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Pediatric stroke thrombectomy study sheds light on off-label procedure
based on data from a retrospective, multicenter study of 73 patients.
Children with high scores on the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) or large-vessel occlusion in the anterior or posterior circulation are at increased risk for morbidity and mortality, but the safety of thrombectomy in children has not been well studied. Several randomized trials have showed its safety and efficacy in adults, wrote Peter Sporns, MD, of the Institute of Clinical Radiology at Universitätsklinikum Muenster (Germany), and colleagues.
In a study published in JAMA Neurology, Dr. Sporns and coauthors reviewed data from pediatric patients aged younger than 18 years who underwent endovascular recanalization between Jan. 1, 2000, and Dec. 31, 2018, at 25 stroke centers in Europe and 2 in the United States.
The primary outcome was change in the PedNIHSS scores and the endovascular recanalization involved “a combination of techniques using distal thrombaspiration and/or clot retrievers,” the researchers wrote.
Neurologic outcomes improved from a median PedNIHSS score of 14.0 at hospital admission to 4.0 at day 7. The average time from stroke onset to hospital admission was 3 hours, and the median time from stroke onset to recanalization was 4 hours.
“The rapidity of recanalization across the large number of centers in the Save ChildS study is a commendable achievement, establishing feasibility for acute pediatric stroke treatment within the short window of time for embolectomy at centers prepared for this event,” wrote Christine Fox, MD, of the University of California, San Francisco, and Nomazulu Dlamini, MBBS, PhD, of the Hospital for Sick Children, Toronto, in an accompanying editorial.
In addition, the median modified Rankin Scale score was 1.0 at discharge and at 6 and 24 months, and the median Pediatric Stroke Outcome Measure score was 1.0 at discharge and 0.5 at 6 and 24 months.
The median age of the patients was 11 years, and approximately half were boys (51%). A total of 63 children (86%) were treated for anterior circulation occlusion, and 10 (14%) were treated for posterior circulation occlusion; (22%) received concomitant intravenous thrombolysis.
Transient vasospasm was the only observed periprocedural complication, seen in four patients, and all cases resolved without clinical sequelae. One patient with a history of a heart anomaly died of cardiac arrest after recanalization. No vascular complications were reported, and the proportion of symptomatic intracerebral hemorrhage events was 1.37 per 100 observations, compared with 2.79 in a meta-analysis of adult studies.
The main limitation of the study was its retrospective design, as well as the absence of a control group, the researchers noted. However, the results “may support clinicians’ practice of off-label thrombectomy in childhood stroke in the absence of high-level evidence.”
The editorial authors emphasized that safety concerns remain despite the relatively low level of complications observed in the current study. “The safety of thrombectomy in children with suspected focal cerebral arteriopathy or bilateral arteriopathies is a particular concern because of the potential to further injure an acutely inflamed or chronically diseased vessel,” they wrote.
“We should be cautious about the interpretation of long-term outcome measures in the Save ChildS study,” Dr. Fox and Dr. Dlamini added, noting that additional multicenter studies are needed “to advance our knowledge of pediatric stroke and inform best practices.”
Dr. Sporns had no financial conflicts to disclose; several coauthors disclosed relationships with multiple pharmaceutical companies. Dr. Fox and Dr. Dlamini had no financial conflicts to disclose.
SOURCES: Sporns P et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3403; Fox C, Dlamini N. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3412.
based on data from a retrospective, multicenter study of 73 patients.
Children with high scores on the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) or large-vessel occlusion in the anterior or posterior circulation are at increased risk for morbidity and mortality, but the safety of thrombectomy in children has not been well studied. Several randomized trials have showed its safety and efficacy in adults, wrote Peter Sporns, MD, of the Institute of Clinical Radiology at Universitätsklinikum Muenster (Germany), and colleagues.
In a study published in JAMA Neurology, Dr. Sporns and coauthors reviewed data from pediatric patients aged younger than 18 years who underwent endovascular recanalization between Jan. 1, 2000, and Dec. 31, 2018, at 25 stroke centers in Europe and 2 in the United States.
The primary outcome was change in the PedNIHSS scores and the endovascular recanalization involved “a combination of techniques using distal thrombaspiration and/or clot retrievers,” the researchers wrote.
Neurologic outcomes improved from a median PedNIHSS score of 14.0 at hospital admission to 4.0 at day 7. The average time from stroke onset to hospital admission was 3 hours, and the median time from stroke onset to recanalization was 4 hours.
“The rapidity of recanalization across the large number of centers in the Save ChildS study is a commendable achievement, establishing feasibility for acute pediatric stroke treatment within the short window of time for embolectomy at centers prepared for this event,” wrote Christine Fox, MD, of the University of California, San Francisco, and Nomazulu Dlamini, MBBS, PhD, of the Hospital for Sick Children, Toronto, in an accompanying editorial.
In addition, the median modified Rankin Scale score was 1.0 at discharge and at 6 and 24 months, and the median Pediatric Stroke Outcome Measure score was 1.0 at discharge and 0.5 at 6 and 24 months.
The median age of the patients was 11 years, and approximately half were boys (51%). A total of 63 children (86%) were treated for anterior circulation occlusion, and 10 (14%) were treated for posterior circulation occlusion; (22%) received concomitant intravenous thrombolysis.
Transient vasospasm was the only observed periprocedural complication, seen in four patients, and all cases resolved without clinical sequelae. One patient with a history of a heart anomaly died of cardiac arrest after recanalization. No vascular complications were reported, and the proportion of symptomatic intracerebral hemorrhage events was 1.37 per 100 observations, compared with 2.79 in a meta-analysis of adult studies.
The main limitation of the study was its retrospective design, as well as the absence of a control group, the researchers noted. However, the results “may support clinicians’ practice of off-label thrombectomy in childhood stroke in the absence of high-level evidence.”
The editorial authors emphasized that safety concerns remain despite the relatively low level of complications observed in the current study. “The safety of thrombectomy in children with suspected focal cerebral arteriopathy or bilateral arteriopathies is a particular concern because of the potential to further injure an acutely inflamed or chronically diseased vessel,” they wrote.
“We should be cautious about the interpretation of long-term outcome measures in the Save ChildS study,” Dr. Fox and Dr. Dlamini added, noting that additional multicenter studies are needed “to advance our knowledge of pediatric stroke and inform best practices.”
Dr. Sporns had no financial conflicts to disclose; several coauthors disclosed relationships with multiple pharmaceutical companies. Dr. Fox and Dr. Dlamini had no financial conflicts to disclose.
SOURCES: Sporns P et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3403; Fox C, Dlamini N. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3412.
based on data from a retrospective, multicenter study of 73 patients.
Children with high scores on the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) or large-vessel occlusion in the anterior or posterior circulation are at increased risk for morbidity and mortality, but the safety of thrombectomy in children has not been well studied. Several randomized trials have showed its safety and efficacy in adults, wrote Peter Sporns, MD, of the Institute of Clinical Radiology at Universitätsklinikum Muenster (Germany), and colleagues.
In a study published in JAMA Neurology, Dr. Sporns and coauthors reviewed data from pediatric patients aged younger than 18 years who underwent endovascular recanalization between Jan. 1, 2000, and Dec. 31, 2018, at 25 stroke centers in Europe and 2 in the United States.
The primary outcome was change in the PedNIHSS scores and the endovascular recanalization involved “a combination of techniques using distal thrombaspiration and/or clot retrievers,” the researchers wrote.
Neurologic outcomes improved from a median PedNIHSS score of 14.0 at hospital admission to 4.0 at day 7. The average time from stroke onset to hospital admission was 3 hours, and the median time from stroke onset to recanalization was 4 hours.
“The rapidity of recanalization across the large number of centers in the Save ChildS study is a commendable achievement, establishing feasibility for acute pediatric stroke treatment within the short window of time for embolectomy at centers prepared for this event,” wrote Christine Fox, MD, of the University of California, San Francisco, and Nomazulu Dlamini, MBBS, PhD, of the Hospital for Sick Children, Toronto, in an accompanying editorial.
In addition, the median modified Rankin Scale score was 1.0 at discharge and at 6 and 24 months, and the median Pediatric Stroke Outcome Measure score was 1.0 at discharge and 0.5 at 6 and 24 months.
The median age of the patients was 11 years, and approximately half were boys (51%). A total of 63 children (86%) were treated for anterior circulation occlusion, and 10 (14%) were treated for posterior circulation occlusion; (22%) received concomitant intravenous thrombolysis.
Transient vasospasm was the only observed periprocedural complication, seen in four patients, and all cases resolved without clinical sequelae. One patient with a history of a heart anomaly died of cardiac arrest after recanalization. No vascular complications were reported, and the proportion of symptomatic intracerebral hemorrhage events was 1.37 per 100 observations, compared with 2.79 in a meta-analysis of adult studies.
The main limitation of the study was its retrospective design, as well as the absence of a control group, the researchers noted. However, the results “may support clinicians’ practice of off-label thrombectomy in childhood stroke in the absence of high-level evidence.”
The editorial authors emphasized that safety concerns remain despite the relatively low level of complications observed in the current study. “The safety of thrombectomy in children with suspected focal cerebral arteriopathy or bilateral arteriopathies is a particular concern because of the potential to further injure an acutely inflamed or chronically diseased vessel,” they wrote.
“We should be cautious about the interpretation of long-term outcome measures in the Save ChildS study,” Dr. Fox and Dr. Dlamini added, noting that additional multicenter studies are needed “to advance our knowledge of pediatric stroke and inform best practices.”
Dr. Sporns had no financial conflicts to disclose; several coauthors disclosed relationships with multiple pharmaceutical companies. Dr. Fox and Dr. Dlamini had no financial conflicts to disclose.
SOURCES: Sporns P et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3403; Fox C, Dlamini N. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3412.
FROM JAMA NEUROLOGY
Increased Parkinson’s disease risk seen with bipolar disorder
Patients with bipolar disorder may be at increased risk of Parkinson’s disease in later life, according to a systematic review and meta-analysis published in JAMA Neurology.
Patrícia R. Faustino, MD, from the faculty of medicine at the University of Lisboa (Portgual), and coauthors reviewed and analyzed seven articles – four cohort studies and three cross-sectional studies – that reported data on idiopathic Parkinson’s disease in patients with bipolar disorder, compared with those without. The meta-analysis found that individuals with a previous diagnosis of bipolar disorder had a 235% higher risk of being later diagnosed with Parkinson’s disease. Even after removing studies with a high risk of bias, the risk was still 3.21 times higher in those with bipolar disorder, compared with those without.
