ICYMI Multiple Sclerosis

The 7-item Generalized Anxiety Disorder Scale (GAD-7) is a reliable and valid measure of anxiety in patients with multiple sclerosis (MS), according to an analysis of the psychometric properties of the scale.

Researchers administered the GAD-7 to 513 patients, and randomly split the sample to conduct an exploratory and confirmatory factor analysis and found:

• The scale showed an acceptable internal consistency and was highly correlated with the Hospital Anxiety and Depression Scale–Anxiety.

• GAD-7 scores were higher in women and patients with secondary progressive MS.

• Higher GAD-7 scores were associated with more depressive symptoms.

Citation: Terrill AL, Hartoonian N, Beier M, Salem R, Alschuler K. The 7-item Generalized Anxiety Disorder Scale as a tool for measuring generalized anxiety in multiple sclerosis. Int J MS Care. 2015;17(2):49-56. doi: 10.7224/1537-2073.2014-008.

The 7-item Generalized Anxiety Disorder Scale (GAD-7) is a reliable and valid measure of anxiety in patients with multiple sclerosis (MS), according to an analysis of the psychometric properties of the scale.

Researchers administered the GAD-7 to 513 patients, and randomly split the sample to conduct an exploratory and confirmatory factor analysis and found:

• The scale showed an acceptable internal consistency and was highly correlated with the Hospital Anxiety and Depression Scale–Anxiety.

• GAD-7 scores were higher in women and patients with secondary progressive MS.

• Higher GAD-7 scores were associated with more depressive symptoms.

Citation: Terrill AL, Hartoonian N, Beier M, Salem R, Alschuler K. The 7-item Generalized Anxiety Disorder Scale as a tool for measuring generalized anxiety in multiple sclerosis. Int J MS Care. 2015;17(2):49-56. doi: 10.7224/1537-2073.2014-008.

The 7-item Generalized Anxiety Disorder Scale (GAD-7) is a reliable and valid measure of anxiety in patients with multiple sclerosis (MS), according to an analysis of the psychometric properties of the scale.

Researchers administered the GAD-7 to 513 patients, and randomly split the sample to conduct an exploratory and confirmatory factor analysis and found:

• The scale showed an acceptable internal consistency and was highly correlated with the Hospital Anxiety and Depression Scale–Anxiety.

• GAD-7 scores were higher in women and patients with secondary progressive MS.

• Higher GAD-7 scores were associated with more depressive symptoms.

Citation: Terrill AL, Hartoonian N, Beier M, Salem R, Alschuler K. The 7-item Generalized Anxiety Disorder Scale as a tool for measuring generalized anxiety in multiple sclerosis. Int J MS Care. 2015;17(2):49-56. doi: 10.7224/1537-2073.2014-008.

Postcontrast T2-weighted, fluid attenuated inversion recovery (FLAIR) MRI is a noninvasive method for testing in vivo markers of subpial demyelination and could be used to determine efficacy of new treatments aimed at eliminating this inflammation in patients with progressive multiple sclerosis (MS). This is the key finding of brain MRI studies collected from 299 MS patients and 37 age-matched neurologically healthy controls.

Expert raters evaluated radiography images and found:

• Focal gadolinium enhancement was present in the leptomeningeal compartment in 25% of MS cases, compared with 2.7% of controls.

• Enhancement was more frequent in patients with progressive MS compared to relapsing-remitting MS, 33% to 19%.

• Enhancing foci remained generally stable during an evaluation period of up to 5.5 years.

Citation: Absinta M, Vuolo L, Rao A, et al. Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis. Neurology. 2015. doi:10.1212/WNL.0000000000001587.

Postcontrast T2-weighted, fluid attenuated inversion recovery (FLAIR) MRI is a noninvasive method for testing in vivo markers of subpial demyelination and could be used to determine efficacy of new treatments aimed at eliminating this inflammation in patients with progressive multiple sclerosis (MS). This is the key finding of brain MRI studies collected from 299 MS patients and 37 age-matched neurologically healthy controls.

Expert raters evaluated radiography images and found:

• Focal gadolinium enhancement was present in the leptomeningeal compartment in 25% of MS cases, compared with 2.7% of controls.

• Enhancement was more frequent in patients with progressive MS compared to relapsing-remitting MS, 33% to 19%.

• Enhancing foci remained generally stable during an evaluation period of up to 5.5 years.

Citation: Absinta M, Vuolo L, Rao A, et al. Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis. Neurology. 2015. doi:10.1212/WNL.0000000000001587.

Postcontrast T2-weighted, fluid attenuated inversion recovery (FLAIR) MRI is a noninvasive method for testing in vivo markers of subpial demyelination and could be used to determine efficacy of new treatments aimed at eliminating this inflammation in patients with progressive multiple sclerosis (MS). This is the key finding of brain MRI studies collected from 299 MS patients and 37 age-matched neurologically healthy controls.

Expert raters evaluated radiography images and found:

• Focal gadolinium enhancement was present in the leptomeningeal compartment in 25% of MS cases, compared with 2.7% of controls.

• Enhancement was more frequent in patients with progressive MS compared to relapsing-remitting MS, 33% to 19%.

• Enhancing foci remained generally stable during an evaluation period of up to 5.5 years.

Citation: Absinta M, Vuolo L, Rao A, et al. Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis. Neurology. 2015. doi:10.1212/WNL.0000000000001587.

Antioxidant Therapy May Have Promising Potential in Concussion Treatment
A study conducted by investigators at West Virginia University suggests that antioxidants may play a key role in reducing the long-term effects of concussions and could potentially offer a unique new approach for treatment.

It is estimated that 3.4 million concussions occur each year in the United States, and concussions are common among athletes and soldiers. The development of a readily available oral supplement would have the potential to improve brain function in a percentage of individuals with concussion.

The study adds to recent findings that concussions can lead to chronic traumatic encephalopathy. Head injuries often result in chronic traumatic encephalopathy, a disease associated with long-term brain damage and behavioral symptoms including memory loss, impulsive behavior, depression, and aggression. The number of retired athletes and veterans diagnosed with chronic traumatic encephalopathy has climbed in recent years.

“Concussions can contribute to long-term changes within the brain, and these changes are the result of cell death, which may be caused by oxidative stress,” said Brandon Lucke-Wold, an MD and PhD student at West Virginia University’s Medical School in Morgantown. “This study shows that antioxidants such as lipoic acid can reduce the long-term deficits when given after a concussion.”

In Mr. Lucke-Wold’s research, rats were separated into three groups: a nonconcussed control group, a group that experienced concussive injury, and another concussed group that received lipoic acid supplementation. Seven days after the concussion, the rats were tested for seemingly impulsive behavior through an elevated maze. The rats exposed to concussion without lipoic acid had increased impulsive behavior and spent more time exploring open spaces, which indicates risk-taking behavior.

“This increase in impulsive behavior was an indication of underlying brain damage,” said Mr. Lucke-Wold. Analysis of the brains of the group receiving supplementation showed markedly decreased impulsive behavior. “These findings make sense because lipoic acid works to help reduce toxic free radicals that can damage cells.

“By understanding the mechanisms behind brain injury following concussion, we can more effectively target treatment interventions to reduce these damaging effects,” Mr. Lucke-Wold concluded.

New Compounds Could Offer Therapy for Various Diseases
Newly developed compounds safely prevented harmful protein aggregation in preliminary tests using animals, according to an international team of more than 18 research groups. The research findings suggest that a new class of drugs may be on the horizon for the more than 30 diseases and conditions that involve protein aggregation, including spinal cord injury, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, diabetes, and cancer.

“Diseases caused by protein aggregation affect millions of people around the world,” said Gal Bitan, PhD, Associate Professor of Neurology at the David Geffen School of Medicine at the University of California, Los Angeles. “We hope that the new compounds will provide therapy for diseases caused by protein aggregation, many of which have no treatment at all.”

The researchers call the compounds that they developed molecular tweezers because of the way they wrap around the lysine amino acid chains that make up most proteins. The compounds are unique in their ability to attack only aggregated proteins, leaving healthy proteins alone.

To develop a new drug, researchers typically screen large libraries of compounds to find ones that affect a protein involved in a disease. Dr. Bitan’s team used a fundamentally different approach to develop the molecular tweezers.

