ICYMI Multiple Sclerosis

INDIANAPOLIS—Investigators are conducting clinical trials of various drugs that may slow clinical worsening in patients with progressive multiple sclerosis (MS), according to an overview provided at the 2015 CMSC Annual Meeting. Two such agents, anti-LINGO-1 antibody and rHIgM22 monoclonal antibody, are under active development in early clinical trials.

“Treatments that promote remyelination are going to prove to be the most effective way to prevent or treat progressive MS,” said Dennis Bourdette, MD, Roy and Eulalia Swank Family Research Professor and Chairman of the Department of Neurology at Oregon Health & Science University (OHSU) School of Medicine in Portland. Investigators are developing cell-based, large-molecule (ie, biologic), and small-molecule (ie, chemically manufactured) therapies that could promote remyelination.

Cell-Based Therapies
One potential treatment is to inject oligodendrocyte precursor cells (OPCs) into the brain and spinal cord. These OPCs then could become oligodendrocytes and produce myelin. Researchers in New York state under the leadership of Drs. Steven Goldman and Burk Jubelt are preparing for a phase I trial of this technique. They plan to use embryonic OPCs and are working with the FDA to establish the appropriate controls for the study.

Current surgical technology should allow the team to inject human OPCs into the brain safely, said Dr. Bourdette. “Researchers have shown that human embryonic-derived OPCs injected into the brains of rodents that have hypomyelination caused by a genetic defect will migrate long distances and myelinate axons.” The goal is for the OPCs to migrate into areas of demyelination in the brain of people with MS and remyelinate axons.

But how far the OPCs will migrate and whether this technique will succeed are open questions, added Dr. Bourdette. The brain of a patient with MS already has OPCs, and adding more OPCs may not promote remyelination, he said. “It might be an approach that is particularly useful, though, in people who are disabled from large plaques in the cervical cord.”

Large-Molecule Approaches
Another approach to promoting remyelination is to block the protein LINGO, which inhibits the differentiation of OPCs into oligodendrocytes. Biogen has developed an anti-LINGO-1 monoclonal antibody that appeared to promote remyelination in patients with optic neuritis during a small phase II trial. Investigators currently are studying this monoclonal antibody in patients with relapsing MS.

A group of investigators at the Mayo Clinic have developed recombinant human IgM22 antibody that promotes OPC differentiation and remyelination in animal models. The drug’s safety has been assessed in a phase I trial. Because the anti-LINGO antibody and the human IgM22 are large molecules, they will not penetrate the brain easily, said Dr. Bourdette. Large doses of these medicines thus will be required to achieve a therapeutic effect.

Small Molecules in Development
Small molecules also could stimulate OPC differentiation. These drugs can be modified to enhance their ability to penetrate the CNS, in contrast with large molecules.

One class of drugs that researchers are studying is thyromimetic medicines, which seek to simulate the effects of thyroid hormone. Thyroid hormone is necessary for OPCs to differentiate into oligodendrocytes and to promote myelination. Patients with hypothyroidism do not produce the normal amount of myelin. Investigators use thyroid hormone to promote OPC differentiation in vitro, and the drug is a potential treatment for patients with MS.

Peter Calabresi, MD, Director of the Division of Neuroimmunology at Johns Hopkins University in Baltimore, and colleagues are preparing to begin a trial of thyroid hormone for promoting remyelination in patients with MS. Although the approach seems promising, “the problem is that you may have to make patients thyrotoxic in order to get enough of thyroid to be beneficial,” said Dr. Bourdette. Thyroid hormone also can be cardiotoxic.

Thyromimetic drugs may represent a better approach, said Dr. Bourdette. These drugs are modifications of the thyroid hormone that have preferential activity for the thyroid hormone receptors on oligodendrocytes, which differ from those on the heart. Investigators thus can make thyromimetic drugs with differential affinities for the brain and OPC. Thomas Scanlan, PhD, Director of the Program in Chemical Biology at OHSU, and colleagues created a thyromimetic drug as a means of lowering cholesterol with minimal effects on the heart. This drug can stimulate OPCs. Researchers at OHSU now are studying the agent in a mouse model of demyelination. “The drug does accelerate remyelination in the mouse model, but not as well as the thyroid hormone,” said Dr. Bourdette. The investigators hypothesize that the thyromimetic drug does not penetrate the brain effectively, and they are modifying the drug to improve its ability to enter the brain.

 

Other investigators are working on developing small-molecule drugs that can stimulate remyelination. There is thus reason to be optimistic that the small-molecule approach to promoting remyelination will prove to be beneficial, said Dr. Bourdette. Providing a strong stimulus to the OPCs may allow them to overcome the toxic environment that they inhabit, he concluded.

—Erik Greb

INDIANAPOLIS—Investigators are conducting clinical trials of various drugs that may slow clinical worsening in patients with progressive multiple sclerosis (MS), according to an overview provided at the 2015 CMSC Annual Meeting. Two such agents, anti-LINGO-1 antibody and rHIgM22 monoclonal antibody, are under active development in early clinical trials.

“Treatments that promote remyelination are going to prove to be the most effective way to prevent or treat progressive MS,” said Dennis Bourdette, MD, Roy and Eulalia Swank Family Research Professor and Chairman of the Department of Neurology at Oregon Health & Science University (OHSU) School of Medicine in Portland. Investigators are developing cell-based, large-molecule (ie, biologic), and small-molecule (ie, chemically manufactured) therapies that could promote remyelination.

Cell-Based Therapies
One potential treatment is to inject oligodendrocyte precursor cells (OPCs) into the brain and spinal cord. These OPCs then could become oligodendrocytes and produce myelin. Researchers in New York state under the leadership of Drs. Steven Goldman and Burk Jubelt are preparing for a phase I trial of this technique. They plan to use embryonic OPCs and are working with the FDA to establish the appropriate controls for the study.

Current surgical technology should allow the team to inject human OPCs into the brain safely, said Dr. Bourdette. “Researchers have shown that human embryonic-derived OPCs injected into the brains of rodents that have hypomyelination caused by a genetic defect will migrate long distances and myelinate axons.” The goal is for the OPCs to migrate into areas of demyelination in the brain of people with MS and remyelinate axons.

But how far the OPCs will migrate and whether this technique will succeed are open questions, added Dr. Bourdette. The brain of a patient with MS already has OPCs, and adding more OPCs may not promote remyelination, he said. “It might be an approach that is particularly useful, though, in people who are disabled from large plaques in the cervical cord.”

Large-Molecule Approaches
Another approach to promoting remyelination is to block the protein LINGO, which inhibits the differentiation of OPCs into oligodendrocytes. Biogen has developed an anti-LINGO-1 monoclonal antibody that appeared to promote remyelination in patients with optic neuritis during a small phase II trial. Investigators currently are studying this monoclonal antibody in patients with relapsing MS.

