American Academy of Neurology (AAN): Annual Meeting 2019

Philadelphia – OV101 (gaboxadol), a type A gamma-aminobutyric acid receptor agonist, was safe, well tolerated, and improved clinical outcomes in a phase 2 trial of adults and adolescents with Angelman syndrome, according to results of a study presented at the annual meeting of the American Academy of Neurology.

Clinician-rated clinical global impressions of improvement (CGI-I) were improved versus placebo in the randomized study, as were other outcomes in post hoc analyses, including measures of sleep and motor function, said Alexander Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, New York.

This study of OV101 was a genetics-driven trial for the rare genetic disorder, which is caused by mutations in UBE3A and characterized by seizures, speech impairments, profound intellectual disability, gait problems, and anxiety, Dr. Kolevzon said in a press conference.

“The only treatments that exist are really very symptomatically driven,” Dr. Kolevzon said. “Here, we are taking a genetics-first approach. Having identified the gene, there is some understanding of what the underlying biology is, and it seems to relate to deficits in tonic inhibition.”

OV101 is a delta-selective type A gamma-aminobutyric acid receptor agonist that may potentially normalize the tonic inhibition that is decreased in Angelman syndrome. “What we think this compound is doing is actually reversing the deficits of tonic inhibition, and sort of restoring that state to these patients,” Dr. Kolevzon said in the press conference.

A total of 78 patients completed the phase 2, randomized study, known as STARS, which had a primary endpoint of safety and tolerability over 12 weeks of treatment with OV101 once daily, twice daily, or placebo. The mean age of the 87 patients who enrolled and had at least one dose of study drug was 22.6 years.

Most adverse events were mild, and frequencies of specific adverse events were similar for OV101 and placebo treatment groups, according to Dr. Kolevzon and his coinvestigators.

Improvements in motor function, sleep, and behavior were seen in a series of exploratory analyses, including global improvement at week 12, as captured by CGI-I, which was significantly improved for daily OV101 versus placebo (P = .0006).

These phase 2 results have informed discussions of which specific endpoints might be incorporated into the design of a planned phase 3 trial in pediatric patients. The CGI-I may be especially useful to measure clinical improvement in Angelman syndrome, which is a very “heterogeneous” disorder, Dr. Kolevzon said in the press conference.

“Every child has a different composite of symptoms, so that is the big challenge,” Dr. Kolevzon said. “I do not think we are going to have one singular outcome. The idea is to have a global measure that really captures heterogeneity across each trial and allows for children to be compared to their baseline, and each as their own control, in essence, but with specific domains in mind.”

Funding for the study came from Ovid Therapeutics. Dr. Kolevzon reported disclosures related to Ovid Therapeutics, as well as Coronis Neurosciences, 5AM Ventures, SEMA4, LabCorp, and AMO Pharma.

Philadelphia – OV101 (gaboxadol), a type A gamma-aminobutyric acid receptor agonist, was safe, well tolerated, and improved clinical outcomes in a phase 2 trial of adults and adolescents with Angelman syndrome, according to results of a study presented at the annual meeting of the American Academy of Neurology.

Clinician-rated clinical global impressions of improvement (CGI-I) were improved versus placebo in the randomized study, as were other outcomes in post hoc analyses, including measures of sleep and motor function, said Alexander Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, New York.

This study of OV101 was a genetics-driven trial for the rare genetic disorder, which is caused by mutations in UBE3A and characterized by seizures, speech impairments, profound intellectual disability, gait problems, and anxiety, Dr. Kolevzon said in a press conference.

“The only treatments that exist are really very symptomatically driven,” Dr. Kolevzon said. “Here, we are taking a genetics-first approach. Having identified the gene, there is some understanding of what the underlying biology is, and it seems to relate to deficits in tonic inhibition.”

OV101 is a delta-selective type A gamma-aminobutyric acid receptor agonist that may potentially normalize the tonic inhibition that is decreased in Angelman syndrome. “What we think this compound is doing is actually reversing the deficits of tonic inhibition, and sort of restoring that state to these patients,” Dr. Kolevzon said in the press conference.

A total of 78 patients completed the phase 2, randomized study, known as STARS, which had a primary endpoint of safety and tolerability over 12 weeks of treatment with OV101 once daily, twice daily, or placebo. The mean age of the 87 patients who enrolled and had at least one dose of study drug was 22.6 years.

Most adverse events were mild, and frequencies of specific adverse events were similar for OV101 and placebo treatment groups, according to Dr. Kolevzon and his coinvestigators.

Improvements in motor function, sleep, and behavior were seen in a series of exploratory analyses, including global improvement at week 12, as captured by CGI-I, which was significantly improved for daily OV101 versus placebo (P = .0006).

These phase 2 results have informed discussions of which specific endpoints might be incorporated into the design of a planned phase 3 trial in pediatric patients. The CGI-I may be especially useful to measure clinical improvement in Angelman syndrome, which is a very “heterogeneous” disorder, Dr. Kolevzon said in the press conference.

“Every child has a different composite of symptoms, so that is the big challenge,” Dr. Kolevzon said. “I do not think we are going to have one singular outcome. The idea is to have a global measure that really captures heterogeneity across each trial and allows for children to be compared to their baseline, and each as their own control, in essence, but with specific domains in mind.”

Funding for the study came from Ovid Therapeutics. Dr. Kolevzon reported disclosures related to Ovid Therapeutics, as well as Coronis Neurosciences, 5AM Ventures, SEMA4, LabCorp, and AMO Pharma.

Philadelphia – OV101 (gaboxadol), a type A gamma-aminobutyric acid receptor agonist, was safe, well tolerated, and improved clinical outcomes in a phase 2 trial of adults and adolescents with Angelman syndrome, according to results of a study presented at the annual meeting of the American Academy of Neurology.

Clinician-rated clinical global impressions of improvement (CGI-I) were improved versus placebo in the randomized study, as were other outcomes in post hoc analyses, including measures of sleep and motor function, said Alexander Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, New York.

This study of OV101 was a genetics-driven trial for the rare genetic disorder, which is caused by mutations in UBE3A and characterized by seizures, speech impairments, profound intellectual disability, gait problems, and anxiety, Dr. Kolevzon said in a press conference.

“The only treatments that exist are really very symptomatically driven,” Dr. Kolevzon said. “Here, we are taking a genetics-first approach. Having identified the gene, there is some understanding of what the underlying biology is, and it seems to relate to deficits in tonic inhibition.”

OV101 is a delta-selective type A gamma-aminobutyric acid receptor agonist that may potentially normalize the tonic inhibition that is decreased in Angelman syndrome. “What we think this compound is doing is actually reversing the deficits of tonic inhibition, and sort of restoring that state to these patients,” Dr. Kolevzon said in the press conference.

A total of 78 patients completed the phase 2, randomized study, known as STARS, which had a primary endpoint of safety and tolerability over 12 weeks of treatment with OV101 once daily, twice daily, or placebo. The mean age of the 87 patients who enrolled and had at least one dose of study drug was 22.6 years.

Most adverse events were mild, and frequencies of specific adverse events were similar for OV101 and placebo treatment groups, according to Dr. Kolevzon and his coinvestigators.

Improvements in motor function, sleep, and behavior were seen in a series of exploratory analyses, including global improvement at week 12, as captured by CGI-I, which was significantly improved for daily OV101 versus placebo (P = .0006).

These phase 2 results have informed discussions of which specific endpoints might be incorporated into the design of a planned phase 3 trial in pediatric patients. The CGI-I may be especially useful to measure clinical improvement in Angelman syndrome, which is a very “heterogeneous” disorder, Dr. Kolevzon said in the press conference.

“Every child has a different composite of symptoms, so that is the big challenge,” Dr. Kolevzon said. “I do not think we are going to have one singular outcome. The idea is to have a global measure that really captures heterogeneity across each trial and allows for children to be compared to their baseline, and each as their own control, in essence, but with specific domains in mind.”

Funding for the study came from Ovid Therapeutics. Dr. Kolevzon reported disclosures related to Ovid Therapeutics, as well as Coronis Neurosciences, 5AM Ventures, SEMA4, LabCorp, and AMO Pharma.

PHILADELPHIA – Oligomeric alpha synuclein levels in tears can help clinicians distinguish between patients with Parkinson’s disease and healthy controls, according to research presented at the annual meeting of the American Academy of Neurology. Chemokine (C-C motif) ligand 2 (CCL2), a cytokine, may be used for the same purpose, according to researchers.

Lacrimal glands have high numbers of cholinergic and other neurons. Parasympathetic and sympathetic neural pathways stimulate the tears that lacrimal grands secrete. It is possible that the production, packaging, and secretion of proteins into tears may alter when nerve function in the lacrimal glands and cornea changes. This idea may be tested by collecting reflex tears (i.e., stimulated tears provoked by an unanesthetized Schirmer’s test).

Mark Lew, MD, professor of clinical neurology at University of Southern California, Los Angeles, and colleagues previously studied patients using basal tears collected from an anesthetized Schirmer’s test. To examine whether the protein composition of reflex tears differs in patients with Parkinson’s disease, compared with healthy controls, they collected reflex tears from 85 patients with Parkinson’s disease and 80 age- and sex-matched healthy controls using an unanesthetized Schirmer’s test. The researchers pooled samples from both eyes to analyze alpha synuclein, CCL2, and total protein using enzyme-linked immunosorbent assays or multiplex ELISA.


Eligible participants were aged 30-85 years and had a Montreal Cognitive Assessment (MoCA) score of 21 or higher. Patients with Parkinson’s disease had a lower MoCA score than controls did, although it was still in the normal range. Tear flow was significantly decreased in patients with Parkinson’s disease, compared with controls.

