ICYMI Multiple Sclerosis

Short-Term Outcomes After Endovascular Treatment for Chronic Cerebrospinal Venous Insufficiency in Patients With MS
A minimally invasive endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) is safe and may produce “significant,” short-term improvement in the physical– and mental health–related quality of life in patients with multiple sclerosis (MS), according to researchers.

“Traditional theories surrounding treatment for MS in large part focus on autoimmune causes for brain pathology and neurologic symptoms. Based on this, treatment has been predominantly medications by mouth or injection,” stated Kenneth Mandato, MD, an interventional radiologist at the Albany Medical Center in New York.

“Interventional radiologists, pioneers in the field of minimally invasive therapies, have been performing … angioplasty for years to treat blocked or narrowed arteries and veins. We have been using angioplasty to open jugular and azygos veins in the neck and chest, respectively, to improve blood flow in people with MS. On follow-up, we have seen many of these individuals report significant symptom relief.”

MS subtypes within the Albany study group included 96 individuals with relapsing-remitting MS, 66 with secondary-progressive MS, and 30 with primary-progressive MS. The study population included those who underwent angioplasty alone and three who underwent angioplasty with a stent placement.

“Results of the study were quite exciting and promising,” stated Dr. Mandato. “We can attest to significant physical improvements reported in greater than 75% of those with relapsing-remitting and primary-progressive forms of MS. Additionally, mental health scores improved in greater than 70% of individuals studied. People with secondary-progressive MS showed statistically significant improvements in both physical and mental health scores at a rate of 59% and 50%, respectively,” he added.

“During a four-month period, we treated 213 individuals; 192 of these patients (141 women; average age, 49) responded to a standard questionnaire that evaluated key quality-of-life components, including changes in physical abilities, health perception, energy/fatigue, sexual function, emotional well-being, cognition, and pain,” explained coauthor Meridith J. Englander, MD, an interventional radiologist at the Albany Medical Center. “We ultimately broke these data down into physical and mental health scores for each person and found improvement in both components of quality of life,” she added. “In addition, we found a trend that patients undergoing this treatment more than 10 years after diagnosis did not respond as well as those with a more recent diagnosis.”

“To address the needs and concerns of those with MS who feel they cannot wait until definitive studies are completed, many doctors are currently offering treatments with the hope of helping individuals with hard-to-manage symptoms of MS,” said Dr. Mandato. “Physicians who perform these treatments hope that this work will provide insights into the design of a prospective, randomized trial that is needed to rigorously evaluate the role of this treatment in MS,” he added.

“As we are still early in fully understanding the condition and its relation to treatment of CCSVI, it is our hope that future double-blinded prospective studies will be performed to further assess the durability of these results,” Dr. Mandato concluded.

Managing Chronic Cerebrospinal Venous Insufficiency in Patients With MS
Performing angioplasty on veins in the neck and chest is safe and may be an effective way to treat the venous abnormalities and provide symptom relief in patients with multiple sclerosis (MS), investigators reported in a second study.

“Our results are important, because there are an estimated 400,000 individuals affected by MS in the United States, some of whom experience symptoms that limit their quality of life in several ways. For many, it can be quite debilitating,” said lead investigator Hector Ferral, MD, an interventional radiologist at NorthShore University HealthSystem in Evanston, Illinois. “These early results show that performing angioplasty on azygos and jugular vein lesions may have a positive impact on the symptoms of those individuals with MS and also could be an effective palliative treatment geared toward improving their quality of life.

“Our experience showed that 95% of the individuals we evaluated had venous obstructions, supporting the concept that venous lesions are common in individuals with MS,” Dr. Ferral continued. “Based on follow-up that included ultrasound one week postprocedure and clinic visits every three months, our results showed that people who have this treatment are not exposed to fatal risks. Portraying venous angioplasty of the azygos and jugular veins as a high-risk procedure is a widespread misconception that needs to be addressed and corrected. In addition to these significant safety findings, we noted that angioplasty provided symptomatic benefit in 55% of the individuals we treated.”

The retrospective review examined results of 105 procedures performed in 94 patients with MS (59 women; age range, 26 to 67). About 50% of participants had relapsing-remitting MS, 39% had secondary-progressive MS, 6.4% had primary-progressive MS, and 4.2% were unknown. Jugular and azygos veins were evaluated with selective venography and intravascular ultrasound. Angioplasty was performed if the imaging confirmed reflux, allowing blood to flow backward, or a greater than 50% decrease in the vessel’s diameter. If necessary, stents were then used to treat nonresponsive lesions or blockages. These individuals were given blood-thinning medications for six weeks after the treatment.

Dr. Ferral’s team reported symptomatic improvement in 55% of the individuals treated, and 38% reported no improvement. Seven percent of patients did not comply with their follow-up visits and were considered to be lost to follow-up. Close to 60% of those with relapsing-remitting MS reported improvement in symptoms, the highest of all the subgroups in this study.

“These important results revealed that for people with MS who experience debilitating symptoms, minimally invasive interventional radiology treatments can be an effective, palliative treatment that also may improve their quality of life,” said Dr. Ferral. “As interventional radiologists, our biggest challenge is to bring to the attention of other specialists, especially those physicians specialized in MS, the evidence that venous lesions, often classified CCSVI, may be a true entity that deserves further attention and serious research,” he explained.

In 2011, members of a Society of Interventional Radiology Foundation’s Research Consensus Panel noted that evaluating patients with MS who have narrowed jugular and azygos veins—and examining the value of widening those veins with angioplasty—warranted careful, well-designed research. The multidisciplinary panel indicated that the “mandatory goal” should be conducting large-scale, pivotal, multicenter trials to explore CCSVI.                     

Short-Term Outcomes After Endovascular Treatment for Chronic Cerebrospinal Venous Insufficiency in Patients With MS
A minimally invasive endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) is safe and may produce “significant,” short-term improvement in the physical– and mental health–related quality of life in patients with multiple sclerosis (MS), according to researchers.

“Traditional theories surrounding treatment for MS in large part focus on autoimmune causes for brain pathology and neurologic symptoms. Based on this, treatment has been predominantly medications by mouth or injection,” stated Kenneth Mandato, MD, an interventional radiologist at the Albany Medical Center in New York.

“Interventional radiologists, pioneers in the field of minimally invasive therapies, have been performing … angioplasty for years to treat blocked or narrowed arteries and veins. We have been using angioplasty to open jugular and azygos veins in the neck and chest, respectively, to improve blood flow in people with MS. On follow-up, we have seen many of these individuals report significant symptom relief.”

MS subtypes within the Albany study group included 96 individuals with relapsing-remitting MS, 66 with secondary-progressive MS, and 30 with primary-progressive MS. The study population included those who underwent angioplasty alone and three who underwent angioplasty with a stent placement.

“Results of the study were quite exciting and promising,” stated Dr. Mandato. “We can attest to significant physical improvements reported in greater than 75% of those with relapsing-remitting and primary-progressive forms of MS. Additionally, mental health scores improved in greater than 70% of individuals studied. People with secondary-progressive MS showed statistically significant improvements in both physical and mental health scores at a rate of 59% and 50%, respectively,” he added.

“During a four-month period, we treated 213 individuals; 192 of these patients (141 women; average age, 49) responded to a standard questionnaire that evaluated key quality-of-life components, including changes in physical abilities, health perception, energy/fatigue, sexual function, emotional well-being, cognition, and pain,” explained coauthor Meridith J. Englander, MD, an interventional radiologist at the Albany Medical Center. “We ultimately broke these data down into physical and mental health scores for each person and found improvement in both components of quality of life,” she added. “In addition, we found a trend that patients undergoing this treatment more than 10 years after diagnosis did not respond as well as those with a more recent diagnosis.”

“To address the needs and concerns of those with MS who feel they cannot wait until definitive studies are completed, many doctors are currently offering treatments with the hope of helping individuals with hard-to-manage symptoms of MS,” said Dr. Mandato. “Physicians who perform these treatments hope that this work will provide insights into the design of a prospective, randomized trial that is needed to rigorously evaluate the role of this treatment in MS,” he added.

“As we are still early in fully understanding the condition and its relation to treatment of CCSVI, it is our hope that future double-blinded prospective studies will be performed to further assess the durability of these results,” Dr. Mandato concluded.

Managing Chronic Cerebrospinal Venous Insufficiency in Patients With MS
Performing angioplasty on veins in the neck and chest is safe and may be an effective way to treat the venous abnormalities and provide symptom relief in patients with multiple sclerosis (MS), investigators reported in a second study.

“Our results are important, because there are an estimated 400,000 individuals affected by MS in the United States, some of whom experience symptoms that limit their quality of life in several ways. For many, it can be quite debilitating,” said lead investigator Hector Ferral, MD, an interventional radiologist at NorthShore University HealthSystem in Evanston, Illinois. “These early results show that performing angioplasty on azygos and jugular vein lesions may have a positive impact on the symptoms of those individuals with MS and also could be an effective palliative treatment geared toward improving their quality of life.

“Our experience showed that 95% of the individuals we evaluated had venous obstructions, supporting the concept that venous lesions are common in individuals with MS,” Dr. Ferral continued. “Based on follow-up that included ultrasound one week postprocedure and clinic visits every three months, our results showed that people who have this treatment are not exposed to fatal risks. Portraying venous angioplasty of the azygos and jugular veins as a high-risk procedure is a widespread misconception that needs to be addressed and corrected. In addition to these significant safety findings, we noted that angioplasty provided symptomatic benefit in 55% of the individuals we treated.”

The retrospective review examined results of 105 procedures performed in 94 patients with MS (59 women; age range, 26 to 67). About 50% of participants had relapsing-remitting MS, 39% had secondary-progressive MS, 6.4% had primary-progressive MS, and 4.2% were unknown. Jugular and azygos veins were evaluated with selective venography and intravascular ultrasound. Angioplasty was performed if the imaging confirmed reflux, allowing blood to flow backward, or a greater than 50% decrease in the vessel’s diameter. If necessary, stents were then used to treat nonresponsive lesions or blockages. These individuals were given blood-thinning medications for six weeks after the treatment.

Dr. Ferral’s team reported symptomatic improvement in 55% of the individuals treated, and 38% reported no improvement. Seven percent of patients did not comply with their follow-up visits and were considered to be lost to follow-up. Close to 60% of those with relapsing-remitting MS reported improvement in symptoms, the highest of all the subgroups in this study.

“These important results revealed that for people with MS who experience debilitating symptoms, minimally invasive interventional radiology treatments can be an effective, palliative treatment that also may improve their quality of life,” said Dr. Ferral. “As interventional radiologists, our biggest challenge is to bring to the attention of other specialists, especially those physicians specialized in MS, the evidence that venous lesions, often classified CCSVI, may be a true entity that deserves further attention and serious research,” he explained.

In 2011, members of a Society of Interventional Radiology Foundation’s Research Consensus Panel noted that evaluating patients with MS who have narrowed jugular and azygos veins—and examining the value of widening those veins with angioplasty—warranted careful, well-designed research. The multidisciplinary panel indicated that the “mandatory goal” should be conducting large-scale, pivotal, multicenter trials to explore CCSVI.                     

Short-Term Outcomes After Endovascular Treatment for Chronic Cerebrospinal Venous Insufficiency in Patients With MS
A minimally invasive endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) is safe and may produce “significant,” short-term improvement in the physical– and mental health–related quality of life in patients with multiple sclerosis (MS), according to researchers.

“Traditional theories surrounding treatment for MS in large part focus on autoimmune causes for brain pathology and neurologic symptoms. Based on this, treatment has been predominantly medications by mouth or injection,” stated Kenneth Mandato, MD, an interventional radiologist at the Albany Medical Center in New York.

“Interventional radiologists, pioneers in the field of minimally invasive therapies, have been performing … angioplasty for years to treat blocked or narrowed arteries and veins. We have been using angioplasty to open jugular and azygos veins in the neck and chest, respectively, to improve blood flow in people with MS. On follow-up, we have seen many of these individuals report significant symptom relief.”

MS subtypes within the Albany study group included 96 individuals with relapsing-remitting MS, 66 with secondary-progressive MS, and 30 with primary-progressive MS. The study population included those who underwent angioplasty alone and three who underwent angioplasty with a stent placement.

“Results of the study were quite exciting and promising,” stated Dr. Mandato. “We can attest to significant physical improvements reported in greater than 75% of those with relapsing-remitting and primary-progressive forms of MS. Additionally, mental health scores improved in greater than 70% of individuals studied. People with secondary-progressive MS showed statistically significant improvements in both physical and mental health scores at a rate of 59% and 50%, respectively,” he added.

“During a four-month period, we treated 213 individuals; 192 of these patients (141 women; average age, 49) responded to a standard questionnaire that evaluated key quality-of-life components, including changes in physical abilities, health perception, energy/fatigue, sexual function, emotional well-being, cognition, and pain,” explained coauthor Meridith J. Englander, MD, an interventional radiologist at the Albany Medical Center. “We ultimately broke these data down into physical and mental health scores for each person and found improvement in both components of quality of life,” she added. “In addition, we found a trend that patients undergoing this treatment more than 10 years after diagnosis did not respond as well as those with a more recent diagnosis.”

“To address the needs and concerns of those with MS who feel they cannot wait until definitive studies are completed, many doctors are currently offering treatments with the hope of helping individuals with hard-to-manage symptoms of MS,” said Dr. Mandato. “Physicians who perform these treatments hope that this work will provide insights into the design of a prospective, randomized trial that is needed to rigorously evaluate the role of this treatment in MS,” he added.

“As we are still early in fully understanding the condition and its relation to treatment of CCSVI, it is our hope that future double-blinded prospective studies will be performed to further assess the durability of these results,” Dr. Mandato concluded.

Managing Chronic Cerebrospinal Venous Insufficiency in Patients With MS
Performing angioplasty on veins in the neck and chest is safe and may be an effective way to treat the venous abnormalities and provide symptom relief in patients with multiple sclerosis (MS), investigators reported in a second study.

“Our results are important, because there are an estimated 400,000 individuals affected by MS in the United States, some of whom experience symptoms that limit their quality of life in several ways. For many, it can be quite debilitating,” said lead investigator Hector Ferral, MD, an interventional radiologist at NorthShore University HealthSystem in Evanston, Illinois. “These early results show that performing angioplasty on azygos and jugular vein lesions may have a positive impact on the symptoms of those individuals with MS and also could be an effective palliative treatment geared toward improving their quality of life.