A group of investigators at the Mayo Clinic have developed recombinant human IgM22 antibody that promotes OPC differentiation and remyelination in animal models. The drug’s safety has been assessed in a phase I trial. Because the anti-LINGO antibody and the human IgM22 are large molecules, they will not penetrate the brain easily, said Dr. Bourdette. Large doses of these medicines thus will be required to achieve a therapeutic effect.

Small Molecules in Development
Small molecules also could stimulate OPC differentiation. These drugs can be modified to enhance their ability to penetrate the CNS, in contrast with large molecules.

One class of drugs that researchers are studying is thyromimetic medicines, which seek to simulate the effects of thyroid hormone. Thyroid hormone is necessary for OPCs to differentiate into oligodendrocytes and to promote myelination. Patients with hypothyroidism do not produce the normal amount of myelin. Investigators use thyroid hormone to promote OPC differentiation in vitro, and the drug is a potential treatment for patients with MS.

Peter Calabresi, MD, Director of the Division of Neuroimmunology at Johns Hopkins University in Baltimore, and colleagues are preparing to begin a trial of thyroid hormone for promoting remyelination in patients with MS. Although the approach seems promising, “the problem is that you may have to make patients thyrotoxic in order to get enough of thyroid to be beneficial,” said Dr. Bourdette. Thyroid hormone also can be cardiotoxic.

Thyromimetic drugs may represent a better approach, said Dr. Bourdette. These drugs are modifications of the thyroid hormone that have preferential activity for the thyroid hormone receptors on oligodendrocytes, which differ from those on the heart. Investigators thus can make thyromimetic drugs with differential affinities for the brain and OPC. Thomas Scanlan, PhD, Director of the Program in Chemical Biology at OHSU, and colleagues created a thyromimetic drug as a means of lowering cholesterol with minimal effects on the heart. This drug can stimulate OPCs. Researchers at OHSU now are studying the agent in a mouse model of demyelination. “The drug does accelerate remyelination in the mouse model, but not as well as the thyroid hormone,” said Dr. Bourdette. The investigators hypothesize that the thyromimetic drug does not penetrate the brain effectively, and they are modifying the drug to improve its ability to enter the brain.

 

Other investigators are working on developing small-molecule drugs that can stimulate remyelination. There is thus reason to be optimistic that the small-molecule approach to promoting remyelination will prove to be beneficial, said Dr. Bourdette. Providing a strong stimulus to the OPCs may allow them to overcome the toxic environment that they inhabit, he concluded.

—Erik Greb

INDIANAPOLIS—Investigators are conducting clinical trials of various drugs that may slow clinical worsening in patients with progressive multiple sclerosis (MS), according to an overview provided at the 2015 CMSC Annual Meeting. Two such agents, anti-LINGO-1 antibody and rHIgM22 monoclonal antibody, are under active development in early clinical trials.

“Treatments that promote remyelination are going to prove to be the most effective way to prevent or treat progressive MS,” said Dennis Bourdette, MD, Roy and Eulalia Swank Family Research Professor and Chairman of the Department of Neurology at Oregon Health & Science University (OHSU) School of Medicine in Portland. Investigators are developing cell-based, large-molecule (ie, biologic), and small-molecule (ie, chemically manufactured) therapies that could promote remyelination.

Cell-Based Therapies
One potential treatment is to inject oligodendrocyte precursor cells (OPCs) into the brain and spinal cord. These OPCs then could become oligodendrocytes and produce myelin. Researchers in New York state under the leadership of Drs. Steven Goldman and Burk Jubelt are preparing for a phase I trial of this technique. They plan to use embryonic OPCs and are working with the FDA to establish the appropriate controls for the study.

Current surgical technology should allow the team to inject human OPCs into the brain safely, said Dr. Bourdette. “Researchers have shown that human embryonic-derived OPCs injected into the brains of rodents that have hypomyelination caused by a genetic defect will migrate long distances and myelinate axons.” The goal is for the OPCs to migrate into areas of demyelination in the brain of people with MS and remyelinate axons.

But how far the OPCs will migrate and whether this technique will succeed are open questions, added Dr. Bourdette. The brain of a patient with MS already has OPCs, and adding more OPCs may not promote remyelination, he said. “It might be an approach that is particularly useful, though, in people who are disabled from large plaques in the cervical cord.”

Large-Molecule Approaches
Another approach to promoting remyelination is to block the protein LINGO, which inhibits the differentiation of OPCs into oligodendrocytes. Biogen has developed an anti-LINGO-1 monoclonal antibody that appeared to promote remyelination in patients with optic neuritis during a small phase II trial. Investigators currently are studying this monoclonal antibody in patients with relapsing MS.

A group of investigators at the Mayo Clinic have developed recombinant human IgM22 antibody that promotes OPC differentiation and remyelination in animal models. The drug’s safety has been assessed in a phase I trial. Because the anti-LINGO antibody and the human IgM22 are large molecules, they will not penetrate the brain easily, said Dr. Bourdette. Large doses of these medicines thus will be required to achieve a therapeutic effect.

Small Molecules in Development
Small molecules also could stimulate OPC differentiation. These drugs can be modified to enhance their ability to penetrate the CNS, in contrast with large molecules.

One class of drugs that researchers are studying is thyromimetic medicines, which seek to simulate the effects of thyroid hormone. Thyroid hormone is necessary for OPCs to differentiate into oligodendrocytes and to promote myelination. Patients with hypothyroidism do not produce the normal amount of myelin. Investigators use thyroid hormone to promote OPC differentiation in vitro, and the drug is a potential treatment for patients with MS.

Peter Calabresi, MD, Director of the Division of Neuroimmunology at Johns Hopkins University in Baltimore, and colleagues are preparing to begin a trial of thyroid hormone for promoting remyelination in patients with MS. Although the approach seems promising, “the problem is that you may have to make patients thyrotoxic in order to get enough of thyroid to be beneficial,” said Dr. Bourdette. Thyroid hormone also can be cardiotoxic.

Thyromimetic drugs may represent a better approach, said Dr. Bourdette. These drugs are modifications of the thyroid hormone that have preferential activity for the thyroid hormone receptors on oligodendrocytes, which differ from those on the heart. Investigators thus can make thyromimetic drugs with differential affinities for the brain and OPC. Thomas Scanlan, PhD, Director of the Program in Chemical Biology at OHSU, and colleagues created a thyromimetic drug as a means of lowering cholesterol with minimal effects on the heart. This drug can stimulate OPCs. Researchers at OHSU now are studying the agent in a mouse model of demyelination. “The drug does accelerate remyelination in the mouse model, but not as well as the thyroid hormone,” said Dr. Bourdette. The investigators hypothesize that the thyromimetic drug does not penetrate the brain effectively, and they are modifying the drug to improve its ability to enter the brain.

 

Other investigators are working on developing small-molecule drugs that can stimulate remyelination. There is thus reason to be optimistic that the small-molecule approach to promoting remyelination will prove to be beneficial, said Dr. Bourdette. Providing a strong stimulus to the OPCs may allow them to overcome the toxic environment that they inhabit, he concluded.