Dr. Lew and colleagues found that the amount of oligomeric alpha synuclein was increased nearly 400% in the tears of patients with Parkinson’s disease, compared with those of healthy controls (4.21 ng/mg tear protein vs. 0.90 ng/mg tear protein). This difference was statistically significant. Similarly, CCL2 was significantly increased in the tears of patients with Parkinson’s disease, compared with those of healthy controls (165.8 pg/mg tear protein vs. 116.3 pg/mg tear protein). Among men, Parkinson’s disease was associated with greater rises in oligomeric alpha synuclein (4.95 ng/mg tear protein vs. 0.89 ng/mg tear protein in healthy controls) and CCL2 (201.5 pg/mg tear protein vs. 117.9 pg/mg tear protein in healthy controls) than in women. The origin of sex differences in these biomarker values requires further study, the investigators said.

Dr. Lew reported receiving research support from the Parkinson’s Study Group, the Michael J. Fox Foundation, Biotie Therapies, NeuroDerm, Enterin, Pharm2B Fellowship Grants, Allergan, and Medtronic.

egreb@mdedge.com

SOURCE: Lew M et al. AAN 2019, Abstract S10.001

PHILADELPHIA – Oligomeric alpha synuclein levels in tears can help clinicians distinguish between patients with Parkinson’s disease and healthy controls, according to research presented at the annual meeting of the American Academy of Neurology. Chemokine (C-C motif) ligand 2 (CCL2), a cytokine, may be used for the same purpose, according to researchers.

Lacrimal glands have high numbers of cholinergic and other neurons. Parasympathetic and sympathetic neural pathways stimulate the tears that lacrimal grands secrete. It is possible that the production, packaging, and secretion of proteins into tears may alter when nerve function in the lacrimal glands and cornea changes. This idea may be tested by collecting reflex tears (i.e., stimulated tears provoked by an unanesthetized Schirmer’s test).

Mark Lew, MD, professor of clinical neurology at University of Southern California, Los Angeles, and colleagues previously studied patients using basal tears collected from an anesthetized Schirmer’s test. To examine whether the protein composition of reflex tears differs in patients with Parkinson’s disease, compared with healthy controls, they collected reflex tears from 85 patients with Parkinson’s disease and 80 age- and sex-matched healthy controls using an unanesthetized Schirmer’s test. The researchers pooled samples from both eyes to analyze alpha synuclein, CCL2, and total protein using enzyme-linked immunosorbent assays or multiplex ELISA.


Eligible participants were aged 30-85 years and had a Montreal Cognitive Assessment (MoCA) score of 21 or higher. Patients with Parkinson’s disease had a lower MoCA score than controls did, although it was still in the normal range. Tear flow was significantly decreased in patients with Parkinson’s disease, compared with controls.

Dr. Lew and colleagues found that the amount of oligomeric alpha synuclein was increased nearly 400% in the tears of patients with Parkinson’s disease, compared with those of healthy controls (4.21 ng/mg tear protein vs. 0.90 ng/mg tear protein). This difference was statistically significant. Similarly, CCL2 was significantly increased in the tears of patients with Parkinson’s disease, compared with those of healthy controls (165.8 pg/mg tear protein vs. 116.3 pg/mg tear protein). Among men, Parkinson’s disease was associated with greater rises in oligomeric alpha synuclein (4.95 ng/mg tear protein vs. 0.89 ng/mg tear protein in healthy controls) and CCL2 (201.5 pg/mg tear protein vs. 117.9 pg/mg tear protein in healthy controls) than in women. The origin of sex differences in these biomarker values requires further study, the investigators said.

Dr. Lew reported receiving research support from the Parkinson’s Study Group, the Michael J. Fox Foundation, Biotie Therapies, NeuroDerm, Enterin, Pharm2B Fellowship Grants, Allergan, and Medtronic.

egreb@mdedge.com

SOURCE: Lew M et al. AAN 2019, Abstract S10.001

PHILADELPHIA – Oligomeric alpha synuclein levels in tears can help clinicians distinguish between patients with Parkinson’s disease and healthy controls, according to research presented at the annual meeting of the American Academy of Neurology. Chemokine (C-C motif) ligand 2 (CCL2), a cytokine, may be used for the same purpose, according to researchers.

Lacrimal glands have high numbers of cholinergic and other neurons. Parasympathetic and sympathetic neural pathways stimulate the tears that lacrimal grands secrete. It is possible that the production, packaging, and secretion of proteins into tears may alter when nerve function in the lacrimal glands and cornea changes. This idea may be tested by collecting reflex tears (i.e., stimulated tears provoked by an unanesthetized Schirmer’s test).

Mark Lew, MD, professor of clinical neurology at University of Southern California, Los Angeles, and colleagues previously studied patients using basal tears collected from an anesthetized Schirmer’s test. To examine whether the protein composition of reflex tears differs in patients with Parkinson’s disease, compared with healthy controls, they collected reflex tears from 85 patients with Parkinson’s disease and 80 age- and sex-matched healthy controls using an unanesthetized Schirmer’s test. The researchers pooled samples from both eyes to analyze alpha synuclein, CCL2, and total protein using enzyme-linked immunosorbent assays or multiplex ELISA.


Eligible participants were aged 30-85 years and had a Montreal Cognitive Assessment (MoCA) score of 21 or higher. Patients with Parkinson’s disease had a lower MoCA score than controls did, although it was still in the normal range. Tear flow was significantly decreased in patients with Parkinson’s disease, compared with controls.

Dr. Lew and colleagues found that the amount of oligomeric alpha synuclein was increased nearly 400% in the tears of patients with Parkinson’s disease, compared with those of healthy controls (4.21 ng/mg tear protein vs. 0.90 ng/mg tear protein). This difference was statistically significant. Similarly, CCL2 was significantly increased in the tears of patients with Parkinson’s disease, compared with those of healthy controls (165.8 pg/mg tear protein vs. 116.3 pg/mg tear protein). Among men, Parkinson’s disease was associated with greater rises in oligomeric alpha synuclein (4.95 ng/mg tear protein vs. 0.89 ng/mg tear protein in healthy controls) and CCL2 (201.5 pg/mg tear protein vs. 117.9 pg/mg tear protein in healthy controls) than in women. The origin of sex differences in these biomarker values requires further study, the investigators said.

Dr. Lew reported receiving research support from the Parkinson’s Study Group, the Michael J. Fox Foundation, Biotie Therapies, NeuroDerm, Enterin, Pharm2B Fellowship Grants, Allergan, and Medtronic.

egreb@mdedge.com

SOURCE: Lew M et al. AAN 2019, Abstract S10.001

PHILADELPHIA – Older adults who report more depressive symptoms may be at greater risk of ischemic stroke, according to preliminary data from a prospective cohort study presented at the annual meeting of the American Academy of Neurology.

Prior research has found that depression may increase the likelihood of hypertension, cardiac morbidity and mortality, and stroke mortality. How depression affects the risk of incident stroke, however, “is underexplored, especially among Latinos and African Americans,” said study author Marialaura Simonetto, MD, of the University of Miami and associates.

To assess the relationship between depressive symptoms and risk of incident ischemic stroke, the researchers analyzed data from more than 1,100 participants in the MRI substudy of the Northern Manhattan Study. The cohort includes older adults who were clinically stroke free at baseline.

Researchers assessed depressive symptoms at baseline using the Center for Epidemiological Studies–Depression Scale (CES-D). Scores range from 0-60, and they considered CES-D scores of 16 or greater to be elevated.

The investigators used Cox proportional hazards models to estimate hazard ratios of incident ischemic stroke after adjusting for age, sex, race, ethnicity, years of education, smoking, physical activity, alcohol consumption, diabetes, and hypertension.

In all, 1,104 participants were included in the analysis. Participants had an average age of 70 years, 61% were women, and 69% were Hispanic. At baseline, 198 participants (18%) had elevated depressive symptoms.

During 14 years of follow-up, 101 participants had incident strokes, 87 of which were ischemic strokes. In adjusted models, participants with elevated depressive symptoms had a significantly greater risk of ischemic stroke (HR, 1.75; 95% confidence interval, 1.06-2.88). “Every 5-point increase in CES-D score conferred a 12% greater risk of ischemic stroke,” the researchers reported.

“Depression is common and often goes untreated,” Dr. Simonetto said in a news release. “If people with depression are at elevated risk of stroke, early detection and treatment will be even more important.”

The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Simonetto reported no disclosures. Coauthors disclosed personal compensation and research support from pharmaceutical and medical device companies.

jremaly@mdedge.com

SOURCE: Simonetto M et al. AAN 2019, Abstract S1.003.

PHILADELPHIA – Older adults who report more depressive symptoms may be at greater risk of ischemic stroke, according to preliminary data from a prospective cohort study presented at the annual meeting of the American Academy of Neurology.

Prior research has found that depression may increase the likelihood of hypertension, cardiac morbidity and mortality, and stroke mortality. How depression affects the risk of incident stroke, however, “is underexplored, especially among Latinos and African Americans,” said study author Marialaura Simonetto, MD, of the University of Miami and associates.

To assess the relationship between depressive symptoms and risk of incident ischemic stroke, the researchers analyzed data from more than 1,100 participants in the MRI substudy of the Northern Manhattan Study. The cohort includes older adults who were clinically stroke free at baseline.

Researchers assessed depressive symptoms at baseline using the Center for Epidemiological Studies–Depression Scale (CES-D). Scores range from 0-60, and they considered CES-D scores of 16 or greater to be elevated.

The investigators used Cox proportional hazards models to estimate hazard ratios of incident ischemic stroke after adjusting for age, sex, race, ethnicity, years of education, smoking, physical activity, alcohol consumption, diabetes, and hypertension.

In all, 1,104 participants were included in the analysis. Participants had an average age of 70 years, 61% were women, and 69% were Hispanic. At baseline, 198 participants (18%) had elevated depressive symptoms.

