User login
Can Metabolomic Profiling Predict Parkinson’s Disease Progression?
Metabolomic profiling of plasma strongly predicts Parkinson’s disease progression, according to a study published February 28 in Neurology. Metabolomic biomarkers may help researchers better understand Parkinson’s disease pathogenesis. 
“Our findings offer novel biomarkers for studying Parkinson’s disease progression and, with them, several new directions for investigation of its pathogenesis,” said Peter A. LeWitt, MD, Professor of Neurology at Henry Ford Hospital and Wayne State University School of Medicine in Detroit. Diagnosing and measuring progression of Parkinson’s disease continues to present many challenges. How to identify biomarkers with high specificity and sensitivity also remains unclear. The latest methodologies of metabolomic analysis can measure a large fraction of low-molecular-weight compounds in biospecimens for characterizing the biochemical environment of the body.
Dr. LeWitt and colleagues sought to determine whether a Parkinson’s disease–specific biochemical signature might be found in plasma and CSF. They used ultra-high performance liquid chromatography linked to gas chromatography and tandem mass spectrometry to measure concentrations of small-molecule constituents of plasma and CSF of 49 unmedicated patients with mild parkinsonism. Participants were between ages 38 and 78, and the mean age was 62.9. Investigators collected specimens twice: at baseline and up to 24 months later. During the study, patients’ mean Unified Parkinson’s Disease Rating Scale (UPDRS) parts II and III scores increased by 47%.
The investigators performed unbiased univariate and multivariate analyses of the measured compounds to determine associations with Parkinson’s disease progression. The analyses included fitting data in multiple linear regressions with variable selection using the Least Absolute
—Erica Tricarico
Suggested Reading
LeWitt PA, Li J, Lu M, et al. Metabolomic biomarkers as strong correlates of Parkinson disease progression. Neurology. 2017;88(9):862-869.
Metabolomic profiling of plasma strongly predicts Parkinson’s disease progression, according to a study published February 28 in Neurology. Metabolomic biomarkers may help researchers better understand Parkinson’s disease pathogenesis.
“Our findings offer novel biomarkers for studying Parkinson’s disease progression and, with them, several new directions for investigation of its pathogenesis,” said Peter A. LeWitt, MD, Professor of Neurology at Henry Ford Hospital and Wayne State University School of Medicine in Detroit. Diagnosing and measuring progression of Parkinson’s disease continues to present many challenges. How to identify biomarkers with high specificity and sensitivity also remains unclear. The latest methodologies of metabolomic analysis can measure a large fraction of low-molecular-weight compounds in biospecimens for characterizing the biochemical environment of the body.
Dr. LeWitt and colleagues sought to determine whether a Parkinson’s disease–specific biochemical signature might be found in plasma and CSF. They used ultra-high performance liquid chromatography linked to gas chromatography and tandem mass spectrometry to measure concentrations of small-molecule constituents of plasma and CSF of 49 unmedicated patients with mild parkinsonism. Participants were between ages 38 and 78, and the mean age was 62.9. Investigators collected specimens twice: at baseline and up to 24 months later. During the study, patients’ mean Unified Parkinson’s Disease Rating Scale (UPDRS) parts II and III scores increased by 47%.
The investigators performed unbiased univariate and multivariate analyses of the measured compounds to determine associations with Parkinson’s disease progression. The analyses included fitting data in multiple linear regressions with variable selection using the Least Absolute
—Erica Tricarico
Suggested Reading
LeWitt PA, Li J, Lu M, et al. Metabolomic biomarkers as strong correlates of Parkinson disease progression. Neurology. 2017;88(9):862-869.
Metabolomic profiling of plasma strongly predicts Parkinson’s disease progression, according to a study published February 28 in Neurology. Metabolomic biomarkers may help researchers better understand Parkinson’s disease pathogenesis.
“Our findings offer novel biomarkers for studying Parkinson’s disease progression and, with them, several new directions for investigation of its pathogenesis,” said Peter A. LeWitt, MD, Professor of Neurology at Henry Ford Hospital and Wayne State University School of Medicine in Detroit. Diagnosing and measuring progression of Parkinson’s disease continues to present many challenges. How to identify biomarkers with high specificity and sensitivity also remains unclear. The latest methodologies of metabolomic analysis can measure a large fraction of low-molecular-weight compounds in biospecimens for characterizing the biochemical environment of the body.
Dr. LeWitt and colleagues sought to determine whether a Parkinson’s disease–specific biochemical signature might be found in plasma and CSF. They used ultra-high performance liquid chromatography linked to gas chromatography and tandem mass spectrometry to measure concentrations of small-molecule constituents of plasma and CSF of 49 unmedicated patients with mild parkinsonism. Participants were between ages 38 and 78, and the mean age was 62.9. Investigators collected specimens twice: at baseline and up to 24 months later. During the study, patients’ mean Unified Parkinson’s Disease Rating Scale (UPDRS) parts II and III scores increased by 47%.
The investigators performed unbiased univariate and multivariate analyses of the measured compounds to determine associations with Parkinson’s disease progression. The analyses included fitting data in multiple linear regressions with variable selection using the Least Absolute
—Erica Tricarico
Suggested Reading
LeWitt PA, Li J, Lu M, et al. Metabolomic biomarkers as strong correlates of Parkinson disease progression. Neurology. 2017;88(9):862-869.
Hepatitis B and C May Increase Risk of Parkinson’s Disease
Hepatitis B and C appear to increase the risk of later Parkinson’s disease, according to a report published online ahead of print March 29 in Neurology. 
The etiology of Parkinson’s disease is complex, and several factors, including environmental toxins and head trauma, may increase the likelihood of the disorder. Two recent epidemiologic studies in Taiwan found an association between hepatitis C and Parkinson’s
To further explore that association, the investigators performed a retrospective cohort study using data from National Health Service hospitals across England for 1999 to 2011. They assessed the risk of Parkinson’s disease among 21,633 people with hepatitis B, 48,428 with hepatitis C, 6,225 with autoimmune hepatitis, 4,234 with chronic active hepatitis, 19,870 with HIV, and 6,132,124 control subjects with other disorders.