“The pathophysiological rationale between bipolar disorder and Parkinson’s disease might be explained by the dopamine dysregulation hypothesis, which states that the cyclical process of bipolar disorder in manic states leads to a down-regulation of dopamine receptor sensitivity (depression phase), which is later compensated by up-regulation (manic state),” the authors wrote. “Over time, this phenomenon may lead to an overall reduction of dopaminergic activity, the prototypical Parkinson’s disease state.”
Subgroup analysis revealed that subgroups with shorter follow-up periods – less than 9 years – had a greater increase in the risk of a later Parkinson’s disease diagnosis. The authors noted that this could represent misdiagnosis of parkinsonism – possibly drug induced – as Parkinson’s disease. The researchers also raised the possibility that the increased risk of Parkinson’s disease in patients with bipolar disorder could relate to long-term lithium use, rather than being a causal relationship. “However, treatment with lithium is foundational in bipolar disorder, and so to separate the causal effect from a potential confounder would be particularly difficult,” they wrote.
One of the studies included did explore the use of lithium, and found that lithium monotherapy was associated with a significant increase in the risk of being diagnosed with Parkinson’s disease or taking antiparkinsonism medication, compared with antidepressant therapy. However the authors commented that the diagnostic code may not differentiate Parkinson’s disease from other causes of parkinsonism.
Given their findings, the authors suggested that, if patients with bipolar disorder present with parkinsonism features, it may not necessarily be drug induced. In these patients, they recommended an investigation for Parkinson’s disease, perhaps using functional neuroimaging “as Parkinson’s disease classically presents with nigrostriatal degeneration while drug-induced parkinsonism does not.”
Two authors declared grants and personal fees from the pharmaceutical sector. No other conflicts of interest were reported.
SOURCE: Faustino PR et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3446.
Patients with bipolar disorder may be at increased risk of Parkinson’s disease in later life, according to a systematic review and meta-analysis published in JAMA Neurology.
Patrícia R. Faustino, MD, from the faculty of medicine at the University of Lisboa (Portgual), and coauthors reviewed and analyzed seven articles – four cohort studies and three cross-sectional studies – that reported data on idiopathic Parkinson’s disease in patients with bipolar disorder, compared with those without. The meta-analysis found that individuals with a previous diagnosis of bipolar disorder had a 235% higher risk of being later diagnosed with Parkinson’s disease. Even after removing studies with a high risk of bias, the risk was still 3.21 times higher in those with bipolar disorder, compared with those without.
“The pathophysiological rationale between bipolar disorder and Parkinson’s disease might be explained by the dopamine dysregulation hypothesis, which states that the cyclical process of bipolar disorder in manic states leads to a down-regulation of dopamine receptor sensitivity (depression phase), which is later compensated by up-regulation (manic state),” the authors wrote. “Over time, this phenomenon may lead to an overall reduction of dopaminergic activity, the prototypical Parkinson’s disease state.”
Subgroup analysis revealed that subgroups with shorter follow-up periods – less than 9 years – had a greater increase in the risk of a later Parkinson’s disease diagnosis. The authors noted that this could represent misdiagnosis of parkinsonism – possibly drug induced – as Parkinson’s disease. The researchers also raised the possibility that the increased risk of Parkinson’s disease in patients with bipolar disorder could relate to long-term lithium use, rather than being a causal relationship. “However, treatment with lithium is foundational in bipolar disorder, and so to separate the causal effect from a potential confounder would be particularly difficult,” they wrote.
One of the studies included did explore the use of lithium, and found that lithium monotherapy was associated with a significant increase in the risk of being diagnosed with Parkinson’s disease or taking antiparkinsonism medication, compared with antidepressant therapy. However the authors commented that the diagnostic code may not differentiate Parkinson’s disease from other causes of parkinsonism.
Given their findings, the authors suggested that, if patients with bipolar disorder present with parkinsonism features, it may not necessarily be drug induced. In these patients, they recommended an investigation for Parkinson’s disease, perhaps using functional neuroimaging “as Parkinson’s disease classically presents with nigrostriatal degeneration while drug-induced parkinsonism does not.”
Two authors declared grants and personal fees from the pharmaceutical sector. No other conflicts of interest were reported.
SOURCE: Faustino PR et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3446.
Patients with bipolar disorder may be at increased risk of Parkinson’s disease in later life, according to a systematic review and meta-analysis published in JAMA Neurology.
Patrícia R. Faustino, MD, from the faculty of medicine at the University of Lisboa (Portgual), and coauthors reviewed and analyzed seven articles – four cohort studies and three cross-sectional studies – that reported data on idiopathic Parkinson’s disease in patients with bipolar disorder, compared with those without. The meta-analysis found that individuals with a previous diagnosis of bipolar disorder had a 235% higher risk of being later diagnosed with Parkinson’s disease. Even after removing studies with a high risk of bias, the risk was still 3.21 times higher in those with bipolar disorder, compared with those without.
“The pathophysiological rationale between bipolar disorder and Parkinson’s disease might be explained by the dopamine dysregulation hypothesis, which states that the cyclical process of bipolar disorder in manic states leads to a down-regulation of dopamine receptor sensitivity (depression phase), which is later compensated by up-regulation (manic state),” the authors wrote. “Over time, this phenomenon may lead to an overall reduction of dopaminergic activity, the prototypical Parkinson’s disease state.”
Subgroup analysis revealed that subgroups with shorter follow-up periods – less than 9 years – had a greater increase in the risk of a later Parkinson’s disease diagnosis. The authors noted that this could represent misdiagnosis of parkinsonism – possibly drug induced – as Parkinson’s disease. The researchers also raised the possibility that the increased risk of Parkinson’s disease in patients with bipolar disorder could relate to long-term lithium use, rather than being a causal relationship. “However, treatment with lithium is foundational in bipolar disorder, and so to separate the causal effect from a potential confounder would be particularly difficult,” they wrote.
One of the studies included did explore the use of lithium, and found that lithium monotherapy was associated with a significant increase in the risk of being diagnosed with Parkinson’s disease or taking antiparkinsonism medication, compared with antidepressant therapy. However the authors commented that the diagnostic code may not differentiate Parkinson’s disease from other causes of parkinsonism.
Given their findings, the authors suggested that, if patients with bipolar disorder present with parkinsonism features, it may not necessarily be drug induced. In these patients, they recommended an investigation for Parkinson’s disease, perhaps using functional neuroimaging “as Parkinson’s disease classically presents with nigrostriatal degeneration while drug-induced parkinsonism does not.”
Two authors declared grants and personal fees from the pharmaceutical sector. No other conflicts of interest were reported.
SOURCE: Faustino PR et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3446.
FROM JAMA NEUROLOGY
Forgetting the Stuff That Dreams Are Made On
Why do we forget some dreams and remember others? Researchers in a study funded by the National Institute of Neurological Disorders and Stroke say our dream memory may be controlled by a group of neurons commonly associated with appetite. Their findings could shed light on a wide range of memory-related conditions, including posttraumatic stress disorder (PTSD) and Alzheimer disease.
Studies have already shown that sleep helps the brain store new memories and eliminate excess information. Recent mouse studies have found that during sleep the brain prunes synaptic connections made between neurons involved in some types of learning.
But this study shows how that might happen.
The researchers have previously demonstrated that narcolepsy might be linked to the loss of hypocretin/orexin-making neurons in the hypothalamus. In this study, they looked at neighboring cells that produce melanin-concentrating hormone (MCH), which is involved in the control of both sleep and appetite. A majority (53%) of hypothalamic MCH cells fired in mice during REM sleep; 35% fired when they were awake, and 12% fired at both times.
Those cells also may play a role in learning and memory, the researchers suggest. To test their theory that MCH cells might help the brain store memories, they used “genetic tools” to turn MCH neurons on and off during memory tests.
Surprisingly, the researchers say, pharmacogenetic activation—turning on the MCH cells—worsened memory; genetic ablation—turning them off—improved memory. Further experiments suggested MCH neurons exclusively played this role during REM sleep.
The results suggest that MCH neurons help the brain actively forget new, possibly unimportant information. “Since dreams are thought to primarily occur during REM sleep,” says Thomas Kilduff, PhD, senior author of the study, “the sleep stage when the MCH cells turn on, activation of these cells may prevent the content of a dream from being stored in the hippocampus—consequently, the dream is quickly forgotten.”
Why do we forget some dreams and remember others? Researchers in a study funded by the National Institute of Neurological Disorders and Stroke say our dream memory may be controlled by a group of neurons commonly associated with appetite. Their findings could shed light on a wide range of memory-related conditions, including posttraumatic stress disorder (PTSD) and Alzheimer disease.
Studies have already shown that sleep helps the brain store new memories and eliminate excess information. Recent mouse studies have found that during sleep the brain prunes synaptic connections made between neurons involved in some types of learning.
But this study shows how that might happen.
The researchers have previously demonstrated that narcolepsy might be linked to the loss of hypocretin/orexin-making neurons in the hypothalamus. In this study, they looked at neighboring cells that produce melanin-concentrating hormone (MCH), which is involved in the control of both sleep and appetite. A majority (53%) of hypothalamic MCH cells fired in mice during REM sleep; 35% fired when they were awake, and 12% fired at both times.
Those cells also may play a role in learning and memory, the researchers suggest. To test their theory that MCH cells might help the brain store memories, they used “genetic tools” to turn MCH neurons on and off during memory tests.
Surprisingly, the researchers say, pharmacogenetic activation—turning on the MCH cells—worsened memory; genetic ablation—turning them off—improved memory. Further experiments suggested MCH neurons exclusively played this role during REM sleep.
The results suggest that MCH neurons help the brain actively forget new, possibly unimportant information. “Since dreams are thought to primarily occur during REM sleep,” says Thomas Kilduff, PhD, senior author of the study, “the sleep stage when the MCH cells turn on, activation of these cells may prevent the content of a dream from being stored in the hippocampus—consequently, the dream is quickly forgotten.”
Why do we forget some dreams and remember others? Researchers in a study funded by the National Institute of Neurological Disorders and Stroke say our dream memory may be controlled by a group of neurons commonly associated with appetite. Their findings could shed light on a wide range of memory-related conditions, including posttraumatic stress disorder (PTSD) and Alzheimer disease.
Studies have already shown that sleep helps the brain store new memories and eliminate excess information. Recent mouse studies have found that during sleep the brain prunes synaptic connections made between neurons involved in some types of learning.
But this study shows how that might happen.