During 14 years of follow-up, 101 participants had incident strokes, 87 of which were ischemic strokes. In adjusted models, participants with elevated depressive symptoms had a significantly greater risk of ischemic stroke (HR, 1.75; 95% confidence interval, 1.06-2.88). “Every 5-point increase in CES-D score conferred a 12% greater risk of ischemic stroke,” the researchers reported.

“Depression is common and often goes untreated,” Dr. Simonetto said in a news release. “If people with depression are at elevated risk of stroke, early detection and treatment will be even more important.”

The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Simonetto reported no disclosures. Coauthors disclosed personal compensation and research support from pharmaceutical and medical device companies.

jremaly@mdedge.com

SOURCE: Simonetto M et al. AAN 2019, Abstract S1.003.

PHILADELPHIA – Older adults who report more depressive symptoms may be at greater risk of ischemic stroke, according to preliminary data from a prospective cohort study presented at the annual meeting of the American Academy of Neurology.

Prior research has found that depression may increase the likelihood of hypertension, cardiac morbidity and mortality, and stroke mortality. How depression affects the risk of incident stroke, however, “is underexplored, especially among Latinos and African Americans,” said study author Marialaura Simonetto, MD, of the University of Miami and associates.

To assess the relationship between depressive symptoms and risk of incident ischemic stroke, the researchers analyzed data from more than 1,100 participants in the MRI substudy of the Northern Manhattan Study. The cohort includes older adults who were clinically stroke free at baseline.

Researchers assessed depressive symptoms at baseline using the Center for Epidemiological Studies–Depression Scale (CES-D). Scores range from 0-60, and they considered CES-D scores of 16 or greater to be elevated.

The investigators used Cox proportional hazards models to estimate hazard ratios of incident ischemic stroke after adjusting for age, sex, race, ethnicity, years of education, smoking, physical activity, alcohol consumption, diabetes, and hypertension.

In all, 1,104 participants were included in the analysis. Participants had an average age of 70 years, 61% were women, and 69% were Hispanic. At baseline, 198 participants (18%) had elevated depressive symptoms.

During 14 years of follow-up, 101 participants had incident strokes, 87 of which were ischemic strokes. In adjusted models, participants with elevated depressive symptoms had a significantly greater risk of ischemic stroke (HR, 1.75; 95% confidence interval, 1.06-2.88). “Every 5-point increase in CES-D score conferred a 12% greater risk of ischemic stroke,” the researchers reported.

“Depression is common and often goes untreated,” Dr. Simonetto said in a news release. “If people with depression are at elevated risk of stroke, early detection and treatment will be even more important.”

The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Simonetto reported no disclosures. Coauthors disclosed personal compensation and research support from pharmaceutical and medical device companies.

jremaly@mdedge.com

SOURCE: Simonetto M et al. AAN 2019, Abstract S1.003.

PHILADELPHIA – Brain volumes of specific regions of interest can be used to classify traumatic brain injury subjects that fall into predetermined symptom categories,” according to a study presented at the annual meeting of the American Academy of Neurology.

Traumatic brain injury (TBI) damages brain tissue and causes subsequent volume loss, which may result in clinical symptoms. It is a prevalent worldwide health problem caused by a mechanical insult to the head, resulting in transient or permanent alteration to brain tissue and/or function. Standard neuroimaging with computerized cranial tomography (CT) and structural magnetic resonance imaging (MRI) is often unrevealing during the evaluation of patients with TBI, particularly those classified as mild TBI. I

In this study, James Rock, MD, of Penn Presbyterian Medical Center and the University of Pennsylvania, and his colleagues sought to examine the value of quantitative analysis of regional brain volumes in the evaluation of TBI. The investigators reviewed the medical records and MRI imaging from 44 patients with TBI evaluated at a Level I trauma center. They also read clinical notes to assess reported symptoms and physical findings.

Regional volumes from TBI subjects were derived using the software package Freesurfer image analysis suite, which utilizes a T1-weighted structural scan to calculate volumetric information. A machine learning algorithm, random forests, was employed across volume measurements from 25 regions of interest to determine the most important regions for classifying subjects based on clinical outcome and symptomology.

Basal ganglia volume showed the highest variable importance with regards to classifying subjects who exhibited symptoms of cognitive dysfunction (Mean Decrease in Gini = 1.067, Mean Decrease in Accuracy = 5.966e-03) in quantitative analysis. Left lateral ventricle volume was important in classifying subjects with motor and vestibular alterations (Mean Decrease in Gini = 2.037, Mean Decrease in Accuracy = 2.92e-02). Left choroid plexus volume was the most important region for classifying subjects with sensation and somatic dysfunction (Mean Decrease in Gini = 0.271, Mean Decrease in Accuracy = 4.82e-03).

The researchers noted that their study is ongoing, in an abstract. “It will be extended to a larger cohort to determine whether volume changes in specific [regions of interest] can act as useful clinical biomarkers for chronic symptoms,” they said.

Dr. Diaz-Arrastia received personal compensation from Neural Analytics, Inc, BrainBox Solutions, Inc, and Bioscience Pharma Partners. Dr. Diaz-Arrastia holds stock and/or stock options in Neural Analytics, Inc. and has received research support from BrainBox Solutions. The other authors reported not having anything to disclose..

gwilliams@mdedge.com

SOURCE: Rock J et al. AAN 2019. Abstract S2.006 .

PHILADELPHIA – Brain volumes of specific regions of interest can be used to classify traumatic brain injury subjects that fall into predetermined symptom categories,” according to a study presented at the annual meeting of the American Academy of Neurology.

Traumatic brain injury (TBI) damages brain tissue and causes subsequent volume loss, which may result in clinical symptoms. It is a prevalent worldwide health problem caused by a mechanical insult to the head, resulting in transient or permanent alteration to brain tissue and/or function. Standard neuroimaging with computerized cranial tomography (CT) and structural magnetic resonance imaging (MRI) is often unrevealing during the evaluation of patients with TBI, particularly those classified as mild TBI. I

In this study, James Rock, MD, of Penn Presbyterian Medical Center and the University of Pennsylvania, and his colleagues sought to examine the value of quantitative analysis of regional brain volumes in the evaluation of TBI. The investigators reviewed the medical records and MRI imaging from 44 patients with TBI evaluated at a Level I trauma center. They also read clinical notes to assess reported symptoms and physical findings.

Regional volumes from TBI subjects were derived using the software package Freesurfer image analysis suite, which utilizes a T1-weighted structural scan to calculate volumetric information. A machine learning algorithm, random forests, was employed across volume measurements from 25 regions of interest to determine the most important regions for classifying subjects based on clinical outcome and symptomology.

Basal ganglia volume showed the highest variable importance with regards to classifying subjects who exhibited symptoms of cognitive dysfunction (Mean Decrease in Gini = 1.067, Mean Decrease in Accuracy = 5.966e-03) in quantitative analysis. Left lateral ventricle volume was important in classifying subjects with motor and vestibular alterations (Mean Decrease in Gini = 2.037, Mean Decrease in Accuracy = 2.92e-02). Left choroid plexus volume was the most important region for classifying subjects with sensation and somatic dysfunction (Mean Decrease in Gini = 0.271, Mean Decrease in Accuracy = 4.82e-03).

The researchers noted that their study is ongoing, in an abstract. “It will be extended to a larger cohort to determine whether volume changes in specific [regions of interest] can act as useful clinical biomarkers for chronic symptoms,” they said.

Dr. Diaz-Arrastia received personal compensation from Neural Analytics, Inc, BrainBox Solutions, Inc, and Bioscience Pharma Partners. Dr. Diaz-Arrastia holds stock and/or stock options in Neural Analytics, Inc. and has received research support from BrainBox Solutions. The other authors reported not having anything to disclose..

gwilliams@mdedge.com

SOURCE: Rock J et al. AAN 2019. Abstract S2.006 .

PHILADELPHIA – Brain volumes of specific regions of interest can be used to classify traumatic brain injury subjects that fall into predetermined symptom categories,” according to a study presented at the annual meeting of the American Academy of Neurology.

Traumatic brain injury (TBI) damages brain tissue and causes subsequent volume loss, which may result in clinical symptoms. It is a prevalent worldwide health problem caused by a mechanical insult to the head, resulting in transient or permanent alteration to brain tissue and/or function. Standard neuroimaging with computerized cranial tomography (CT) and structural magnetic resonance imaging (MRI) is often unrevealing during the evaluation of patients with TBI, particularly those classified as mild TBI. I

In this study, James Rock, MD, of Penn Presbyterian Medical Center and the University of Pennsylvania, and his colleagues sought to examine the value of quantitative analysis of regional brain volumes in the evaluation of TBI. The investigators reviewed the medical records and MRI imaging from 44 patients with TBI evaluated at a Level I trauma center. They also read clinical notes to assess reported symptoms and physical findings.

Regional volumes from TBI subjects were derived using the software package Freesurfer image analysis suite, which utilizes a T1-weighted structural scan to calculate volumetric information. A machine learning algorithm, random forests, was employed across volume measurements from 25 regions of interest to determine the most important regions for classifying subjects based on clinical outcome and symptomology.

Basal ganglia volume showed the highest variable importance with regards to classifying subjects who exhibited symptoms of cognitive dysfunction (Mean Decrease in Gini = 1.067, Mean Decrease in Accuracy = 5.966e-03) in quantitative analysis. Left lateral ventricle volume was important in classifying subjects with motor and vestibular alterations (Mean Decrease in Gini = 2.037, Mean Decrease in Accuracy = 2.92e-02). Left choroid plexus volume was the most important region for classifying subjects with sensation and somatic dysfunction (Mean Decrease in Gini = 0.271, Mean Decrease in Accuracy = 4.82e-03).