The risk of developing Parkinson’s disease was elevated following hospitalization for hepatitis B (relative risk [RR], 1.76) and hepatitis C (RR, 1.51). “These findings may be explained by a specific aspect of viral hepatitis (rather than a general hepatic inflammatory process or general use of antivirals), but whether this reflects shared disease mechanisms, shared genetic or environmental susceptibility, sequelae of viral hepatitis per se, or a consequence of treatment remains to be determined,” Dr. Pakpoor and her associates said.
The reason for this association is not yet known. “Neurotropic features of hepatitis C have been described previously and include the potential for cognitive impairment, independent of hepatic encephalopathy. Further, all essential hepatitis C virus receptors have been shown to be expressed on the brain microvascular endothelium … suggesting one mechanism by which the virus may affect the CNS,” they noted.
In addition, parkinsonism has been described as an adverse effect of treatment with interferon and ribavirin, which are commonly used in hepatitis C infection. Parkinsonism also is known to develop in association with liver cirrhosis. Cirrhosis status was not available for the members of this study cohort.
More studies are needed to confirm this association and verify that it is causal. Such research will also provide insight into pathophysiologic pathways of Parkinson’s disease, “which may be important to understanding the development of Parkinson’s disease more broadly,” Dr. Pakpoor and her associates said.
—Mary Ann Moon
Suggested Reading
Pakpoor J, Noyce A, Goldacre R, et al. Viral hepatitis and Parkinson disease: A national record-linkage study. Neurology. 2017 Mar 29 [Epub ahead of print].
Hepatitis B and C appear to increase the risk of later Parkinson’s disease, according to a report published online ahead of print March 29 in Neurology.
The etiology of Parkinson’s disease is complex, and several factors, including environmental toxins and head trauma, may increase the likelihood of the disorder. Two recent epidemiologic studies in Taiwan found an association between hepatitis C and Parkinson’s
To further explore that association, the investigators performed a retrospective cohort study using data from National Health Service hospitals across England for 1999 to 2011. They assessed the risk of Parkinson’s disease among 21,633 people with hepatitis B, 48,428 with hepatitis C, 6,225 with autoimmune hepatitis, 4,234 with chronic active hepatitis, 19,870 with HIV, and 6,132,124 control subjects with other disorders.
The risk of developing Parkinson’s disease was elevated following hospitalization for hepatitis B (relative risk [RR], 1.76) and hepatitis C (RR, 1.51). “These findings may be explained by a specific aspect of viral hepatitis (rather than a general hepatic inflammatory process or general use of antivirals), but whether this reflects shared disease mechanisms, shared genetic or environmental susceptibility, sequelae of viral hepatitis per se, or a consequence of treatment remains to be determined,” Dr. Pakpoor and her associates said.
The reason for this association is not yet known. “Neurotropic features of hepatitis C have been described previously and include the potential for cognitive impairment, independent of hepatic encephalopathy. Further, all essential hepatitis C virus receptors have been shown to be expressed on the brain microvascular endothelium … suggesting one mechanism by which the virus may affect the CNS,” they noted.
In addition, parkinsonism has been described as an adverse effect of treatment with interferon and ribavirin, which are commonly used in hepatitis C infection. Parkinsonism also is known to develop in association with liver cirrhosis. Cirrhosis status was not available for the members of this study cohort.
More studies are needed to confirm this association and verify that it is causal. Such research will also provide insight into pathophysiologic pathways of Parkinson’s disease, “which may be important to understanding the development of Parkinson’s disease more broadly,” Dr. Pakpoor and her associates said.
—Mary Ann Moon
Suggested Reading
Pakpoor J, Noyce A, Goldacre R, et al. Viral hepatitis and Parkinson disease: A national record-linkage study. Neurology. 2017 Mar 29 [Epub ahead of print].
Hepatitis B and C appear to increase the risk of later Parkinson’s disease, according to a report published online ahead of print March 29 in Neurology.
The etiology of Parkinson’s disease is complex, and several factors, including environmental toxins and head trauma, may increase the likelihood of the disorder. Two recent epidemiologic studies in Taiwan found an association between hepatitis C and Parkinson’s
To further explore that association, the investigators performed a retrospective cohort study using data from National Health Service hospitals across England for 1999 to 2011. They assessed the risk of Parkinson’s disease among 21,633 people with hepatitis B, 48,428 with hepatitis C, 6,225 with autoimmune hepatitis, 4,234 with chronic active hepatitis, 19,870 with HIV, and 6,132,124 control subjects with other disorders.
The risk of developing Parkinson’s disease was elevated following hospitalization for hepatitis B (relative risk [RR], 1.76) and hepatitis C (RR, 1.51). “These findings may be explained by a specific aspect of viral hepatitis (rather than a general hepatic inflammatory process or general use of antivirals), but whether this reflects shared disease mechanisms, shared genetic or environmental susceptibility, sequelae of viral hepatitis per se, or a consequence of treatment remains to be determined,” Dr. Pakpoor and her associates said.
The reason for this association is not yet known. “Neurotropic features of hepatitis C have been described previously and include the potential for cognitive impairment, independent of hepatic encephalopathy. Further, all essential hepatitis C virus receptors have been shown to be expressed on the brain microvascular endothelium … suggesting one mechanism by which the virus may affect the CNS,” they noted.
In addition, parkinsonism has been described as an adverse effect of treatment with interferon and ribavirin, which are commonly used in hepatitis C infection. Parkinsonism also is known to develop in association with liver cirrhosis. Cirrhosis status was not available for the members of this study cohort.
More studies are needed to confirm this association and verify that it is causal. Such research will also provide insight into pathophysiologic pathways of Parkinson’s disease, “which may be important to understanding the development of Parkinson’s disease more broadly,” Dr. Pakpoor and her associates said.
—Mary Ann Moon
Suggested Reading
Pakpoor J, Noyce A, Goldacre R, et al. Viral hepatitis and Parkinson disease: A national record-linkage study. Neurology. 2017 Mar 29 [Epub ahead of print].
Early-Onset Parkinson’s Disease Psychosis May Be Linked to Amyloid Pathology
Patients with newly diagnosed Parkinson’s disease and reduced CSF amyloid β1–42 may be more likely to develop Parkinson’s disease psychosis within three to four years, according to a study published in the April issue of the Journal of Neurology, Neurosurgery and Psychiatry. The type of psychotic symptom (eg, illusions or formed hallucinations) may indicate a specific profile of visual, cognitive, cortical, and hippocampal involvement in Parkinson’s disease, said the authors. 