“We looked at the molecular and atomic interactions of proteins to understand what leads to their abnormal clumping,” Dr. Bitan said. “Then we developed a tailored solution. So, unlike many other drugs, we understand how and why our drug works.”

The team is in the process of testing multiple versions of the tweezers, each with a slightly different molecular makeup. For CLR01, one of the most promising versions, the researchers have demonstrated therapeutic benefits in two rodent models of Alzheimer’s disease, two fish and one mouse model of Parkinson’s disease, a fish model of spinal cord injury, and a mouse model of familial amyloidotic polyneuropathy, a rare disease in which protein aggregation affects the nervous system, heart, and kidneys.

“Our data suggest that CLR01 or a derivative thereof may become a drug for a number of diseases that involve protein aggregation,” Dr. Bitan said. “We also found a high safety window for CLR01.”

In one of the safety tests, mice receiving a daily dose of CLR01 that was 250 times higher than the therapeutic dose for one month showed no behavioral or physiologic signs of distress or damage. In fact, blood cholesterol in the mice decreased by 40%, a possible positive side effect of CLR01.

The researchers are continuing to study CLR01 in animal models of various diseases and are working to secure funding for more animal studies. The investigators are also making improvements that would allow CLR01 to be administered in a pill or capsule rather than requiring an injection.

Neurologic Diseases Share Common Blood–Brain Barrier Defects
Although stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and traumatic brain injury each affect the CNS differently, they share common defects in the blood–brain barrier that can be traced to a single set of genes, according to a new study. The findings could yield new approaches for treating brain diseases.

To protect the brain from harm, endothelial cells lining the blood vessels around the brain form a barrier that lets only specific molecules move from the blood to the brain. In people with certain diseases or brain injuries, the barrier doesn’t work properly and can allow dangerous molecules or pathogens into the brain.

“Our goal is to identify the mechanisms that lead to this disruption of the blood–brain barrier in stroke, multiple sclerosis, epilepsy, ALS, and traumatic brain injury,” said Richard Daneman, PhD, fellow at the University of California, San Diego, and leader of the research team. “For these diseases, the blood–brain barrier dysfunction is a significant contributor to symptoms and disease progression, so if we can stop the endothelial cells from going down this path, we could possibly limit the progression and the severity of these diseases.”

To identify molecular pathways and genes that are important for blood–brain barrier dysfunction, Dr. Daneman developed a way to isolate blood–brain barrier endothelial cells and compare gene expression in cells from healthy brain tissue to cells from the brains of mouse models of stroke, multiple sclerosis, epilepsy, traumatic brain injury, and ALS.

“Even though the diseases we looked at all have different triggers, we see very similar genes changing in all the different diseases within the brain endothelial cells,” said Dr. Daneman. “The fact that we found a common pathway means we could potentially find a single therapeutic target that could stop these different neurological diseases from occurring or progressing.”

To learn more about the exact function of genes that they identified as being involved in blood–brain barrier dysfunction, the researchers plan to create genetically modified mice with brain endothelial cells that either overexpress or lack a given gene. “If we can develop methods to stop these genes from being turned on, we may be able to limit the blood–brain barrier dysfunction,” Dr. Daneman said.

Genetic Variability in the Platelet Linked to Increased Risk for Clotting
Coronary heart disease and stroke, two of the leading causes of death in the United States, are associated with heightened platelet reactivity. An underlying reason for the variability in the risk of clotting may result from a genetic variation in a receptor on the surface of the platelet, according to researchers. In addition, people with this genetic variant may be less protected from clotting and thrombosis when taking current antiplatelet therapies such as aspirin and other blood-thinning medications.

Antiplatelet therapy has helped to reduce mortality associated with heart attacks and strokes significantly. Some individuals taking antiplatelet drugs are not fully protected from platelet clot formation, however. For example, black individuals are disproportionately affected by these diseases, compared with white individuals, even after adjusting for clinical and demographic factors.

Benjamin Tourdot, PhD, a postdoctoral fellow on a research team led by Michael Holinstat, PhD, Associate Professor of Pharmacology at the University of Michigan in Ann Arbor, recently discovered a genetic variant in a key platelet receptor, PAR4, that enhances platelet reactivity and is more frequently expressed in blacks than whites.

Although the genetic variation is more common in blacks than in whites, it is relatively common in both races. Approximately 76% of blacks and 36% of whites express at least one copy of the gene responsible for the hyper-responsiveness.

To determine whether individuals with the hyper-responsive form of PAR4 may be less protected following a myocardial infarction or stroke even after receiving recommended antiplatelet therapy, the investigators compared healthy individuals and cardiac patients with and without the mutation for their responsiveness to PAR4. Participants were taking standard-of-care antiplatelet therapy (ie, aspirin and Plavix). The preliminary data demonstrated that, independent of race, individuals with a copy of the hyperactive variant of PAR4 have an increase in PAR4-mediated platelet reactivity, compared with individuals without the variant, even in the presence of antiplatelet therapy.

This research could identify the PAR4 T120A variant as a potential risk factor for thrombosis and would require a new approach to treating patients with this genetic variant, including the development of PAR4 antagonists. A greater understanding of which patients benefit the most from current therapeutic strategies and which patients remain at elevated risk for a thrombotic event will aid in the development of new therapeutic targets for at-risk populations.

This study illustrates potential benefits of the personalized medicine approach to therapeutic intervention and challenges the one-size-fits-all approach, which often leaves at-risk populations without adequate protection from thrombotic events and stroke.

More Reasons Why Getting a Good Night’s Sleep Is Important
Not getting enough sleep not only makes our minds less alert, but our bodies, too. Studies have suggested that losing several hours of sleep can slow the body’s metabolism. A team of researchers from the University of South Carolina and Arizona State University found that metabolic effects are seen even when sleep is shortened by two hours.

In this study, 15 healthy nonobese young adult volunteers completed two oral glucose tolerance tests. One was after three days of sleep restricted by two hours each day, and the other was after three days of ad libitum sleep. Plasma samples were collected before and 30, 60, 90, and 120 minutes after consumption of a glucose drink to determine glucose and insulin concentrations. Fasting C-peptide concentration was also determined.

The researchers observed that glucose concentrations before and 30, 60, 90, and 120 minutes following consumption of glucose were not different during the two glucose tolerance tests. Glucose area under the curve was also similar. Insulin concentrations before and 60, 90, and 120 minutes following consumption of glucose were not different, but insulin concentration 30 minutes following consumption of glucose was higher after restricted sleep (31.4 uIU/mL) than ad libitum sleep (23.7 uIU/mL). Insulin area under the curve and fasting C-peptide concentration were also greater following restricted sleep than ad libitum sleep. Sleeping two hours less thus increased insulin concentration, suggesting that cutting sleep even a little can alter metabolism.

“Our study was conducted in a group of young healthy adults after only three days of shortened sleep by two hours,” said Xuewen Wang, PhD, Assistant Professor of Exercise Science at the University of South Carolina in Columbia. “The study findings are important because this amount of shortened sleep is often seen in real life. Our next step is to find out whether the sleep pattern of shortened sleep during the week and catching-up sleep during the weekend affects glucose metabolism in the longer term. We are also interested in finding out the responses in individuals who already have impaired glucose metabolism.”

Antioxidant Therapy May Have Promising Potential in Concussion Treatment
A study conducted by investigators at West Virginia University suggests that antioxidants may play a key role in reducing the long-term effects of concussions and could potentially offer a unique new approach for treatment.

It is estimated that 3.4 million concussions occur each year in the United States, and concussions are common among athletes and soldiers. The development of a readily available oral supplement would have the potential to improve brain function in a percentage of individuals with concussion.

The study adds to recent findings that concussions can lead to chronic traumatic encephalopathy. Head injuries often result in chronic traumatic encephalopathy, a disease associated with long-term brain damage and behavioral symptoms including memory loss, impulsive behavior, depression, and aggression. The number of retired athletes and veterans diagnosed with chronic traumatic encephalopathy has climbed in recent years.

“Concussions can contribute to long-term changes within the brain, and these changes are the result of cell death, which may be caused by oxidative stress,” said Brandon Lucke-Wold, an MD and PhD student at West Virginia University’s Medical School in Morgantown. “This study shows that antioxidants such as lipoic acid can reduce the long-term deficits when given after a concussion.”

