AAN: American Academy of Neurology

LOS ANGELES—Among patients with intractable focal epilepsy who have failed one or more epilepsy surgeries, reoperation may provide long-term seizure control, according to research presented at the 70th Annual Meeting of the American Academy of Neurology. Patients with prior epilepsy surgery are less likely to achieve seizure freedom, however, compared with patients undergoing initial epilepsy surgery, the researchers said.

“It is possible to achieve long-term seizure control in patients with failed prior epilepsy surgery,” said Ruta Yardi, MD, a researcher at the Cleveland Clinic, and colleagues. “A lesional MRI, specific prior post-operative pathology, and fewer prior resections seem to predict better outcomes.” These results might be helpful in selecting patients who may be candidates for reoperation, the investigators said.

Epilepsy surgery is the most effective treatment option for patients with medically refractory focal epilepsy, but initial surgeries may not be successful. A small percentage of patients who do not benefit from a first surgery may be evaluated for another resection, however, data for how outcomes vary with successive surgeries are limited, Dr. Yardi and colleagues said.

To assess longitudinal seizure outcomes following reoperations in patients with intractable focal epilepsy and identify prognostic factors that influence these outcomes, Dr. Yardi and colleagues retrospectively studied 898 patients (448 female; about a third pediatric) who underwent epilepsy surgery at the Cleveland Clinic from 1995 to 2016. The investigators collected and analyzed baseline characteristics, known predictors of seizure outcome, surgical data, pathology, and postoperative seizure recurrence.

The primary outcome was complete seizure freedom (ie, Engel Class IA) at last follow-up. In addition, the researchers analyzed the data using Kaplan Meier survival curves and univariate and multivariate hazard modeling.

The analysis included 788 patients without prior surgery, 92 patients with one prior surgery, and 18 patients with two or more prior surgeries. Two years after the most recent epilepsy surgery, 58% of patients with no prior surgery were seizure-free, compared with 49% of patients who had one prior surgery and 39% of patients who had two or more prior surgeries. Patients with more than one surgery were more likely to have an Engel outcome score greater than Class I.

Variables that correlated with better seizure outcome in the univariate analysis included female gender; a lesional initial MRI; no history of generalization; and mesial temporal sclerosis, malformations of cortical development, or tumor on pathology. In the multivariate model, gender, history of generalization, and number of prior surgeries remained statistically significant.

—Jake Remaly

LOS ANGELES—Among patients with intractable focal epilepsy who have failed one or more epilepsy surgeries, reoperation may provide long-term seizure control, according to research presented at the 70th Annual Meeting of the American Academy of Neurology. Patients with prior epilepsy surgery are less likely to achieve seizure freedom, however, compared with patients undergoing initial epilepsy surgery, the researchers said.

“It is possible to achieve long-term seizure control in patients with failed prior epilepsy surgery,” said Ruta Yardi, MD, a researcher at the Cleveland Clinic, and colleagues. “A lesional MRI, specific prior post-operative pathology, and fewer prior resections seem to predict better outcomes.” These results might be helpful in selecting patients who may be candidates for reoperation, the investigators said.

Epilepsy surgery is the most effective treatment option for patients with medically refractory focal epilepsy, but initial surgeries may not be successful. A small percentage of patients who do not benefit from a first surgery may be evaluated for another resection, however, data for how outcomes vary with successive surgeries are limited, Dr. Yardi and colleagues said.

To assess longitudinal seizure outcomes following reoperations in patients with intractable focal epilepsy and identify prognostic factors that influence these outcomes, Dr. Yardi and colleagues retrospectively studied 898 patients (448 female; about a third pediatric) who underwent epilepsy surgery at the Cleveland Clinic from 1995 to 2016. The investigators collected and analyzed baseline characteristics, known predictors of seizure outcome, surgical data, pathology, and postoperative seizure recurrence.

The primary outcome was complete seizure freedom (ie, Engel Class IA) at last follow-up. In addition, the researchers analyzed the data using Kaplan Meier survival curves and univariate and multivariate hazard modeling.

The analysis included 788 patients without prior surgery, 92 patients with one prior surgery, and 18 patients with two or more prior surgeries. Two years after the most recent epilepsy surgery, 58% of patients with no prior surgery were seizure-free, compared with 49% of patients who had one prior surgery and 39% of patients who had two or more prior surgeries. Patients with more than one surgery were more likely to have an Engel outcome score greater than Class I.

Variables that correlated with better seizure outcome in the univariate analysis included female gender; a lesional initial MRI; no history of generalization; and mesial temporal sclerosis, malformations of cortical development, or tumor on pathology. In the multivariate model, gender, history of generalization, and number of prior surgeries remained statistically significant.

—Jake Remaly

LOS ANGELES—Among patients with intractable focal epilepsy who have failed one or more epilepsy surgeries, reoperation may provide long-term seizure control, according to research presented at the 70th Annual Meeting of the American Academy of Neurology. Patients with prior epilepsy surgery are less likely to achieve seizure freedom, however, compared with patients undergoing initial epilepsy surgery, the researchers said.

“It is possible to achieve long-term seizure control in patients with failed prior epilepsy surgery,” said Ruta Yardi, MD, a researcher at the Cleveland Clinic, and colleagues. “A lesional MRI, specific prior post-operative pathology, and fewer prior resections seem to predict better outcomes.” These results might be helpful in selecting patients who may be candidates for reoperation, the investigators said.

Epilepsy surgery is the most effective treatment option for patients with medically refractory focal epilepsy, but initial surgeries may not be successful. A small percentage of patients who do not benefit from a first surgery may be evaluated for another resection, however, data for how outcomes vary with successive surgeries are limited, Dr. Yardi and colleagues said.

To assess longitudinal seizure outcomes following reoperations in patients with intractable focal epilepsy and identify prognostic factors that influence these outcomes, Dr. Yardi and colleagues retrospectively studied 898 patients (448 female; about a third pediatric) who underwent epilepsy surgery at the Cleveland Clinic from 1995 to 2016. The investigators collected and analyzed baseline characteristics, known predictors of seizure outcome, surgical data, pathology, and postoperative seizure recurrence.

The primary outcome was complete seizure freedom (ie, Engel Class IA) at last follow-up. In addition, the researchers analyzed the data using Kaplan Meier survival curves and univariate and multivariate hazard modeling.

The analysis included 788 patients without prior surgery, 92 patients with one prior surgery, and 18 patients with two or more prior surgeries. Two years after the most recent epilepsy surgery, 58% of patients with no prior surgery were seizure-free, compared with 49% of patients who had one prior surgery and 39% of patients who had two or more prior surgeries. Patients with more than one surgery were more likely to have an Engel outcome score greater than Class I.

Variables that correlated with better seizure outcome in the univariate analysis included female gender; a lesional initial MRI; no history of generalization; and mesial temporal sclerosis, malformations of cortical development, or tumor on pathology. In the multivariate model, gender, history of generalization, and number of prior surgeries remained statistically significant.

