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American Academy of Neurology (AAN): Annual Meeting
Risk factors identified for in-hospital death after stroke
SAN DIEGO – The top two significant risk factors of in-hospital mortality following acute stroke are having a hemorrhagic stroke and having hyperhomocysteinemia, results from a large database analysis demonstrated.
Using information from the Nationwide Inpatient Database for 2006 to 2010, Dr. Nassim Naderi of the department of neurology at the University of California, Irvine, and colleagues set out to evaluate the effect of patient characteristics, comorbidities, stroke type, and teaching status of the hospital on in-patient mortality following acute stroke. They included patients admitted for acute stroke, excluded those admitted for transient ischemic attack, and used multivariate regression analysis to identify risk factors predictive of in-hospital mortality.
During a poster session at the annual meeting of the American Academy of Neurology, the researchers reported results from 2,567,100 patients admitted with a diagnosis of acute stroke. Most (82%) were ischemic while the remainder were hemorrhagic. Slightly more than half of the patients (52%) were female, 70% were white, and their mean age was 71 years. Hypertension was the most common associated comorbidity (77%), followed by hyperlipidemia (41%), diabetes (31%), coronary artery disease (24%), and atrial fibrillation and smoking (both at 21%).
The overall rate of in-hospital mortality was 8.42%. By stroke type, 5.43% of those with ischemic stroke died in the hospital, compared with 22.35% of those with hemorrhagic stroke. Multivariate regression analysis revealed eight major risk factors of in-hospital mortality for acute stroke: having hemorrhagic stroke (adjusted odds ratio of 4.89), hyperhomocysteinemia (AOR 4.70), hyperlipidemia (AOR 1.90), heart failure (AOR 1.49), age over 65 (AOR 1.42), chronic kidney disease (AOR 1.31), liver disease (AOR 1.31), and cocaine use (AOR 1.22).
Another seven risk factors had a statistically significant impact on the odds of in-hospital mortality following acute stroke, but they were less clinically significant. These were white race (AOR 1.15), female gender (AOR 1.11), coronary artery disease (AOR 1.09), being treated in a teaching hospital (AOR 1.09), peripheral vascular disease (AOR 1.07), chronic lung disease (AOR 1.04), and alcohol abuse (AOR 1.04).
"The present finding suggests that patients at increased risk of mortality can be identified and additional treatment for prevention might be warranted," the researchers concluded in their poster.
Dr. Naderi and all other authors except one said they had no relevant financial disclosures. One author reported receiving personal compensation for activities and research support from numerous companies.
SAN DIEGO – The top two significant risk factors of in-hospital mortality following acute stroke are having a hemorrhagic stroke and having hyperhomocysteinemia, results from a large database analysis demonstrated.
Using information from the Nationwide Inpatient Database for 2006 to 2010, Dr. Nassim Naderi of the department of neurology at the University of California, Irvine, and colleagues set out to evaluate the effect of patient characteristics, comorbidities, stroke type, and teaching status of the hospital on in-patient mortality following acute stroke. They included patients admitted for acute stroke, excluded those admitted for transient ischemic attack, and used multivariate regression analysis to identify risk factors predictive of in-hospital mortality.
During a poster session at the annual meeting of the American Academy of Neurology, the researchers reported results from 2,567,100 patients admitted with a diagnosis of acute stroke. Most (82%) were ischemic while the remainder were hemorrhagic. Slightly more than half of the patients (52%) were female, 70% were white, and their mean age was 71 years. Hypertension was the most common associated comorbidity (77%), followed by hyperlipidemia (41%), diabetes (31%), coronary artery disease (24%), and atrial fibrillation and smoking (both at 21%).
The overall rate of in-hospital mortality was 8.42%. By stroke type, 5.43% of those with ischemic stroke died in the hospital, compared with 22.35% of those with hemorrhagic stroke. Multivariate regression analysis revealed eight major risk factors of in-hospital mortality for acute stroke: having hemorrhagic stroke (adjusted odds ratio of 4.89), hyperhomocysteinemia (AOR 4.70), hyperlipidemia (AOR 1.90), heart failure (AOR 1.49), age over 65 (AOR 1.42), chronic kidney disease (AOR 1.31), liver disease (AOR 1.31), and cocaine use (AOR 1.22).
Another seven risk factors had a statistically significant impact on the odds of in-hospital mortality following acute stroke, but they were less clinically significant. These were white race (AOR 1.15), female gender (AOR 1.11), coronary artery disease (AOR 1.09), being treated in a teaching hospital (AOR 1.09), peripheral vascular disease (AOR 1.07), chronic lung disease (AOR 1.04), and alcohol abuse (AOR 1.04).
"The present finding suggests that patients at increased risk of mortality can be identified and additional treatment for prevention might be warranted," the researchers concluded in their poster.
Dr. Naderi and all other authors except one said they had no relevant financial disclosures. One author reported receiving personal compensation for activities and research support from numerous companies.
SAN DIEGO – The top two significant risk factors of in-hospital mortality following acute stroke are having a hemorrhagic stroke and having hyperhomocysteinemia, results from a large database analysis demonstrated.
Using information from the Nationwide Inpatient Database for 2006 to 2010, Dr. Nassim Naderi of the department of neurology at the University of California, Irvine, and colleagues set out to evaluate the effect of patient characteristics, comorbidities, stroke type, and teaching status of the hospital on in-patient mortality following acute stroke. They included patients admitted for acute stroke, excluded those admitted for transient ischemic attack, and used multivariate regression analysis to identify risk factors predictive of in-hospital mortality.
During a poster session at the annual meeting of the American Academy of Neurology, the researchers reported results from 2,567,100 patients admitted with a diagnosis of acute stroke. Most (82%) were ischemic while the remainder were hemorrhagic. Slightly more than half of the patients (52%) were female, 70% were white, and their mean age was 71 years. Hypertension was the most common associated comorbidity (77%), followed by hyperlipidemia (41%), diabetes (31%), coronary artery disease (24%), and atrial fibrillation and smoking (both at 21%).
The overall rate of in-hospital mortality was 8.42%. By stroke type, 5.43% of those with ischemic stroke died in the hospital, compared with 22.35% of those with hemorrhagic stroke. Multivariate regression analysis revealed eight major risk factors of in-hospital mortality for acute stroke: having hemorrhagic stroke (adjusted odds ratio of 4.89), hyperhomocysteinemia (AOR 4.70), hyperlipidemia (AOR 1.90), heart failure (AOR 1.49), age over 65 (AOR 1.42), chronic kidney disease (AOR 1.31), liver disease (AOR 1.31), and cocaine use (AOR 1.22).
Another seven risk factors had a statistically significant impact on the odds of in-hospital mortality following acute stroke, but they were less clinically significant. These were white race (AOR 1.15), female gender (AOR 1.11), coronary artery disease (AOR 1.09), being treated in a teaching hospital (AOR 1.09), peripheral vascular disease (AOR 1.07), chronic lung disease (AOR 1.04), and alcohol abuse (AOR 1.04).
"The present finding suggests that patients at increased risk of mortality can be identified and additional treatment for prevention might be warranted," the researchers concluded in their poster.
Dr. Naderi and all other authors except one said they had no relevant financial disclosures. One author reported receiving personal compensation for activities and research support from numerous companies.
AT THE 2013 AAN ANNUAL MEETING
Major finding: The leading risk factor for in-hospital mortality following acute stroke was having a hemorrhagic stroke (adjusted odds ratio of 4.89).
Data source: An analysis of 2,567,100 patients from the Nationwide Inpatient Database who were admitted with a diagnosis of acute stroke between 2006 and 2010.
Disclosures: Dr. Naderi and all other authors except one said they had no disclosures. One author reported receiving personal compensation for activities and research support from numerous companies.
REM sleep problems predict Parkinson's, Lewy body dementia
SAN DIEGO – REM sleep behavior disorder is the earliest indication that patients are destined to develop Parkinson’s disease, Lewy body dementia, or another synucleinopathy; it precedes the onset of motor and cognitive problems by years, according to a growing body of research.
Its presence also distinguishes synucleinopathies from Alzheimer’s disease and other problems that can have similar early presentations.
REM sleep behavior disorder (RBD) "diagnoses disease" and "identifies prodromal disease. The rule is very simple: RBD equals synucleinopathy, and it works almost every time," said Dr. Ronald Postuma of the department of neurology at McGill University in Montreal, and a leading researcher in the field.
"The way I explain RBD to patients is that ‘normally, when most people dream, they are paralyzed, but you are not. Therefore, you are capable of acting out the content of your dreams.’ Injury is relatively common," he said, but RBD can be subtle, too, with no more than gestures during sleep.
Dr. Postuma made his comments at the annual meeting of the American Academy of Neurology, following the presentation there of a new addition to the evidence base, an autopsy study led by the Mayo Clinic in Rochester, Minn., and recently published online (Sleep Med. 2013 [doi:10.1016/j.sleep.2012.10.015]).
The Mayo team analyzed neuropathologic findings from 172 patients diagnosed with RBD before death. They found that "among [the 170] neurodegenerative disorders associated with RBD, 160 (94%) were synucleinopathies." Among them were 136 patients with Lewy bodies and 19 with multiple-system atrophy. The remaining few had findings consistent with Alzheimer’s disease or other nonsynucleinopathies.
In life, RBD was diagnosed at a mean age of 62 years of age. It preceded the eventual diagnosis of Parkinsonism in 151 patients by a mean of 6 years. The diagnosis of RBD preceded death by a mean of 13 years.
"Lewy body disease was by far the most common underlying neurologic disorder. The chunk of the rest was multiple-system atrophy. We’ve been looking for [cases of] Alzheimer’s associated with RBD for well over 10 years, and they are just hard to find." The findings "again underscore the selectivity of RBD for synucleinopathy. [They] argue that the selective vulnerability involves ... REM sleep circuitry," said lead investigator Dr. Bradley Boeve, chair of the division of behavioral neurology at Mayo.
Most of the subjects (83%) were men. Eighty-two were diagnosed with RBD by polysomnography, the gold-standard; 98% of the PSG-confirmed cases had a synucleinopathy at autopsy, Dr. Boeve noted.
The remainder had been diagnosed by history, which "can really be quite good" so long as sleep apnea and other confounders are kept in mind, said Dr. Postuma, who was not involved in the project.
The take-home message is that "if you have a patient with a neurodegenerative disorder in front of you, if the patient doesn’t have RBD and that patient is demented, the chances are [that they don’t] have [Lewy body dementia]. In contrast, if you have a pretty good history of RBD but don’t have a PSG [polysomnography] to confirm it, there’s a 94% chance that you have a synucleinopathy. If you do have PSG, there’s a 98% chance of having a synucleinopathy," Dr. Postuma said.
"I don’t think there is any marker in clinical medicine that has anything close to this amount of relative risk for developing a neurodegenerative disease. This is completely unique. Asking about REM sleep behavior disorder in your clinics tomorrow will help you diagnose disease," he said.
Investigators from Barcelona, Spain, came to similar conclusions in a paper published online April 2 in Lancet Neurology (doi:10.1016/S1474-4422[13]70056-5).
For most, RBD "represents the prodromal phase of a Lewy body disorder ... such as Parkinson’s disease (PD) or dementia with Lewy bodies. ... [RBD] is a candidate for the study of early events and progression of this prodromal phase, and to test disease-modifying strategies to slow or stop the neurodegenerative process," they concluded.
The Spanish team followed 44 RBD cases diagnosed between 1991 and 2003. By 2012, 36 (82%) had developed a synucleinopathy, among them 16 patients with Parkinson’s disease, 14 with Lewy body dementia, and 1 with multiple system atrophy. "The rates of neurological-disease-free survival from time of [RBD] diagnosis were 65.2% at 5 years, 26.6% at 10 years, and 7.5% at 14 years," they reported.
Most RBD patients "developed a Lewy body disorder with time. Patients who remained disease-free at follow-up showed markers of increased short-term risk for developing PD," including lesions "in the brainstem nuclei that regulate REM sleep atonia," the Spanish researchers found.
The findings "emphatically confirm the incredible risk that patients with RBD have for developing neurodegenerative disease. This is completely unique, this ability to identify a neurodegenerative disease 10 years before it can be diagnosed. It provides profound opportunities to study early stages of disease and perhaps to test preventative treatments that could be applied to Parkinson’s disease and related disorders," Dr. Postuma said when asked to comment on the Spanish study.
"I don’t think you could imagine a better group to intervene with neuroprotective therapy than this one," he said.
Dr. Boeve’s research has been supported by Cephalon, Allon Therapeutics, and GE Healthcare. Dr. Postuma disclosed personal support from Teva and Novartis.