—Erik Greb

Gray matter fraction (GMF) change is more meaningful than white matter fraction (WMF) as a marker of tissue loss and may be useful to augment whole brain atrophy measurements in MS clinical trials, according to a study of 140 patients with relapsing-remitting MS who were randomized to intramuscular interferon (IFN) beta-1a or placebo. Researchers found:

• Significantly less GM atrophy (during year 2), but not WM atrophy (at any point), was seen with IFN beta-1a compared with placebo.

• Pseudoatrophy effects were more apparent in WM than in GM; in year 1, greater WM volume loss was seen with IFN beta-1a than with placebo, but GM volume loss was similar between groups. 

• Risk of sustained disability progression was significantly associated with GM atrophy, but not WM atrophy.
 
Citation: Fisher E, Nakamura K, Lee JC, You X, Sperling B, Rudick RA. Effect of intramuscular interferon beta-1a on gray matter atrophy in relapsing−remitting multiple sclerosis: a retrospective analysis. [Published online ahead of print August 3, 2015]. Mult Scler. doi: 10.1177/1352458515599072.

Commentary: Understanding a disease requires thorough analysis of its impact. Multiple sclerosis is classically known as a white matter disease. It is also known that MS white matter plaques are in typical subcortical locations. This has been the tenet of MS care and diagnosis by MRI.  However, it is also a tenet that MRI changes do not always correlate with clinical exam or disease impact. Many people involved in MS care and research have explored the reason for this discrepancy.  This important article is another step along the path of understanding.  MS plaques have now been identified within the white matter of the gray matter.  This article provides more evidence that the disease impacts gray matter as well as white matter. The atrophy in gray matter correlates more with disease impact and burden than the atrophy in white matter.  MS should no longer be considered a disease of white matter or white matter atrophy. Perhaps it’s time to update our diagnostic approach, monitoring of disease impact and progression, and therapeutic intervention efficacy measures as well as the metrics of how we measure disease impact. —Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY

Gray matter fraction (GMF) change is more meaningful than white matter fraction (WMF) as a marker of tissue loss and may be useful to augment whole brain atrophy measurements in MS clinical trials, according to a study of 140 patients with relapsing-remitting MS who were randomized to intramuscular interferon (IFN) beta-1a or placebo. Researchers found:

• Significantly less GM atrophy (during year 2), but not WM atrophy (at any point), was seen with IFN beta-1a compared with placebo.

• Pseudoatrophy effects were more apparent in WM than in GM; in year 1, greater WM volume loss was seen with IFN beta-1a than with placebo, but GM volume loss was similar between groups. 

• Risk of sustained disability progression was significantly associated with GM atrophy, but not WM atrophy.
 
Citation: Fisher E, Nakamura K, Lee JC, You X, Sperling B, Rudick RA. Effect of intramuscular interferon beta-1a on gray matter atrophy in relapsing−remitting multiple sclerosis: a retrospective analysis. [Published online ahead of print August 3, 2015]. Mult Scler. doi: 10.1177/1352458515599072.

Commentary: Understanding a disease requires thorough analysis of its impact. Multiple sclerosis is classically known as a white matter disease. It is also known that MS white matter plaques are in typical subcortical locations. This has been the tenet of MS care and diagnosis by MRI.  However, it is also a tenet that MRI changes do not always correlate with clinical exam or disease impact. Many people involved in MS care and research have explored the reason for this discrepancy.  This important article is another step along the path of understanding.  MS plaques have now been identified within the white matter of the gray matter.  This article provides more evidence that the disease impacts gray matter as well as white matter. The atrophy in gray matter correlates more with disease impact and burden than the atrophy in white matter.  MS should no longer be considered a disease of white matter or white matter atrophy. Perhaps it’s time to update our diagnostic approach, monitoring of disease impact and progression, and therapeutic intervention efficacy measures as well as the metrics of how we measure disease impact. —Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY

Gray matter fraction (GMF) change is more meaningful than white matter fraction (WMF) as a marker of tissue loss and may be useful to augment whole brain atrophy measurements in MS clinical trials, according to a study of 140 patients with relapsing-remitting MS who were randomized to intramuscular interferon (IFN) beta-1a or placebo. Researchers found:

• Significantly less GM atrophy (during year 2), but not WM atrophy (at any point), was seen with IFN beta-1a compared with placebo.

• Pseudoatrophy effects were more apparent in WM than in GM; in year 1, greater WM volume loss was seen with IFN beta-1a than with placebo, but GM volume loss was similar between groups. 

• Risk of sustained disability progression was significantly associated with GM atrophy, but not WM atrophy.
 
Citation: Fisher E, Nakamura K, Lee JC, You X, Sperling B, Rudick RA. Effect of intramuscular interferon beta-1a on gray matter atrophy in relapsing−remitting multiple sclerosis: a retrospective analysis. [Published online ahead of print August 3, 2015]. Mult Scler. doi: 10.1177/1352458515599072.

Commentary: Understanding a disease requires thorough analysis of its impact. Multiple sclerosis is classically known as a white matter disease. It is also known that MS white matter plaques are in typical subcortical locations. This has been the tenet of MS care and diagnosis by MRI.  However, it is also a tenet that MRI changes do not always correlate with clinical exam or disease impact. Many people involved in MS care and research have explored the reason for this discrepancy.  This important article is another step along the path of understanding.  MS plaques have now been identified within the white matter of the gray matter.  This article provides more evidence that the disease impacts gray matter as well as white matter. The atrophy in gray matter correlates more with disease impact and burden than the atrophy in white matter.  MS should no longer be considered a disease of white matter or white matter atrophy. Perhaps it’s time to update our diagnostic approach, monitoring of disease impact and progression, and therapeutic intervention efficacy measures as well as the metrics of how we measure disease impact. —Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY

Patient characteristics that may help predict disease outcomes include number of relapses in the past 2 years, new MRI lesions in year 1, higher number of relapses in year 1, MRI activity, and the presence of neutralizing antibodies, according to a study of 857 patients with relapsing-remitting MS who were treated with interferon beta-1b. All 857 patients were included in the analysis of clinical outcomes and 765 of those were included in the MRI outcomes analysis. Researchers found:

• Future occurrence of relapses was predicted by a higher number of relapses in the past 2 years, ≥ 3 new MRI lesions in year 1, and, especially, a higher number of relapses in year 1.

• Future MRI activity was principally predicted by age, MRI activity, and the presence of neutralizing antibodies in year 1.

Citation: Hartung HP, Kappos L, Goodin DS, et al. Predictors of disease activity in 857 patients with MS treated with interferon beta-1b. [Published online ahead of print August 5, 2015]. J Neurol. doi: 10.1007/s00415-015-7862-9.

Patient characteristics that may help predict disease outcomes include number of relapses in the past 2 years, new MRI lesions in year 1, higher number of relapses in year 1, MRI activity, and the presence of neutralizing antibodies, according to a study of 857 patients with relapsing-remitting MS who were treated with interferon beta-1b. All 857 patients were included in the analysis of clinical outcomes and 765 of those were included in the MRI outcomes analysis. Researchers found:

• Future occurrence of relapses was predicted by a higher number of relapses in the past 2 years, ≥ 3 new MRI lesions in year 1, and, especially, a higher number of relapses in year 1.