—Jake Remaly

LOS ANGELES—Among older adults, the presence of a greater number of sensory impairments is associated with an increased risk of dementia, according to research presented at the 70th Annual Meeting of the American Academy of Neurology.

Sensory impairments are common among older adults and are associated with dementia, but no study has examined multisensory impairment and risk of dementia by incorporating measures of hearing, vision, smell, and touch, said Willa D. Brenowitz, PhD, MPH, a researcher in the Department of Epidemiology and Biostatistics at the University of California, San Francisco, and colleagues.

To evaluate whether the presence of multiple sensory impairments is associated with a greater risk of dementia, compared with a single or no sensory impairment, Dr. Brenowitz and colleagues studied 1,843 participants from the Health, Aging, and Body Composition Study. Participants were ages 70 to 79 and did not have dementia at baseline.

Investigators used sensory assessments that were conducted during the study years 3–5 to determine whether participants had visual impairment (ie, visual acuity ≤ 20/40 or log contrast sensitivity < 1.55), moderate to severe hearing loss (> 40 decibels hearing level based on pure tone average at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz), poor smell (lowest tertile of 12-item Cross Cultural Smell Identification Test), or impaired touch (peripheral nerve insensitivity based on a 10-g monofilament test or vibration detection threshold).

Investigators followed participants for up to 10 years. Incident dementia was based on hospitalization records, dementia medications, or a decline in Modified Mini-Mental State Exam of 1.5 standard deviations or greater. The researchers evaluated the association between number of sensory impairments and risk of dementia using Cox proportional hazard models adjusted for demographics and health conditions.

Sensory impairments were common, the researchers said. In all, 28% had visual impairments, 35% had hearing loss, 22% had poor smell, 12% had peripheral nerve insensitivity, and 25% had multiple impairments. An increasing number of impairments was associated with risk of dementia in a graded fashion. Compared with no sensory impairment, having one sensory impairment was associated with a 50% greater risk of dementia, two impairments was associated with a twofold greater risk of dementia, and three or four impairments was associated with a 2.8-fold greater risk of dementia.

“It is possible that sensory impairment, especially multiple [impairments], could limit an older adult’s engagement in protective lifestyle factors such as cognitive, physical, and social activity, thereby increasing dementia risk,” Dr. Brenowitz and colleagues said.

Clinical assessment of sensory function may help identify patients at high risk of dementia, the researchers said. Further studies are needed to determine whether multisensory impairment is a risk factor for dementia or an indicator of neurodegeneration, they said.

—Jake Remaly

LOS ANGELES—Among older adults, the presence of a greater number of sensory impairments is associated with an increased risk of dementia, according to research presented at the 70th Annual Meeting of the American Academy of Neurology.

Sensory impairments are common among older adults and are associated with dementia, but no study has examined multisensory impairment and risk of dementia by incorporating measures of hearing, vision, smell, and touch, said Willa D. Brenowitz, PhD, MPH, a researcher in the Department of Epidemiology and Biostatistics at the University of California, San Francisco, and colleagues.

To evaluate whether the presence of multiple sensory impairments is associated with a greater risk of dementia, compared with a single or no sensory impairment, Dr. Brenowitz and colleagues studied 1,843 participants from the Health, Aging, and Body Composition Study. Participants were ages 70 to 79 and did not have dementia at baseline.

Investigators used sensory assessments that were conducted during the study years 3–5 to determine whether participants had visual impairment (ie, visual acuity ≤ 20/40 or log contrast sensitivity < 1.55), moderate to severe hearing loss (> 40 decibels hearing level based on pure tone average at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz), poor smell (lowest tertile of 12-item Cross Cultural Smell Identification Test), or impaired touch (peripheral nerve insensitivity based on a 10-g monofilament test or vibration detection threshold).

Investigators followed participants for up to 10 years. Incident dementia was based on hospitalization records, dementia medications, or a decline in Modified Mini-Mental State Exam of 1.5 standard deviations or greater. The researchers evaluated the association between number of sensory impairments and risk of dementia using Cox proportional hazard models adjusted for demographics and health conditions.

Sensory impairments were common, the researchers said. In all, 28% had visual impairments, 35% had hearing loss, 22% had poor smell, 12% had peripheral nerve insensitivity, and 25% had multiple impairments. An increasing number of impairments was associated with risk of dementia in a graded fashion. Compared with no sensory impairment, having one sensory impairment was associated with a 50% greater risk of dementia, two impairments was associated with a twofold greater risk of dementia, and three or four impairments was associated with a 2.8-fold greater risk of dementia.

“It is possible that sensory impairment, especially multiple [impairments], could limit an older adult’s engagement in protective lifestyle factors such as cognitive, physical, and social activity, thereby increasing dementia risk,” Dr. Brenowitz and colleagues said.

Clinical assessment of sensory function may help identify patients at high risk of dementia, the researchers said. Further studies are needed to determine whether multisensory impairment is a risk factor for dementia or an indicator of neurodegeneration, they said.

—Jake Remaly

LOS ANGELES—Among older adults, the presence of a greater number of sensory impairments is associated with an increased risk of dementia, according to research presented at the 70th Annual Meeting of the American Academy of Neurology.

Sensory impairments are common among older adults and are associated with dementia, but no study has examined multisensory impairment and risk of dementia by incorporating measures of hearing, vision, smell, and touch, said Willa D. Brenowitz, PhD, MPH, a researcher in the Department of Epidemiology and Biostatistics at the University of California, San Francisco, and colleagues.

To evaluate whether the presence of multiple sensory impairments is associated with a greater risk of dementia, compared with a single or no sensory impairment, Dr. Brenowitz and colleagues studied 1,843 participants from the Health, Aging, and Body Composition Study. Participants were ages 70 to 79 and did not have dementia at baseline.

Investigators used sensory assessments that were conducted during the study years 3–5 to determine whether participants had visual impairment (ie, visual acuity ≤ 20/40 or log contrast sensitivity < 1.55), moderate to severe hearing loss (> 40 decibels hearing level based on pure tone average at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz), poor smell (lowest tertile of 12-item Cross Cultural Smell Identification Test), or impaired touch (peripheral nerve insensitivity based on a 10-g monofilament test or vibration detection threshold).

Investigators followed participants for up to 10 years. Incident dementia was based on hospitalization records, dementia medications, or a decline in Modified Mini-Mental State Exam of 1.5 standard deviations or greater. The researchers evaluated the association between number of sensory impairments and risk of dementia using Cox proportional hazard models adjusted for demographics and health conditions.

Sensory impairments were common, the researchers said. In all, 28% had visual impairments, 35% had hearing loss, 22% had poor smell, 12% had peripheral nerve insensitivity, and 25% had multiple impairments. An increasing number of impairments was associated with risk of dementia in a graded fashion. Compared with no sensory impairment, having one sensory impairment was associated with a 50% greater risk of dementia, two impairments was associated with a twofold greater risk of dementia, and three or four impairments was associated with a 2.8-fold greater risk of dementia.

“It is possible that sensory impairment, especially multiple [impairments], could limit an older adult’s engagement in protective lifestyle factors such as cognitive, physical, and social activity, thereby increasing dementia risk,” Dr. Brenowitz and colleagues said.