The researchers noted that their study is ongoing, in an abstract. “It will be extended to a larger cohort to determine whether volume changes in specific [regions of interest] can act as useful clinical biomarkers for chronic symptoms,” they said.

Dr. Diaz-Arrastia received personal compensation from Neural Analytics, Inc, BrainBox Solutions, Inc, and Bioscience Pharma Partners. Dr. Diaz-Arrastia holds stock and/or stock options in Neural Analytics, Inc. and has received research support from BrainBox Solutions. The other authors reported not having anything to disclose..

gwilliams@mdedge.com

SOURCE: Rock J et al. AAN 2019. Abstract S2.006 .

PHILADELPHIA – Fremanezumab was efficacious in migraine patients who had not benefited from taking other migraine preventive medication, according to a poster presented at the annual meeting of the American Academy of Neurology.

To assess the efficacy of fremanezumab in patients with migraine who had not received relief from trying at least one prior preventive migraine medication, Peter McAllister, MD and colleagues analyzed data from 2 phase 3 trials (HALO EM and HALO CM). Trial participants had either episodic or chronic migraine, confirmed during a 28-day pretreatment baseline period, then received subcutaneous fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), monthly (for chronic migraine: 675 mg at baseline and 225 mg at weeks 4 and 8; for episodic migraine: 225 mg at baseline and weeks 4 and 8), or placebo (at baseline and weeks 4 and 8).

The present analysis included data from 186 patients with episodic migraine and 407 patients with chronic migraine, which represents the subgroup of study participants in the larger HALO trials who had failed at least one prior preventive migraine medication. Dr. McAllister, who is cofounder and chief medical officer at the New England Institute for Clinical Research in Stamford, Connecticut, and his colleagues, assessed mean changes from baseline in the monthly average number of headache days of at least moderate severity or the monthly average number of migraine days during the 12-week treatment period.

In patients with chronic migraine, fremanezumab yielded greater reductions in the number of headache days of at least moderate severity (quarterly [least-squares mean change]: –4.0, P less than 0.0001; monthly: –4.5, P less than 0.0001) compared with placebo (–1.8). There were similar reductions in the number of migraine days (quarterly: –4.1, P = 0.0027; monthly: –4.8, P less than 0.0001) compared with placebo (–2.3).

In patients with episodic migraine, fremanezumab yielded greater reductions in the number of headache days of at least moderate severity (quarterly: –3.1, P less than 0.0001; monthly: –3.2, P less than 0.0001) compared with placebo (–0.8). There were similar reductions in the number of migraine days (quarterly: –3.3, P = 0.0015; monthly: –3.7, P less than 0.0001) compared with placebo (–1.3).

“The phase 3 HALO CM and HALO EM trials showed that fremanezumab is efficacious in patients who failed one or more prior preventive medication, a potentially difficult-to-treat population,” Dr. McAllister and colleagues said in their poster.

“Effect sizes in this subgroup were greater than those in the overall trial population,” they said. In addition, “both quarterly and monthly fremanezumab were well-tolerated in this subgroup.”

This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

gwilliams@mdedge.com

SOURCE: McAllister P et al. AAN 2019. P1.10-011.

PHILADELPHIA – Fremanezumab was efficacious in migraine patients who had not benefited from taking other migraine preventive medication, according to a poster presented at the annual meeting of the American Academy of Neurology.

To assess the efficacy of fremanezumab in patients with migraine who had not received relief from trying at least one prior preventive migraine medication, Peter McAllister, MD and colleagues analyzed data from 2 phase 3 trials (HALO EM and HALO CM). Trial participants had either episodic or chronic migraine, confirmed during a 28-day pretreatment baseline period, then received subcutaneous fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), monthly (for chronic migraine: 675 mg at baseline and 225 mg at weeks 4 and 8; for episodic migraine: 225 mg at baseline and weeks 4 and 8), or placebo (at baseline and weeks 4 and 8).

The present analysis included data from 186 patients with episodic migraine and 407 patients with chronic migraine, which represents the subgroup of study participants in the larger HALO trials who had failed at least one prior preventive migraine medication. Dr. McAllister, who is cofounder and chief medical officer at the New England Institute for Clinical Research in Stamford, Connecticut, and his colleagues, assessed mean changes from baseline in the monthly average number of headache days of at least moderate severity or the monthly average number of migraine days during the 12-week treatment period.

In patients with chronic migraine, fremanezumab yielded greater reductions in the number of headache days of at least moderate severity (quarterly [least-squares mean change]: –4.0, P less than 0.0001; monthly: –4.5, P less than 0.0001) compared with placebo (–1.8). There were similar reductions in the number of migraine days (quarterly: –4.1, P = 0.0027; monthly: –4.8, P less than 0.0001) compared with placebo (–2.3).

In patients with episodic migraine, fremanezumab yielded greater reductions in the number of headache days of at least moderate severity (quarterly: –3.1, P less than 0.0001; monthly: –3.2, P less than 0.0001) compared with placebo (–0.8). There were similar reductions in the number of migraine days (quarterly: –3.3, P = 0.0015; monthly: –3.7, P less than 0.0001) compared with placebo (–1.3).

“The phase 3 HALO CM and HALO EM trials showed that fremanezumab is efficacious in patients who failed one or more prior preventive medication, a potentially difficult-to-treat population,” Dr. McAllister and colleagues said in their poster.

“Effect sizes in this subgroup were greater than those in the overall trial population,” they said. In addition, “both quarterly and monthly fremanezumab were well-tolerated in this subgroup.”

This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

gwilliams@mdedge.com

SOURCE: McAllister P et al. AAN 2019. P1.10-011.

PHILADELPHIA – Fremanezumab was efficacious in migraine patients who had not benefited from taking other migraine preventive medication, according to a poster presented at the annual meeting of the American Academy of Neurology.

To assess the efficacy of fremanezumab in patients with migraine who had not received relief from trying at least one prior preventive migraine medication, Peter McAllister, MD and colleagues analyzed data from 2 phase 3 trials (HALO EM and HALO CM). Trial participants had either episodic or chronic migraine, confirmed during a 28-day pretreatment baseline period, then received subcutaneous fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), monthly (for chronic migraine: 675 mg at baseline and 225 mg at weeks 4 and 8; for episodic migraine: 225 mg at baseline and weeks 4 and 8), or placebo (at baseline and weeks 4 and 8).

The present analysis included data from 186 patients with episodic migraine and 407 patients with chronic migraine, which represents the subgroup of study participants in the larger HALO trials who had failed at least one prior preventive migraine medication. Dr. McAllister, who is cofounder and chief medical officer at the New England Institute for Clinical Research in Stamford, Connecticut, and his colleagues, assessed mean changes from baseline in the monthly average number of headache days of at least moderate severity or the monthly average number of migraine days during the 12-week treatment period.

In patients with chronic migraine, fremanezumab yielded greater reductions in the number of headache days of at least moderate severity (quarterly [least-squares mean change]: –4.0, P less than 0.0001; monthly: –4.5, P less than 0.0001) compared with placebo (–1.8). There were similar reductions in the number of migraine days (quarterly: –4.1, P = 0.0027; monthly: –4.8, P less than 0.0001) compared with placebo (–2.3).

In patients with episodic migraine, fremanezumab yielded greater reductions in the number of headache days of at least moderate severity (quarterly: –3.1, P less than 0.0001; monthly: –3.2, P less than 0.0001) compared with placebo (–0.8). There were similar reductions in the number of migraine days (quarterly: –3.3, P = 0.0015; monthly: –3.7, P less than 0.0001) compared with placebo (–1.3).

“The phase 3 HALO CM and HALO EM trials showed that fremanezumab is efficacious in patients who failed one or more prior preventive medication, a potentially difficult-to-treat population,” Dr. McAllister and colleagues said in their poster.

“Effect sizes in this subgroup were greater than those in the overall trial population,” they said. In addition, “both quarterly and monthly fremanezumab were well-tolerated in this subgroup.”

This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

gwilliams@mdedge.com

SOURCE: McAllister P et al. AAN 2019. P1.10-011.

PHILADELPHIA – Multiple sclerosis (MS) disease activity may not flare up after pregnancy, according to a study to be presented at the annual meeting of the American Academy of Neurology.

Bonnie Becker/MDedge News

“We did not observe any rebound disease activity,” said Annette Langer-Gould, MD, PhD, and her research colleagues in their report.

The findings contrast with those of 20-year-old studies that first identified a lower risk of relapse during pregnancy but signficant rebound disease activity in the early postpartum period. The initial studies were conducted before disease-modifying treatments (DMTs) were available and before neurologists used MRI to help diagnose MS after one attack, noted Dr. Langer-Gould in a statement.

In the large, contemporary cohort of patients with MS, the annualized relapse rate was 0.39 pre-pregnancy, 0.07-0.14 during pregnancy, 0.27 in the first 3 months postpartum, and 0.37 at 4-6 months postpartum. Exclusive breastfeeding significantly reduced the risk of postpartum relapses by 42% (adjusted hazard ratio = 0.58). Women who supplemented breast milk with formula within 2 months of delivery had the same risk of relapse as women who did not breastfeed, however.

“These results are exciting, as MS is more common among women of childbearing age than in any other group,” said Dr. Langer-Gould, who is regional lead for clinical and translational neuroscience at Kaiser Permanente Southern California in Pasadena, in the statement. “This shows us that women with MS today can have children, breastfeed, and resume their treatment without experiencing an increased risk of relapses during the postpartum period.”

To describe the risk of postpartum relapses and identify potential risk factors for relapse the investigators analyzed prospectively collected data from 466 pregnancies among 375 women with MS from the complete electronic health record at Kaiser Permanente Southern and Northern California between 2008 and 2016. The researchers also used surveys to collect information about treatment history, breastfeeding, and relapses. They used multivariable models to account for intraclass clustering and disease severity.