SAN DIEGO – REM sleep behavior disorder is the earliest indication that patients are destined to develop Parkinson’s disease, Lewy body dementia, or another synucleinopathy; it precedes the onset of motor and cognitive problems by years, according to a growing body of research.
Its presence also distinguishes synucleinopathies from Alzheimer’s disease and other problems that can have similar early presentations.
REM sleep behavior disorder (RBD) "diagnoses disease" and "identifies prodromal disease. The rule is very simple: RBD equals synucleinopathy, and it works almost every time," said Dr. Ronald Postuma of the department of neurology at McGill University in Montreal, and a leading researcher in the field.
"The way I explain RBD to patients is that ‘normally, when most people dream, they are paralyzed, but you are not. Therefore, you are capable of acting out the content of your dreams.’ Injury is relatively common," he said, but RBD can be subtle, too, with no more than gestures during sleep.
Dr. Postuma made his comments at the annual meeting of the American Academy of Neurology, following the presentation there of a new addition to the evidence base, an autopsy study led by the Mayo Clinic in Rochester, Minn., and recently published online (Sleep Med. 2013 [doi:10.1016/j.sleep.2012.10.015]).
The Mayo team analyzed neuropathologic findings from 172 patients diagnosed with RBD before death. They found that "among [the 170] neurodegenerative disorders associated with RBD, 160 (94%) were synucleinopathies." Among them were 136 patients with Lewy bodies and 19 with multiple-system atrophy. The remaining few had findings consistent with Alzheimer’s disease or other nonsynucleinopathies.
In life, RBD was diagnosed at a mean age of 62 years of age. It preceded the eventual diagnosis of Parkinsonism in 151 patients by a mean of 6 years. The diagnosis of RBD preceded death by a mean of 13 years.
"Lewy body disease was by far the most common underlying neurologic disorder. The chunk of the rest was multiple-system atrophy. We’ve been looking for [cases of] Alzheimer’s associated with RBD for well over 10 years, and they are just hard to find." The findings "again underscore the selectivity of RBD for synucleinopathy. [They] argue that the selective vulnerability involves ... REM sleep circuitry," said lead investigator Dr. Bradley Boeve, chair of the division of behavioral neurology at Mayo.
Most of the subjects (83%) were men. Eighty-two were diagnosed with RBD by polysomnography, the gold-standard; 98% of the PSG-confirmed cases had a synucleinopathy at autopsy, Dr. Boeve noted.
The remainder had been diagnosed by history, which "can really be quite good" so long as sleep apnea and other confounders are kept in mind, said Dr. Postuma, who was not involved in the project.
The take-home message is that "if you have a patient with a neurodegenerative disorder in front of you, if the patient doesn’t have RBD and that patient is demented, the chances are [that they don’t] have [Lewy body dementia]. In contrast, if you have a pretty good history of RBD but don’t have a PSG [polysomnography] to confirm it, there’s a 94% chance that you have a synucleinopathy. If you do have PSG, there’s a 98% chance of having a synucleinopathy," Dr. Postuma said.
"I don’t think there is any marker in clinical medicine that has anything close to this amount of relative risk for developing a neurodegenerative disease. This is completely unique. Asking about REM sleep behavior disorder in your clinics tomorrow will help you diagnose disease," he said.
Investigators from Barcelona, Spain, came to similar conclusions in a paper published online April 2 in Lancet Neurology (doi:10.1016/S1474-4422[13]70056-5).
For most, RBD "represents the prodromal phase of a Lewy body disorder ... such as Parkinson’s disease (PD) or dementia with Lewy bodies. ... [RBD] is a candidate for the study of early events and progression of this prodromal phase, and to test disease-modifying strategies to slow or stop the neurodegenerative process," they concluded.
The Spanish team followed 44 RBD cases diagnosed between 1991 and 2003. By 2012, 36 (82%) had developed a synucleinopathy, among them 16 patients with Parkinson’s disease, 14 with Lewy body dementia, and 1 with multiple system atrophy. "The rates of neurological-disease-free survival from time of [RBD] diagnosis were 65.2% at 5 years, 26.6% at 10 years, and 7.5% at 14 years," they reported.
Most RBD patients "developed a Lewy body disorder with time. Patients who remained disease-free at follow-up showed markers of increased short-term risk for developing PD," including lesions "in the brainstem nuclei that regulate REM sleep atonia," the Spanish researchers found.
The findings "emphatically confirm the incredible risk that patients with RBD have for developing neurodegenerative disease. This is completely unique, this ability to identify a neurodegenerative disease 10 years before it can be diagnosed. It provides profound opportunities to study early stages of disease and perhaps to test preventative treatments that could be applied to Parkinson’s disease and related disorders," Dr. Postuma said when asked to comment on the Spanish study.
"I don’t think you could imagine a better group to intervene with neuroprotective therapy than this one," he said.
Dr. Boeve’s research has been supported by Cephalon, Allon Therapeutics, and GE Healthcare. Dr. Postuma disclosed personal support from Teva and Novartis.
SAN DIEGO – REM sleep behavior disorder is the earliest indication that patients are destined to develop Parkinson’s disease, Lewy body dementia, or another synucleinopathy; it precedes the onset of motor and cognitive problems by years, according to a growing body of research.
Its presence also distinguishes synucleinopathies from Alzheimer’s disease and other problems that can have similar early presentations.
REM sleep behavior disorder (RBD) "diagnoses disease" and "identifies prodromal disease. The rule is very simple: RBD equals synucleinopathy, and it works almost every time," said Dr. Ronald Postuma of the department of neurology at McGill University in Montreal, and a leading researcher in the field.
"The way I explain RBD to patients is that ‘normally, when most people dream, they are paralyzed, but you are not. Therefore, you are capable of acting out the content of your dreams.’ Injury is relatively common," he said, but RBD can be subtle, too, with no more than gestures during sleep.
Dr. Postuma made his comments at the annual meeting of the American Academy of Neurology, following the presentation there of a new addition to the evidence base, an autopsy study led by the Mayo Clinic in Rochester, Minn., and recently published online (Sleep Med. 2013 [doi:10.1016/j.sleep.2012.10.015]).
The Mayo team analyzed neuropathologic findings from 172 patients diagnosed with RBD before death. They found that "among [the 170] neurodegenerative disorders associated with RBD, 160 (94%) were synucleinopathies." Among them were 136 patients with Lewy bodies and 19 with multiple-system atrophy. The remaining few had findings consistent with Alzheimer’s disease or other nonsynucleinopathies.
In life, RBD was diagnosed at a mean age of 62 years of age. It preceded the eventual diagnosis of Parkinsonism in 151 patients by a mean of 6 years. The diagnosis of RBD preceded death by a mean of 13 years.
"Lewy body disease was by far the most common underlying neurologic disorder. The chunk of the rest was multiple-system atrophy. We’ve been looking for [cases of] Alzheimer’s associated with RBD for well over 10 years, and they are just hard to find." The findings "again underscore the selectivity of RBD for synucleinopathy. [They] argue that the selective vulnerability involves ... REM sleep circuitry," said lead investigator Dr. Bradley Boeve, chair of the division of behavioral neurology at Mayo.
Most of the subjects (83%) were men. Eighty-two were diagnosed with RBD by polysomnography, the gold-standard; 98% of the PSG-confirmed cases had a synucleinopathy at autopsy, Dr. Boeve noted.
The remainder had been diagnosed by history, which "can really be quite good" so long as sleep apnea and other confounders are kept in mind, said Dr. Postuma, who was not involved in the project.
The take-home message is that "if you have a patient with a neurodegenerative disorder in front of you, if the patient doesn’t have RBD and that patient is demented, the chances are [that they don’t] have [Lewy body dementia]. In contrast, if you have a pretty good history of RBD but don’t have a PSG [polysomnography] to confirm it, there’s a 94% chance that you have a synucleinopathy. If you do have PSG, there’s a 98% chance of having a synucleinopathy," Dr. Postuma said.
"I don’t think there is any marker in clinical medicine that has anything close to this amount of relative risk for developing a neurodegenerative disease. This is completely unique. Asking about REM sleep behavior disorder in your clinics tomorrow will help you diagnose disease," he said.
Investigators from Barcelona, Spain, came to similar conclusions in a paper published online April 2 in Lancet Neurology (doi:10.1016/S1474-4422[13]70056-5).
For most, RBD "represents the prodromal phase of a Lewy body disorder ... such as Parkinson’s disease (PD) or dementia with Lewy bodies. ... [RBD] is a candidate for the study of early events and progression of this prodromal phase, and to test disease-modifying strategies to slow or stop the neurodegenerative process," they concluded.
The Spanish team followed 44 RBD cases diagnosed between 1991 and 2003. By 2012, 36 (82%) had developed a synucleinopathy, among them 16 patients with Parkinson’s disease, 14 with Lewy body dementia, and 1 with multiple system atrophy. "The rates of neurological-disease-free survival from time of [RBD] diagnosis were 65.2% at 5 years, 26.6% at 10 years, and 7.5% at 14 years," they reported.
Most RBD patients "developed a Lewy body disorder with time. Patients who remained disease-free at follow-up showed markers of increased short-term risk for developing PD," including lesions "in the brainstem nuclei that regulate REM sleep atonia," the Spanish researchers found.
The findings "emphatically confirm the incredible risk that patients with RBD have for developing neurodegenerative disease. This is completely unique, this ability to identify a neurodegenerative disease 10 years before it can be diagnosed. It provides profound opportunities to study early stages of disease and perhaps to test preventative treatments that could be applied to Parkinson’s disease and related disorders," Dr. Postuma said when asked to comment on the Spanish study.
"I don’t think you could imagine a better group to intervene with neuroprotective therapy than this one," he said.
Dr. Boeve’s research has been supported by Cephalon, Allon Therapeutics, and GE Healthcare. Dr. Postuma disclosed personal support from Teva and Novartis.
AT THE 2013 AAN ANNUAL MEETING
Major finding: More than 90% of patients with REM sleep behavior disorder will develop Parkinson’s disease or Lewy body dementia.
Data source: A study of brain autopsies on 172 people diagnosed in life with REM sleep behavior disorder.
Disclosures: The lead investigator disclosed research support from Cephalon, Allon Therapeutics, and GE Healthcare.
Manage most SEGAs with rapamycin analogs, not surgery
SAN DIEGO – Medical management with sirolimus or everolimus for pediatric patients with tuberous sclerosis complex and subependymal giant cell astrocytomas is more effective and safer than surgery, researchers from the University of Cincinnati and University of California, Los Angeles, have found.
Although the benign tumors have traditionally been left to surgeons, it’s become clear in recent years that rapamycin analogs are effective, too. The question has been "which [approach] is best? Medical management "is known to be pretty mild compared to the surgery," but it’s not curative, explained lead investigator Susanne Yoon, the University of Cincinnati medical student who presented the results at the annual meeting of the American Academy of Neurology.
The team compared outcomes for 23 SEGA (subependymal giant cell astrocytoma) patients who underwent surgery, 81 who took sirolimus or everolimus, and 9 who got both. The surgery patients were diagnosed when they were about 10 years old and were followed for a median of 8.9 years; the medical patients were about 7 years old when diagnosed, and were followed for a median of 2.8 years. Boys made up the majority of both groups.
None of the children who took a rapamycin analog needed surgery; tumors shrank by more than half in 61% (45). The drugs caused infections, weight change, or hyperlipidemia in some, but only 13% (11) needed to stop the drug or go to the hospital because of side effects.
Meanwhile, surgery cured just 39% (9) of the children who got it, sometimes after two or three operations; 61% (14) of those patients had prolonged hospitalizations or were hospitalized due to postoperative complications that included intracranial hemorrhage in 8, hydrocephalus/shunt malfunction in 6, neurologic impairment, and seizures.
"Not only does medical management win in efficacy, but it also wins in the safety issues. Rapalog [rapamycin] therapy, alone or in combination, is becoming a cornerstone of tumor management" in neurocutaneous disorders, said Dr. David H. Viskochil, professor of pediatrics at the University of Utah, Salt Lake City, commenting on the study.
"Of course, there are emergent situations where you’ve just got to go in and get the tumor out; you can’t wait 3 months to see" if drugs work. "But if a child is just starting to show some symptoms and not deteriorating, then you can start with medicine first and see what happens," he said.
"The question is if you got [SEGAs] really early, would surgical cure be much more likely? The studies aren’t quite there yet," he said in an interview.
Ms. Yoon and Dr. Viskochil said they have no disclosures.
SAN DIEGO – Medical management with sirolimus or everolimus for pediatric patients with tuberous sclerosis complex and subependymal giant cell astrocytomas is more effective and safer than surgery, researchers from the University of Cincinnati and University of California, Los Angeles, have found.