Clinical assessment of sensory function may help identify patients at high risk of dementia, the researchers said. Further studies are needed to determine whether multisensory impairment is a risk factor for dementia or an indicator of neurodegeneration, they said.

—Jake Remaly

LOS ANGELES—A strict gluten-free diet may help protect against the nerve pain that some patients with gluten sensitivity experience, according to a preliminary study presented at the American Academy of Neurology’s 70th Annual Meeting. “These findings are exciting because it might mean that a relatively simple change in diet could help alleviate painful symptoms tied to gluten neuropathy,” said lead author Panagiotis Zis, MD, PhD, Honorary Senior Lecturer at the University of Sheffield, United Kingdom. “While our study shows an association between a self-reported gluten-free diet and less pain, it does not show that one causes the other.”

Gluten neuropathy is the second most common neurologic manifestation of gluten sensitivity, after cerebellar ataxia. It is defined as an idiopathic neuropathy, in the absence of an alternative etiology despite extensive investigations, and in the presence of serologic evidence of gluten sensitivity (IgA and/or IgG antigliadin antibodies).

To establish the prevalence of pain in patients with gluten neuropathy and to describe any contributory factors, Dr. Zis and colleagues invited all consecutive patients with gluten neuropathy attending a specialist gluten/neurology clinic to participate in their study. Pain was assessed via the DN4 questionnaire and the visual analog scale. The Overall Neuropathy Limitations Scale (ONLS) was used to assess the severity of neuropathy. The Mental Health Index (MHI-5) was used to measure participants’ general mental health status.

In all, 60 patients (76.7% males, mean age 70) with gluten neuropathy were recruited. Pain was present in 33 patients (55.0%). Comparison between groups of painful and non-painful gluten neuropathy did not show significant differences regarding age, gender, neuropathy severity, or neuropathy type. Patients with painless gluten neuropathy were more likely to be on a strict gluten-free diet (55.6% vs 21.2%). Patients with painful gluten neuropathy presented with significantly worse MHI-5 score (75.9 vs 87.4). Multivariate analysis showed that, after adjusting for age, gender, and MHI-5 score, adherence to a strict gluten-free diet was associated with lowering the odds of peripheral neuropathic pain by 88.7%.

 “This study is promising because it shows that a gluten-free diet may help lower the risk of pain for people with gluten neuropathy,” Dr. Zis said. “More research is needed to confirm these results and to determine whether the gluten-free diet led to the reduction in pain.”

LOS ANGELES—A strict gluten-free diet may help protect against the nerve pain that some patients with gluten sensitivity experience, according to a preliminary study presented at the American Academy of Neurology’s 70th Annual Meeting. “These findings are exciting because it might mean that a relatively simple change in diet could help alleviate painful symptoms tied to gluten neuropathy,” said lead author Panagiotis Zis, MD, PhD, Honorary Senior Lecturer at the University of Sheffield, United Kingdom. “While our study shows an association between a self-reported gluten-free diet and less pain, it does not show that one causes the other.”

Gluten neuropathy is the second most common neurologic manifestation of gluten sensitivity, after cerebellar ataxia. It is defined as an idiopathic neuropathy, in the absence of an alternative etiology despite extensive investigations, and in the presence of serologic evidence of gluten sensitivity (IgA and/or IgG antigliadin antibodies).

To establish the prevalence of pain in patients with gluten neuropathy and to describe any contributory factors, Dr. Zis and colleagues invited all consecutive patients with gluten neuropathy attending a specialist gluten/neurology clinic to participate in their study. Pain was assessed via the DN4 questionnaire and the visual analog scale. The Overall Neuropathy Limitations Scale (ONLS) was used to assess the severity of neuropathy. The Mental Health Index (MHI-5) was used to measure participants’ general mental health status.

In all, 60 patients (76.7% males, mean age 70) with gluten neuropathy were recruited. Pain was present in 33 patients (55.0%). Comparison between groups of painful and non-painful gluten neuropathy did not show significant differences regarding age, gender, neuropathy severity, or neuropathy type. Patients with painless gluten neuropathy were more likely to be on a strict gluten-free diet (55.6% vs 21.2%). Patients with painful gluten neuropathy presented with significantly worse MHI-5 score (75.9 vs 87.4). Multivariate analysis showed that, after adjusting for age, gender, and MHI-5 score, adherence to a strict gluten-free diet was associated with lowering the odds of peripheral neuropathic pain by 88.7%.

 “This study is promising because it shows that a gluten-free diet may help lower the risk of pain for people with gluten neuropathy,” Dr. Zis said. “More research is needed to confirm these results and to determine whether the gluten-free diet led to the reduction in pain.”

LOS ANGELES—A strict gluten-free diet may help protect against the nerve pain that some patients with gluten sensitivity experience, according to a preliminary study presented at the American Academy of Neurology’s 70th Annual Meeting. “These findings are exciting because it might mean that a relatively simple change in diet could help alleviate painful symptoms tied to gluten neuropathy,” said lead author Panagiotis Zis, MD, PhD, Honorary Senior Lecturer at the University of Sheffield, United Kingdom. “While our study shows an association between a self-reported gluten-free diet and less pain, it does not show that one causes the other.”

Gluten neuropathy is the second most common neurologic manifestation of gluten sensitivity, after cerebellar ataxia. It is defined as an idiopathic neuropathy, in the absence of an alternative etiology despite extensive investigations, and in the presence of serologic evidence of gluten sensitivity (IgA and/or IgG antigliadin antibodies).

To establish the prevalence of pain in patients with gluten neuropathy and to describe any contributory factors, Dr. Zis and colleagues invited all consecutive patients with gluten neuropathy attending a specialist gluten/neurology clinic to participate in their study. Pain was assessed via the DN4 questionnaire and the visual analog scale. The Overall Neuropathy Limitations Scale (ONLS) was used to assess the severity of neuropathy. The Mental Health Index (MHI-5) was used to measure participants’ general mental health status.

In all, 60 patients (76.7% males, mean age 70) with gluten neuropathy were recruited. Pain was present in 33 patients (55.0%). Comparison between groups of painful and non-painful gluten neuropathy did not show significant differences regarding age, gender, neuropathy severity, or neuropathy type. Patients with painless gluten neuropathy were more likely to be on a strict gluten-free diet (55.6% vs 21.2%). Patients with painful gluten neuropathy presented with significantly worse MHI-5 score (75.9 vs 87.4). Multivariate analysis showed that, after adjusting for age, gender, and MHI-5 score, adherence to a strict gluten-free diet was associated with lowering the odds of peripheral neuropathic pain by 88.7%.

 “This study is promising because it shows that a gluten-free diet may help lower the risk of pain for people with gluten neuropathy,” Dr. Zis said. “More research is needed to confirm these results and to determine whether the gluten-free diet led to the reduction in pain.”

LOS ANGELES—Sodium oxybate reduces cataplexy and excessive sleepiness in children with narcolepsy type 1, according to a study described at the 70th Annual Meeting of the American Academy of Neurology. The treatment’s safety profile in this population is similar to that in adults.