“Our experience showed that 95% of the individuals we evaluated had venous obstructions, supporting the concept that venous lesions are common in individuals with MS,” Dr. Ferral continued. “Based on follow-up that included ultrasound one week postprocedure and clinic visits every three months, our results showed that people who have this treatment are not exposed to fatal risks. Portraying venous angioplasty of the azygos and jugular veins as a high-risk procedure is a widespread misconception that needs to be addressed and corrected. In addition to these significant safety findings, we noted that angioplasty provided symptomatic benefit in 55% of the individuals we treated.”

The retrospective review examined results of 105 procedures performed in 94 patients with MS (59 women; age range, 26 to 67). About 50% of participants had relapsing-remitting MS, 39% had secondary-progressive MS, 6.4% had primary-progressive MS, and 4.2% were unknown. Jugular and azygos veins were evaluated with selective venography and intravascular ultrasound. Angioplasty was performed if the imaging confirmed reflux, allowing blood to flow backward, or a greater than 50% decrease in the vessel’s diameter. If necessary, stents were then used to treat nonresponsive lesions or blockages. These individuals were given blood-thinning medications for six weeks after the treatment.

Dr. Ferral’s team reported symptomatic improvement in 55% of the individuals treated, and 38% reported no improvement. Seven percent of patients did not comply with their follow-up visits and were considered to be lost to follow-up. Close to 60% of those with relapsing-remitting MS reported improvement in symptoms, the highest of all the subgroups in this study.

“These important results revealed that for people with MS who experience debilitating symptoms, minimally invasive interventional radiology treatments can be an effective, palliative treatment that also may improve their quality of life,” said Dr. Ferral. “As interventional radiologists, our biggest challenge is to bring to the attention of other specialists, especially those physicians specialized in MS, the evidence that venous lesions, often classified CCSVI, may be a true entity that deserves further attention and serious research,” he explained.

In 2011, members of a Society of Interventional Radiology Foundation’s Research Consensus Panel noted that evaluating patients with MS who have narrowed jugular and azygos veins—and examining the value of widening those veins with angioplasty—warranted careful, well-designed research. The multidisciplinary panel indicated that the “mandatory goal” should be conducting large-scale, pivotal, multicenter trials to explore CCSVI.                     

Adults with a higher level of daily physical activity may have a decreased risk of Alzheimer’s disease, according to research published in the online April 18 Neurology. Researchers objectively measured the continuous exercise and nonexercise physical activity of 716 older subjects without dementia by using actigraphy monitoring for up to 10 days. During an average follow-up of four years, 71 persons were diagnosed with clinical Alzheimer’s disease, and the investigators identified an inverse association between total daily physical activity and Alzheimer’s disease (hazard ratio, 0.477) after adjusting for age, sex, and education. This association remained following further adjustments for self-reported physical, social, and cognitive activities; APOE allele status; and current level of motor function, depressive symptoms, and chronic health conditions. “A higher level of total daily physical activity is associated with reduced risk of Alzheimer’s disease,” the investigators concluded.

The herpes zoster vaccine is associated with a small increased risk of allergic reactions in the week following vaccination but is generally safe and well tolerated, according to a study published in the May Journal of Internal Medicine. Researchers analyzed data from 193,083 persons ages 50 and older who had received a zoster vaccine from January 2007 to December 2008 and who were included in the Vaccine Safety Datalink project. A case-centered approach and a self-controlled case series approach were used for analysis. Although results showed that risk of allergic reaction significantly increased within one to seven days of vaccination (RR, 2.13), the investigators identified no increased risk for cerebrovascular or cardiovascular events, meningitis, encephalitis, encephalopathy, Ramsay–Hunt syndrome, or Bell’s palsy. According to the study authors, this research supports the safety results from the zoster vaccine’s prelicensure clinical trials.

Consumption of low-fat dairy products may reduce the risk of stroke, according to research published in the online April 19 Stroke. In a prospective cohort study, researchers followed 74,961 Swedish women and men who were free from cancer and cardiovascular disease. During a mean 10.2-year follow-up, 4,089 cases of stroke were recorded among the cohort, including 3,159 cerebral infarctions, 583 hemorrhagic strokes, and 347 unspecified strokes. Analysis showed an inverse association between consumption of low-fat dairy food and risk of total stroke and cerebral infarction, with multivariable relative risks for the highest compared with the lowest quintile of low-fat dairy consumption of .88 for total stroke and .87 for cerebral infarction. “These results suggest that low-fat dairy consumption is inversely associated with the risk of stroke,” the researchers concluded.

Cognitive abilities decline more rapidly at the end of life than before the terminal period, and late-life participation in mentally stimulating activities might enhance cognitive functioning, according to two studies published in the online April 4 Neurology. In one study, 174 persons without dementia completed a battery of cognitive performance tests at annual intervals for six to 15 years prior to death, after which researchers assessed participants’ brains for evidence of Alzheimer’s disease. Although cognitive decline prior to the terminal period was relatively gradual, cognition declined rapidly during the terminal period. In the second study, 1,076 dementia-free older persons annually completed clinical evaluations (mean, 4.9 years) regarding cognitive performance as well as participation in mentally stimulating activities. Investigators found that cognitive activity participation and cognitive functioning declined at moderately correlative rates. “The results suggest that more frequent mental stimulation in old age leads to better cognitive functioning,” the researchers stated.

Patients with chronic temporal lobe epilepsy have extensive brain abnormalities and age-accelerated ventricular expansion that may have a significant neurodevelopmental impact, according to research published in the online April 3 Epilepsia. Investigators compared differences in brain structure as well as patterns of age-related change in 55 patients with chronic temporal lobe epilepsy with childhood or adolescent onset and 53 healthy controls. Using MRI studies, the researchers identified extensive anatomic abnormalities in patients with chronic temporal lobe epilepsy. Furthermore, participants with epilepsy showed age-accelerated changes in the third and lateral ventricles, though age-related changes in other regions of interest were mostly comparable with those of controls. “These cumulative structural abnormalities appear to represent a significant anatomic burden for persons with epilepsy, the consequences of which remain to be determined as they progress into elder years,” the study authors said.

Treatment with omega-3 fatty acid supplements is not correlated with reduction in disease activity in patients with relapsing-remitting multiple sclerosis (MS), according to a study published in the online April 16 issue of Archives of Neurology. From 2004 to 2008, investigators conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial of 96 patients ages 18 to 55 with active relapsing-remitting MS. Half the participants were randomized to placebo, half were randomized to receive omega-3 fatty acids, and, after six months of treatment, all patients received 44 µg of interferon beta-1a three times per week for another 18 months. Results showed that MRI measurements of gadolinium-enhancing lesions were similar among groups in the first six months, and no difference in relapse rate was found after six or 24 months.

Patients with Parkinson’s disease often have persistent ocular tremors that prevent eye stability during fixation, which suggests that modern, precise oculomotor testing of this feature could serve as a biomarker for early diagnosis of Parkinson’s disease, researchers reported in the online April 9 Archives of Neurology. The investigators conducted a case-control study with 112 patients with Parkinson’s disease, 18 de novo, untreated patients, and 60 age-matched controls. Patients’ oculomotor parameters were assessed with precise eye-tracking technology, and oculomotor function between groups during fixation was compared with oculomotor function while tracking a randomly displaced target on a computer monitor. All 112 patients with Parkinson’s disease showed oscillatory fixation instability. “The pervasiveness and specificity of [ocular tremor] suggest that modern, precise oculomotor testing could provide a valuable early physiological biomarker for diagnosing Parkinson’s disease,” the study authors concluded.

Wrist-worn biosensors that continuously record the sympathetically mediated electrodermal activity (EDA) of patients with epilepsy show autonomic correlates of postictal EEG suppression that may serve as biomarkers for risk of sudden death in epilepsy, according to research published in the online April 25 Neurology. Researchers recorded a total of 34 seizures (22 complex partial; 12 tonic-clonic) in patients with refractory epilepsy who wore the wrist sensors. Analysis of the postictal period showed heightened heart rate and a surge in EDA at the same time as persistent suppression of parasympathetic-modulated high-frequency (HF) power of heart rate. In addition, increased EDA response amplitude was associated with increased duration of EEG suppression (r = 0.81), and decreased HF power was associated with increased duration of EEG suppression (r = -0.87). “The magnitude of both sympathetic activation and parasympathetic suppression increases with duration of EEG suppression after tonic-clonic seizures,” the investigators stated.

The suggested immobilization test (SIT) may assist clinicians in diagnosing restless legs syndrome (RLS) in patients with Parkinson’s disease, according to research published in the March 21 online Movement Disorders. The investigators compared SIT scores and polysomnography measures of 50 patients with Parkinson’s disease (25 with RLS), 25 patients with primary RLS, and 25 controls matched for age and sex. Results indicated that patients with Parkinson’s disease and RLS had increased mean leg discomfort scores and high leg discomfort at the end of the test compared with patients with Parkinson’s disease but without RLS. In addition, the SIT showed sensitivity of 91% and specificity of 72% for RLS diagnosis in patients with Parkinson’s disease during symptomatic time intervals. “The sensory SIT is a simple test that may help diagnose RLS in patients with Parkinson’s disease,” the researchers concluded. 

Adults with a higher level of daily physical activity may have a decreased risk of Alzheimer’s disease, according to research published in the online April 18 Neurology. Researchers objectively measured the continuous exercise and nonexercise physical activity of 716 older subjects without dementia by using actigraphy monitoring for up to 10 days. During an average follow-up of four years, 71 persons were diagnosed with clinical Alzheimer’s disease, and the investigators identified an inverse association between total daily physical activity and Alzheimer’s disease (hazard ratio, 0.477) after adjusting for age, sex, and education. This association remained following further adjustments for self-reported physical, social, and cognitive activities; APOE allele status; and current level of motor function, depressive symptoms, and chronic health conditions. “A higher level of total daily physical activity is associated with reduced risk of Alzheimer’s disease,” the investigators concluded.

The herpes zoster vaccine is associated with a small increased risk of allergic reactions in the week following vaccination but is generally safe and well tolerated, according to a study published in the May Journal of Internal Medicine. Researchers analyzed data from 193,083 persons ages 50 and older who had received a zoster vaccine from January 2007 to December 2008 and who were included in the Vaccine Safety Datalink project. A case-centered approach and a self-controlled case series approach were used for analysis. Although results showed that risk of allergic reaction significantly increased within one to seven days of vaccination (RR, 2.13), the investigators identified no increased risk for cerebrovascular or cardiovascular events, meningitis, encephalitis, encephalopathy, Ramsay–Hunt syndrome, or Bell’s palsy. According to the study authors, this research supports the safety results from the zoster vaccine’s prelicensure clinical trials.

Consumption of low-fat dairy products may reduce the risk of stroke, according to research published in the online April 19 Stroke. In a prospective cohort study, researchers followed 74,961 Swedish women and men who were free from cancer and cardiovascular disease. During a mean 10.2-year follow-up, 4,089 cases of stroke were recorded among the cohort, including 3,159 cerebral infarctions, 583 hemorrhagic strokes, and 347 unspecified strokes. Analysis showed an inverse association between consumption of low-fat dairy food and risk of total stroke and cerebral infarction, with multivariable relative risks for the highest compared with the lowest quintile of low-fat dairy consumption of .88 for total stroke and .87 for cerebral infarction. “These results suggest that low-fat dairy consumption is inversely associated with the risk of stroke,” the researchers concluded.

Cognitive abilities decline more rapidly at the end of life than before the terminal period, and late-life participation in mentally stimulating activities might enhance cognitive functioning, according to two studies published in the online April 4 Neurology. In one study, 174 persons without dementia completed a battery of cognitive performance tests at annual intervals for six to 15 years prior to death, after which researchers assessed participants’ brains for evidence of Alzheimer’s disease. Although cognitive decline prior to the terminal period was relatively gradual, cognition declined rapidly during the terminal period. In the second study, 1,076 dementia-free older persons annually completed clinical evaluations (mean, 4.9 years) regarding cognitive performance as well as participation in mentally stimulating activities. Investigators found that cognitive activity participation and cognitive functioning declined at moderately correlative rates. “The results suggest that more frequent mental stimulation in old age leads to better cognitive functioning,” the researchers stated.

Patients with chronic temporal lobe epilepsy have extensive brain abnormalities and age-accelerated ventricular expansion that may have a significant neurodevelopmental impact, according to research published in the online April 3 Epilepsia. Investigators compared differences in brain structure as well as patterns of age-related change in 55 patients with chronic temporal lobe epilepsy with childhood or adolescent onset and 53 healthy controls. Using MRI studies, the researchers identified extensive anatomic abnormalities in patients with chronic temporal lobe epilepsy. Furthermore, participants with epilepsy showed age-accelerated changes in the third and lateral ventricles, though age-related changes in other regions of interest were mostly comparable with those of controls. “These cumulative structural abnormalities appear to represent a significant anatomic burden for persons with epilepsy, the consequences of which remain to be determined as they progress into elder years,” the study authors said.

Treatment with omega-3 fatty acid supplements is not correlated with reduction in disease activity in patients with relapsing-remitting multiple sclerosis (MS), according to a study published in the online April 16 issue of Archives of Neurology. From 2004 to 2008, investigators conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial of 96 patients ages 18 to 55 with active relapsing-remitting MS. Half the participants were randomized to placebo, half were randomized to receive omega-3 fatty acids, and, after six months of treatment, all patients received 44 µg of interferon beta-1a three times per week for another 18 months. Results showed that MRI measurements of gadolinium-enhancing lesions were similar among groups in the first six months, and no difference in relapse rate was found after six or 24 months.

Patients with Parkinson’s disease often have persistent ocular tremors that prevent eye stability during fixation, which suggests that modern, precise oculomotor testing of this feature could serve as a biomarker for early diagnosis of Parkinson’s disease, researchers reported in the online April 9 Archives of Neurology. The investigators conducted a case-control study with 112 patients with Parkinson’s disease, 18 de novo, untreated patients, and 60 age-matched controls. Patients’ oculomotor parameters were assessed with precise eye-tracking technology, and oculomotor function between groups during fixation was compared with oculomotor function while tracking a randomly displaced target on a computer monitor. All 112 patients with Parkinson’s disease showed oscillatory fixation instability. “The pervasiveness and specificity of [ocular tremor] suggest that modern, precise oculomotor testing could provide a valuable early physiological biomarker for diagnosing Parkinson’s disease,” the study authors concluded.

Wrist-worn biosensors that continuously record the sympathetically mediated electrodermal activity (EDA) of patients with epilepsy show autonomic correlates of postictal EEG suppression that may serve as biomarkers for risk of sudden death in epilepsy, according to research published in the online April 25 Neurology. Researchers recorded a total of 34 seizures (22 complex partial; 12 tonic-clonic) in patients with refractory epilepsy who wore the wrist sensors. Analysis of the postictal period showed heightened heart rate and a surge in EDA at the same time as persistent suppression of parasympathetic-modulated high-frequency (HF) power of heart rate. In addition, increased EDA response amplitude was associated with increased duration of EEG suppression (r = 0.81), and decreased HF power was associated with increased duration of EEG suppression (r = -0.87). “The magnitude of both sympathetic activation and parasympathetic suppression increases with duration of EEG suppression after tonic-clonic seizures,” the investigators stated.