“Our finding may suggest [that] early-onset Parkinson’s disease psychosis is a biomarker for the subsequent development of Alzheimer pathology,” said Dominic H. Ffytche, MD, PhD, of the Department of Old Age Psychiatry and Dementia at King’s College London.
Previous studies have indicated that visual hallucinations and illusions may be caused by specific cognitive and higher visual function deficits. Patients who develop these symptoms early in the disease course have greater rates of cognitive decline and progression to dementia, said the authors. No studies have investigated whether cognitive and higher visual function deficits are found before the onset of Parkinson’s disease, however.
Dr. Ffytche and colleagues examined the profile of cognitive, biomarker, and other risk factors before the onset of illusions and hallucinations in the Parkinson’s Progression Markers Initiative (PPMI) data set.
The PPMI is an observational multicenter study of newly diagnosed, untreated patients and healthy controls. It includes standardized, clinical, imaging, CSF, and cognitive assessments at three-month intervals during the first year and at six-month intervals in subsequent years. Assessment tools include the Montreal Cognitive Assessment, the Benton Judgement of Line Orientation, and the Unified Parkinson’s Disease Rating Scale.
Dr. Ffytche’s group included 195 healthy controls and 423 patients with Parkinson’s disease in its analysis. They compared baseline assessments in patients who developed illusions or hallucinations within three to four years of follow-up and in patients who did not develop these symptoms.
Of all patients with Parkinson’s disease, 115 people reported psychotic symptoms (predominantly illusions) at a median time of 19.5 months. At baseline, these patients had reduced CSF amyloid β1–42, lower olfaction scores, higher depression scores, and increased REM sleep behavior disorder symptoms, compared with patients without early-onset Parkinson’s disease psychosis. No differences in cognitive, higher visual, or structural imaging measures were observed, however. Dr. Ffytche and colleagues also found a subset of 21 participants with early-onset formed hallucinations who had reduced higher visual function at baseline; cortical thinning in the parietal, occipital, and frontal cortex; and reduced hippocampal volume.
One limitation of the study was its lack of phenomenologic detail about the symptoms of Parkinson’s disease psychosis. In addition, information was collected about symptoms during the week before each given assessment, thus some symptoms that occurred between assessments were missed.
—Erica Tricarico
Suggested Reading
Ffytche DH, Pereira JB, Ballard C, et al. Risk factors for early psychosis in PD: insights from the Parkinson’s Progression Markers Initiative. J Neurol Neurosurg Psychiatry. 2017;88(4):325-331.
Patients with newly diagnosed Parkinson’s disease and reduced CSF amyloid β1–42 may be more likely to develop Parkinson’s disease psychosis within three to four years, according to a study published in the April issue of the Journal of Neurology, Neurosurgery and Psychiatry. The type of psychotic symptom (eg, illusions or formed hallucinations) may indicate a specific profile of visual, cognitive, cortical, and hippocampal involvement in Parkinson’s disease, said the authors.
“Our finding may suggest [that] early-onset Parkinson’s disease psychosis is a biomarker for the subsequent development of Alzheimer pathology,” said Dominic H. Ffytche, MD, PhD, of the Department of Old Age Psychiatry and Dementia at King’s College London.
Previous studies have indicated that visual hallucinations and illusions may be caused by specific cognitive and higher visual function deficits. Patients who develop these symptoms early in the disease course have greater rates of cognitive decline and progression to dementia, said the authors. No studies have investigated whether cognitive and higher visual function deficits are found before the onset of Parkinson’s disease, however.
Dr. Ffytche and colleagues examined the profile of cognitive, biomarker, and other risk factors before the onset of illusions and hallucinations in the Parkinson’s Progression Markers Initiative (PPMI) data set.
The PPMI is an observational multicenter study of newly diagnosed, untreated patients and healthy controls. It includes standardized, clinical, imaging, CSF, and cognitive assessments at three-month intervals during the first year and at six-month intervals in subsequent years. Assessment tools include the Montreal Cognitive Assessment, the Benton Judgement of Line Orientation, and the Unified Parkinson’s Disease Rating Scale.
Dr. Ffytche’s group included 195 healthy controls and 423 patients with Parkinson’s disease in its analysis. They compared baseline assessments in patients who developed illusions or hallucinations within three to four years of follow-up and in patients who did not develop these symptoms.
Of all patients with Parkinson’s disease, 115 people reported psychotic symptoms (predominantly illusions) at a median time of 19.5 months. At baseline, these patients had reduced CSF amyloid β1–42, lower olfaction scores, higher depression scores, and increased REM sleep behavior disorder symptoms, compared with patients without early-onset Parkinson’s disease psychosis. No differences in cognitive, higher visual, or structural imaging measures were observed, however. Dr. Ffytche and colleagues also found a subset of 21 participants with early-onset formed hallucinations who had reduced higher visual function at baseline; cortical thinning in the parietal, occipital, and frontal cortex; and reduced hippocampal volume.
One limitation of the study was its lack of phenomenologic detail about the symptoms of Parkinson’s disease psychosis. In addition, information was collected about symptoms during the week before each given assessment, thus some symptoms that occurred between assessments were missed.
—Erica Tricarico
Suggested Reading
Ffytche DH, Pereira JB, Ballard C, et al. Risk factors for early psychosis in PD: insights from the Parkinson’s Progression Markers Initiative. J Neurol Neurosurg Psychiatry. 2017;88(4):325-331.
Patients with newly diagnosed Parkinson’s disease and reduced CSF amyloid β1–42 may be more likely to develop Parkinson’s disease psychosis within three to four years, according to a study published in the April issue of the Journal of Neurology, Neurosurgery and Psychiatry. The type of psychotic symptom (eg, illusions or formed hallucinations) may indicate a specific profile of visual, cognitive, cortical, and hippocampal involvement in Parkinson’s disease, said the authors.
“Our finding may suggest [that] early-onset Parkinson’s disease psychosis is a biomarker for the subsequent development of Alzheimer pathology,” said Dominic H. Ffytche, MD, PhD, of the Department of Old Age Psychiatry and Dementia at King’s College London.