Although symptoms of narcolepsy often begin during childhood or adolescence, few studies have evaluated treatments for narcolepsy in pediatric patients. Sodium oxybate is approved for the treatment of cataplexy and excessive daytime sleepiness in adults with narcolepsy, but it had not previously been studied in a large pediatric narcolepsy trial. Chad Ruoff, MD, Clinical Assistant Professor of Psychiatry and Behavioral Sciences at the Stanford Center for Sleep Sciences and Medicine in California, and colleagues conducted a double-blind, placebo-controlled, randomized-withdrawal study to evaluate the efficacy and safety of sodium oxybate in pediatric patients with narcolepsy type 1.

A Randomized-Withdrawal Study

Eligible participants were children and adolescents between ages 7 and 16 who had been diagnosed with narcolepsy type 1 and had cataplexy. Patients who were on stable doses of sodium oxybate and patients who were sodium-oxybate-naïve were included. Patients with evidence of sleep-disordered breathing were excluded.

Sodium-oxybate-naïve participants were titrated to a stable dose. After a stable-dose period, all participants began a two-week, double-blind, placebo-controlled withdrawal period. The investigators randomized participants in equal groups to continue sodium oxybate or to be switched to placebo. At the end of the double-blind period, all participants received open-label sodium oxybate treatment. Efficacy assessments compared measurements during or at the end of the double-blind period with those taken the last two weeks of the stable-dose period. The study’s primary end point was change in weekly number of cataplexy attacks.

Study Was Terminated Early

Dr. Ruoff and colleagues randomized 63 participants. Approximately 41% of the population was between ages 7 and 11, 44% was female, and 38% was receiving sodium oxybate at baseline. A preplanned interim analysis of 35 participants indicated that sodium oxybate was effective, based on the primary end point result. The double-blind, randomized-withdrawal period thus was terminated early.

For the total group of 63 randomized participants, weekly cataplexy attacks were significantly increased in the placebo group (median, 12.7/week), compared with the sodium-oxybate-treated group (median, 0.3/week). Cataplexy severity, assessed using the Clinical Global Impression of Change (CGI-C), was worse in the placebo group than in the sodium-oxybate group. For 65% of participants in the placebo group, cataplexy was rated “much worse” or “very much worse,” compared with 17% of the sodium-oxybate group. Excessive sleepiness, assessed using the Epworth Sleepiness Scale for Children and Adolescents, also was worse in the placebo group (median increase, 3.0 points) than in the sodium-oxybate group (no change). In addition, the CGI-C for narcolepsy overall was worse in the placebo group.

Treatment-emergent adverse events occurring in more than 10% of the overall sample were enuresis, nausea, vomiting, headache, and decreased weight. These adverse events had been reported in previous trials of sodium oxybate in adults with narcolepsy.

The study was sponsored by Jazz Pharmaceuticals.

LOS ANGELES—Sodium oxybate reduces cataplexy and excessive sleepiness in children with narcolepsy type 1, according to a study described at the 70th Annual Meeting of the American Academy of Neurology. The treatment’s safety profile in this population is similar to that in adults.

Although symptoms of narcolepsy often begin during childhood or adolescence, few studies have evaluated treatments for narcolepsy in pediatric patients. Sodium oxybate is approved for the treatment of cataplexy and excessive daytime sleepiness in adults with narcolepsy, but it had not previously been studied in a large pediatric narcolepsy trial. Chad Ruoff, MD, Clinical Assistant Professor of Psychiatry and Behavioral Sciences at the Stanford Center for Sleep Sciences and Medicine in California, and colleagues conducted a double-blind, placebo-controlled, randomized-withdrawal study to evaluate the efficacy and safety of sodium oxybate in pediatric patients with narcolepsy type 1.

A Randomized-Withdrawal Study

Eligible participants were children and adolescents between ages 7 and 16 who had been diagnosed with narcolepsy type 1 and had cataplexy. Patients who were on stable doses of sodium oxybate and patients who were sodium-oxybate-naïve were included. Patients with evidence of sleep-disordered breathing were excluded.

Sodium-oxybate-naïve participants were titrated to a stable dose. After a stable-dose period, all participants began a two-week, double-blind, placebo-controlled withdrawal period. The investigators randomized participants in equal groups to continue sodium oxybate or to be switched to placebo. At the end of the double-blind period, all participants received open-label sodium oxybate treatment. Efficacy assessments compared measurements during or at the end of the double-blind period with those taken the last two weeks of the stable-dose period. The study’s primary end point was change in weekly number of cataplexy attacks.

Study Was Terminated Early

Dr. Ruoff and colleagues randomized 63 participants. Approximately 41% of the population was between ages 7 and 11, 44% was female, and 38% was receiving sodium oxybate at baseline. A preplanned interim analysis of 35 participants indicated that sodium oxybate was effective, based on the primary end point result. The double-blind, randomized-withdrawal period thus was terminated early.

For the total group of 63 randomized participants, weekly cataplexy attacks were significantly increased in the placebo group (median, 12.7/week), compared with the sodium-oxybate-treated group (median, 0.3/week). Cataplexy severity, assessed using the Clinical Global Impression of Change (CGI-C), was worse in the placebo group than in the sodium-oxybate group. For 65% of participants in the placebo group, cataplexy was rated “much worse” or “very much worse,” compared with 17% of the sodium-oxybate group. Excessive sleepiness, assessed using the Epworth Sleepiness Scale for Children and Adolescents, also was worse in the placebo group (median increase, 3.0 points) than in the sodium-oxybate group (no change). In addition, the CGI-C for narcolepsy overall was worse in the placebo group.

Treatment-emergent adverse events occurring in more than 10% of the overall sample were enuresis, nausea, vomiting, headache, and decreased weight. These adverse events had been reported in previous trials of sodium oxybate in adults with narcolepsy.

The study was sponsored by Jazz Pharmaceuticals.

LOS ANGELES—Sodium oxybate reduces cataplexy and excessive sleepiness in children with narcolepsy type 1, according to a study described at the 70th Annual Meeting of the American Academy of Neurology. The treatment’s safety profile in this population is similar to that in adults.

Although symptoms of narcolepsy often begin during childhood or adolescence, few studies have evaluated treatments for narcolepsy in pediatric patients. Sodium oxybate is approved for the treatment of cataplexy and excessive daytime sleepiness in adults with narcolepsy, but it had not previously been studied in a large pediatric narcolepsy trial. Chad Ruoff, MD, Clinical Assistant Professor of Psychiatry and Behavioral Sciences at the Stanford Center for Sleep Sciences and Medicine in California, and colleagues conducted a double-blind, placebo-controlled, randomized-withdrawal study to evaluate the efficacy and safety of sodium oxybate in pediatric patients with narcolepsy type 1.

A Randomized-Withdrawal Study

Eligible participants were children and adolescents between ages 7 and 16 who had been diagnosed with narcolepsy type 1 and had cataplexy. Patients who were on stable doses of sodium oxybate and patients who were sodium-oxybate-naïve were included. Patients with evidence of sleep-disordered breathing were excluded.

