Neurology

PHILADELPHIA – Adults with focal epilepsy report a range of high-disturbance symptoms and disease-related impacts on their daily lives at different disease stages, illustrating the complexity of the disease from the patient perspective, said Jacqueline French, MD, a professor at the Comprehensive Epilepsy Center at New York University.

“This underscores the need to consider these experiences, and potentially the stage of disease, when developing patient-reported outcome measures,” she said at the annual meeting of the American Academy of Neurology.

To describe the patient’s experience of living with epilepsy, including the occurrence of disease-related signs and symptoms and impact on daily life at different disease stages, Dr. French conducted qualitative, semistructured interviews with adults with focal epilepsy at the following stages: early (1 year or less since diagnosis), middle (1-5 years since diagnosis), and late (more than 5 years since diagnosis). The patients had varying seizure frequency and treatment experiences. They were asked to describe the symptoms and functional impact they had experienced related to epilepsy, and then to rate the degree to which each symptom and impact “bothered” them, using a disturbance rating scale from 0 (not at all) to 10 (extremely).

A total of 62 patients who were aged 18-60 years (mean age, 37 years; 73% female) were interviewed. In all, 19 of the patients had early-stage disease, 17 had middle-stage, and 26 had late-stage disease. Symptoms reported with the highest frequency and highest average disturbance (AD) ratings across all cohorts included twitching/tremors (80% of patients; AD, 5.3), confusion (78%; AD, 7.8), difficulty talking (75%; AD, 8.1), impaired/loss of consciousness (70%; AD, 6.8), stiffening (65%; AD, 5.4), déjà vu (62%; AD, 5.1), difficulty remembering (60%; AD, 8.5), and dizziness/light-headedness (58%; AD, 6.4).

The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (74%; AD, 7.1), limited ability to work and/or go to school (61%; AD, 6.7), limitations on leisure and social activities (58%; AD, 6.3), and memory loss (47%; AD, 8.4).

Dr French noted that, although disease experiences were similar among the cohorts, some heterogeneity across patient subgroups was observed.

Eisai sponsored the study.

gwilliams@mdedge.com

PHILADELPHIA – Adults with focal epilepsy report a range of high-disturbance symptoms and disease-related impacts on their daily lives at different disease stages, illustrating the complexity of the disease from the patient perspective, said Jacqueline French, MD, a professor at the Comprehensive Epilepsy Center at New York University.

“This underscores the need to consider these experiences, and potentially the stage of disease, when developing patient-reported outcome measures,” she said at the annual meeting of the American Academy of Neurology.

To describe the patient’s experience of living with epilepsy, including the occurrence of disease-related signs and symptoms and impact on daily life at different disease stages, Dr. French conducted qualitative, semistructured interviews with adults with focal epilepsy at the following stages: early (1 year or less since diagnosis), middle (1-5 years since diagnosis), and late (more than 5 years since diagnosis). The patients had varying seizure frequency and treatment experiences. They were asked to describe the symptoms and functional impact they had experienced related to epilepsy, and then to rate the degree to which each symptom and impact “bothered” them, using a disturbance rating scale from 0 (not at all) to 10 (extremely).

A total of 62 patients who were aged 18-60 years (mean age, 37 years; 73% female) were interviewed. In all, 19 of the patients had early-stage disease, 17 had middle-stage, and 26 had late-stage disease. Symptoms reported with the highest frequency and highest average disturbance (AD) ratings across all cohorts included twitching/tremors (80% of patients; AD, 5.3), confusion (78%; AD, 7.8), difficulty talking (75%; AD, 8.1), impaired/loss of consciousness (70%; AD, 6.8), stiffening (65%; AD, 5.4), déjà vu (62%; AD, 5.1), difficulty remembering (60%; AD, 8.5), and dizziness/light-headedness (58%; AD, 6.4).

The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (74%; AD, 7.1), limited ability to work and/or go to school (61%; AD, 6.7), limitations on leisure and social activities (58%; AD, 6.3), and memory loss (47%; AD, 8.4).

Dr French noted that, although disease experiences were similar among the cohorts, some heterogeneity across patient subgroups was observed.

Eisai sponsored the study.

gwilliams@mdedge.com

PHILADELPHIA – Adults with focal epilepsy report a range of high-disturbance symptoms and disease-related impacts on their daily lives at different disease stages, illustrating the complexity of the disease from the patient perspective, said Jacqueline French, MD, a professor at the Comprehensive Epilepsy Center at New York University.

“This underscores the need to consider these experiences, and potentially the stage of disease, when developing patient-reported outcome measures,” she said at the annual meeting of the American Academy of Neurology.

To describe the patient’s experience of living with epilepsy, including the occurrence of disease-related signs and symptoms and impact on daily life at different disease stages, Dr. French conducted qualitative, semistructured interviews with adults with focal epilepsy at the following stages: early (1 year or less since diagnosis), middle (1-5 years since diagnosis), and late (more than 5 years since diagnosis). The patients had varying seizure frequency and treatment experiences. They were asked to describe the symptoms and functional impact they had experienced related to epilepsy, and then to rate the degree to which each symptom and impact “bothered” them, using a disturbance rating scale from 0 (not at all) to 10 (extremely).

A total of 62 patients who were aged 18-60 years (mean age, 37 years; 73% female) were interviewed. In all, 19 of the patients had early-stage disease, 17 had middle-stage, and 26 had late-stage disease. Symptoms reported with the highest frequency and highest average disturbance (AD) ratings across all cohorts included twitching/tremors (80% of patients; AD, 5.3), confusion (78%; AD, 7.8), difficulty talking (75%; AD, 8.1), impaired/loss of consciousness (70%; AD, 6.8), stiffening (65%; AD, 5.4), déjà vu (62%; AD, 5.1), difficulty remembering (60%; AD, 8.5), and dizziness/light-headedness (58%; AD, 6.4).

The high-frequency/high-disturbance daily impact of epilepsy included the inability to drive (74%; AD, 7.1), limited ability to work and/or go to school (61%; AD, 6.7), limitations on leisure and social activities (58%; AD, 6.3), and memory loss (47%; AD, 8.4).

Dr French noted that, although disease experiences were similar among the cohorts, some heterogeneity across patient subgroups was observed.

Eisai sponsored the study.

gwilliams@mdedge.com

PHILADELPHIA – Physical activity is associated with slower cognitive decline in de novo patients with Parkinson’s disease, according to Sneha Mantri, MD, of Duke University in Durham, N.C., and colleagues, who presented the results of their study at the annual meeting of the American Academy of Neurology.

Physical activity is an important component of the management of Parkinson’s disease and is shown to mitigate cognitive decline among patients with moderate disease, said Dr. Mantri and colleagues. “Exercise levels in de novo and early disease may influence risk of future cognitive decline; early disease also presents an opportunity for early intervention and possible disease modification,” Dr. Mantri said.

Physical activity levels in early disease are known to be low, but the effects of activity on cognition are currently unclear. To assess the relationship between physical activity and cognition, Dr. Mantri and colleagues examined patients with Parkinson’s disease who were enrolled in the prospective Parkinson’s Progression Markers Initiative (PPMI) cohort. At annual study visits, participants completed the Physical Activity Scale for the Elderly (PASE), a validated self-reported questionnaire assessing household, leisure, and work activities over the previous 7 days. The researchers used a linear mixed-effects model to compare rates of change in the Montreal Cognitive Assessment (MoCA) according to PASE scores; covariates included age, sex, Unified Parkinson’s Disease Rating Scale (UPDRS) part III score, and baseline MoCA.