• Future MRI activity was principally predicted by age, MRI activity, and the presence of neutralizing antibodies in year 1.

Citation: Hartung HP, Kappos L, Goodin DS, et al. Predictors of disease activity in 857 patients with MS treated with interferon beta-1b. [Published online ahead of print August 5, 2015]. J Neurol. doi: 10.1007/s00415-015-7862-9.

Patient characteristics that may help predict disease outcomes include number of relapses in the past 2 years, new MRI lesions in year 1, higher number of relapses in year 1, MRI activity, and the presence of neutralizing antibodies, according to a study of 857 patients with relapsing-remitting MS who were treated with interferon beta-1b. All 857 patients were included in the analysis of clinical outcomes and 765 of those were included in the MRI outcomes analysis. Researchers found:

• Future occurrence of relapses was predicted by a higher number of relapses in the past 2 years, ≥ 3 new MRI lesions in year 1, and, especially, a higher number of relapses in year 1.

• Future MRI activity was principally predicted by age, MRI activity, and the presence of neutralizing antibodies in year 1.

Citation: Hartung HP, Kappos L, Goodin DS, et al. Predictors of disease activity in 857 patients with MS treated with interferon beta-1b. [Published online ahead of print August 5, 2015]. J Neurol. doi: 10.1007/s00415-015-7862-9.

Higher serum high-density lipoprotein (HDL) is associated with lower levels of blood brain barrier (BBB) injury and decreased CD80+ and CD80+CD19+ cell extravasation into the cerebrospinal fluid (CSF), according to a study of 154 patients with MS who were receiving interferon beta-1a therapy following their first clinical demyelinating event. Researchers found:

• Higher levels of serum HDL cholesterol (HDL-C) and apolipoprotein A-1 were associated with lower CSF total protein level, CSF albumin level, albumin quotient, and CSF IgC level.

• HDL-C was also associated with CSF CD80+ amd with CSF CD80+CD19+ cell frequencies.

Citation: Fellows K, Uher T, Browne RW, et al. Protective associations of HDL with blood brain barrier injury in multiple sclerosis patients. [Published online ahead of print August 4, 2015]. J Lipid Res. doi: 10.1194/jlr.M060970.

Higher serum high-density lipoprotein (HDL) is associated with lower levels of blood brain barrier (BBB) injury and decreased CD80+ and CD80+CD19+ cell extravasation into the cerebrospinal fluid (CSF), according to a study of 154 patients with MS who were receiving interferon beta-1a therapy following their first clinical demyelinating event. Researchers found:

• Higher levels of serum HDL cholesterol (HDL-C) and apolipoprotein A-1 were associated with lower CSF total protein level, CSF albumin level, albumin quotient, and CSF IgC level.

• HDL-C was also associated with CSF CD80+ amd with CSF CD80+CD19+ cell frequencies.

Citation: Fellows K, Uher T, Browne RW, et al. Protective associations of HDL with blood brain barrier injury in multiple sclerosis patients. [Published online ahead of print August 4, 2015]. J Lipid Res. doi: 10.1194/jlr.M060970.

Higher serum high-density lipoprotein (HDL) is associated with lower levels of blood brain barrier (BBB) injury and decreased CD80+ and CD80+CD19+ cell extravasation into the cerebrospinal fluid (CSF), according to a study of 154 patients with MS who were receiving interferon beta-1a therapy following their first clinical demyelinating event. Researchers found:

• Higher levels of serum HDL cholesterol (HDL-C) and apolipoprotein A-1 were associated with lower CSF total protein level, CSF albumin level, albumin quotient, and CSF IgC level.

• HDL-C was also associated with CSF CD80+ amd with CSF CD80+CD19+ cell frequencies.

Citation: Fellows K, Uher T, Browne RW, et al. Protective associations of HDL with blood brain barrier injury in multiple sclerosis patients. [Published online ahead of print August 4, 2015]. J Lipid Res. doi: 10.1194/jlr.M060970.

Alcohol dependence and smoking were associated with anxiety and depression, according to a study of 949 patients with MS. Researchers found:

• Alcohol dependence was associated with an increased odds ratio of anxiety (OR=1.84) and depression (OR=1.53).

• Smoking was associated with increased odds of anxiety (OR=1.29) and depression (OR=1.37).

• Alcohol dependence was associated with increased incidence of depression but not anxiety.

• Depression was associated with increased incidence of alcohol dependence.

Citation: McKay KA, Tremlett H, Fisk JD, et al. Adverse health behaviours are associated with depression and anxiety in multiple sclerosis: a prospective multisite study. [Published online ahead of print August 5, 2015]. Mult Scler. doi: 10.1177/1352458515599073.

Alcohol dependence and smoking were associated with anxiety and depression, according to a study of 949 patients with MS. Researchers found:

• Alcohol dependence was associated with an increased odds ratio of anxiety (OR=1.84) and depression (OR=1.53).

• Smoking was associated with increased odds of anxiety (OR=1.29) and depression (OR=1.37).

• Alcohol dependence was associated with increased incidence of depression but not anxiety.

• Depression was associated with increased incidence of alcohol dependence.

Citation: McKay KA, Tremlett H, Fisk JD, et al. Adverse health behaviours are associated with depression and anxiety in multiple sclerosis: a prospective multisite study. [Published online ahead of print August 5, 2015]. Mult Scler. doi: 10.1177/1352458515599073.

Alcohol dependence and smoking were associated with anxiety and depression, according to a study of 949 patients with MS. Researchers found:

• Alcohol dependence was associated with an increased odds ratio of anxiety (OR=1.84) and depression (OR=1.53).

• Smoking was associated with increased odds of anxiety (OR=1.29) and depression (OR=1.37).

• Alcohol dependence was associated with increased incidence of depression but not anxiety.

• Depression was associated with increased incidence of alcohol dependence.

Citation: McKay KA, Tremlett H, Fisk JD, et al. Adverse health behaviours are associated with depression and anxiety in multiple sclerosis: a prospective multisite study. [Published online ahead of print August 5, 2015]. Mult Scler. doi: 10.1177/1352458515599073.

The telephone is an effective method for engaging participants in and extending the reach of care for individuals with MS, according to a study of 163 adults with MS, aged 25 to 76 years, and with fatigue, chronic pain, and/or moderate depressive symptoms. Patients were randomized to either a telephone-delivered self-management intervention (T-SM) or a telephone-delivered MS education intervention (T-ED). Researchers found:

• 58% of those in the T-SM group and 46% of those in the T-ED group had a > 50% reduction in 1 or more symptoms; a difference that was not statistically significant.

• Participants in both groups significantly improved from baseline to post-treatment in primary and secondary outcome measures.

• T-SM participants reported significantly higher treatment satisfaction and therapeutic alliance and greater improvements in activation, positive affect, and social roles.