The researchers have previously demonstrated that narcolepsy might be linked to the loss of hypocretin/orexin-making neurons in the hypothalamus. In this study, they looked at neighboring cells that produce melanin-concentrating hormone (MCH), which is involved in the control of both sleep and appetite. A majority (53%) of hypothalamic MCH cells fired in mice during REM sleep; 35% fired when they were awake, and 12% fired at both times.
Those cells also may play a role in learning and memory, the researchers suggest. To test their theory that MCH cells might help the brain store memories, they used “genetic tools” to turn MCH neurons on and off during memory tests.
Surprisingly, the researchers say, pharmacogenetic activation—turning on the MCH cells—worsened memory; genetic ablation—turning them off—improved memory. Further experiments suggested MCH neurons exclusively played this role during REM sleep.
The results suggest that MCH neurons help the brain actively forget new, possibly unimportant information. “Since dreams are thought to primarily occur during REM sleep,” says Thomas Kilduff, PhD, senior author of the study, “the sleep stage when the MCH cells turn on, activation of these cells may prevent the content of a dream from being stored in the hippocampus—consequently, the dream is quickly forgotten.”
Urine Reveals Biomarker for Potential TBI
Even a mild blast to the brain can cause long-term, life-changing health problems, says Riyi Shi, professor of neuroscience and biomedical engineering at Purdue University in Lafayette, Indiana. However, the effects can be subtle: “The individual appears to be fine, and it’s difficult to tell if you just look at a person. But the fact is that these types of hits are multiplied over years and often ignored until someone reaches an age when other factors come into play.”
Treating the incidents sooner can help mitigate later-life issues, such as Parkinson disease (PD). Shi led a study that found checking the urine within 7 days following a blast incident—even a mild one—provides faster diagnosis when brain injury is suspected.
A simple urine analysis reveals elevations in the neurotoxin acrolein, Shi says, which is a biomarker for brain injury. In the study, the researchers evaluated the changes of α-synuclein and tyrosine hydroxylase, hallmarks of PD, and acrolein, a marker of oxidative stress. The researchers say in animal models of PD and traumatic brain injury (TBI), acrolein is “likely a point of pathogenic convergence.”
They found that after a single mild blast TBI, acrolein was elevated for up to a week, systemically in urine, and in whole brain tissue, specifically the substantia nigra and striatum. The elevation was accompanied by heightened α-synuclein oligomerization, dopaminergic dysregulation, and acrolein/α-synuclein interaction in the same brain regions. Taken together, the researchers say, the data suggest that acrolein likely plays a key role in inducing PD following blast TBI.
The presence of the biomarker “alerts us to the injury, creating an opportunity for intervention,” Shi says. “This early detection and subsequent treatment window could offer tremendous benefits for long-term patient neurologic health.”
Even a mild blast to the brain can cause long-term, life-changing health problems, says Riyi Shi, professor of neuroscience and biomedical engineering at Purdue University in Lafayette, Indiana. However, the effects can be subtle: “The individual appears to be fine, and it’s difficult to tell if you just look at a person. But the fact is that these types of hits are multiplied over years and often ignored until someone reaches an age when other factors come into play.”
Treating the incidents sooner can help mitigate later-life issues, such as Parkinson disease (PD). Shi led a study that found checking the urine within 7 days following a blast incident—even a mild one—provides faster diagnosis when brain injury is suspected.
A simple urine analysis reveals elevations in the neurotoxin acrolein, Shi says, which is a biomarker for brain injury. In the study, the researchers evaluated the changes of α-synuclein and tyrosine hydroxylase, hallmarks of PD, and acrolein, a marker of oxidative stress. The researchers say in animal models of PD and traumatic brain injury (TBI), acrolein is “likely a point of pathogenic convergence.”
They found that after a single mild blast TBI, acrolein was elevated for up to a week, systemically in urine, and in whole brain tissue, specifically the substantia nigra and striatum. The elevation was accompanied by heightened α-synuclein oligomerization, dopaminergic dysregulation, and acrolein/α-synuclein interaction in the same brain regions. Taken together, the researchers say, the data suggest that acrolein likely plays a key role in inducing PD following blast TBI.
The presence of the biomarker “alerts us to the injury, creating an opportunity for intervention,” Shi says. “This early detection and subsequent treatment window could offer tremendous benefits for long-term patient neurologic health.”
Even a mild blast to the brain can cause long-term, life-changing health problems, says Riyi Shi, professor of neuroscience and biomedical engineering at Purdue University in Lafayette, Indiana. However, the effects can be subtle: “The individual appears to be fine, and it’s difficult to tell if you just look at a person. But the fact is that these types of hits are multiplied over years and often ignored until someone reaches an age when other factors come into play.”
Treating the incidents sooner can help mitigate later-life issues, such as Parkinson disease (PD). Shi led a study that found checking the urine within 7 days following a blast incident—even a mild one—provides faster diagnosis when brain injury is suspected.
A simple urine analysis reveals elevations in the neurotoxin acrolein, Shi says, which is a biomarker for brain injury. In the study, the researchers evaluated the changes of α-synuclein and tyrosine hydroxylase, hallmarks of PD, and acrolein, a marker of oxidative stress. The researchers say in animal models of PD and traumatic brain injury (TBI), acrolein is “likely a point of pathogenic convergence.”
They found that after a single mild blast TBI, acrolein was elevated for up to a week, systemically in urine, and in whole brain tissue, specifically the substantia nigra and striatum. The elevation was accompanied by heightened α-synuclein oligomerization, dopaminergic dysregulation, and acrolein/α-synuclein interaction in the same brain regions. Taken together, the researchers say, the data suggest that acrolein likely plays a key role in inducing PD following blast TBI.
The presence of the biomarker “alerts us to the injury, creating an opportunity for intervention,” Shi says. “This early detection and subsequent treatment window could offer tremendous benefits for long-term patient neurologic health.”
Congenital heart disease in children linked to increased autism risk
A new study of children who were born with congenital heart disease (CHD) has found that they have increased odds of developing autism spectrum disorder.
“To our knowledge, this is the only study in which there has been a comparison between [autism spectrum disorder] and multiple CHD subtypes,” wrote Eric R. Sigmon, MD, of Emory University, Atlanta, and coauthors. “Our findings are consistent with previous studies of CHD developmental outcomes, which have shown an increased risk of developmental and academic delay after CHD diagnosis and treatment.” The study was published in Pediatrics.
To further investigate the association between CHD and autism, the researchers performed a case-control study using the Military Health System administrative database. They uncovered 8,760 cases of children with autism spectrum disorder and matched each one with three controls (n = 26,280). From that sample size, they identified 1,063 children with CHD: 401 in the autism spectrum disorder group and 662 in the control group.
Before analysis, children with autism spectrum disorder had an odds ratio of 1.85 of having any form of CHD, compared with controls (95% confidence interval, 1.63-2.10). After adjustment for covariates – including genetic syndromes, maternal age and morbidity, perinatal morbidity, and neonatal complications – the OR was 1.33 (95% CI, 1.16-1.52).
In the sensitivity analysis – which included only 593 children with CHD – the OR was a similar 1.32 (95% CI, 1.10-1.59).
Left heart obstructive lesion was significantly associated with autism spectrum disorder after covariate adjustment (OR, 1.42; 95% CI, 1.04-1.93), but the finding was no longer significant in the sensitivity analysis.
The authors noted the potential limitations of their study, including the general weaknesses of administrative data, which they attempted to counter with the sensitive analysis. In addition, they recognized that children with either autism spectrum disorder or CHD “tend to present for care more frequently,” which could have created an ascertainment bias.
In an accompanying editorial, Johanna Calderon, PhD, David C. Bellinger, PhD, and Jane W. Newburger, MD, MPH, stated that more work needs to be done to further quantify the relationship between CHD and autism spectrum disorder (Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2019-2752). The three authors – all affiliated with Boston Children’s Hospital and Harvard Medical School, also in Boston – reiterated the acknowledgment from Dr. Sigmon and coauthors that the “etiologic pathways that might explain” the link between the two remains unknown. They also noted their surprise that autism spectrum disorder risk appears to be increased in children with modestly severe forms of CHD, stating that this finding required additional investigation.
“Despite the strengths of this study,” they wrote, “it raises more questions than answers.”
The study was funded by the Congressional Directed Medical Research Programs Autism Research Award. The authors reported no conflicts of interest.
SOURCE: Sigmon ER at al. Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2018-4114.
A new study of children who were born with congenital heart disease (CHD) has found that they have increased odds of developing autism spectrum disorder.
“To our knowledge, this is the only study in which there has been a comparison between [autism spectrum disorder] and multiple CHD subtypes,” wrote Eric R. Sigmon, MD, of Emory University, Atlanta, and coauthors. “Our findings are consistent with previous studies of CHD developmental outcomes, which have shown an increased risk of developmental and academic delay after CHD diagnosis and treatment.” The study was published in Pediatrics.
To further investigate the association between CHD and autism, the researchers performed a case-control study using the Military Health System administrative database. They uncovered 8,760 cases of children with autism spectrum disorder and matched each one with three controls (n = 26,280). From that sample size, they identified 1,063 children with CHD: 401 in the autism spectrum disorder group and 662 in the control group.
Before analysis, children with autism spectrum disorder had an odds ratio of 1.85 of having any form of CHD, compared with controls (95% confidence interval, 1.63-2.10). After adjustment for covariates – including genetic syndromes, maternal age and morbidity, perinatal morbidity, and neonatal complications – the OR was 1.33 (95% CI, 1.16-1.52).
In the sensitivity analysis – which included only 593 children with CHD – the OR was a similar 1.32 (95% CI, 1.10-1.59).
Left heart obstructive lesion was significantly associated with autism spectrum disorder after covariate adjustment (OR, 1.42; 95% CI, 1.04-1.93), but the finding was no longer significant in the sensitivity analysis.
The authors noted the potential limitations of their study, including the general weaknesses of administrative data, which they attempted to counter with the sensitive analysis. In addition, they recognized that children with either autism spectrum disorder or CHD “tend to present for care more frequently,” which could have created an ascertainment bias.
In an accompanying editorial, Johanna Calderon, PhD, David C. Bellinger, PhD, and Jane W. Newburger, MD, MPH, stated that more work needs to be done to further quantify the relationship between CHD and autism spectrum disorder (Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2019-2752). The three authors – all affiliated with Boston Children’s Hospital and Harvard Medical School, also in Boston – reiterated the acknowledgment from Dr. Sigmon and coauthors that the “etiologic pathways that might explain” the link between the two remains unknown. They also noted their surprise that autism spectrum disorder risk appears to be increased in children with modestly severe forms of CHD, stating that this finding required additional investigation.
“Despite the strengths of this study,” they wrote, “it raises more questions than answers.”