Previous studies have indicated that visual hallucinations and illusions may be caused by specific cognitive and higher visual function deficits. Patients who develop these symptoms early in the disease course have greater rates of cognitive decline and progression to dementia, said the authors. No studies have investigated whether cognitive and higher visual function deficits are found before the onset of Parkinson’s disease, however.
Dr. Ffytche and colleagues examined the profile of cognitive, biomarker, and other risk factors before the onset of illusions and hallucinations in the Parkinson’s Progression Markers Initiative (PPMI) data set.
The PPMI is an observational multicenter study of newly diagnosed, untreated patients and healthy controls. It includes standardized, clinical, imaging, CSF, and cognitive assessments at three-month intervals during the first year and at six-month intervals in subsequent years. Assessment tools include the Montreal Cognitive Assessment, the Benton Judgement of Line Orientation, and the Unified Parkinson’s Disease Rating Scale.
Dr. Ffytche’s group included 195 healthy controls and 423 patients with Parkinson’s disease in its analysis. They compared baseline assessments in patients who developed illusions or hallucinations within three to four years of follow-up and in patients who did not develop these symptoms.
Of all patients with Parkinson’s disease, 115 people reported psychotic symptoms (predominantly illusions) at a median time of 19.5 months. At baseline, these patients had reduced CSF amyloid β1–42, lower olfaction scores, higher depression scores, and increased REM sleep behavior disorder symptoms, compared with patients without early-onset Parkinson’s disease psychosis. No differences in cognitive, higher visual, or structural imaging measures were observed, however. Dr. Ffytche and colleagues also found a subset of 21 participants with early-onset formed hallucinations who had reduced higher visual function at baseline; cortical thinning in the parietal, occipital, and frontal cortex; and reduced hippocampal volume.
One limitation of the study was its lack of phenomenologic detail about the symptoms of Parkinson’s disease psychosis. In addition, information was collected about symptoms during the week before each given assessment, thus some symptoms that occurred between assessments were missed.
—Erica Tricarico
Suggested Reading
Ffytche DH, Pereira JB, Ballard C, et al. Risk factors for early psychosis in PD: insights from the Parkinson’s Progression Markers Initiative. J Neurol Neurosurg Psychiatry. 2017;88(4):325-331.
No Link Found Between Spike Frequency and Surgical Outcomes
An increase in spike frequency does not help clinicians predict the outcome of surgery in patients with temporal lobe epilepsy. To reach that conclusion, researchers used scalp video monitoring data from patients who had anterior temporal lobe epilepsy to look for interictal epileptiform abnormalities, comparing patients with more than 60 spikes/hour to those with fewer spikes. They found no significant differences in seizure outcomes among patients who had undergone anterior temporal lobectomy.
Ngo L, Sperling MR, Skidmore C, Mintzer S, Nei M. Absolute spike frequency as a predictor of surgical outcome in temporal lobe epilepsy. Seizure. 2017;47:83-86.
An increase in spike frequency does not help clinicians predict the outcome of surgery in patients with temporal lobe epilepsy. To reach that conclusion, researchers used scalp video monitoring data from patients who had anterior temporal lobe epilepsy to look for interictal epileptiform abnormalities, comparing patients with more than 60 spikes/hour to those with fewer spikes. They found no significant differences in seizure outcomes among patients who had undergone anterior temporal lobectomy.
Ngo L, Sperling MR, Skidmore C, Mintzer S, Nei M. Absolute spike frequency as a predictor of surgical outcome in temporal lobe epilepsy. Seizure. 2017;47:83-86.
An increase in spike frequency does not help clinicians predict the outcome of surgery in patients with temporal lobe epilepsy. To reach that conclusion, researchers used scalp video monitoring data from patients who had anterior temporal lobe epilepsy to look for interictal epileptiform abnormalities, comparing patients with more than 60 spikes/hour to those with fewer spikes. They found no significant differences in seizure outcomes among patients who had undergone anterior temporal lobectomy.
Ngo L, Sperling MR, Skidmore C, Mintzer S, Nei M. Absolute spike frequency as a predictor of surgical outcome in temporal lobe epilepsy. Seizure. 2017;47:83-86.
Patients With Refractory Focal Epilepsy Have Older Brains
Patients with refractory focal epilepsy seem to have older brains, suggests a study that used whole brain T1-weighted MRI scans to estimate the predicted brain age versus chronological age. On average, the difference between predicted brain age and chronological age in patients with refractory focal epilepsy was 4.5 years greater than the researchers observed in healthy adults. The researchers also found that an earlier onset of refractory focal epilepsy was linked to increased brain age.
Pardoe H, Cole JH, Blackmon K ,et al. Structural brain changes in medically refractory focal epilepsy resemble premature brain aging. Epilepsy Res. 2017;133:28-32.
Patients with refractory focal epilepsy seem to have older brains, suggests a study that used whole brain T1-weighted MRI scans to estimate the predicted brain age versus chronological age. On average, the difference between predicted brain age and chronological age in patients with refractory focal epilepsy was 4.5 years greater than the researchers observed in healthy adults. The researchers also found that an earlier onset of refractory focal epilepsy was linked to increased brain age.
Pardoe H, Cole JH, Blackmon K ,et al. Structural brain changes in medically refractory focal epilepsy resemble premature brain aging. Epilepsy Res. 2017;133:28-32.
Patients with refractory focal epilepsy seem to have older brains, suggests a study that used whole brain T1-weighted MRI scans to estimate the predicted brain age versus chronological age. On average, the difference between predicted brain age and chronological age in patients with refractory focal epilepsy was 4.5 years greater than the researchers observed in healthy adults. The researchers also found that an earlier onset of refractory focal epilepsy was linked to increased brain age.
Pardoe H, Cole JH, Blackmon K ,et al. Structural brain changes in medically refractory focal epilepsy resemble premature brain aging. Epilepsy Res. 2017;133:28-32.
The Risk of Seizures Following Stroke
About 5% of patients who have had an ischemic stroke develop seizures, according to an analysis of data from the Framingham Heart Study. When researchers looked at the incidence of strokes between 1982 and 2003 and followed patients for 20 years, they found strokes had occurred in 469 patients, 25 of whom had experienced a seizure (5.3%). A third of these seizures happened within the first 24 hours of the stroke onset; half occurred within 30 days.