• Improvements were generally maintained at 6 and 12 months.
 
Citation: Ehde DM, Elzea JL, Verrall AM, Gibbons LE, Smith A, Amtmann D. Efficacy of a telephone-delivered self-management intervention for persons with multiple sclerosis: a randomized controlled trial with a one-year follow-up. [Published online ahead of print August 5, 2015]. Arch Phys Med Rehabil. doi: 10.1016/j.apmr.2015.07.015.

The telephone is an effective method for engaging participants in and extending the reach of care for individuals with MS, according to a study of 163 adults with MS, aged 25 to 76 years, and with fatigue, chronic pain, and/or moderate depressive symptoms. Patients were randomized to either a telephone-delivered self-management intervention (T-SM) or a telephone-delivered MS education intervention (T-ED). Researchers found:

• 58% of those in the T-SM group and 46% of those in the T-ED group had a > 50% reduction in 1 or more symptoms; a difference that was not statistically significant.

• Participants in both groups significantly improved from baseline to post-treatment in primary and secondary outcome measures.

• T-SM participants reported significantly higher treatment satisfaction and therapeutic alliance and greater improvements in activation, positive affect, and social roles.

• Improvements were generally maintained at 6 and 12 months.
 
Citation: Ehde DM, Elzea JL, Verrall AM, Gibbons LE, Smith A, Amtmann D. Efficacy of a telephone-delivered self-management intervention for persons with multiple sclerosis: a randomized controlled trial with a one-year follow-up. [Published online ahead of print August 5, 2015]. Arch Phys Med Rehabil. doi: 10.1016/j.apmr.2015.07.015.

The telephone is an effective method for engaging participants in and extending the reach of care for individuals with MS, according to a study of 163 adults with MS, aged 25 to 76 years, and with fatigue, chronic pain, and/or moderate depressive symptoms. Patients were randomized to either a telephone-delivered self-management intervention (T-SM) or a telephone-delivered MS education intervention (T-ED). Researchers found:

• 58% of those in the T-SM group and 46% of those in the T-ED group had a > 50% reduction in 1 or more symptoms; a difference that was not statistically significant.

• Participants in both groups significantly improved from baseline to post-treatment in primary and secondary outcome measures.

• T-SM participants reported significantly higher treatment satisfaction and therapeutic alliance and greater improvements in activation, positive affect, and social roles.

• Improvements were generally maintained at 6 and 12 months.
 
Citation: Ehde DM, Elzea JL, Verrall AM, Gibbons LE, Smith A, Amtmann D. Efficacy of a telephone-delivered self-management intervention for persons with multiple sclerosis: a randomized controlled trial with a one-year follow-up. [Published online ahead of print August 5, 2015]. Arch Phys Med Rehabil. doi: 10.1016/j.apmr.2015.07.015.

INDIANAPOLIS—The community of organisms housed in the intestines—the gut microbiome—may differ significantly between patients with multiple sclerosis (MS) and healthy controls, preliminary study results show.

“The most exciting possibility is that the gut holds the key to the cause of MS, especially since it has been theorized that MS may be caused by a virus or bacterium,” said Howard L. Weiner, MD, at the 2015 CMSC Annual Meeting. “It is also possible that the microbiome, diet, oral tolerance, and antibiotic use relates to MS susceptibility. Modulating the microbiome with probiotics or specific bacteria may be a way to treat MS.” These findings could help pave the way toward developing a vaccine to prevent the disease from occurring, Dr. Weiner added.

Modulating the Immune Response
Microbiota in the human body reside in various areas, including the oral cavity, the vagina, and the skin. As many as 500 trillion bacteria and other organisms live in the 300 m² of the intestinal tract, explained Dr. Weiner, Robert L. Kroc Professor of Neurology at Harvard Medical School in Boston; founder of the Partners MS Center in Brookline, Massachusetts; and Codirector of the Center for Neurologic Diseases at the Brigham and Women’s Hospital in Boston.

“There are more genes in our gut than in any other part of our body,” he said. “The gut is probably the largest lymphoid organ in the body and it is where you can induce all kinds of immune responses.”

In a relapsing-remitting mouse model of spontaneously developing experimental autoimmune encephalomyelitis (EAE), animals raised in a normal environment became sick, whereas those raised in a germ-free environment did not. The germ-free animals developed EAE, however, after microbial exposure (ie, consuming feces).

“This [result] is clear proof that the gut is important for immune mechanisms in EAE,” Dr. Weiner said. Other animal research has shown that colonization with Bacteroides fragilis can modulate EAE, he added.

In an ongoing, unpublished study involving an animal model of EAE, Dr. Weiner and colleagues are collecting feces at various stages of disease from onset to recovery. “We then feed the feces to healthy animals. Our preliminary results show that healthy animals fed feces from the peak of disease developed immunity against EAE. It seems that protective organisms develop in the gut as the animals are recovering from disease.”

The Human Microbiome
One study showed that the gut of patients with rheumatoid arthritis is enriched with Prevotella copri. “However, we don’t have a clear handle on the effect of microbiota on human disease because there are so few studies on the subject.”

In a recent study, Dr. Weiner and colleagues collected blood and stool samples from 63 patients with MS and 43 healthy controls. Of the patients with MS, 18 were being treated with beta interferon and 14 with glatiramer acetate; 29 were untreated. Exclusion criteria included antibiotic or probiotic use; recent gastroenteritis; a history of irritable bowel disease, rheumatoid arthritis, or systemic lupus erythematosus; recent travel history; history of bowel surgery; and treatment with prednisone, mycophenolate mofetil, mitoxantrone, rituximab, IV immunoglobulin, or methotrexate.

“We extracted the genetic material from the stool samples and sequenced the hypervariable regions of the 16S using three platforms,” Dr. Weiner said. “We used a Roche 454 sequencing system, as well as Illumina sequencing, which is deeper, but more restrictive. Then we performed validation with quantitative polymerase chain reaction analysis.”

There was no difference in the diversity of bacteria in the gut between patients with MS and controls. However, Methanobrevibacter smithii and Akkermansia muciniphila were increased and Butyricimonas virosa was decreased in patients with MS.

“This is an interesting finding, as Butyricimonas produces butyrate, which typically is reduced in MS and other autoimmune diseases. Because butyrate induces regulatory cells, this [result] goes along with our theories about MS.”

Network analysis indicated that Methanobrevibacter, Akkermansia, and Butyricimonas were linked to the same gene module in monocytes. “This finding implies that the changes in the gut for these organisms in MS patients are not independent of each other,” Dr. Weiner said. “More research is needed to confirm this [finding], but we certainly have found some interesting leads.”

Collinsella aerofaciens, Slackia exigua, and Prevotella were decreased in untreated patients with MS. Patients receiving glatiramer or interferon therapy had increased Prevotella, Sarcina lutea, and Sutterella wadsworthensis. “In the future, we plan to test patients who are on other MS drugs, as well.”