A total of 379 patients completed at least one PASE questionnaire over the course of the study. PASE scores in this cohort have been previously described (Mantri S et al. J Park Dis. 2018;8[1]:107-11). Although overall rates of cognitive decline are known to be modest in this early cohort, PASE over time has a significant effect on MoCA during follow-up (P = 0.02) which suggest that higher levels of activity throughout disease are associated with better cognitive performance.
 

Dr. Mantri had nothing to disclose. Among her coauthors, Dr. Tropea received personal compensation from Genzyme and Medtronics and research support from Sanofi. Dr. Morley had nothing to disclose.

gwilliams@mdedge.com

SOURCE: Mantri S et al. AAN 2019, Abstract P2.8-021.

PHILADELPHIA – Physical activity is associated with slower cognitive decline in de novo patients with Parkinson’s disease, according to Sneha Mantri, MD, of Duke University in Durham, N.C., and colleagues, who presented the results of their study at the annual meeting of the American Academy of Neurology.

Physical activity is an important component of the management of Parkinson’s disease and is shown to mitigate cognitive decline among patients with moderate disease, said Dr. Mantri and colleagues. “Exercise levels in de novo and early disease may influence risk of future cognitive decline; early disease also presents an opportunity for early intervention and possible disease modification,” Dr. Mantri said.

Physical activity levels in early disease are known to be low, but the effects of activity on cognition are currently unclear. To assess the relationship between physical activity and cognition, Dr. Mantri and colleagues examined patients with Parkinson’s disease who were enrolled in the prospective Parkinson’s Progression Markers Initiative (PPMI) cohort. At annual study visits, participants completed the Physical Activity Scale for the Elderly (PASE), a validated self-reported questionnaire assessing household, leisure, and work activities over the previous 7 days. The researchers used a linear mixed-effects model to compare rates of change in the Montreal Cognitive Assessment (MoCA) according to PASE scores; covariates included age, sex, Unified Parkinson’s Disease Rating Scale (UPDRS) part III score, and baseline MoCA.

A total of 379 patients completed at least one PASE questionnaire over the course of the study. PASE scores in this cohort have been previously described (Mantri S et al. J Park Dis. 2018;8[1]:107-11). Although overall rates of cognitive decline are known to be modest in this early cohort, PASE over time has a significant effect on MoCA during follow-up (P = 0.02) which suggest that higher levels of activity throughout disease are associated with better cognitive performance.
 

Dr. Mantri had nothing to disclose. Among her coauthors, Dr. Tropea received personal compensation from Genzyme and Medtronics and research support from Sanofi. Dr. Morley had nothing to disclose.

gwilliams@mdedge.com

SOURCE: Mantri S et al. AAN 2019, Abstract P2.8-021.

PHILADELPHIA – Physical activity is associated with slower cognitive decline in de novo patients with Parkinson’s disease, according to Sneha Mantri, MD, of Duke University in Durham, N.C., and colleagues, who presented the results of their study at the annual meeting of the American Academy of Neurology.

Physical activity is an important component of the management of Parkinson’s disease and is shown to mitigate cognitive decline among patients with moderate disease, said Dr. Mantri and colleagues. “Exercise levels in de novo and early disease may influence risk of future cognitive decline; early disease also presents an opportunity for early intervention and possible disease modification,” Dr. Mantri said.

Physical activity levels in early disease are known to be low, but the effects of activity on cognition are currently unclear. To assess the relationship between physical activity and cognition, Dr. Mantri and colleagues examined patients with Parkinson’s disease who were enrolled in the prospective Parkinson’s Progression Markers Initiative (PPMI) cohort. At annual study visits, participants completed the Physical Activity Scale for the Elderly (PASE), a validated self-reported questionnaire assessing household, leisure, and work activities over the previous 7 days. The researchers used a linear mixed-effects model to compare rates of change in the Montreal Cognitive Assessment (MoCA) according to PASE scores; covariates included age, sex, Unified Parkinson’s Disease Rating Scale (UPDRS) part III score, and baseline MoCA.

A total of 379 patients completed at least one PASE questionnaire over the course of the study. PASE scores in this cohort have been previously described (Mantri S et al. J Park Dis. 2018;8[1]:107-11). Although overall rates of cognitive decline are known to be modest in this early cohort, PASE over time has a significant effect on MoCA during follow-up (P = 0.02) which suggest that higher levels of activity throughout disease are associated with better cognitive performance.
 

Dr. Mantri had nothing to disclose. Among her coauthors, Dr. Tropea received personal compensation from Genzyme and Medtronics and research support from Sanofi. Dr. Morley had nothing to disclose.

gwilliams@mdedge.com

SOURCE: Mantri S et al. AAN 2019, Abstract P2.8-021.

Philadelphia – Adjunctive cannabidiol (CBD) reduces seizure frequency in patients with Dravet syndrome, according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.

“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”

Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.

The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.

Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.


The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.

The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.

“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.

GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.

egreb@mdedge.com

SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.

Philadelphia – Adjunctive cannabidiol (CBD) reduces seizure frequency in patients with Dravet syndrome, according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.

“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”

Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.

The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.

Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.


The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.

The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.

“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.

GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.

egreb@mdedge.com

SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.

Philadelphia – Adjunctive cannabidiol (CBD) reduces seizure frequency in patients with Dravet syndrome, according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.

“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”

Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.

The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.

Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.


The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.

The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.

“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.

GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.

egreb@mdedge.com

SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.

PHILADELPHIA – The association between vitamin D insufficiency and multiple sclerosis (MS) outcome in children with acquired demyelinating syndromes (ADS) partly relates to skin pigmentation, according to research described at the annual meeting of the American Academy of Neurology. Future research will be required to understand the interactions between dietary vitamin D ingestion, sun exposure, pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and the genetic influences of vitamin D pathways with MS risk.

Race, vitamin D status, HLA-DRB1*15 genotype, and place of residence during childhood all affect the risk of MS. The place of residence also can affect exposure to ultraviolet radiation and, thus, dermal pigmentation.

Candice Dunn, a clinical research coordinator at the Children’s Hospital of Philadelphia, and colleagues conducted a prospective study to determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25[OH]D) levels measured at baseline, and skin tone are associated with MS outcome in children with ADS. They enrolled 259 children with incident ADS in a multisite study in Toronto and Philadelphia (latitudes 43° to 51°). The investigators measured non–sun-exposed upper inner arm melanin content using the DSM II ColorMeter device. They measured 25(OH)D concentrations in serum obtained within 60 days of symptom onset and compared them with laboratory-reported normative values. Vitamin D insufficiency was defined as 25(OH)D less than 75 nmol/L. Ms. Dunn and colleagues quantified HLA-DRB1*15 alleles using allele-specific polymerase chain reaction amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.

In all, 68 children were diagnosed with MS, 191 remained monophasic (monoADS). Approximately 46% of children with MS were HLA-DRB1*15-positive, compared with 29.9% of monoADS children. In addition, children with MS had significantly lower 25(OH)D levels (mean, 45.4 nmol/L) than monoADS children (mean, 61.9 nmol/L) at baseline. Non–sun-exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (mean melanin index, 46.4) and monoADS (mean melanin index, 43.5). Furthermore, 25(OH)D levels correlated with upper inner arm melanin index in the MS group, but not in children with monoADS.