In Mr. Lucke-Wold’s research, rats were separated into three groups: a nonconcussed control group, a group that experienced concussive injury, and another concussed group that received lipoic acid supplementation. Seven days after the concussion, the rats were tested for seemingly impulsive behavior through an elevated maze. The rats exposed to concussion without lipoic acid had increased impulsive behavior and spent more time exploring open spaces, which indicates risk-taking behavior.

“This increase in impulsive behavior was an indication of underlying brain damage,” said Mr. Lucke-Wold. Analysis of the brains of the group receiving supplementation showed markedly decreased impulsive behavior. “These findings make sense because lipoic acid works to help reduce toxic free radicals that can damage cells.

“By understanding the mechanisms behind brain injury following concussion, we can more effectively target treatment interventions to reduce these damaging effects,” Mr. Lucke-Wold concluded.

New Compounds Could Offer Therapy for Various Diseases
Newly developed compounds safely prevented harmful protein aggregation in preliminary tests using animals, according to an international team of more than 18 research groups. The research findings suggest that a new class of drugs may be on the horizon for the more than 30 diseases and conditions that involve protein aggregation, including spinal cord injury, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, diabetes, and cancer.

“Diseases caused by protein aggregation affect millions of people around the world,” said Gal Bitan, PhD, Associate Professor of Neurology at the David Geffen School of Medicine at the University of California, Los Angeles. “We hope that the new compounds will provide therapy for diseases caused by protein aggregation, many of which have no treatment at all.”

The researchers call the compounds that they developed molecular tweezers because of the way they wrap around the lysine amino acid chains that make up most proteins. The compounds are unique in their ability to attack only aggregated proteins, leaving healthy proteins alone.

To develop a new drug, researchers typically screen large libraries of compounds to find ones that affect a protein involved in a disease. Dr. Bitan’s team used a fundamentally different approach to develop the molecular tweezers.

“We looked at the molecular and atomic interactions of proteins to understand what leads to their abnormal clumping,” Dr. Bitan said. “Then we developed a tailored solution. So, unlike many other drugs, we understand how and why our drug works.”

The team is in the process of testing multiple versions of the tweezers, each with a slightly different molecular makeup. For CLR01, one of the most promising versions, the researchers have demonstrated therapeutic benefits in two rodent models of Alzheimer’s disease, two fish and one mouse model of Parkinson’s disease, a fish model of spinal cord injury, and a mouse model of familial amyloidotic polyneuropathy, a rare disease in which protein aggregation affects the nervous system, heart, and kidneys.

“Our data suggest that CLR01 or a derivative thereof may become a drug for a number of diseases that involve protein aggregation,” Dr. Bitan said. “We also found a high safety window for CLR01.”

In one of the safety tests, mice receiving a daily dose of CLR01 that was 250 times higher than the therapeutic dose for one month showed no behavioral or physiologic signs of distress or damage. In fact, blood cholesterol in the mice decreased by 40%, a possible positive side effect of CLR01.

The researchers are continuing to study CLR01 in animal models of various diseases and are working to secure funding for more animal studies. The investigators are also making improvements that would allow CLR01 to be administered in a pill or capsule rather than requiring an injection.

Neurologic Diseases Share Common Blood–Brain Barrier Defects
Although stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and traumatic brain injury each affect the CNS differently, they share common defects in the blood–brain barrier that can be traced to a single set of genes, according to a new study. The findings could yield new approaches for treating brain diseases.

To protect the brain from harm, endothelial cells lining the blood vessels around the brain form a barrier that lets only specific molecules move from the blood to the brain. In people with certain diseases or brain injuries, the barrier doesn’t work properly and can allow dangerous molecules or pathogens into the brain.

“Our goal is to identify the mechanisms that lead to this disruption of the blood–brain barrier in stroke, multiple sclerosis, epilepsy, ALS, and traumatic brain injury,” said Richard Daneman, PhD, fellow at the University of California, San Diego, and leader of the research team. “For these diseases, the blood–brain barrier dysfunction is a significant contributor to symptoms and disease progression, so if we can stop the endothelial cells from going down this path, we could possibly limit the progression and the severity of these diseases.”

To identify molecular pathways and genes that are important for blood–brain barrier dysfunction, Dr. Daneman developed a way to isolate blood–brain barrier endothelial cells and compare gene expression in cells from healthy brain tissue to cells from the brains of mouse models of stroke, multiple sclerosis, epilepsy, traumatic brain injury, and ALS.

“Even though the diseases we looked at all have different triggers, we see very similar genes changing in all the different diseases within the brain endothelial cells,” said Dr. Daneman. “The fact that we found a common pathway means we could potentially find a single therapeutic target that could stop these different neurological diseases from occurring or progressing.”

To learn more about the exact function of genes that they identified as being involved in blood–brain barrier dysfunction, the researchers plan to create genetically modified mice with brain endothelial cells that either overexpress or lack a given gene. “If we can develop methods to stop these genes from being turned on, we may be able to limit the blood–brain barrier dysfunction,” Dr. Daneman said.

Genetic Variability in the Platelet Linked to Increased Risk for Clotting
Coronary heart disease and stroke, two of the leading causes of death in the United States, are associated with heightened platelet reactivity. An underlying reason for the variability in the risk of clotting may result from a genetic variation in a receptor on the surface of the platelet, according to researchers. In addition, people with this genetic variant may be less protected from clotting and thrombosis when taking current antiplatelet therapies such as aspirin and other blood-thinning medications.

Antiplatelet therapy has helped to reduce mortality associated with heart attacks and strokes significantly. Some individuals taking antiplatelet drugs are not fully protected from platelet clot formation, however. For example, black individuals are disproportionately affected by these diseases, compared with white individuals, even after adjusting for clinical and demographic factors.

Benjamin Tourdot, PhD, a postdoctoral fellow on a research team led by Michael Holinstat, PhD, Associate Professor of Pharmacology at the University of Michigan in Ann Arbor, recently discovered a genetic variant in a key platelet receptor, PAR4, that enhances platelet reactivity and is more frequently expressed in blacks than whites.

Although the genetic variation is more common in blacks than in whites, it is relatively common in both races. Approximately 76% of blacks and 36% of whites express at least one copy of the gene responsible for the hyper-responsiveness.

To determine whether individuals with the hyper-responsive form of PAR4 may be less protected following a myocardial infarction or stroke even after receiving recommended antiplatelet therapy, the investigators compared healthy individuals and cardiac patients with and without the mutation for their responsiveness to PAR4. Participants were taking standard-of-care antiplatelet therapy (ie, aspirin and Plavix). The preliminary data demonstrated that, independent of race, individuals with a copy of the hyperactive variant of PAR4 have an increase in PAR4-mediated platelet reactivity, compared with individuals without the variant, even in the presence of antiplatelet therapy.

This research could identify the PAR4 T120A variant as a potential risk factor for thrombosis and would require a new approach to treating patients with this genetic variant, including the development of PAR4 antagonists. A greater understanding of which patients benefit the most from current therapeutic strategies and which patients remain at elevated risk for a thrombotic event will aid in the development of new therapeutic targets for at-risk populations.

This study illustrates potential benefits of the personalized medicine approach to therapeutic intervention and challenges the one-size-fits-all approach, which often leaves at-risk populations without adequate protection from thrombotic events and stroke.

More Reasons Why Getting a Good Night’s Sleep Is Important
Not getting enough sleep not only makes our minds less alert, but our bodies, too. Studies have suggested that losing several hours of sleep can slow the body’s metabolism. A team of researchers from the University of South Carolina and Arizona State University found that metabolic effects are seen even when sleep is shortened by two hours.

In this study, 15 healthy nonobese young adult volunteers completed two oral glucose tolerance tests. One was after three days of sleep restricted by two hours each day, and the other was after three days of ad libitum sleep. Plasma samples were collected before and 30, 60, 90, and 120 minutes after consumption of a glucose drink to determine glucose and insulin concentrations. Fasting C-peptide concentration was also determined.