Spotlight on Methanobrevibacter
“We looked closely at Methanobrevibacter, which is not a bacterium, but is actually an archaeon,” Dr. Weiner noted. “We took 10 patients with Methanobrevibacter and 10 patients without it to see if there were any differences in their monocytes and lymphocytes.” The researchers found that monocytes and T cells had unique transcription profiles in Methanobrevibacter-positive patients.

 

Antigen array profiles measuring the activity of serum antibodies showed increased reactivity to tetracosonoic acid in Methanobrevibacter-positive patients with MS. Patients with high reactivity to Methanobrevibacter lysates also had increased expression of a specific gene module within T cells. Reactivity to Methanobrevibacter lipids in patients with MS was strongly associated with interferon γ and tumor necrosis factor α pathways in T cells. “This is an important finding because it is believed that interferon γ and tumor necrosis factor α play an important role in MS,” said Dr. Weiner.

Keeping in mind that Methanobrevibacter is a methane-producing organism, he and his colleagues performed breath tests on a separate group of 30 patients with MS and 30 healthy controls. Breath methane concentrations were elevated in patients with MS, compared with controls. “This [finding] also raises the possibility that breath tests are an easier way to look into the gut than taking stool samples,” Dr. Weiner said.

Future Considerations
According to Dr. Weiner, future explorations should include longitudinal studies of stool samples from patients with MS, examininations of how changes in gut bacteria relate to MRI findings and disability, and trials of probiotics.

 

—Adriene Marshall

INDIANAPOLIS—The community of organisms housed in the intestines—the gut microbiome—may differ significantly between patients with multiple sclerosis (MS) and healthy controls, preliminary study results show.

“The most exciting possibility is that the gut holds the key to the cause of MS, especially since it has been theorized that MS may be caused by a virus or bacterium,” said Howard L. Weiner, MD, at the 2015 CMSC Annual Meeting. “It is also possible that the microbiome, diet, oral tolerance, and antibiotic use relates to MS susceptibility. Modulating the microbiome with probiotics or specific bacteria may be a way to treat MS.” These findings could help pave the way toward developing a vaccine to prevent the disease from occurring, Dr. Weiner added.

Modulating the Immune Response
Microbiota in the human body reside in various areas, including the oral cavity, the vagina, and the skin. As many as 500 trillion bacteria and other organisms live in the 300 m² of the intestinal tract, explained Dr. Weiner, Robert L. Kroc Professor of Neurology at Harvard Medical School in Boston; founder of the Partners MS Center in Brookline, Massachusetts; and Codirector of the Center for Neurologic Diseases at the Brigham and Women’s Hospital in Boston.

“There are more genes in our gut than in any other part of our body,” he said. “The gut is probably the largest lymphoid organ in the body and it is where you can induce all kinds of immune responses.”

In a relapsing-remitting mouse model of spontaneously developing experimental autoimmune encephalomyelitis (EAE), animals raised in a normal environment became sick, whereas those raised in a germ-free environment did not. The germ-free animals developed EAE, however, after microbial exposure (ie, consuming feces).

“This [result] is clear proof that the gut is important for immune mechanisms in EAE,” Dr. Weiner said. Other animal research has shown that colonization with Bacteroides fragilis can modulate EAE, he added.

In an ongoing, unpublished study involving an animal model of EAE, Dr. Weiner and colleagues are collecting feces at various stages of disease from onset to recovery. “We then feed the feces to healthy animals. Our preliminary results show that healthy animals fed feces from the peak of disease developed immunity against EAE. It seems that protective organisms develop in the gut as the animals are recovering from disease.”

The Human Microbiome
One study showed that the gut of patients with rheumatoid arthritis is enriched with Prevotella copri. “However, we don’t have a clear handle on the effect of microbiota on human disease because there are so few studies on the subject.”

In a recent study, Dr. Weiner and colleagues collected blood and stool samples from 63 patients with MS and 43 healthy controls. Of the patients with MS, 18 were being treated with beta interferon and 14 with glatiramer acetate; 29 were untreated. Exclusion criteria included antibiotic or probiotic use; recent gastroenteritis; a history of irritable bowel disease, rheumatoid arthritis, or systemic lupus erythematosus; recent travel history; history of bowel surgery; and treatment with prednisone, mycophenolate mofetil, mitoxantrone, rituximab, IV immunoglobulin, or methotrexate.

“We extracted the genetic material from the stool samples and sequenced the hypervariable regions of the 16S using three platforms,” Dr. Weiner said. “We used a Roche 454 sequencing system, as well as Illumina sequencing, which is deeper, but more restrictive. Then we performed validation with quantitative polymerase chain reaction analysis.”

There was no difference in the diversity of bacteria in the gut between patients with MS and controls. However, Methanobrevibacter smithii and Akkermansia muciniphila were increased and Butyricimonas virosa was decreased in patients with MS.

“This is an interesting finding, as Butyricimonas produces butyrate, which typically is reduced in MS and other autoimmune diseases. Because butyrate induces regulatory cells, this [result] goes along with our theories about MS.”

Network analysis indicated that Methanobrevibacter, Akkermansia, and Butyricimonas were linked to the same gene module in monocytes. “This finding implies that the changes in the gut for these organisms in MS patients are not independent of each other,” Dr. Weiner said. “More research is needed to confirm this [finding], but we certainly have found some interesting leads.”

Collinsella aerofaciens, Slackia exigua, and Prevotella were decreased in untreated patients with MS. Patients receiving glatiramer or interferon therapy had increased Prevotella, Sarcina lutea, and Sutterella wadsworthensis. “In the future, we plan to test patients who are on other MS drugs, as well.”

Spotlight on Methanobrevibacter
“We looked closely at Methanobrevibacter, which is not a bacterium, but is actually an archaeon,” Dr. Weiner noted. “We took 10 patients with Methanobrevibacter and 10 patients without it to see if there were any differences in their monocytes and lymphocytes.” The researchers found that monocytes and T cells had unique transcription profiles in Methanobrevibacter-positive patients.

 

Antigen array profiles measuring the activity of serum antibodies showed increased reactivity to tetracosonoic acid in Methanobrevibacter-positive patients with MS. Patients with high reactivity to Methanobrevibacter lysates also had increased expression of a specific gene module within T cells. Reactivity to Methanobrevibacter lipids in patients with MS was strongly associated with interferon γ and tumor necrosis factor α pathways in T cells. “This is an important finding because it is believed that interferon γ and tumor necrosis factor α play an important role in MS,” said Dr. Weiner.

Keeping in mind that Methanobrevibacter is a methane-producing organism, he and his colleagues performed breath tests on a separate group of 30 patients with MS and 30 healthy controls. Breath methane concentrations were elevated in patients with MS, compared with controls. “This [finding] also raises the possibility that breath tests are an easier way to look into the gut than taking stool samples,” Dr. Weiner said.

Future Considerations
According to Dr. Weiner, future explorations should include longitudinal studies of stool samples from patients with MS, examininations of how changes in gut bacteria relate to MRI findings and disability, and trials of probiotics.