In 38% of the pregnancies, the mother had not received treatment in the year before conception. In 14.6%, the mother had a clinically isolated syndrome; in 8.4%, the mother had a relapse during pregnancy.

Resuming modestly effective DMTs such as interferon-betas and glatiramer acetate did not affect relapse risk.

In the postpartum year, 26.4% of mothers relapsed, 87% breastfed, 35% breastfed exclusively, and 41.2% resumed using DMT.

The lack of rebound disease activity in this cohort could be related to the high rate of exclusive breastfeeding, as well as the inclusion of women from a population-based setting and the inclusion of women who had incorrectly been diagnosed with MS after a single relapse. Few patients in this cohort had been treated with natalizumab or fingolimod prior to pregnancy, so the study does not address the potential harms of stopping these drugs or the potential benefits of breastfeeding among patients treated with these drugs.

The study was supported by the National Multiple Sclerosis Society. The researchers had no disclosures.

jremaly@mdedge.com

SOURCE: Langer-Gould A et al. AAN 2019, Abstract S6.007.

PHILADELPHIA – Multiple sclerosis (MS) disease activity may not flare up after pregnancy, according to a study to be presented at the annual meeting of the American Academy of Neurology.

Bonnie Becker/MDedge News

“We did not observe any rebound disease activity,” said Annette Langer-Gould, MD, PhD, and her research colleagues in their report.

The findings contrast with those of 20-year-old studies that first identified a lower risk of relapse during pregnancy but signficant rebound disease activity in the early postpartum period. The initial studies were conducted before disease-modifying treatments (DMTs) were available and before neurologists used MRI to help diagnose MS after one attack, noted Dr. Langer-Gould in a statement.

In the large, contemporary cohort of patients with MS, the annualized relapse rate was 0.39 pre-pregnancy, 0.07-0.14 during pregnancy, 0.27 in the first 3 months postpartum, and 0.37 at 4-6 months postpartum. Exclusive breastfeeding significantly reduced the risk of postpartum relapses by 42% (adjusted hazard ratio = 0.58). Women who supplemented breast milk with formula within 2 months of delivery had the same risk of relapse as women who did not breastfeed, however.

“These results are exciting, as MS is more common among women of childbearing age than in any other group,” said Dr. Langer-Gould, who is regional lead for clinical and translational neuroscience at Kaiser Permanente Southern California in Pasadena, in the statement. “This shows us that women with MS today can have children, breastfeed, and resume their treatment without experiencing an increased risk of relapses during the postpartum period.”

To describe the risk of postpartum relapses and identify potential risk factors for relapse the investigators analyzed prospectively collected data from 466 pregnancies among 375 women with MS from the complete electronic health record at Kaiser Permanente Southern and Northern California between 2008 and 2016. The researchers also used surveys to collect information about treatment history, breastfeeding, and relapses. They used multivariable models to account for intraclass clustering and disease severity.


In 38% of the pregnancies, the mother had not received treatment in the year before conception. In 14.6%, the mother had a clinically isolated syndrome; in 8.4%, the mother had a relapse during pregnancy.

Resuming modestly effective DMTs such as interferon-betas and glatiramer acetate did not affect relapse risk.

In the postpartum year, 26.4% of mothers relapsed, 87% breastfed, 35% breastfed exclusively, and 41.2% resumed using DMT.

The lack of rebound disease activity in this cohort could be related to the high rate of exclusive breastfeeding, as well as the inclusion of women from a population-based setting and the inclusion of women who had incorrectly been diagnosed with MS after a single relapse. Few patients in this cohort had been treated with natalizumab or fingolimod prior to pregnancy, so the study does not address the potential harms of stopping these drugs or the potential benefits of breastfeeding among patients treated with these drugs.

The study was supported by the National Multiple Sclerosis Society. The researchers had no disclosures.

jremaly@mdedge.com

SOURCE: Langer-Gould A et al. AAN 2019, Abstract S6.007.

PHILADELPHIA – Multiple sclerosis (MS) disease activity may not flare up after pregnancy, according to a study to be presented at the annual meeting of the American Academy of Neurology.

Bonnie Becker/MDedge News

“We did not observe any rebound disease activity,” said Annette Langer-Gould, MD, PhD, and her research colleagues in their report.

The findings contrast with those of 20-year-old studies that first identified a lower risk of relapse during pregnancy but signficant rebound disease activity in the early postpartum period. The initial studies were conducted before disease-modifying treatments (DMTs) were available and before neurologists used MRI to help diagnose MS after one attack, noted Dr. Langer-Gould in a statement.

In the large, contemporary cohort of patients with MS, the annualized relapse rate was 0.39 pre-pregnancy, 0.07-0.14 during pregnancy, 0.27 in the first 3 months postpartum, and 0.37 at 4-6 months postpartum. Exclusive breastfeeding significantly reduced the risk of postpartum relapses by 42% (adjusted hazard ratio = 0.58). Women who supplemented breast milk with formula within 2 months of delivery had the same risk of relapse as women who did not breastfeed, however.

“These results are exciting, as MS is more common among women of childbearing age than in any other group,” said Dr. Langer-Gould, who is regional lead for clinical and translational neuroscience at Kaiser Permanente Southern California in Pasadena, in the statement. “This shows us that women with MS today can have children, breastfeed, and resume their treatment without experiencing an increased risk of relapses during the postpartum period.”

To describe the risk of postpartum relapses and identify potential risk factors for relapse the investigators analyzed prospectively collected data from 466 pregnancies among 375 women with MS from the complete electronic health record at Kaiser Permanente Southern and Northern California between 2008 and 2016. The researchers also used surveys to collect information about treatment history, breastfeeding, and relapses. They used multivariable models to account for intraclass clustering and disease severity.


In 38% of the pregnancies, the mother had not received treatment in the year before conception. In 14.6%, the mother had a clinically isolated syndrome; in 8.4%, the mother had a relapse during pregnancy.

Resuming modestly effective DMTs such as interferon-betas and glatiramer acetate did not affect relapse risk.

In the postpartum year, 26.4% of mothers relapsed, 87% breastfed, 35% breastfed exclusively, and 41.2% resumed using DMT.

The lack of rebound disease activity in this cohort could be related to the high rate of exclusive breastfeeding, as well as the inclusion of women from a population-based setting and the inclusion of women who had incorrectly been diagnosed with MS after a single relapse. Few patients in this cohort had been treated with natalizumab or fingolimod prior to pregnancy, so the study does not address the potential harms of stopping these drugs or the potential benefits of breastfeeding among patients treated with these drugs.

The study was supported by the National Multiple Sclerosis Society. The researchers had no disclosures.

jremaly@mdedge.com

SOURCE: Langer-Gould A et al. AAN 2019, Abstract S6.007.

PHILADELPHIA - The antihypertensive medication isradipine did not slow progression of disability in patients with early Parkinson’s disease, results of a phase 3 study show. There was no significant difference in Unified Parkinson’s Disease Rating Scale (UPDRS) scores between patients who received the calcium channel blocker isradipine and those who received placebo, according to the final results of the STEADY-PD III study, which will be presented at the annual meeting of the American Academy of Neurology.

Use of the drug to treat high blood pressure has been linked to lower risk of developing Parkinson’s disease, said study author Tanya Simuni, MD, a professor of neurology at Northwestern University, Chicago, in a news release.

“Unfortunately, the people who were taking isradipine did not have any difference in their Parkinson’s symptoms over the 3 years of the study, compared with the people who took a placebo,” Dr. Simuni said in the press release.

Hopes were high that isradipine might be the first drug to slow progression of Parkinson’s disease after promising animal studies and a phase 2 study showing no safety concerns, according to the news release.

The STEADY-PD III study, which was conducted at 54 Parkinson Study Group sites in the United States and Canada, included 336 participants with early Parkinson’s disease randomized to isradipine 10 mg daily or placebo. The median age of patients in the study was 62 years, and 68% were male. The median time from diagnosis was 0.9 years, and the mean UPDRS I-III score at baseline was 23.1, according to an abstract describing the study results.

The primary endpoint was change in UPDRS Part I-III score measured in the ON state from baseline to month 36 of treatment. That change over 36 months was 2.99 points in the isradipine arm and 3.26 points in the placebo arm, for a treatment effect of 0.27 points (95% confidence interval, –2.5 to 3.0; P = 0.85), investigators reported in the abstract. Adjustment for use of symptomatic therapy did not affect the comparison, the researchers noted.

Isradipine had no effect on secondary outcomes, including change in UPDRS-III in the OFF state, use of dopaminergic therapy, motor complications, or quality of life, investigators said in the abstract. Edema was the most notable side effect of isradipine treatment, investigators said.

These findings are “disappointing” but will not deter researchers in their work to find a treatment that will slow Parkinson’s disease progression, Dr. Simuni said in the news release. “Negative results are important because they provide a clear answer, especially for a drug that is commercially available,” she added.

Secondary analyses in progress will explore “biological and clinical correlates of disease progression” among the study participants, researchers said in their study abstract.

The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and also received some funding from The Michael J. Fox Foundation for Parkinson’s Research. Dr. Simuni reported disclosures related to AbbVie, Acadia, Accorda, Adamas, Allergan, Anavex, Biogen, Denali, the Michael J. Fox Foundation, Neurocrine, NeuroDerm, NINDS, the Parkinson Foundation, PhotoPharmics, Revance, Roche, Sanofi, Sunovion, Sun Pharma, Takeda, Teva, Voyager, and US World Meds.

PHILADELPHIA - The antihypertensive medication isradipine did not slow progression of disability in patients with early Parkinson’s disease, results of a phase 3 study show. There was no significant difference in Unified Parkinson’s Disease Rating Scale (UPDRS) scores between patients who received the calcium channel blocker isradipine and those who received placebo, according to the final results of the STEADY-PD III study, which will be presented at the annual meeting of the American Academy of Neurology.

