer. People who had pre-existing autoimmune disorders were five times more likely to develop Guillain-Barré syndrome after surgery than those without autoimmune disorders.
Patients with Parkinson's disease and orthostatic hypotension have transient, posture-mediated changes in cognition, according to a study published online ahead of print November 30, 2016, in Neurology. To investigate the relation between orthostatic hypotension and posture-mediated cognitive impairment in Parkinson disease, researchers used a cross-sectional and within-group design. Participants included 18 patients with Parkinson's disease and orthostatic hypotension, 19 patients with Parkinson's disease but without orthostatic hypotension, and 18 healthy controls. Participants underwent neuropsychologic tests in the supine and upright-tilted positions. When relative performances were compared with each other, postural changes had no significant impact on participants with Parkinson's disease but without orthostatic hypotension, compared with the control group. Participants with Parkinson's disease and orthostatic hypotension, however, were more susceptible to posture-related impairment on several tests.
Low concentrations of neonatal vitamin D are associated with an increased risk of multiple sclerosis (MS), according to a study published online ahead of print November 30, 2016, in Neurology. Researchers conducted a matched case-control study. Dried blood spots samples from 521 patients with MS were identified in the Danish Newborn Screening Biobank. For every patient with MS, one to two controls with the same sex and birth date were retrieved from the Biobank. Lower levels of 25-hydroxyvitamin D in neonates were associated with an increased risk of MS. In the analysis by quintiles, MS risk was highest among individuals in the bottom quintile and lowest among those in the top quintile of 25-hydroxyvitamin D, with an odds ratio for top versus bottom of 0.53.
Children exposed to valproate in the womb are at an increased risk of having a malformation at birth, and the dose of valproate that the child is exposed to determines the level of risk, according to a study published November 7, 2016, in the Cochrane Database of Systematic Reviews. Researchers analyzed 50 studies, with 31 contributing to a meta-analysis. Children exposed to valproate were at a higher risk of malformation, compared with children born to women without epilepsy and to women with untreated epilepsy. Investigators found significantly higher rates of specific malformations associating phenobarbital exposure with cardiac malformations and valproate exposure with neural tube, cardiac, orofacial, craniofacial, skeletal, and limb malformations, compared with other antiepileptic drugs. Dose of exposure mediated the risk of malformation following valproate exposure.
—Kimberly Williams
Machine learning beats clinical prediction of temporal lobe epilepsy surgery outcomes
HOUSTON – A machine learning interpretation of presurgical MRI studies did a better job of predicting which patients would have a successful outcome after anterior temporal lobectomy for temporal lobe epilepsy than did commonly-used clinical indicators in a prospective cohort study.
Xiaosong He, PhD, and his associates used two different machine learning classification methods to find two markers for thalamocortical connectedness that best predicted a good surgical outcome for temporal lobe epilepsy (TLE) in a small sample of patients. They presented their findings during a poster session of the annual meeting of the American Epilepsy Society.
After selecting a variety of possible predictors and building a model using resting state functional MRI (rsfMRI) data from 48 patients, the investigators then validated the prediction accuracies with rsfMRI data from 8 patients.
In predicting which TLE patients would have a good surgical outcome, models built with machine learning techniques using rsfMRI functional connectivity values had sensitivity ranging from 80% to 89% and specificity ranging from 52% to 57%. By comparison, models using clinical predictors only had sensitivity of 66% to 83% and specificity of 29% to 33%.
Dr. He and his coauthors dichotomized the surgical outcome for 56 patients who underwent TLE surgery into good outcome (n = 35) for those achieving and Engel class I and poor outcome (n = 21, class II-IV) at 1 year post surgery. All patients had a 5-minute rsfMRI scan before surgery.
MRI has been helpful in elucidating the importance of thalamocortical network pathology in TLE. Dr. He and his associates had previously used rsfMRI to examine the strength of functional connectivity between thalamic regions and their corresponding cortical regions in patients with TLE. Analysis of rsfMRI data of “both the left and right TLE groups showed that compared to controls there was a pattern of decreased thalamocortical [functional connectivity] in multiple thalamic segments,” wrote Dr. He and his collaborators (Epilepsia. 2015;56[10]:1571-9).
For the validation cohort, the two measures of connectedness found most predictive of a good surgical outcome were degree centrality and eigenvector centrality. In the graph theory and network analysis used in mapping functional connectivity, centrality refers to how highly connected one node, or data point, is to other data.
In the present study, the investigators used the Automated Anatomical Labeling cortical parcellation map to identify 45 cortical regions of interest per hemisphere, for a total of 90 cortical regions. They built a matrix with five topological parameters (global efficiency, global clustering coefficient, degree centrality, betweenness centrality, and eigenvector centrality) and the 90 cortical regions, yielding 272 variables. When nine commonly-used clinical predictors of surgical outcome (age, gender, handedness, laterality of TLE, epilepsy onset age and duration, seizure focality, interictal-spike type, and the presence of hippocampal sclerosis) were included, the model was made up of 281 variables.
The investigators used two different machine learning classification methods, called support vector machine and random forest, to build models that included various combinations of the 281 variables based on data from the initial 48 patients. The models were then tested with data from the remaining 8 patients.