The study was funded by the Congressional Directed Medical Research Programs Autism Research Award. The authors reported no conflicts of interest.
SOURCE: Sigmon ER at al. Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2018-4114.
A new study of children who were born with congenital heart disease (CHD) has found that they have increased odds of developing autism spectrum disorder.
“To our knowledge, this is the only study in which there has been a comparison between [autism spectrum disorder] and multiple CHD subtypes,” wrote Eric R. Sigmon, MD, of Emory University, Atlanta, and coauthors. “Our findings are consistent with previous studies of CHD developmental outcomes, which have shown an increased risk of developmental and academic delay after CHD diagnosis and treatment.” The study was published in Pediatrics.
To further investigate the association between CHD and autism, the researchers performed a case-control study using the Military Health System administrative database. They uncovered 8,760 cases of children with autism spectrum disorder and matched each one with three controls (n = 26,280). From that sample size, they identified 1,063 children with CHD: 401 in the autism spectrum disorder group and 662 in the control group.
Before analysis, children with autism spectrum disorder had an odds ratio of 1.85 of having any form of CHD, compared with controls (95% confidence interval, 1.63-2.10). After adjustment for covariates – including genetic syndromes, maternal age and morbidity, perinatal morbidity, and neonatal complications – the OR was 1.33 (95% CI, 1.16-1.52).
In the sensitivity analysis – which included only 593 children with CHD – the OR was a similar 1.32 (95% CI, 1.10-1.59).
Left heart obstructive lesion was significantly associated with autism spectrum disorder after covariate adjustment (OR, 1.42; 95% CI, 1.04-1.93), but the finding was no longer significant in the sensitivity analysis.
The authors noted the potential limitations of their study, including the general weaknesses of administrative data, which they attempted to counter with the sensitive analysis. In addition, they recognized that children with either autism spectrum disorder or CHD “tend to present for care more frequently,” which could have created an ascertainment bias.
In an accompanying editorial, Johanna Calderon, PhD, David C. Bellinger, PhD, and Jane W. Newburger, MD, MPH, stated that more work needs to be done to further quantify the relationship between CHD and autism spectrum disorder (Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2019-2752). The three authors – all affiliated with Boston Children’s Hospital and Harvard Medical School, also in Boston – reiterated the acknowledgment from Dr. Sigmon and coauthors that the “etiologic pathways that might explain” the link between the two remains unknown. They also noted their surprise that autism spectrum disorder risk appears to be increased in children with modestly severe forms of CHD, stating that this finding required additional investigation.
“Despite the strengths of this study,” they wrote, “it raises more questions than answers.”
The study was funded by the Congressional Directed Medical Research Programs Autism Research Award. The authors reported no conflicts of interest.
SOURCE: Sigmon ER at al. Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2018-4114.
FROM PEDIATRICS
Key clinical point: Children born with congenital heart disease have higher odds of developing autism, especially with certain forms of CHD, such as atrial and ventricular septal defects.
Major finding: After sensitivity analysis, children with congenital heart disease had increased odds of autism, compared with controls (odds ratio, 1.32; 95% confidence interval, 1.10-1.59).
Study details: A case-control study of children enrolled in the U.S. Military Health System from 2001 to 2013.
Disclosures: The study was funded by the Congressional Directed Medical Research Programs Autism Research Award. The authors reported no conflicts of interest.
Source: Sigmon ER at al. Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2018-4114.
Investigators use ARMSS score to predict future MS-related disability
STOCKHOLM – , according to research presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. The resulting measurement is stable, not highly sensitive to age, and appropriate for research applications. “It could give a clinician an earlier indication of the potential disease course of a patient,” said Ryan Ramanujam, PhD, assistant professor of translational neuroepidemiology at Karolinska Institutet in Stockholm.
Researchers who study MS use various scores to measure disease severity, including the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS). These scores cannot predict a patient’s future status, however, and they do not remain stable throughout the course of a patient’s disease. Fitting a linear model over a series of scores over time can provide a misleading impression of a patient’s disease progression. “What we need is a metric to give a holistic overview of disease course, regardless of when it’s measured in a patient’s disease progression,” said Dr. Ramanujam. Such a measurement could aid the search for genes that affect MS severity, he added.
Examining disability by patient age
Dr. Ramanujam and colleagues constructed their measure using the ARMSS score, which ranks EDSS score by age instead of by disease duration. The ARMSS score ranges from 0 to 10, and the median value is 5 for all patients at a given age. Investigators can calculate the score using a previously published global matrix of values for ARMSS and MSSS available in the R package ms.sev.
The investigators found that the ARMSS score is slightly superior to the MSSS in detecting small increases in EDSS. One benefit of the ARMSS score, compared with the MSSS, is that it allows investigators to study patients for whom time of disease onset is unknown. The ARMSS score also removes potential systematic bias that might result from a neurologist’s retrospective assignment of date of disease onset, said Dr. Ramanujam.
He and his colleagues used ARMSS to compare patients’ disease course with what is expected for that patient (i.e., an ARMSS that remains stable at 5). They extracted data for 15,831 patients participating in the Swedish MS registry, including age and EDSS score at each neurological visit. Eligible patients had serial EDSS scores for 10 years. Dr. Ramanujam and colleagues included 4,514 patients in their analysis.
Measures at 2 years correlated with those at 10 years
The researchers created what they called the ARMSS integral by calculating the ARMSS score’s change from 5 at each examination (e.g., −0.5 or 1). “The ARMSS integral can be thought of as the cumulative disability that a patient accrues over his or her disease course, relative to the average patient, who had the disease for the same ages,” said Dr. Ramanujam. At 2 years of follow-up and at 10 years of follow-up, the distribution of ARMSS integrals for the study population followed a normal pattern.
Next, the investigators sought to compare patients by standardizing their follow-up time. To do this, they calculated what they called the ARMSS-rate by dividing each patient’s ARMSS integral by the number of years of follow-up. The ARMSS-rate offers a “snapshot of disease severity and progression,” said Dr. Ramanujam. When the researchers compared ARMSS-rates at 2 years and 10 years for each patient, they found that the measure was “extremely stable over time and strongly correlated with future disability.” The correlation improved slightly when the researchers compared ARMSS-rates at 4 years and 10 years.
The investigators then categorized patients based on their ARMSS-rate at 2 years (e.g., 0 to 1, 1 to 2, 2 to 3). When they compared the values in these categories with the median ARMSS-rates for the same individuals over the subsequent 8 years, they found strong group-level correlations.
To analyze correlations on an individual level, Dr. Ramanujam and colleagues examined the ability of different metrics at the time closest to 2 years of follow-up to predict those measured at 10 years. They assigned the value 1 to the most severe quartile of outcomes and the value 0 to all other quartiles. For predictors and outcomes, the investigators examined ARMSS-rate and the integral of progression index, which they calculated using the integral of EDSS. They also included EDSS at 10 years as an outcome for progression index.
For predicting the subsequent 8 years of ARMSS-rates, ARMSS-rate at 2 years had an area under the curve (AUC) of 0.921. When the investigators performed the same analysis using a cohort of patients with MS from British Columbia, Canada, they obtained an AUC of 0.887. Progression index at 2 years had an AUC of 0.61 for predicting the most severe quartile of the next 8 years. Compared with this result, ARMSS integral up to 2 years was slightly better at predicting EDSS at 10 years, said Dr. Ramanujam. The progression index poorly predicted the most severe quartile of EDSS at 10 years.
The main limitation of the ARMSS integral and ARMSS-rate is that they are based on EDSS, he added. The EDSS gives great weight to mobility and largely does not measure cognitive disability. “Future metrics could therefore include additional data such as MRI, Symbol Digit Modalities Test, or neurofilament light levels,” said Dr. Ramanujam. “Also, self-assessment could be one area to improve in the future.”
Dr. Ramanujam had no conflicts of interest to disclose. He receives funding from the MultipleMS Project, which is part of the EU Horizon 2020 Framework.
STOCKHOLM – , according to research presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. The resulting measurement is stable, not highly sensitive to age, and appropriate for research applications. “It could give a clinician an earlier indication of the potential disease course of a patient,” said Ryan Ramanujam, PhD, assistant professor of translational neuroepidemiology at Karolinska Institutet in Stockholm.
Researchers who study MS use various scores to measure disease severity, including the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS). These scores cannot predict a patient’s future status, however, and they do not remain stable throughout the course of a patient’s disease. Fitting a linear model over a series of scores over time can provide a misleading impression of a patient’s disease progression. “What we need is a metric to give a holistic overview of disease course, regardless of when it’s measured in a patient’s disease progression,” said Dr. Ramanujam. Such a measurement could aid the search for genes that affect MS severity, he added.
Examining disability by patient age
Dr. Ramanujam and colleagues constructed their measure using the ARMSS score, which ranks EDSS score by age instead of by disease duration. The ARMSS score ranges from 0 to 10, and the median value is 5 for all patients at a given age. Investigators can calculate the score using a previously published global matrix of values for ARMSS and MSSS available in the R package ms.sev.
The investigators found that the ARMSS score is slightly superior to the MSSS in detecting small increases in EDSS. One benefit of the ARMSS score, compared with the MSSS, is that it allows investigators to study patients for whom time of disease onset is unknown. The ARMSS score also removes potential systematic bias that might result from a neurologist’s retrospective assignment of date of disease onset, said Dr. Ramanujam.
He and his colleagues used ARMSS to compare patients’ disease course with what is expected for that patient (i.e., an ARMSS that remains stable at 5). They extracted data for 15,831 patients participating in the Swedish MS registry, including age and EDSS score at each neurological visit. Eligible patients had serial EDSS scores for 10 years. Dr. Ramanujam and colleagues included 4,514 patients in their analysis.
Measures at 2 years correlated with those at 10 years
The researchers created what they called the ARMSS integral by calculating the ARMSS score’s change from 5 at each examination (e.g., −0.5 or 1). “The ARMSS integral can be thought of as the cumulative disability that a patient accrues over his or her disease course, relative to the average patient, who had the disease for the same ages,” said Dr. Ramanujam. At 2 years of follow-up and at 10 years of follow-up, the distribution of ARMSS integrals for the study population followed a normal pattern.
Next, the investigators sought to compare patients by standardizing their follow-up time. To do this, they calculated what they called the ARMSS-rate by dividing each patient’s ARMSS integral by the number of years of follow-up. The ARMSS-rate offers a “snapshot of disease severity and progression,” said Dr. Ramanujam. When the researchers compared ARMSS-rates at 2 years and 10 years for each patient, they found that the measure was “extremely stable over time and strongly correlated with future disability.” The correlation improved slightly when the researchers compared ARMSS-rates at 4 years and 10 years.