Stefanidou M, Das RR, Beiser AS, et al. Incidence of seizures following initial ischemic stroke in a community-based cohort: The Framingham Heart Study. Seizure. 2017;47:105-110.
About 5% of patients who have had an ischemic stroke develop seizures, according to an analysis of data from the Framingham Heart Study. When researchers looked at the incidence of strokes between 1982 and 2003 and followed patients for 20 years, they found strokes had occurred in 469 patients, 25 of whom had experienced a seizure (5.3%). A third of these seizures happened within the first 24 hours of the stroke onset; half occurred within 30 days.
Stefanidou M, Das RR, Beiser AS, et al. Incidence of seizures following initial ischemic stroke in a community-based cohort: The Framingham Heart Study. Seizure. 2017;47:105-110.
About 5% of patients who have had an ischemic stroke develop seizures, according to an analysis of data from the Framingham Heart Study. When researchers looked at the incidence of strokes between 1982 and 2003 and followed patients for 20 years, they found strokes had occurred in 469 patients, 25 of whom had experienced a seizure (5.3%). A third of these seizures happened within the first 24 hours of the stroke onset; half occurred within 30 days.
Stefanidou M, Das RR, Beiser AS, et al. Incidence of seizures following initial ischemic stroke in a community-based cohort: The Framingham Heart Study. Seizure. 2017;47:105-110.
Smoking During Pregnancy May Damage Offspring’s Retinal Nerve Fiber Layer
Retinal nerve fiber layer defects are a defining feature of optic neuropathies and have been implicated in several neurodegenerative disorders, including multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease. Both maternal smoking during pregnancy and low birth weight have been implicated in impaired development of the retina.
The Copenhagen Child Cohort 2000 Eye Study
Mr. Ashina and colleagues sought to investigate the associations of maternal smoking during pregnancy and low birth weight with retinal nerve fiber layer thickness in preadolescent children. They examined data from a prospective, population-based, birth cohort study that included all children (n = 6,090) born in 2000 in Copenhagen. Maternal smoking data were collected through parental interviews. Birth weight, pregnancy, and medical history data were obtained from the Danish Medical Birth Registry. As a follow-up, the researchers performed eye examinations on 1,406 of these children from May 1, 2011, to October 31, 2012, when the children were age 11 or 12.
Of the 1,406 children in the study, 1,323 were included in the analysis. Mean age was 11.7. Nearly half of the children (47.8%) were boys. The mean retinal nerve fiber layer thickness was 104 mm. In 227 children whose mothers had smoked during pregnancy, the peripapillary retinal nerve fiber layer was 5.7 mm thinner than in children whose mothers had not smoked during pregnancy, after adjusting for age, sex, birth weight, height, body weight, Tanner stage of pubertal development, axial length, and spherical equivalent refractive error. In children with low birth weight (ie, < 2,500 g), the retinal nerve fiber layer was 3.5 mm thinner than in children with normal birth weight, after adjustment for all variables.
“The results of this study add evidence to existing recommendations to avoid smoking during pregnancy and support measures that promote maternal and fetal health,” the researchers said.
A Public Health Message
In an invited commentary that accompanied the study, Christopher Kai-Shun Leung, MD, from the Department of Ophthalmology and Visual Sciences at Hong Kong Eye Hospital and Chinese University of Hong Kong in Kowloon, said that “although a difference of 5 to 6 mm in average circumpapillary retinal nerve fiber layer thickness is unlikely to translate into a detectable difference in visual function in children aged 12 to 13 years, the risk of subsequent development of visual impairment should not be overlooked.” Furthermore, he noted, “whether a thinner retinal nerve fiber layer in the children of mothers who smoked during pregnancy w
—Glenn S. Williams
Suggested Reading
Ashina H, Li XQ, Olsen EM, et al. Association of maternal smoking during pregnancy and birth weight with retinal nerve fiber layer thickness in children aged 11 or 12 years: The Copenhagen Child Cohort 2000 Eye Study. JAMA Ophthalmol. 2017 March 2 [Epub ahead of print].
Leung CK. Evaluation of retinal nerve fiber layer thinning with Fourier-domain optical coherence tomography. JAMA Ophthalmol. 2017 March 2 [Epub ahead of print].
Retinal nerve fiber layer defects are a defining feature of optic neuropathies and have been implicated in several neurodegenerative disorders, including multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease. Both maternal smoking during pregnancy and low birth weight have been implicated in impaired development of the retina.
The Copenhagen Child Cohort 2000 Eye Study
Mr. Ashina and colleagues sought to investigate the associations of maternal smoking during pregnancy and low birth weight with retinal nerve fiber layer thickness in preadolescent children. They examined data from a prospective, population-based, birth cohort study that included all children (n = 6,090) born in 2000 in Copenhagen. Maternal smoking data were collected through parental interviews. Birth weight, pregnancy, and medical history data were obtained from the Danish Medical Birth Registry. As a follow-up, the researchers performed eye examinations on 1,406 of these children from May 1, 2011, to October 31, 2012, when the children were age 11 or 12.
Of the 1,406 children in the study, 1,323 were included in the analysis. Mean age was 11.7. Nearly half of the children (47.8%) were boys. The mean retinal nerve fiber layer thickness was 104 mm. In 227 children whose mothers had smoked during pregnancy, the peripapillary retinal nerve fiber layer was 5.7 mm thinner than in children whose mothers had not smoked during pregnancy, after adjusting for age, sex, birth weight, height, body weight, Tanner stage of pubertal development, axial length, and spherical equivalent refractive error. In children with low birth weight (ie, < 2,500 g), the retinal nerve fiber layer was 3.5 mm thinner than in children with normal birth weight, after adjustment for all variables.
“The results of this study add evidence to existing recommendations to avoid smoking during pregnancy and support measures that promote maternal and fetal health,” the researchers said.