The suggested immobilization test (SIT) may assist clinicians in diagnosing restless legs syndrome (RLS) in patients with Parkinson’s disease, according to research published in the March 21 online Movement Disorders. The investigators compared SIT scores and polysomnography measures of 50 patients with Parkinson’s disease (25 with RLS), 25 patients with primary RLS, and 25 controls matched for age and sex. Results indicated that patients with Parkinson’s disease and RLS had increased mean leg discomfort scores and high leg discomfort at the end of the test compared with patients with Parkinson’s disease but without RLS. In addition, the SIT showed sensitivity of 91% and specificity of 72% for RLS diagnosis in patients with Parkinson’s disease during symptomatic time intervals. “The sensory SIT is a simple test that may help diagnose RLS in patients with Parkinson’s disease,” the researchers concluded. 

Adults with a higher level of daily physical activity may have a decreased risk of Alzheimer’s disease, according to research published in the online April 18 Neurology. Researchers objectively measured the continuous exercise and nonexercise physical activity of 716 older subjects without dementia by using actigraphy monitoring for up to 10 days. During an average follow-up of four years, 71 persons were diagnosed with clinical Alzheimer’s disease, and the investigators identified an inverse association between total daily physical activity and Alzheimer’s disease (hazard ratio, 0.477) after adjusting for age, sex, and education. This association remained following further adjustments for self-reported physical, social, and cognitive activities; APOE allele status; and current level of motor function, depressive symptoms, and chronic health conditions. “A higher level of total daily physical activity is associated with reduced risk of Alzheimer’s disease,” the investigators concluded.

The herpes zoster vaccine is associated with a small increased risk of allergic reactions in the week following vaccination but is generally safe and well tolerated, according to a study published in the May Journal of Internal Medicine. Researchers analyzed data from 193,083 persons ages 50 and older who had received a zoster vaccine from January 2007 to December 2008 and who were included in the Vaccine Safety Datalink project. A case-centered approach and a self-controlled case series approach were used for analysis. Although results showed that risk of allergic reaction significantly increased within one to seven days of vaccination (RR, 2.13), the investigators identified no increased risk for cerebrovascular or cardiovascular events, meningitis, encephalitis, encephalopathy, Ramsay–Hunt syndrome, or Bell’s palsy. According to the study authors, this research supports the safety results from the zoster vaccine’s prelicensure clinical trials.

Consumption of low-fat dairy products may reduce the risk of stroke, according to research published in the online April 19 Stroke. In a prospective cohort study, researchers followed 74,961 Swedish women and men who were free from cancer and cardiovascular disease. During a mean 10.2-year follow-up, 4,089 cases of stroke were recorded among the cohort, including 3,159 cerebral infarctions, 583 hemorrhagic strokes, and 347 unspecified strokes. Analysis showed an inverse association between consumption of low-fat dairy food and risk of total stroke and cerebral infarction, with multivariable relative risks for the highest compared with the lowest quintile of low-fat dairy consumption of .88 for total stroke and .87 for cerebral infarction. “These results suggest that low-fat dairy consumption is inversely associated with the risk of stroke,” the researchers concluded.

Cognitive abilities decline more rapidly at the end of life than before the terminal period, and late-life participation in mentally stimulating activities might enhance cognitive functioning, according to two studies published in the online April 4 Neurology. In one study, 174 persons without dementia completed a battery of cognitive performance tests at annual intervals for six to 15 years prior to death, after which researchers assessed participants’ brains for evidence of Alzheimer’s disease. Although cognitive decline prior to the terminal period was relatively gradual, cognition declined rapidly during the terminal period. In the second study, 1,076 dementia-free older persons annually completed clinical evaluations (mean, 4.9 years) regarding cognitive performance as well as participation in mentally stimulating activities. Investigators found that cognitive activity participation and cognitive functioning declined at moderately correlative rates. “The results suggest that more frequent mental stimulation in old age leads to better cognitive functioning,” the researchers stated.

Patients with chronic temporal lobe epilepsy have extensive brain abnormalities and age-accelerated ventricular expansion that may have a significant neurodevelopmental impact, according to research published in the online April 3 Epilepsia. Investigators compared differences in brain structure as well as patterns of age-related change in 55 patients with chronic temporal lobe epilepsy with childhood or adolescent onset and 53 healthy controls. Using MRI studies, the researchers identified extensive anatomic abnormalities in patients with chronic temporal lobe epilepsy. Furthermore, participants with epilepsy showed age-accelerated changes in the third and lateral ventricles, though age-related changes in other regions of interest were mostly comparable with those of controls. “These cumulative structural abnormalities appear to represent a significant anatomic burden for persons with epilepsy, the consequences of which remain to be determined as they progress into elder years,” the study authors said.

Treatment with omega-3 fatty acid supplements is not correlated with reduction in disease activity in patients with relapsing-remitting multiple sclerosis (MS), according to a study published in the online April 16 issue of Archives of Neurology. From 2004 to 2008, investigators conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial of 96 patients ages 18 to 55 with active relapsing-remitting MS. Half the participants were randomized to placebo, half were randomized to receive omega-3 fatty acids, and, after six months of treatment, all patients received 44 µg of interferon beta-1a three times per week for another 18 months. Results showed that MRI measurements of gadolinium-enhancing lesions were similar among groups in the first six months, and no difference in relapse rate was found after six or 24 months.

Patients with Parkinson’s disease often have persistent ocular tremors that prevent eye stability during fixation, which suggests that modern, precise oculomotor testing of this feature could serve as a biomarker for early diagnosis of Parkinson’s disease, researchers reported in the online April 9 Archives of Neurology. The investigators conducted a case-control study with 112 patients with Parkinson’s disease, 18 de novo, untreated patients, and 60 age-matched controls. Patients’ oculomotor parameters were assessed with precise eye-tracking technology, and oculomotor function between groups during fixation was compared with oculomotor function while tracking a randomly displaced target on a computer monitor. All 112 patients with Parkinson’s disease showed oscillatory fixation instability. “The pervasiveness and specificity of [ocular tremor] suggest that modern, precise oculomotor testing could provide a valuable early physiological biomarker for diagnosing Parkinson’s disease,” the study authors concluded.

Wrist-worn biosensors that continuously record the sympathetically mediated electrodermal activity (EDA) of patients with epilepsy show autonomic correlates of postictal EEG suppression that may serve as biomarkers for risk of sudden death in epilepsy, according to research published in the online April 25 Neurology. Researchers recorded a total of 34 seizures (22 complex partial; 12 tonic-clonic) in patients with refractory epilepsy who wore the wrist sensors. Analysis of the postictal period showed heightened heart rate and a surge in EDA at the same time as persistent suppression of parasympathetic-modulated high-frequency (HF) power of heart rate. In addition, increased EDA response amplitude was associated with increased duration of EEG suppression (r = 0.81), and decreased HF power was associated with increased duration of EEG suppression (r = -0.87). “The magnitude of both sympathetic activation and parasympathetic suppression increases with duration of EEG suppression after tonic-clonic seizures,” the investigators stated.

The suggested immobilization test (SIT) may assist clinicians in diagnosing restless legs syndrome (RLS) in patients with Parkinson’s disease, according to research published in the March 21 online Movement Disorders. The investigators compared SIT scores and polysomnography measures of 50 patients with Parkinson’s disease (25 with RLS), 25 patients with primary RLS, and 25 controls matched for age and sex. Results indicated that patients with Parkinson’s disease and RLS had increased mean leg discomfort scores and high leg discomfort at the end of the test compared with patients with Parkinson’s disease but without RLS. In addition, the SIT showed sensitivity of 91% and specificity of 72% for RLS diagnosis in patients with Parkinson’s disease during symptomatic time intervals. “The sensory SIT is a simple test that may help diagnose RLS in patients with Parkinson’s disease,” the researchers concluded. 

Adipose tissue in patients with multiple sclerosis is marked by an activated lipolytic metabolic state.

AMSTERDAM—Patients with multiple sclerosis (MS) have an altered metabolic flexibility after glucose load, both at rest and during exercise, researchers reported at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

Persons with MS had a higher baseline respiratory quotient at rest than healthy controls did, which may indicate that the former have a higher rate of carbohydrate oxidation and a lower rate of lipid oxidation than the latter do. Also, after 40 minutes of light exercise, patients with MS showed greater energy expenditure than controls did.

Measuring Metabolismin Patients With MS
One symptom of MS is an intolerance to exercise, but it is not clear whether this symptom results from a metabolic change. To test the hypothesis that altered metabolic flexibility contributes to exercise intolerance in patients with MS, Anja Mähler, a nutritionist at the Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Charité University Medicine, Berlin, and colleagues conducted a prospective study of 16 patients (eight men), with MS who were taking glatiramer acetate.

The patients’ mean age was 45, their mean BMI was 25.2, and they had had MS for a median of 133 months. Eight healthy men and eight healthy women also were studied as controls. The mean age of members of the control group was 40, and their mean BMI was 23.3.

In two separate tests, the researchers compared the groups’ postprandial and exercise activity metabolism with their resting metabolism, both after an oral glucose load. Blood marker metabolites and calorimetry were used to study systemic metabolism, and adipose tissue and skeletal muscle microdialysis were used to examine local metabolism.

Altered Metabolic Flexibility Could Result From MS
After an oral glucose load, patients with MS expended slightly less postprandial energy than controls did. Baseline and postprandial respiratory quotients, however, were higher in patients with MS than in controls, which indicated that the patients had higher carbohydrate and lower lipid oxidation rates than did controls. In addition, higher baseline and postprandial levels of dialysate glucose and lactate in adipose tissue in patients with MS indicated an activated lipolytic metabolic state.

The respiratory quotient kinetics were different in patients with MS than in controls during exercise, according to the study. Respiratory quotient did not reach a plateau in patients with MS as it did in controls.

The altered metabolic flexibility in patients with MS at rest and during exercise “might be attributed to an autonomic dysfunction,” said the investigators. The activated lipolytic metabolic state seen in the adipose tissue of patients with MS “could be caused by local monocyte/macrophage infiltration due to systemic inflammation,” they remarked. Future studies should investigate whether these two factors contribute to mitochondrial dysfunction in patients with MS, the investigators concluded.   

Adipose tissue in patients with multiple sclerosis is marked by an activated lipolytic metabolic state.

AMSTERDAM—Patients with multiple sclerosis (MS) have an altered metabolic flexibility after glucose load, both at rest and during exercise, researchers reported at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

Persons with MS had a higher baseline respiratory quotient at rest than healthy controls did, which may indicate that the former have a higher rate of carbohydrate oxidation and a lower rate of lipid oxidation than the latter do. Also, after 40 minutes of light exercise, patients with MS showed greater energy expenditure than controls did.

Measuring Metabolismin Patients With MS
One symptom of MS is an intolerance to exercise, but it is not clear whether this symptom results from a metabolic change. To test the hypothesis that altered metabolic flexibility contributes to exercise intolerance in patients with MS, Anja Mähler, a nutritionist at the Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Charité University Medicine, Berlin, and colleagues conducted a prospective study of 16 patients (eight men), with MS who were taking glatiramer acetate.

The patients’ mean age was 45, their mean BMI was 25.2, and they had had MS for a median of 133 months. Eight healthy men and eight healthy women also were studied as controls. The mean age of members of the control group was 40, and their mean BMI was 23.3.

In two separate tests, the researchers compared the groups’ postprandial and exercise activity metabolism with their resting metabolism, both after an oral glucose load. Blood marker metabolites and calorimetry were used to study systemic metabolism, and adipose tissue and skeletal muscle microdialysis were used to examine local metabolism.

Altered Metabolic Flexibility Could Result From MS
After an oral glucose load, patients with MS expended slightly less postprandial energy than controls did. Baseline and postprandial respiratory quotients, however, were higher in patients with MS than in controls, which indicated that the patients had higher carbohydrate and lower lipid oxidation rates than did controls. In addition, higher baseline and postprandial levels of dialysate glucose and lactate in adipose tissue in patients with MS indicated an activated lipolytic metabolic state.

The respiratory quotient kinetics were different in patients with MS than in controls during exercise, according to the study. Respiratory quotient did not reach a plateau in patients with MS as it did in controls.

The altered metabolic flexibility in patients with MS at rest and during exercise “might be attributed to an autonomic dysfunction,” said the investigators. The activated lipolytic metabolic state seen in the adipose tissue of patients with MS “could be caused by local monocyte/macrophage infiltration due to systemic inflammation,” they remarked. Future studies should investigate whether these two factors contribute to mitochondrial dysfunction in patients with MS, the investigators concluded.   

Adipose tissue in patients with multiple sclerosis is marked by an activated lipolytic metabolic state.

AMSTERDAM—Patients with multiple sclerosis (MS) have an altered metabolic flexibility after glucose load, both at rest and during exercise, researchers reported at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

Persons with MS had a higher baseline respiratory quotient at rest than healthy controls did, which may indicate that the former have a higher rate of carbohydrate oxidation and a lower rate of lipid oxidation than the latter do. Also, after 40 minutes of light exercise, patients with MS showed greater energy expenditure than controls did.

Measuring Metabolismin Patients With MS
One symptom of MS is an intolerance to exercise, but it is not clear whether this symptom results from a metabolic change. To test the hypothesis that altered metabolic flexibility contributes to exercise intolerance in patients with MS, Anja Mähler, a nutritionist at the Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Charité University Medicine, Berlin, and colleagues conducted a prospective study of 16 patients (eight men), with MS who were taking glatiramer acetate.

The patients’ mean age was 45, their mean BMI was 25.2, and they had had MS for a median of 133 months. Eight healthy men and eight healthy women also were studied as controls. The mean age of members of the control group was 40, and their mean BMI was 23.3.

In two separate tests, the researchers compared the groups’ postprandial and exercise activity metabolism with their resting metabolism, both after an oral glucose load. Blood marker metabolites and calorimetry were used to study systemic metabolism, and adipose tissue and skeletal muscle microdialysis were used to examine local metabolism.

Altered Metabolic Flexibility Could Result From MS
After an oral glucose load, patients with MS expended slightly less postprandial energy than controls did. Baseline and postprandial respiratory quotients, however, were higher in patients with MS than in controls, which indicated that the patients had higher carbohydrate and lower lipid oxidation rates than did controls. In addition, higher baseline and postprandial levels of dialysate glucose and lactate in adipose tissue in patients with MS indicated an activated lipolytic metabolic state.