The researchers observed that glucose concentrations before and 30, 60, 90, and 120 minutes following consumption of glucose were not different during the two glucose tolerance tests. Glucose area under the curve was also similar. Insulin concentrations before and 60, 90, and 120 minutes following consumption of glucose were not different, but insulin concentration 30 minutes following consumption of glucose was higher after restricted sleep (31.4 uIU/mL) than ad libitum sleep (23.7 uIU/mL). Insulin area under the curve and fasting C-peptide concentration were also greater following restricted sleep than ad libitum sleep. Sleeping two hours less thus increased insulin concentration, suggesting that cutting sleep even a little can alter metabolism.

“Our study was conducted in a group of young healthy adults after only three days of shortened sleep by two hours,” said Xuewen Wang, PhD, Assistant Professor of Exercise Science at the University of South Carolina in Columbia. “The study findings are important because this amount of shortened sleep is often seen in real life. Our next step is to find out whether the sleep pattern of shortened sleep during the week and catching-up sleep during the weekend affects glucose metabolism in the longer term. We are also interested in finding out the responses in individuals who already have impaired glucose metabolism.”

Antioxidant Therapy May Have Promising Potential in Concussion Treatment
A study conducted by investigators at West Virginia University suggests that antioxidants may play a key role in reducing the long-term effects of concussions and could potentially offer a unique new approach for treatment.

It is estimated that 3.4 million concussions occur each year in the United States, and concussions are common among athletes and soldiers. The development of a readily available oral supplement would have the potential to improve brain function in a percentage of individuals with concussion.

The study adds to recent findings that concussions can lead to chronic traumatic encephalopathy. Head injuries often result in chronic traumatic encephalopathy, a disease associated with long-term brain damage and behavioral symptoms including memory loss, impulsive behavior, depression, and aggression. The number of retired athletes and veterans diagnosed with chronic traumatic encephalopathy has climbed in recent years.

“Concussions can contribute to long-term changes within the brain, and these changes are the result of cell death, which may be caused by oxidative stress,” said Brandon Lucke-Wold, an MD and PhD student at West Virginia University’s Medical School in Morgantown. “This study shows that antioxidants such as lipoic acid can reduce the long-term deficits when given after a concussion.”

In Mr. Lucke-Wold’s research, rats were separated into three groups: a nonconcussed control group, a group that experienced concussive injury, and another concussed group that received lipoic acid supplementation. Seven days after the concussion, the rats were tested for seemingly impulsive behavior through an elevated maze. The rats exposed to concussion without lipoic acid had increased impulsive behavior and spent more time exploring open spaces, which indicates risk-taking behavior.

“This increase in impulsive behavior was an indication of underlying brain damage,” said Mr. Lucke-Wold. Analysis of the brains of the group receiving supplementation showed markedly decreased impulsive behavior. “These findings make sense because lipoic acid works to help reduce toxic free radicals that can damage cells.

“By understanding the mechanisms behind brain injury following concussion, we can more effectively target treatment interventions to reduce these damaging effects,” Mr. Lucke-Wold concluded.

New Compounds Could Offer Therapy for Various Diseases
Newly developed compounds safely prevented harmful protein aggregation in preliminary tests using animals, according to an international team of more than 18 research groups. The research findings suggest that a new class of drugs may be on the horizon for the more than 30 diseases and conditions that involve protein aggregation, including spinal cord injury, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, diabetes, and cancer.

“Diseases caused by protein aggregation affect millions of people around the world,” said Gal Bitan, PhD, Associate Professor of Neurology at the David Geffen School of Medicine at the University of California, Los Angeles. “We hope that the new compounds will provide therapy for diseases caused by protein aggregation, many of which have no treatment at all.”

The researchers call the compounds that they developed molecular tweezers because of the way they wrap around the lysine amino acid chains that make up most proteins. The compounds are unique in their ability to attack only aggregated proteins, leaving healthy proteins alone.

To develop a new drug, researchers typically screen large libraries of compounds to find ones that affect a protein involved in a disease. Dr. Bitan’s team used a fundamentally different approach to develop the molecular tweezers.

“We looked at the molecular and atomic interactions of proteins to understand what leads to their abnormal clumping,” Dr. Bitan said. “Then we developed a tailored solution. So, unlike many other drugs, we understand how and why our drug works.”

The team is in the process of testing multiple versions of the tweezers, each with a slightly different molecular makeup. For CLR01, one of the most promising versions, the researchers have demonstrated therapeutic benefits in two rodent models of Alzheimer’s disease, two fish and one mouse model of Parkinson’s disease, a fish model of spinal cord injury, and a mouse model of familial amyloidotic polyneuropathy, a rare disease in which protein aggregation affects the nervous system, heart, and kidneys.

“Our data suggest that CLR01 or a derivative thereof may become a drug for a number of diseases that involve protein aggregation,” Dr. Bitan said. “We also found a high safety window for CLR01.”

In one of the safety tests, mice receiving a daily dose of CLR01 that was 250 times higher than the therapeutic dose for one month showed no behavioral or physiologic signs of distress or damage. In fact, blood cholesterol in the mice decreased by 40%, a possible positive side effect of CLR01.

The researchers are continuing to study CLR01 in animal models of various diseases and are working to secure funding for more animal studies. The investigators are also making improvements that would allow CLR01 to be administered in a pill or capsule rather than requiring an injection.

Neurologic Diseases Share Common Blood–Brain Barrier Defects
Although stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and traumatic brain injury each affect the CNS differently, they share common defects in the blood–brain barrier that can be traced to a single set of genes, according to a new study. The findings could yield new approaches for treating brain diseases.

To protect the brain from harm, endothelial cells lining the blood vessels around the brain form a barrier that lets only specific molecules move from the blood to the brain. In people with certain diseases or brain injuries, the barrier doesn’t work properly and can allow dangerous molecules or pathogens into the brain.

“Our goal is to identify the mechanisms that lead to this disruption of the blood–brain barrier in stroke, multiple sclerosis, epilepsy, ALS, and traumatic brain injury,” said Richard Daneman, PhD, fellow at the University of California, San Diego, and leader of the research team. “For these diseases, the blood–brain barrier dysfunction is a significant contributor to symptoms and disease progression, so if we can stop the endothelial cells from going down this path, we could possibly limit the progression and the severity of these diseases.”

To identify molecular pathways and genes that are important for blood–brain barrier dysfunction, Dr. Daneman developed a way to isolate blood–brain barrier endothelial cells and compare gene expression in cells from healthy brain tissue to cells from the brains of mouse models of stroke, multiple sclerosis, epilepsy, traumatic brain injury, and ALS.

“Even though the diseases we looked at all have different triggers, we see very similar genes changing in all the different diseases within the brain endothelial cells,” said Dr. Daneman. “The fact that we found a common pathway means we could potentially find a single therapeutic target that could stop these different neurological diseases from occurring or progressing.”

To learn more about the exact function of genes that they identified as being involved in blood–brain barrier dysfunction, the researchers plan to create genetically modified mice with brain endothelial cells that either overexpress or lack a given gene. “If we can develop methods to stop these genes from being turned on, we may be able to limit the blood–brain barrier dysfunction,” Dr. Daneman said.

Genetic Variability in the Platelet Linked to Increased Risk for Clotting
Coronary heart disease and stroke, two of the leading causes of death in the United States, are associated with heightened platelet reactivity. An underlying reason for the variability in the risk of clotting may result from a genetic variation in a receptor on the surface of the platelet, according to researchers. In addition, people with this genetic variant may be less protected from clotting and thrombosis when taking current antiplatelet therapies such as aspirin and other blood-thinning medications.

Antiplatelet therapy has helped to reduce mortality associated with heart attacks and strokes significantly. Some individuals taking antiplatelet drugs are not fully protected from platelet clot formation, however. For example, black individuals are disproportionately affected by these diseases, compared with white individuals, even after adjusting for clinical and demographic factors.

Benjamin Tourdot, PhD, a postdoctoral fellow on a research team led by Michael Holinstat, PhD, Associate Professor of Pharmacology at the University of Michigan in Ann Arbor, recently discovered a genetic variant in a key platelet receptor, PAR4, that enhances platelet reactivity and is more frequently expressed in blacks than whites.