A Public Health Message
In an invited commentary that accompanied the study, Christopher Kai-Shun Leung, MD, from the Department of Ophthalmology and Visual Sciences at Hong Kong Eye Hospital and Chinese University of Hong Kong in Kowloon, said that “although a difference of 5 to 6 mm in average circumpapillary retinal nerve fiber layer thickness is unlikely to translate into a detectable difference in visual function in children aged 12 to 13 years, the risk of subsequent development of visual impairment should not be overlooked.” Furthermore, he noted, “whether a thinner retinal nerve fiber layer in the children of mothers who smoked during pregnancy w
—Glenn S. Williams
Suggested Reading
Ashina H, Li XQ, Olsen EM, et al. Association of maternal smoking during pregnancy and birth weight with retinal nerve fiber layer thickness in children aged 11 or 12 years: The Copenhagen Child Cohort 2000 Eye Study. JAMA Ophthalmol. 2017 March 2 [Epub ahead of print].
Leung CK. Evaluation of retinal nerve fiber layer thinning with Fourier-domain optical coherence tomography. JAMA Ophthalmol. 2017 March 2 [Epub ahead of print].
Retinal nerve fiber layer defects are a defining feature of optic neuropathies and have been implicated in several neurodegenerative disorders, including multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease. Both maternal smoking during pregnancy and low birth weight have been implicated in impaired development of the retina.
The Copenhagen Child Cohort 2000 Eye Study
Mr. Ashina and colleagues sought to investigate the associations of maternal smoking during pregnancy and low birth weight with retinal nerve fiber layer thickness in preadolescent children. They examined data from a prospective, population-based, birth cohort study that included all children (n = 6,090) born in 2000 in Copenhagen. Maternal smoking data were collected through parental interviews. Birth weight, pregnancy, and medical history data were obtained from the Danish Medical Birth Registry. As a follow-up, the researchers performed eye examinations on 1,406 of these children from May 1, 2011, to October 31, 2012, when the children were age 11 or 12.
Of the 1,406 children in the study, 1,323 were included in the analysis. Mean age was 11.7. Nearly half of the children (47.8%) were boys. The mean retinal nerve fiber layer thickness was 104 mm. In 227 children whose mothers had smoked during pregnancy, the peripapillary retinal nerve fiber layer was 5.7 mm thinner than in children whose mothers had not smoked during pregnancy, after adjusting for age, sex, birth weight, height, body weight, Tanner stage of pubertal development, axial length, and spherical equivalent refractive error. In children with low birth weight (ie, < 2,500 g), the retinal nerve fiber layer was 3.5 mm thinner than in children with normal birth weight, after adjustment for all variables.
“The results of this study add evidence to existing recommendations to avoid smoking during pregnancy and support measures that promote maternal and fetal health,” the researchers said.
A Public Health Message
In an invited commentary that accompanied the study, Christopher Kai-Shun Leung, MD, from the Department of Ophthalmology and Visual Sciences at Hong Kong Eye Hospital and Chinese University of Hong Kong in Kowloon, said that “although a difference of 5 to 6 mm in average circumpapillary retinal nerve fiber layer thickness is unlikely to translate into a detectable difference in visual function in children aged 12 to 13 years, the risk of subsequent development of visual impairment should not be overlooked.” Furthermore, he noted, “whether a thinner retinal nerve fiber layer in the children of mothers who smoked during pregnancy w
—Glenn S. Williams
Suggested Reading
Ashina H, Li XQ, Olsen EM, et al. Association of maternal smoking during pregnancy and birth weight with retinal nerve fiber layer thickness in children aged 11 or 12 years: The Copenhagen Child Cohort 2000 Eye Study. JAMA Ophthalmol. 2017 March 2 [Epub ahead of print].
Leung CK. Evaluation of retinal nerve fiber layer thinning with Fourier-domain optical coherence tomography. JAMA Ophthalmol. 2017 March 2 [Epub ahead of print].
Outpatient Visits Involving CNS Polypharmacy Rising Among Elderly
The number of outpatient visits involving CNS polypharmacy by adults aged 65 and older more than doubled between 2004 and 2013, especially among those who reside in rural areas, according to research published online ahead of print February 13 in JAMA Internal Medicine.
“With each new revision of the Beers Criteria, the list of psychotropic medications considered potentially inappropriate in the elderly has grown,” said Donovan T. Maust, MD, Assistant Professor of Geriatric Psychiatry at the University of Michigan in Ann Arbor. “Opioids have recently been included in a Beers measure of CNS polypharmacy. Prescribing related drug combinations also received increased regulatory attention when the US Food and Drug Administration recently ordered a black box warning to alert patients of serious risks, including death, caused by opioids coprescribed with CNS depressants,” he said. 
Dr. Maust and his colleagues analyzed data on 97,910 outpatients age 65 and older from the National Ambulatory Medical Care Survey (NAMCS) from 2004 through 2013. Patients met Beers CNS polypharmacy criteria if three or more of the following medications were initiated or continued: antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonists, tricyclic antidepressants, selective serotonin reuptake inhibitors, and opioids. The researchers recorded as many as three visit diagnoses and included information collected from NAMCS such as chronic medical conditions, whether psychotherapy was provided or ordered, whether stress management or other mental health counseling services were provided or ordered, and time spent with physician.
Dr. Maust and his associates found that annual CNS polypharmacy visits by adults age 65 or older increased from 1.50 million in 2004 to 3.68 million in 2013, or from 0.6% of visits in 2004 to 1.4% in 2013 (adjusted odds ratio [AOR], 3.12). The largest increases were observed among rural visits and among visits with no mental health or pain diagnoses (AOR, 4.99 and 2.65, respectively).
More than two-thirds of polypharmacy visits (68%) were by women, and 17% were by individuals who lived in rural areas. In addition, nearly half of polypharmacy visits studied (46%) included neither mental health nor pain diagnoses. No significant demographic differences were observed between polypharmacy visits with and without opioids. “Older adults have become more open to mental health treatment,” the researchers concluded. “Because of limited access to specialty care and a preference to receive treatment in primary care settings, it is unsurprising that mental health treatment has expanded in nonpsychiatric settings.”
—Doug Brunk
Suggested Reading
Maust DT, Gerlach LB, Gibson A, et al. Trends in central nervous system-active polypharmacy among older adults seen in outpatient care in the United States. JAMA Intern Med. 2017 Feb 13 [Epub ahead of print].
The number of outpatient visits involving CNS polypharmacy by adults aged 65 and older more than doubled between 2004 and 2013, especially among those who reside in rural areas, according to research published online ahead of print February 13 in JAMA Internal Medicine.