The respiratory quotient kinetics were different in patients with MS than in controls during exercise, according to the study. Respiratory quotient did not reach a plateau in patients with MS as it did in controls.

The altered metabolic flexibility in patients with MS at rest and during exercise “might be attributed to an autonomic dysfunction,” said the investigators. The activated lipolytic metabolic state seen in the adipose tissue of patients with MS “could be caused by local monocyte/macrophage infiltration due to systemic inflammation,” they remarked. Future studies should investigate whether these two factors contribute to mitochondrial dysfunction in patients with MS, the investigators concluded.   

Low levels of vitamin D can increase MS risk but low gestational levels of 25(OH)D have no effect on MS risk.

AMSTERDAM—Levels of vitamin D greater than or equal to 75 nmol/L are associated with a 61% lower risk for multiple sclerosis (MS), researchers reported at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis. Gestational vitamin D levels do not affect the risk for MS in children, however.

Jonatan Salzer, a graduate student in clinical neuroscience at Umeå University in Sweden, and associates conducted a study to estimate the risk for MS by examining levels of 25(OH)D in prospectively collected blood samples from patients with MS and controls. The investigators also sought to evaluate the risk for MS in children by studying levels of 25(OH)D during pregnancy.

The researchers created a database of MS cases and mothers of patients with MS in the four northern counties of Sweden. The database was cross-linked to various biobanks that contained serum and plasma samples taken between 1976 and 2005. The researchers found 192 MS cases with prospectively collected samples for their study of risk factors of MS, and 37 gestational samples taken during pregnancies in which the offspring had later developed MS, as the basis for their inquiry into gestational risk factors of MS. Controls were matched for sex, biobank, sampling date, and age.

Decreasing Levels of Vitamin D
Analysis showed that 3.6% of MS cases and 7.8% of controls had levels of 25(OH)D ≥75 nmol/L, which is the cutoff for normal levels, as defined by the American Endocrine Society. The investigators found a negative correlation between 25(OH)D levels and sampling year for samples collected from May through October (ie, the 25(OH)D levels were lower in later samples).

Also, the risk for 25(OH)D levels <75 nmol/L in controls was three times higher in samples taken after 1985 than it was in samples taken before 1985. Overall, the risk of having 25(OH)D levels <75 nmol/L increased from 1976 to 2005, according to Mr. Salzer.

Changes in the population’s summer behavior, including increasing use of sunscreen, wearing clothes that cover more of the body, and a reduction in time spent outdoors, could explain the overall decrease in vitamin D levels, said Mr. Salzer. “If this finding can be replicated in other cohorts, and applies to the time before 1976, perhaps it is the key to why MS incidence is increasing,” he added.

No effect on MS risk was observed when the investigators grouped 25(OH)D levels into other categories, such as median, tertiles, and quintiles. This result occurred “because of the high prevalence of 25(OH)D levels <75 nmol/L in northern Sweden” and “suggests that higher levels are needed to protect against MS,” said Mr. Salzer.

The results contradict the findings of the 2011 diet questionnaire study conducted by Mirzaei et al. The investigators noted that their results “must be treated with caution,” however, because of the small sample size. “There is a need for expanded study material on vitamin D levels, in which samples are collected from gestation through adolescence,” Mr. Salzer said.

A Call to Revise Recommended Doses of Vitamin D
It may be reasonable to “adjust the supplementation recommendations to increase the doses and include the entire population, with the goal of no one having levels below 75 nmol/L” concluded Mr. Salzer.   

Low levels of vitamin D can increase MS risk but low gestational levels of 25(OH)D have no effect on MS risk.

AMSTERDAM—Levels of vitamin D greater than or equal to 75 nmol/L are associated with a 61% lower risk for multiple sclerosis (MS), researchers reported at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis. Gestational vitamin D levels do not affect the risk for MS in children, however.

Jonatan Salzer, a graduate student in clinical neuroscience at Umeå University in Sweden, and associates conducted a study to estimate the risk for MS by examining levels of 25(OH)D in prospectively collected blood samples from patients with MS and controls. The investigators also sought to evaluate the risk for MS in children by studying levels of 25(OH)D during pregnancy.

The researchers created a database of MS cases and mothers of patients with MS in the four northern counties of Sweden. The database was cross-linked to various biobanks that contained serum and plasma samples taken between 1976 and 2005. The researchers found 192 MS cases with prospectively collected samples for their study of risk factors of MS, and 37 gestational samples taken during pregnancies in which the offspring had later developed MS, as the basis for their inquiry into gestational risk factors of MS. Controls were matched for sex, biobank, sampling date, and age.

Decreasing Levels of Vitamin D
Analysis showed that 3.6% of MS cases and 7.8% of controls had levels of 25(OH)D ≥75 nmol/L, which is the cutoff for normal levels, as defined by the American Endocrine Society. The investigators found a negative correlation between 25(OH)D levels and sampling year for samples collected from May through October (ie, the 25(OH)D levels were lower in later samples).

Also, the risk for 25(OH)D levels <75 nmol/L in controls was three times higher in samples taken after 1985 than it was in samples taken before 1985. Overall, the risk of having 25(OH)D levels <75 nmol/L increased from 1976 to 2005, according to Mr. Salzer.

Changes in the population’s summer behavior, including increasing use of sunscreen, wearing clothes that cover more of the body, and a reduction in time spent outdoors, could explain the overall decrease in vitamin D levels, said Mr. Salzer. “If this finding can be replicated in other cohorts, and applies to the time before 1976, perhaps it is the key to why MS incidence is increasing,” he added.

No effect on MS risk was observed when the investigators grouped 25(OH)D levels into other categories, such as median, tertiles, and quintiles. This result occurred “because of the high prevalence of 25(OH)D levels <75 nmol/L in northern Sweden” and “suggests that higher levels are needed to protect against MS,” said Mr. Salzer.

The results contradict the findings of the 2011 diet questionnaire study conducted by Mirzaei et al. The investigators noted that their results “must be treated with caution,” however, because of the small sample size. “There is a need for expanded study material on vitamin D levels, in which samples are collected from gestation through adolescence,” Mr. Salzer said.

A Call to Revise Recommended Doses of Vitamin D
It may be reasonable to “adjust the supplementation recommendations to increase the doses and include the entire population, with the goal of no one having levels below 75 nmol/L” concluded Mr. Salzer.   

Low levels of vitamin D can increase MS risk but low gestational levels of 25(OH)D have no effect on MS risk.

AMSTERDAM—Levels of vitamin D greater than or equal to 75 nmol/L are associated with a 61% lower risk for multiple sclerosis (MS), researchers reported at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis. Gestational vitamin D levels do not affect the risk for MS in children, however.

Jonatan Salzer, a graduate student in clinical neuroscience at Umeå University in Sweden, and associates conducted a study to estimate the risk for MS by examining levels of 25(OH)D in prospectively collected blood samples from patients with MS and controls. The investigators also sought to evaluate the risk for MS in children by studying levels of 25(OH)D during pregnancy.

The researchers created a database of MS cases and mothers of patients with MS in the four northern counties of Sweden. The database was cross-linked to various biobanks that contained serum and plasma samples taken between 1976 and 2005. The researchers found 192 MS cases with prospectively collected samples for their study of risk factors of MS, and 37 gestational samples taken during pregnancies in which the offspring had later developed MS, as the basis for their inquiry into gestational risk factors of MS. Controls were matched for sex, biobank, sampling date, and age.

Decreasing Levels of Vitamin D
Analysis showed that 3.6% of MS cases and 7.8% of controls had levels of 25(OH)D ≥75 nmol/L, which is the cutoff for normal levels, as defined by the American Endocrine Society. The investigators found a negative correlation between 25(OH)D levels and sampling year for samples collected from May through October (ie, the 25(OH)D levels were lower in later samples).

Also, the risk for 25(OH)D levels <75 nmol/L in controls was three times higher in samples taken after 1985 than it was in samples taken before 1985. Overall, the risk of having 25(OH)D levels <75 nmol/L increased from 1976 to 2005, according to Mr. Salzer.

Changes in the population’s summer behavior, including increasing use of sunscreen, wearing clothes that cover more of the body, and a reduction in time spent outdoors, could explain the overall decrease in vitamin D levels, said Mr. Salzer. “If this finding can be replicated in other cohorts, and applies to the time before 1976, perhaps it is the key to why MS incidence is increasing,” he added.

No effect on MS risk was observed when the investigators grouped 25(OH)D levels into other categories, such as median, tertiles, and quintiles. This result occurred “because of the high prevalence of 25(OH)D levels <75 nmol/L in northern Sweden” and “suggests that higher levels are needed to protect against MS,” said Mr. Salzer.

The results contradict the findings of the 2011 diet questionnaire study conducted by Mirzaei et al. The investigators noted that their results “must be treated with caution,” however, because of the small sample size. “There is a need for expanded study material on vitamin D levels, in which samples are collected from gestation through adolescence,” Mr. Salzer said.

A Call to Revise Recommended Doses of Vitamin D
It may be reasonable to “adjust the supplementation recommendations to increase the doses and include the entire population, with the goal of no one having levels below 75 nmol/L” concluded Mr. Salzer.   

Symptoms of migraine aura may resemble those of multiple sclerosis (MS) relapse, and some MS drugs may cause headache.

STOWE, VT—Migraine and multiple sclerosis (MS) can have similar symptoms and often are comorbid diseases, according to Angela Applebee, MD, who spoke at the Headache Cooperative of New England’s 22nd Annual Headache Symposium. Neurologists should know which MS therapies can contribute to headache and which migraine drugs to prescribe with caution if a patient is taking certain new MS therapies, said Dr. Applebee, Assistant Professor of Neurology at the University of Vermont in Burlington.

The Link Between Migraine and MS
“The most convincing study of the link between migraine and MS” is the Nursing Health Study, said Dr. Applebee. That prospective study, during which investigators at New York University sent surveys to 116,000 nurses from 1989 to 1995, found that patients with migraine had a 39% higher risk of developing MS than nonmigraneurs. The absolute risk of developing MS was 0.15% higher, which means that migraine is a modest predictor of MS. Stronger predictors of MS include factors such as DRB1*1501 haplotype or history of infectious mononucleosis.

The study also found that patients with MS had a 33% greater chance of being diagnosed with migraine during follow-up. This difference was nonsignificant, however, said Dr. Applebee.

Differentiating Between Migraine Aura and MS Relapse
Migraine aura and MS relapse may have similar symptoms, but several principles can help neurologists distinguish between the two. First, aura tends not to last as long as MS relapse. In general, migraine aura lasts from five to 60 minutes, with the exception of the rare hemiplegic migraine variant. In MS relapse, on the other hand, new or worsening previous symptoms usually occur for 24 hours. “When I’m doing a history on a new patient, I’m trying to determine whether the symptom is always there, or whether it comes and goes, to help determine whether it could be a relapse or an aura,” Dr. Applebee explained.

Second, the symptoms of migraine aura tend to be consistent, but those of MS relapse tend to vary. A stress such as an infection, however, can cause an MS relapse characterized by a recurrence of old symptoms.

Also, each occurrence of migraine usually is related to the same areas of the brain. In contrast, each MS relapse, by definition, affects a different area of the brain than the previous MS relapse had affected. “If the optic nerve is first involved [in a relapse], another area of the brain should be next involved,” said Dr. Applebee. “Different areas of the brain don’t have to be involved in migraine,” she added.

Between 20% and 30% of auras entail visual and sensory disturbance. If an MS relapse entails a visual disturbance, it tends to include the symptoms of optic neuritis, such as pain when moving the eye and cloudy vision. MS relapses also may be associated with nystagmus or diplopia, said Dr. Applebee.

Drugs for MS May Cause Headache
Several drugs used to treat MS may cause headache. Natalizumab, a once-per-month infusion, can cause a postinfusion headache that lasts 24 hours before resolving itself completely. “If you premedicate prior to the infusion, this tends not to be an issue, and I haven’t seen that patients with migraine are more predisposed to having headaches with natalizumab,” advised Dr. Applebee.

Interferon therapies, which are given by subcutaneous or intramuscular injection, sometimes cause flulike symptoms that last from three to six months after the start of therapy. “If you teach patients to premedicate prior to their injections, it can minimize the flulike symptoms,” said Dr. Applebee. “Patients with migraine tend to have more difficulty in controlling their migraines when they first go on interferon therapy.” This difficulty, however, is not a contraindication for using interferon therapies in these patients, she added.

A patient with MS also may experience headache for the first four weeks after starting to take fingolimod, which the FDA approved in 2010. After four weeks, the headache usually resolves itself. Initiating treatment with fingolimod sometimes causes a pounding headache in patients with no previous history of headache. The drug also may make it difficult for patients with migraine to control their headache, but pulse steroids can provide relief, said Dr. Applebee.

Monitoring Fingolimod Use in Patients With Comorbid Cardiac Problems
Because fingolimod acts on the S1P1 receptors, patients may have a decreased heart rate within the first six hours of their first dose of the drug. The drug may lead to first- and second-degree heart block.

“When we dose these patients, we do a baseline ECG in our office, monitor them for six hours with vitals every hour, and then have a second ECG performed prior to exit,” noted Dr. Applebee. Patients with abnormal ECGs should be admitted to the hospital to ensure that they can tolerate the medication, she observed.

“In general, calcium-channel blockers and beta-blockers, if possible, should be avoided for migraine prophylactic therapy in these patients because of the possible interaction with fingolimod,” advised Dr. Applebee.

A recent study found that a beta-blocker in combination with fingolimod decreased heart rate to a statistically significant degree. A calcium-channel blocker did not have this effect, however, when it was administered with fingolimod. If a patient with MS and cardiac problems is taking fingolimod, a neurologist should consult his or her primary care doctor to determine the most appropriate medication for prophylaxis, concluded Dr. Applebee.   

Symptoms of migraine aura may resemble those of multiple sclerosis (MS) relapse, and some MS drugs may cause headache.

STOWE, VT—Migraine and multiple sclerosis (MS) can have similar symptoms and often are comorbid diseases, according to Angela Applebee, MD, who spoke at the Headache Cooperative of New England’s 22nd Annual Headache Symposium. Neurologists should know which MS therapies can contribute to headache and which migraine drugs to prescribe with caution if a patient is taking certain new MS therapies, said Dr. Applebee, Assistant Professor of Neurology at the University of Vermont in Burlington.