 

—Adriene Marshall

INDIANAPOLIS—The community of organisms housed in the intestines—the gut microbiome—may differ significantly between patients with multiple sclerosis (MS) and healthy controls, preliminary study results show.

“The most exciting possibility is that the gut holds the key to the cause of MS, especially since it has been theorized that MS may be caused by a virus or bacterium,” said Howard L. Weiner, MD, at the 2015 CMSC Annual Meeting. “It is also possible that the microbiome, diet, oral tolerance, and antibiotic use relates to MS susceptibility. Modulating the microbiome with probiotics or specific bacteria may be a way to treat MS.” These findings could help pave the way toward developing a vaccine to prevent the disease from occurring, Dr. Weiner added.

Modulating the Immune Response
Microbiota in the human body reside in various areas, including the oral cavity, the vagina, and the skin. As many as 500 trillion bacteria and other organisms live in the 300 m² of the intestinal tract, explained Dr. Weiner, Robert L. Kroc Professor of Neurology at Harvard Medical School in Boston; founder of the Partners MS Center in Brookline, Massachusetts; and Codirector of the Center for Neurologic Diseases at the Brigham and Women’s Hospital in Boston.

“There are more genes in our gut than in any other part of our body,” he said. “The gut is probably the largest lymphoid organ in the body and it is where you can induce all kinds of immune responses.”

In a relapsing-remitting mouse model of spontaneously developing experimental autoimmune encephalomyelitis (EAE), animals raised in a normal environment became sick, whereas those raised in a germ-free environment did not. The germ-free animals developed EAE, however, after microbial exposure (ie, consuming feces).

“This [result] is clear proof that the gut is important for immune mechanisms in EAE,” Dr. Weiner said. Other animal research has shown that colonization with Bacteroides fragilis can modulate EAE, he added.

In an ongoing, unpublished study involving an animal model of EAE, Dr. Weiner and colleagues are collecting feces at various stages of disease from onset to recovery. “We then feed the feces to healthy animals. Our preliminary results show that healthy animals fed feces from the peak of disease developed immunity against EAE. It seems that protective organisms develop in the gut as the animals are recovering from disease.”

The Human Microbiome
One study showed that the gut of patients with rheumatoid arthritis is enriched with Prevotella copri. “However, we don’t have a clear handle on the effect of microbiota on human disease because there are so few studies on the subject.”

In a recent study, Dr. Weiner and colleagues collected blood and stool samples from 63 patients with MS and 43 healthy controls. Of the patients with MS, 18 were being treated with beta interferon and 14 with glatiramer acetate; 29 were untreated. Exclusion criteria included antibiotic or probiotic use; recent gastroenteritis; a history of irritable bowel disease, rheumatoid arthritis, or systemic lupus erythematosus; recent travel history; history of bowel surgery; and treatment with prednisone, mycophenolate mofetil, mitoxantrone, rituximab, IV immunoglobulin, or methotrexate.

“We extracted the genetic material from the stool samples and sequenced the hypervariable regions of the 16S using three platforms,” Dr. Weiner said. “We used a Roche 454 sequencing system, as well as Illumina sequencing, which is deeper, but more restrictive. Then we performed validation with quantitative polymerase chain reaction analysis.”

There was no difference in the diversity of bacteria in the gut between patients with MS and controls. However, Methanobrevibacter smithii and Akkermansia muciniphila were increased and Butyricimonas virosa was decreased in patients with MS.

“This is an interesting finding, as Butyricimonas produces butyrate, which typically is reduced in MS and other autoimmune diseases. Because butyrate induces regulatory cells, this [result] goes along with our theories about MS.”

Network analysis indicated that Methanobrevibacter, Akkermansia, and Butyricimonas were linked to the same gene module in monocytes. “This finding implies that the changes in the gut for these organisms in MS patients are not independent of each other,” Dr. Weiner said. “More research is needed to confirm this [finding], but we certainly have found some interesting leads.”

Collinsella aerofaciens, Slackia exigua, and Prevotella were decreased in untreated patients with MS. Patients receiving glatiramer or interferon therapy had increased Prevotella, Sarcina lutea, and Sutterella wadsworthensis. “In the future, we plan to test patients who are on other MS drugs, as well.”

Spotlight on Methanobrevibacter
“We looked closely at Methanobrevibacter, which is not a bacterium, but is actually an archaeon,” Dr. Weiner noted. “We took 10 patients with Methanobrevibacter and 10 patients without it to see if there were any differences in their monocytes and lymphocytes.” The researchers found that monocytes and T cells had unique transcription profiles in Methanobrevibacter-positive patients.

 

Antigen array profiles measuring the activity of serum antibodies showed increased reactivity to tetracosonoic acid in Methanobrevibacter-positive patients with MS. Patients with high reactivity to Methanobrevibacter lysates also had increased expression of a specific gene module within T cells. Reactivity to Methanobrevibacter lipids in patients with MS was strongly associated with interferon γ and tumor necrosis factor α pathways in T cells. “This is an important finding because it is believed that interferon γ and tumor necrosis factor α play an important role in MS,” said Dr. Weiner.

Keeping in mind that Methanobrevibacter is a methane-producing organism, he and his colleagues performed breath tests on a separate group of 30 patients with MS and 30 healthy controls. Breath methane concentrations were elevated in patients with MS, compared with controls. “This [finding] also raises the possibility that breath tests are an easier way to look into the gut than taking stool samples,” Dr. Weiner said.

Future Considerations
According to Dr. Weiner, future explorations should include longitudinal studies of stool samples from patients with MS, examininations of how changes in gut bacteria relate to MRI findings and disability, and trials of probiotics.

 

—Adriene Marshall

INDIANAPOLIS—Disease-modifying therapies approved for relapsing-remitting multiple sclerosis (MS) do not slow clinical worsening in progressive MS, according to research reviewed at the 2015 CMSC Annual Meeting. These anti-inflammatory medicines can decrease the risk of relapses and the formation of new T2 lesions, however. They therefore may benefit patients with active progressive MS.

Mitoxantrone is the only medicine that is FDA-approved for the treatment of secondary progressive MS. Few neurologists recommend this chemotherapy drug because it has limited efficacy in progressive MS, is highly cardiotoxic, and increases the risk of leukemia, said Dennis Bourdette, MD, Roy and Eulalia Swank Family Research Professor and Chairman of the Department of Neurology at Oregon Health & Science University School of Medicine in Portland.

No Effect on EDSS Worsening
Researchers have studied the efficacy of several therapies for relapsing-remitting MS among patients with secondary progressive MS. A European trial found that interferon beta-1b delayed worsening of Expanded Disability Status Scale (EDSS) score in people with progressive disease. A subsequent North American trial had opposite results, although investigators observed that the drug decreased relapses and the formation of new T2 lesions.

In another study, researchers administered 60 µg of intramuscular interferon beta-1a once per week to patients with secondary progressive MS. The standard dose of interferon beta-1a for treating relapsing-remitting MS is 30 µg. Although the treatment delayed worsening on the MS Functional Composite, it did not delay worsening of EDSS score, and the FDA did not approve it for secondary progressive MS. Interferon beta-1a decreased relapses and the formation of new T2 lesions in patients with secondary progressive MS, however.