“With each new revision of the Beers Criteria, the list of psychotropic medications considered potentially inappropriate in the elderly has grown,” said Donovan T. Maust, MD, Assistant Professor of Geriatric Psychiatry at the University of Michigan in Ann Arbor. “Opioids have recently been included in a Beers measure of CNS polypharmacy. Prescribing related drug combinations also received increased regulatory attention when the US Food and Drug Administration recently ordered a black box warning to alert patients of serious risks, including death, caused by opioids coprescribed with CNS depressants,” he said.
Dr. Maust and his colleagues analyzed data on 97,910 outpatients age 65 and older from the National Ambulatory Medical Care Survey (NAMCS) from 2004 through 2013. Patients met Beers CNS polypharmacy criteria if three or more of the following medications were initiated or continued: antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonists, tricyclic antidepressants, selective serotonin reuptake inhibitors, and opioids. The researchers recorded as many as three visit diagnoses and included information collected from NAMCS such as chronic medical conditions, whether psychotherapy was provided or ordered, whether stress management or other mental health counseling services were provided or ordered, and time spent with physician.
Dr. Maust and his associates found that annual CNS polypharmacy visits by adults age 65 or older increased from 1.50 million in 2004 to 3.68 million in 2013, or from 0.6% of visits in 2004 to 1.4% in 2013 (adjusted odds ratio [AOR], 3.12). The largest increases were observed among rural visits and among visits with no mental health or pain diagnoses (AOR, 4.99 and 2.65, respectively).
More than two-thirds of polypharmacy visits (68%) were by women, and 17% were by individuals who lived in rural areas. In addition, nearly half of polypharmacy visits studied (46%) included neither mental health nor pain diagnoses. No significant demographic differences were observed between polypharmacy visits with and without opioids. “Older adults have become more open to mental health treatment,” the researchers concluded. “Because of limited access to specialty care and a preference to receive treatment in primary care settings, it is unsurprising that mental health treatment has expanded in nonpsychiatric settings.”
—Doug Brunk
Suggested Reading
Maust DT, Gerlach LB, Gibson A, et al. Trends in central nervous system-active polypharmacy among older adults seen in outpatient care in the United States. JAMA Intern Med. 2017 Feb 13 [Epub ahead of print].
The number of outpatient visits involving CNS polypharmacy by adults aged 65 and older more than doubled between 2004 and 2013, especially among those who reside in rural areas, according to research published online ahead of print February 13 in JAMA Internal Medicine.
“With each new revision of the Beers Criteria, the list of psychotropic medications considered potentially inappropriate in the elderly has grown,” said Donovan T. Maust, MD, Assistant Professor of Geriatric Psychiatry at the University of Michigan in Ann Arbor. “Opioids have recently been included in a Beers measure of CNS polypharmacy. Prescribing related drug combinations also received increased regulatory attention when the US Food and Drug Administration recently ordered a black box warning to alert patients of serious risks, including death, caused by opioids coprescribed with CNS depressants,” he said.
Dr. Maust and his colleagues analyzed data on 97,910 outpatients age 65 and older from the National Ambulatory Medical Care Survey (NAMCS) from 2004 through 2013. Patients met Beers CNS polypharmacy criteria if three or more of the following medications were initiated or continued: antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonists, tricyclic antidepressants, selective serotonin reuptake inhibitors, and opioids. The researchers recorded as many as three visit diagnoses and included information collected from NAMCS such as chronic medical conditions, whether psychotherapy was provided or ordered, whether stress management or other mental health counseling services were provided or ordered, and time spent with physician.
Dr. Maust and his associates found that annual CNS polypharmacy visits by adults age 65 or older increased from 1.50 million in 2004 to 3.68 million in 2013, or from 0.6% of visits in 2004 to 1.4% in 2013 (adjusted odds ratio [AOR], 3.12). The largest increases were observed among rural visits and among visits with no mental health or pain diagnoses (AOR, 4.99 and 2.65, respectively).
More than two-thirds of polypharmacy visits (68%) were by women, and 17% were by individuals who lived in rural areas. In addition, nearly half of polypharmacy visits studied (46%) included neither mental health nor pain diagnoses. No significant demographic differences were observed between polypharmacy visits with and without opioids. “Older adults have become more open to mental health treatment,” the researchers concluded. “Because of limited access to specialty care and a preference to receive treatment in primary care settings, it is unsurprising that mental health treatment has expanded in nonpsychiatric settings.”
—Doug Brunk
Suggested Reading
Maust DT, Gerlach LB, Gibson A, et al. Trends in central nervous system-active polypharmacy among older adults seen in outpatient care in the United States. JAMA Intern Med. 2017 Feb 13 [Epub ahead of print].
Pitolisant Reduces Cataplexy Attacks in Narcolepsy
Pitolisant, a histamine H3 receptor inverse agonist, is well tolerated and effectively reduces cataplexy, according to data published in the March issue of Lancet Neurology. If the drug’s effect is confirmed in long-term studies, pitolisant could become a first-line therapy for cataplexy in patients with narcolepsy, who currently have few treatment options, according to the authors.
Two types of drugs are used to treat cataplexy. Antidepressants are used off-label and not well supported by evidence. Sodium oxybate is effective, but may cause serious adverse events.
Zoltán Szakács, MD, a doctor at the State Health Center in Budapest, and colleagues enrolled patients with narcolepsy from 16 sleep centers in nine countries into a randomized, double-blind, placebo-controlled trial. Eligible participants were age 18, had narcolepsy with cataplexy, had at least three cataplexies per week, and had excessive daytime sleepiness. Patients were randomized to pitolisant or placebo once per day. During a three-week flexible dosing period, patients randomized to pitolisant received 5 mg for the first week, 10 mg for the second week, and for the third week, a dose of between 5 mg and 20 mg, on the basis of safety and efficacy. A four-week period of stable dosing followed. Finally, patients underwent a one-week withdrawal period.
In all, 54 patients received pitolisant, and 51 received placebo. During the stable dosing period, the weekly cataplexy rate was decreased by 75% in patients who received pitolisant and by 38% among controls. The effect was significant regardless of the patient’s stable dose of pitolisant. Use of concomitant anticataplectic treatment before study initiation did not affect the results. The drug also improved scores on the Epworth Sleepiness Scale and maintenance of wakefulness test.