The Link Between Migraine and MS
“The most convincing study of the link between migraine and MS” is the Nursing Health Study, said Dr. Applebee. That prospective study, during which investigators at New York University sent surveys to 116,000 nurses from 1989 to 1995, found that patients with migraine had a 39% higher risk of developing MS than nonmigraneurs. The absolute risk of developing MS was 0.15% higher, which means that migraine is a modest predictor of MS. Stronger predictors of MS include factors such as DRB1*1501 haplotype or history of infectious mononucleosis.

The study also found that patients with MS had a 33% greater chance of being diagnosed with migraine during follow-up. This difference was nonsignificant, however, said Dr. Applebee.

Differentiating Between Migraine Aura and MS Relapse
Migraine aura and MS relapse may have similar symptoms, but several principles can help neurologists distinguish between the two. First, aura tends not to last as long as MS relapse. In general, migraine aura lasts from five to 60 minutes, with the exception of the rare hemiplegic migraine variant. In MS relapse, on the other hand, new or worsening previous symptoms usually occur for 24 hours. “When I’m doing a history on a new patient, I’m trying to determine whether the symptom is always there, or whether it comes and goes, to help determine whether it could be a relapse or an aura,” Dr. Applebee explained.

Second, the symptoms of migraine aura tend to be consistent, but those of MS relapse tend to vary. A stress such as an infection, however, can cause an MS relapse characterized by a recurrence of old symptoms.

Also, each occurrence of migraine usually is related to the same areas of the brain. In contrast, each MS relapse, by definition, affects a different area of the brain than the previous MS relapse had affected. “If the optic nerve is first involved [in a relapse], another area of the brain should be next involved,” said Dr. Applebee. “Different areas of the brain don’t have to be involved in migraine,” she added.

Between 20% and 30% of auras entail visual and sensory disturbance. If an MS relapse entails a visual disturbance, it tends to include the symptoms of optic neuritis, such as pain when moving the eye and cloudy vision. MS relapses also may be associated with nystagmus or diplopia, said Dr. Applebee.

Drugs for MS May Cause Headache
Several drugs used to treat MS may cause headache. Natalizumab, a once-per-month infusion, can cause a postinfusion headache that lasts 24 hours before resolving itself completely. “If you premedicate prior to the infusion, this tends not to be an issue, and I haven’t seen that patients with migraine are more predisposed to having headaches with natalizumab,” advised Dr. Applebee.

Interferon therapies, which are given by subcutaneous or intramuscular injection, sometimes cause flulike symptoms that last from three to six months after the start of therapy. “If you teach patients to premedicate prior to their injections, it can minimize the flulike symptoms,” said Dr. Applebee. “Patients with migraine tend to have more difficulty in controlling their migraines when they first go on interferon therapy.” This difficulty, however, is not a contraindication for using interferon therapies in these patients, she added.

A patient with MS also may experience headache for the first four weeks after starting to take fingolimod, which the FDA approved in 2010. After four weeks, the headache usually resolves itself. Initiating treatment with fingolimod sometimes causes a pounding headache in patients with no previous history of headache. The drug also may make it difficult for patients with migraine to control their headache, but pulse steroids can provide relief, said Dr. Applebee.

Monitoring Fingolimod Use in Patients With Comorbid Cardiac Problems
Because fingolimod acts on the S1P1 receptors, patients may have a decreased heart rate within the first six hours of their first dose of the drug. The drug may lead to first- and second-degree heart block.

“When we dose these patients, we do a baseline ECG in our office, monitor them for six hours with vitals every hour, and then have a second ECG performed prior to exit,” noted Dr. Applebee. Patients with abnormal ECGs should be admitted to the hospital to ensure that they can tolerate the medication, she observed.

“In general, calcium-channel blockers and beta-blockers, if possible, should be avoided for migraine prophylactic therapy in these patients because of the possible interaction with fingolimod,” advised Dr. Applebee.

A recent study found that a beta-blocker in combination with fingolimod decreased heart rate to a statistically significant degree. A calcium-channel blocker did not have this effect, however, when it was administered with fingolimod. If a patient with MS and cardiac problems is taking fingolimod, a neurologist should consult his or her primary care doctor to determine the most appropriate medication for prophylaxis, concluded Dr. Applebee.   

Symptoms of migraine aura may resemble those of multiple sclerosis (MS) relapse, and some MS drugs may cause headache.

STOWE, VT—Migraine and multiple sclerosis (MS) can have similar symptoms and often are comorbid diseases, according to Angela Applebee, MD, who spoke at the Headache Cooperative of New England’s 22nd Annual Headache Symposium. Neurologists should know which MS therapies can contribute to headache and which migraine drugs to prescribe with caution if a patient is taking certain new MS therapies, said Dr. Applebee, Assistant Professor of Neurology at the University of Vermont in Burlington.

The Link Between Migraine and MS
“The most convincing study of the link between migraine and MS” is the Nursing Health Study, said Dr. Applebee. That prospective study, during which investigators at New York University sent surveys to 116,000 nurses from 1989 to 1995, found that patients with migraine had a 39% higher risk of developing MS than nonmigraneurs. The absolute risk of developing MS was 0.15% higher, which means that migraine is a modest predictor of MS. Stronger predictors of MS include factors such as DRB1*1501 haplotype or history of infectious mononucleosis.

The study also found that patients with MS had a 33% greater chance of being diagnosed with migraine during follow-up. This difference was nonsignificant, however, said Dr. Applebee.

Differentiating Between Migraine Aura and MS Relapse
Migraine aura and MS relapse may have similar symptoms, but several principles can help neurologists distinguish between the two. First, aura tends not to last as long as MS relapse. In general, migraine aura lasts from five to 60 minutes, with the exception of the rare hemiplegic migraine variant. In MS relapse, on the other hand, new or worsening previous symptoms usually occur for 24 hours. “When I’m doing a history on a new patient, I’m trying to determine whether the symptom is always there, or whether it comes and goes, to help determine whether it could be a relapse or an aura,” Dr. Applebee explained.

Second, the symptoms of migraine aura tend to be consistent, but those of MS relapse tend to vary. A stress such as an infection, however, can cause an MS relapse characterized by a recurrence of old symptoms.

Also, each occurrence of migraine usually is related to the same areas of the brain. In contrast, each MS relapse, by definition, affects a different area of the brain than the previous MS relapse had affected. “If the optic nerve is first involved [in a relapse], another area of the brain should be next involved,” said Dr. Applebee. “Different areas of the brain don’t have to be involved in migraine,” she added.

Between 20% and 30% of auras entail visual and sensory disturbance. If an MS relapse entails a visual disturbance, it tends to include the symptoms of optic neuritis, such as pain when moving the eye and cloudy vision. MS relapses also may be associated with nystagmus or diplopia, said Dr. Applebee.

Drugs for MS May Cause Headache
Several drugs used to treat MS may cause headache. Natalizumab, a once-per-month infusion, can cause a postinfusion headache that lasts 24 hours before resolving itself completely. “If you premedicate prior to the infusion, this tends not to be an issue, and I haven’t seen that patients with migraine are more predisposed to having headaches with natalizumab,” advised Dr. Applebee.

Interferon therapies, which are given by subcutaneous or intramuscular injection, sometimes cause flulike symptoms that last from three to six months after the start of therapy. “If you teach patients to premedicate prior to their injections, it can minimize the flulike symptoms,” said Dr. Applebee. “Patients with migraine tend to have more difficulty in controlling their migraines when they first go on interferon therapy.” This difficulty, however, is not a contraindication for using interferon therapies in these patients, she added.

A patient with MS also may experience headache for the first four weeks after starting to take fingolimod, which the FDA approved in 2010. After four weeks, the headache usually resolves itself. Initiating treatment with fingolimod sometimes causes a pounding headache in patients with no previous history of headache. The drug also may make it difficult for patients with migraine to control their headache, but pulse steroids can provide relief, said Dr. Applebee.

Monitoring Fingolimod Use in Patients With Comorbid Cardiac Problems
Because fingolimod acts on the S1P1 receptors, patients may have a decreased heart rate within the first six hours of their first dose of the drug. The drug may lead to first- and second-degree heart block.

“When we dose these patients, we do a baseline ECG in our office, monitor them for six hours with vitals every hour, and then have a second ECG performed prior to exit,” noted Dr. Applebee. Patients with abnormal ECGs should be admitted to the hospital to ensure that they can tolerate the medication, she observed.

“In general, calcium-channel blockers and beta-blockers, if possible, should be avoided for migraine prophylactic therapy in these patients because of the possible interaction with fingolimod,” advised Dr. Applebee.

A recent study found that a beta-blocker in combination with fingolimod decreased heart rate to a statistically significant degree. A calcium-channel blocker did not have this effect, however, when it was administered with fingolimod. If a patient with MS and cardiac problems is taking fingolimod, a neurologist should consult his or her primary care doctor to determine the most appropriate medication for prophylaxis, concluded Dr. Applebee.   

Women ages 65 and older with retinopathy are more likely to have cognitive decline and larger ischemic lesion volumes, researchers reported in the March 14 online Neurology. Using fundus photography to assess retinopathy and the modified Mini-Mental State Examination (3MSE) to assess cognitive performance over time, the investigators studied 511 women who were enrolled in the Women’s Health Initiative Memory Study and the Sight Examination Study. After a 10-year follow-up period, women with retinopathy had lower 3MSE scores, 47% larger ischemic volumes in the total brain, and 68% larger ischemic volumes in the parietal lobe. According to the researchers, the association between retinopathy and cognitive impairment, as well as larger ischemic lesion volumes, “strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes.”
Regular use of statins is associated with a modest reduction in the risk of Parkinson’s disease, according to a study in the March Archives of Neurology. The prospective study included 38,192 men and 90,874 women participating in two ongoing US cohorts. Those enrolled were followed for 12 years, during which 644 cases (338 women) of Parkinson’s disease were documented. The investigators found that current statin users had a lower risk of Parkinson’s disease, compared with nonusers. Furthermore, participants younger than 60 at baseline had a significant association between Parkinson’s disease risk and statin use, while those who were older did not have such an association. “The possibility that some statins may reduce Parkinson’s disease risk deserves further consideration,” the study authors stated.

Labels for statin drugs will now include information about memory loss and confusion side effects experienced by some patients, according to changes issued by the FDA. The statin drugs include atorvastatin, fluvastatin, lovastatin, lovastatin extended-release, pitavastatin, pravastatin, rosuvastatin, and simvastatin, as well as combination products. According to the FDA, the cognitive effects experienced by patients taking statins were usually not serious and were reversed by stopping statin use. In addition to describing cognitive effects, label changes to the statins will provide information on blood sugar increases experienced by some patients and regarding a greater risk of being diagnosed with type 2 diabetes mellitus. The updated labels also identify contraindications for lovastatin and remove the recommendation for routine periodic monitoring of liver enzymes in patients taking statins. The FDA emphasized that health care professionals and patients should be aware of the most current information on statin risks, while remaining assured that statins provide an important health benefit.

The FDA has approved the Avonex pen and a new dose titration regimen for once-a-week treatment of Avonex in patients with relapsing forms of multiple sclerosis (MS). Patients may experience less injection anxiety and pain by using the Avonex pen, which has an automated injection device and a smaller needle than the currently available Avonex Prefilled Syringe. Data from an open-label, multicenter, phase IIIb study showed that approximately nine of 10 patients successfully used the device, and 94% of patients preferred the Avonex pen to the Avonex Prefilled Syringe. In addition, a randomized, phase I study found that the new dose titration regimen, which gradually escalates the dose of Avonex (Biogen Idec; Weston, Massachusetts) at treatment initiation, reduced the incidence and severity of flulike symptoms.

Women who have multiple pregnancies may have a reduced risk of multiple sclerosis (MS), according to research published in the March 7 online Neurology. Investigators reviewed the cases of 282 men and women who had a first clinical diagnosis of CNS demyelination between 2003 and 2006. These 282 patients (ages 18 to 59) were compared with a matched control group of 542 patients who did not have a first clinical diagnosis of CNS demyelination. Among women, having a higher number of offspring was associated with a lower risk of a first clinical diagnosis of CNS demyelination. “These findings are consistent with a cumulative beneficial effect of pregnancy,” the study authors stated. They speculated that societal trends toward having children at a later age and having fewer children overall may help explain the increasing rate of MS cases in women.

Women ages 65 and older with retinopathy are more likely to have cognitive decline and larger ischemic lesion volumes, researchers reported in the March 14 online Neurology. Using fundus photography to assess retinopathy and the modified Mini-Mental State Examination (3MSE) to assess cognitive performance over time, the investigators studied 511 women who were enrolled in the Women’s Health Initiative Memory Study and the Sight Examination Study. After a 10-year follow-up period, women with retinopathy had lower 3MSE scores, 47% larger ischemic volumes in the total brain, and 68% larger ischemic volumes in the parietal lobe. According to the researchers, the association between retinopathy and cognitive impairment, as well as larger ischemic lesion volumes, “strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes.”
Regular use of statins is associated with a modest reduction in the risk of Parkinson’s disease, according to a study in the March Archives of Neurology. The prospective study included 38,192 men and 90,874 women participating in two ongoing US cohorts. Those enrolled were followed for 12 years, during which 644 cases (338 women) of Parkinson’s disease were documented. The investigators found that current statin users had a lower risk of Parkinson’s disease, compared with nonusers. Furthermore, participants younger than 60 at baseline had a significant association between Parkinson’s disease risk and statin use, while those who were older did not have such an association. “The possibility that some statins may reduce Parkinson’s disease risk deserves further consideration,” the study authors stated.

Labels for statin drugs will now include information about memory loss and confusion side effects experienced by some patients, according to changes issued by the FDA. The statin drugs include atorvastatin, fluvastatin, lovastatin, lovastatin extended-release, pitavastatin, pravastatin, rosuvastatin, and simvastatin, as well as combination products. According to the FDA, the cognitive effects experienced by patients taking statins were usually not serious and were reversed by stopping statin use. In addition to describing cognitive effects, label changes to the statins will provide information on blood sugar increases experienced by some patients and regarding a greater risk of being diagnosed with type 2 diabetes mellitus. The updated labels also identify contraindications for lovastatin and remove the recommendation for routine periodic monitoring of liver enzymes in patients taking statins. The FDA emphasized that health care professionals and patients should be aware of the most current information on statin risks, while remaining assured that statins provide an important health benefit.

The FDA has approved the Avonex pen and a new dose titration regimen for once-a-week treatment of Avonex in patients with relapsing forms of multiple sclerosis (MS). Patients may experience less injection anxiety and pain by using the Avonex pen, which has an automated injection device and a smaller needle than the currently available Avonex Prefilled Syringe. Data from an open-label, multicenter, phase IIIb study showed that approximately nine of 10 patients successfully used the device, and 94% of patients preferred the Avonex pen to the Avonex Prefilled Syringe. In addition, a randomized, phase I study found that the new dose titration regimen, which gradually escalates the dose of Avonex (Biogen Idec; Weston, Massachusetts) at treatment initiation, reduced the incidence and severity of flulike symptoms.