Although the benign tumors have traditionally been left to surgeons, it’s become clear in recent years that rapamycin analogs are effective, too. The question has been "which [approach] is best? Medical management "is known to be pretty mild compared to the surgery," but it’s not curative, explained lead investigator Susanne Yoon, the University of Cincinnati medical student who presented the results at the annual meeting of the American Academy of Neurology.
The team compared outcomes for 23 SEGA (subependymal giant cell astrocytoma) patients who underwent surgery, 81 who took sirolimus or everolimus, and 9 who got both. The surgery patients were diagnosed when they were about 10 years old and were followed for a median of 8.9 years; the medical patients were about 7 years old when diagnosed, and were followed for a median of 2.8 years. Boys made up the majority of both groups.
None of the children who took a rapamycin analog needed surgery; tumors shrank by more than half in 61% (45). The drugs caused infections, weight change, or hyperlipidemia in some, but only 13% (11) needed to stop the drug or go to the hospital because of side effects.
Meanwhile, surgery cured just 39% (9) of the children who got it, sometimes after two or three operations; 61% (14) of those patients had prolonged hospitalizations or were hospitalized due to postoperative complications that included intracranial hemorrhage in 8, hydrocephalus/shunt malfunction in 6, neurologic impairment, and seizures.
"Not only does medical management win in efficacy, but it also wins in the safety issues. Rapalog [rapamycin] therapy, alone or in combination, is becoming a cornerstone of tumor management" in neurocutaneous disorders, said Dr. David H. Viskochil, professor of pediatrics at the University of Utah, Salt Lake City, commenting on the study.
"Of course, there are emergent situations where you’ve just got to go in and get the tumor out; you can’t wait 3 months to see" if drugs work. "But if a child is just starting to show some symptoms and not deteriorating, then you can start with medicine first and see what happens," he said.
"The question is if you got [SEGAs] really early, would surgical cure be much more likely? The studies aren’t quite there yet," he said in an interview.
Ms. Yoon and Dr. Viskochil said they have no disclosures.
SAN DIEGO – Medical management with sirolimus or everolimus for pediatric patients with tuberous sclerosis complex and subependymal giant cell astrocytomas is more effective and safer than surgery, researchers from the University of Cincinnati and University of California, Los Angeles, have found.
Although the benign tumors have traditionally been left to surgeons, it’s become clear in recent years that rapamycin analogs are effective, too. The question has been "which [approach] is best? Medical management "is known to be pretty mild compared to the surgery," but it’s not curative, explained lead investigator Susanne Yoon, the University of Cincinnati medical student who presented the results at the annual meeting of the American Academy of Neurology.
The team compared outcomes for 23 SEGA (subependymal giant cell astrocytoma) patients who underwent surgery, 81 who took sirolimus or everolimus, and 9 who got both. The surgery patients were diagnosed when they were about 10 years old and were followed for a median of 8.9 years; the medical patients were about 7 years old when diagnosed, and were followed for a median of 2.8 years. Boys made up the majority of both groups.
None of the children who took a rapamycin analog needed surgery; tumors shrank by more than half in 61% (45). The drugs caused infections, weight change, or hyperlipidemia in some, but only 13% (11) needed to stop the drug or go to the hospital because of side effects.
Meanwhile, surgery cured just 39% (9) of the children who got it, sometimes after two or three operations; 61% (14) of those patients had prolonged hospitalizations or were hospitalized due to postoperative complications that included intracranial hemorrhage in 8, hydrocephalus/shunt malfunction in 6, neurologic impairment, and seizures.
"Not only does medical management win in efficacy, but it also wins in the safety issues. Rapalog [rapamycin] therapy, alone or in combination, is becoming a cornerstone of tumor management" in neurocutaneous disorders, said Dr. David H. Viskochil, professor of pediatrics at the University of Utah, Salt Lake City, commenting on the study.
"Of course, there are emergent situations where you’ve just got to go in and get the tumor out; you can’t wait 3 months to see" if drugs work. "But if a child is just starting to show some symptoms and not deteriorating, then you can start with medicine first and see what happens," he said.
"The question is if you got [SEGAs] really early, would surgical cure be much more likely? The studies aren’t quite there yet," he said in an interview.
Ms. Yoon and Dr. Viskochil said they have no disclosures.
AT THE 2013 AAN ANNUAL MEETING
Major finding: Rapamycin analogs shrink SEGA tumors by more than 50% in a majority of children, and obviate the need for surgery.
Data source: Comparison of surgical and medical treatment of SEGA tumors in 113 children.
Disclosures: Ms. Yoon and Dr. Viskochil said they have no disclosures.
Fingolimod slows MS brain atrophy within 6 months
SAN DIEGO – Fingolimod slows brain atrophy in patients with multiple sclerosis and is the only approved drug that does so within the first 6 months of treatment, according to Dr. Jeffrey Cohen of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic in Ohio.
The findings come from a combined analysis of the drug’s three clinical trials: FREEDOMS (Efficacy and Safety of Fingolimod in Patients With Relapsing-Remitting Multiple Sclerosis) and FREEDOMS II, which pitted 0.5 mg and 1.25 mg daily against placebo for 2 years, and TRANSFORMS (FREEDOMS With Optional Extension Phase), which pitted those doses against weekly intramuscular interferon beta-1a (Avonex) for a year. Brain volumes were assessed by MRI SIENA (structural image evaluation, using normalization, of atrophy) at baseline and 6, 12, and 24 months. More than 3,000 patients 18-55 years old with clinically active relapsing-remitting MS participated.
"There was a consistent" 31%-36% reduction in the rate of brain volume loss with both doses of fingolimod (Gilenya) "as compared to placebo and interferon beta-1a. There was no clear-cut dose effect between the two" doses, said Dr. Cohen, the lead investigator and the director of the Mellen center’s experimental therapeutics program.
In the two trials with placebo arms, fingolimod patients had volume losses of about 0.85%, compared with 1.31% in placebo patients. In the remaining trial, brain volume loss was about 0.31% with fingolimod and about 0.45% with interferon beta-1a.
The "benefit was seen as early as 6 months, in both FREEDOMS and FREEDOMS II. In this analysis of the overall study cohort, there was no apparent early acceleration of brain volume loss, in other words, no pseudoatrophy," Dr. Cohen said at the annual meeting of the American Academy of Neurology.
Other approved MS therapies have shown either no significant effect on brain atrophy or a benefit only in the second year of treatment, as with natalizumab (Tysabri) and glatiramer acetate (Copaxone), he said.
The study investigators found that baseline brain atrophy correlated best with baseline T1 and T2 lesion volume, disability, age, and disease duration and severity. Both high baseline T2 lesion volume and active gadolinium-enhancing T1 lesions predicted brain volume loss during the trial. Volume loss in the study correlated best with worsening disability and increasing numbers of T2 lesions.
The drug seemed to protect brain volume in patients who got it, regardless of baseline characteristics.
There were weak correlations between accumulations of T2 lesions and disability during the study, perhaps because "brain volume and measures of disability don’t change much over 2 years," Dr. Cohen said.
Novartis, the maker of fingolimod, paid for the study. Dr. Cohen disclosed compensation or research support from Novartis, Biogen Idec, Genzyme, Lilly, Serono, and Teva.
SAN DIEGO – Fingolimod slows brain atrophy in patients with multiple sclerosis and is the only approved drug that does so within the first 6 months of treatment, according to Dr. Jeffrey Cohen of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic in Ohio.
The findings come from a combined analysis of the drug’s three clinical trials: FREEDOMS (Efficacy and Safety of Fingolimod in Patients With Relapsing-Remitting Multiple Sclerosis) and FREEDOMS II, which pitted 0.5 mg and 1.25 mg daily against placebo for 2 years, and TRANSFORMS (FREEDOMS With Optional Extension Phase), which pitted those doses against weekly intramuscular interferon beta-1a (Avonex) for a year. Brain volumes were assessed by MRI SIENA (structural image evaluation, using normalization, of atrophy) at baseline and 6, 12, and 24 months. More than 3,000 patients 18-55 years old with clinically active relapsing-remitting MS participated.
"There was a consistent" 31%-36% reduction in the rate of brain volume loss with both doses of fingolimod (Gilenya) "as compared to placebo and interferon beta-1a. There was no clear-cut dose effect between the two" doses, said Dr. Cohen, the lead investigator and the director of the Mellen center’s experimental therapeutics program.
In the two trials with placebo arms, fingolimod patients had volume losses of about 0.85%, compared with 1.31% in placebo patients. In the remaining trial, brain volume loss was about 0.31% with fingolimod and about 0.45% with interferon beta-1a.
The "benefit was seen as early as 6 months, in both FREEDOMS and FREEDOMS II. In this analysis of the overall study cohort, there was no apparent early acceleration of brain volume loss, in other words, no pseudoatrophy," Dr. Cohen said at the annual meeting of the American Academy of Neurology.
Other approved MS therapies have shown either no significant effect on brain atrophy or a benefit only in the second year of treatment, as with natalizumab (Tysabri) and glatiramer acetate (Copaxone), he said.
The study investigators found that baseline brain atrophy correlated best with baseline T1 and T2 lesion volume, disability, age, and disease duration and severity. Both high baseline T2 lesion volume and active gadolinium-enhancing T1 lesions predicted brain volume loss during the trial. Volume loss in the study correlated best with worsening disability and increasing numbers of T2 lesions.
The drug seemed to protect brain volume in patients who got it, regardless of baseline characteristics.
There were weak correlations between accumulations of T2 lesions and disability during the study, perhaps because "brain volume and measures of disability don’t change much over 2 years," Dr. Cohen said.
Novartis, the maker of fingolimod, paid for the study. Dr. Cohen disclosed compensation or research support from Novartis, Biogen Idec, Genzyme, Lilly, Serono, and Teva.
SAN DIEGO – Fingolimod slows brain atrophy in patients with multiple sclerosis and is the only approved drug that does so within the first 6 months of treatment, according to Dr. Jeffrey Cohen of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic in Ohio.
The findings come from a combined analysis of the drug’s three clinical trials: FREEDOMS (Efficacy and Safety of Fingolimod in Patients With Relapsing-Remitting Multiple Sclerosis) and FREEDOMS II, which pitted 0.5 mg and 1.25 mg daily against placebo for 2 years, and TRANSFORMS (FREEDOMS With Optional Extension Phase), which pitted those doses against weekly intramuscular interferon beta-1a (Avonex) for a year. Brain volumes were assessed by MRI SIENA (structural image evaluation, using normalization, of atrophy) at baseline and 6, 12, and 24 months. More than 3,000 patients 18-55 years old with clinically active relapsing-remitting MS participated.
"There was a consistent" 31%-36% reduction in the rate of brain volume loss with both doses of fingolimod (Gilenya) "as compared to placebo and interferon beta-1a. There was no clear-cut dose effect between the two" doses, said Dr. Cohen, the lead investigator and the director of the Mellen center’s experimental therapeutics program.
In the two trials with placebo arms, fingolimod patients had volume losses of about 0.85%, compared with 1.31% in placebo patients. In the remaining trial, brain volume loss was about 0.31% with fingolimod and about 0.45% with interferon beta-1a.
The "benefit was seen as early as 6 months, in both FREEDOMS and FREEDOMS II. In this analysis of the overall study cohort, there was no apparent early acceleration of brain volume loss, in other words, no pseudoatrophy," Dr. Cohen said at the annual meeting of the American Academy of Neurology.
Other approved MS therapies have shown either no significant effect on brain atrophy or a benefit only in the second year of treatment, as with natalizumab (Tysabri) and glatiramer acetate (Copaxone), he said.
The study investigators found that baseline brain atrophy correlated best with baseline T1 and T2 lesion volume, disability, age, and disease duration and severity. Both high baseline T2 lesion volume and active gadolinium-enhancing T1 lesions predicted brain volume loss during the trial. Volume loss in the study correlated best with worsening disability and increasing numbers of T2 lesions.
The drug seemed to protect brain volume in patients who got it, regardless of baseline characteristics.
There were weak correlations between accumulations of T2 lesions and disability during the study, perhaps because "brain volume and measures of disability don’t change much over 2 years," Dr. Cohen said.
Novartis, the maker of fingolimod, paid for the study. Dr. Cohen disclosed compensation or research support from Novartis, Biogen Idec, Genzyme, Lilly, Serono, and Teva.
AT THE 2013 AAN ANNUAL MEETING
Major finding: Fingolimod slows MS brain atrophy by 31%-36%; the benefit begins within the first 6 months of treatment.
Data source: A combined analysis of three phase 3 trials involving more than 3,000 patients with relapsing-remitting MS.
Disclosures: Novartis, the maker of fingolimod, paid for the study. Dr. Cohen disclosed compensation or research support from Novartis, Biogen Idec, Genzyme, Lilly, Serono, and Teva.