Although the genetic variation is more common in blacks than in whites, it is relatively common in both races. Approximately 76% of blacks and 36% of whites express at least one copy of the gene responsible for the hyper-responsiveness.

To determine whether individuals with the hyper-responsive form of PAR4 may be less protected following a myocardial infarction or stroke even after receiving recommended antiplatelet therapy, the investigators compared healthy individuals and cardiac patients with and without the mutation for their responsiveness to PAR4. Participants were taking standard-of-care antiplatelet therapy (ie, aspirin and Plavix). The preliminary data demonstrated that, independent of race, individuals with a copy of the hyperactive variant of PAR4 have an increase in PAR4-mediated platelet reactivity, compared with individuals without the variant, even in the presence of antiplatelet therapy.

This research could identify the PAR4 T120A variant as a potential risk factor for thrombosis and would require a new approach to treating patients with this genetic variant, including the development of PAR4 antagonists. A greater understanding of which patients benefit the most from current therapeutic strategies and which patients remain at elevated risk for a thrombotic event will aid in the development of new therapeutic targets for at-risk populations.

This study illustrates potential benefits of the personalized medicine approach to therapeutic intervention and challenges the one-size-fits-all approach, which often leaves at-risk populations without adequate protection from thrombotic events and stroke.

More Reasons Why Getting a Good Night’s Sleep Is Important
Not getting enough sleep not only makes our minds less alert, but our bodies, too. Studies have suggested that losing several hours of sleep can slow the body’s metabolism. A team of researchers from the University of South Carolina and Arizona State University found that metabolic effects are seen even when sleep is shortened by two hours.

In this study, 15 healthy nonobese young adult volunteers completed two oral glucose tolerance tests. One was after three days of sleep restricted by two hours each day, and the other was after three days of ad libitum sleep. Plasma samples were collected before and 30, 60, 90, and 120 minutes after consumption of a glucose drink to determine glucose and insulin concentrations. Fasting C-peptide concentration was also determined.

The researchers observed that glucose concentrations before and 30, 60, 90, and 120 minutes following consumption of glucose were not different during the two glucose tolerance tests. Glucose area under the curve was also similar. Insulin concentrations before and 60, 90, and 120 minutes following consumption of glucose were not different, but insulin concentration 30 minutes following consumption of glucose was higher after restricted sleep (31.4 uIU/mL) than ad libitum sleep (23.7 uIU/mL). Insulin area under the curve and fasting C-peptide concentration were also greater following restricted sleep than ad libitum sleep. Sleeping two hours less thus increased insulin concentration, suggesting that cutting sleep even a little can alter metabolism.

“Our study was conducted in a group of young healthy adults after only three days of shortened sleep by two hours,” said Xuewen Wang, PhD, Assistant Professor of Exercise Science at the University of South Carolina in Columbia. “The study findings are important because this amount of shortened sleep is often seen in real life. Our next step is to find out whether the sleep pattern of shortened sleep during the week and catching-up sleep during the weekend affects glucose metabolism in the longer term. We are also interested in finding out the responses in individuals who already have impaired glucose metabolism.”

For patients who have active multiple sclerosis (MS) despite using injectable immunomodulators, switching to the oral immunomodulator fingolimod yields fewer relapses and less disability than does switching to a different injectable immunomodulator, according to a report published in the April issue of JAMA Neurology.

To compare MS outcomes using different treatment regimens, researchers used information from the MSBase registry, which collects observational data on the disorder as part of routine patient care. For this study, the investigators retrospectively analyzed data entered between 1996 and 2014 for 527 patients with MS who had breakthrough disease while receiving injectable immunomodulators (typically an interferon beta or glatiramer acetate preparation) and who switched to either oral fingolimod (148 patients) or a different interferon beta or glatiramer agent (379 patients) up to 12 months after on-treatment clinical disease activity.

The two groups were propensity matched for baseline clinical and demographic variables, including patient age, area of residence, disease duration, total number of previous treatments, disability score, number of relapses, and previous medications. The groups were followed for a median of 13 months (range, three to 80 months) after switching therapies, said Anna He, MBBS, a neurologist at Royal Melbourne Hospital in Australia, and her associates. Head-to-head analyses of relapse and disability outcomes used paired, weighted, negative binomial models or frailty proportional hazards models adjusted for MRI variables.

Patients who switched to fingolimod had a lower mean annualized relapse rate, compared with the other patients (0.31 vs 0.42). The fingolimod group had a decreased risk of relapse (hazard ratio [HR], 0.74), compared with patients who switched to a different injectable therapy. Patients who switched to fingolimod also had a 47% decreased risk of progression of disability. In addition, the fingolimod group had a markedly increased likelihood of disability regression (HR, 2.0). Furthermore, the rate of continuing on the new treatment at two years was higher with fingolimod (82.5%) than with a different injectable (73.2%), said Dr. He and her associates.

“Although analyses of observational data do not serve as a substitute for trial data, our study provides real-world evidence, representative of clinical practice in tertiary MS centers, to support clinical decision-making that is highly relevant to the management of active MS,” said the investigators.

—Mary Ann Moon

For patients who have active multiple sclerosis (MS) despite using injectable immunomodulators, switching to the oral immunomodulator fingolimod yields fewer relapses and less disability than does switching to a different injectable immunomodulator, according to a report published in the April issue of JAMA Neurology.

To compare MS outcomes using different treatment regimens, researchers used information from the MSBase registry, which collects observational data on the disorder as part of routine patient care. For this study, the investigators retrospectively analyzed data entered between 1996 and 2014 for 527 patients with MS who had breakthrough disease while receiving injectable immunomodulators (typically an interferon beta or glatiramer acetate preparation) and who switched to either oral fingolimod (148 patients) or a different interferon beta or glatiramer agent (379 patients) up to 12 months after on-treatment clinical disease activity.

The two groups were propensity matched for baseline clinical and demographic variables, including patient age, area of residence, disease duration, total number of previous treatments, disability score, number of relapses, and previous medications. The groups were followed for a median of 13 months (range, three to 80 months) after switching therapies, said Anna He, MBBS, a neurologist at Royal Melbourne Hospital in Australia, and her associates. Head-to-head analyses of relapse and disability outcomes used paired, weighted, negative binomial models or frailty proportional hazards models adjusted for MRI variables.

Patients who switched to fingolimod had a lower mean annualized relapse rate, compared with the other patients (0.31 vs 0.42). The fingolimod group had a decreased risk of relapse (hazard ratio [HR], 0.74), compared with patients who switched to a different injectable therapy. Patients who switched to fingolimod also had a 47% decreased risk of progression of disability. In addition, the fingolimod group had a markedly increased likelihood of disability regression (HR, 2.0). Furthermore, the rate of continuing on the new treatment at two years was higher with fingolimod (82.5%) than with a different injectable (73.2%), said Dr. He and her associates.

“Although analyses of observational data do not serve as a substitute for trial data, our study provides real-world evidence, representative of clinical practice in tertiary MS centers, to support clinical decision-making that is highly relevant to the management of active MS,” said the investigators.

—Mary Ann Moon

For patients who have active multiple sclerosis (MS) despite using injectable immunomodulators, switching to the oral immunomodulator fingolimod yields fewer relapses and less disability than does switching to a different injectable immunomodulator, according to a report published in the April issue of JAMA Neurology.

To compare MS outcomes using different treatment regimens, researchers used information from the MSBase registry, which collects observational data on the disorder as part of routine patient care. For this study, the investigators retrospectively analyzed data entered between 1996 and 2014 for 527 patients with MS who had breakthrough disease while receiving injectable immunomodulators (typically an interferon beta or glatiramer acetate preparation) and who switched to either oral fingolimod (148 patients) or a different interferon beta or glatiramer agent (379 patients) up to 12 months after on-treatment clinical disease activity.

The two groups were propensity matched for baseline clinical and demographic variables, including patient age, area of residence, disease duration, total number of previous treatments, disability score, number of relapses, and previous medications. The groups were followed for a median of 13 months (range, three to 80 months) after switching therapies, said Anna He, MBBS, a neurologist at Royal Melbourne Hospital in Australia, and her associates. Head-to-head analyses of relapse and disability outcomes used paired, weighted, negative binomial models or frailty proportional hazards models adjusted for MRI variables.