Sodium-oxybate-naïve participants were titrated to a stable dose. After a stable-dose period, all participants began a two-week, double-blind, placebo-controlled withdrawal period. The investigators randomized participants in equal groups to continue sodium oxybate or to be switched to placebo. At the end of the double-blind period, all participants received open-label sodium oxybate treatment. Efficacy assessments compared measurements during or at the end of the double-blind period with those taken the last two weeks of the stable-dose period. The study’s primary end point was change in weekly number of cataplexy attacks.

Study Was Terminated Early

Dr. Ruoff and colleagues randomized 63 participants. Approximately 41% of the population was between ages 7 and 11, 44% was female, and 38% was receiving sodium oxybate at baseline. A preplanned interim analysis of 35 participants indicated that sodium oxybate was effective, based on the primary end point result. The double-blind, randomized-withdrawal period thus was terminated early.

For the total group of 63 randomized participants, weekly cataplexy attacks were significantly increased in the placebo group (median, 12.7/week), compared with the sodium-oxybate-treated group (median, 0.3/week). Cataplexy severity, assessed using the Clinical Global Impression of Change (CGI-C), was worse in the placebo group than in the sodium-oxybate group. For 65% of participants in the placebo group, cataplexy was rated “much worse” or “very much worse,” compared with 17% of the sodium-oxybate group. Excessive sleepiness, assessed using the Epworth Sleepiness Scale for Children and Adolescents, also was worse in the placebo group (median increase, 3.0 points) than in the sodium-oxybate group (no change). In addition, the CGI-C for narcolepsy overall was worse in the placebo group.

Treatment-emergent adverse events occurring in more than 10% of the overall sample were enuresis, nausea, vomiting, headache, and decreased weight. These adverse events had been reported in previous trials of sodium oxybate in adults with narcolepsy.

The study was sponsored by Jazz Pharmaceuticals.

LOS ANGELES—Eating fish at least once per week or eating fish one to three times per month, in addition to taking daily fish oil supplements, may be associated with a reduced risk of multiple sclerosis (MS), according to a preliminary study presented at the American Academy of Neurology’s 70th Annual Meeting. These findings suggest that the omega-3 fatty acids found in fish may be associated with lowering the risk of developing MS.

“Consuming fish that contain omega-3 fatty acids has been shown to have a variety of health benefits, so we wanted to see if this simple lifestyle modification, regularly eating fish and taking fish oil supplements, could reduce the risk of MS,” said lead study author Annette Langer-Gould, MD, PhD, Regional Lead for Clinical and Translational Neuroscience for the Southern California Permanente Medical Group in Pasadena, and Clinical Assistant Professor at the Keck School of Medicine of the University of Southern California in Los Angeles.

For this study, researchers examined the diets of 1,153 people (average age 36) from the MS Sunshine Study, a multi-ethnic matched case-control study of incident MS or clinically isolated syndrome (CIS), recruited from Kaiser Permanente Southern California.

Researchers queried participants about how much fish they consumed regularly. Investigators also examined 13 single nucleotide polymorphisms (SNPs) in FADS1, FADS2, and ELOV2, which regulate fatty acid biosynthesis.

High fish intake was defined as either eating one serving of fish per week or eating one to three servings per month in addition to taking daily fish oil supplements. Low intake was defined as less than one serving of fish per month and no fish oil supplements.

High fish intake was associated with a 45% reduced risk of MS or CIS, when compared with those who ate fish less than once a month and did not take fish oil supplements. A total of 180 of participants with MS had high fish intake compared with 251 of the healthy controls.

In addition, two SNPs, rs174611 and rs174618, in FADS2 were independently associated with a lower risk of MS, even after accounting for high fish intake. This suggests that some people may have a genetic advantage when it comes to regulating fatty acid levels, the researchers noted.

While the study suggests that omega-3 fatty acids, and how they are processed by the body, may play an important role in reducing MS risk. Dr. Langer-Gould and colleagues emphasized that their findings show an association, and not cause and effect. More research is needed to confirm the findings and to examine how omega-3 fatty acids may affect inflammation, metabolism, and nerve function.

The study was supported by the National Institute of Neurological Disorders and Stroke.

LOS ANGELES—Eating fish at least once per week or eating fish one to three times per month, in addition to taking daily fish oil supplements, may be associated with a reduced risk of multiple sclerosis (MS), according to a preliminary study presented at the American Academy of Neurology’s 70th Annual Meeting. These findings suggest that the omega-3 fatty acids found in fish may be associated with lowering the risk of developing MS.

“Consuming fish that contain omega-3 fatty acids has been shown to have a variety of health benefits, so we wanted to see if this simple lifestyle modification, regularly eating fish and taking fish oil supplements, could reduce the risk of MS,” said lead study author Annette Langer-Gould, MD, PhD, Regional Lead for Clinical and Translational Neuroscience for the Southern California Permanente Medical Group in Pasadena, and Clinical Assistant Professor at the Keck School of Medicine of the University of Southern California in Los Angeles.

For this study, researchers examined the diets of 1,153 people (average age 36) from the MS Sunshine Study, a multi-ethnic matched case-control study of incident MS or clinically isolated syndrome (CIS), recruited from Kaiser Permanente Southern California.

Researchers queried participants about how much fish they consumed regularly. Investigators also examined 13 single nucleotide polymorphisms (SNPs) in FADS1, FADS2, and ELOV2, which regulate fatty acid biosynthesis.

High fish intake was defined as either eating one serving of fish per week or eating one to three servings per month in addition to taking daily fish oil supplements. Low intake was defined as less than one serving of fish per month and no fish oil supplements.

High fish intake was associated with a 45% reduced risk of MS or CIS, when compared with those who ate fish less than once a month and did not take fish oil supplements. A total of 180 of participants with MS had high fish intake compared with 251 of the healthy controls.

In addition, two SNPs, rs174611 and rs174618, in FADS2 were independently associated with a lower risk of MS, even after accounting for high fish intake. This suggests that some people may have a genetic advantage when it comes to regulating fatty acid levels, the researchers noted.

While the study suggests that omega-3 fatty acids, and how they are processed by the body, may play an important role in reducing MS risk. Dr. Langer-Gould and colleagues emphasized that their findings show an association, and not cause and effect. More research is needed to confirm the findings and to examine how omega-3 fatty acids may affect inflammation, metabolism, and nerve function.

The study was supported by the National Institute of Neurological Disorders and Stroke.

LOS ANGELES—Eating fish at least once per week or eating fish one to three times per month, in addition to taking daily fish oil supplements, may be associated with a reduced risk of multiple sclerosis (MS), according to a preliminary study presented at the American Academy of Neurology’s 70th Annual Meeting. These findings suggest that the omega-3 fatty acids found in fish may be associated with lowering the risk of developing MS.

“Consuming fish that contain omega-3 fatty acids has been shown to have a variety of health benefits, so we wanted to see if this simple lifestyle modification, regularly eating fish and taking fish oil supplements, could reduce the risk of MS,” said lead study author Annette Langer-Gould, MD, PhD, Regional Lead for Clinical and Translational Neuroscience for the Southern California Permanente Medical Group in Pasadena, and Clinical Assistant Professor at the Keck School of Medicine of the University of Southern California in Los Angeles.