Ms. Dunn had nothing to disclose, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
 

egreb@mdedge.com

SOURCE: Dunn C et al. AAN 2019, Abstract S19.007.

PHILADELPHIA – The association between vitamin D insufficiency and multiple sclerosis (MS) outcome in children with acquired demyelinating syndromes (ADS) partly relates to skin pigmentation, according to research described at the annual meeting of the American Academy of Neurology. Future research will be required to understand the interactions between dietary vitamin D ingestion, sun exposure, pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and the genetic influences of vitamin D pathways with MS risk.

Race, vitamin D status, HLA-DRB1*15 genotype, and place of residence during childhood all affect the risk of MS. The place of residence also can affect exposure to ultraviolet radiation and, thus, dermal pigmentation.

Candice Dunn, a clinical research coordinator at the Children’s Hospital of Philadelphia, and colleagues conducted a prospective study to determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25[OH]D) levels measured at baseline, and skin tone are associated with MS outcome in children with ADS. They enrolled 259 children with incident ADS in a multisite study in Toronto and Philadelphia (latitudes 43° to 51°). The investigators measured non–sun-exposed upper inner arm melanin content using the DSM II ColorMeter device. They measured 25(OH)D concentrations in serum obtained within 60 days of symptom onset and compared them with laboratory-reported normative values. Vitamin D insufficiency was defined as 25(OH)D less than 75 nmol/L. Ms. Dunn and colleagues quantified HLA-DRB1*15 alleles using allele-specific polymerase chain reaction amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.

In all, 68 children were diagnosed with MS, 191 remained monophasic (monoADS). Approximately 46% of children with MS were HLA-DRB1*15-positive, compared with 29.9% of monoADS children. In addition, children with MS had significantly lower 25(OH)D levels (mean, 45.4 nmol/L) than monoADS children (mean, 61.9 nmol/L) at baseline. Non–sun-exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (mean melanin index, 46.4) and monoADS (mean melanin index, 43.5). Furthermore, 25(OH)D levels correlated with upper inner arm melanin index in the MS group, but not in children with monoADS.

Ms. Dunn had nothing to disclose, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
 

egreb@mdedge.com

SOURCE: Dunn C et al. AAN 2019, Abstract S19.007.

PHILADELPHIA – The association between vitamin D insufficiency and multiple sclerosis (MS) outcome in children with acquired demyelinating syndromes (ADS) partly relates to skin pigmentation, according to research described at the annual meeting of the American Academy of Neurology. Future research will be required to understand the interactions between dietary vitamin D ingestion, sun exposure, pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and the genetic influences of vitamin D pathways with MS risk.

Race, vitamin D status, HLA-DRB1*15 genotype, and place of residence during childhood all affect the risk of MS. The place of residence also can affect exposure to ultraviolet radiation and, thus, dermal pigmentation.

Candice Dunn, a clinical research coordinator at the Children’s Hospital of Philadelphia, and colleagues conducted a prospective study to determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25[OH]D) levels measured at baseline, and skin tone are associated with MS outcome in children with ADS. They enrolled 259 children with incident ADS in a multisite study in Toronto and Philadelphia (latitudes 43° to 51°). The investigators measured non–sun-exposed upper inner arm melanin content using the DSM II ColorMeter device. They measured 25(OH)D concentrations in serum obtained within 60 days of symptom onset and compared them with laboratory-reported normative values. Vitamin D insufficiency was defined as 25(OH)D less than 75 nmol/L. Ms. Dunn and colleagues quantified HLA-DRB1*15 alleles using allele-specific polymerase chain reaction amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.

In all, 68 children were diagnosed with MS, 191 remained monophasic (monoADS). Approximately 46% of children with MS were HLA-DRB1*15-positive, compared with 29.9% of monoADS children. In addition, children with MS had significantly lower 25(OH)D levels (mean, 45.4 nmol/L) than monoADS children (mean, 61.9 nmol/L) at baseline. Non–sun-exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (mean melanin index, 46.4) and monoADS (mean melanin index, 43.5). Furthermore, 25(OH)D levels correlated with upper inner arm melanin index in the MS group, but not in children with monoADS.

Ms. Dunn had nothing to disclose, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
 

egreb@mdedge.com

SOURCE: Dunn C et al. AAN 2019, Abstract S19.007.

PHILADELPHIA – Approaches to managing tics in patients with Tourette syndrome or chronic tic disorders “should be individualized, and the choice should be the result of a collaborative decision among patient, caregiver, and clinician, during which the benefits and harms of individual treatments as well as the presence of comorbid disorders are considered,” according to Tamara Pringsheim, MD, lead author of a practice guideline published May 6, 2019, by the American Academy of Neurology, and her collaborators.

The panel of nine physicians, two psychologists, and two patient representatives developed the recommendations based on a comprehensive systematic literature review. They concluded that treatments may decrease the frequency and severity of tics but rarely eliminate them.

The guideline was endorsed by the Child Neurology Society and the European Academy of Neurology and is the first such guideline for American neurologists, said Dr. Pringsheim of the University of Calgary (Alta.). Like recent Canadian and European guidelines, it strongly supports the Comprehensive Behavioral Intervention for Tics (CBIT) as a treatment option for tics.

After examining which medical, behavioral, and neurostimulation interventions, compared with placebo or other active interventions, improve tic severity and tic-related impairment in children and adults with Tourette syndrome or a chronic tic disorder, the guideline writers recommended that the evidence was strongest for CBIT as a first-line treatment, relative to other behavioral treatments and medications.

If symptoms affect a patient’s daily life, doctors should consider CBIT, said guideline author John Piacentini, PhD, of the University of California, Los Angeles, at the annual meeting of the American Academy of Neurology. “This treatment combines habit-reversal training, which teaches patients how to control their urges to tic, with other behavioral strategies to reduce stress and other factors that often make tics worse.”

Patients typically see results from CBIT in 8-12 weeks. More CBIT providers are needed, however, to make the treatment readily available to all patients, he said.

The guideline panel members said that there was moderate confidence in the evidence for reduced tic severity for the following therapeutic approaches, compared with placebo: haloperidol, risperidone, aripiprazole (children only), tiapride (children only), clonidine, onabotulinumtoxinA injections, ningdong granule (as formulated by Zhao), (children only), and ling granule (children only). There was low or very low confidence in the evidence for all other therapies for reducing tic severity.
 

Comorbid conditions

Many people with tic disorders have neurodevelopmental or psychiatric conditions such as ADHD, obsessive-compulsive disorder, and mood and anxiety disorders. The guideline recommends that people with tics be evaluated for these conditions.

Alpha2-adrenergic agonists may improve symptoms of tic disorders and ADHD, the authors said. There was moderate confidence in the evidence for reduced tic severity for people with a comorbid diagnosis of ADHD with clonidine plus methylphenidate (children only) and methylphenidate alone (children only), compared with placebo.

Adults with severe Tourette syndrome who are resistant to medical and behavioral therapy may benefit from deep brain stimulation (DBS), the guideline states. There was moderate confidence in the evidence for reduced tic severity for DBS of the globus pallidus, compared with sham DBS, as an option for adults with severe tics who have failed CBIT and drugs. These patients first must be screened by a mental health professional and continue to be monitored throughout DBS treatment.

Adults with Tourette syndrome who self-treat their tics with cannabis in states where cannabis is legal should see a doctor who can monitor the use of cannabis for efficacy and adverse effects, the guideline says.