Of the 35 patients with a good outcome, 18 had a left-sided epileptogenic temporal lobe; for the 21 patients with a poor outcome, the left temporal lobe was epileptogenic in 8. The mean age was similar for both groups: 41.25 years in those with good outcome, and 38.58 years in those with a poor outcome. Age at epilepsy onset also was similar, with each group having had epilepsy for about 17 years at the time of surgery. A total of 15 of the 20 patients with good outcome had seizure focality, compared with 10 of the 11 with poor outcome. Of those with a good outcome, 29 had an ipsilateral interactive spike, while 15 of those with poor outcomes had an ipsilateral interactive spike.
Since the random forest model best predicted surgical outcomes in the small sample size tested, the investigators plan to further fine-tune the random forest parameters to increase the robustness of their model.
Dr. He reported no conflicts of interest.
[email protected]
On Twitter @karioakes
HOUSTON – A machine learning interpretation of presurgical MRI studies did a better job of predicting which patients would have a successful outcome after anterior temporal lobectomy for temporal lobe epilepsy than did commonly-used clinical indicators in a prospective cohort study.
Xiaosong He, PhD, and his associates used two different machine learning classification methods to find two markers for thalamocortical connectedness that best predicted a good surgical outcome for temporal lobe epilepsy (TLE) in a small sample of patients. They presented their findings during a poster session of the annual meeting of the American Epilepsy Society.
After selecting a variety of possible predictors and building a model using resting state functional MRI (rsfMRI) data from 48 patients, the investigators then validated the prediction accuracies with rsfMRI data from 8 patients.
In predicting which TLE patients would have a good surgical outcome, models built with machine learning techniques using rsfMRI functional connectivity values had sensitivity ranging from 80% to 89% and specificity ranging from 52% to 57%. By comparison, models using clinical predictors only had sensitivity of 66% to 83% and specificity of 29% to 33%.
Dr. He and his coauthors dichotomized the surgical outcome for 56 patients who underwent TLE surgery into good outcome (n = 35) for those achieving and Engel class I and poor outcome (n = 21, class II-IV) at 1 year post surgery. All patients had a 5-minute rsfMRI scan before surgery.
MRI has been helpful in elucidating the importance of thalamocortical network pathology in TLE. Dr. He and his associates had previously used rsfMRI to examine the strength of functional connectivity between thalamic regions and their corresponding cortical regions in patients with TLE. Analysis of rsfMRI data of “both the left and right TLE groups showed that compared to controls there was a pattern of decreased thalamocortical [functional connectivity] in multiple thalamic segments,” wrote Dr. He and his collaborators (Epilepsia. 2015;56[10]:1571-9).
For the validation cohort, the two measures of connectedness found most predictive of a good surgical outcome were degree centrality and eigenvector centrality. In the graph theory and network analysis used in mapping functional connectivity, centrality refers to how highly connected one node, or data point, is to other data.
In the present study, the investigators used the Automated Anatomical Labeling cortical parcellation map to identify 45 cortical regions of interest per hemisphere, for a total of 90 cortical regions. They built a matrix with five topological parameters (global efficiency, global clustering coefficient, degree centrality, betweenness centrality, and eigenvector centrality) and the 90 cortical regions, yielding 272 variables. When nine commonly-used clinical predictors of surgical outcome (age, gender, handedness, laterality of TLE, epilepsy onset age and duration, seizure focality, interictal-spike type, and the presence of hippocampal sclerosis) were included, the model was made up of 281 variables.
The investigators used two different machine learning classification methods, called support vector machine and random forest, to build models that included various combinations of the 281 variables based on data from the initial 48 patients. The models were then tested with data from the remaining 8 patients.
Of the 35 patients with a good outcome, 18 had a left-sided epileptogenic temporal lobe; for the 21 patients with a poor outcome, the left temporal lobe was epileptogenic in 8. The mean age was similar for both groups: 41.25 years in those with good outcome, and 38.58 years in those with a poor outcome. Age at epilepsy onset also was similar, with each group having had epilepsy for about 17 years at the time of surgery. A total of 15 of the 20 patients with good outcome had seizure focality, compared with 10 of the 11 with poor outcome. Of those with a good outcome, 29 had an ipsilateral interactive spike, while 15 of those with poor outcomes had an ipsilateral interactive spike.
Since the random forest model best predicted surgical outcomes in the small sample size tested, the investigators plan to further fine-tune the random forest parameters to increase the robustness of their model.
Dr. He reported no conflicts of interest.
[email protected]
On Twitter @karioakes
HOUSTON – A machine learning interpretation of presurgical MRI studies did a better job of predicting which patients would have a successful outcome after anterior temporal lobectomy for temporal lobe epilepsy than did commonly-used clinical indicators in a prospective cohort study.
Xiaosong He, PhD, and his associates used two different machine learning classification methods to find two markers for thalamocortical connectedness that best predicted a good surgical outcome for temporal lobe epilepsy (TLE) in a small sample of patients. They presented their findings during a poster session of the annual meeting of the American Epilepsy Society.
After selecting a variety of possible predictors and building a model using resting state functional MRI (rsfMRI) data from 48 patients, the investigators then validated the prediction accuracies with rsfMRI data from 8 patients.