Patients who switched to fingolimod had a lower mean annualized relapse rate, compared with the other patients (0.31 vs 0.42). The fingolimod group had a decreased risk of relapse (hazard ratio [HR], 0.74), compared with patients who switched to a different injectable therapy. Patients who switched to fingolimod also had a 47% decreased risk of progression of disability. In addition, the fingolimod group had a markedly increased likelihood of disability regression (HR, 2.0). Furthermore, the rate of continuing on the new treatment at two years was higher with fingolimod (82.5%) than with a different injectable (73.2%), said Dr. He and her associates.

“Although analyses of observational data do not serve as a substitute for trial data, our study provides real-world evidence, representative of clinical practice in tertiary MS centers, to support clinical decision-making that is highly relevant to the management of active MS,” said the investigators.

—Mary Ann Moon

WASHINGTON, DC—A common anticonvulsant may protect the eyesight of patients with multiple sclerosis (MS), according to a study presented at the American Academy of Neurology’s 67th Annual Meeting. “About half of people with MS experience optic neuritis at some point in their life,” said study author Raj Kapoor, MD, with the National Hospital for Neurology and Neurosurgery in London. “The condition can cause sudden total or partial blindness, foggy or blackened vision, and pain. Even though eyesight can recover eventually, each attack still damages the nerve and the eye.”

For the study, Dr. Kapoor and colleagues randomly selected 86 patients with acute optic neuritis within two weeks of symptom onset to receive either phenytoin or a placebo for three months. The researchers then used medical imaging to measure the thickness of the retina at the beginning of the study and then six months later. Each patient’s eyesight (including sharpness and color perception) was also tested.

On average, the group who took phenytoin had 30% less damage to the nerve fiber layer, compared with those who received the placebo. The volume of the macula was 34% higher in those who took phenytoin than those who received the placebo. As expected after a single attack, patients’ vision successfully recovered, and there weren’t any significant differences in visual outcomes over the long term between the two groups.

“Eyesight is key to many important aspects of life, such as working, driving, and participating in social activities,” said Dr. Kapoor. “If this finding is confirmed by larger studies, it could lead to a treatment that may prevent nerve damage and blindness in MS and could help other attacks of MS, serving a major unmet need.”

The study was supported by the National Multiple Sclerosis Society, the Multiple Sclerosis Society of Great Britain and Northern Ireland, an unrestricted grant from Novartis, the National Institute for Health Research Clinical Research Network, and University College London Hospitals Biomedical Research Center.

WASHINGTON, DC—A common anticonvulsant may protect the eyesight of patients with multiple sclerosis (MS), according to a study presented at the American Academy of Neurology’s 67th Annual Meeting. “About half of people with MS experience optic neuritis at some point in their life,” said study author Raj Kapoor, MD, with the National Hospital for Neurology and Neurosurgery in London. “The condition can cause sudden total or partial blindness, foggy or blackened vision, and pain. Even though eyesight can recover eventually, each attack still damages the nerve and the eye.”

For the study, Dr. Kapoor and colleagues randomly selected 86 patients with acute optic neuritis within two weeks of symptom onset to receive either phenytoin or a placebo for three months. The researchers then used medical imaging to measure the thickness of the retina at the beginning of the study and then six months later. Each patient’s eyesight (including sharpness and color perception) was also tested.

On average, the group who took phenytoin had 30% less damage to the nerve fiber layer, compared with those who received the placebo. The volume of the macula was 34% higher in those who took phenytoin than those who received the placebo. As expected after a single attack, patients’ vision successfully recovered, and there weren’t any significant differences in visual outcomes over the long term between the two groups.

“Eyesight is key to many important aspects of life, such as working, driving, and participating in social activities,” said Dr. Kapoor. “If this finding is confirmed by larger studies, it could lead to a treatment that may prevent nerve damage and blindness in MS and could help other attacks of MS, serving a major unmet need.”

The study was supported by the National Multiple Sclerosis Society, the Multiple Sclerosis Society of Great Britain and Northern Ireland, an unrestricted grant from Novartis, the National Institute for Health Research Clinical Research Network, and University College London Hospitals Biomedical Research Center.

WASHINGTON, DC—A common anticonvulsant may protect the eyesight of patients with multiple sclerosis (MS), according to a study presented at the American Academy of Neurology’s 67th Annual Meeting. “About half of people with MS experience optic neuritis at some point in their life,” said study author Raj Kapoor, MD, with the National Hospital for Neurology and Neurosurgery in London. “The condition can cause sudden total or partial blindness, foggy or blackened vision, and pain. Even though eyesight can recover eventually, each attack still damages the nerve and the eye.”

For the study, Dr. Kapoor and colleagues randomly selected 86 patients with acute optic neuritis within two weeks of symptom onset to receive either phenytoin or a placebo for three months. The researchers then used medical imaging to measure the thickness of the retina at the beginning of the study and then six months later. Each patient’s eyesight (including sharpness and color perception) was also tested.

On average, the group who took phenytoin had 30% less damage to the nerve fiber layer, compared with those who received the placebo. The volume of the macula was 34% higher in those who took phenytoin than those who received the placebo. As expected after a single attack, patients’ vision successfully recovered, and there weren’t any significant differences in visual outcomes over the long term between the two groups.

“Eyesight is key to many important aspects of life, such as working, driving, and participating in social activities,” said Dr. Kapoor. “If this finding is confirmed by larger studies, it could lead to a treatment that may prevent nerve damage and blindness in MS and could help other attacks of MS, serving a major unmet need.”

The study was supported by the National Multiple Sclerosis Society, the Multiple Sclerosis Society of Great Britain and Northern Ireland, an unrestricted grant from Novartis, the National Institute for Health Research Clinical Research Network, and University College London Hospitals Biomedical Research Center.

WASHINGTON, DC—A significant minority of patients with multiple sclerosis (MS) who were in remission for at least five years before discontinuing disease-modifying therapy (DMT) experienced disease worsening upon stopping their medication, according to research presented at the 67th Annual Meeting of the American Academy of Neurology.

Ilya Kister, MD, Assistant Professor of Neurology at the NYU Langone Multiple Sclerosis Comprehensive Care Center, and colleagues analyzed data from the MSBase Registry, an international database that collects physician-submitted data on approximately 30,000 patients, to study relapse rate and disability progression after first-line DMT is discontinued in previously stable patients.

“If and when MS patients can safely discontinue DMT treatment is an important question that frequently comes up in clinical practice, especially with regard to patients who have been clinically and radiologically stable for a long time,” the researchers said. Some patients grow tired of taking their medicine, or feel it doesn’t work, and may stop taking it with or without their doctors’ consent, said Dr. Kister, the study’s lead author. Patients also might not be able to afford medication copayments or might encounter other insurance issues, according to the National MS Society.

The researchers identified 182 patients who met their inclusion criteria. Patients were age 40 or older at baseline and had stable Expanded Disability Status Scale (EDSS) scores and no relapse for at least five years prior to baseline. Patients were treated continuously with DMT for at least three years before the therapy was discontinued, and patients were followed for at least three years after stopping their medication. Patients who reinitiated DMT within three months were considered “DMT switchers” and excluded from the analysis.

Approximately one in four patients experienced a clinician-confirmed relapse, and approximately one in three patients had confirmed disability progression. Confirmed disability progression was defined as an increase of at least one point in EDSS score above a baseline score of 1–5.5, confirmed at repeat assessment at least three months or one year later.

Reasons for stopping DMTs included lack of improvement (9%), perceived disease progression (10%), intolerance (8%), inconvenience (8%), adverse event (6%), and unknown (66%). During the post-discontinuation period (median 4.2 years), 44 (24.2%) patients had a relapse, 36 (of 113, 31.9%) had three-month disability progression, and 12 patients (10.6%) had relapse and disability progression.

DMTs were restarted by 77 of 182 patients (42%) after three or more months, with a median time to restart of 22 months. Those who restarted DMT had a 59% decrease in the rate of disability progression compared with those who did not restart DMT, researchers said. Those who did and did not restart DMT had similar relapse rates.

“Decisions regarding stopping disease-modifying therapy may have implications for short and long-term prognosis. We know a lot about what happens when therapy is started, but we know very little about what happens when therapy is stopped,” Dr. Kister said. The researchers call for a randomized DMT discontinuation trial in stable, older patients to help answer whether and when patients may stop DMT.