For this study, researchers examined the diets of 1,153 people (average age 36) from the MS Sunshine Study, a multi-ethnic matched case-control study of incident MS or clinically isolated syndrome (CIS), recruited from Kaiser Permanente Southern California.

Researchers queried participants about how much fish they consumed regularly. Investigators also examined 13 single nucleotide polymorphisms (SNPs) in FADS1, FADS2, and ELOV2, which regulate fatty acid biosynthesis.

High fish intake was defined as either eating one serving of fish per week or eating one to three servings per month in addition to taking daily fish oil supplements. Low intake was defined as less than one serving of fish per month and no fish oil supplements.

High fish intake was associated with a 45% reduced risk of MS or CIS, when compared with those who ate fish less than once a month and did not take fish oil supplements. A total of 180 of participants with MS had high fish intake compared with 251 of the healthy controls.

In addition, two SNPs, rs174611 and rs174618, in FADS2 were independently associated with a lower risk of MS, even after accounting for high fish intake. This suggests that some people may have a genetic advantage when it comes to regulating fatty acid levels, the researchers noted.

While the study suggests that omega-3 fatty acids, and how they are processed by the body, may play an important role in reducing MS risk. Dr. Langer-Gould and colleagues emphasized that their findings show an association, and not cause and effect. More research is needed to confirm the findings and to examine how omega-3 fatty acids may affect inflammation, metabolism, and nerve function.

The study was supported by the National Institute of Neurological Disorders and Stroke.

LOS ANGELES—Treatment for as long as four years with adjunctive perampanel is safe and effective for adolescents with secondarily generalized seizures or primary generalized tonic-clonic seizures, according to a post hoc study presented at the 70th Annual Meeting of the American Academy of Neurology. “These post hoc results are encouraging, given the refractory nature of these seizure types,” said the investigators.

Perampanel has regulatory approval for the treatment of partial seizures with or without secondarily generalized seizures, and for the adjunctive treatment of primary generalized tonic-clonic seizures in patients age 12 and younger with epilepsy. Phase II and III randomized, double-blind, placebo-controlled trials indicated that adjunctive perampanel (at doses of 12 mg/day or less) was effective and tolerable in patients with these types of seizures in idiopathic generalized epilepsy. The participants who completed these studies were eligible to enter one of four open-label extension studies.

Jesus Eric Piña-Garza, MD, a pediatric neurologist at the Children’s Hospital at TriStar Centennial in Nashville, and colleagues used data from these open-label extension studies to assess the long-term efficacy and safety of adjunctive perampanel in patients from ages 12 to 17 with secondarily generalized seizures or primary generalized tonic-clonic seizures.

The extension studies incorporated a blinded conversion period that lasted for six to 16 weeks, during which perampanel dose was optimized (at 12 mg/day or less), and a maintenance phase that lasted for 27 to 256 weeks. Total drug exposure was as long as five years. All patients received perampanel during these studies. Efficacy and safety assessments, which were performed for as long as four years, included median percent change in seizure frequency per 28 days and 50% and 75% responder and seizure-freedom rates. Investigators also monitored treatment-emergent adverse events.

The investigators included 129 adolescent patients in the safety analysis set, including 109 with secondarily generalized seizures and 19 with primary generalized tonic-clonic seizures. During the first year, median percent reductions in seizure frequency per 28 days were 62.8% for patients with secondarily generalized seizures and 84.0% for patients with primary generalized tonic-clonic seizures. During year four, median percent reductions in seizure frequency per 28 days were 73.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures. The 50% responder rates were 56.9% for patients with secondarily generalized seizures and 63.2% for patients with primary generalized tonic-clonic seizures in year one, and 65.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures in year four.

For each seizure type, the incidence of treatment-emergent adverse events was highest during the first year of perampanel exposure. The most common treatment-emergent adverse events were dizziness, somnolence, and nasopharyngitis.

The study was supported by Eisai.

LOS ANGELES—Treatment for as long as four years with adjunctive perampanel is safe and effective for adolescents with secondarily generalized seizures or primary generalized tonic-clonic seizures, according to a post hoc study presented at the 70th Annual Meeting of the American Academy of Neurology. “These post hoc results are encouraging, given the refractory nature of these seizure types,” said the investigators.

Perampanel has regulatory approval for the treatment of partial seizures with or without secondarily generalized seizures, and for the adjunctive treatment of primary generalized tonic-clonic seizures in patients age 12 and younger with epilepsy. Phase II and III randomized, double-blind, placebo-controlled trials indicated that adjunctive perampanel (at doses of 12 mg/day or less) was effective and tolerable in patients with these types of seizures in idiopathic generalized epilepsy. The participants who completed these studies were eligible to enter one of four open-label extension studies.

Jesus Eric Piña-Garza, MD, a pediatric neurologist at the Children’s Hospital at TriStar Centennial in Nashville, and colleagues used data from these open-label extension studies to assess the long-term efficacy and safety of adjunctive perampanel in patients from ages 12 to 17 with secondarily generalized seizures or primary generalized tonic-clonic seizures.

The extension studies incorporated a blinded conversion period that lasted for six to 16 weeks, during which perampanel dose was optimized (at 12 mg/day or less), and a maintenance phase that lasted for 27 to 256 weeks. Total drug exposure was as long as five years. All patients received perampanel during these studies. Efficacy and safety assessments, which were performed for as long as four years, included median percent change in seizure frequency per 28 days and 50% and 75% responder and seizure-freedom rates. Investigators also monitored treatment-emergent adverse events.

The investigators included 129 adolescent patients in the safety analysis set, including 109 with secondarily generalized seizures and 19 with primary generalized tonic-clonic seizures. During the first year, median percent reductions in seizure frequency per 28 days were 62.8% for patients with secondarily generalized seizures and 84.0% for patients with primary generalized tonic-clonic seizures. During year four, median percent reductions in seizure frequency per 28 days were 73.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures. The 50% responder rates were 56.9% for patients with secondarily generalized seizures and 63.2% for patients with primary generalized tonic-clonic seizures in year one, and 65.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures in year four.

For each seizure type, the incidence of treatment-emergent adverse events was highest during the first year of perampanel exposure. The most common treatment-emergent adverse events were dizziness, somnolence, and nasopharyngitis.

The study was supported by Eisai.

LOS ANGELES—Treatment for as long as four years with adjunctive perampanel is safe and effective for adolescents with secondarily generalized seizures or primary generalized tonic-clonic seizures, according to a post hoc study presented at the 70th Annual Meeting of the American Academy of Neurology. “These post hoc results are encouraging, given the refractory nature of these seizure types,” said the investigators.