In predicting which TLE patients would have a good surgical outcome, models built with machine learning techniques using rsfMRI functional connectivity values had sensitivity ranging from 80% to 89% and specificity ranging from 52% to 57%. By comparison, models using clinical predictors only had sensitivity of 66% to 83% and specificity of 29% to 33%.
Dr. He and his coauthors dichotomized the surgical outcome for 56 patients who underwent TLE surgery into good outcome (n = 35) for those achieving and Engel class I and poor outcome (n = 21, class II-IV) at 1 year post surgery. All patients had a 5-minute rsfMRI scan before surgery.
MRI has been helpful in elucidating the importance of thalamocortical network pathology in TLE. Dr. He and his associates had previously used rsfMRI to examine the strength of functional connectivity between thalamic regions and their corresponding cortical regions in patients with TLE. Analysis of rsfMRI data of “both the left and right TLE groups showed that compared to controls there was a pattern of decreased thalamocortical [functional connectivity] in multiple thalamic segments,” wrote Dr. He and his collaborators (Epilepsia. 2015;56[10]:1571-9).
For the validation cohort, the two measures of connectedness found most predictive of a good surgical outcome were degree centrality and eigenvector centrality. In the graph theory and network analysis used in mapping functional connectivity, centrality refers to how highly connected one node, or data point, is to other data.
In the present study, the investigators used the Automated Anatomical Labeling cortical parcellation map to identify 45 cortical regions of interest per hemisphere, for a total of 90 cortical regions. They built a matrix with five topological parameters (global efficiency, global clustering coefficient, degree centrality, betweenness centrality, and eigenvector centrality) and the 90 cortical regions, yielding 272 variables. When nine commonly-used clinical predictors of surgical outcome (age, gender, handedness, laterality of TLE, epilepsy onset age and duration, seizure focality, interictal-spike type, and the presence of hippocampal sclerosis) were included, the model was made up of 281 variables.
The investigators used two different machine learning classification methods, called support vector machine and random forest, to build models that included various combinations of the 281 variables based on data from the initial 48 patients. The models were then tested with data from the remaining 8 patients.
Of the 35 patients with a good outcome, 18 had a left-sided epileptogenic temporal lobe; for the 21 patients with a poor outcome, the left temporal lobe was epileptogenic in 8. The mean age was similar for both groups: 41.25 years in those with good outcome, and 38.58 years in those with a poor outcome. Age at epilepsy onset also was similar, with each group having had epilepsy for about 17 years at the time of surgery. A total of 15 of the 20 patients with good outcome had seizure focality, compared with 10 of the 11 with poor outcome. Of those with a good outcome, 29 had an ipsilateral interactive spike, while 15 of those with poor outcomes had an ipsilateral interactive spike.
Since the random forest model best predicted surgical outcomes in the small sample size tested, the investigators plan to further fine-tune the random forest parameters to increase the robustness of their model.
Dr. He reported no conflicts of interest.
[email protected]
On Twitter @karioakes
AT AES 2016
Key clinical point:
Major finding: Models built with machine learning techniques using resting state fMRI functional connectivity values had sensitivity ranging from 80% to 89% and specificity ranging from 52% to 57%.
Data source: A prospective study of 56 patients with temporal lobe epilepsy.
Disclosures: Dr. He reported no conflicts of interest.
New and Noteworthy Information—December 2016
Economic background does not affect the clinical course or long-term seizure outcome of childhood epilepsy, according to a study in Nova Scotia, Canada, published online ahead of print November 4 in Epilepsia. Researchers examined data for 421 patients with childhood epilepsy and 10 or more years of follow-up. Overall, 33% of families had poor income, 38% had adequate income, and 30% were well-off. Terminal remission occurred in 65% of the poor, 61% of the adequate, and 61% of the well-off populations. Intractable epilepsy, status epilepticus, number of antiepileptic drugs used, and the number of generalized tonic-clonic or focal with secondary generalization seizures through the clinical course was the same in all groups. Neither paternal nor maternal education was associated with remission. Poor children had significantly more adverse social outcomes, however.
A genetic variant near melatonin receptor 1A (MTNR1A) may be associated with job-related exhaustion in shift workers, according to a study published online ahead of print October 10 in Sleep. Researchers assessed intolerance to shift work with job-related exhaustion symptoms in shift workers using the emotional exhaustion subscale of the Maslach Burnout Inventory-General Survey and performed a genome-wide association study. Job-related exhaustion was associated with the rs12506228 variation, located downstream of MTNR1A, in shift workers included in the Finnish national Health 2000 survey. The risk allele was also associated with reduced in silico gene expression levels of MTNR1A in brain tissue and with changes in DNA methylation in the 5' regulatory region of MTNR1A. The risk variant may lead to reduced melatonin signaling in the brain.
In healthy postmenopausal women, reproductive life events related to sex hormones are positively related to aspects of cognition in later life, according to a study published November 7 in the Journal of the American Geriatrics Society. Researchers evaluated 830 menopausal women using a cognitive battery and a structured reproductive history questionnaire. On multivariable modeling, age at menarche of 13 or older was inversely associated with global cognition. Having a last pregnancy after age 35 was positively associated with verbal memory. Use of hormonal contraceptives was positively associated with global cognition and verbal memory. The association between hormonal contraceptive use and verbal memory and executive function was strongest for more than 10 years of use. Reproductive period was positively associated with global cognition and executive function.