Women who have multiple pregnancies may have a reduced risk of multiple sclerosis (MS), according to research published in the March 7 online Neurology. Investigators reviewed the cases of 282 men and women who had a first clinical diagnosis of CNS demyelination between 2003 and 2006. These 282 patients (ages 18 to 59) were compared with a matched control group of 542 patients who did not have a first clinical diagnosis of CNS demyelination. Among women, having a higher number of offspring was associated with a lower risk of a first clinical diagnosis of CNS demyelination. “These findings are consistent with a cumulative beneficial effect of pregnancy,” the study authors stated. They speculated that societal trends toward having children at a later age and having fewer children overall may help explain the increasing rate of MS cases in women.

Women ages 65 and older with retinopathy are more likely to have cognitive decline and larger ischemic lesion volumes, researchers reported in the March 14 online Neurology. Using fundus photography to assess retinopathy and the modified Mini-Mental State Examination (3MSE) to assess cognitive performance over time, the investigators studied 511 women who were enrolled in the Women’s Health Initiative Memory Study and the Sight Examination Study. After a 10-year follow-up period, women with retinopathy had lower 3MSE scores, 47% larger ischemic volumes in the total brain, and 68% larger ischemic volumes in the parietal lobe. According to the researchers, the association between retinopathy and cognitive impairment, as well as larger ischemic lesion volumes, “strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes.”
Regular use of statins is associated with a modest reduction in the risk of Parkinson’s disease, according to a study in the March Archives of Neurology. The prospective study included 38,192 men and 90,874 women participating in two ongoing US cohorts. Those enrolled were followed for 12 years, during which 644 cases (338 women) of Parkinson’s disease were documented. The investigators found that current statin users had a lower risk of Parkinson’s disease, compared with nonusers. Furthermore, participants younger than 60 at baseline had a significant association between Parkinson’s disease risk and statin use, while those who were older did not have such an association. “The possibility that some statins may reduce Parkinson’s disease risk deserves further consideration,” the study authors stated.

Labels for statin drugs will now include information about memory loss and confusion side effects experienced by some patients, according to changes issued by the FDA. The statin drugs include atorvastatin, fluvastatin, lovastatin, lovastatin extended-release, pitavastatin, pravastatin, rosuvastatin, and simvastatin, as well as combination products. According to the FDA, the cognitive effects experienced by patients taking statins were usually not serious and were reversed by stopping statin use. In addition to describing cognitive effects, label changes to the statins will provide information on blood sugar increases experienced by some patients and regarding a greater risk of being diagnosed with type 2 diabetes mellitus. The updated labels also identify contraindications for lovastatin and remove the recommendation for routine periodic monitoring of liver enzymes in patients taking statins. The FDA emphasized that health care professionals and patients should be aware of the most current information on statin risks, while remaining assured that statins provide an important health benefit.

The FDA has approved the Avonex pen and a new dose titration regimen for once-a-week treatment of Avonex in patients with relapsing forms of multiple sclerosis (MS). Patients may experience less injection anxiety and pain by using the Avonex pen, which has an automated injection device and a smaller needle than the currently available Avonex Prefilled Syringe. Data from an open-label, multicenter, phase IIIb study showed that approximately nine of 10 patients successfully used the device, and 94% of patients preferred the Avonex pen to the Avonex Prefilled Syringe. In addition, a randomized, phase I study found that the new dose titration regimen, which gradually escalates the dose of Avonex (Biogen Idec; Weston, Massachusetts) at treatment initiation, reduced the incidence and severity of flulike symptoms.

Women who have multiple pregnancies may have a reduced risk of multiple sclerosis (MS), according to research published in the March 7 online Neurology. Investigators reviewed the cases of 282 men and women who had a first clinical diagnosis of CNS demyelination between 2003 and 2006. These 282 patients (ages 18 to 59) were compared with a matched control group of 542 patients who did not have a first clinical diagnosis of CNS demyelination. Among women, having a higher number of offspring was associated with a lower risk of a first clinical diagnosis of CNS demyelination. “These findings are consistent with a cumulative beneficial effect of pregnancy,” the study authors stated. They speculated that societal trends toward having children at a later age and having fewer children overall may help explain the increasing rate of MS cases in women.

Although measles antibody levels decrease in the general population, an increase is evident in the serum and CSF of patients with MS.

AMSTERDAM—The level of measles virus antibody increases with age and duration of multiple sclerosis (MS) in the serum and CSF of patients with MS, according to research presented at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).

The synthesis of measles antibodies continues to increase many years after MS has been diagnosed, according to the study. In healthy controls, however, levels of measles antibody decrease slightly with age.

Comparing Antibody Titres in MS Patients and the General Population
After a healthy person is infected with or vaccinated against measles, his or her measles antibody titres decrease over time. But most patients with MS have higher measles antibody titres in their serum and CSF than the general population does, according to Cecilia Ahlgren, PhD, of the Institute of Clinical Neuroscience at Sahlgrenska University Hospital in Gothenburg, Sweden.

Dr. Ahlgren and her colleagues tested the level of measles antibody in the serum and CSF of 161 patients with MS between the ages of 15 and 49. The age of MS onset among the patients ranged from 10 to 39.

The team included a control group of 50 healthy blood donors who each gave samples of their serum and CSF. Members of the control group ranged in age from 18 to 57.

The investigators sought to determine whether increased synthesis of measles antibody was a systemic phenomenon or was confined to the CSF. They analyzed the levels of measles antibody in serum and CSF through enzyme-linked immunosorbent assay. The researchers then analyzed correlations between antibody titres and age, and antibody titres and MS duration using linear regression.

MS May Sound a General Alarm in the Body
Measles antibody levels increased with age and MS duration, and antibody synthesis occurred in the CSF and serum, according to Dr. Ahlgren and her colleagues. Increasing measles antibody titres are most likely “part of a polyspecific immune response, probably with no pathogenic role,” they wrote.

B cells and plasma cells are considered important in the production of antibodies, but the researchers were not certain about whether B cell follicles caused the increased antibody production seen in the study. Because increased antibody titres were found in the serum as well as the CSF, “our results point to a more general activation of B cells and plasma cells,” concluded the investigators.

Although measles antibody levels decrease in the general population, an increase is evident in the serum and CSF of patients with MS.

AMSTERDAM—The level of measles virus antibody increases with age and duration of multiple sclerosis (MS) in the serum and CSF of patients with MS, according to research presented at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).

The synthesis of measles antibodies continues to increase many years after MS has been diagnosed, according to the study. In healthy controls, however, levels of measles antibody decrease slightly with age.

Comparing Antibody Titres in MS Patients and the General Population
After a healthy person is infected with or vaccinated against measles, his or her measles antibody titres decrease over time. But most patients with MS have higher measles antibody titres in their serum and CSF than the general population does, according to Cecilia Ahlgren, PhD, of the Institute of Clinical Neuroscience at Sahlgrenska University Hospital in Gothenburg, Sweden.

Dr. Ahlgren and her colleagues tested the level of measles antibody in the serum and CSF of 161 patients with MS between the ages of 15 and 49. The age of MS onset among the patients ranged from 10 to 39.

The team included a control group of 50 healthy blood donors who each gave samples of their serum and CSF. Members of the control group ranged in age from 18 to 57.

The investigators sought to determine whether increased synthesis of measles antibody was a systemic phenomenon or was confined to the CSF. They analyzed the levels of measles antibody in serum and CSF through enzyme-linked immunosorbent assay. The researchers then analyzed correlations between antibody titres and age, and antibody titres and MS duration using linear regression.

MS May Sound a General Alarm in the Body
Measles antibody levels increased with age and MS duration, and antibody synthesis occurred in the CSF and serum, according to Dr. Ahlgren and her colleagues. Increasing measles antibody titres are most likely “part of a polyspecific immune response, probably with no pathogenic role,” they wrote.

B cells and plasma cells are considered important in the production of antibodies, but the researchers were not certain about whether B cell follicles caused the increased antibody production seen in the study. Because increased antibody titres were found in the serum as well as the CSF, “our results point to a more general activation of B cells and plasma cells,” concluded the investigators.

Although measles antibody levels decrease in the general population, an increase is evident in the serum and CSF of patients with MS.

AMSTERDAM—The level of measles virus antibody increases with age and duration of multiple sclerosis (MS) in the serum and CSF of patients with MS, according to research presented at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).

The synthesis of measles antibodies continues to increase many years after MS has been diagnosed, according to the study. In healthy controls, however, levels of measles antibody decrease slightly with age.

Comparing Antibody Titres in MS Patients and the General Population
After a healthy person is infected with or vaccinated against measles, his or her measles antibody titres decrease over time. But most patients with MS have higher measles antibody titres in their serum and CSF than the general population does, according to Cecilia Ahlgren, PhD, of the Institute of Clinical Neuroscience at Sahlgrenska University Hospital in Gothenburg, Sweden.

Dr. Ahlgren and her colleagues tested the level of measles antibody in the serum and CSF of 161 patients with MS between the ages of 15 and 49. The age of MS onset among the patients ranged from 10 to 39.

The team included a control group of 50 healthy blood donors who each gave samples of their serum and CSF. Members of the control group ranged in age from 18 to 57.

The investigators sought to determine whether increased synthesis of measles antibody was a systemic phenomenon or was confined to the CSF. They analyzed the levels of measles antibody in serum and CSF through enzyme-linked immunosorbent assay. The researchers then analyzed correlations between antibody titres and age, and antibody titres and MS duration using linear regression.

MS May Sound a General Alarm in the Body
Measles antibody levels increased with age and MS duration, and antibody synthesis occurred in the CSF and serum, according to Dr. Ahlgren and her colleagues. Increasing measles antibody titres are most likely “part of a polyspecific immune response, probably with no pathogenic role,” they wrote.

B cells and plasma cells are considered important in the production of antibodies, but the researchers were not certain about whether B cell follicles caused the increased antibody production seen in the study. Because increased antibody titres were found in the serum as well as the CSF, “our results point to a more general activation of B cells and plasma cells,” concluded the investigators.

Studies show that gray matter atrophy correlates with disability progression and drives whole brain atrophy in MS.

AMSTERDAM—Gray matter atrophy may serve as an effective outcome measure for clinical trials in multiple sclerosis (MS), said Richard A. Rudick, MD, Vice Chair of the Neurological Institute at the Cleveland Clinic. He described the latest research on gray matter atrophy at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).
According to Dr. Rudick, conventional MRI techniques almost entirely overlook gray matter pathology, even though 65% of the brain is composed of gray matter. “As a result, all of our focus has been on white matter, and the conventional MRI really just visualizes a small portion of the underlying pathology. [Gray matter pathology] is truly a Trojan horse in MS.”

Although gray matter lesions are still difficult to measure and not discernable using traditional MRI, gray matter atrophy appears to be a highly feasible metric for indirectly determining the impact of gray matter lesions. “Gray matter atrophy can be measured precisely with available techniques,” said Dr. Rudick.

Dr. Rudick described the clinical relevance of gray matter atrophy in MS, including how it correlates with lesions, disability, and whole brain atrophy, as well as its potential to mitigate complications when used as an outcome metric for MS clinical trials.

Resolving Pseudoatrophy Complications
Previous studies have attempted to use whole brain atrophy as a clinical trial measure, but these efforts have been complicated by the issue of pseudoatrophy, which occurs when MS therapies resolve edema and cause a rapid loss of tissue that resembles atrophy.

However, a recent posthoc analysis showed that pseudoatrophy was found in white matter rather than in gray matter. “So the significance of this, I believe, is that there doesn’t appear to be as much fluid shift in the gray matter as in the white matter,” Dr. Rudick commented. “And I think this [difference] would significantly simplify the design of clinical trials focused on atrophy if we were to focus on gray matter.”

Based on initial sample calculations, Dr. Rudick expects that future studies will require 60 to 80 patients per arm for moderate effect sizes.

Gray Matter Atrophy Influences Whole Brain Atrophy
Gray matter atrophy may serve as a valuable clinical trial metric, because it occurs early in the course of MS and increases as the disease advances, Dr. Rudick explained.

Data from an ongoing longitudinal study by Elizabeth Fisher, PhD, of the Cleveland Clinic Lerner Research Institute, and colleagues, suggest that accelerating whole brain atrophy over time is mostly driven by gray matter atrophy. The study is comparing healthy controls with patients progressing from clinically isolated syndrome to relapsing-remitting MS, as well as secondary and secondary progressive MS.

Dr. Rudick noted that white matter atrophy showed little change during the four-year study period. However, “when we look at the gray matter atrophy, it explodes, actually. It goes up to fourteenfold, compared with the healthy controls. So the accelerating atrophy over time is largely driven by increasing gray matter atrophy.”

Correlation With Disability
Gray matter atrophy also correlates with MS disability progression, according to six recent cross-sectional studies. In some of the studies, researchers analyzed multiple regression models and found that gray matter fraction, a method of quantifying gray matter atrophy, correlated with clinical outcomes better than other MRI variables, including white matter atrophy.

In addition, seven longitudinal studies have consistently demonstrated that gray matter atrophy shows a stronger correlation with disability progression than does white matter atrophy or lesions. Of the studies, two found that gray matter atrophy predicted conversion from clinically isolated syndrome to MS.

Modest Correlation With Lesions
Researchers have found that gray matter atrophy correlates somewhat with lesions as well. A three-year longitudinal study by Calabrese observed 76 patients with relapsing-remitting MS and 31 patients with secondary progressive MS. The investigators determined that cortical lesions at baseline predicted a change in gray matter volume, though the effect was modest in patients with relapsing-remitting MS and was not significant in patients with secondary progressive MS.

“My interpretation of this is that there is a connection between cortical lesions and cortical atrophy, but, at least using current techniques, this relationship is rather weak,” said Dr. Rudick. He pointed out that current methods for quantifying gray matter volume, such as gray matter fractional volume, may sometimes misclassify lesions due to their signal intensity. The potential for misclassification becomes more problematic in cases of advancing MS with numerous lesions.

In relation to quantifying gray matter atrophy, “it’s not clear whether gray matter fraction or cortical thickness or region of interest is the optimal approach,” said Dr. Rudick.

He also noted that the effect of drugs on gray matter atrophy might be of interest to researchers. However, not enough data are available to draw conclusions.