The investigators then categorized patients based on their ARMSS-rate at 2 years (e.g., 0 to 1, 1 to 2, 2 to 3). When they compared the values in these categories with the median ARMSS-rates for the same individuals over the subsequent 8 years, they found strong group-level correlations.
To analyze correlations on an individual level, Dr. Ramanujam and colleagues examined the ability of different metrics at the time closest to 2 years of follow-up to predict those measured at 10 years. They assigned the value 1 to the most severe quartile of outcomes and the value 0 to all other quartiles. For predictors and outcomes, the investigators examined ARMSS-rate and the integral of progression index, which they calculated using the integral of EDSS. They also included EDSS at 10 years as an outcome for progression index.
For predicting the subsequent 8 years of ARMSS-rates, ARMSS-rate at 2 years had an area under the curve (AUC) of 0.921. When the investigators performed the same analysis using a cohort of patients with MS from British Columbia, Canada, they obtained an AUC of 0.887. Progression index at 2 years had an AUC of 0.61 for predicting the most severe quartile of the next 8 years. Compared with this result, ARMSS integral up to 2 years was slightly better at predicting EDSS at 10 years, said Dr. Ramanujam. The progression index poorly predicted the most severe quartile of EDSS at 10 years.
The main limitation of the ARMSS integral and ARMSS-rate is that they are based on EDSS, he added. The EDSS gives great weight to mobility and largely does not measure cognitive disability. “Future metrics could therefore include additional data such as MRI, Symbol Digit Modalities Test, or neurofilament light levels,” said Dr. Ramanujam. “Also, self-assessment could be one area to improve in the future.”
Dr. Ramanujam had no conflicts of interest to disclose. He receives funding from the MultipleMS Project, which is part of the EU Horizon 2020 Framework.
STOCKHOLM – , according to research presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. The resulting measurement is stable, not highly sensitive to age, and appropriate for research applications. “It could give a clinician an earlier indication of the potential disease course of a patient,” said Ryan Ramanujam, PhD, assistant professor of translational neuroepidemiology at Karolinska Institutet in Stockholm.
Researchers who study MS use various scores to measure disease severity, including the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS). These scores cannot predict a patient’s future status, however, and they do not remain stable throughout the course of a patient’s disease. Fitting a linear model over a series of scores over time can provide a misleading impression of a patient’s disease progression. “What we need is a metric to give a holistic overview of disease course, regardless of when it’s measured in a patient’s disease progression,” said Dr. Ramanujam. Such a measurement could aid the search for genes that affect MS severity, he added.
Examining disability by patient age
Dr. Ramanujam and colleagues constructed their measure using the ARMSS score, which ranks EDSS score by age instead of by disease duration. The ARMSS score ranges from 0 to 10, and the median value is 5 for all patients at a given age. Investigators can calculate the score using a previously published global matrix of values for ARMSS and MSSS available in the R package ms.sev.
The investigators found that the ARMSS score is slightly superior to the MSSS in detecting small increases in EDSS. One benefit of the ARMSS score, compared with the MSSS, is that it allows investigators to study patients for whom time of disease onset is unknown. The ARMSS score also removes potential systematic bias that might result from a neurologist’s retrospective assignment of date of disease onset, said Dr. Ramanujam.
He and his colleagues used ARMSS to compare patients’ disease course with what is expected for that patient (i.e., an ARMSS that remains stable at 5). They extracted data for 15,831 patients participating in the Swedish MS registry, including age and EDSS score at each neurological visit. Eligible patients had serial EDSS scores for 10 years. Dr. Ramanujam and colleagues included 4,514 patients in their analysis.
Measures at 2 years correlated with those at 10 years
The researchers created what they called the ARMSS integral by calculating the ARMSS score’s change from 5 at each examination (e.g., −0.5 or 1). “The ARMSS integral can be thought of as the cumulative disability that a patient accrues over his or her disease course, relative to the average patient, who had the disease for the same ages,” said Dr. Ramanujam. At 2 years of follow-up and at 10 years of follow-up, the distribution of ARMSS integrals for the study population followed a normal pattern.
Next, the investigators sought to compare patients by standardizing their follow-up time. To do this, they calculated what they called the ARMSS-rate by dividing each patient’s ARMSS integral by the number of years of follow-up. The ARMSS-rate offers a “snapshot of disease severity and progression,” said Dr. Ramanujam. When the researchers compared ARMSS-rates at 2 years and 10 years for each patient, they found that the measure was “extremely stable over time and strongly correlated with future disability.” The correlation improved slightly when the researchers compared ARMSS-rates at 4 years and 10 years.
The investigators then categorized patients based on their ARMSS-rate at 2 years (e.g., 0 to 1, 1 to 2, 2 to 3). When they compared the values in these categories with the median ARMSS-rates for the same individuals over the subsequent 8 years, they found strong group-level correlations.
To analyze correlations on an individual level, Dr. Ramanujam and colleagues examined the ability of different metrics at the time closest to 2 years of follow-up to predict those measured at 10 years. They assigned the value 1 to the most severe quartile of outcomes and the value 0 to all other quartiles. For predictors and outcomes, the investigators examined ARMSS-rate and the integral of progression index, which they calculated using the integral of EDSS. They also included EDSS at 10 years as an outcome for progression index.
For predicting the subsequent 8 years of ARMSS-rates, ARMSS-rate at 2 years had an area under the curve (AUC) of 0.921. When the investigators performed the same analysis using a cohort of patients with MS from British Columbia, Canada, they obtained an AUC of 0.887. Progression index at 2 years had an AUC of 0.61 for predicting the most severe quartile of the next 8 years. Compared with this result, ARMSS integral up to 2 years was slightly better at predicting EDSS at 10 years, said Dr. Ramanujam. The progression index poorly predicted the most severe quartile of EDSS at 10 years.
The main limitation of the ARMSS integral and ARMSS-rate is that they are based on EDSS, he added. The EDSS gives great weight to mobility and largely does not measure cognitive disability. “Future metrics could therefore include additional data such as MRI, Symbol Digit Modalities Test, or neurofilament light levels,” said Dr. Ramanujam. “Also, self-assessment could be one area to improve in the future.”
Dr. Ramanujam had no conflicts of interest to disclose. He receives funding from the MultipleMS Project, which is part of the EU Horizon 2020 Framework.
REPORTING FROM ECTRIMS 2019
Intensive cognitive training may be needed for memory gains in MS
STOCKHOLM – Cognitive rehabilitation to address memory deficits in multiple sclerosis (MS) can take a page from efforts to help those with other conditions, but practitioners and patients should realize that more intensive interventions are likely to be of greater benefit in MS.
in addressing the memory problems frequently seen in MS, Piet Bouman reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Hippocampal pathology can underlie the high-impact memory deficits that are seen frequently in patients with MS, noted Mr. Bouman, a doctoral student at Amsterdam University Medical Centers, and his collaborators. However, they observed, which strategies might best ameliorate hippocampal memory loss for those with MS is an open question.
To address this knowledge gap, Mr. Bouman and his coauthors conducted a systematic review and meta-analysis that aimed to determine which memory interventions in current use most help hippocampal memory functioning. The authors did not limit the review to MS, but included other conditions where hippocampal lesions, atrophy, or changes in connection or functioning may affect memory. These include healthy aging, mild cognitive impairment, and Alzheimer’s disease.
Included in the search for studies were those that used either cognitive or exercise interventions and also evaluated both visuospatial and verbal memory using validated measures, such as the Brief Visuospatial Memory Test or the California Verbal Learning Test.
After reviewing an initial 6,697 articles, the authors used Cochrane criteria to eliminate studies that were at high risk of bias. In the end, 141 studies were selected for the final review, and 82 of these were included in the meta-analysis. Eighteen studies involving 895 individuals addressed healthy aging; 39 studies enrolled 2,256 patients with mild cognitive impairment; 8 studies enrolled 223 patients with Alzheimer’s disease; and 26 studies involving 1,174 patients looked at cognitive impairment in the MS population.
To express the efficacy of the interventions across the various studies, Mr. Bouman and collaborators used the ratio of the difference in mean outcomes between groups and the standard deviation in outcome among participants. This ratio, commonly used to harmonize data in meta-analyses, is termed standardized mean difference.
Individuals representing the healthy aging population saw the most benefit from interventions to address memory loss, with a standardized mean difference of 0.48. Patients with mild cognitive impairment saw a standardized mean difference of 0.46, followed by patients with Alzheimer’s disease with a standardized mean difference of 0.43. Patients with MS lagged far behind in their response to interventions to improve memory, with a standardized mean difference of 0.34.
Looking at the different kinds of interventions, exercise interventions showed moderate effectiveness, with a standardized mean difference of 0.46. By contrast, high intensity cognitive training working on memory strategies was the most effective intervention, said Mr. Bouman and his coauthors: This intervention showed a standardized mean difference of 1.03.
Among the varying conditions associated with hippocampal memory loss, MS-related memory problems saw the least response to intervention, “which might be a result of a more widespread pattern of cognitive decline in MS,” noted Mr. Bouman and coauthors.
“Future studies should work from the realization that memory rehabilitation in MS might require a different approach” than that used in healthy aging, mild cognitive impairment, and Alzheimer’s disease, wrote the authors.
Their review revealed “persistent methodological flaws” in the literature, they noted. These included small sample sizes and selection bias.
Mr. Bouman reported that he had no disclosures. One coauthor reported financial relationships with Sanofi Genzyme, Merck-Serono and Biogen Idec. Another reported financial relationships with Merck-Serono, Bogen, Novartis, Genzyme, and Teva Pharmaceuticals.
SOURCE: Bouman P et al. ECTRIMS 2019. Abstract P1439.
STOCKHOLM – Cognitive rehabilitation to address memory deficits in multiple sclerosis (MS) can take a page from efforts to help those with other conditions, but practitioners and patients should realize that more intensive interventions are likely to be of greater benefit in MS.
in addressing the memory problems frequently seen in MS, Piet Bouman reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Hippocampal pathology can underlie the high-impact memory deficits that are seen frequently in patients with MS, noted Mr. Bouman, a doctoral student at Amsterdam University Medical Centers, and his collaborators. However, they observed, which strategies might best ameliorate hippocampal memory loss for those with MS is an open question.
To address this knowledge gap, Mr. Bouman and his coauthors conducted a systematic review and meta-analysis that aimed to determine which memory interventions in current use most help hippocampal memory functioning. The authors did not limit the review to MS, but included other conditions where hippocampal lesions, atrophy, or changes in connection or functioning may affect memory. These include healthy aging, mild cognitive impairment, and Alzheimer’s disease.