Physical fitness, BMI, IQ, and stress resilience in young adulthood may be associated with the development of amyotrophic lateral sclerosis (ALS) at an early age, according to a study published in the October issue of the European Journal of Neurology. Data on physical fitness, BMI, IQ, and stress resilience were collected from 1,838,376 Swedish men ages 17 to 20 at conscription from 1968 to 2010. During follow-up, 439 participants developed ALS. People with physical fitness above the highest tertile had a higher risk of ALS before age 45. People with BMI greater than or equal to 25 had a lower risk of ALS at all ages. Individuals with IQ above the highest tertile had a significantly increased risk of ALS at an age of 56 and older.
Short sleep is associated with greater intake of sugared caffeinated sodas, according to a study published online ahead of print November 9 in Sleep Health. Using data from the 2005 to 2012 National Health and Nutrition Examination Survey, researchers examined self-reported sleep duration and beverage intake from two 24-hour dietary recalls among 18,779 adults. Adults who slept for seven to eight hours each night were considered the reference group. In fully adjusted models, people who slept for five hours or less had 21% higher sugar-sweetened beverage consumption. When analyzed by beverage type, this difference was attributed to caffeinated sugary beverages. Longer sleepers consumed fewer servings of coffee and water. There were no associations between self-reported sleep duration and consumption of 100% juice, tea, or diet drinks.
Treadmill training plus virtual reality reduces fall rates, compared with treadmill training alone, according to a study published September 17 in the Lancet. Adults ages 60 to 90 with motor and cognitive deficits and a high risk of falls were randomly assigned to receive six weeks of treadmill training plus virtual reality or treadmill training alone. Data from 282 participants were included in the prespecified, modified intention-to-treat analysis. In the six months after training, the incident rate of falls was significantly lower in the treadmill-training-plus-virtual-reality group than it had been before training. The incident rate did not decrease significantly in the treadmill-training-alone group. Six months after training, the incident rate of falls was also significantly lower in the treadmill-training-plus-virtual-reality group than in the treadmill-training group.
Current research does not support specific recommendations for treating hypertension to preserve cognition, according to a scientific statement by the American Heart Association published online ahead of print October 10 in Hypertension. A panel of experts reviewed the literature on hypertension, the treatment of hypertension, and the relationship between hypertension and cognition, and summarized the available data. They found that hypertension disrupts the structure and function of cerebral blood vessels, leads to ischemic damage of white matter regions critical for cognitive function, and may promote Alzheimer pathology. They found strong evidence of a negative influence of mid-life hypertension on late-life cognitive function, but the cognitive effect of late-life hypertension is unclear. Observational studies indicate that high blood pressure damages the brain's blood vessels, leading to reduced blood flow to brain cells.
Manual-based cognitive behavioral therapy for insomnia delivered by nonclinician sleep coaches improves sleep in older adults with chronic insomnia, according to a study published in the September issue of the Journal of the American Geriatrics Society. Researchers studied veterans age 60 or older who met diagnostic criteria for insomnia of three months' duration or longer. Nonclinician sleep coaches delivered five sessions of manual-based cognitive behavioral therapy for insomnia, including stimulus control, sleep restriction, sleep hygiene, and cognitive therapy, with weekly telephone behavioral sleep medicine supervision. Controls received sleep education. Intervention subjects had greater improvement than controls between baseline and post-treatment, baseline and six months, and baseline and 12 months in sleep onset latency, total wake time, sleep efficiency, Pittsburgh Sleep Quality Index, and Insomnia Severity Index.
Antioxidants, carotenes, fruits, and vegetables are associated with higher amyotrophic lateral sclerosis (ALS) function at baseline, according to a study published online ahead of print October 24 in JAMA Neurology. A cross-sectional baseline analysis of the ALS Multicenter Cohort Study of Oxidative Stress was conducted at 16 ALS clinics throughout the United States. Baseline data were available on 302 patients (124 women) with ALS (median age, 63.2). Regression analysis of nutrients found that higher intakes of antioxidants and carotenes from vegetables were associated with higher ALS Functional Rating Scale-Revised (ALSFRS-R) scores or percentage forced vital capacity. Empirically weighted indices using the weighted quantile sum regression method of "good" micronutrients and "good" food groups were positively associated with ALSFRS-R scores and percentage forced vital capacity.
Fluselenamyl detects amyloid clumps better than current FDA-approved compounds, according to a study published online ahead of print November 2 in Scientific Reports. To determine whether fluselenamyl can detect amyloid beta plaques in the brain, researchers used the compound to stain brain slices from people who had died of Alzheimer's disease and from people of similar ages who had died of other causes (ie, controls). Fluselenamyl labeled diffuse and fibrillar plaques in brain sections of patients with Alzheimer's disease, but did not interact with biomarker proteins of other neurodegenerative diseases, thereby indicating specificity for detecting amyloid beta in Alzheimer's disease. Overall, fluselenamyl demonstrated potent binding affinity to autopsy-confirmed Alzheimer's disease homogenates. The binding affinity was superior to that of [18F]-AV-45, [18F]-florbetaben, and [18F]-flutemetamol.