Adverse effects of therapy

The panel also examined the risks of harm, including weight gain, elevated prolactin levels, sedation, drug-induced movement disorders, hypotension, bradycardia, and ECG changes with medical treatments, compared with placebo or other active interventions. In regard to weight gain, the panel concluded with moderate confidence that people with tics receiving risperidone or aripiprazole (children only) are probably more likely to gain weight than people receiving placebo. There was low confidence for associations between specific therapies and elevated prolactin levels.

Compared with people receiving placebo, there was moderate confidence that tiapride is probably associated with higher rates of physical tiredness and sleep disturbances (children only), that clonidine is probably associated with sedation, and that guanfacine is probably associated with drowsiness (children only). There was moderate evidence that pimozide is probably associated with extrapyramidal symptoms. There was low confidence that any specific treatment led to hypotension, bradycardia, or ECG changes.

Additional guideline specifics

The guideline’s practice recommendations include explaining the natural history of tic disorders to patients and caregivers and evaluating patients for functional impairment. Watchful waiting is an acceptable approach in people who do not experience functional impairment, and patients receiving medications for tics must have periodic reevaluations for the need for ongoing medical treatment. People with Tourette syndrome should be referred to resources for psychoeducation for teachers and peers, such as the Tourette Association of America.

Comorbid ADHD occurs in 30%-50% of patients with tics. If screening for ADHD is positive, the burden of ADHD symptoms should be assessed and those with functionally impairing ADHD should be treated for the disorder. Similarly, obsessive-compulsive behaviors occur in 10%-50% of those with Tourette syndrome. If an assessment finds comorbid obsessive-compulsive disorder, it should be treated.

Other psychiatric comorbidities with Tourette syndrome include anxiety disorders, oppositional defiant disorder, and mood disorders. When screening for these conditions, one must inquire about suicidal thoughts and suicide attempts and refer to appropriate resources if present, according to the guidelines.

Individuals with tics and comorbid ADHD should be advised that alpha2-adrenergic agonists may provide benefit for both conditions. Alpha2-adrenergic agonists should be prescribed for the treatment of tics when the benefits of treatment outweigh the risks and patients must be counseled regarding common side effects of alpha2-adrenergic agonists, including sedation. Heart rate and blood pressure must be monitored in patients with tics treated with alpha2-adrenergic agonists. If prescribing extended-release guanfacine, one must monitor the QTc interval in patients with a history of cardiac conditions, patients taking other QT-prolonging agents, or patients with a family history of long QT syndrome. If discontinuing alpha2-adrenergic agonists, they must gradually be tapered to avoid rebound hypertension.

If considering antipsychotic therapies, patients must be counseled on the relative risk for extrapyramidal, hormonal, and metabolic adverse effects to inform decision making on which antipsychotic should be prescribed. Before prescribing antipsychotics for tics, ECGs must be performed. The QTc interval must be measured before and after starting pimozide or ziprasidone, or if antipsychotics are coadministered with other drugs that can prolong the QT interval. The lowest effective dose should be prescribed to decrease the risk of adverse effects, and patients should be monitored for drug-induced movement disorders and for metabolic and hormonal adverse effects of antipsychotics. When attempting to discontinue antipsychotics for tics, the medications should be gradually tapered over weeks to months to avoid withdrawal dyskinesias.

If topiramate is prescribed, patients must be counseled regarding common adverse effects, including cognitive and language problems, somnolence, weight loss, and an increased risk of renal stones.

Some patients with Tourette syndrome use cannabis as a self-medication for tics and comorbidities. Because of the risks associated with cannabis use and widespread self-medication with cannabis for tics, where regional legislation and resources allow, physicians must offer to direct patients to appropriate medical supervision when cannabis is used as self-medication for tics. Appropriate medical supervision would entail education and monitoring for efficacy and adverse effects, according to the guidelines.

Where regional legislation allows, physicians prescribing cannabis-based medication must prescribe the lowest effective dose to decrease the risk of adverse effects. Physicians prescribing cannabis-based medication must inform patients that medication may impair driving ability. Physicians prescribing cannabis-based medication to patients with Tourette syndrome must periodically reevaluate the need for ongoing treatment.

A multidisciplinary evaluation is needed to establish when the benefits of treatment outweigh the risks for prescribing DBS for medication-resistant motor and phonic tics. The DSM-5 diagnosis of Tourette syndrome must be confirmed and exclude secondary and functional tic-like movements when considering DBS for medication-resistant tics. A mental health professional must screen patients preoperatively and follow patients postoperatively for psychiatric disorders that may impede the long-term success of the therapy. Physicians must confirm that multiple classes of medication (antipsychotics, dopamine depleters, alpha1 agonists) and behavioral therapy have been administered (or are contraindicated) before prescribing DBS for tics.

The practice guideline was developed with financial support from AAN. Dr. Pringsheim reported no disclosures. Dr. Piacentini reported receiving funding for travel and speaking from foundations and universities and has received royalties from publishers. In addition, he has performed behavior therapy for tics for approximately 50% of his clinical time and has received financial or material support from Pfizer, the National Institute of Mental Health, and foundations.

jremaly@mdedge.com

SOURCE: Pringsheim T et al. Neurology. 2019 May 6. doi: 10.1212/WNL.0000000000007466.

PHILADELPHIA – Approaches to managing tics in patients with Tourette syndrome or chronic tic disorders “should be individualized, and the choice should be the result of a collaborative decision among patient, caregiver, and clinician, during which the benefits and harms of individual treatments as well as the presence of comorbid disorders are considered,” according to Tamara Pringsheim, MD, lead author of a practice guideline published May 6, 2019, by the American Academy of Neurology, and her collaborators.

The panel of nine physicians, two psychologists, and two patient representatives developed the recommendations based on a comprehensive systematic literature review. They concluded that treatments may decrease the frequency and severity of tics but rarely eliminate them.

The guideline was endorsed by the Child Neurology Society and the European Academy of Neurology and is the first such guideline for American neurologists, said Dr. Pringsheim of the University of Calgary (Alta.). Like recent Canadian and European guidelines, it strongly supports the Comprehensive Behavioral Intervention for Tics (CBIT) as a treatment option for tics.

After examining which medical, behavioral, and neurostimulation interventions, compared with placebo or other active interventions, improve tic severity and tic-related impairment in children and adults with Tourette syndrome or a chronic tic disorder, the guideline writers recommended that the evidence was strongest for CBIT as a first-line treatment, relative to other behavioral treatments and medications.

If symptoms affect a patient’s daily life, doctors should consider CBIT, said guideline author John Piacentini, PhD, of the University of California, Los Angeles, at the annual meeting of the American Academy of Neurology. “This treatment combines habit-reversal training, which teaches patients how to control their urges to tic, with other behavioral strategies to reduce stress and other factors that often make tics worse.”

Patients typically see results from CBIT in 8-12 weeks. More CBIT providers are needed, however, to make the treatment readily available to all patients, he said.

The guideline panel members said that there was moderate confidence in the evidence for reduced tic severity for the following therapeutic approaches, compared with placebo: haloperidol, risperidone, aripiprazole (children only), tiapride (children only), clonidine, onabotulinumtoxinA injections, ningdong granule (as formulated by Zhao), (children only), and ling granule (children only). There was low or very low confidence in the evidence for all other therapies for reducing tic severity.
 