Looking forward, he suggested that gray matter atrophy may play an important role in future clinical trials. “I believe gray matter atrophy is an attractive outcome measure for MS clinical trials, because it seems to be very important, it’s feasible, and I think it should be fairly straightforward,” concluded Dr. Rudick.   

Studies show that gray matter atrophy correlates with disability progression and drives whole brain atrophy in MS.

AMSTERDAM—Gray matter atrophy may serve as an effective outcome measure for clinical trials in multiple sclerosis (MS), said Richard A. Rudick, MD, Vice Chair of the Neurological Institute at the Cleveland Clinic. He described the latest research on gray matter atrophy at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).
According to Dr. Rudick, conventional MRI techniques almost entirely overlook gray matter pathology, even though 65% of the brain is composed of gray matter. “As a result, all of our focus has been on white matter, and the conventional MRI really just visualizes a small portion of the underlying pathology. [Gray matter pathology] is truly a Trojan horse in MS.”

Although gray matter lesions are still difficult to measure and not discernable using traditional MRI, gray matter atrophy appears to be a highly feasible metric for indirectly determining the impact of gray matter lesions. “Gray matter atrophy can be measured precisely with available techniques,” said Dr. Rudick.

Dr. Rudick described the clinical relevance of gray matter atrophy in MS, including how it correlates with lesions, disability, and whole brain atrophy, as well as its potential to mitigate complications when used as an outcome metric for MS clinical trials.

Resolving Pseudoatrophy Complications
Previous studies have attempted to use whole brain atrophy as a clinical trial measure, but these efforts have been complicated by the issue of pseudoatrophy, which occurs when MS therapies resolve edema and cause a rapid loss of tissue that resembles atrophy.

However, a recent posthoc analysis showed that pseudoatrophy was found in white matter rather than in gray matter. “So the significance of this, I believe, is that there doesn’t appear to be as much fluid shift in the gray matter as in the white matter,” Dr. Rudick commented. “And I think this [difference] would significantly simplify the design of clinical trials focused on atrophy if we were to focus on gray matter.”

Based on initial sample calculations, Dr. Rudick expects that future studies will require 60 to 80 patients per arm for moderate effect sizes.

Gray Matter Atrophy Influences Whole Brain Atrophy
Gray matter atrophy may serve as a valuable clinical trial metric, because it occurs early in the course of MS and increases as the disease advances, Dr. Rudick explained.

Data from an ongoing longitudinal study by Elizabeth Fisher, PhD, of the Cleveland Clinic Lerner Research Institute, and colleagues, suggest that accelerating whole brain atrophy over time is mostly driven by gray matter atrophy. The study is comparing healthy controls with patients progressing from clinically isolated syndrome to relapsing-remitting MS, as well as secondary and secondary progressive MS.

Dr. Rudick noted that white matter atrophy showed little change during the four-year study period. However, “when we look at the gray matter atrophy, it explodes, actually. It goes up to fourteenfold, compared with the healthy controls. So the accelerating atrophy over time is largely driven by increasing gray matter atrophy.”

Correlation With Disability
Gray matter atrophy also correlates with MS disability progression, according to six recent cross-sectional studies. In some of the studies, researchers analyzed multiple regression models and found that gray matter fraction, a method of quantifying gray matter atrophy, correlated with clinical outcomes better than other MRI variables, including white matter atrophy.

In addition, seven longitudinal studies have consistently demonstrated that gray matter atrophy shows a stronger correlation with disability progression than does white matter atrophy or lesions. Of the studies, two found that gray matter atrophy predicted conversion from clinically isolated syndrome to MS.

Modest Correlation With Lesions
Researchers have found that gray matter atrophy correlates somewhat with lesions as well. A three-year longitudinal study by Calabrese observed 76 patients with relapsing-remitting MS and 31 patients with secondary progressive MS. The investigators determined that cortical lesions at baseline predicted a change in gray matter volume, though the effect was modest in patients with relapsing-remitting MS and was not significant in patients with secondary progressive MS.

“My interpretation of this is that there is a connection between cortical lesions and cortical atrophy, but, at least using current techniques, this relationship is rather weak,” said Dr. Rudick. He pointed out that current methods for quantifying gray matter volume, such as gray matter fractional volume, may sometimes misclassify lesions due to their signal intensity. The potential for misclassification becomes more problematic in cases of advancing MS with numerous lesions.

In relation to quantifying gray matter atrophy, “it’s not clear whether gray matter fraction or cortical thickness or region of interest is the optimal approach,” said Dr. Rudick.

He also noted that the effect of drugs on gray matter atrophy might be of interest to researchers. However, not enough data are available to draw conclusions.

Looking forward, he suggested that gray matter atrophy may play an important role in future clinical trials. “I believe gray matter atrophy is an attractive outcome measure for MS clinical trials, because it seems to be very important, it’s feasible, and I think it should be fairly straightforward,” concluded Dr. Rudick.   

Studies show that gray matter atrophy correlates with disability progression and drives whole brain atrophy in MS.

AMSTERDAM—Gray matter atrophy may serve as an effective outcome measure for clinical trials in multiple sclerosis (MS), said Richard A. Rudick, MD, Vice Chair of the Neurological Institute at the Cleveland Clinic. He described the latest research on gray matter atrophy at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).
According to Dr. Rudick, conventional MRI techniques almost entirely overlook gray matter pathology, even though 65% of the brain is composed of gray matter. “As a result, all of our focus has been on white matter, and the conventional MRI really just visualizes a small portion of the underlying pathology. [Gray matter pathology] is truly a Trojan horse in MS.”

Although gray matter lesions are still difficult to measure and not discernable using traditional MRI, gray matter atrophy appears to be a highly feasible metric for indirectly determining the impact of gray matter lesions. “Gray matter atrophy can be measured precisely with available techniques,” said Dr. Rudick.

Dr. Rudick described the clinical relevance of gray matter atrophy in MS, including how it correlates with lesions, disability, and whole brain atrophy, as well as its potential to mitigate complications when used as an outcome metric for MS clinical trials.

Resolving Pseudoatrophy Complications
Previous studies have attempted to use whole brain atrophy as a clinical trial measure, but these efforts have been complicated by the issue of pseudoatrophy, which occurs when MS therapies resolve edema and cause a rapid loss of tissue that resembles atrophy.

However, a recent posthoc analysis showed that pseudoatrophy was found in white matter rather than in gray matter. “So the significance of this, I believe, is that there doesn’t appear to be as much fluid shift in the gray matter as in the white matter,” Dr. Rudick commented. “And I think this [difference] would significantly simplify the design of clinical trials focused on atrophy if we were to focus on gray matter.”

Based on initial sample calculations, Dr. Rudick expects that future studies will require 60 to 80 patients per arm for moderate effect sizes.

Gray Matter Atrophy Influences Whole Brain Atrophy
Gray matter atrophy may serve as a valuable clinical trial metric, because it occurs early in the course of MS and increases as the disease advances, Dr. Rudick explained.

Data from an ongoing longitudinal study by Elizabeth Fisher, PhD, of the Cleveland Clinic Lerner Research Institute, and colleagues, suggest that accelerating whole brain atrophy over time is mostly driven by gray matter atrophy. The study is comparing healthy controls with patients progressing from clinically isolated syndrome to relapsing-remitting MS, as well as secondary and secondary progressive MS.

Dr. Rudick noted that white matter atrophy showed little change during the four-year study period. However, “when we look at the gray matter atrophy, it explodes, actually. It goes up to fourteenfold, compared with the healthy controls. So the accelerating atrophy over time is largely driven by increasing gray matter atrophy.”

Correlation With Disability
Gray matter atrophy also correlates with MS disability progression, according to six recent cross-sectional studies. In some of the studies, researchers analyzed multiple regression models and found that gray matter fraction, a method of quantifying gray matter atrophy, correlated with clinical outcomes better than other MRI variables, including white matter atrophy.

In addition, seven longitudinal studies have consistently demonstrated that gray matter atrophy shows a stronger correlation with disability progression than does white matter atrophy or lesions. Of the studies, two found that gray matter atrophy predicted conversion from clinically isolated syndrome to MS.

Modest Correlation With Lesions
Researchers have found that gray matter atrophy correlates somewhat with lesions as well. A three-year longitudinal study by Calabrese observed 76 patients with relapsing-remitting MS and 31 patients with secondary progressive MS. The investigators determined that cortical lesions at baseline predicted a change in gray matter volume, though the effect was modest in patients with relapsing-remitting MS and was not significant in patients with secondary progressive MS.

“My interpretation of this is that there is a connection between cortical lesions and cortical atrophy, but, at least using current techniques, this relationship is rather weak,” said Dr. Rudick. He pointed out that current methods for quantifying gray matter volume, such as gray matter fractional volume, may sometimes misclassify lesions due to their signal intensity. The potential for misclassification becomes more problematic in cases of advancing MS with numerous lesions.

In relation to quantifying gray matter atrophy, “it’s not clear whether gray matter fraction or cortical thickness or region of interest is the optimal approach,” said Dr. Rudick.

He also noted that the effect of drugs on gray matter atrophy might be of interest to researchers. However, not enough data are available to draw conclusions.

Looking forward, he suggested that gray matter atrophy may play an important role in future clinical trials. “I believe gray matter atrophy is an attractive outcome measure for MS clinical trials, because it seems to be very important, it’s feasible, and I think it should be fairly straightforward,” concluded Dr. Rudick.   

A referral to a neurologist may be a mitigating factor for expanded treatment with medication among patients with MS.

AMSTERDAM—About half of insured patients with multiple sclerosis (MS) in the United States do not take disease-modifying drugs within four years of diagnosis, according to a study presented at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

Comorbid conditions, such as depression and inflammatory arthritis, may influence patients’ decision not to use medication. Consultation with a neurologist, however, was associated with expanded use of therapeutic drugs, which increased yearly, according to the study.

The reasons that so many patients with MS do not take medication are unclear. “Some of these patients had not seen a neurologist. Some had forms of MS where there is no treatment. Others have mild MS and preferred no treatment,” Lawrence Steinman, MD, Professor of Neurology and Neurological Sciences at the Stanford University School of Medicine in Palo Alto, California, told Neurology Reviews. “These are just speculative comments,” he added.

Although the benefits of pharmaceutical treatments for MS have been established, it is uncertain which patient populations are more likely to take disease-modifying drugs. A group led by Dr. Steinman studied insurance claims to determine the patient characteristics associated with use of therapeutic drugs.

Using insurance claims made between January 1, 2005, and December 31, 2007, the researchers created a cohort of 32,083 patients with MS, each of whom had had six months of continuous insurance coverage before filling his or her first prescription. The patients’ mean age was roughly 45, and about 75% of patients were female. The team excluded from the study patients first dispensed with immunosuppressants or other medicines.

Among patients treated with a drug, 9,541 first used interferon agents, and 5,212 began by using glatiramer acetate. During the six-month baseline period, the mean age of the treated patients was 45. The cohort included 16,434 patients who used no therapy during the observation period. The mean age of untreated patients during the six-month baseline period was 46.

A greater proportion (ie, 56%) of treated patients than nontreated patients (ie, 37%) was employed full time. Between 0.8% and 1.3% of treated patients filed a long-term disability claim, compared with 0.6% of the nontreated group. About 55% of treated patients visited a neurologist, compared with 46% of nontreated patients.

Dr. Steinman and his colleagues predicted patients’ use of interferon agents or glatiramer acetate in a logistic regression using patients’ baseline variables (eg, age, gender, comorbidities, and geographic region).

A greater proportion of patients in the northeast (ie, 53%) used disease-modifying drugs than in any other region of the US. The south had the lowest percentage of treated patients (ie, 45%). Patients who previously had used interferon or glatiramer acetate were much more likely to use a drug than patients who had not, according to the study.

A referral to a neurologist may be a mitigating factor for expanded treatment with medication among patients with MS.

AMSTERDAM—About half of insured patients with multiple sclerosis (MS) in the United States do not take disease-modifying drugs within four years of diagnosis, according to a study presented at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

Comorbid conditions, such as depression and inflammatory arthritis, may influence patients’ decision not to use medication. Consultation with a neurologist, however, was associated with expanded use of therapeutic drugs, which increased yearly, according to the study.

The reasons that so many patients with MS do not take medication are unclear. “Some of these patients had not seen a neurologist. Some had forms of MS where there is no treatment. Others have mild MS and preferred no treatment,” Lawrence Steinman, MD, Professor of Neurology and Neurological Sciences at the Stanford University School of Medicine in Palo Alto, California, told Neurology Reviews. “These are just speculative comments,” he added.

Although the benefits of pharmaceutical treatments for MS have been established, it is uncertain which patient populations are more likely to take disease-modifying drugs. A group led by Dr. Steinman studied insurance claims to determine the patient characteristics associated with use of therapeutic drugs.

Using insurance claims made between January 1, 2005, and December 31, 2007, the researchers created a cohort of 32,083 patients with MS, each of whom had had six months of continuous insurance coverage before filling his or her first prescription. The patients’ mean age was roughly 45, and about 75% of patients were female. The team excluded from the study patients first dispensed with immunosuppressants or other medicines.

Among patients treated with a drug, 9,541 first used interferon agents, and 5,212 began by using glatiramer acetate. During the six-month baseline period, the mean age of the treated patients was 45. The cohort included 16,434 patients who used no therapy during the observation period. The mean age of untreated patients during the six-month baseline period was 46.

A greater proportion (ie, 56%) of treated patients than nontreated patients (ie, 37%) was employed full time. Between 0.8% and 1.3% of treated patients filed a long-term disability claim, compared with 0.6% of the nontreated group. About 55% of treated patients visited a neurologist, compared with 46% of nontreated patients.

Dr. Steinman and his colleagues predicted patients’ use of interferon agents or glatiramer acetate in a logistic regression using patients’ baseline variables (eg, age, gender, comorbidities, and geographic region).

A greater proportion of patients in the northeast (ie, 53%) used disease-modifying drugs than in any other region of the US. The south had the lowest percentage of treated patients (ie, 45%). Patients who previously had used interferon or glatiramer acetate were much more likely to use a drug than patients who had not, according to the study.

A referral to a neurologist may be a mitigating factor for expanded treatment with medication among patients with MS.

AMSTERDAM—About half of insured patients with multiple sclerosis (MS) in the United States do not take disease-modifying drugs within four years of diagnosis, according to a study presented at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

Comorbid conditions, such as depression and inflammatory arthritis, may influence patients’ decision not to use medication. Consultation with a neurologist, however, was associated with expanded use of therapeutic drugs, which increased yearly, according to the study.

The reasons that so many patients with MS do not take medication are unclear. “Some of these patients had not seen a neurologist. Some had forms of MS where there is no treatment. Others have mild MS and preferred no treatment,” Lawrence Steinman, MD, Professor of Neurology and Neurological Sciences at the Stanford University School of Medicine in Palo Alto, California, told Neurology Reviews. “These are just speculative comments,” he added.