Preserved hippocampal volumes are associated with increased risk of probable dementia with Lewy bodies, rather than Alzheimer's disease, in patients with mild cognitive impairment (MCI), according to a study published online ahead of print November 2 in Neurology. In the study, 160 people with MCI underwent MRI to measure hippocampal size. During a median follow-up of two years, 38% of people developed Alzheimer's disease, and 13% of people developed probable dementia with Lewy bodies. The people who had no hippocampal shrinkage were 5.8 times more likely to develop probable dementia with Lewy bodies than people who had hippocampal atrophy. Approximately 85% of people who developed dementia with Lewy bodies had a normal hippocampal volume. Furthermore, 61% of people who developed Alzheimer's disease had hippocampal atrophy.
Use of a media device at bedtime is significantly associated with inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness, according to a systematic review published online ahead of print October 31 in JAMA Pediatrics. Researchers examined published studies of school-age children between ages six and 19 with information about portable screen-based media devices and sleep outcomes. The final analysis included 125,198 children with an average age of 14.5. Children who had access to, but did not use, media devices at night were more likely to have inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness. Teachers, health care professionals, and parents should cooperate to minimize device access at bedtime, according to the researchers. Future studies should evaluate devices' influence on sleep hygiene, they added.
The FDA has approved the Amplatzer Patent Foramen Ovale (PFO) Occluder device, which reduces the risk of stroke in patients who previously had a stroke believed to be caused by a blood clot that passed through a PFO. The Amplatzer PFO Occluder is inserted through a catheter that is placed in a leg vein and advanced to the heart. In a randomized study, 499 participants ages 18 to 60 were treated with the Amplatzer PFO Occluder and blood-thinning medications and compared with 481 participants treated with blood-thinning medications alone. There was a 50% reduction in the rate of new strokes in participants using the Amplatzer PFO Occluder and blood-thinning medications, compared with participants taking medications alone. St. Jude Medical, headquartered in Plymouth, Minnesota, markets the Amplatzer PFO Occluder.
—Kimberly Williams
Economic background does not affect the clinical course or long-term seizure outcome of childhood epilepsy, according to a study in Nova Scotia, Canada, published online ahead of print November 4 in Epilepsia. Researchers examined data for 421 patients with childhood epilepsy and 10 or more years of follow-up. Overall, 33% of families had poor income, 38% had adequate income, and 30% were well-off. Terminal remission occurred in 65% of the poor, 61% of the adequate, and 61% of the well-off populations. Intractable epilepsy, status epilepticus, number of antiepileptic drugs used, and the number of generalized tonic-clonic or focal with secondary generalization seizures through the clinical course was the same in all groups. Neither paternal nor maternal education was associated with remission. Poor children had significantly more adverse social outcomes, however.
A genetic variant near melatonin receptor 1A (MTNR1A) may be associated with job-related exhaustion in shift workers, according to a study published online ahead of print October 10 in Sleep. Researchers assessed intolerance to shift work with job-related exhaustion symptoms in shift workers using the emotional exhaustion subscale of the Maslach Burnout Inventory-General Survey and performed a genome-wide association study. Job-related exhaustion was associated with the rs12506228 variation, located downstream of MTNR1A, in shift workers included in the Finnish national Health 2000 survey. The risk allele was also associated with reduced in silico gene expression levels of MTNR1A in brain tissue and with changes in DNA methylation in the 5' regulatory region of MTNR1A. The risk variant may lead to reduced melatonin signaling in the brain.
In healthy postmenopausal women, reproductive life events related to sex hormones are positively related to aspects of cognition in later life, according to a study published November 7 in the Journal of the American Geriatrics Society. Researchers evaluated 830 menopausal women using a cognitive battery and a structured reproductive history questionnaire. On multivariable modeling, age at menarche of 13 or older was inversely associated with global cognition. Having a last pregnancy after age 35 was positively associated with verbal memory. Use of hormonal contraceptives was positively associated with global cognition and verbal memory. The association between hormonal contraceptive use and verbal memory and executive function was strongest for more than 10 years of use. Reproductive period was positively associated with global cognition and executive function.
Physical fitness, BMI, IQ, and stress resilience in young adulthood may be associated with the development of amyotrophic lateral sclerosis (ALS) at an early age, according to a study published in the October issue of the European Journal of Neurology. Data on physical fitness, BMI, IQ, and stress resilience were collected from 1,838,376 Swedish men ages 17 to 20 at conscription from 1968 to 2010. During follow-up, 439 participants developed ALS. People with physical fitness above the highest tertile had a higher risk of ALS before age 45. People with BMI greater than or equal to 25 had a lower risk of ALS at all ages. Individuals with IQ above the highest tertile had a significantly increased risk of ALS at an age of 56 and older.