Included in the search for studies were those that used either cognitive or exercise interventions and also evaluated both visuospatial and verbal memory using validated measures, such as the Brief Visuospatial Memory Test or the California Verbal Learning Test.
After reviewing an initial 6,697 articles, the authors used Cochrane criteria to eliminate studies that were at high risk of bias. In the end, 141 studies were selected for the final review, and 82 of these were included in the meta-analysis. Eighteen studies involving 895 individuals addressed healthy aging; 39 studies enrolled 2,256 patients with mild cognitive impairment; 8 studies enrolled 223 patients with Alzheimer’s disease; and 26 studies involving 1,174 patients looked at cognitive impairment in the MS population.
To express the efficacy of the interventions across the various studies, Mr. Bouman and collaborators used the ratio of the difference in mean outcomes between groups and the standard deviation in outcome among participants. This ratio, commonly used to harmonize data in meta-analyses, is termed standardized mean difference.
Individuals representing the healthy aging population saw the most benefit from interventions to address memory loss, with a standardized mean difference of 0.48. Patients with mild cognitive impairment saw a standardized mean difference of 0.46, followed by patients with Alzheimer’s disease with a standardized mean difference of 0.43. Patients with MS lagged far behind in their response to interventions to improve memory, with a standardized mean difference of 0.34.
Looking at the different kinds of interventions, exercise interventions showed moderate effectiveness, with a standardized mean difference of 0.46. By contrast, high intensity cognitive training working on memory strategies was the most effective intervention, said Mr. Bouman and his coauthors: This intervention showed a standardized mean difference of 1.03.
Among the varying conditions associated with hippocampal memory loss, MS-related memory problems saw the least response to intervention, “which might be a result of a more widespread pattern of cognitive decline in MS,” noted Mr. Bouman and coauthors.
“Future studies should work from the realization that memory rehabilitation in MS might require a different approach” than that used in healthy aging, mild cognitive impairment, and Alzheimer’s disease, wrote the authors.
Their review revealed “persistent methodological flaws” in the literature, they noted. These included small sample sizes and selection bias.
Mr. Bouman reported that he had no disclosures. One coauthor reported financial relationships with Sanofi Genzyme, Merck-Serono and Biogen Idec. Another reported financial relationships with Merck-Serono, Bogen, Novartis, Genzyme, and Teva Pharmaceuticals.
SOURCE: Bouman P et al. ECTRIMS 2019. Abstract P1439.
STOCKHOLM – Cognitive rehabilitation to address memory deficits in multiple sclerosis (MS) can take a page from efforts to help those with other conditions, but practitioners and patients should realize that more intensive interventions are likely to be of greater benefit in MS.
in addressing the memory problems frequently seen in MS, Piet Bouman reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Hippocampal pathology can underlie the high-impact memory deficits that are seen frequently in patients with MS, noted Mr. Bouman, a doctoral student at Amsterdam University Medical Centers, and his collaborators. However, they observed, which strategies might best ameliorate hippocampal memory loss for those with MS is an open question.
To address this knowledge gap, Mr. Bouman and his coauthors conducted a systematic review and meta-analysis that aimed to determine which memory interventions in current use most help hippocampal memory functioning. The authors did not limit the review to MS, but included other conditions where hippocampal lesions, atrophy, or changes in connection or functioning may affect memory. These include healthy aging, mild cognitive impairment, and Alzheimer’s disease.
Included in the search for studies were those that used either cognitive or exercise interventions and also evaluated both visuospatial and verbal memory using validated measures, such as the Brief Visuospatial Memory Test or the California Verbal Learning Test.
After reviewing an initial 6,697 articles, the authors used Cochrane criteria to eliminate studies that were at high risk of bias. In the end, 141 studies were selected for the final review, and 82 of these were included in the meta-analysis. Eighteen studies involving 895 individuals addressed healthy aging; 39 studies enrolled 2,256 patients with mild cognitive impairment; 8 studies enrolled 223 patients with Alzheimer’s disease; and 26 studies involving 1,174 patients looked at cognitive impairment in the MS population.
To express the efficacy of the interventions across the various studies, Mr. Bouman and collaborators used the ratio of the difference in mean outcomes between groups and the standard deviation in outcome among participants. This ratio, commonly used to harmonize data in meta-analyses, is termed standardized mean difference.
Individuals representing the healthy aging population saw the most benefit from interventions to address memory loss, with a standardized mean difference of 0.48. Patients with mild cognitive impairment saw a standardized mean difference of 0.46, followed by patients with Alzheimer’s disease with a standardized mean difference of 0.43. Patients with MS lagged far behind in their response to interventions to improve memory, with a standardized mean difference of 0.34.
Looking at the different kinds of interventions, exercise interventions showed moderate effectiveness, with a standardized mean difference of 0.46. By contrast, high intensity cognitive training working on memory strategies was the most effective intervention, said Mr. Bouman and his coauthors: This intervention showed a standardized mean difference of 1.03.
Among the varying conditions associated with hippocampal memory loss, MS-related memory problems saw the least response to intervention, “which might be a result of a more widespread pattern of cognitive decline in MS,” noted Mr. Bouman and coauthors.
“Future studies should work from the realization that memory rehabilitation in MS might require a different approach” than that used in healthy aging, mild cognitive impairment, and Alzheimer’s disease, wrote the authors.
Their review revealed “persistent methodological flaws” in the literature, they noted. These included small sample sizes and selection bias.
Mr. Bouman reported that he had no disclosures. One coauthor reported financial relationships with Sanofi Genzyme, Merck-Serono and Biogen Idec. Another reported financial relationships with Merck-Serono, Bogen, Novartis, Genzyme, and Teva Pharmaceuticals.
SOURCE: Bouman P et al. ECTRIMS 2019. Abstract P1439.
REPORTING FROM ECTRIMS 2019
Dysregulated sleep is common in children with eosinophilic esophagitis
, Rasintra Siriwat, MD, and colleagues have ascertained.
Children with eosinophilic esophagitis (EoE) also were found to have a high prevalence of atopic diseases, including allergic rhinitis and eczema – findings that could be driving the breathing problems, said Dr. Siriwat, a neurology fellow at the Cleveland Clinic, and coauthors.
The retrospective study comprised 81 children with a diagnosis of EoE who were referred to sleep clinics. In this group, 46 of the children had active EoE (having gastrointestinal symptoms, including feeding difficulties, dysphagia, reflux, nausea/vomiting, or epigastric pain at presentation). The other 35 had an EoE diagnosis but no symptoms on presentation and were categorized as having inactive EoE. Most were male (71.6%) and white (92.5%). The mean age in the cohort was 10 years and the mean body mass index for all subjects was 22 kg/m2. A control group of 192 children without an EoE diagnosis who had overnight polysomnography were included in the analysis.
Allergic-type comorbidities were common among those with active EoE, including allergic rhinitis (55.5%), food allergy (39.5%), and eczema (26%). In addition, a quarter had attention-deficit/hyperactivity disorder, 22% an autism spectrum disorder, 21% a neurological disease, and 29% a psychiatric disorder.
Several sleep complaints were common in the entire EoE cohort, including snoring (76.5 %), restless sleep (66.6%), legs jerking or leg discomfort (43.2%), and daytime sleepiness (58%).
All children underwent an overnight polysomnography. Compared with controls, the children with EoE had significantly higher non-REM2 sleep, significantly lower non-REM3 sleep, lower REM, increased periodic leg movement disorder, and increased arousal index.
“Of note, we found a much higher percentage of [periodic leg movement disorder] in active EoE compared to inactive EoE,” the authors said.
The most common sleep diagnosis for the children with EoE was sleep-disordered breathing. Of 62 children with EoE and sleep disordered breathing, 37% had obstructive sleep apnea (OSA). Two patients had central sleep apnea and five had nocturnal hypoventilation. Children with EoE also reported parasomnia symptoms such as sleep talking (35.8%), sleepwalking (16%), bruxism (23.4%), night terrors (28.4%), and nocturnal enuresis (21.2%).
Of the 59 children with leg movement, 20 had periodic limb movement disorder and 5 were diagnosed with restless leg syndrome. Two were diagnosed with narcolepsy and three with hypersomnia. Four children had a circadian rhythm disorder.
“Notably, the majority of children with EoE had symptoms of sleep-disordered breathing, and more than one-third of total subjects were diagnosed with OSA,” the authors noted. “However, most of them were mild-moderate OSA. It should be noted that the prevalence of OSA in the pediatric population is 1%-5% mostly between the ages of 2-8 years, while the mean age of our subjects was 10 years old. The high prevalence of mild-moderate OSA in the EoE population might be explained by the relationship between EoE and atopic disease.”
Dr. Siriwat had no financial disclosures. The study was supported by Cincinnati Children’s Hospital Research Fund.
SOURCE: Siriwat R et al. Sleep Med. 2019 Sep 11. doi: 10.1016/j.sleep.2019.08.018.
, Rasintra Siriwat, MD, and colleagues have ascertained.
Children with eosinophilic esophagitis (EoE) also were found to have a high prevalence of atopic diseases, including allergic rhinitis and eczema – findings that could be driving the breathing problems, said Dr. Siriwat, a neurology fellow at the Cleveland Clinic, and coauthors.
The retrospective study comprised 81 children with a diagnosis of EoE who were referred to sleep clinics. In this group, 46 of the children had active EoE (having gastrointestinal symptoms, including feeding difficulties, dysphagia, reflux, nausea/vomiting, or epigastric pain at presentation). The other 35 had an EoE diagnosis but no symptoms on presentation and were categorized as having inactive EoE. Most were male (71.6%) and white (92.5%). The mean age in the cohort was 10 years and the mean body mass index for all subjects was 22 kg/m2. A control group of 192 children without an EoE diagnosis who had overnight polysomnography were included in the analysis.
Allergic-type comorbidities were common among those with active EoE, including allergic rhinitis (55.5%), food allergy (39.5%), and eczema (26%). In addition, a quarter had attention-deficit/hyperactivity disorder, 22% an autism spectrum disorder, 21% a neurological disease, and 29% a psychiatric disorder.
Several sleep complaints were common in the entire EoE cohort, including snoring (76.5 %), restless sleep (66.6%), legs jerking or leg discomfort (43.2%), and daytime sleepiness (58%).
All children underwent an overnight polysomnography. Compared with controls, the children with EoE had significantly higher non-REM2 sleep, significantly lower non-REM3 sleep, lower REM, increased periodic leg movement disorder, and increased arousal index.