Comorbid conditions

Many people with tic disorders have neurodevelopmental or psychiatric conditions such as ADHD, obsessive-compulsive disorder, and mood and anxiety disorders. The guideline recommends that people with tics be evaluated for these conditions.

Alpha2-adrenergic agonists may improve symptoms of tic disorders and ADHD, the authors said. There was moderate confidence in the evidence for reduced tic severity for people with a comorbid diagnosis of ADHD with clonidine plus methylphenidate (children only) and methylphenidate alone (children only), compared with placebo.

Adults with severe Tourette syndrome who are resistant to medical and behavioral therapy may benefit from deep brain stimulation (DBS), the guideline states. There was moderate confidence in the evidence for reduced tic severity for DBS of the globus pallidus, compared with sham DBS, as an option for adults with severe tics who have failed CBIT and drugs. These patients first must be screened by a mental health professional and continue to be monitored throughout DBS treatment.

Adults with Tourette syndrome who self-treat their tics with cannabis in states where cannabis is legal should see a doctor who can monitor the use of cannabis for efficacy and adverse effects, the guideline says.

Adverse effects of therapy

The panel also examined the risks of harm, including weight gain, elevated prolactin levels, sedation, drug-induced movement disorders, hypotension, bradycardia, and ECG changes with medical treatments, compared with placebo or other active interventions. In regard to weight gain, the panel concluded with moderate confidence that people with tics receiving risperidone or aripiprazole (children only) are probably more likely to gain weight than people receiving placebo. There was low confidence for associations between specific therapies and elevated prolactin levels.

Compared with people receiving placebo, there was moderate confidence that tiapride is probably associated with higher rates of physical tiredness and sleep disturbances (children only), that clonidine is probably associated with sedation, and that guanfacine is probably associated with drowsiness (children only). There was moderate evidence that pimozide is probably associated with extrapyramidal symptoms. There was low confidence that any specific treatment led to hypotension, bradycardia, or ECG changes.

Additional guideline specifics

The guideline’s practice recommendations include explaining the natural history of tic disorders to patients and caregivers and evaluating patients for functional impairment. Watchful waiting is an acceptable approach in people who do not experience functional impairment, and patients receiving medications for tics must have periodic reevaluations for the need for ongoing medical treatment. People with Tourette syndrome should be referred to resources for psychoeducation for teachers and peers, such as the Tourette Association of America.

Comorbid ADHD occurs in 30%-50% of patients with tics. If screening for ADHD is positive, the burden of ADHD symptoms should be assessed and those with functionally impairing ADHD should be treated for the disorder. Similarly, obsessive-compulsive behaviors occur in 10%-50% of those with Tourette syndrome. If an assessment finds comorbid obsessive-compulsive disorder, it should be treated.

Other psychiatric comorbidities with Tourette syndrome include anxiety disorders, oppositional defiant disorder, and mood disorders. When screening for these conditions, one must inquire about suicidal thoughts and suicide attempts and refer to appropriate resources if present, according to the guidelines.

Individuals with tics and comorbid ADHD should be advised that alpha2-adrenergic agonists may provide benefit for both conditions. Alpha2-adrenergic agonists should be prescribed for the treatment of tics when the benefits of treatment outweigh the risks and patients must be counseled regarding common side effects of alpha2-adrenergic agonists, including sedation. Heart rate and blood pressure must be monitored in patients with tics treated with alpha2-adrenergic agonists. If prescribing extended-release guanfacine, one must monitor the QTc interval in patients with a history of cardiac conditions, patients taking other QT-prolonging agents, or patients with a family history of long QT syndrome. If discontinuing alpha2-adrenergic agonists, they must gradually be tapered to avoid rebound hypertension.

If considering antipsychotic therapies, patients must be counseled on the relative risk for extrapyramidal, hormonal, and metabolic adverse effects to inform decision making on which antipsychotic should be prescribed. Before prescribing antipsychotics for tics, ECGs must be performed. The QTc interval must be measured before and after starting pimozide or ziprasidone, or if antipsychotics are coadministered with other drugs that can prolong the QT interval. The lowest effective dose should be prescribed to decrease the risk of adverse effects, and patients should be monitored for drug-induced movement disorders and for metabolic and hormonal adverse effects of antipsychotics. When attempting to discontinue antipsychotics for tics, the medications should be gradually tapered over weeks to months to avoid withdrawal dyskinesias.

If topiramate is prescribed, patients must be counseled regarding common adverse effects, including cognitive and language problems, somnolence, weight loss, and an increased risk of renal stones.

Some patients with Tourette syndrome use cannabis as a self-medication for tics and comorbidities. Because of the risks associated with cannabis use and widespread self-medication with cannabis for tics, where regional legislation and resources allow, physicians must offer to direct patients to appropriate medical supervision when cannabis is used as self-medication for tics. Appropriate medical supervision would entail education and monitoring for efficacy and adverse effects, according to the guidelines.

Where regional legislation allows, physicians prescribing cannabis-based medication must prescribe the lowest effective dose to decrease the risk of adverse effects. Physicians prescribing cannabis-based medication must inform patients that medication may impair driving ability. Physicians prescribing cannabis-based medication to patients with Tourette syndrome must periodically reevaluate the need for ongoing treatment.

A multidisciplinary evaluation is needed to establish when the benefits of treatment outweigh the risks for prescribing DBS for medication-resistant motor and phonic tics. The DSM-5 diagnosis of Tourette syndrome must be confirmed and exclude secondary and functional tic-like movements when considering DBS for medication-resistant tics. A mental health professional must screen patients preoperatively and follow patients postoperatively for psychiatric disorders that may impede the long-term success of the therapy. Physicians must confirm that multiple classes of medication (antipsychotics, dopamine depleters, alpha1 agonists) and behavioral therapy have been administered (or are contraindicated) before prescribing DBS for tics.

The practice guideline was developed with financial support from AAN. Dr. Pringsheim reported no disclosures. Dr. Piacentini reported receiving funding for travel and speaking from foundations and universities and has received royalties from publishers. In addition, he has performed behavior therapy for tics for approximately 50% of his clinical time and has received financial or material support from Pfizer, the National Institute of Mental Health, and foundations.

jremaly@mdedge.com

SOURCE: Pringsheim T et al. Neurology. 2019 May 6. doi: 10.1212/WNL.0000000000007466.

PHILADELPHIA – Approaches to managing tics in patients with Tourette syndrome or chronic tic disorders “should be individualized, and the choice should be the result of a collaborative decision among patient, caregiver, and clinician, during which the benefits and harms of individual treatments as well as the presence of comorbid disorders are considered,” according to Tamara Pringsheim, MD, lead author of a practice guideline published May 6, 2019, by the American Academy of Neurology, and her collaborators.

The panel of nine physicians, two psychologists, and two patient representatives developed the recommendations based on a comprehensive systematic literature review. They concluded that treatments may decrease the frequency and severity of tics but rarely eliminate them.

The guideline was endorsed by the Child Neurology Society and the European Academy of Neurology and is the first such guideline for American neurologists, said Dr. Pringsheim of the University of Calgary (Alta.). Like recent Canadian and European guidelines, it strongly supports the Comprehensive Behavioral Intervention for Tics (CBIT) as a treatment option for tics.

After examining which medical, behavioral, and neurostimulation interventions, compared with placebo or other active interventions, improve tic severity and tic-related impairment in children and adults with Tourette syndrome or a chronic tic disorder, the guideline writers recommended that the evidence was strongest for CBIT as a first-line treatment, relative to other behavioral treatments and medications.