Although the benefits of pharmaceutical treatments for MS have been established, it is uncertain which patient populations are more likely to take disease-modifying drugs. A group led by Dr. Steinman studied insurance claims to determine the patient characteristics associated with use of therapeutic drugs.

Using insurance claims made between January 1, 2005, and December 31, 2007, the researchers created a cohort of 32,083 patients with MS, each of whom had had six months of continuous insurance coverage before filling his or her first prescription. The patients’ mean age was roughly 45, and about 75% of patients were female. The team excluded from the study patients first dispensed with immunosuppressants or other medicines.

Among patients treated with a drug, 9,541 first used interferon agents, and 5,212 began by using glatiramer acetate. During the six-month baseline period, the mean age of the treated patients was 45. The cohort included 16,434 patients who used no therapy during the observation period. The mean age of untreated patients during the six-month baseline period was 46.

A greater proportion (ie, 56%) of treated patients than nontreated patients (ie, 37%) was employed full time. Between 0.8% and 1.3% of treated patients filed a long-term disability claim, compared with 0.6% of the nontreated group. About 55% of treated patients visited a neurologist, compared with 46% of nontreated patients.

Dr. Steinman and his colleagues predicted patients’ use of interferon agents or glatiramer acetate in a logistic regression using patients’ baseline variables (eg, age, gender, comorbidities, and geographic region).

A greater proportion of patients in the northeast (ie, 53%) used disease-modifying drugs than in any other region of the US. The south had the lowest percentage of treated patients (ie, 45%). Patients who previously had used interferon or glatiramer acetate were much more likely to use a drug than patients who had not, according to the study.

Patients with early-stage multiple sclerosis (MS) show cortical demyelinating lesions that are numerous, inflammatory, and strongly linked with meningeal inflammation, according to a study published in the December 8, 2011, New England Journal of Medicine.

Prior research into cortical lesions has centered on autopsies of patients with a long history of chronic, progressive MS and has supported the hypothesis that these lesions are not inflammatory. However, the new study, coauthored by Claudia F. Lucchinetti, MD, Professor of Neurology at the Mayo Clinic Rochester in Minnesota, examined biopsies of cortical tissues obtained from white-matter lesions in patients with early-stage MS, all diagnosed within days or weeks of presentation.

“We found that cortical demyelination is common early in MS, and our characterization of the lesion underscored its inflammatory character. Cortical demyelination that occurs close to the onset of MS differs substantially from that seen in chronic MS,” stated Dr. Lucchinetti. “These findings do not support a primary (non-inflammatory) neurodegenerative process during early-stage MS.”

Examining Patients With Early-Stage MS
The collaborative study involved researchers at the Mayo Clinic and co-lead author Richard Ransohoff, MD, Professor of Neurology at the Cleveland Clinic, and included 563 participants who underwent white-matter biopsies, most with the intention of detecting suspected tumors that were later designated as MS.

The median age of the cohort at biopsy was 40.5, and patients were diagnosed with MS according to the McDonald or Poser criteria. Patients with other diseases of the CNS were excluded from the study.

“A separate paper is addressing the details on the clinical spectrum in the cohort,” Dr. Lucchinetti told Neurology Reviews.

Of the 563 eligible patients with MS, only 138 had enough cortex in their biopsies to allow evaluation of the prevalence and character of cortical demyelination.

The investigators used immunohistochemistry to characterize patients’ cortical lesions in four areas—demyelinating activity, inflammatory infiltrates, the presence of meningeal inflammation, and topical association between cortical demyelination and meningeal inflammation. 

Identifying Demyelination and Inflammation
Overall, cortical demyelination was identified in 53 (38%) patients (104 lesions and 222 tissue blocks) of the 138 with sufficient cortex to allow analysis, and cortical demyelination was not present in 85 patients (121 tissue blocks). After undergoing long-term, comprehensive follow-up, 25 patients with cortical demyelination, as well as 33 patients without cortical demyelination, showed definite MS.

Dr. Lucchinetti’s group also looked for CD3+ T cells in 71 lesions from patients with an acceptable amount of representative tissue, and they documented perivascular CD3+ T-cell inflammation in 58 of 71 cortical plaques (82%). “Leukocortical lesions were highly inflammatory,” the researchers noted. “The majority of intracortical and subpial plaques contained perivascular CD3+ and CD8+ T-cell infiltrates.” The investigators also observed macrophage-associated demyelination in 32 of 78 lesions (41%).

Furthermore, in patients with confirmed clinically isolated syndrome (CIS) or MS, there was a strong link between meningeal inflammation and cortical demyelination. “Remarkably, there was a 90% probability that moderate-to-marked meningeal inflammation was topographically associated with cortical demyelination,” the study authors wrote. 

Gray Matter Implications
MS has traditionally been viewed as a disease of the white matter, though in recent years researchers have acknowledged the role of gray matter disease as part of MS progression. However, until now, investigators had not seen strong evidence supporting the idea that the immune system plays an active role in the gray matter of patients with MS. Myelin-laden macrophages, the sign of an active plaque, were not previously observed in cortical tissue, and many researchers have viewed MS as a degenerative rather than inflammatory disease.

In an accompanying editorial, Peter A. Calabresi, MD, Professor of Neurology at the Johns Hopkins School of Medicine in Baltimore, called the findings “provocative” and said that they “provide definitive evidence that inflammatory disease of the gray matter commences early in the pathogenesis of some cases of MS.”

The results enhance the understanding of MS as an inflammatory disease, which might allow researchers to explore different treatment approaches, according to Dr. Calabresi.

“Other studies have led to the concept that the underlying substrate of permanent disability in MS is not inflammation or demyelination, both of which are potentially reversible, but rather neuroaxonal disease,” stated Dr. Calabresi. “The study by Lucchinetti et al suggests that cortical neuronal loss is directly associated with inflammatory demyelination, and therefore early therapeutic efforts to suppress inflammation may be neuroprotective in both gray-matter and white-matter compartments.”   

—Lauren LeBano

Patients with early-stage multiple sclerosis (MS) show cortical demyelinating lesions that are numerous, inflammatory, and strongly linked with meningeal inflammation, according to a study published in the December 8, 2011, New England Journal of Medicine.

Prior research into cortical lesions has centered on autopsies of patients with a long history of chronic, progressive MS and has supported the hypothesis that these lesions are not inflammatory. However, the new study, coauthored by Claudia F. Lucchinetti, MD, Professor of Neurology at the Mayo Clinic Rochester in Minnesota, examined biopsies of cortical tissues obtained from white-matter lesions in patients with early-stage MS, all diagnosed within days or weeks of presentation.

“We found that cortical demyelination is common early in MS, and our characterization of the lesion underscored its inflammatory character. Cortical demyelination that occurs close to the onset of MS differs substantially from that seen in chronic MS,” stated Dr. Lucchinetti. “These findings do not support a primary (non-inflammatory) neurodegenerative process during early-stage MS.”

Examining Patients With Early-Stage MS
The collaborative study involved researchers at the Mayo Clinic and co-lead author Richard Ransohoff, MD, Professor of Neurology at the Cleveland Clinic, and included 563 participants who underwent white-matter biopsies, most with the intention of detecting suspected tumors that were later designated as MS.

The median age of the cohort at biopsy was 40.5, and patients were diagnosed with MS according to the McDonald or Poser criteria. Patients with other diseases of the CNS were excluded from the study.

“A separate paper is addressing the details on the clinical spectrum in the cohort,” Dr. Lucchinetti told Neurology Reviews.

Of the 563 eligible patients with MS, only 138 had enough cortex in their biopsies to allow evaluation of the prevalence and character of cortical demyelination.

The investigators used immunohistochemistry to characterize patients’ cortical lesions in four areas—demyelinating activity, inflammatory infiltrates, the presence of meningeal inflammation, and topical association between cortical demyelination and meningeal inflammation. 

Identifying Demyelination and Inflammation
Overall, cortical demyelination was identified in 53 (38%) patients (104 lesions and 222 tissue blocks) of the 138 with sufficient cortex to allow analysis, and cortical demyelination was not present in 85 patients (121 tissue blocks). After undergoing long-term, comprehensive follow-up, 25 patients with cortical demyelination, as well as 33 patients without cortical demyelination, showed definite MS.

Dr. Lucchinetti’s group also looked for CD3+ T cells in 71 lesions from patients with an acceptable amount of representative tissue, and they documented perivascular CD3+ T-cell inflammation in 58 of 71 cortical plaques (82%). “Leukocortical lesions were highly inflammatory,” the researchers noted. “The majority of intracortical and subpial plaques contained perivascular CD3+ and CD8+ T-cell infiltrates.” The investigators also observed macrophage-associated demyelination in 32 of 78 lesions (41%).

Furthermore, in patients with confirmed clinically isolated syndrome (CIS) or MS, there was a strong link between meningeal inflammation and cortical demyelination. “Remarkably, there was a 90% probability that moderate-to-marked meningeal inflammation was topographically associated with cortical demyelination,” the study authors wrote. 

Gray Matter Implications
MS has traditionally been viewed as a disease of the white matter, though in recent years researchers have acknowledged the role of gray matter disease as part of MS progression. However, until now, investigators had not seen strong evidence supporting the idea that the immune system plays an active role in the gray matter of patients with MS. Myelin-laden macrophages, the sign of an active plaque, were not previously observed in cortical tissue, and many researchers have viewed MS as a degenerative rather than inflammatory disease.

In an accompanying editorial, Peter A. Calabresi, MD, Professor of Neurology at the Johns Hopkins School of Medicine in Baltimore, called the findings “provocative” and said that they “provide definitive evidence that inflammatory disease of the gray matter commences early in the pathogenesis of some cases of MS.”

The results enhance the understanding of MS as an inflammatory disease, which might allow researchers to explore different treatment approaches, according to Dr. Calabresi.

“Other studies have led to the concept that the underlying substrate of permanent disability in MS is not inflammation or demyelination, both of which are potentially reversible, but rather neuroaxonal disease,” stated Dr. Calabresi. “The study by Lucchinetti et al suggests that cortical neuronal loss is directly associated with inflammatory demyelination, and therefore early therapeutic efforts to suppress inflammation may be neuroprotective in both gray-matter and white-matter compartments.”   

—Lauren LeBano

Patients with early-stage multiple sclerosis (MS) show cortical demyelinating lesions that are numerous, inflammatory, and strongly linked with meningeal inflammation, according to a study published in the December 8, 2011, New England Journal of Medicine.

Prior research into cortical lesions has centered on autopsies of patients with a long history of chronic, progressive MS and has supported the hypothesis that these lesions are not inflammatory. However, the new study, coauthored by Claudia F. Lucchinetti, MD, Professor of Neurology at the Mayo Clinic Rochester in Minnesota, examined biopsies of cortical tissues obtained from white-matter lesions in patients with early-stage MS, all diagnosed within days or weeks of presentation.

“We found that cortical demyelination is common early in MS, and our characterization of the lesion underscored its inflammatory character. Cortical demyelination that occurs close to the onset of MS differs substantially from that seen in chronic MS,” stated Dr. Lucchinetti. “These findings do not support a primary (non-inflammatory) neurodegenerative process during early-stage MS.”

Examining Patients With Early-Stage MS
The collaborative study involved researchers at the Mayo Clinic and co-lead author Richard Ransohoff, MD, Professor of Neurology at the Cleveland Clinic, and included 563 participants who underwent white-matter biopsies, most with the intention of detecting suspected tumors that were later designated as MS.

The median age of the cohort at biopsy was 40.5, and patients were diagnosed with MS according to the McDonald or Poser criteria. Patients with other diseases of the CNS were excluded from the study.

“A separate paper is addressing the details on the clinical spectrum in the cohort,” Dr. Lucchinetti told Neurology Reviews.

Of the 563 eligible patients with MS, only 138 had enough cortex in their biopsies to allow evaluation of the prevalence and character of cortical demyelination.

The investigators used immunohistochemistry to characterize patients’ cortical lesions in four areas—demyelinating activity, inflammatory infiltrates, the presence of meningeal inflammation, and topical association between cortical demyelination and meningeal inflammation. 

Identifying Demyelination and Inflammation
Overall, cortical demyelination was identified in 53 (38%) patients (104 lesions and 222 tissue blocks) of the 138 with sufficient cortex to allow analysis, and cortical demyelination was not present in 85 patients (121 tissue blocks). After undergoing long-term, comprehensive follow-up, 25 patients with cortical demyelination, as well as 33 patients without cortical demyelination, showed definite MS.

Dr. Lucchinetti’s group also looked for CD3+ T cells in 71 lesions from patients with an acceptable amount of representative tissue, and they documented perivascular CD3+ T-cell inflammation in 58 of 71 cortical plaques (82%). “Leukocortical lesions were highly inflammatory,” the researchers noted. “The majority of intracortical and subpial plaques contained perivascular CD3+ and CD8+ T-cell infiltrates.” The investigators also observed macrophage-associated demyelination in 32 of 78 lesions (41%).

Furthermore, in patients with confirmed clinically isolated syndrome (CIS) or MS, there was a strong link between meningeal inflammation and cortical demyelination. “Remarkably, there was a 90% probability that moderate-to-marked meningeal inflammation was topographically associated with cortical demyelination,” the study authors wrote. 

Gray Matter Implications
MS has traditionally been viewed as a disease of the white matter, though in recent years researchers have acknowledged the role of gray matter disease as part of MS progression. However, until now, investigators had not seen strong evidence supporting the idea that the immune system plays an active role in the gray matter of patients with MS. Myelin-laden macrophages, the sign of an active plaque, were not previously observed in cortical tissue, and many researchers have viewed MS as a degenerative rather than inflammatory disease.

In an accompanying editorial, Peter A. Calabresi, MD, Professor of Neurology at the Johns Hopkins School of Medicine in Baltimore, called the findings “provocative” and said that they “provide definitive evidence that inflammatory disease of the gray matter commences early in the pathogenesis of some cases of MS.”

The results enhance the understanding of MS as an inflammatory disease, which might allow researchers to explore different treatment approaches, according to Dr. Calabresi.

“Other studies have led to the concept that the underlying substrate of permanent disability in MS is not inflammation or demyelination, both of which are potentially reversible, but rather neuroaxonal disease,” stated Dr. Calabresi. “The study by Lucchinetti et al suggests that cortical neuronal loss is directly associated with inflammatory demyelination, and therefore early therapeutic efforts to suppress inflammation may be neuroprotective in both gray-matter and white-matter compartments.”   

—Lauren LeBano