Use of the drug to treat high blood pressure has been linked to lower risk of developing Parkinson’s disease, said study author Tanya Simuni, MD, a professor of neurology at Northwestern University, Chicago, in a news release.

“Unfortunately, the people who were taking isradipine did not have any difference in their Parkinson’s symptoms over the 3 years of the study, compared with the people who took a placebo,” Dr. Simuni said in the press release.

Hopes were high that isradipine might be the first drug to slow progression of Parkinson’s disease after promising animal studies and a phase 2 study showing no safety concerns, according to the news release.

The STEADY-PD III study, which was conducted at 54 Parkinson Study Group sites in the United States and Canada, included 336 participants with early Parkinson’s disease randomized to isradipine 10 mg daily or placebo. The median age of patients in the study was 62 years, and 68% were male. The median time from diagnosis was 0.9 years, and the mean UPDRS I-III score at baseline was 23.1, according to an abstract describing the study results.

The primary endpoint was change in UPDRS Part I-III score measured in the ON state from baseline to month 36 of treatment. That change over 36 months was 2.99 points in the isradipine arm and 3.26 points in the placebo arm, for a treatment effect of 0.27 points (95% confidence interval, –2.5 to 3.0; P = 0.85), investigators reported in the abstract. Adjustment for use of symptomatic therapy did not affect the comparison, the researchers noted.

Isradipine had no effect on secondary outcomes, including change in UPDRS-III in the OFF state, use of dopaminergic therapy, motor complications, or quality of life, investigators said in the abstract. Edema was the most notable side effect of isradipine treatment, investigators said.

These findings are “disappointing” but will not deter researchers in their work to find a treatment that will slow Parkinson’s disease progression, Dr. Simuni said in the news release. “Negative results are important because they provide a clear answer, especially for a drug that is commercially available,” she added.

Secondary analyses in progress will explore “biological and clinical correlates of disease progression” among the study participants, researchers said in their study abstract.

The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and also received some funding from The Michael J. Fox Foundation for Parkinson’s Research. Dr. Simuni reported disclosures related to AbbVie, Acadia, Accorda, Adamas, Allergan, Anavex, Biogen, Denali, the Michael J. Fox Foundation, Neurocrine, NeuroDerm, NINDS, the Parkinson Foundation, PhotoPharmics, Revance, Roche, Sanofi, Sunovion, Sun Pharma, Takeda, Teva, Voyager, and US World Meds.

PHILADELPHIA - The antihypertensive medication isradipine did not slow progression of disability in patients with early Parkinson’s disease, results of a phase 3 study show. There was no significant difference in Unified Parkinson’s Disease Rating Scale (UPDRS) scores between patients who received the calcium channel blocker isradipine and those who received placebo, according to the final results of the STEADY-PD III study, which will be presented at the annual meeting of the American Academy of Neurology.

Use of the drug to treat high blood pressure has been linked to lower risk of developing Parkinson’s disease, said study author Tanya Simuni, MD, a professor of neurology at Northwestern University, Chicago, in a news release.

“Unfortunately, the people who were taking isradipine did not have any difference in their Parkinson’s symptoms over the 3 years of the study, compared with the people who took a placebo,” Dr. Simuni said in the press release.

Hopes were high that isradipine might be the first drug to slow progression of Parkinson’s disease after promising animal studies and a phase 2 study showing no safety concerns, according to the news release.

The STEADY-PD III study, which was conducted at 54 Parkinson Study Group sites in the United States and Canada, included 336 participants with early Parkinson’s disease randomized to isradipine 10 mg daily or placebo. The median age of patients in the study was 62 years, and 68% were male. The median time from diagnosis was 0.9 years, and the mean UPDRS I-III score at baseline was 23.1, according to an abstract describing the study results.

The primary endpoint was change in UPDRS Part I-III score measured in the ON state from baseline to month 36 of treatment. That change over 36 months was 2.99 points in the isradipine arm and 3.26 points in the placebo arm, for a treatment effect of 0.27 points (95% confidence interval, –2.5 to 3.0; P = 0.85), investigators reported in the abstract. Adjustment for use of symptomatic therapy did not affect the comparison, the researchers noted.

Isradipine had no effect on secondary outcomes, including change in UPDRS-III in the OFF state, use of dopaminergic therapy, motor complications, or quality of life, investigators said in the abstract. Edema was the most notable side effect of isradipine treatment, investigators said.

These findings are “disappointing” but will not deter researchers in their work to find a treatment that will slow Parkinson’s disease progression, Dr. Simuni said in the news release. “Negative results are important because they provide a clear answer, especially for a drug that is commercially available,” she added.

Secondary analyses in progress will explore “biological and clinical correlates of disease progression” among the study participants, researchers said in their study abstract.

The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and also received some funding from The Michael J. Fox Foundation for Parkinson’s Research. Dr. Simuni reported disclosures related to AbbVie, Acadia, Accorda, Adamas, Allergan, Anavex, Biogen, Denali, the Michael J. Fox Foundation, Neurocrine, NeuroDerm, NINDS, the Parkinson Foundation, PhotoPharmics, Revance, Roche, Sanofi, Sunovion, Sun Pharma, Takeda, Teva, Voyager, and US World Meds.

PHILADELPHIA - A once-daily dose of opicapone, a catechol-O-methyltransferase (COMT) inhibitor, added to levodopa was associated with improvements of up to 2 hours in on-time without dyskinesia in patients with Parkinson’s disease and motor fluctuations, according to an analysis of two pivotal studies and their respective 1-year extension studies.

The 2-hour improvement was considered clinically meaningful, although the average patient in the studies had about 6 hours of off-time, said investigator Peter LeWitt, MD, of Henry Ford Hospital in West Bloomfield, Mich., and the department of neurology at Wayne State University, Detroit. Dr. LeWitt and colleagues will present the data at the annual meeting of the American Academy of Neurology.

“While this is a substantial improvement, it is 2 hours improvement over a total of 6 hours of off-time, which is not perfect,” Dr. LeWitt said in an interview. “So how could we do better is the challenge for all of us who are doing research.”

Opicapone is under development in the United States; it is currently approved in the European Union as adjunctive therapy to preparations of levodopa/DOPA decarboxylase inhibitors for patients with Parkinson’s disease and end-of-dose motor fluctuations.

The ability of opicapone to prolong the clinical actions of levodopa has been evaluated in BIPARK-1 and BIPARK-2. These two international phase 3 studies evaluated the third-generation COMT inhibitor against placebo and, in the case of BIPARK-1, against the COMT inhibitor entacapone as an active control. Each study was 14-15 weeks in duration and included a 1-year open-label phase.

In BIPARK-1, on-time without troublesome dyskinesia was significantly increased for opicapone 50 mg versus placebo, with an absolute increase of 1.9 versus 0.9 hours, respectively, from baseline to week 14 or 15 (P = .002), investigators said. Similarly, BIPARK-2 data showed an increase in this endpoint, at 1.7 versus 0.9 hours for opicapone and placebo, respectively (P = .025).

The 50-mg dose of opicapone was received by 115 patients in BIPARK-1 and 147 patients in BIPARK-2, while placebo was received by 120 and 135 patients in those two studies, respectively.

In the long-term extension studies, the mean change in on-time without dyskinesia from baseline to the end of the open-label endpoint was 2.0 hours for all 494 opicapone-treated patients in BIPARK-1 and 1.8 hours for all 339 opicapone-treated patients in BIPARK-2.

Dyskinesia was reported as a treatment-emergent adverse effect for 17.4% of opicapone-treated patients and 6.2% of placebo-treated patients, according to results of a pooled safety analysis of BIPARK-1 and BIPARK-2. However, only 1.9% of opicapone-treated patients and 0.4% of placebo-treated patients had treatment-emergent dyskinesia leading to discontinuation, and the dyskinesia was considered serious in 0.3% of the opicapone group and 0.0% of the placebo group, investigators added.

Neurocrine Biosciences has announced plans to file a New Drug Application for opicapone for Parkinson’s disease in the United States. That filing is expected to take place in the second quarter of 2019, according to an April 29 press release.

Dr. LeWitt disclosed that he has served as an advisor to Neurocrine Biosciences. He also provided disclosures related to Acadia, Acorda, Adamas, BioElectron Technology, Biotie, Britannia, Intec, Jazz Pharmaceuticals, Lundbeck, the Michael J. Fox Foundation for Parkinson’s Research, Merz, NeuroDerm, the Parkinson Study Group, Pfizer, Prexton, Sage, Scion, Sunovion, SynAgile, and US WorldMeds.

SOURCE: LeWitt P et al. AAN 2019, Abstract S4.003.

PHILADELPHIA - A once-daily dose of opicapone, a catechol-O-methyltransferase (COMT) inhibitor, added to levodopa was associated with improvements of up to 2 hours in on-time without dyskinesia in patients with Parkinson’s disease and motor fluctuations, according to an analysis of two pivotal studies and their respective 1-year extension studies.

The 2-hour improvement was considered clinically meaningful, although the average patient in the studies had about 6 hours of off-time, said investigator Peter LeWitt, MD, of Henry Ford Hospital in West Bloomfield, Mich., and the department of neurology at Wayne State University, Detroit. Dr. LeWitt and colleagues will present the data at the annual meeting of the American Academy of Neurology.

“While this is a substantial improvement, it is 2 hours improvement over a total of 6 hours of off-time, which is not perfect,” Dr. LeWitt said in an interview. “So how could we do better is the challenge for all of us who are doing research.”

Opicapone is under development in the United States; it is currently approved in the European Union as adjunctive therapy to preparations of levodopa/DOPA decarboxylase inhibitors for patients with Parkinson’s disease and end-of-dose motor fluctuations.