Low HDL, high LDL cholesterol linked to cerebral amyloidosis
SAN DIEGO – A low level of HDL cholesterol and a high level of LDL cholesterol was associated with elevated cerebral amyloid-beta in a small sample of elderly individuals with high vascular risk, representing one of the best efforts yet to determine the relationship between cholesterol and susceptibility to brain amyloidosis seen in Alzheimer’s disease.
"Epidemiologic literature has suggested that higher cholesterol values, particularly at midlife, are associated with an increased risk of Alzheimer’s disease," Bruce R. Reed, Ph.D., said at the annual meeting of the American Academy of Neurology. "This is a complicated literature; it’s not entirely consistent. But there are fairly strong findings."
In addition, a number of large observational studies have found a substantial reduction in Alzheimer’s disease risk associated with statin use, "though randomized, controlled trials have been negative," said Dr. Reed, associate director of the University of California, Davis, Alzheimer’s disease research center. "But the epidemiologic work has taken on additional interest because of basic science work that has shown that cholesterol plays an important role in the processing of amyloid."
In an effort to investigate the relationship between cholesterol levels and contemporaneous cerebral amyloid-beta, Dr. Reed and his associates studied 66 men and women in the Aging Brain study, a longitudinal project that examines vascular contributions to dementia. The mean age of the 66 study participants was 78 years, and 44 (67%) had a history of stroke or TIA, myocardial infarction, and/or coronary artery bypass grafting. Nearly half (31) had a Clinical Dementia Rating Scale (CDR) score of 0 (normal), and of the remaining 35 individuals, 32 had a score of 0.5 (mild cognitive impairment) and 3 had a score of 1 (demented).
The researchers assayed fasting HDL and LDL cholesterol and triglycerides and used 11-C labeled Pittsburgh compound B (PIB) PET to measure cerebral amyloid-beta. The primary predictors were total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Secondary measures included VLDL cholesterol, apolipoprotein A-I and apolipoprotein B. "Apolipoprotein A-I is the primary protein of HDL cholesterol; it’s involved in reverse cholesterol transport," Dr. Reed said. "Apolipoprotein B is thought to be the atherogenic constituent of LDL cholesterol."
Regional distribution volume ratio (DVR) values were calculated using a cerebellar reference region. "The level of amyloid-beta was quantified with global PIB index, which was the mean DVR in regions susceptible to amyloidosis," Dr. Reed said.
In a multiple regression model that adjusted for age and sex, both HDL and LDL cholesterol had significant, independent effects on the PIB index. Specifically, lower HDL and higher LDL were both associated with a higher PIB index (P = .01) while adding apo E–epsilon 4 status to the model left the association essentially unchanged. Apo E–epsilon 4 had an independent effect on PIB in the expected direction (P = .03). Using identical modeling, the researchers found that higher apo A-1 and lower apo B both were associated with a higher PIB index that remained significant after researchers adjusted for apo E–epsilon 4 status.
Nearly three-quarters of study participants (71%) were on cholesterol-lowering drugs and 65% were on a statin. When the investigators adjusted the model for cholesterol treatment, it did not modify the results. "We modeled this in a number of ways and the treatment effects were not significant," Dr. Reed said. "The apolipoprotein A-1 and apolipoprotein B effects mirrored the effects of HDL and LDL."
The precise mechanism of action behind the findings remains unclear, Dr. Reed, said, but it is believed that cholesterol levels – primary HDL – modulate the synthesis, transport, toxicity, and clearance of amyloid-beta. "In vitro and animal work supports the idea that higher cholesterol appears to promote both gamma- and beta-secretase activity," he said. "It seems to shift amyloid precursor protein processing away from the alpha-secretase pathway, and it promotes amyloid-beta aggregation."
He emphasized that the relationship between serum cholesterol and brain cholesterol is complex. "Serum cholesterol and brain cholesterol are separate pools; cholesterol in the brain is locally synthesized and doesn’t correlate with cholesterol in the periphery," he said. "Also, cholesterol metabolism and levels change throughout adulthood, and the deposition of amyloid-beta occurs over 10-20 years. This is much more than a short-term, single, direct relationship."
The study findings "need replication, but replication may require a cohort with high vascular risk burden," he said. "The role of serum lipids in amyloid-beta regulation is of great interest because of the potential to modify amyloid-beta deposition through the modification of vascular risk."
The study was funded by the National Institutes of Health. Dr. Reed reported having no relevant financial disclosures.
SAN DIEGO – A low level of HDL cholesterol and a high level of LDL cholesterol was associated with elevated cerebral amyloid-beta in a small sample of elderly individuals with high vascular risk, representing one of the best efforts yet to determine the relationship between cholesterol and susceptibility to brain amyloidosis seen in Alzheimer’s disease.
"Epidemiologic literature has suggested that higher cholesterol values, particularly at midlife, are associated with an increased risk of Alzheimer’s disease," Bruce R. Reed, Ph.D., said at the annual meeting of the American Academy of Neurology. "This is a complicated literature; it’s not entirely consistent. But there are fairly strong findings."
In addition, a number of large observational studies have found a substantial reduction in Alzheimer’s disease risk associated with statin use, "though randomized, controlled trials have been negative," said Dr. Reed, associate director of the University of California, Davis, Alzheimer’s disease research center. "But the epidemiologic work has taken on additional interest because of basic science work that has shown that cholesterol plays an important role in the processing of amyloid."
In an effort to investigate the relationship between cholesterol levels and contemporaneous cerebral amyloid-beta, Dr. Reed and his associates studied 66 men and women in the Aging Brain study, a longitudinal project that examines vascular contributions to dementia. The mean age of the 66 study participants was 78 years, and 44 (67%) had a history of stroke or TIA, myocardial infarction, and/or coronary artery bypass grafting. Nearly half (31) had a Clinical Dementia Rating Scale (CDR) score of 0 (normal), and of the remaining 35 individuals, 32 had a score of 0.5 (mild cognitive impairment) and 3 had a score of 1 (demented).
The researchers assayed fasting HDL and LDL cholesterol and triglycerides and used 11-C labeled Pittsburgh compound B (PIB) PET to measure cerebral amyloid-beta. The primary predictors were total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Secondary measures included VLDL cholesterol, apolipoprotein A-I and apolipoprotein B. "Apolipoprotein A-I is the primary protein of HDL cholesterol; it’s involved in reverse cholesterol transport," Dr. Reed said. "Apolipoprotein B is thought to be the atherogenic constituent of LDL cholesterol."
Regional distribution volume ratio (DVR) values were calculated using a cerebellar reference region. "The level of amyloid-beta was quantified with global PIB index, which was the mean DVR in regions susceptible to amyloidosis," Dr. Reed said.
In a multiple regression model that adjusted for age and sex, both HDL and LDL cholesterol had significant, independent effects on the PIB index. Specifically, lower HDL and higher LDL were both associated with a higher PIB index (P = .01) while adding apo E–epsilon 4 status to the model left the association essentially unchanged. Apo E–epsilon 4 had an independent effect on PIB in the expected direction (P = .03). Using identical modeling, the researchers found that higher apo A-1 and lower apo B both were associated with a higher PIB index that remained significant after researchers adjusted for apo E–epsilon 4 status.
Nearly three-quarters of study participants (71%) were on cholesterol-lowering drugs and 65% were on a statin. When the investigators adjusted the model for cholesterol treatment, it did not modify the results. "We modeled this in a number of ways and the treatment effects were not significant," Dr. Reed said. "The apolipoprotein A-1 and apolipoprotein B effects mirrored the effects of HDL and LDL."
The precise mechanism of action behind the findings remains unclear, Dr. Reed, said, but it is believed that cholesterol levels – primary HDL – modulate the synthesis, transport, toxicity, and clearance of amyloid-beta. "In vitro and animal work supports the idea that higher cholesterol appears to promote both gamma- and beta-secretase activity," he said. "It seems to shift amyloid precursor protein processing away from the alpha-secretase pathway, and it promotes amyloid-beta aggregation."
He emphasized that the relationship between serum cholesterol and brain cholesterol is complex. "Serum cholesterol and brain cholesterol are separate pools; cholesterol in the brain is locally synthesized and doesn’t correlate with cholesterol in the periphery," he said. "Also, cholesterol metabolism and levels change throughout adulthood, and the deposition of amyloid-beta occurs over 10-20 years. This is much more than a short-term, single, direct relationship."
The study findings "need replication, but replication may require a cohort with high vascular risk burden," he said. "The role of serum lipids in amyloid-beta regulation is of great interest because of the potential to modify amyloid-beta deposition through the modification of vascular risk."
The study was funded by the National Institutes of Health. Dr. Reed reported having no relevant financial disclosures.
SAN DIEGO – A low level of HDL cholesterol and a high level of LDL cholesterol was associated with elevated cerebral amyloid-beta in a small sample of elderly individuals with high vascular risk, representing one of the best efforts yet to determine the relationship between cholesterol and susceptibility to brain amyloidosis seen in Alzheimer’s disease.
"Epidemiologic literature has suggested that higher cholesterol values, particularly at midlife, are associated with an increased risk of Alzheimer’s disease," Bruce R. Reed, Ph.D., said at the annual meeting of the American Academy of Neurology. "This is a complicated literature; it’s not entirely consistent. But there are fairly strong findings."
In addition, a number of large observational studies have found a substantial reduction in Alzheimer’s disease risk associated with statin use, "though randomized, controlled trials have been negative," said Dr. Reed, associate director of the University of California, Davis, Alzheimer’s disease research center. "But the epidemiologic work has taken on additional interest because of basic science work that has shown that cholesterol plays an important role in the processing of amyloid."
In an effort to investigate the relationship between cholesterol levels and contemporaneous cerebral amyloid-beta, Dr. Reed and his associates studied 66 men and women in the Aging Brain study, a longitudinal project that examines vascular contributions to dementia. The mean age of the 66 study participants was 78 years, and 44 (67%) had a history of stroke or TIA, myocardial infarction, and/or coronary artery bypass grafting. Nearly half (31) had a Clinical Dementia Rating Scale (CDR) score of 0 (normal), and of the remaining 35 individuals, 32 had a score of 0.5 (mild cognitive impairment) and 3 had a score of 1 (demented).
The researchers assayed fasting HDL and LDL cholesterol and triglycerides and used 11-C labeled Pittsburgh compound B (PIB) PET to measure cerebral amyloid-beta. The primary predictors were total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Secondary measures included VLDL cholesterol, apolipoprotein A-I and apolipoprotein B. "Apolipoprotein A-I is the primary protein of HDL cholesterol; it’s involved in reverse cholesterol transport," Dr. Reed said. "Apolipoprotein B is thought to be the atherogenic constituent of LDL cholesterol."
Regional distribution volume ratio (DVR) values were calculated using a cerebellar reference region. "The level of amyloid-beta was quantified with global PIB index, which was the mean DVR in regions susceptible to amyloidosis," Dr. Reed said.
In a multiple regression model that adjusted for age and sex, both HDL and LDL cholesterol had significant, independent effects on the PIB index. Specifically, lower HDL and higher LDL were both associated with a higher PIB index (P = .01) while adding apo E–epsilon 4 status to the model left the association essentially unchanged. Apo E–epsilon 4 had an independent effect on PIB in the expected direction (P = .03). Using identical modeling, the researchers found that higher apo A-1 and lower apo B both were associated with a higher PIB index that remained significant after researchers adjusted for apo E–epsilon 4 status.
Nearly three-quarters of study participants (71%) were on cholesterol-lowering drugs and 65% were on a statin. When the investigators adjusted the model for cholesterol treatment, it did not modify the results. "We modeled this in a number of ways and the treatment effects were not significant," Dr. Reed said. "The apolipoprotein A-1 and apolipoprotein B effects mirrored the effects of HDL and LDL."
The precise mechanism of action behind the findings remains unclear, Dr. Reed, said, but it is believed that cholesterol levels – primary HDL – modulate the synthesis, transport, toxicity, and clearance of amyloid-beta. "In vitro and animal work supports the idea that higher cholesterol appears to promote both gamma- and beta-secretase activity," he said. "It seems to shift amyloid precursor protein processing away from the alpha-secretase pathway, and it promotes amyloid-beta aggregation."
He emphasized that the relationship between serum cholesterol and brain cholesterol is complex. "Serum cholesterol and brain cholesterol are separate pools; cholesterol in the brain is locally synthesized and doesn’t correlate with cholesterol in the periphery," he said. "Also, cholesterol metabolism and levels change throughout adulthood, and the deposition of amyloid-beta occurs over 10-20 years. This is much more than a short-term, single, direct relationship."