WASHINGTON, DC—A significant minority of patients with multiple sclerosis (MS) who were in remission for at least five years before discontinuing disease-modifying therapy (DMT) experienced disease worsening upon stopping their medication, according to research presented at the 67th Annual Meeting of the American Academy of Neurology.

Ilya Kister, MD, Assistant Professor of Neurology at the NYU Langone Multiple Sclerosis Comprehensive Care Center, and colleagues analyzed data from the MSBase Registry, an international database that collects physician-submitted data on approximately 30,000 patients, to study relapse rate and disability progression after first-line DMT is discontinued in previously stable patients.

“If and when MS patients can safely discontinue DMT treatment is an important question that frequently comes up in clinical practice, especially with regard to patients who have been clinically and radiologically stable for a long time,” the researchers said. Some patients grow tired of taking their medicine, or feel it doesn’t work, and may stop taking it with or without their doctors’ consent, said Dr. Kister, the study’s lead author. Patients also might not be able to afford medication copayments or might encounter other insurance issues, according to the National MS Society.

The researchers identified 182 patients who met their inclusion criteria. Patients were age 40 or older at baseline and had stable Expanded Disability Status Scale (EDSS) scores and no relapse for at least five years prior to baseline. Patients were treated continuously with DMT for at least three years before the therapy was discontinued, and patients were followed for at least three years after stopping their medication. Patients who reinitiated DMT within three months were considered “DMT switchers” and excluded from the analysis.

Approximately one in four patients experienced a clinician-confirmed relapse, and approximately one in three patients had confirmed disability progression. Confirmed disability progression was defined as an increase of at least one point in EDSS score above a baseline score of 1–5.5, confirmed at repeat assessment at least three months or one year later.

Reasons for stopping DMTs included lack of improvement (9%), perceived disease progression (10%), intolerance (8%), inconvenience (8%), adverse event (6%), and unknown (66%). During the post-discontinuation period (median 4.2 years), 44 (24.2%) patients had a relapse, 36 (of 113, 31.9%) had three-month disability progression, and 12 patients (10.6%) had relapse and disability progression.

DMTs were restarted by 77 of 182 patients (42%) after three or more months, with a median time to restart of 22 months. Those who restarted DMT had a 59% decrease in the rate of disability progression compared with those who did not restart DMT, researchers said. Those who did and did not restart DMT had similar relapse rates.

“Decisions regarding stopping disease-modifying therapy may have implications for short and long-term prognosis. We know a lot about what happens when therapy is started, but we know very little about what happens when therapy is stopped,” Dr. Kister said. The researchers call for a randomized DMT discontinuation trial in stable, older patients to help answer whether and when patients may stop DMT.

WASHINGTON, DC—A significant minority of patients with multiple sclerosis (MS) who were in remission for at least five years before discontinuing disease-modifying therapy (DMT) experienced disease worsening upon stopping their medication, according to research presented at the 67th Annual Meeting of the American Academy of Neurology.

Ilya Kister, MD, Assistant Professor of Neurology at the NYU Langone Multiple Sclerosis Comprehensive Care Center, and colleagues analyzed data from the MSBase Registry, an international database that collects physician-submitted data on approximately 30,000 patients, to study relapse rate and disability progression after first-line DMT is discontinued in previously stable patients.

“If and when MS patients can safely discontinue DMT treatment is an important question that frequently comes up in clinical practice, especially with regard to patients who have been clinically and radiologically stable for a long time,” the researchers said. Some patients grow tired of taking their medicine, or feel it doesn’t work, and may stop taking it with or without their doctors’ consent, said Dr. Kister, the study’s lead author. Patients also might not be able to afford medication copayments or might encounter other insurance issues, according to the National MS Society.

The researchers identified 182 patients who met their inclusion criteria. Patients were age 40 or older at baseline and had stable Expanded Disability Status Scale (EDSS) scores and no relapse for at least five years prior to baseline. Patients were treated continuously with DMT for at least three years before the therapy was discontinued, and patients were followed for at least three years after stopping their medication. Patients who reinitiated DMT within three months were considered “DMT switchers” and excluded from the analysis.

Approximately one in four patients experienced a clinician-confirmed relapse, and approximately one in three patients had confirmed disability progression. Confirmed disability progression was defined as an increase of at least one point in EDSS score above a baseline score of 1–5.5, confirmed at repeat assessment at least three months or one year later.

Reasons for stopping DMTs included lack of improvement (9%), perceived disease progression (10%), intolerance (8%), inconvenience (8%), adverse event (6%), and unknown (66%). During the post-discontinuation period (median 4.2 years), 44 (24.2%) patients had a relapse, 36 (of 113, 31.9%) had three-month disability progression, and 12 patients (10.6%) had relapse and disability progression.

DMTs were restarted by 77 of 182 patients (42%) after three or more months, with a median time to restart of 22 months. Those who restarted DMT had a 59% decrease in the rate of disability progression compared with those who did not restart DMT, researchers said. Those who did and did not restart DMT had similar relapse rates.

“Decisions regarding stopping disease-modifying therapy may have implications for short and long-term prognosis. We know a lot about what happens when therapy is started, but we know very little about what happens when therapy is stopped,” Dr. Kister said. The researchers call for a randomized DMT discontinuation trial in stable, older patients to help answer whether and when patients may stop DMT.

WASHINGTON, DC—Drinking coffee may be associated with a lower risk of developing multiple sclerosis (MS), according to a study presented at the American Academy of Neurology’s 67th Annual Meeting. “Caffeine intake has been associated with a reduced risk of Parkinson’s and Alzheimer’s diseases, and our study shows that coffee intake may also protect against MS, supporting the idea that the drug may have protective effects for the brain,” said study author Ellen Mowry, MD, MCR, of Johns Hopkins University School of Medicine in Baltimore.

For the study, researchers looked at two population-based case–control studies—a Swedish study of 1,629 patients with MS and 2,807 healthy controls, and a Kaiser Permanente Northern California study of 1,159 patients with MS and 1,172 healthy controls. The studies characterized coffee consumption among patients with MS one and five years before MS symptoms began (as well as 10 years before MS symptoms began in the Swedish study) and compared it with coffee consumption of people who did not have MS at similar time periods. The study also accounted for other factors such as age, sex, smoking, BMI, and sun exposure habits.

The Swedish study found that compared with people who drank at least six cups of coffee per day during the year before symptoms appeared, those who did not drink coffee had about a one and a half times increased risk of developing MS. Drinking large amounts of coffee five or 10 years before symptoms started was similarly protective.

In the US study, people who did not drink coffee were also about one and a half times more likely to develop the disease than those who drank four or more cups of coffee per day in the year before symptoms started to develop the disease.

“Caffeine should be studied for its impact on relapses and long-term disability in MS as well,” said Dr. Mowry.

The study was supported by the Swedish Medical Research Council; the Swedish Research Council for Health, Working Life and Welfare; the Knut and Alice Wallenberg, AFA, and Swedish Brain Foundations; the Swedish Association for Persons with Neurological Disabilities; and the U.S. National Institute of Neurological Disorders and Stroke, the National Institute of Environmental Health Sciences, and the National Institute on Aging.

WASHINGTON, DC—Drinking coffee may be associated with a lower risk of developing multiple sclerosis (MS), according to a study presented at the American Academy of Neurology’s 67th Annual Meeting. “Caffeine intake has been associated with a reduced risk of Parkinson’s and Alzheimer’s diseases, and our study shows that coffee intake may also protect against MS, supporting the idea that the drug may have protective effects for the brain,” said study author Ellen Mowry, MD, MCR, of Johns Hopkins University School of Medicine in Baltimore.

For the study, researchers looked at two population-based case–control studies—a Swedish study of 1,629 patients with MS and 2,807 healthy controls, and a Kaiser Permanente Northern California study of 1,159 patients with MS and 1,172 healthy controls. The studies characterized coffee consumption among patients with MS one and five years before MS symptoms began (as well as 10 years before MS symptoms began in the Swedish study) and compared it with coffee consumption of people who did not have MS at similar time periods. The study also accounted for other factors such as age, sex, smoking, BMI, and sun exposure habits.