The ability of opicapone to prolong the clinical actions of levodopa has been evaluated in BIPARK-1 and BIPARK-2. These two international phase 3 studies evaluated the third-generation COMT inhibitor against placebo and, in the case of BIPARK-1, against the COMT inhibitor entacapone as an active control. Each study was 14-15 weeks in duration and included a 1-year open-label phase.

In BIPARK-1, on-time without troublesome dyskinesia was significantly increased for opicapone 50 mg versus placebo, with an absolute increase of 1.9 versus 0.9 hours, respectively, from baseline to week 14 or 15 (P = .002), investigators said. Similarly, BIPARK-2 data showed an increase in this endpoint, at 1.7 versus 0.9 hours for opicapone and placebo, respectively (P = .025).

The 50-mg dose of opicapone was received by 115 patients in BIPARK-1 and 147 patients in BIPARK-2, while placebo was received by 120 and 135 patients in those two studies, respectively.

In the long-term extension studies, the mean change in on-time without dyskinesia from baseline to the end of the open-label endpoint was 2.0 hours for all 494 opicapone-treated patients in BIPARK-1 and 1.8 hours for all 339 opicapone-treated patients in BIPARK-2.

Dyskinesia was reported as a treatment-emergent adverse effect for 17.4% of opicapone-treated patients and 6.2% of placebo-treated patients, according to results of a pooled safety analysis of BIPARK-1 and BIPARK-2. However, only 1.9% of opicapone-treated patients and 0.4% of placebo-treated patients had treatment-emergent dyskinesia leading to discontinuation, and the dyskinesia was considered serious in 0.3% of the opicapone group and 0.0% of the placebo group, investigators added.

Neurocrine Biosciences has announced plans to file a New Drug Application for opicapone for Parkinson’s disease in the United States. That filing is expected to take place in the second quarter of 2019, according to an April 29 press release.

Dr. LeWitt disclosed that he has served as an advisor to Neurocrine Biosciences. He also provided disclosures related to Acadia, Acorda, Adamas, BioElectron Technology, Biotie, Britannia, Intec, Jazz Pharmaceuticals, Lundbeck, the Michael J. Fox Foundation for Parkinson’s Research, Merz, NeuroDerm, the Parkinson Study Group, Pfizer, Prexton, Sage, Scion, Sunovion, SynAgile, and US WorldMeds.

SOURCE: LeWitt P et al. AAN 2019, Abstract S4.003.

PHILADELPHIA - A once-daily dose of opicapone, a catechol-O-methyltransferase (COMT) inhibitor, added to levodopa was associated with improvements of up to 2 hours in on-time without dyskinesia in patients with Parkinson’s disease and motor fluctuations, according to an analysis of two pivotal studies and their respective 1-year extension studies.

The 2-hour improvement was considered clinically meaningful, although the average patient in the studies had about 6 hours of off-time, said investigator Peter LeWitt, MD, of Henry Ford Hospital in West Bloomfield, Mich., and the department of neurology at Wayne State University, Detroit. Dr. LeWitt and colleagues will present the data at the annual meeting of the American Academy of Neurology.

“While this is a substantial improvement, it is 2 hours improvement over a total of 6 hours of off-time, which is not perfect,” Dr. LeWitt said in an interview. “So how could we do better is the challenge for all of us who are doing research.”

Opicapone is under development in the United States; it is currently approved in the European Union as adjunctive therapy to preparations of levodopa/DOPA decarboxylase inhibitors for patients with Parkinson’s disease and end-of-dose motor fluctuations.

The ability of opicapone to prolong the clinical actions of levodopa has been evaluated in BIPARK-1 and BIPARK-2. These two international phase 3 studies evaluated the third-generation COMT inhibitor against placebo and, in the case of BIPARK-1, against the COMT inhibitor entacapone as an active control. Each study was 14-15 weeks in duration and included a 1-year open-label phase.

In BIPARK-1, on-time without troublesome dyskinesia was significantly increased for opicapone 50 mg versus placebo, with an absolute increase of 1.9 versus 0.9 hours, respectively, from baseline to week 14 or 15 (P = .002), investigators said. Similarly, BIPARK-2 data showed an increase in this endpoint, at 1.7 versus 0.9 hours for opicapone and placebo, respectively (P = .025).

The 50-mg dose of opicapone was received by 115 patients in BIPARK-1 and 147 patients in BIPARK-2, while placebo was received by 120 and 135 patients in those two studies, respectively.

In the long-term extension studies, the mean change in on-time without dyskinesia from baseline to the end of the open-label endpoint was 2.0 hours for all 494 opicapone-treated patients in BIPARK-1 and 1.8 hours for all 339 opicapone-treated patients in BIPARK-2.

Dyskinesia was reported as a treatment-emergent adverse effect for 17.4% of opicapone-treated patients and 6.2% of placebo-treated patients, according to results of a pooled safety analysis of BIPARK-1 and BIPARK-2. However, only 1.9% of opicapone-treated patients and 0.4% of placebo-treated patients had treatment-emergent dyskinesia leading to discontinuation, and the dyskinesia was considered serious in 0.3% of the opicapone group and 0.0% of the placebo group, investigators added.

Neurocrine Biosciences has announced plans to file a New Drug Application for opicapone for Parkinson’s disease in the United States. That filing is expected to take place in the second quarter of 2019, according to an April 29 press release.

Dr. LeWitt disclosed that he has served as an advisor to Neurocrine Biosciences. He also provided disclosures related to Acadia, Acorda, Adamas, BioElectron Technology, Biotie, Britannia, Intec, Jazz Pharmaceuticals, Lundbeck, the Michael J. Fox Foundation for Parkinson’s Research, Merz, NeuroDerm, the Parkinson Study Group, Pfizer, Prexton, Sage, Scion, Sunovion, SynAgile, and US WorldMeds.

SOURCE: LeWitt P et al. AAN 2019, Abstract S4.003.

PHILADELPHIA – Witnessed apneas during sleep are associated with increased tau accumulation in the entorhinal cortex, according to data that will be presented at the annual meeting of the American Academy of Neurology. Tau accumulation is a biomarker of Alzheimer’s disease, and the finding suggests a possible explanation for the apparent association between sleep disruption and dementia.

“Our research results raise the possibility that sleep apnea affects tau accumulation,” said Diego Z. Carvalho, MD, of the Mayo Clinic in Rochester, Minn., in a press release. “But it is also possible that higher levels of tau in other regions may predispose a person to sleep apnea, so longer studies are now needed to solve this chicken-and-egg problem.”

Previous research had suggested an association between sleep disruption and increased risk of dementia. Obstructive sleep apnea in particular has been associated with this increased risk. The pathological processes that account for this association are unknown, however.

Dr. Carvalho and colleagues decided to evaluate whether apneas during sleep, reported by the patient or an informant, were associated with high levels of tau in cognitively normal elderly individuals. The investigators identified 288 participants in the Mayo Clinic Study of Aging for their analysis. Eligible participants were aged 65 years or older, had no cognitive impairment, had undergone tau PET and amyloid PET scans, and had completed a questionnaire that solicited information about witnessed apneas during sleep (either from patients or bed partners). Dr. Carvalho’s group took the entorhinal cortex as its region of interest because it is highly susceptible to tau accumulation. The entorhinal cortex is involved in memory, navigation, and the perception of time. They chose the cerebellum crus as their reference region.

The investigators created a linear model to evaluate the association between tau in the entorhinal cortex and witnessed apneas. They controlled the data for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global amyloid.

In all, 43 participants (15%) had witnessed apneas during sleep. Witnessed apneas were significantly associated with tau in the entorhinal cortex. After controlling for potential confounders, Dr. Carvalho and colleagues estimated a 0.049 elevation in the entorhinal cortex tau standardized uptake value ratio (95% confidence interval, 0.011–0.087; P = 0.012).

The study had a relatively small sample size, and its results require validation. Other important limitations include the absence of sleep studies to confirm the presence and severity of sleep apnea and a lack of information about whether participants already were receiving treatment for sleep apnea.

The National Institutes of Health supported the study.
 

egreb@mdedge.com

SOURCE: Carvalho D et al. AAN 2019, Abstract P3.6-021.

PHILADELPHIA – Witnessed apneas during sleep are associated with increased tau accumulation in the entorhinal cortex, according to data that will be presented at the annual meeting of the American Academy of Neurology. Tau accumulation is a biomarker of Alzheimer’s disease, and the finding suggests a possible explanation for the apparent association between sleep disruption and dementia.

“Our research results raise the possibility that sleep apnea affects tau accumulation,” said Diego Z. Carvalho, MD, of the Mayo Clinic in Rochester, Minn., in a press release. “But it is also possible that higher levels of tau in other regions may predispose a person to sleep apnea, so longer studies are now needed to solve this chicken-and-egg problem.”

Previous research had suggested an association between sleep disruption and increased risk of dementia. Obstructive sleep apnea in particular has been associated with this increased risk. The pathological processes that account for this association are unknown, however.

Dr. Carvalho and colleagues decided to evaluate whether apneas during sleep, reported by the patient or an informant, were associated with high levels of tau in cognitively normal elderly individuals. The investigators identified 288 participants in the Mayo Clinic Study of Aging for their analysis. Eligible participants were aged 65 years or older, had no cognitive impairment, had undergone tau PET and amyloid PET scans, and had completed a questionnaire that solicited information about witnessed apneas during sleep (either from patients or bed partners). Dr. Carvalho’s group took the entorhinal cortex as its region of interest because it is highly susceptible to tau accumulation. The entorhinal cortex is involved in memory, navigation, and the perception of time. They chose the cerebellum crus as their reference region.

The investigators created a linear model to evaluate the association between tau in the entorhinal cortex and witnessed apneas. They controlled the data for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global amyloid.