The study findings "need replication, but replication may require a cohort with high vascular risk burden," he said. "The role of serum lipids in amyloid-beta regulation is of great interest because of the potential to modify amyloid-beta deposition through the modification of vascular risk."
The study was funded by the National Institutes of Health. Dr. Reed reported having no relevant financial disclosures.
AT THE 2013 AAN ANNUAL MEETING
Major finding: In a multiple regression model that adjusted for age and sex, lower HDL and higher LDL cholesterol were both associated with a higher PIB index (P = .01).
Data source: An analysis of 66 men and women in the Aging Brain study, a longitudinal project that examines vascular contributions to dementia.
Disclosures: The study was funded by the National Institutes of Health. Dr. Reed reported having no relevant financial disclosures.
Beta-D-glucan promising for fungal meningitis detection
SAN DIEGO – Researchers at Johns Hopkins University are working on a better way to detect fungal meningitis, according to lead investigator, Dr. Jennifer Lyons.
The efforts come in the wake of a recent nationwide outbreak in which hundreds of people were sickened and dozens died from spinal steroid injections contaminated with environmental fungi.
"Many patients developed serious central nervous system complications" following the shots, "but definitive fungal identification [was] elusive," Dr. Lyons and her colleagues noted in their abstract at the annual meeting of the American Academy of Neurology.
Cerebrospinal fluid (CSF) culture is the usual diagnostic test, and sometimes also a CSF polymerase-chain reaction (PCR) assay "that’s largely unvalidated. The CDC has been using it in this [recent] outbreak. It basically amplifies fungal elements, [but it has a] very, very low sensitivity. You can have an infection and be completely missed by this assay," she said in an interview, noting that less than a third of the recent cases were positive by PCR.
A better approach might be to check CSF for Beta D-glucan (BG), a protein in the cell wall of many fungi, including Candida and Aspergillus, and the organism implicated in the outbreak, Exserohilum rostratum.
The hope is that BG testing will help in "the diagnosis and therapeutic monitoring of fungal meningitis, [and that] sequential quantification could assist in determination of therapy duration," the abstract notes.
"CSF is an immune-privileged site, so you should have no BG in your CSF." Even so, "nobody [tests for it] except in research studies, said Dr. Lyons, a fellow in neuroimmunology and neurological infections at Johns Hopkins in Baltimore.
She and her colleagues used the Fungitell assay (Beacon Diagnostic Laboratories), a serum BG test, to check for BG in CSF samples from six patients who were sick after getting the suspect shots. They had been on voriconazole for a few days to a few weeks.
Four patients met the CDC definition for probable meningitis but had negative cultures. PCR testing in three patients was negative. All four patients with probable meningitis had detectable BG in their CSF samples.
One patient was sampled before and after 2 weeks of voriconazole treatment. Treatment corresponded with a drop in her BG titer.
Although sick, the two other patients did not meet the CDC’s criteria for probable meningitis. They had no detectable BG in their CSF.
"For every single [fungal meningitis] case we suspected, [the test] was positive. That said, it’s hard to hang your hat on this. We have a very small N; this is just an observation," Dr. Lyons said.
"The next step is to validate the assay by defining cutoff values and false positives. We are trying to get something in the works," she said.
Dr. Lyons said she has no relevant commercial disclosures.
SAN DIEGO – Researchers at Johns Hopkins University are working on a better way to detect fungal meningitis, according to lead investigator, Dr. Jennifer Lyons.
The efforts come in the wake of a recent nationwide outbreak in which hundreds of people were sickened and dozens died from spinal steroid injections contaminated with environmental fungi.
"Many patients developed serious central nervous system complications" following the shots, "but definitive fungal identification [was] elusive," Dr. Lyons and her colleagues noted in their abstract at the annual meeting of the American Academy of Neurology.
Cerebrospinal fluid (CSF) culture is the usual diagnostic test, and sometimes also a CSF polymerase-chain reaction (PCR) assay "that’s largely unvalidated. The CDC has been using it in this [recent] outbreak. It basically amplifies fungal elements, [but it has a] very, very low sensitivity. You can have an infection and be completely missed by this assay," she said in an interview, noting that less than a third of the recent cases were positive by PCR.
A better approach might be to check CSF for Beta D-glucan (BG), a protein in the cell wall of many fungi, including Candida and Aspergillus, and the organism implicated in the outbreak, Exserohilum rostratum.
The hope is that BG testing will help in "the diagnosis and therapeutic monitoring of fungal meningitis, [and that] sequential quantification could assist in determination of therapy duration," the abstract notes.
"CSF is an immune-privileged site, so you should have no BG in your CSF." Even so, "nobody [tests for it] except in research studies, said Dr. Lyons, a fellow in neuroimmunology and neurological infections at Johns Hopkins in Baltimore.
She and her colleagues used the Fungitell assay (Beacon Diagnostic Laboratories), a serum BG test, to check for BG in CSF samples from six patients who were sick after getting the suspect shots. They had been on voriconazole for a few days to a few weeks.
Four patients met the CDC definition for probable meningitis but had negative cultures. PCR testing in three patients was negative. All four patients with probable meningitis had detectable BG in their CSF samples.
One patient was sampled before and after 2 weeks of voriconazole treatment. Treatment corresponded with a drop in her BG titer.
Although sick, the two other patients did not meet the CDC’s criteria for probable meningitis. They had no detectable BG in their CSF.
"For every single [fungal meningitis] case we suspected, [the test] was positive. That said, it’s hard to hang your hat on this. We have a very small N; this is just an observation," Dr. Lyons said.
"The next step is to validate the assay by defining cutoff values and false positives. We are trying to get something in the works," she said.
Dr. Lyons said she has no relevant commercial disclosures.
SAN DIEGO – Researchers at Johns Hopkins University are working on a better way to detect fungal meningitis, according to lead investigator, Dr. Jennifer Lyons.
The efforts come in the wake of a recent nationwide outbreak in which hundreds of people were sickened and dozens died from spinal steroid injections contaminated with environmental fungi.
"Many patients developed serious central nervous system complications" following the shots, "but definitive fungal identification [was] elusive," Dr. Lyons and her colleagues noted in their abstract at the annual meeting of the American Academy of Neurology.
Cerebrospinal fluid (CSF) culture is the usual diagnostic test, and sometimes also a CSF polymerase-chain reaction (PCR) assay "that’s largely unvalidated. The CDC has been using it in this [recent] outbreak. It basically amplifies fungal elements, [but it has a] very, very low sensitivity. You can have an infection and be completely missed by this assay," she said in an interview, noting that less than a third of the recent cases were positive by PCR.
A better approach might be to check CSF for Beta D-glucan (BG), a protein in the cell wall of many fungi, including Candida and Aspergillus, and the organism implicated in the outbreak, Exserohilum rostratum.
The hope is that BG testing will help in "the diagnosis and therapeutic monitoring of fungal meningitis, [and that] sequential quantification could assist in determination of therapy duration," the abstract notes.
"CSF is an immune-privileged site, so you should have no BG in your CSF." Even so, "nobody [tests for it] except in research studies, said Dr. Lyons, a fellow in neuroimmunology and neurological infections at Johns Hopkins in Baltimore.
She and her colleagues used the Fungitell assay (Beacon Diagnostic Laboratories), a serum BG test, to check for BG in CSF samples from six patients who were sick after getting the suspect shots. They had been on voriconazole for a few days to a few weeks.
Four patients met the CDC definition for probable meningitis but had negative cultures. PCR testing in three patients was negative. All four patients with probable meningitis had detectable BG in their CSF samples.
One patient was sampled before and after 2 weeks of voriconazole treatment. Treatment corresponded with a drop in her BG titer.
Although sick, the two other patients did not meet the CDC’s criteria for probable meningitis. They had no detectable BG in their CSF.
"For every single [fungal meningitis] case we suspected, [the test] was positive. That said, it’s hard to hang your hat on this. We have a very small N; this is just an observation," Dr. Lyons said.
"The next step is to validate the assay by defining cutoff values and false positives. We are trying to get something in the works," she said.
Dr. Lyons said she has no relevant commercial disclosures.
AT THE 2013 AAN ANNUAL MEETING
Major finding: In four patients with probable fungal meningitis, CSF samples tested positive for beta-D-glucan, whereas standard culture and PCR testing were negative.
Data Source: Observational study in six patients who received epidural steroid injections contaminated by environmental fungi.
Disclosures: The lead investigator said she has no commercial conflicts.
Stereotactic laser ablation found feasible for hypothalamic hamartoma
SAN DIEGO – Magnetic resonance-guided stereotactic laser ablation is a safe and effective option in the treatment of hypothalamic hamartoma, results from a multicenter pilot study showed.
At the annual meeting of the American Academy of Neurology, Dr. Daniel J. Curry reported results from 20 patients who have undergone treatment with a Food and Drug Administration–cleared neurosurgical tissue coagulation system called Visualase. Hypothalamic hamartoma (HH) is a rare disorder of pediatric epilepsy with an estimated prevalence of 1:50,000-100,000, said Dr. Curry, director of pediatric surgical epilepsy and functional neurosurgery at Texas Children’s Hospital, Houston.
"The main presentation is the mirthless laughter of gelastic seizures, but patients can have other seizure types," he said. "The diagnosis is frequently delayed, and high seizure burden in the brain can lead to epileptic encephalopathy. Seizures are notoriously resistant to medical managements necessitating surgical intervention ... open, endoscopic, or ablative."
To date, surgical intervention has been limited due to modest outcomes, with 37%-50% achieving seizure freedom. The location of HH tumors makes surgical intervention difficult, and as a result 7%-10% of patients have permanent surgical morbidity.
For the technique using the Visualase, Dr. Curry and his associates at four other medical centers in the United States performed the surgical technique through a single 4-mm incision, a 3.2-mm burr hole, and a 1.65-mm cannula trajectory with Visualase under real-time MR thermography, first with a confirmation test at about 3 W, followed by higher doses of 6-10 W for 50-120 seconds. Temperature limits were set to protect the hypothalamus and basilar artery and optic tract. The surgery had an immediate effect, and patients stayed in the hospital for a mean of 2 days.
The primary measure was seizure frequency at 1 year while the secondary measure was the complication profile of stereotactic laser ablation in epilepsy.
Of the 20 patients, 5 were adults, and the entire study population ranged in age from 22 months to 34 years. A total of 21 ablations were performed in the 20 patients. Dr. Curry reported that all but four patients were seizure free after the procedure. However, the rate of seizures diminished among the four who were not seizure free.
Seizures recurred in one of the pediatric patients. "We re-ablated him and he is now seizure free," Dr. Curry said.
Complications to date have included two missed targets, one case of IV phenytoin toxicity, one case of transient diabetes insipidus, two cases of transient hemiparesis, and one subarachnoid hemorrhage. Perioperative, temporary weight gain was detected in most patients. "With lack of hormonal disturbance, this is thought to be due to the perioperative, high-dose steroid use," Dr. Curry explained.
Postoperative interviews with parents of study participants "have revealed significant improvements in intellectual development, concentration, and interactiveness," he said. "Most families report improvement of mood, decreased behavioral disorders, and rage attacks."
To date, only two patients have completed formal postoperative neuropsychological testing. "There were no significant declines in memory in either patient," Dr. Curry said. One had improved math skills and reading comprehension while the other complained of memory dysfunction but was not below normal on testing.
"We have learned that laser ablation of hypothalamic hamartoma can be accomplished safely," Dr. Curry concluded. "More studies are needed to explain the antiepileptic effect in settings of incomplete radiologic destruction of the target and to advance thermal planning."
Dr. Curry said that he had no relevant financial conflicts to disclose.
SAN DIEGO – Magnetic resonance-guided stereotactic laser ablation is a safe and effective option in the treatment of hypothalamic hamartoma, results from a multicenter pilot study showed.
At the annual meeting of the American Academy of Neurology, Dr. Daniel J. Curry reported results from 20 patients who have undergone treatment with a Food and Drug Administration–cleared neurosurgical tissue coagulation system called Visualase. Hypothalamic hamartoma (HH) is a rare disorder of pediatric epilepsy with an estimated prevalence of 1:50,000-100,000, said Dr. Curry, director of pediatric surgical epilepsy and functional neurosurgery at Texas Children’s Hospital, Houston.
"The main presentation is the mirthless laughter of gelastic seizures, but patients can have other seizure types," he said. "The diagnosis is frequently delayed, and high seizure burden in the brain can lead to epileptic encephalopathy. Seizures are notoriously resistant to medical managements necessitating surgical intervention ... open, endoscopic, or ablative."
To date, surgical intervention has been limited due to modest outcomes, with 37%-50% achieving seizure freedom. The location of HH tumors makes surgical intervention difficult, and as a result 7%-10% of patients have permanent surgical morbidity.