If symptoms affect a patient’s daily life, doctors should consider CBIT, said guideline author John Piacentini, PhD, of the University of California, Los Angeles, at the annual meeting of the American Academy of Neurology. “This treatment combines habit-reversal training, which teaches patients how to control their urges to tic, with other behavioral strategies to reduce stress and other factors that often make tics worse.”

Patients typically see results from CBIT in 8-12 weeks. More CBIT providers are needed, however, to make the treatment readily available to all patients, he said.

The guideline panel members said that there was moderate confidence in the evidence for reduced tic severity for the following therapeutic approaches, compared with placebo: haloperidol, risperidone, aripiprazole (children only), tiapride (children only), clonidine, onabotulinumtoxinA injections, ningdong granule (as formulated by Zhao), (children only), and ling granule (children only). There was low or very low confidence in the evidence for all other therapies for reducing tic severity.
 

Comorbid conditions

Many people with tic disorders have neurodevelopmental or psychiatric conditions such as ADHD, obsessive-compulsive disorder, and mood and anxiety disorders. The guideline recommends that people with tics be evaluated for these conditions.

Alpha2-adrenergic agonists may improve symptoms of tic disorders and ADHD, the authors said. There was moderate confidence in the evidence for reduced tic severity for people with a comorbid diagnosis of ADHD with clonidine plus methylphenidate (children only) and methylphenidate alone (children only), compared with placebo.

Adults with severe Tourette syndrome who are resistant to medical and behavioral therapy may benefit from deep brain stimulation (DBS), the guideline states. There was moderate confidence in the evidence for reduced tic severity for DBS of the globus pallidus, compared with sham DBS, as an option for adults with severe tics who have failed CBIT and drugs. These patients first must be screened by a mental health professional and continue to be monitored throughout DBS treatment.

Adults with Tourette syndrome who self-treat their tics with cannabis in states where cannabis is legal should see a doctor who can monitor the use of cannabis for efficacy and adverse effects, the guideline says.

Adverse effects of therapy

The panel also examined the risks of harm, including weight gain, elevated prolactin levels, sedation, drug-induced movement disorders, hypotension, bradycardia, and ECG changes with medical treatments, compared with placebo or other active interventions. In regard to weight gain, the panel concluded with moderate confidence that people with tics receiving risperidone or aripiprazole (children only) are probably more likely to gain weight than people receiving placebo. There was low confidence for associations between specific therapies and elevated prolactin levels.

Compared with people receiving placebo, there was moderate confidence that tiapride is probably associated with higher rates of physical tiredness and sleep disturbances (children only), that clonidine is probably associated with sedation, and that guanfacine is probably associated with drowsiness (children only). There was moderate evidence that pimozide is probably associated with extrapyramidal symptoms. There was low confidence that any specific treatment led to hypotension, bradycardia, or ECG changes.

Additional guideline specifics

The guideline’s practice recommendations include explaining the natural history of tic disorders to patients and caregivers and evaluating patients for functional impairment. Watchful waiting is an acceptable approach in people who do not experience functional impairment, and patients receiving medications for tics must have periodic reevaluations for the need for ongoing medical treatment. People with Tourette syndrome should be referred to resources for psychoeducation for teachers and peers, such as the Tourette Association of America.

Comorbid ADHD occurs in 30%-50% of patients with tics. If screening for ADHD is positive, the burden of ADHD symptoms should be assessed and those with functionally impairing ADHD should be treated for the disorder. Similarly, obsessive-compulsive behaviors occur in 10%-50% of those with Tourette syndrome. If an assessment finds comorbid obsessive-compulsive disorder, it should be treated.

Other psychiatric comorbidities with Tourette syndrome include anxiety disorders, oppositional defiant disorder, and mood disorders. When screening for these conditions, one must inquire about suicidal thoughts and suicide attempts and refer to appropriate resources if present, according to the guidelines.

Individuals with tics and comorbid ADHD should be advised that alpha2-adrenergic agonists may provide benefit for both conditions. Alpha2-adrenergic agonists should be prescribed for the treatment of tics when the benefits of treatment outweigh the risks and patients must be counseled regarding common side effects of alpha2-adrenergic agonists, including sedation. Heart rate and blood pressure must be monitored in patients with tics treated with alpha2-adrenergic agonists. If prescribing extended-release guanfacine, one must monitor the QTc interval in patients with a history of cardiac conditions, patients taking other QT-prolonging agents, or patients with a family history of long QT syndrome. If discontinuing alpha2-adrenergic agonists, they must gradually be tapered to avoid rebound hypertension.

If considering antipsychotic therapies, patients must be counseled on the relative risk for extrapyramidal, hormonal, and metabolic adverse effects to inform decision making on which antipsychotic should be prescribed. Before prescribing antipsychotics for tics, ECGs must be performed. The QTc interval must be measured before and after starting pimozide or ziprasidone, or if antipsychotics are coadministered with other drugs that can prolong the QT interval. The lowest effective dose should be prescribed to decrease the risk of adverse effects, and patients should be monitored for drug-induced movement disorders and for metabolic and hormonal adverse effects of antipsychotics. When attempting to discontinue antipsychotics for tics, the medications should be gradually tapered over weeks to months to avoid withdrawal dyskinesias.

If topiramate is prescribed, patients must be counseled regarding common adverse effects, including cognitive and language problems, somnolence, weight loss, and an increased risk of renal stones.

Some patients with Tourette syndrome use cannabis as a self-medication for tics and comorbidities. Because of the risks associated with cannabis use and widespread self-medication with cannabis for tics, where regional legislation and resources allow, physicians must offer to direct patients to appropriate medical supervision when cannabis is used as self-medication for tics. Appropriate medical supervision would entail education and monitoring for efficacy and adverse effects, according to the guidelines.

Where regional legislation allows, physicians prescribing cannabis-based medication must prescribe the lowest effective dose to decrease the risk of adverse effects. Physicians prescribing cannabis-based medication must inform patients that medication may impair driving ability. Physicians prescribing cannabis-based medication to patients with Tourette syndrome must periodically reevaluate the need for ongoing treatment.

A multidisciplinary evaluation is needed to establish when the benefits of treatment outweigh the risks for prescribing DBS for medication-resistant motor and phonic tics. The DSM-5 diagnosis of Tourette syndrome must be confirmed and exclude secondary and functional tic-like movements when considering DBS for medication-resistant tics. A mental health professional must screen patients preoperatively and follow patients postoperatively for psychiatric disorders that may impede the long-term success of the therapy. Physicians must confirm that multiple classes of medication (antipsychotics, dopamine depleters, alpha1 agonists) and behavioral therapy have been administered (or are contraindicated) before prescribing DBS for tics.

The practice guideline was developed with financial support from AAN. Dr. Pringsheim reported no disclosures. Dr. Piacentini reported receiving funding for travel and speaking from foundations and universities and has received royalties from publishers. In addition, he has performed behavior therapy for tics for approximately 50% of his clinical time and has received financial or material support from Pfizer, the National Institute of Mental Health, and foundations.

jremaly@mdedge.com

SOURCE: Pringsheim T et al. Neurology. 2019 May 6. doi: 10.1212/WNL.0000000000007466.

PHILADELPHIA – A disproportionate number of breakthrough strokes were observed among patients receiving rivaroxaban for nonvalvular atrial fibrillation in a stroke unit, according to a small, single-center, retrospective study presented at the annual meeting of the American Academy of Neurology.