Short sleep is associated with greater intake of sugared caffeinated sodas, according to a study published online ahead of print November 9 in Sleep Health. Using data from the 2005 to 2012 National Health and Nutrition Examination Survey, researchers examined self-reported sleep duration and beverage intake from two 24-hour dietary recalls among 18,779 adults. Adults who slept for seven to eight hours each night were considered the reference group. In fully adjusted models, people who slept for five hours or less had 21% higher sugar-sweetened beverage consumption. When analyzed by beverage type, this difference was attributed to caffeinated sugary beverages. Longer sleepers consumed fewer servings of coffee and water. There were no associations between self-reported sleep duration and consumption of 100% juice, tea, or diet drinks.
Treadmill training plus virtual reality reduces fall rates, compared with treadmill training alone, according to a study published September 17 in the Lancet. Adults ages 60 to 90 with motor and cognitive deficits and a high risk of falls were randomly assigned to receive six weeks of treadmill training plus virtual reality or treadmill training alone. Data from 282 participants were included in the prespecified, modified intention-to-treat analysis. In the six months after training, the incident rate of falls was significantly lower in the treadmill-training-plus-virtual-reality group than it had been before training. The incident rate did not decrease significantly in the treadmill-training-alone group. Six months after training, the incident rate of falls was also significantly lower in the treadmill-training-plus-virtual-reality group than in the treadmill-training group.
Current research does not support specific recommendations for treating hypertension to preserve cognition, according to a scientific statement by the American Heart Association published online ahead of print October 10 in Hypertension. A panel of experts reviewed the literature on hypertension, the treatment of hypertension, and the relationship between hypertension and cognition, and summarized the available data. They found that hypertension disrupts the structure and function of cerebral blood vessels, leads to ischemic damage of white matter regions critical for cognitive function, and may promote Alzheimer pathology. They found strong evidence of a negative influence of mid-life hypertension on late-life cognitive function, but the cognitive effect of late-life hypertension is unclear. Observational studies indicate that high blood pressure damages the brain's blood vessels, leading to reduced blood flow to brain cells.
Manual-based cognitive behavioral therapy for insomnia delivered by nonclinician sleep coaches improves sleep in older adults with chronic insomnia, according to a study published in the September issue of the Journal of the American Geriatrics Society. Researchers studied veterans age 60 or older who met diagnostic criteria for insomnia of three months' duration or longer. Nonclinician sleep coaches delivered five sessions of manual-based cognitive behavioral therapy for insomnia, including stimulus control, sleep restriction, sleep hygiene, and cognitive therapy, with weekly telephone behavioral sleep medicine supervision. Controls received sleep education. Intervention subjects had greater improvement than controls between baseline and post-treatment, baseline and six months, and baseline and 12 months in sleep onset latency, total wake time, sleep efficiency, Pittsburgh Sleep Quality Index, and Insomnia Severity Index.
Antioxidants, carotenes, fruits, and vegetables are associated with higher amyotrophic lateral sclerosis (ALS) function at baseline, according to a study published online ahead of print October 24 in JAMA Neurology. A cross-sectional baseline analysis of the ALS Multicenter Cohort Study of Oxidative Stress was conducted at 16 ALS clinics throughout the United States. Baseline data were available on 302 patients (124 women) with ALS (median age, 63.2). Regression analysis of nutrients found that higher intakes of antioxidants and carotenes from vegetables were associated with higher ALS Functional Rating Scale-Revised (ALSFRS-R) scores or percentage forced vital capacity. Empirically weighted indices using the weighted quantile sum regression method of "good" micronutrients and "good" food groups were positively associated with ALSFRS-R scores and percentage forced vital capacity.
Fluselenamyl detects amyloid clumps better than current FDA-approved compounds, according to a study published online ahead of print November 2 in Scientific Reports. To determine whether fluselenamyl can detect amyloid beta plaques in the brain, researchers used the compound to stain brain slices from people who had died of Alzheimer's disease and from people of similar ages who had died of other causes (ie, controls). Fluselenamyl labeled diffuse and fibrillar plaques in brain sections of patients with Alzheimer's disease, but did not interact with biomarker proteins of other neurodegenerative diseases, thereby indicating specificity for detecting amyloid beta in Alzheimer's disease. Overall, fluselenamyl demonstrated potent binding affinity to autopsy-confirmed Alzheimer's disease homogenates. The binding affinity was superior to that of [18F]-AV-45, [18F]-florbetaben, and [18F]-flutemetamol.
Preserved hippocampal volumes are associated with increased risk of probable dementia with Lewy bodies, rather than Alzheimer's disease, in patients with mild cognitive impairment (MCI), according to a study published online ahead of print November 2 in Neurology. In the study, 160 people with MCI underwent MRI to measure hippocampal size. During a median follow-up of two years, 38% of people developed Alzheimer's disease, and 13% of people developed probable dementia with Lewy bodies. The people who had no hippocampal shrinkage were 5.8 times more likely to develop probable dementia with Lewy bodies than people who had hippocampal atrophy. Approximately 85% of people who developed dementia with Lewy bodies had a normal hippocampal volume. Furthermore, 61% of people who developed Alzheimer's disease had hippocampal atrophy.