For the technique using the Visualase, Dr. Curry and his associates at four other medical centers in the United States performed the surgical technique through a single 4-mm incision, a 3.2-mm burr hole, and a 1.65-mm cannula trajectory with Visualase under real-time MR thermography, first with a confirmation test at about 3 W, followed by higher doses of 6-10 W for 50-120 seconds. Temperature limits were set to protect the hypothalamus and basilar artery and optic tract. The surgery had an immediate effect, and patients stayed in the hospital for a mean of 2 days.
The primary measure was seizure frequency at 1 year while the secondary measure was the complication profile of stereotactic laser ablation in epilepsy.
Of the 20 patients, 5 were adults, and the entire study population ranged in age from 22 months to 34 years. A total of 21 ablations were performed in the 20 patients. Dr. Curry reported that all but four patients were seizure free after the procedure. However, the rate of seizures diminished among the four who were not seizure free.
Seizures recurred in one of the pediatric patients. "We re-ablated him and he is now seizure free," Dr. Curry said.
Complications to date have included two missed targets, one case of IV phenytoin toxicity, one case of transient diabetes insipidus, two cases of transient hemiparesis, and one subarachnoid hemorrhage. Perioperative, temporary weight gain was detected in most patients. "With lack of hormonal disturbance, this is thought to be due to the perioperative, high-dose steroid use," Dr. Curry explained.
Postoperative interviews with parents of study participants "have revealed significant improvements in intellectual development, concentration, and interactiveness," he said. "Most families report improvement of mood, decreased behavioral disorders, and rage attacks."
To date, only two patients have completed formal postoperative neuropsychological testing. "There were no significant declines in memory in either patient," Dr. Curry said. One had improved math skills and reading comprehension while the other complained of memory dysfunction but was not below normal on testing.
"We have learned that laser ablation of hypothalamic hamartoma can be accomplished safely," Dr. Curry concluded. "More studies are needed to explain the antiepileptic effect in settings of incomplete radiologic destruction of the target and to advance thermal planning."
Dr. Curry said that he had no relevant financial conflicts to disclose.
SAN DIEGO – Magnetic resonance-guided stereotactic laser ablation is a safe and effective option in the treatment of hypothalamic hamartoma, results from a multicenter pilot study showed.
At the annual meeting of the American Academy of Neurology, Dr. Daniel J. Curry reported results from 20 patients who have undergone treatment with a Food and Drug Administration–cleared neurosurgical tissue coagulation system called Visualase. Hypothalamic hamartoma (HH) is a rare disorder of pediatric epilepsy with an estimated prevalence of 1:50,000-100,000, said Dr. Curry, director of pediatric surgical epilepsy and functional neurosurgery at Texas Children’s Hospital, Houston.
"The main presentation is the mirthless laughter of gelastic seizures, but patients can have other seizure types," he said. "The diagnosis is frequently delayed, and high seizure burden in the brain can lead to epileptic encephalopathy. Seizures are notoriously resistant to medical managements necessitating surgical intervention ... open, endoscopic, or ablative."
To date, surgical intervention has been limited due to modest outcomes, with 37%-50% achieving seizure freedom. The location of HH tumors makes surgical intervention difficult, and as a result 7%-10% of patients have permanent surgical morbidity.
For the technique using the Visualase, Dr. Curry and his associates at four other medical centers in the United States performed the surgical technique through a single 4-mm incision, a 3.2-mm burr hole, and a 1.65-mm cannula trajectory with Visualase under real-time MR thermography, first with a confirmation test at about 3 W, followed by higher doses of 6-10 W for 50-120 seconds. Temperature limits were set to protect the hypothalamus and basilar artery and optic tract. The surgery had an immediate effect, and patients stayed in the hospital for a mean of 2 days.
The primary measure was seizure frequency at 1 year while the secondary measure was the complication profile of stereotactic laser ablation in epilepsy.
Of the 20 patients, 5 were adults, and the entire study population ranged in age from 22 months to 34 years. A total of 21 ablations were performed in the 20 patients. Dr. Curry reported that all but four patients were seizure free after the procedure. However, the rate of seizures diminished among the four who were not seizure free.
Seizures recurred in one of the pediatric patients. "We re-ablated him and he is now seizure free," Dr. Curry said.
Complications to date have included two missed targets, one case of IV phenytoin toxicity, one case of transient diabetes insipidus, two cases of transient hemiparesis, and one subarachnoid hemorrhage. Perioperative, temporary weight gain was detected in most patients. "With lack of hormonal disturbance, this is thought to be due to the perioperative, high-dose steroid use," Dr. Curry explained.
Postoperative interviews with parents of study participants "have revealed significant improvements in intellectual development, concentration, and interactiveness," he said. "Most families report improvement of mood, decreased behavioral disorders, and rage attacks."
To date, only two patients have completed formal postoperative neuropsychological testing. "There were no significant declines in memory in either patient," Dr. Curry said. One had improved math skills and reading comprehension while the other complained of memory dysfunction but was not below normal on testing.
"We have learned that laser ablation of hypothalamic hamartoma can be accomplished safely," Dr. Curry concluded. "More studies are needed to explain the antiepileptic effect in settings of incomplete radiologic destruction of the target and to advance thermal planning."
Dr. Curry said that he had no relevant financial conflicts to disclose.
AT THE 2013 AAN ANNUAL MEETING
Major finding: After 20 patients with hypothalamic hamartoma underwent MR-guided stereotactic laser ablation, all but 4 were seizure free.
Data source: A multicenter pilot study of 21 ablations performed in patients who ranged in age from 22 months to 34 years.
Disclosures: Dr. Curry said that he had no relevant financial conflicts to disclose.
FDG-PET strongest independent predictor of Alzheimer's dementia in MCI
SAN DIEGO – PET imaging with 18-fluorodeoxyglucose is the strongest individual positive predictive biomarker of short-term incident dementia in mild cognitive impairment in the most current iterations of Alzheimer’s disease diagnostic criteria, results from a multicenter analysis of 73 patients suggest.
"Since this was a relatively small population of patients, future studies are needed to confirm the results and to assess the incremental diagnostic value and cost-benefit ratio," Dr. Giovanni Frisoni said at the annual meeting of the American Academy of Neurology.
Dr. Frisoni, of the National Alzheimer’s Center in Brescia, Italy, and his associates conducted a secondary analysis of 73 patients with mild cognitive impairment (MCI) who were treated at clinics in Brescia, Amsterdam, and Stockholm, in an effort to compare the prognostic accuracy of individual criterions in the two current diagnostic criteria for short- to mid-term incident Alzheimer’s dementia in patients with MCI: those published by an International Working Group (IWG) in 2007 and those published in 2011 by the National Institute on Aging and the Alzheimer’s Association (NIA-AA).
The patients were followed for an average of 39 months (at least 1 year for all). They had a mean age of 66 years, and 57% were women. The investigators obtained data on biomarkers of amyloidosis (abnormal amyloid-beta-42 [A-beta-42] in cerebrospinal fluid) and neurodegeneration (hippocampal atrophy on MRI measured with FreeSurfer software, temporo-parietal hypometabolism measured with 18-fluorodeoxyglucose [18-FDG]-PET, and abnormal tau protein levels in cerebrospinal fluid).
"This is a pretty rare group of patients," Dr. Frisoni said.
The researchers then compared positive and negative likelihood ratios of individual items in the IWG and NIA-AA criteria. Dr. Frisoni reported that during the follow-up period, 29 of the patients progressed to Alzheimer’s disease and 44 remained stable. Among IWG criteria, positivity to any biomarker had the lowest negative likelihood ratio (0.00) for Alzheimer’s disease, while positivity to 18-FDG-PET had the highest positive likelihood ratio (5.82) and a low negative likelihood ratio (0.24).
Among NIA-AA criteria, positivity to neurodegeneration as measured by 18-FDG-PET, MRI, or cerebrospinal fluid tau markers, regardless of amyloidosis status, had the lowest negative likelihood ratio (0.06), while positivity to A-beta-42 and 18-FDG-PET or A-beta-42 and hippocampal atrophy had the highest positive likelihood ratios (6.45 and 5.56, respectively).
The study was supported by the Swedish Research Council and by a grant from the Italian Ministry of Health. Dr. Frisoni disclosed that he has received personal compensation for activities with Eli Lilly, Bristol-Myers Squibb, Bayer, and several other companies.
SAN DIEGO – PET imaging with 18-fluorodeoxyglucose is the strongest individual positive predictive biomarker of short-term incident dementia in mild cognitive impairment in the most current iterations of Alzheimer’s disease diagnostic criteria, results from a multicenter analysis of 73 patients suggest.
"Since this was a relatively small population of patients, future studies are needed to confirm the results and to assess the incremental diagnostic value and cost-benefit ratio," Dr. Giovanni Frisoni said at the annual meeting of the American Academy of Neurology.
Dr. Frisoni, of the National Alzheimer’s Center in Brescia, Italy, and his associates conducted a secondary analysis of 73 patients with mild cognitive impairment (MCI) who were treated at clinics in Brescia, Amsterdam, and Stockholm, in an effort to compare the prognostic accuracy of individual criterions in the two current diagnostic criteria for short- to mid-term incident Alzheimer’s dementia in patients with MCI: those published by an International Working Group (IWG) in 2007 and those published in 2011 by the National Institute on Aging and the Alzheimer’s Association (NIA-AA).
The patients were followed for an average of 39 months (at least 1 year for all). They had a mean age of 66 years, and 57% were women. The investigators obtained data on biomarkers of amyloidosis (abnormal amyloid-beta-42 [A-beta-42] in cerebrospinal fluid) and neurodegeneration (hippocampal atrophy on MRI measured with FreeSurfer software, temporo-parietal hypometabolism measured with 18-fluorodeoxyglucose [18-FDG]-PET, and abnormal tau protein levels in cerebrospinal fluid).
"This is a pretty rare group of patients," Dr. Frisoni said.
The researchers then compared positive and negative likelihood ratios of individual items in the IWG and NIA-AA criteria. Dr. Frisoni reported that during the follow-up period, 29 of the patients progressed to Alzheimer’s disease and 44 remained stable. Among IWG criteria, positivity to any biomarker had the lowest negative likelihood ratio (0.00) for Alzheimer’s disease, while positivity to 18-FDG-PET had the highest positive likelihood ratio (5.82) and a low negative likelihood ratio (0.24).
Among NIA-AA criteria, positivity to neurodegeneration as measured by 18-FDG-PET, MRI, or cerebrospinal fluid tau markers, regardless of amyloidosis status, had the lowest negative likelihood ratio (0.06), while positivity to A-beta-42 and 18-FDG-PET or A-beta-42 and hippocampal atrophy had the highest positive likelihood ratios (6.45 and 5.56, respectively).
The study was supported by the Swedish Research Council and by a grant from the Italian Ministry of Health. Dr. Frisoni disclosed that he has received personal compensation for activities with Eli Lilly, Bristol-Myers Squibb, Bayer, and several other companies.
SAN DIEGO – PET imaging with 18-fluorodeoxyglucose is the strongest individual positive predictive biomarker of short-term incident dementia in mild cognitive impairment in the most current iterations of Alzheimer’s disease diagnostic criteria, results from a multicenter analysis of 73 patients suggest.
"Since this was a relatively small population of patients, future studies are needed to confirm the results and to assess the incremental diagnostic value and cost-benefit ratio," Dr. Giovanni Frisoni said at the annual meeting of the American Academy of Neurology.
Dr. Frisoni, of the National Alzheimer’s Center in Brescia, Italy, and his associates conducted a secondary analysis of 73 patients with mild cognitive impairment (MCI) who were treated at clinics in Brescia, Amsterdam, and Stockholm, in an effort to compare the prognostic accuracy of individual criterions in the two current diagnostic criteria for short- to mid-term incident Alzheimer’s dementia in patients with MCI: those published by an International Working Group (IWG) in 2007 and those published in 2011 by the National Institute on Aging and the Alzheimer’s Association (NIA-AA).
The patients were followed for an average of 39 months (at least 1 year for all). They had a mean age of 66 years, and 57% were women. The investigators obtained data on biomarkers of amyloidosis (abnormal amyloid-beta-42 [A-beta-42] in cerebrospinal fluid) and neurodegeneration (hippocampal atrophy on MRI measured with FreeSurfer software, temporo-parietal hypometabolism measured with 18-fluorodeoxyglucose [18-FDG]-PET, and abnormal tau protein levels in cerebrospinal fluid).
"This is a pretty rare group of patients," Dr. Frisoni said.