Perampanel has regulatory approval for the treatment of partial seizures with or without secondarily generalized seizures, and for the adjunctive treatment of primary generalized tonic-clonic seizures in patients age 12 and younger with epilepsy. Phase II and III randomized, double-blind, placebo-controlled trials indicated that adjunctive perampanel (at doses of 12 mg/day or less) was effective and tolerable in patients with these types of seizures in idiopathic generalized epilepsy. The participants who completed these studies were eligible to enter one of four open-label extension studies.

Jesus Eric Piña-Garza, MD, a pediatric neurologist at the Children’s Hospital at TriStar Centennial in Nashville, and colleagues used data from these open-label extension studies to assess the long-term efficacy and safety of adjunctive perampanel in patients from ages 12 to 17 with secondarily generalized seizures or primary generalized tonic-clonic seizures.

The extension studies incorporated a blinded conversion period that lasted for six to 16 weeks, during which perampanel dose was optimized (at 12 mg/day or less), and a maintenance phase that lasted for 27 to 256 weeks. Total drug exposure was as long as five years. All patients received perampanel during these studies. Efficacy and safety assessments, which were performed for as long as four years, included median percent change in seizure frequency per 28 days and 50% and 75% responder and seizure-freedom rates. Investigators also monitored treatment-emergent adverse events.

The investigators included 129 adolescent patients in the safety analysis set, including 109 with secondarily generalized seizures and 19 with primary generalized tonic-clonic seizures. During the first year, median percent reductions in seizure frequency per 28 days were 62.8% for patients with secondarily generalized seizures and 84.0% for patients with primary generalized tonic-clonic seizures. During year four, median percent reductions in seizure frequency per 28 days were 73.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures. The 50% responder rates were 56.9% for patients with secondarily generalized seizures and 63.2% for patients with primary generalized tonic-clonic seizures in year one, and 65.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures in year four.

For each seizure type, the incidence of treatment-emergent adverse events was highest during the first year of perampanel exposure. The most common treatment-emergent adverse events were dizziness, somnolence, and nasopharyngitis.

The study was supported by Eisai.

The tears of people with established Parkinson’s disease have protein signatures distinct from those of healthy controls, researchers have learned.

Mark Lew, MD, and his colleagues at the University of Southern California, Los Angeles, used a noninvasive method to collect the tears and readily available assays to detect the proteins, paving the way for future studies of these proteins as biomarkers in early Parkinson’s disease (PD).

The researchers will report on their study at the annual meeting of the American Academy of Neurology in Los Angeles on April 22.

This research from Dr. Lew and his colleagues joins a host of ongoing efforts to find biomarkers for PD that can be used in the early stages of the disease, before motor dysfunction occurs. Other research groups are working on biomarkers in saliva and salivary glands, skin, blood, and cerebrospinal fluid. “Right now, a diagnosis of Parkinson’s disease is based on clinical history and then examination and then, potentially, on response to medication,” said Dr. Lew, professor of neurology, the vice chair of the department of neurology, and the director of the division of movement disorders at USC. “The difficulty is really being able to definitively be able to diagnose patients with early disease.”

Dr. Lew and his coinvestigators measured the levels of the protein alpha-synuclein in the tears of 55 people with PD and compared them with levels in the tears of 27 age- and sex-matched controls. They also measured oligomeric alpha-synuclein, an abnormal form of the protein whose aggregates are implicated in nerve damage in PD.

The test administered is based on a Schirmer’s test, which is used in ophthalmology to measure tear production. A strip of paper is placed in the lower eyelid pouch to collect tears, which the researchers then can analyze using commercially available assays.

Dr. Lew and his colleagues found levels of the oligomeric form of alpha-synuclein to be significantly greater in PD patients than they were in controls: an average of 1.45 ng/mg of tear protein, compared with 0.27 ng/mg in controls (P = .0007).

Total alpha-synuclein was decreased significantly in PD patients relative to healthy controls.

While the team looked at the levels of two additional proteins, CC chemokine ligand 2 and DJ-1 (Parkinson’s disease protein 7), neither of them varied significantly between PD patients and non-PD controls.

“We’re cautiously optimistic, and I don’t want to overstate the results because it’s still a relatively small group of subjects – we need to more than double the control population to make sure our results are maintained,” Dr. Lew said in an interview in advance of the meeting. “But it’s very exciting.”

At AAN, Dr. Lew’s research group will present findings from a larger cohort of both patients and controls. “Our expectation is that things will look similar and we will continue to see a significant difference in the oligomeric form of alpha-synuclein,” the tear protein associated with PD.

The idea of using tear proteins as biomarkers for PD came as a result of a collaboration with scientists working in USC’s ophthalmology lab, who had previously worked on tear biomarkers in other disorders, including Sjogren’s syndrome, Dr. Lew said.

Dr. Lew said that, if the initial results bear out in a larger cohort, the next step is to test the tears of people with genetic or atypical forms of PD and compare the results with those for idiopathic forms. “These atypical forms, like progressive supranuclear palsy [PSP] and multiple system atrophy [MSA], can be very difficult to tell apart clinically in the early stages. If we had a simple test to do that, it would be very helpful.”

A reliable biomarker, if it can be shown to be sensitive early in disease, also would have implications for the timing of disease-modifying interventions, such as the monoclonal antibodies or gene therapies that are currently being investigated.

“We don’t have those therapies now, but in a few years we very well could,” Dr. Lew said. “If we could identify patients early and if we had a therapy that we could give them that was disease-modifying, or neuroprotective, you’d want to start much earlier than we currently do.”

This study from Dr. Lew and his colleagues was supported by the Michael J. Fox Foundation and the Plotkin Foundation. Dr. Lew has received personal compensation for consulting for, serving on a scientific advisory board for, speaking for, or other activities with Teva Pharmaceutical Industries, US WorldMeds, AbbVie, Lundbeck, Acadia Pharmaceuticals, UCB, Revance Therapeutics, and Adamas Pharmaceuticals. Dr. Lew has received research support from Acorda Therapeutics, Biotie Therapies, NeuroDerm, and Lilly. None of the other authors had anything to disclose.

SOURCE: Feigenbaum D et al. Abstract 4209.

The tears of people with established Parkinson’s disease have protein signatures distinct from those of healthy controls, researchers have learned.

Mark Lew, MD, and his colleagues at the University of Southern California, Los Angeles, used a noninvasive method to collect the tears and readily available assays to detect the proteins, paving the way for future studies of these proteins as biomarkers in early Parkinson’s disease (PD).

The researchers will report on their study at the annual meeting of the American Academy of Neurology in Los Angeles on April 22.

This research from Dr. Lew and his colleagues joins a host of ongoing efforts to find biomarkers for PD that can be used in the early stages of the disease, before motor dysfunction occurs. Other research groups are working on biomarkers in saliva and salivary glands, skin, blood, and cerebrospinal fluid. “Right now, a diagnosis of Parkinson’s disease is based on clinical history and then examination and then, potentially, on response to medication,” said Dr. Lew, professor of neurology, the vice chair of the department of neurology, and the director of the division of movement disorders at USC. “The difficulty is really being able to definitively be able to diagnose patients with early disease.”