The researchers reviewed all patients presenting to a tertiary care stroke unit in Australia from January 2015 to June 2018.

A total of 56 patients (median age was 74 years; 61% were male) had received direct oral anticoagulant (DOAC) therapy and then had an ischemic stroke. Of those patients, 37 (66%) had strokes while receiving the treatment; 14 patients (25%) had a stroke after recently stopping a DOAC, often prior to a medical procedure; and 5 patients (9%) were not adherent to their DOAC regimen.

Of the 37 patients who had strokes during DOAC treatment, 48% were on rivaroxaban, 9% were on dabigatran, and 9% were on apixaban, Fiona Chan, MD, of The Princess Alexandra Hospital, Brisbane, Australia, and coinvestigators reported in a poster presentation.

While these findings need to be replicated in a larger study, they do “raise concern for inadequate stroke prevention within this cohort,” they said.

Moreover, the findings illustrate the importance of bridging anticoagulation prior to procedures, when appropriate, to minimize stroke risk, they added, as 25% of the strokes had occurred in patients who recently stopped the DOACs due to procedures.

To determine which DOAC was most often associated with breakthrough ischemic strokes in patients with nonvalvular atrial fibrillation, the investigators compared the proportion of DOACs prescribed in Australia to the proportion of observed strokes in their cohort.

Despite accounting for about 51% of Australian DOAC prescriptions, rivaroxaban represented nearly 73% of breakthrough strokes among the patients who had strokes while receiving the treatment (P = .001), the investigators reported.

Conversely, apixaban accounted for about 35% of prescriptions but 14% of the breakthrough strokes (P = .0007), while dabigatran accounted for 14% of prescriptions and 14% of the strokes (P = 0.99), the investigators said in their poster.

One limitation of this retrospective study is that the patient cohort came from a single specialized center, and may not reflect the true incidence of nonvalvular atrial fibrillation across Australia, the researchers noted.

Dr. Chan and coinvestigators reported that they had no relevant financial disclosures.

SOURCE: Chan F et al. AAN 2019. P1.3-001.

PHILADELPHIA – A disproportionate number of breakthrough strokes were observed among patients receiving rivaroxaban for nonvalvular atrial fibrillation in a stroke unit, according to a small, single-center, retrospective study presented at the annual meeting of the American Academy of Neurology.

The researchers reviewed all patients presenting to a tertiary care stroke unit in Australia from January 2015 to June 2018.

A total of 56 patients (median age was 74 years; 61% were male) had received direct oral anticoagulant (DOAC) therapy and then had an ischemic stroke. Of those patients, 37 (66%) had strokes while receiving the treatment; 14 patients (25%) had a stroke after recently stopping a DOAC, often prior to a medical procedure; and 5 patients (9%) were not adherent to their DOAC regimen.

Of the 37 patients who had strokes during DOAC treatment, 48% were on rivaroxaban, 9% were on dabigatran, and 9% were on apixaban, Fiona Chan, MD, of The Princess Alexandra Hospital, Brisbane, Australia, and coinvestigators reported in a poster presentation.

While these findings need to be replicated in a larger study, they do “raise concern for inadequate stroke prevention within this cohort,” they said.

Moreover, the findings illustrate the importance of bridging anticoagulation prior to procedures, when appropriate, to minimize stroke risk, they added, as 25% of the strokes had occurred in patients who recently stopped the DOACs due to procedures.

To determine which DOAC was most often associated with breakthrough ischemic strokes in patients with nonvalvular atrial fibrillation, the investigators compared the proportion of DOACs prescribed in Australia to the proportion of observed strokes in their cohort.

Despite accounting for about 51% of Australian DOAC prescriptions, rivaroxaban represented nearly 73% of breakthrough strokes among the patients who had strokes while receiving the treatment (P = .001), the investigators reported.

Conversely, apixaban accounted for about 35% of prescriptions but 14% of the breakthrough strokes (P = .0007), while dabigatran accounted for 14% of prescriptions and 14% of the strokes (P = 0.99), the investigators said in their poster.

One limitation of this retrospective study is that the patient cohort came from a single specialized center, and may not reflect the true incidence of nonvalvular atrial fibrillation across Australia, the researchers noted.

Dr. Chan and coinvestigators reported that they had no relevant financial disclosures.

SOURCE: Chan F et al. AAN 2019. P1.3-001.

PHILADELPHIA – A disproportionate number of breakthrough strokes were observed among patients receiving rivaroxaban for nonvalvular atrial fibrillation in a stroke unit, according to a small, single-center, retrospective study presented at the annual meeting of the American Academy of Neurology.

The researchers reviewed all patients presenting to a tertiary care stroke unit in Australia from January 2015 to June 2018.

A total of 56 patients (median age was 74 years; 61% were male) had received direct oral anticoagulant (DOAC) therapy and then had an ischemic stroke. Of those patients, 37 (66%) had strokes while receiving the treatment; 14 patients (25%) had a stroke after recently stopping a DOAC, often prior to a medical procedure; and 5 patients (9%) were not adherent to their DOAC regimen.

Of the 37 patients who had strokes during DOAC treatment, 48% were on rivaroxaban, 9% were on dabigatran, and 9% were on apixaban, Fiona Chan, MD, of The Princess Alexandra Hospital, Brisbane, Australia, and coinvestigators reported in a poster presentation.

While these findings need to be replicated in a larger study, they do “raise concern for inadequate stroke prevention within this cohort,” they said.

Moreover, the findings illustrate the importance of bridging anticoagulation prior to procedures, when appropriate, to minimize stroke risk, they added, as 25% of the strokes had occurred in patients who recently stopped the DOACs due to procedures.

To determine which DOAC was most often associated with breakthrough ischemic strokes in patients with nonvalvular atrial fibrillation, the investigators compared the proportion of DOACs prescribed in Australia to the proportion of observed strokes in their cohort.

Despite accounting for about 51% of Australian DOAC prescriptions, rivaroxaban represented nearly 73% of breakthrough strokes among the patients who had strokes while receiving the treatment (P = .001), the investigators reported.

Conversely, apixaban accounted for about 35% of prescriptions but 14% of the breakthrough strokes (P = .0007), while dabigatran accounted for 14% of prescriptions and 14% of the strokes (P = 0.99), the investigators said in their poster.

One limitation of this retrospective study is that the patient cohort came from a single specialized center, and may not reflect the true incidence of nonvalvular atrial fibrillation across Australia, the researchers noted.

Dr. Chan and coinvestigators reported that they had no relevant financial disclosures.

SOURCE: Chan F et al. AAN 2019. P1.3-001.

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 – 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.

State laws that give pharmacists direct authority to dispense naloxone are linked to significant drops in opioid-related fatal overdoses, investigators reported.

By contrast, state laws that stopped short of allowing pharmacists to directly dispense the opioid antagonist did not appear to impact mortality, according to the report, which appears in JAMA Internal Medicine (2019 May 6. doi: 10.1001/jamainternmed.2019.0272).

The report, based on state-level trends tracked from 2005 to 2016, indicates that fatal opioid overdoses fell by nearly one-third in states that adopted direct dispensing laws as compared with states that adopted other naloxone laws.

That finding suggests that the policy type determines whether a naloxone law is useful in combating fatal opioid overdoses, said Rahi Abouk, PhD, of William Paterson University, Wayne, N.J. and co-authors of the paper.