The researchers then compared positive and negative likelihood ratios of individual items in the IWG and NIA-AA criteria. Dr. Frisoni reported that during the follow-up period, 29 of the patients progressed to Alzheimer’s disease and 44 remained stable. Among IWG criteria, positivity to any biomarker had the lowest negative likelihood ratio (0.00) for Alzheimer’s disease, while positivity to 18-FDG-PET had the highest positive likelihood ratio (5.82) and a low negative likelihood ratio (0.24).
Among NIA-AA criteria, positivity to neurodegeneration as measured by 18-FDG-PET, MRI, or cerebrospinal fluid tau markers, regardless of amyloidosis status, had the lowest negative likelihood ratio (0.06), while positivity to A-beta-42 and 18-FDG-PET or A-beta-42 and hippocampal atrophy had the highest positive likelihood ratios (6.45 and 5.56, respectively).
The study was supported by the Swedish Research Council and by a grant from the Italian Ministry of Health. Dr. Frisoni disclosed that he has received personal compensation for activities with Eli Lilly, Bristol-Myers Squibb, Bayer, and several other companies.
AT THE 2013 AAN ANNUAL MEETING
Major finding: In predicting short-term incident dementia in mild cognitive impairment, positivity to FDG-PET had the highest positive likelihood ratio (5.82) in the International Working Group diagnostic criteria and the highest positive likelihood ratio in combination with amyloid-beta-42 cerebrospinal level (6.45) in the National Institute on Aging–Alzheimer’s Association diagnostic criteria.
Data source: A study of 73 patients with mild cognitive impairment who were treated at clinics in Brescia, Italy; Amsterdam; and Stockholm.
Disclosures: The study was supported by the Swedish Research Council and by a grant from the Italian Ministry of Health. Dr. Frisoni disclosed that he has received personal compensation for activities with Eli Lilly, Bristol-Myers Squibb, Bayer, and several other companies.
Early surgical menopause linked to cognitive decline
SAN DIEGO – Earlier age at surgical menopause may be associated with a steeper decline in cognitive function and increased Alzheimer’s disease–related neuropathologic scores, preliminary results from two longitudinal studies have shown.
"Our findings support a growing literature on the impact of surgical menopause on cognitive function, and add granularity to these outcome measures," Dr. Riley M. Bove said at the annual meeting of the American Academy of Neurology. "In light of the sometimes conflicting and sometimes controversial findings related to modifying factors such as hormone replacement therapy [HRT], we believe that ongoing investigations are warranted."
In an effort to determine the impact of reproductive decline on the spectrum of cognitive decline, Dr. Bove, a neurologist at Brigham and Women’s Hospital, Boston, and her associates studied 1,884 women enrolled in two ongoing longitudinal studies: the Memory and Aging Project (MAP), a study of older men and women in assisted living facilities that was launched in 1997, and the Religious Orders Study (ROS), a study of Catholic priests, nuns, and brothers that was launched in 1994.
"Observational studies have noted that the loss of estrogen associated with menopause, including surgical menopause, may be associated with cognitive decline," Dr. Bove said. "In animal models estrogen has been found to be neuroprotective. However, in humans the evidence is a lot more complex. The results of the Womens Health Initiative Memory Study a decade ago did find adverse effects of hormone replacement therapy initiated in women in their 60s. Since then a window of opportunity hypothesis has emerged, according to which HRT perimenopausally may be protective, but following this window, it may be neutral or even harmful. We aimed to look at longitudinal changes in cognition, risk of an Alzheimer’s diagnosis, and neuropathologic measures related to Alzheimer’s disease. Our hypothesis was that earlier surgical menopause is associated with earlier risk of cognitive decline."
Study participants, who have been followed for up to 19 years, underwent a baseline clinical and reproductive history, annual clinical and cognitive evaluations, and annual blood draws. The researchers examined the association between age at menarche and menopause, number of cycling years, and ever use and duration of HRT.
During annual cognitive tests, the researchers evaluated five composite domains that were weighted toward memory and categorized by factor analysis. The domains include episodic memory (seven tests), semantic memory (three tests), working memory (three tests), perceptual speed (two tests), and visuospatial ability (two tests). They also established a global cognition composite score, which was a sum of the 17 individual tests.
Dr. Bove and her associates considered a clinical diagnosis of Alzheimer’s based on clinical criteria and neuropathologic measures. The three Alzheimer’s disease–associated measures were neuritic plaques, neurofibrillary tangles, and diffuse plaques, as well as a global AD pathology score, which was an average of these three measures. Age at menopause was a continuous variable. All models controlled for age, smoking, and years of education.
Of the total women studied, all were free of dementia at enrollment, their mean age was 78 years, and 91% were non-Hispanic white. On average, compared with women in the ROS study, those in the MAP study were older (79.6 vs. 75.9 years, respectively); were less educated (14.1 vs. 17.9 years); were more likely to smoke (38% vs. 8%); had an earlier age at menarche (12.8 vs. 13.1); had a later age at menopause (47.3 vs. 46.6); and had a slightly higher number of cycling years (34.5 vs. 33.4).
Of the 1,884 women, 1,277 reported having natural menopause, and 607 reported having surgical menopause. More women in the surgical menopause group reported HRT use (53% vs. 27%, respectively). "Approximately 90% of HRT use was oral, so we collapsed all of the different forms of HRT use into one group," she explained.
Among women who had undergone surgical menopause, early age at menopause was associated with a faster decline in global cognition (P = .0007), as well as faster declines in episodic memory (P = .0003) and semantic memory (P = .0022). "We did not find the similar association in the natural menopause group," Dr. Bove said.
However, the researchers observed no significant association between age at surgical menopause and risk of clinical Alzheimer’s (P = .093) nor in the pathologic diagnosis of Alzheimer’s (P = .053). Early age at surgical menopause was associated with significantly lower scores in global AD pathology (P = .038) and neuritic plaques (P = .013) but not in neurofibrillary tangles (P = .138) or diffuse plaques (P = .490).
Dr. Bove also reported that there were no associations between HRT use ever vs. never in any of the outcomes examined, "even when HRT use was stratified according to its timing of initiation relative to menopause. Additionally, we did not find a significant association between duration of HRT use and any of the neurologic outcomes."
She acknowledged certain limitations of the study, including the fact that study participants were required to be nondemented at baseline. "This may have led to exclusion bias if there were early effects of menopause on cognitive function," Dr. Bove said. "The cognitive outcomes were weighted toward memory, and the reproductive histories were patient reported and retrospective, so there’s a limited definition of surgical menopause. We don’t have any information as to whether the oophorectomies were unilateral or bilateral, or the indication for the surgeries. There was also limited data about HRT use."
Dr. Bove said that she had no relevant financial disclosures.
SAN DIEGO – Earlier age at surgical menopause may be associated with a steeper decline in cognitive function and increased Alzheimer’s disease–related neuropathologic scores, preliminary results from two longitudinal studies have shown.
"Our findings support a growing literature on the impact of surgical menopause on cognitive function, and add granularity to these outcome measures," Dr. Riley M. Bove said at the annual meeting of the American Academy of Neurology. "In light of the sometimes conflicting and sometimes controversial findings related to modifying factors such as hormone replacement therapy [HRT], we believe that ongoing investigations are warranted."
In an effort to determine the impact of reproductive decline on the spectrum of cognitive decline, Dr. Bove, a neurologist at Brigham and Women’s Hospital, Boston, and her associates studied 1,884 women enrolled in two ongoing longitudinal studies: the Memory and Aging Project (MAP), a study of older men and women in assisted living facilities that was launched in 1997, and the Religious Orders Study (ROS), a study of Catholic priests, nuns, and brothers that was launched in 1994.
"Observational studies have noted that the loss of estrogen associated with menopause, including surgical menopause, may be associated with cognitive decline," Dr. Bove said. "In animal models estrogen has been found to be neuroprotective. However, in humans the evidence is a lot more complex. The results of the Womens Health Initiative Memory Study a decade ago did find adverse effects of hormone replacement therapy initiated in women in their 60s. Since then a window of opportunity hypothesis has emerged, according to which HRT perimenopausally may be protective, but following this window, it may be neutral or even harmful. We aimed to look at longitudinal changes in cognition, risk of an Alzheimer’s diagnosis, and neuropathologic measures related to Alzheimer’s disease. Our hypothesis was that earlier surgical menopause is associated with earlier risk of cognitive decline."
Study participants, who have been followed for up to 19 years, underwent a baseline clinical and reproductive history, annual clinical and cognitive evaluations, and annual blood draws. The researchers examined the association between age at menarche and menopause, number of cycling years, and ever use and duration of HRT.
During annual cognitive tests, the researchers evaluated five composite domains that were weighted toward memory and categorized by factor analysis. The domains include episodic memory (seven tests), semantic memory (three tests), working memory (three tests), perceptual speed (two tests), and visuospatial ability (two tests). They also established a global cognition composite score, which was a sum of the 17 individual tests.
Dr. Bove and her associates considered a clinical diagnosis of Alzheimer’s based on clinical criteria and neuropathologic measures. The three Alzheimer’s disease–associated measures were neuritic plaques, neurofibrillary tangles, and diffuse plaques, as well as a global AD pathology score, which was an average of these three measures. Age at menopause was a continuous variable. All models controlled for age, smoking, and years of education.
Of the total women studied, all were free of dementia at enrollment, their mean age was 78 years, and 91% were non-Hispanic white. On average, compared with women in the ROS study, those in the MAP study were older (79.6 vs. 75.9 years, respectively); were less educated (14.1 vs. 17.9 years); were more likely to smoke (38% vs. 8%); had an earlier age at menarche (12.8 vs. 13.1); had a later age at menopause (47.3 vs. 46.6); and had a slightly higher number of cycling years (34.5 vs. 33.4).
Of the 1,884 women, 1,277 reported having natural menopause, and 607 reported having surgical menopause. More women in the surgical menopause group reported HRT use (53% vs. 27%, respectively). "Approximately 90% of HRT use was oral, so we collapsed all of the different forms of HRT use into one group," she explained.
Among women who had undergone surgical menopause, early age at menopause was associated with a faster decline in global cognition (P = .0007), as well as faster declines in episodic memory (P = .0003) and semantic memory (P = .0022). "We did not find the similar association in the natural menopause group," Dr. Bove said.
However, the researchers observed no significant association between age at surgical menopause and risk of clinical Alzheimer’s (P = .093) nor in the pathologic diagnosis of Alzheimer’s (P = .053). Early age at surgical menopause was associated with significantly lower scores in global AD pathology (P = .038) and neuritic plaques (P = .013) but not in neurofibrillary tangles (P = .138) or diffuse plaques (P = .490).
Dr. Bove also reported that there were no associations between HRT use ever vs. never in any of the outcomes examined, "even when HRT use was stratified according to its timing of initiation relative to menopause. Additionally, we did not find a significant association between duration of HRT use and any of the neurologic outcomes."
She acknowledged certain limitations of the study, including the fact that study participants were required to be nondemented at baseline. "This may have led to exclusion bias if there were early effects of menopause on cognitive function," Dr. Bove said. "The cognitive outcomes were weighted toward memory, and the reproductive histories were patient reported and retrospective, so there’s a limited definition of surgical menopause. We don’t have any information as to whether the oophorectomies were unilateral or bilateral, or the indication for the surgeries. There was also limited data about HRT use."
Dr. Bove said that she had no relevant financial disclosures.
SAN DIEGO – Earlier age at surgical menopause may be associated with a steeper decline in cognitive function and increased Alzheimer’s disease–related neuropathologic scores, preliminary results from two longitudinal studies have shown.
"Our findings support a growing literature on the impact of surgical menopause on cognitive function, and add granularity to these outcome measures," Dr. Riley M. Bove said at the annual meeting of the American Academy of Neurology. "In light of the sometimes conflicting and sometimes controversial findings related to modifying factors such as hormone replacement therapy [HRT], we believe that ongoing investigations are warranted."
In an effort to determine the impact of reproductive decline on the spectrum of cognitive decline, Dr. Bove, a neurologist at Brigham and Women’s Hospital, Boston, and her associates studied 1,884 women enrolled in two ongoing longitudinal studies: the Memory and Aging Project (MAP), a study of older men and women in assisted living facilities that was launched in 1997, and the Religious Orders Study (ROS), a study of Catholic priests, nuns, and brothers that was launched in 1994.
"Observational studies have noted that the loss of estrogen associated with menopause, including surgical menopause, may be associated with cognitive decline," Dr. Bove said. "In animal models estrogen has been found to be neuroprotective. However, in humans the evidence is a lot more complex. The results of the Womens Health Initiative Memory Study a decade ago did find adverse effects of hormone replacement therapy initiated in women in their 60s. Since then a window of opportunity hypothesis has emerged, according to which HRT perimenopausally may be protective, but following this window, it may be neutral or even harmful. We aimed to look at longitudinal changes in cognition, risk of an Alzheimer’s diagnosis, and neuropathologic measures related to Alzheimer’s disease. Our hypothesis was that earlier surgical menopause is associated with earlier risk of cognitive decline."