Use of a media device at bedtime is significantly associated with inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness, according to a systematic review published online ahead of print October 31 in JAMA Pediatrics. Researchers examined published studies of school-age children between ages six and 19 with information about portable screen-based media devices and sleep outcomes. The final analysis included 125,198 children with an average age of 14.5. Children who had access to, but did not use, media devices at night were more likely to have inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness. Teachers, health care professionals, and parents should cooperate to minimize device access at bedtime, according to the researchers. Future studies should evaluate devices' influence on sleep hygiene, they added.
The FDA has approved the Amplatzer Patent Foramen Ovale (PFO) Occluder device, which reduces the risk of stroke in patients who previously had a stroke believed to be caused by a blood clot that passed through a PFO. The Amplatzer PFO Occluder is inserted through a catheter that is placed in a leg vein and advanced to the heart. In a randomized study, 499 participants ages 18 to 60 were treated with the Amplatzer PFO Occluder and blood-thinning medications and compared with 481 participants treated with blood-thinning medications alone. There was a 50% reduction in the rate of new strokes in participants using the Amplatzer PFO Occluder and blood-thinning medications, compared with participants taking medications alone. St. Jude Medical, headquartered in Plymouth, Minnesota, markets the Amplatzer PFO Occluder.
—Kimberly Williams
Economic background does not affect the clinical course or long-term seizure outcome of childhood epilepsy, according to a study in Nova Scotia, Canada, published online ahead of print November 4 in Epilepsia. Researchers examined data for 421 patients with childhood epilepsy and 10 or more years of follow-up. Overall, 33% of families had poor income, 38% had adequate income, and 30% were well-off. Terminal remission occurred in 65% of the poor, 61% of the adequate, and 61% of the well-off populations. Intractable epilepsy, status epilepticus, number of antiepileptic drugs used, and the number of generalized tonic-clonic or focal with secondary generalization seizures through the clinical course was the same in all groups. Neither paternal nor maternal education was associated with remission. Poor children had significantly more adverse social outcomes, however.
A genetic variant near melatonin receptor 1A (MTNR1A) may be associated with job-related exhaustion in shift workers, according to a study published online ahead of print October 10 in Sleep. Researchers assessed intolerance to shift work with job-related exhaustion symptoms in shift workers using the emotional exhaustion subscale of the Maslach Burnout Inventory-General Survey and performed a genome-wide association study. Job-related exhaustion was associated with the rs12506228 variation, located downstream of MTNR1A, in shift workers included in the Finnish national Health 2000 survey. The risk allele was also associated with reduced in silico gene expression levels of MTNR1A in brain tissue and with changes in DNA methylation in the 5' regulatory region of MTNR1A. The risk variant may lead to reduced melatonin signaling in the brain.
In healthy postmenopausal women, reproductive life events related to sex hormones are positively related to aspects of cognition in later life, according to a study published November 7 in the Journal of the American Geriatrics Society. Researchers evaluated 830 menopausal women using a cognitive battery and a structured reproductive history questionnaire. On multivariable modeling, age at menarche of 13 or older was inversely associated with global cognition. Having a last pregnancy after age 35 was positively associated with verbal memory. Use of hormonal contraceptives was positively associated with global cognition and verbal memory. The association between hormonal contraceptive use and verbal memory and executive function was strongest for more than 10 years of use. Reproductive period was positively associated with global cognition and executive function.
Physical fitness, BMI, IQ, and stress resilience in young adulthood may be associated with the development of amyotrophic lateral sclerosis (ALS) at an early age, according to a study published in the October issue of the European Journal of Neurology. Data on physical fitness, BMI, IQ, and stress resilience were collected from 1,838,376 Swedish men ages 17 to 20 at conscription from 1968 to 2010. During follow-up, 439 participants developed ALS. People with physical fitness above the highest tertile had a higher risk of ALS before age 45. People with BMI greater than or equal to 25 had a lower risk of ALS at all ages. Individuals with IQ above the highest tertile had a significantly increased risk of ALS at an age of 56 and older.
Short sleep is associated with greater intake of sugared caffeinated sodas, according to a study published online ahead of print November 9 in Sleep Health. Using data from the 2005 to 2012 National Health and Nutrition Examination Survey, researchers examined self-reported sleep duration and beverage intake from two 24-hour dietary recalls among 18,779 adults. Adults who slept for seven to eight hours each night were considered the reference group. In fully adjusted models, people who slept for five hours or less had 21% higher sugar-sweetened beverage consumption. When analyzed by beverage type, this difference was attributed to caffeinated sugary beverages. Longer sleepers consumed fewer servings of coffee and water. There were no associations between self-reported sleep duration and consumption of 100% juice, tea, or diet drinks.
Treadmill training plus virtual reality reduces fall rates, compared with treadmill training alone, according to a study published September 17 in the Lancet. Adults ages 60 to 90 with motor and cognitive deficits and a high risk of falls were randomly assigned to receive six weeks of treadmill training plus virtual reality or treadmill training alone. Data from 282 participants were included in the prespecified, modified intention-to-treat analysis. In the six months after training, the incident rate of falls was significantly lower in the treadmill-training-plus-virtual-reality group than it had been before training. The incident rate did not decrease significantly in the treadmill-training-alone group. Six months after training, the incident rate of falls was also significantly lower in the treadmill-training-plus-virtual-reality group than in the treadmill-training group.