The pitolisant group had a significantly higher rate of treatment-related adverse events than did the placebo group (28% vs 12%). The researchers recorded no serious adverse events, but observed one case of severe nausea in the pitolisant group.
The study’s main limitation is that the diagnosis of narcolepsy was based on nonspecific criteria, said Christian R. Baumann, Professor of Neurology at University Hospital Zurich, in an accompanying editorial. “The fact that reported mean sleep latencies in the cohort of Szakács and colleagues (4.2–4.7 min) were higher than those reported in other cohorts, including ours (2.6–2.9 min), leaves some uncertainty about patient inclusion,” he added.
Nevertheless, the study may contribute to the regulatory approval of pitolisant. “This is good news for clinicians, since we need more treatment options to better tailor individualized therapy for patients with narcolepsy,” said Dr. Baumann.
—Erik Greb
Suggested Reading
Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(3):200-207.
Baumann CR. Wide implications of a trial on pitolisant for cataplexy. Lancet Neurol. 2017;16(3):173-174.
Pitolisant, a histamine H3 receptor inverse agonist, is well tolerated and effectively reduces cataplexy, according to data published in the March issue of Lancet Neurology. If the drug’s effect is confirmed in long-term studies, pitolisant could become a first-line therapy for cataplexy in patients with narcolepsy, who currently have few treatment options, according to the authors.
Two types of drugs are used to treat cataplexy. Antidepressants are used off-label and not well supported by evidence. Sodium oxybate is effective, but may cause serious adverse events.
Zoltán Szakács, MD, a doctor at the State Health Center in Budapest, and colleagues enrolled patients with narcolepsy from 16 sleep centers in nine countries into a randomized, double-blind, placebo-controlled trial. Eligible participants were age 18, had narcolepsy with cataplexy, had at least three cataplexies per week, and had excessive daytime sleepiness. Patients were randomized to pitolisant or placebo once per day. During a three-week flexible dosing period, patients randomized to pitolisant received 5 mg for the first week, 10 mg for the second week, and for the third week, a dose of between 5 mg and 20 mg, on the basis of safety and efficacy. A four-week period of stable dosing followed. Finally, patients underwent a one-week withdrawal period.
In all, 54 patients received pitolisant, and 51 received placebo. During the stable dosing period, the weekly cataplexy rate was decreased by 75% in patients who received pitolisant and by 38% among controls. The effect was significant regardless of the patient’s stable dose of pitolisant. Use of concomitant anticataplectic treatment before study initiation did not affect the results. The drug also improved scores on the Epworth Sleepiness Scale and maintenance of wakefulness test.
The pitolisant group had a significantly higher rate of treatment-related adverse events than did the placebo group (28% vs 12%). The researchers recorded no serious adverse events, but observed one case of severe nausea in the pitolisant group.
The study’s main limitation is that the diagnosis of narcolepsy was based on nonspecific criteria, said Christian R. Baumann, Professor of Neurology at University Hospital Zurich, in an accompanying editorial. “The fact that reported mean sleep latencies in the cohort of Szakács and colleagues (4.2–4.7 min) were higher than those reported in other cohorts, including ours (2.6–2.9 min), leaves some uncertainty about patient inclusion,” he added.
Nevertheless, the study may contribute to the regulatory approval of pitolisant. “This is good news for clinicians, since we need more treatment options to better tailor individualized therapy for patients with narcolepsy,” said Dr. Baumann.
—Erik Greb
Suggested Reading
Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(3):200-207.
Baumann CR. Wide implications of a trial on pitolisant for cataplexy. Lancet Neurol. 2017;16(3):173-174.
Pitolisant, a histamine H3 receptor inverse agonist, is well tolerated and effectively reduces cataplexy, according to data published in the March issue of Lancet Neurology. If the drug’s effect is confirmed in long-term studies, pitolisant could become a first-line therapy for cataplexy in patients with narcolepsy, who currently have few treatment options, according to the authors.
Two types of drugs are used to treat cataplexy. Antidepressants are used off-label and not well supported by evidence. Sodium oxybate is effective, but may cause serious adverse events.
Zoltán Szakács, MD, a doctor at the State Health Center in Budapest, and colleagues enrolled patients with narcolepsy from 16 sleep centers in nine countries into a randomized, double-blind, placebo-controlled trial. Eligible participants were age 18, had narcolepsy with cataplexy, had at least three cataplexies per week, and had excessive daytime sleepiness. Patients were randomized to pitolisant or placebo once per day. During a three-week flexible dosing period, patients randomized to pitolisant received 5 mg for the first week, 10 mg for the second week, and for the third week, a dose of between 5 mg and 20 mg, on the basis of safety and efficacy. A four-week period of stable dosing followed. Finally, patients underwent a one-week withdrawal period.
In all, 54 patients received pitolisant, and 51 received placebo. During the stable dosing period, the weekly cataplexy rate was decreased by 75% in patients who received pitolisant and by 38% among controls. The effect was significant regardless of the patient’s stable dose of pitolisant. Use of concomitant anticataplectic treatment before study initiation did not affect the results. The drug also improved scores on the Epworth Sleepiness Scale and maintenance of wakefulness test.
The pitolisant group had a significantly higher rate of treatment-related adverse events than did the placebo group (28% vs 12%). The researchers recorded no serious adverse events, but observed one case of severe nausea in the pitolisant group.
The study’s main limitation is that the diagnosis of narcolepsy was based on nonspecific criteria, said Christian R. Baumann, Professor of Neurology at University Hospital Zurich, in an accompanying editorial. “The fact that reported mean sleep latencies in the cohort of Szakács and colleagues (4.2–4.7 min) were higher than those reported in other cohorts, including ours (2.6–2.9 min), leaves some uncertainty about patient inclusion,” he added.
Nevertheless, the study may contribute to the regulatory approval of pitolisant. “This is good news for clinicians, since we need more treatment options to better tailor individualized therapy for patients with narcolepsy,” said Dr. Baumann.
—Erik Greb
Suggested Reading
Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(3):200-207.
Baumann CR. Wide implications of a trial on pitolisant for cataplexy. Lancet Neurol. 2017;16(3):173-174.