Study participants, who have been followed for up to 19 years, underwent a baseline clinical and reproductive history, annual clinical and cognitive evaluations, and annual blood draws. The researchers examined the association between age at menarche and menopause, number of cycling years, and ever use and duration of HRT.
During annual cognitive tests, the researchers evaluated five composite domains that were weighted toward memory and categorized by factor analysis. The domains include episodic memory (seven tests), semantic memory (three tests), working memory (three tests), perceptual speed (two tests), and visuospatial ability (two tests). They also established a global cognition composite score, which was a sum of the 17 individual tests.
Dr. Bove and her associates considered a clinical diagnosis of Alzheimer’s based on clinical criteria and neuropathologic measures. The three Alzheimer’s disease–associated measures were neuritic plaques, neurofibrillary tangles, and diffuse plaques, as well as a global AD pathology score, which was an average of these three measures. Age at menopause was a continuous variable. All models controlled for age, smoking, and years of education.
Of the total women studied, all were free of dementia at enrollment, their mean age was 78 years, and 91% were non-Hispanic white. On average, compared with women in the ROS study, those in the MAP study were older (79.6 vs. 75.9 years, respectively); were less educated (14.1 vs. 17.9 years); were more likely to smoke (38% vs. 8%); had an earlier age at menarche (12.8 vs. 13.1); had a later age at menopause (47.3 vs. 46.6); and had a slightly higher number of cycling years (34.5 vs. 33.4).
Of the 1,884 women, 1,277 reported having natural menopause, and 607 reported having surgical menopause. More women in the surgical menopause group reported HRT use (53% vs. 27%, respectively). "Approximately 90% of HRT use was oral, so we collapsed all of the different forms of HRT use into one group," she explained.
Among women who had undergone surgical menopause, early age at menopause was associated with a faster decline in global cognition (P = .0007), as well as faster declines in episodic memory (P = .0003) and semantic memory (P = .0022). "We did not find the similar association in the natural menopause group," Dr. Bove said.
However, the researchers observed no significant association between age at surgical menopause and risk of clinical Alzheimer’s (P = .093) nor in the pathologic diagnosis of Alzheimer’s (P = .053). Early age at surgical menopause was associated with significantly lower scores in global AD pathology (P = .038) and neuritic plaques (P = .013) but not in neurofibrillary tangles (P = .138) or diffuse plaques (P = .490).
Dr. Bove also reported that there were no associations between HRT use ever vs. never in any of the outcomes examined, "even when HRT use was stratified according to its timing of initiation relative to menopause. Additionally, we did not find a significant association between duration of HRT use and any of the neurologic outcomes."
She acknowledged certain limitations of the study, including the fact that study participants were required to be nondemented at baseline. "This may have led to exclusion bias if there were early effects of menopause on cognitive function," Dr. Bove said. "The cognitive outcomes were weighted toward memory, and the reproductive histories were patient reported and retrospective, so there’s a limited definition of surgical menopause. We don’t have any information as to whether the oophorectomies were unilateral or bilateral, or the indication for the surgeries. There was also limited data about HRT use."
Dr. Bove said that she had no relevant financial disclosures.
AT THE 2013 AAN ANNUAL MEETING
Major finding: Among women who had undergone surgical menopause, early age at menopause was associated with a faster decline in global cognition (P = .0007) as well as faster declines in episodic memory (P = .0003) and semantic memory (P = .0022).
Data source: Findings from 1,884 women enrolled in two ongoing longitudinal studies: the Memory and Aging Project (MAP), a study of older men and women in assisted living facilities that was launched in 1997, and the Religious Orders Study (ROS), a study of Catholic priests, nuns, and brothers that was launched in 1994.
Disclosures: Dr. Bove said she had no relevant financial disclosures.
Reports indicate dalfampridine may worsen trigeminal neuralgia
SAN DIEGO – A new adverse event may be emerging for dalfampridine – trigeminal neuralgia in multiple sclerosis patients with a preexisting trigeminal injury, or worsening of the condition in those who already have it, according to Dr. Gary Birnbaum, director of the Multiple Sclerosis Treatment and Research Center at the Minneapolis Clinic of Neurology.
Within a month of starting the drug at his clinic, three women with well-controlled trigeminal neuralgia "had very significant increases in the severity of their trigeminal pain," he said.
Stopping the drug brought some temporary relief to two, but they soon relapsed and their pain is now "very, very difficult to control," requiring substantially higher pain medication doses than before, he said.
In the third woman, the pain continued despite stopping the drug and no longer responded to pain medication. It was so severe that she contemplated suicide; she eventually had a trigeminal rhizotomy.
They had "very, very severe pain after" starting dalfampridine (Ampyra), "and it didn’t get better" when it was stopped. "That is what’s disquieting about it," Dr. Birnbaum said at the American Academy of Neurology (AAN) annual meeting.
A fourth patient developed trigeminal neuralgia after 18 months on the drug; the side of his face had only been numb previously. He now requires pain medications for the condition. Brain MRIs of all four patients were stable.
"Irreversible injury [appears] to have occurred in our three patients, and perhaps even in the fourth. Dalfampridine needs to be used with caution in multiple sclerosis patients with preexisting trigeminal neuralgia as well as in those with evidence of preexisting trigeminal nerve injuries," Dr. Birnbaum said.
When prescribing the drug, "I have to tell [patients] now that there’s a possibility that their trigeminal neuralgia may get worse, and it may not get better if they stop [the drug]. They have to take that into consideration," he said in an interview.
The four cases are not the first to be reported since the potassium channel blocker was approved for MS in 2010 to improve walking.
Investigators from the Mayo Clinic in Scottsdale, Ariz., reported two cases at AAN’s 2012 annual conference, both within a month of starting the drug and both in patients whose trigeminal neuralgia had been in remission. One patient responded to pain medications, the other needed a rhizotomy.
"As I talk to [physicians] about these data," people come up and say, "I’ve seen the same thing," Dr. Birnbaum said.
Dalfampridine improves action potential conduction in demyelinated axons. Perhaps when sensory nerves – such as the trigeminal – have a preexisting injury, that effect can lead to a type of "metabolic exhaustion" that makes the injury worse.
"Could there be a similar phenomenon with motor nerves? Perhaps one sees an initial improvement in motor function, but in the long term could this perhaps be deleterious? I have no data to support that, but the implication is that [it’s] a possibility," he said.
Dr. Birnbaum is a paid consultant to TEVA, Serono, Genzyme, Questcor, and Biogen Idec. Biogen Idec and Hoffman-LaRoche have both supported his research.
SAN DIEGO – A new adverse event may be emerging for dalfampridine – trigeminal neuralgia in multiple sclerosis patients with a preexisting trigeminal injury, or worsening of the condition in those who already have it, according to Dr. Gary Birnbaum, director of the Multiple Sclerosis Treatment and Research Center at the Minneapolis Clinic of Neurology.
Within a month of starting the drug at his clinic, three women with well-controlled trigeminal neuralgia "had very significant increases in the severity of their trigeminal pain," he said.
Stopping the drug brought some temporary relief to two, but they soon relapsed and their pain is now "very, very difficult to control," requiring substantially higher pain medication doses than before, he said.
In the third woman, the pain continued despite stopping the drug and no longer responded to pain medication. It was so severe that she contemplated suicide; she eventually had a trigeminal rhizotomy.
They had "very, very severe pain after" starting dalfampridine (Ampyra), "and it didn’t get better" when it was stopped. "That is what’s disquieting about it," Dr. Birnbaum said at the American Academy of Neurology (AAN) annual meeting.
A fourth patient developed trigeminal neuralgia after 18 months on the drug; the side of his face had only been numb previously. He now requires pain medications for the condition. Brain MRIs of all four patients were stable.
"Irreversible injury [appears] to have occurred in our three patients, and perhaps even in the fourth. Dalfampridine needs to be used with caution in multiple sclerosis patients with preexisting trigeminal neuralgia as well as in those with evidence of preexisting trigeminal nerve injuries," Dr. Birnbaum said.
When prescribing the drug, "I have to tell [patients] now that there’s a possibility that their trigeminal neuralgia may get worse, and it may not get better if they stop [the drug]. They have to take that into consideration," he said in an interview.
The four cases are not the first to be reported since the potassium channel blocker was approved for MS in 2010 to improve walking.
Investigators from the Mayo Clinic in Scottsdale, Ariz., reported two cases at AAN’s 2012 annual conference, both within a month of starting the drug and both in patients whose trigeminal neuralgia had been in remission. One patient responded to pain medications, the other needed a rhizotomy.
"As I talk to [physicians] about these data," people come up and say, "I’ve seen the same thing," Dr. Birnbaum said.
Dalfampridine improves action potential conduction in demyelinated axons. Perhaps when sensory nerves – such as the trigeminal – have a preexisting injury, that effect can lead to a type of "metabolic exhaustion" that makes the injury worse.
"Could there be a similar phenomenon with motor nerves? Perhaps one sees an initial improvement in motor function, but in the long term could this perhaps be deleterious? I have no data to support that, but the implication is that [it’s] a possibility," he said.
Dr. Birnbaum is a paid consultant to TEVA, Serono, Genzyme, Questcor, and Biogen Idec. Biogen Idec and Hoffman-LaRoche have both supported his research.
SAN DIEGO – A new adverse event may be emerging for dalfampridine – trigeminal neuralgia in multiple sclerosis patients with a preexisting trigeminal injury, or worsening of the condition in those who already have it, according to Dr. Gary Birnbaum, director of the Multiple Sclerosis Treatment and Research Center at the Minneapolis Clinic of Neurology.
Within a month of starting the drug at his clinic, three women with well-controlled trigeminal neuralgia "had very significant increases in the severity of their trigeminal pain," he said.
Stopping the drug brought some temporary relief to two, but they soon relapsed and their pain is now "very, very difficult to control," requiring substantially higher pain medication doses than before, he said.
In the third woman, the pain continued despite stopping the drug and no longer responded to pain medication. It was so severe that she contemplated suicide; she eventually had a trigeminal rhizotomy.
They had "very, very severe pain after" starting dalfampridine (Ampyra), "and it didn’t get better" when it was stopped. "That is what’s disquieting about it," Dr. Birnbaum said at the American Academy of Neurology (AAN) annual meeting.
A fourth patient developed trigeminal neuralgia after 18 months on the drug; the side of his face had only been numb previously. He now requires pain medications for the condition. Brain MRIs of all four patients were stable.
"Irreversible injury [appears] to have occurred in our three patients, and perhaps even in the fourth. Dalfampridine needs to be used with caution in multiple sclerosis patients with preexisting trigeminal neuralgia as well as in those with evidence of preexisting trigeminal nerve injuries," Dr. Birnbaum said.
When prescribing the drug, "I have to tell [patients] now that there’s a possibility that their trigeminal neuralgia may get worse, and it may not get better if they stop [the drug]. They have to take that into consideration," he said in an interview.
The four cases are not the first to be reported since the potassium channel blocker was approved for MS in 2010 to improve walking.
Investigators from the Mayo Clinic in Scottsdale, Ariz., reported two cases at AAN’s 2012 annual conference, both within a month of starting the drug and both in patients whose trigeminal neuralgia had been in remission. One patient responded to pain medications, the other needed a rhizotomy.
"As I talk to [physicians] about these data," people come up and say, "I’ve seen the same thing," Dr. Birnbaum said.
Dalfampridine improves action potential conduction in demyelinated axons. Perhaps when sensory nerves – such as the trigeminal – have a preexisting injury, that effect can lead to a type of "metabolic exhaustion" that makes the injury worse.
"Could there be a similar phenomenon with motor nerves? Perhaps one sees an initial improvement in motor function, but in the long term could this perhaps be deleterious? I have no data to support that, but the implication is that [it’s] a possibility," he said.
Dr. Birnbaum is a paid consultant to TEVA, Serono, Genzyme, Questcor, and Biogen Idec. Biogen Idec and Hoffman-LaRoche have both supported his research.
AT THE 2013 AAN ANNUAL MEETING
Major finding: There have been five reports of trigeminal neuralgia getting worse within 1 month of starting dalfampridine, and one report of new-onset trigeminal neuralgia in a patient with a preexisting trigeminal injury.
Data Source: Case reports from the Minneapolis Clinic of Neurology and Mayo Clinic in Scottsdale, Ariz.
Disclosures: Dr. Birnbaum is a paid consultant to TEVA, Serono, Genzyme, Questcor, and Biogen Idec. Biogen Idec and Hoffman-LaRoche have both supported his research.