The Swedish study found that compared with people who drank at least six cups of coffee per day during the year before symptoms appeared, those who did not drink coffee had about a one and a half times increased risk of developing MS. Drinking large amounts of coffee five or 10 years before symptoms started was similarly protective.

In the US study, people who did not drink coffee were also about one and a half times more likely to develop the disease than those who drank four or more cups of coffee per day in the year before symptoms started to develop the disease.

“Caffeine should be studied for its impact on relapses and long-term disability in MS as well,” said Dr. Mowry.

The study was supported by the Swedish Medical Research Council; the Swedish Research Council for Health, Working Life and Welfare; the Knut and Alice Wallenberg, AFA, and Swedish Brain Foundations; the Swedish Association for Persons with Neurological Disabilities; and the U.S. National Institute of Neurological Disorders and Stroke, the National Institute of Environmental Health Sciences, and the National Institute on Aging.

WASHINGTON, DC—Drinking coffee may be associated with a lower risk of developing multiple sclerosis (MS), according to a study presented at the American Academy of Neurology’s 67th Annual Meeting. “Caffeine intake has been associated with a reduced risk of Parkinson’s and Alzheimer’s diseases, and our study shows that coffee intake may also protect against MS, supporting the idea that the drug may have protective effects for the brain,” said study author Ellen Mowry, MD, MCR, of Johns Hopkins University School of Medicine in Baltimore.

For the study, researchers looked at two population-based case–control studies—a Swedish study of 1,629 patients with MS and 2,807 healthy controls, and a Kaiser Permanente Northern California study of 1,159 patients with MS and 1,172 healthy controls. The studies characterized coffee consumption among patients with MS one and five years before MS symptoms began (as well as 10 years before MS symptoms began in the Swedish study) and compared it with coffee consumption of people who did not have MS at similar time periods. The study also accounted for other factors such as age, sex, smoking, BMI, and sun exposure habits.

The Swedish study found that compared with people who drank at least six cups of coffee per day during the year before symptoms appeared, those who did not drink coffee had about a one and a half times increased risk of developing MS. Drinking large amounts of coffee five or 10 years before symptoms started was similarly protective.

In the US study, people who did not drink coffee were also about one and a half times more likely to develop the disease than those who drank four or more cups of coffee per day in the year before symptoms started to develop the disease.

“Caffeine should be studied for its impact on relapses and long-term disability in MS as well,” said Dr. Mowry.

The study was supported by the Swedish Medical Research Council; the Swedish Research Council for Health, Working Life and Welfare; the Knut and Alice Wallenberg, AFA, and Swedish Brain Foundations; the Swedish Association for Persons with Neurological Disabilities; and the U.S. National Institute of Neurological Disorders and Stroke, the National Institute of Environmental Health Sciences, and the National Institute on Aging.

WASHINGTON, DC—A new study suggests that an investigational drug for multiple sclerosis (MS) may repair myelin, according to a study presented at the American Academy of Neurology’s 67th Annual Meeting. “This study, for the first time, provides biological evidence of repair of damaged myelin in the human brain and advances the field of neuroreparative therapies,” said study lead author Diego Cadavid, MD, a Senior Director at Biogen Idec in Cambridge, Massachusetts.

The phase 2 study involved 82 patients who had their first incident of acute optic neuritis. All participants were treated with high dose steroids and randomly selected with equal probability to receive either the experimental antibody, called anti-LINGO-1, or a placebo once every four weeks, for a total of six doses. Participants were assessed every four weeks for six months and at a final visit at eight months. The drug’s effectiveness in repairing myelin was evaluated by comparing the recovery of the optic nerve latency in the damaged eye at six and eight months to the normal unaffected eye at the start of the study.

The main finding of the study focused on the latency of the visual evoked potential (VEP). The results showed that patients treated with anti-LINGO-1 who did not miss more than one dose (per protocol population) had significantly improved conduction, as measured by latency recovery, compared with people who received the placebo. At six months, those who received the drug improved on average by 7.55 milliseconds, or 34%, compared with placebo. The effect continued to eight months with an average improvement of 9.13 milliseconds or 41% over placebo.

In addition, the percentage of subjects whose VEP latency in the affected eye recovered to normal or nearly normal (ie, within 10% of that of the normal eye) more than doubled from 26% on placebo to 53% on the drug.

A substudy using an exploratory method of measuring latency called multifocal VEP revealed similar treatment effects. “More studies are needed to evaluate whether these changes lead to clinical improvement,” said Dr. Cadavid. A second study of anti-LINGO-1 in patients with MS is ongoing.

The study was supported by Biogen Idec.

WASHINGTON, DC—A new study suggests that an investigational drug for multiple sclerosis (MS) may repair myelin, according to a study presented at the American Academy of Neurology’s 67th Annual Meeting. “This study, for the first time, provides biological evidence of repair of damaged myelin in the human brain and advances the field of neuroreparative therapies,” said study lead author Diego Cadavid, MD, a Senior Director at Biogen Idec in Cambridge, Massachusetts.

The phase 2 study involved 82 patients who had their first incident of acute optic neuritis. All participants were treated with high dose steroids and randomly selected with equal probability to receive either the experimental antibody, called anti-LINGO-1, or a placebo once every four weeks, for a total of six doses. Participants were assessed every four weeks for six months and at a final visit at eight months. The drug’s effectiveness in repairing myelin was evaluated by comparing the recovery of the optic nerve latency in the damaged eye at six and eight months to the normal unaffected eye at the start of the study.

The main finding of the study focused on the latency of the visual evoked potential (VEP). The results showed that patients treated with anti-LINGO-1 who did not miss more than one dose (per protocol population) had significantly improved conduction, as measured by latency recovery, compared with people who received the placebo. At six months, those who received the drug improved on average by 7.55 milliseconds, or 34%, compared with placebo. The effect continued to eight months with an average improvement of 9.13 milliseconds or 41% over placebo.

In addition, the percentage of subjects whose VEP latency in the affected eye recovered to normal or nearly normal (ie, within 10% of that of the normal eye) more than doubled from 26% on placebo to 53% on the drug.

A substudy using an exploratory method of measuring latency called multifocal VEP revealed similar treatment effects. “More studies are needed to evaluate whether these changes lead to clinical improvement,” said Dr. Cadavid. A second study of anti-LINGO-1 in patients with MS is ongoing.

The study was supported by Biogen Idec.

WASHINGTON, DC—A new study suggests that an investigational drug for multiple sclerosis (MS) may repair myelin, according to a study presented at the American Academy of Neurology’s 67th Annual Meeting. “This study, for the first time, provides biological evidence of repair of damaged myelin in the human brain and advances the field of neuroreparative therapies,” said study lead author Diego Cadavid, MD, a Senior Director at Biogen Idec in Cambridge, Massachusetts.

The phase 2 study involved 82 patients who had their first incident of acute optic neuritis. All participants were treated with high dose steroids and randomly selected with equal probability to receive either the experimental antibody, called anti-LINGO-1, or a placebo once every four weeks, for a total of six doses. Participants were assessed every four weeks for six months and at a final visit at eight months. The drug’s effectiveness in repairing myelin was evaluated by comparing the recovery of the optic nerve latency in the damaged eye at six and eight months to the normal unaffected eye at the start of the study.

The main finding of the study focused on the latency of the visual evoked potential (VEP). The results showed that patients treated with anti-LINGO-1 who did not miss more than one dose (per protocol population) had significantly improved conduction, as measured by latency recovery, compared with people who received the placebo. At six months, those who received the drug improved on average by 7.55 milliseconds, or 34%, compared with placebo. The effect continued to eight months with an average improvement of 9.13 milliseconds or 41% over placebo.

In addition, the percentage of subjects whose VEP latency in the affected eye recovered to normal or nearly normal (ie, within 10% of that of the normal eye) more than doubled from 26% on placebo to 53% on the drug.

A substudy using an exploratory method of measuring latency called multifocal VEP revealed similar treatment effects. “More studies are needed to evaluate whether these changes lead to clinical improvement,” said Dr. Cadavid. A second study of anti-LINGO-1 in patients with MS is ongoing.

The study was supported by Biogen Idec.