Dr. Lew and his coinvestigators measured the levels of the protein alpha-synuclein in the tears of 55 people with PD and compared them with levels in the tears of 27 age- and sex-matched controls. They also measured oligomeric alpha-synuclein, an abnormal form of the protein whose aggregates are implicated in nerve damage in PD.

The test administered is based on a Schirmer’s test, which is used in ophthalmology to measure tear production. A strip of paper is placed in the lower eyelid pouch to collect tears, which the researchers then can analyze using commercially available assays.

Dr. Lew and his colleagues found levels of the oligomeric form of alpha-synuclein to be significantly greater in PD patients than they were in controls: an average of 1.45 ng/mg of tear protein, compared with 0.27 ng/mg in controls (P = .0007).

Total alpha-synuclein was decreased significantly in PD patients relative to healthy controls.

While the team looked at the levels of two additional proteins, CC chemokine ligand 2 and DJ-1 (Parkinson’s disease protein 7), neither of them varied significantly between PD patients and non-PD controls.

“We’re cautiously optimistic, and I don’t want to overstate the results because it’s still a relatively small group of subjects – we need to more than double the control population to make sure our results are maintained,” Dr. Lew said in an interview in advance of the meeting. “But it’s very exciting.”

At AAN, Dr. Lew’s research group will present findings from a larger cohort of both patients and controls. “Our expectation is that things will look similar and we will continue to see a significant difference in the oligomeric form of alpha-synuclein,” the tear protein associated with PD.

The idea of using tear proteins as biomarkers for PD came as a result of a collaboration with scientists working in USC’s ophthalmology lab, who had previously worked on tear biomarkers in other disorders, including Sjogren’s syndrome, Dr. Lew said.

Dr. Lew said that, if the initial results bear out in a larger cohort, the next step is to test the tears of people with genetic or atypical forms of PD and compare the results with those for idiopathic forms. “These atypical forms, like progressive supranuclear palsy [PSP] and multiple system atrophy [MSA], can be very difficult to tell apart clinically in the early stages. If we had a simple test to do that, it would be very helpful.”

A reliable biomarker, if it can be shown to be sensitive early in disease, also would have implications for the timing of disease-modifying interventions, such as the monoclonal antibodies or gene therapies that are currently being investigated.

“We don’t have those therapies now, but in a few years we very well could,” Dr. Lew said. “If we could identify patients early and if we had a therapy that we could give them that was disease-modifying, or neuroprotective, you’d want to start much earlier than we currently do.”

This study from Dr. Lew and his colleagues was supported by the Michael J. Fox Foundation and the Plotkin Foundation. Dr. Lew has received personal compensation for consulting for, serving on a scientific advisory board for, speaking for, or other activities with Teva Pharmaceutical Industries, US WorldMeds, AbbVie, Lundbeck, Acadia Pharmaceuticals, UCB, Revance Therapeutics, and Adamas Pharmaceuticals. Dr. Lew has received research support from Acorda Therapeutics, Biotie Therapies, NeuroDerm, and Lilly. None of the other authors had anything to disclose.

SOURCE: Feigenbaum D et al. Abstract 4209.

The tears of people with established Parkinson’s disease have protein signatures distinct from those of healthy controls, researchers have learned.

Mark Lew, MD, and his colleagues at the University of Southern California, Los Angeles, used a noninvasive method to collect the tears and readily available assays to detect the proteins, paving the way for future studies of these proteins as biomarkers in early Parkinson’s disease (PD).

The researchers will report on their study at the annual meeting of the American Academy of Neurology in Los Angeles on April 22.

This research from Dr. Lew and his colleagues joins a host of ongoing efforts to find biomarkers for PD that can be used in the early stages of the disease, before motor dysfunction occurs. Other research groups are working on biomarkers in saliva and salivary glands, skin, blood, and cerebrospinal fluid. “Right now, a diagnosis of Parkinson’s disease is based on clinical history and then examination and then, potentially, on response to medication,” said Dr. Lew, professor of neurology, the vice chair of the department of neurology, and the director of the division of movement disorders at USC. “The difficulty is really being able to definitively be able to diagnose patients with early disease.”

Dr. Lew and his coinvestigators measured the levels of the protein alpha-synuclein in the tears of 55 people with PD and compared them with levels in the tears of 27 age- and sex-matched controls. They also measured oligomeric alpha-synuclein, an abnormal form of the protein whose aggregates are implicated in nerve damage in PD.

The test administered is based on a Schirmer’s test, which is used in ophthalmology to measure tear production. A strip of paper is placed in the lower eyelid pouch to collect tears, which the researchers then can analyze using commercially available assays.

Dr. Lew and his colleagues found levels of the oligomeric form of alpha-synuclein to be significantly greater in PD patients than they were in controls: an average of 1.45 ng/mg of tear protein, compared with 0.27 ng/mg in controls (P = .0007).

Total alpha-synuclein was decreased significantly in PD patients relative to healthy controls.

While the team looked at the levels of two additional proteins, CC chemokine ligand 2 and DJ-1 (Parkinson’s disease protein 7), neither of them varied significantly between PD patients and non-PD controls.

“We’re cautiously optimistic, and I don’t want to overstate the results because it’s still a relatively small group of subjects – we need to more than double the control population to make sure our results are maintained,” Dr. Lew said in an interview in advance of the meeting. “But it’s very exciting.”

At AAN, Dr. Lew’s research group will present findings from a larger cohort of both patients and controls. “Our expectation is that things will look similar and we will continue to see a significant difference in the oligomeric form of alpha-synuclein,” the tear protein associated with PD.

The idea of using tear proteins as biomarkers for PD came as a result of a collaboration with scientists working in USC’s ophthalmology lab, who had previously worked on tear biomarkers in other disorders, including Sjogren’s syndrome, Dr. Lew said.

Dr. Lew said that, if the initial results bear out in a larger cohort, the next step is to test the tears of people with genetic or atypical forms of PD and compare the results with those for idiopathic forms. “These atypical forms, like progressive supranuclear palsy [PSP] and multiple system atrophy [MSA], can be very difficult to tell apart clinically in the early stages. If we had a simple test to do that, it would be very helpful.”

A reliable biomarker, if it can be shown to be sensitive early in disease, also would have implications for the timing of disease-modifying interventions, such as the monoclonal antibodies or gene therapies that are currently being investigated.

“We don’t have those therapies now, but in a few years we very well could,” Dr. Lew said. “If we could identify patients early and if we had a therapy that we could give them that was disease-modifying, or neuroprotective, you’d want to start much earlier than we currently do.”

This study from Dr. Lew and his colleagues was supported by the Michael J. Fox Foundation and the Plotkin Foundation. Dr. Lew has received personal compensation for consulting for, serving on a scientific advisory board for, speaking for, or other activities with Teva Pharmaceutical Industries, US WorldMeds, AbbVie, Lundbeck, Acadia Pharmaceuticals, UCB, Revance Therapeutics, and Adamas Pharmaceuticals. Dr. Lew has received research support from Acorda Therapeutics, Biotie Therapies, NeuroDerm, and Lilly. None of the other authors had anything to disclose.

SOURCE: Feigenbaum D et al. Abstract 4209.