In all, 43 participants (15%) had witnessed apneas during sleep. Witnessed apneas were significantly associated with tau in the entorhinal cortex. After controlling for potential confounders, Dr. Carvalho and colleagues estimated a 0.049 elevation in the entorhinal cortex tau standardized uptake value ratio (95% confidence interval, 0.011–0.087; P = 0.012).

The study had a relatively small sample size, and its results require validation. Other important limitations include the absence of sleep studies to confirm the presence and severity of sleep apnea and a lack of information about whether participants already were receiving treatment for sleep apnea.

The National Institutes of Health supported the study.
 

egreb@mdedge.com

SOURCE: Carvalho D et al. AAN 2019, Abstract P3.6-021.

PHILADELPHIA – Witnessed apneas during sleep are associated with increased tau accumulation in the entorhinal cortex, according to data that will be presented at the annual meeting of the American Academy of Neurology. Tau accumulation is a biomarker of Alzheimer’s disease, and the finding suggests a possible explanation for the apparent association between sleep disruption and dementia.

“Our research results raise the possibility that sleep apnea affects tau accumulation,” said Diego Z. Carvalho, MD, of the Mayo Clinic in Rochester, Minn., in a press release. “But it is also possible that higher levels of tau in other regions may predispose a person to sleep apnea, so longer studies are now needed to solve this chicken-and-egg problem.”

Previous research had suggested an association between sleep disruption and increased risk of dementia. Obstructive sleep apnea in particular has been associated with this increased risk. The pathological processes that account for this association are unknown, however.

Dr. Carvalho and colleagues decided to evaluate whether apneas during sleep, reported by the patient or an informant, were associated with high levels of tau in cognitively normal elderly individuals. The investigators identified 288 participants in the Mayo Clinic Study of Aging for their analysis. Eligible participants were aged 65 years or older, had no cognitive impairment, had undergone tau PET and amyloid PET scans, and had completed a questionnaire that solicited information about witnessed apneas during sleep (either from patients or bed partners). Dr. Carvalho’s group took the entorhinal cortex as its region of interest because it is highly susceptible to tau accumulation. The entorhinal cortex is involved in memory, navigation, and the perception of time. They chose the cerebellum crus as their reference region.

The investigators created a linear model to evaluate the association between tau in the entorhinal cortex and witnessed apneas. They controlled the data for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global amyloid.

In all, 43 participants (15%) had witnessed apneas during sleep. Witnessed apneas were significantly associated with tau in the entorhinal cortex. After controlling for potential confounders, Dr. Carvalho and colleagues estimated a 0.049 elevation in the entorhinal cortex tau standardized uptake value ratio (95% confidence interval, 0.011–0.087; P = 0.012).

The study had a relatively small sample size, and its results require validation. Other important limitations include the absence of sleep studies to confirm the presence and severity of sleep apnea and a lack of information about whether participants already were receiving treatment for sleep apnea.

The National Institutes of Health supported the study.
 

egreb@mdedge.com

SOURCE: Carvalho D et al. AAN 2019, Abstract P3.6-021.

Medical cannabis is safe, effective, and may reduce opioid use in elderly patients with chronic medical conditions, results of a recent retrospective chart review suggest. Treatment with medical cannabis improved pain, sleep, anxiety, and neuropathy in patients aged 75 years of age and older, and was associated with reduced use of opioids in about one-third of cases, according to authors of the study, which will be presented at the annual meeting of the American Academy of Neurology.

LPETTET/Getty Images

“Our findings are promising and can help fuel further research into medical marijuana as an additional option for this group of people who often have chronic conditions,” said lead investigator Laszlo Mechtler, MD, of Dent Neurologic Institute in Buffalo, N.Y., in a news release. However, additional randomized, placebo-controlled studies are needed to confirm results of this study, Dr. Mechtler added.

The chart review focused on 204 elderly patients who participated in New York State’s medical marijuana program and were followed in a neurologic outpatient setting. The cohort included 129 female and 75 male patients, ranging in age from 75 to 102 years, with a mean age of 81 years. The medical marijuana was taken by mouth as a liquid extract tincture, capsule, or in an electronic vaporizer.

With an average exposure time of 16.8 weeks, 69% of patients experienced symptomatic benefit, according to patient self-report. The most commonly reported benefit was relief of chronic pain in 49%, while improvements in sleep, neuropathy, and anxiety were reported in 18%, 15%, and 10%, respectively. Reductions in opioid pain medication were noted in about one-third of cases, they found.

While 34% of patients had adverse effects on medical marijuana, only 21% reported adverse effects after cannabinoid doses were adjusted, investigators said. Adverse effects led to discontinuation of medical cannabis in seven patients, or 3.4% of the overall cohort. Somnolence, disequilibrium, and gastrointestinal disturbance were the most common adverse effects, occurring in 13%, 7%, and 7% of patients, respectively. Euphoria was reported in 3% of patients.

Among patients who had no reported adverse effects, the most commonly used formulation was a balanced 1:1 tincture of tetrahydrocannabinol to cannabidiol, investigators said.

Further trials could explore optimal dosing of medical cannabis in elderly patients and shed more light on adverse effects such as somnolence and disequilibrium, according to Dr. Mechtler and colleagues.

The study was supported by the Dent Family Foundation.

SOURCE: Bargnes V et al. AAN 2019, Abstract P4.1-014.

Medical cannabis is safe, effective, and may reduce opioid use in elderly patients with chronic medical conditions, results of a recent retrospective chart review suggest. Treatment with medical cannabis improved pain, sleep, anxiety, and neuropathy in patients aged 75 years of age and older, and was associated with reduced use of opioids in about one-third of cases, according to authors of the study, which will be presented at the annual meeting of the American Academy of Neurology.

LPETTET/Getty Images

“Our findings are promising and can help fuel further research into medical marijuana as an additional option for this group of people who often have chronic conditions,” said lead investigator Laszlo Mechtler, MD, of Dent Neurologic Institute in Buffalo, N.Y., in a news release. However, additional randomized, placebo-controlled studies are needed to confirm results of this study, Dr. Mechtler added.

The chart review focused on 204 elderly patients who participated in New York State’s medical marijuana program and were followed in a neurologic outpatient setting. The cohort included 129 female and 75 male patients, ranging in age from 75 to 102 years, with a mean age of 81 years. The medical marijuana was taken by mouth as a liquid extract tincture, capsule, or in an electronic vaporizer.

With an average exposure time of 16.8 weeks, 69% of patients experienced symptomatic benefit, according to patient self-report. The most commonly reported benefit was relief of chronic pain in 49%, while improvements in sleep, neuropathy, and anxiety were reported in 18%, 15%, and 10%, respectively. Reductions in opioid pain medication were noted in about one-third of cases, they found.

While 34% of patients had adverse effects on medical marijuana, only 21% reported adverse effects after cannabinoid doses were adjusted, investigators said. Adverse effects led to discontinuation of medical cannabis in seven patients, or 3.4% of the overall cohort. Somnolence, disequilibrium, and gastrointestinal disturbance were the most common adverse effects, occurring in 13%, 7%, and 7% of patients, respectively. Euphoria was reported in 3% of patients.

Among patients who had no reported adverse effects, the most commonly used formulation was a balanced 1:1 tincture of tetrahydrocannabinol to cannabidiol, investigators said.

Further trials could explore optimal dosing of medical cannabis in elderly patients and shed more light on adverse effects such as somnolence and disequilibrium, according to Dr. Mechtler and colleagues.

The study was supported by the Dent Family Foundation.

SOURCE: Bargnes V et al. AAN 2019, Abstract P4.1-014.

Medical cannabis is safe, effective, and may reduce opioid use in elderly patients with chronic medical conditions, results of a recent retrospective chart review suggest. Treatment with medical cannabis improved pain, sleep, anxiety, and neuropathy in patients aged 75 years of age and older, and was associated with reduced use of opioids in about one-third of cases, according to authors of the study, which will be presented at the annual meeting of the American Academy of Neurology.

LPETTET/Getty Images

“Our findings are promising and can help fuel further research into medical marijuana as an additional option for this group of people who often have chronic conditions,” said lead investigator Laszlo Mechtler, MD, of Dent Neurologic Institute in Buffalo, N.Y., in a news release. However, additional randomized, placebo-controlled studies are needed to confirm results of this study, Dr. Mechtler added.

The chart review focused on 204 elderly patients who participated in New York State’s medical marijuana program and were followed in a neurologic outpatient setting. The cohort included 129 female and 75 male patients, ranging in age from 75 to 102 years, with a mean age of 81 years. The medical marijuana was taken by mouth as a liquid extract tincture, capsule, or in an electronic vaporizer.

With an average exposure time of 16.8 weeks, 69% of patients experienced symptomatic benefit, according to patient self-report. The most commonly reported benefit was relief of chronic pain in 49%, while improvements in sleep, neuropathy, and anxiety were reported in 18%, 15%, and 10%, respectively. Reductions in opioid pain medication were noted in about one-third of cases, they found.

While 34% of patients had adverse effects on medical marijuana, only 21% reported adverse effects after cannabinoid doses were adjusted, investigators said. Adverse effects led to discontinuation of medical cannabis in seven patients, or 3.4% of the overall cohort. Somnolence, disequilibrium, and gastrointestinal disturbance were the most common adverse effects, occurring in 13%, 7%, and 7% of patients, respectively. Euphoria was reported in 3% of patients.

Among patients who had no reported adverse effects, the most commonly used formulation was a balanced 1:1 tincture of tetrahydrocannabinol to cannabidiol, investigators said.

Further trials could explore optimal dosing of medical cannabis in elderly patients and shed more light on adverse effects such as somnolence and disequilibrium, according to Dr. Mechtler and colleagues.

The study was supported by the Dent Family Foundation.

SOURCE: Bargnes V et al. AAN 2019, Abstract P4.1-014.