“Of note, we found a much higher percentage of [periodic leg movement disorder] in active EoE compared to inactive EoE,” the authors said.
The most common sleep diagnosis for the children with EoE was sleep-disordered breathing. Of 62 children with EoE and sleep disordered breathing, 37% had obstructive sleep apnea (OSA). Two patients had central sleep apnea and five had nocturnal hypoventilation. Children with EoE also reported parasomnia symptoms such as sleep talking (35.8%), sleepwalking (16%), bruxism (23.4%), night terrors (28.4%), and nocturnal enuresis (21.2%).
Of the 59 children with leg movement, 20 had periodic limb movement disorder and 5 were diagnosed with restless leg syndrome. Two were diagnosed with narcolepsy and three with hypersomnia. Four children had a circadian rhythm disorder.
“Notably, the majority of children with EoE had symptoms of sleep-disordered breathing, and more than one-third of total subjects were diagnosed with OSA,” the authors noted. “However, most of them were mild-moderate OSA. It should be noted that the prevalence of OSA in the pediatric population is 1%-5% mostly between the ages of 2-8 years, while the mean age of our subjects was 10 years old. The high prevalence of mild-moderate OSA in the EoE population might be explained by the relationship between EoE and atopic disease.”
Dr. Siriwat had no financial disclosures. The study was supported by Cincinnati Children’s Hospital Research Fund.
SOURCE: Siriwat R et al. Sleep Med. 2019 Sep 11. doi: 10.1016/j.sleep.2019.08.018.
, Rasintra Siriwat, MD, and colleagues have ascertained.
Children with eosinophilic esophagitis (EoE) also were found to have a high prevalence of atopic diseases, including allergic rhinitis and eczema – findings that could be driving the breathing problems, said Dr. Siriwat, a neurology fellow at the Cleveland Clinic, and coauthors.
The retrospective study comprised 81 children with a diagnosis of EoE who were referred to sleep clinics. In this group, 46 of the children had active EoE (having gastrointestinal symptoms, including feeding difficulties, dysphagia, reflux, nausea/vomiting, or epigastric pain at presentation). The other 35 had an EoE diagnosis but no symptoms on presentation and were categorized as having inactive EoE. Most were male (71.6%) and white (92.5%). The mean age in the cohort was 10 years and the mean body mass index for all subjects was 22 kg/m2. A control group of 192 children without an EoE diagnosis who had overnight polysomnography were included in the analysis.
Allergic-type comorbidities were common among those with active EoE, including allergic rhinitis (55.5%), food allergy (39.5%), and eczema (26%). In addition, a quarter had attention-deficit/hyperactivity disorder, 22% an autism spectrum disorder, 21% a neurological disease, and 29% a psychiatric disorder.
Several sleep complaints were common in the entire EoE cohort, including snoring (76.5 %), restless sleep (66.6%), legs jerking or leg discomfort (43.2%), and daytime sleepiness (58%).
All children underwent an overnight polysomnography. Compared with controls, the children with EoE had significantly higher non-REM2 sleep, significantly lower non-REM3 sleep, lower REM, increased periodic leg movement disorder, and increased arousal index.
“Of note, we found a much higher percentage of [periodic leg movement disorder] in active EoE compared to inactive EoE,” the authors said.
The most common sleep diagnosis for the children with EoE was sleep-disordered breathing. Of 62 children with EoE and sleep disordered breathing, 37% had obstructive sleep apnea (OSA). Two patients had central sleep apnea and five had nocturnal hypoventilation. Children with EoE also reported parasomnia symptoms such as sleep talking (35.8%), sleepwalking (16%), bruxism (23.4%), night terrors (28.4%), and nocturnal enuresis (21.2%).
Of the 59 children with leg movement, 20 had periodic limb movement disorder and 5 were diagnosed with restless leg syndrome. Two were diagnosed with narcolepsy and three with hypersomnia. Four children had a circadian rhythm disorder.
“Notably, the majority of children with EoE had symptoms of sleep-disordered breathing, and more than one-third of total subjects were diagnosed with OSA,” the authors noted. “However, most of them were mild-moderate OSA. It should be noted that the prevalence of OSA in the pediatric population is 1%-5% mostly between the ages of 2-8 years, while the mean age of our subjects was 10 years old. The high prevalence of mild-moderate OSA in the EoE population might be explained by the relationship between EoE and atopic disease.”
Dr. Siriwat had no financial disclosures. The study was supported by Cincinnati Children’s Hospital Research Fund.
SOURCE: Siriwat R et al. Sleep Med. 2019 Sep 11. doi: 10.1016/j.sleep.2019.08.018.
FROM SLEEP MEDICINE
C-Path and NORD team up to speed development of treatments for rare disorders
ROCKVILLE, MD – according to information provided at a launch event held Sept. 18, 2019.
By integrating data in a regulatory-grade format suitable for analytics, the RDCA-DAP hopes to accelerate the understanding of disease progression – including source of variability to optimize the characterization of subpopulations – develop clinical outcome measures and biomarkers, facilitate the development of mathematical models of disease, and promote innovative clinical trial designs.
The RDCA-DAP works as a database that will house patient-level data from a variety of sources, including clinical trials, longitudinal observational studies, patient registries, and other sources, such as real-world data collected from electronic health records across a wide range of rare diseases from all over the world. Data will then be made available to researchers to help speed the development of new treatments.
“The database and analytics we are creating will enable us to obtain new insight into these rare diseases,” C-Path President and CEO Joseph Scheeren, PharmD, said at the launch event. “Not only within specific diseases, but also we hope across related diseases.”
The key to the platform’s success will be data. “We need access to clinical data from the industry, patient groups, and academia,” Dr. Scheeren said. “Even more so, the RDCA-DAP will need to incorporate data from many sources. In addition to data from clinical trials conducted by industry and academia, we will want to access data from patients, hospitals, and any organization that can provide data.”
Dr. Scheeren said the data will take many forms, including numeric data, images, genomic information, and other forms of clinical information.
“The database will be able to handle these diverse datasets,” he said, adding that C-Path is preparing to be able to analyze the data sets “with the most sophisticated tools available.”
Dr. Scheeren made a call for all interested stakeholders with rare disease data to contribute to the platform.
NORD President and CEO Peter Saltonstall echoed that call. “We need data. We are accepting it immediately.”
Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, applauded the new platform. “I think foundations and patient advocacy groups and others that have been trying to help in this space have realized that simply funding basic research, although it is necessary and really important, it is not enough to get those therapies in the hands of doctors and patients,” she said. “You have to enable translation of research for that disease.”
Dr. Woodcock noted that the cures may not even come from that basic research, but rather from “left field” using research into cancer or another disease state, something that will be enabled by the disease-agnostic platform being created by C-Path and NORD. She said that the platform will not only put all the data in one spot, but will help to create a standardized set of disease definitions to help make the data useful across all research.
ROCKVILLE, MD – according to information provided at a launch event held Sept. 18, 2019.
By integrating data in a regulatory-grade format suitable for analytics, the RDCA-DAP hopes to accelerate the understanding of disease progression – including source of variability to optimize the characterization of subpopulations – develop clinical outcome measures and biomarkers, facilitate the development of mathematical models of disease, and promote innovative clinical trial designs.
The RDCA-DAP works as a database that will house patient-level data from a variety of sources, including clinical trials, longitudinal observational studies, patient registries, and other sources, such as real-world data collected from electronic health records across a wide range of rare diseases from all over the world. Data will then be made available to researchers to help speed the development of new treatments.
“The database and analytics we are creating will enable us to obtain new insight into these rare diseases,” C-Path President and CEO Joseph Scheeren, PharmD, said at the launch event. “Not only within specific diseases, but also we hope across related diseases.”
The key to the platform’s success will be data. “We need access to clinical data from the industry, patient groups, and academia,” Dr. Scheeren said. “Even more so, the RDCA-DAP will need to incorporate data from many sources. In addition to data from clinical trials conducted by industry and academia, we will want to access data from patients, hospitals, and any organization that can provide data.”
Dr. Scheeren said the data will take many forms, including numeric data, images, genomic information, and other forms of clinical information.
“The database will be able to handle these diverse datasets,” he said, adding that C-Path is preparing to be able to analyze the data sets “with the most sophisticated tools available.”
Dr. Scheeren made a call for all interested stakeholders with rare disease data to contribute to the platform.
NORD President and CEO Peter Saltonstall echoed that call. “We need data. We are accepting it immediately.”
Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, applauded the new platform. “I think foundations and patient advocacy groups and others that have been trying to help in this space have realized that simply funding basic research, although it is necessary and really important, it is not enough to get those therapies in the hands of doctors and patients,” she said. “You have to enable translation of research for that disease.”
Dr. Woodcock noted that the cures may not even come from that basic research, but rather from “left field” using research into cancer or another disease state, something that will be enabled by the disease-agnostic platform being created by C-Path and NORD. She said that the platform will not only put all the data in one spot, but will help to create a standardized set of disease definitions to help make the data useful across all research.
ROCKVILLE, MD – according to information provided at a launch event held Sept. 18, 2019.
By integrating data in a regulatory-grade format suitable for analytics, the RDCA-DAP hopes to accelerate the understanding of disease progression – including source of variability to optimize the characterization of subpopulations – develop clinical outcome measures and biomarkers, facilitate the development of mathematical models of disease, and promote innovative clinical trial designs.
The RDCA-DAP works as a database that will house patient-level data from a variety of sources, including clinical trials, longitudinal observational studies, patient registries, and other sources, such as real-world data collected from electronic health records across a wide range of rare diseases from all over the world. Data will then be made available to researchers to help speed the development of new treatments.
“The database and analytics we are creating will enable us to obtain new insight into these rare diseases,” C-Path President and CEO Joseph Scheeren, PharmD, said at the launch event. “Not only within specific diseases, but also we hope across related diseases.”
The key to the platform’s success will be data. “We need access to clinical data from the industry, patient groups, and academia,” Dr. Scheeren said. “Even more so, the RDCA-DAP will need to incorporate data from many sources. In addition to data from clinical trials conducted by industry and academia, we will want to access data from patients, hospitals, and any organization that can provide data.”
Dr. Scheeren said the data will take many forms, including numeric data, images, genomic information, and other forms of clinical information.
“The database will be able to handle these diverse datasets,” he said, adding that C-Path is preparing to be able to analyze the data sets “with the most sophisticated tools available.”
Dr. Scheeren made a call for all interested stakeholders with rare disease data to contribute to the platform.
NORD President and CEO Peter Saltonstall echoed that call. “We need data. We are accepting it immediately.”
Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, applauded the new platform. “I think foundations and patient advocacy groups and others that have been trying to help in this space have realized that simply funding basic research, although it is necessary and really important, it is not enough to get those therapies in the hands of doctors and patients,” she said. “You have to enable translation of research for that disease.”
Dr. Woodcock noted that the cures may not even come from that basic research, but rather from “left field” using research into cancer or another disease state, something that will be enabled by the disease-agnostic platform being created by C-Path and NORD. She said that the platform will not only put all the data in one spot, but will help to create a standardized set of disease definitions to help make the data useful across all research.
Viral cause of acute flaccid myelitis eludes detection
A study of 305 cases of acute flaccid myelitis has found further evidence of a viral etiology but is yet to identify a single pathogen as the primary cause.
Writing in Pediatrics, researchers published an analysis of patients presenting with acute flaccid limb weakness from January 2015 to December 2017 across 43 states.
A total of 25 cases were judged as probable for acute flaccid myelitis (AFM) because they met clinical criteria and had a white blood cell count above 5 cells per mm3 in cerebrospinal fluid, while 193 were judged as confirmed cases based on the additional presence of spinal cord gray matter lesions on MRI.
Overall, 83% of patients had experienced fever, cough, runny nose, vomiting, and/or diarrhea for a median of 5 days before limb weakness began. Two-thirds of patients had experienced a respiratory illness, 62% had experienced a fever, and 29% had experienced gastrointestinal illness.
Overall, 47% of the 193 patients who had specimens tested at a Centers for Disease Control and Prevention or non-CDC laboratory had a pathogen found at any site, 10% had a pathogen detected from a sterile site such as cerebrospinal fluid or sera, and 42% had a pathogen detected from a nonsterile site.
Among 72 patients who had serum specimens tested at the CDC, 2 were positive for enteroviruses. Among the 90 patients who had upper respiratory specimens tested, 36% were positive for either enteroviruses or rhinoviruses.
A number of stool specimens were also tested; 15% were positive for enteroviruses or rhinoviruses and one was positive for parechovirus.
Cerebrospinal fluid was tested in 170 patients, of which 4 were positive for enteroviruses. The testing also found adenovirus, Epstein-Barr virus, human herpesvirus 6, and mycoplasma in six patients. Sera testing of 123 patients found 9 were positive for enteroviruses, West Nile virus, mycoplasma, and coxsackievirus B.
“In our summary of national AFM surveillance from 2015 to 2017, we demonstrate that cases were widely distributed across the United States, the majority of cases occurred in late summer or fall, children were predominantly affected, there is a spectrum of clinical severity, and no single pathogen was identified as the primary cause of AFM,” wrote Tracy Ayers, PhD, from the National Center for Immunization and Respiratory Diseases, and coauthors. “We conclude that symptoms of a viral syndrome within the week before limb weakness, detection of viral pathogens from sterile and nonsterile sites from almost half of patients, and seasonality of AFM incidence, particularly during the 2016 peak year, strongly suggest a viral etiology, including [enteroviruses].”
The authors of an accompanying editorial noted that the clinical syndrome of acute flaccid paralysis caused by myelitis in the gray matter of the spinal cord has previously been associated with a range of viruses, including poliovirus, enteroviruses, and flaviviruses, so a single etiology to explain all cases would not be expected.
“The central question remains: What is driving seasonal biennial nationwide outbreaks of AFM since 2014?” wrote Kevin Messaca, MD, and colleagues from the University of Colorado at Denver, Aurora.
Two authors declared consultancies, grants, and research contracts with the pharmaceutical sector. No other conflicts of interest were declared. One editorial author declared funding from the National Institute of Allergy and Infectious Diseases.
SOURCE: Ayers T et al. Pediatrics. 2019 Oct 7. doi: 10.1542/peds.2019-1619.
*Updated 10/14/2019.
A study of 305 cases of acute flaccid myelitis has found further evidence of a viral etiology but is yet to identify a single pathogen as the primary cause.
Writing in Pediatrics, researchers published an analysis of patients presenting with acute flaccid limb weakness from January 2015 to December 2017 across 43 states.
A total of 25 cases were judged as probable for acute flaccid myelitis (AFM) because they met clinical criteria and had a white blood cell count above 5 cells per mm3 in cerebrospinal fluid, while 193 were judged as confirmed cases based on the additional presence of spinal cord gray matter lesions on MRI.
Overall, 83% of patients had experienced fever, cough, runny nose, vomiting, and/or diarrhea for a median of 5 days before limb weakness began. Two-thirds of patients had experienced a respiratory illness, 62% had experienced a fever, and 29% had experienced gastrointestinal illness.
Overall, 47% of the 193 patients who had specimens tested at a Centers for Disease Control and Prevention or non-CDC laboratory had a pathogen found at any site, 10% had a pathogen detected from a sterile site such as cerebrospinal fluid or sera, and 42% had a pathogen detected from a nonsterile site.
Among 72 patients who had serum specimens tested at the CDC, 2 were positive for enteroviruses. Among the 90 patients who had upper respiratory specimens tested, 36% were positive for either enteroviruses or rhinoviruses.
A number of stool specimens were also tested; 15% were positive for enteroviruses or rhinoviruses and one was positive for parechovirus.
Cerebrospinal fluid was tested in 170 patients, of which 4 were positive for enteroviruses. The testing also found adenovirus, Epstein-Barr virus, human herpesvirus 6, and mycoplasma in six patients. Sera testing of 123 patients found 9 were positive for enteroviruses, West Nile virus, mycoplasma, and coxsackievirus B.
“In our summary of national AFM surveillance from 2015 to 2017, we demonstrate that cases were widely distributed across the United States, the majority of cases occurred in late summer or fall, children were predominantly affected, there is a spectrum of clinical severity, and no single pathogen was identified as the primary cause of AFM,” wrote Tracy Ayers, PhD, from the National Center for Immunization and Respiratory Diseases, and coauthors. “We conclude that symptoms of a viral syndrome within the week before limb weakness, detection of viral pathogens from sterile and nonsterile sites from almost half of patients, and seasonality of AFM incidence, particularly during the 2016 peak year, strongly suggest a viral etiology, including [enteroviruses].”
The authors of an accompanying editorial noted that the clinical syndrome of acute flaccid paralysis caused by myelitis in the gray matter of the spinal cord has previously been associated with a range of viruses, including poliovirus, enteroviruses, and flaviviruses, so a single etiology to explain all cases would not be expected.
“The central question remains: What is driving seasonal biennial nationwide outbreaks of AFM since 2014?” wrote Kevin Messaca, MD, and colleagues from the University of Colorado at Denver, Aurora.
Two authors declared consultancies, grants, and research contracts with the pharmaceutical sector. No other conflicts of interest were declared. One editorial author declared funding from the National Institute of Allergy and Infectious Diseases.
SOURCE: Ayers T et al. Pediatrics. 2019 Oct 7. doi: 10.1542/peds.2019-1619.
*Updated 10/14/2019.
A study of 305 cases of acute flaccid myelitis has found further evidence of a viral etiology but is yet to identify a single pathogen as the primary cause.
Writing in Pediatrics, researchers published an analysis of patients presenting with acute flaccid limb weakness from January 2015 to December 2017 across 43 states.
A total of 25 cases were judged as probable for acute flaccid myelitis (AFM) because they met clinical criteria and had a white blood cell count above 5 cells per mm3 in cerebrospinal fluid, while 193 were judged as confirmed cases based on the additional presence of spinal cord gray matter lesions on MRI.
Overall, 83% of patients had experienced fever, cough, runny nose, vomiting, and/or diarrhea for a median of 5 days before limb weakness began. Two-thirds of patients had experienced a respiratory illness, 62% had experienced a fever, and 29% had experienced gastrointestinal illness.
Overall, 47% of the 193 patients who had specimens tested at a Centers for Disease Control and Prevention or non-CDC laboratory had a pathogen found at any site, 10% had a pathogen detected from a sterile site such as cerebrospinal fluid or sera, and 42% had a pathogen detected from a nonsterile site.
Among 72 patients who had serum specimens tested at the CDC, 2 were positive for enteroviruses. Among the 90 patients who had upper respiratory specimens tested, 36% were positive for either enteroviruses or rhinoviruses.
A number of stool specimens were also tested; 15% were positive for enteroviruses or rhinoviruses and one was positive for parechovirus.
Cerebrospinal fluid was tested in 170 patients, of which 4 were positive for enteroviruses. The testing also found adenovirus, Epstein-Barr virus, human herpesvirus 6, and mycoplasma in six patients. Sera testing of 123 patients found 9 were positive for enteroviruses, West Nile virus, mycoplasma, and coxsackievirus B.
“In our summary of national AFM surveillance from 2015 to 2017, we demonstrate that cases were widely distributed across the United States, the majority of cases occurred in late summer or fall, children were predominantly affected, there is a spectrum of clinical severity, and no single pathogen was identified as the primary cause of AFM,” wrote Tracy Ayers, PhD, from the National Center for Immunization and Respiratory Diseases, and coauthors. “We conclude that symptoms of a viral syndrome within the week before limb weakness, detection of viral pathogens from sterile and nonsterile sites from almost half of patients, and seasonality of AFM incidence, particularly during the 2016 peak year, strongly suggest a viral etiology, including [enteroviruses].”
The authors of an accompanying editorial noted that the clinical syndrome of acute flaccid paralysis caused by myelitis in the gray matter of the spinal cord has previously been associated with a range of viruses, including poliovirus, enteroviruses, and flaviviruses, so a single etiology to explain all cases would not be expected.
“The central question remains: What is driving seasonal biennial nationwide outbreaks of AFM since 2014?” wrote Kevin Messaca, MD, and colleagues from the University of Colorado at Denver, Aurora.
Two authors declared consultancies, grants, and research contracts with the pharmaceutical sector. No other conflicts of interest were declared. One editorial author declared funding from the National Institute of Allergy and Infectious Diseases.
SOURCE: Ayers T et al. Pediatrics. 2019 Oct 7. doi: 10.1542/peds.2019-1619.
*Updated 10/14/2019.
FROM PEDIATRICS
Key clinical point: Acute flaccid myelitis shows a strong suggestion of viral etiology but a single causal virus is not identified.
Major finding: Patients with acute flaccid myelitis show infection with a range of viruses including enteroviruses.
Study details: A study of 305 cases of acute flaccid myelitis in the United States.
Disclosures: Two authors declared consultancies, grants, and research contracts with the pharmaceutical sector. No other conflicts of interest were declared.
Source: Ayers T et al. Pediatrics. 2019 Oct 7. doi: 10.1542/peds.2019-1619.