“Enabling distribution through various sources, or requiring gatekeepers, will not be as beneficial,” Dr. Abouk and co-authors said in their report.

The current rate of deaths from fentanyl, heroin, and prescription analgesic overdose has outpaced all previous drug epidemics on record, and even surpasses the number of deaths in the peak year of the HIV epidemic of the 1980s, Dr. Abouk and colleagues wrote in their paper.

The number of states with naloxone access laws grew from just 2 in 2005 to 47 by 2016, including 9 states that granted direct authority to pharmacists and 38 that granted indirect authority, according to the researchers.

The analysis of overdose trends from 2005 to 2016 was based on naloxone distribution data from state Medicaid agencies and opioid-related mortality data from a national statistics system. Forty percent of nonelderly adults with an opioid addiction are covered by Medicaid, the researchers said.

They found that naloxone laws granting pharmacists direct dispensing authority were linked to a drop in opioid deaths that increased in magnitude over time, according to researchers. The mean number of opioid deaths dropped by 27% in the second year after adoption of direct authority laws, relative to opioid deaths in states with indirect access laws, while in subsequent years, deaths dropped by 34%.

Emergency department visits related to opioids increased by 15% in direct authority states 3 or more years after adoption, as compared to states that did not adopt direct authority laws. According to investigators, that translated into 15 additional opioid-related emergency department visits each month.

That increase suggests that, alongside direct dispensing laws, “useful interventions” and connections to treatment are needed for the emergency department, according to Dr. Abouk and colleagues.

“This is the location where such programs may be the most effective,” they said in their report.

Future research should be done to determine whether removing gatekeepers increases the value of naloxone distribution policies, they concluded in the report.

Dr. Abouk had no disclosures. Co-authors on the study reported funding and conflict of interest disclosures related to the National Institute on Drug Abuse and the Centers for Disease Control and Prevention.

SOURCE: Abouk R, et al. JAMA Intern Med. 2019 May 6. doi:10.1001/jamainternmed.2019.0272.

State laws that give pharmacists direct authority to dispense naloxone are linked to significant drops in opioid-related fatal overdoses, investigators reported.

By contrast, state laws that stopped short of allowing pharmacists to directly dispense the opioid antagonist did not appear to impact mortality, according to the report, which appears in JAMA Internal Medicine (2019 May 6. doi: 10.1001/jamainternmed.2019.0272).

The report, based on state-level trends tracked from 2005 to 2016, indicates that fatal opioid overdoses fell by nearly one-third in states that adopted direct dispensing laws as compared with states that adopted other naloxone laws.

That finding suggests that the policy type determines whether a naloxone law is useful in combating fatal opioid overdoses, said Rahi Abouk, PhD, of William Paterson University, Wayne, N.J. and co-authors of the paper.

“Enabling distribution through various sources, or requiring gatekeepers, will not be as beneficial,” Dr. Abouk and co-authors said in their report.

The current rate of deaths from fentanyl, heroin, and prescription analgesic overdose has outpaced all previous drug epidemics on record, and even surpasses the number of deaths in the peak year of the HIV epidemic of the 1980s, Dr. Abouk and colleagues wrote in their paper.

The number of states with naloxone access laws grew from just 2 in 2005 to 47 by 2016, including 9 states that granted direct authority to pharmacists and 38 that granted indirect authority, according to the researchers.

The analysis of overdose trends from 2005 to 2016 was based on naloxone distribution data from state Medicaid agencies and opioid-related mortality data from a national statistics system. Forty percent of nonelderly adults with an opioid addiction are covered by Medicaid, the researchers said.

They found that naloxone laws granting pharmacists direct dispensing authority were linked to a drop in opioid deaths that increased in magnitude over time, according to researchers. The mean number of opioid deaths dropped by 27% in the second year after adoption of direct authority laws, relative to opioid deaths in states with indirect access laws, while in subsequent years, deaths dropped by 34%.

Emergency department visits related to opioids increased by 15% in direct authority states 3 or more years after adoption, as compared to states that did not adopt direct authority laws. According to investigators, that translated into 15 additional opioid-related emergency department visits each month.

That increase suggests that, alongside direct dispensing laws, “useful interventions” and connections to treatment are needed for the emergency department, according to Dr. Abouk and colleagues.

“This is the location where such programs may be the most effective,” they said in their report.

Future research should be done to determine whether removing gatekeepers increases the value of naloxone distribution policies, they concluded in the report.

Dr. Abouk had no disclosures. Co-authors on the study reported funding and conflict of interest disclosures related to the National Institute on Drug Abuse and the Centers for Disease Control and Prevention.

SOURCE: Abouk R, et al. JAMA Intern Med. 2019 May 6. doi:10.1001/jamainternmed.2019.0272.

State laws that give pharmacists direct authority to dispense naloxone are linked to significant drops in opioid-related fatal overdoses, investigators reported.

By contrast, state laws that stopped short of allowing pharmacists to directly dispense the opioid antagonist did not appear to impact mortality, according to the report, which appears in JAMA Internal Medicine (2019 May 6. doi: 10.1001/jamainternmed.2019.0272).

The report, based on state-level trends tracked from 2005 to 2016, indicates that fatal opioid overdoses fell by nearly one-third in states that adopted direct dispensing laws as compared with states that adopted other naloxone laws.

That finding suggests that the policy type determines whether a naloxone law is useful in combating fatal opioid overdoses, said Rahi Abouk, PhD, of William Paterson University, Wayne, N.J. and co-authors of the paper.

“Enabling distribution through various sources, or requiring gatekeepers, will not be as beneficial,” Dr. Abouk and co-authors said in their report.

The current rate of deaths from fentanyl, heroin, and prescription analgesic overdose has outpaced all previous drug epidemics on record, and even surpasses the number of deaths in the peak year of the HIV epidemic of the 1980s, Dr. Abouk and colleagues wrote in their paper.

The number of states with naloxone access laws grew from just 2 in 2005 to 47 by 2016, including 9 states that granted direct authority to pharmacists and 38 that granted indirect authority, according to the researchers.

The analysis of overdose trends from 2005 to 2016 was based on naloxone distribution data from state Medicaid agencies and opioid-related mortality data from a national statistics system. Forty percent of nonelderly adults with an opioid addiction are covered by Medicaid, the researchers said.

They found that naloxone laws granting pharmacists direct dispensing authority were linked to a drop in opioid deaths that increased in magnitude over time, according to researchers. The mean number of opioid deaths dropped by 27% in the second year after adoption of direct authority laws, relative to opioid deaths in states with indirect access laws, while in subsequent years, deaths dropped by 34%.

Emergency department visits related to opioids increased by 15% in direct authority states 3 or more years after adoption, as compared to states that did not adopt direct authority laws. According to investigators, that translated into 15 additional opioid-related emergency department visits each month.

That increase suggests that, alongside direct dispensing laws, “useful interventions” and connections to treatment are needed for the emergency department, according to Dr. Abouk and colleagues.

“This is the location where such programs may be the most effective,” they said in their report.

Future research should be done to determine whether removing gatekeepers increases the value of naloxone distribution policies, they concluded in the report.

Dr. Abouk had no disclosures. Co-authors on the study reported funding and conflict of interest disclosures related to the National Institute on Drug Abuse and the Centers for Disease Control and Prevention.

SOURCE: Abouk R, et al. JAMA Intern Med. 2019 May 6. doi:10.1001/jamainternmed.2019.0272.

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 .