Current research does not support specific recommendations for treating hypertension to preserve cognition, according to a scientific statement by the American Heart Association published online ahead of print October 10 in Hypertension. A panel of experts reviewed the literature on hypertension, the treatment of hypertension, and the relationship between hypertension and cognition, and summarized the available data. They found that hypertension disrupts the structure and function of cerebral blood vessels, leads to ischemic damage of white matter regions critical for cognitive function, and may promote Alzheimer pathology. They found strong evidence of a negative influence of mid-life hypertension on late-life cognitive function, but the cognitive effect of late-life hypertension is unclear. Observational studies indicate that high blood pressure damages the brain's blood vessels, leading to reduced blood flow to brain cells.
Manual-based cognitive behavioral therapy for insomnia delivered by nonclinician sleep coaches improves sleep in older adults with chronic insomnia, according to a study published in the September issue of the Journal of the American Geriatrics Society. Researchers studied veterans age 60 or older who met diagnostic criteria for insomnia of three months' duration or longer. Nonclinician sleep coaches delivered five sessions of manual-based cognitive behavioral therapy for insomnia, including stimulus control, sleep restriction, sleep hygiene, and cognitive therapy, with weekly telephone behavioral sleep medicine supervision. Controls received sleep education. Intervention subjects had greater improvement than controls between baseline and post-treatment, baseline and six months, and baseline and 12 months in sleep onset latency, total wake time, sleep efficiency, Pittsburgh Sleep Quality Index, and Insomnia Severity Index.
Antioxidants, carotenes, fruits, and vegetables are associated with higher amyotrophic lateral sclerosis (ALS) function at baseline, according to a study published online ahead of print October 24 in JAMA Neurology. A cross-sectional baseline analysis of the ALS Multicenter Cohort Study of Oxidative Stress was conducted at 16 ALS clinics throughout the United States. Baseline data were available on 302 patients (124 women) with ALS (median age, 63.2). Regression analysis of nutrients found that higher intakes of antioxidants and carotenes from vegetables were associated with higher ALS Functional Rating Scale-Revised (ALSFRS-R) scores or percentage forced vital capacity. Empirically weighted indices using the weighted quantile sum regression method of "good" micronutrients and "good" food groups were positively associated with ALSFRS-R scores and percentage forced vital capacity.
Fluselenamyl detects amyloid clumps better than current FDA-approved compounds, according to a study published online ahead of print November 2 in Scientific Reports. To determine whether fluselenamyl can detect amyloid beta plaques in the brain, researchers used the compound to stain brain slices from people who had died of Alzheimer's disease and from people of similar ages who had died of other causes (ie, controls). Fluselenamyl labeled diffuse and fibrillar plaques in brain sections of patients with Alzheimer's disease, but did not interact with biomarker proteins of other neurodegenerative diseases, thereby indicating specificity for detecting amyloid beta in Alzheimer's disease. Overall, fluselenamyl demonstrated potent binding affinity to autopsy-confirmed Alzheimer's disease homogenates. The binding affinity was superior to that of [18F]-AV-45, [18F]-florbetaben, and [18F]-flutemetamol.
Preserved hippocampal volumes are associated with increased risk of probable dementia with Lewy bodies, rather than Alzheimer's disease, in patients with mild cognitive impairment (MCI), according to a study published online ahead of print November 2 in Neurology. In the study, 160 people with MCI underwent MRI to measure hippocampal size. During a median follow-up of two years, 38% of people developed Alzheimer's disease, and 13% of people developed probable dementia with Lewy bodies. The people who had no hippocampal shrinkage were 5.8 times more likely to develop probable dementia with Lewy bodies than people who had hippocampal atrophy. Approximately 85% of people who developed dementia with Lewy bodies had a normal hippocampal volume. Furthermore, 61% of people who developed Alzheimer's disease had hippocampal atrophy.
Use of a media device at bedtime is significantly associated with inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness, according to a systematic review published online ahead of print October 31 in JAMA Pediatrics. Researchers examined published studies of school-age children between ages six and 19 with information about portable screen-based media devices and sleep outcomes. The final analysis included 125,198 children with an average age of 14.5. Children who had access to, but did not use, media devices at night were more likely to have inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness. Teachers, health care professionals, and parents should cooperate to minimize device access at bedtime, according to the researchers. Future studies should evaluate devices' influence on sleep hygiene, they added.
The FDA has approved the Amplatzer Patent Foramen Ovale (PFO) Occluder device, which reduces the risk of stroke in patients who previously had a stroke believed to be caused by a blood clot that passed through a PFO. The Amplatzer PFO Occluder is inserted through a catheter that is placed in a leg vein and advanced to the heart. In a randomized study, 499 participants ages 18 to 60 were treated with the Amplatzer PFO Occluder and blood-thinning medications and compared with 481 participants treated with blood-thinning medications alone. There was a 50% reduction in the rate of new strokes in participants using the Amplatzer PFO Occluder and blood-thinning medications, compared with participants taking medications alone. St. Jude Medical, headquartered in Plymouth, Minnesota, markets the Amplatzer PFO Occluder.
—Kimberly Williams