Trials of medicines approved for relapsing-remitting MS in patients with primary progressive MS have yielded similar results. Studies suggest that glatiramer acetate, rituximab, and fingolimod do not delay worsening of EDSS score among these patients, but do decrease the number of new T2 lesions.

Researchers are examining several other therapies, including natalizu­mab and ibudilast, in patients with progressive MS. “I’m not particularly optimistic that agents such as natalizumab that are anti-inflammatory therapies are going to be effective in altering the progressive component of MS,” said Dr. Bourdette.

A Joint Decision Between Doctors and Patients
Despite the failures of these medicines in progressive MS in clinical trials, neurologists should not give their patients the impression that nothing can be done, he continued. Much can be done with symptomatic therapies to improve the quality of life of patients with progressive MS. In addition, current disease-modifying therapies might be appropriate for some patients with progressive MS, but physicians must counsel these patients about the pros and cons of taking a disease-modifying therapy.

Some patients begin treatment after receiving a diagnosis of relapsing-remitting MS and later present with evidence of progressive myelopathy. These patients no longer have relapses or new T2 lesions and have developed secondary progressive MS. “We don’t have strong evidence to guide us about whether we should continue the therapy or not” for these patients, said Dr. Bourdette. One small study suggested that some of these patients do well after they stop taking their current therapies, but “we need better evidence.”

Neurologists should discuss openly with patients with secondary progressive MS the advantages and disadvantages of stopping therapy. Although cessation of treatment may have advantages, it could reveal a previously hidden relapsing component of the disease. A decision about treatment should be made jointly after a discussion of the patient’s goals and concerns, said Dr. Bourdette. If the decision is to stop treatment, the neurologist should develop a monitoring plan that includes periodic MRIs.

Rather than treatment cessation, some patients may ask about escalation. Clinical experience and current clinical trial evidence, however, suggest that more aggressive immunosuppression only increases these patients’ risk of complications without providing benefit. “I don’t think escalation without any evidence of active inflammatory disease is a good idea,” said Dr. Bourdette.

Other patients present with progressive MS and evidence of active inflammatory disease, such as a history of recent relapses or gadolinium-enhancing lesions, but are not receiving any therapy. Such patients should be strongly encouraged to participate in a clinical trial if they are eligible. “It’s important to try to help enroll in those studies,” said Dr. Bourdette.

The patient cannot make an informed decision about treatment unless he or she understands that the goal of the therapy would be to prevent relapses and the formation of new lesions, not to stop disease progression. For some patients, an occasional small gadolinium-enhancing lesion without relapses would not justify the initiation of a therapy. If the neurologist and patient decide to begin treatment, the neurologist should recommend the safest medicine available, most likely one of the injectable drugs, said Dr. Bourdette.

 

Other patients present with progressive disease, but without evidence of active inflammatory disease, and are not taking any medication. These patients also can be encouraged to participate in a clinical trial if they are eligible. “It’s important to explain the status of the evidence, which basically does not justify putting them on a disease-modifying therapy,” said Dr. Bourdette. If, after a discussion with the neurologist, a patient decides to try a drug, the patient should use the safest medication available and understand that the treatment is off label, he concluded.

—Erik Greb

INDIANAPOLIS—Disease-modifying therapies approved for relapsing-remitting multiple sclerosis (MS) do not slow clinical worsening in progressive MS, according to research reviewed at the 2015 CMSC Annual Meeting. These anti-inflammatory medicines can decrease the risk of relapses and the formation of new T2 lesions, however. They therefore may benefit patients with active progressive MS.

Mitoxantrone is the only medicine that is FDA-approved for the treatment of secondary progressive MS. Few neurologists recommend this chemotherapy drug because it has limited efficacy in progressive MS, is highly cardiotoxic, and increases the risk of leukemia, said Dennis Bourdette, MD, Roy and Eulalia Swank Family Research Professor and Chairman of the Department of Neurology at Oregon Health & Science University School of Medicine in Portland.

No Effect on EDSS Worsening
Researchers have studied the efficacy of several therapies for relapsing-remitting MS among patients with secondary progressive MS. A European trial found that interferon beta-1b delayed worsening of Expanded Disability Status Scale (EDSS) score in people with progressive disease. A subsequent North American trial had opposite results, although investigators observed that the drug decreased relapses and the formation of new T2 lesions.

In another study, researchers administered 60 µg of intramuscular interferon beta-1a once per week to patients with secondary progressive MS. The standard dose of interferon beta-1a for treating relapsing-remitting MS is 30 µg. Although the treatment delayed worsening on the MS Functional Composite, it did not delay worsening of EDSS score, and the FDA did not approve it for secondary progressive MS. Interferon beta-1a decreased relapses and the formation of new T2 lesions in patients with secondary progressive MS, however.

Trials of medicines approved for relapsing-remitting MS in patients with primary progressive MS have yielded similar results. Studies suggest that glatiramer acetate, rituximab, and fingolimod do not delay worsening of EDSS score among these patients, but do decrease the number of new T2 lesions.

Researchers are examining several other therapies, including natalizu­mab and ibudilast, in patients with progressive MS. “I’m not particularly optimistic that agents such as natalizumab that are anti-inflammatory therapies are going to be effective in altering the progressive component of MS,” said Dr. Bourdette.

A Joint Decision Between Doctors and Patients
Despite the failures of these medicines in progressive MS in clinical trials, neurologists should not give their patients the impression that nothing can be done, he continued. Much can be done with symptomatic therapies to improve the quality of life of patients with progressive MS. In addition, current disease-modifying therapies might be appropriate for some patients with progressive MS, but physicians must counsel these patients about the pros and cons of taking a disease-modifying therapy.

Some patients begin treatment after receiving a diagnosis of relapsing-remitting MS and later present with evidence of progressive myelopathy. These patients no longer have relapses or new T2 lesions and have developed secondary progressive MS. “We don’t have strong evidence to guide us about whether we should continue the therapy or not” for these patients, said Dr. Bourdette. One small study suggested that some of these patients do well after they stop taking their current therapies, but “we need better evidence.”

Neurologists should discuss openly with patients with secondary progressive MS the advantages and disadvantages of stopping therapy. Although cessation of treatment may have advantages, it could reveal a previously hidden relapsing component of the disease. A decision about treatment should be made jointly after a discussion of the patient’s goals and concerns, said Dr. Bourdette. If the decision is to stop treatment, the neurologist should develop a monitoring plan that includes periodic MRIs.

Rather than treatment cessation, some patients may ask about escalation. Clinical experience and current clinical trial evidence, however, suggest that more aggressive immunosuppression only increases these patients’ risk of complications without providing benefit. “I don’t think escalation without any evidence of active inflammatory disease is a good idea,” said Dr. Bourdette.

Other patients present with progressive MS and evidence of active inflammatory disease, such as a history of recent relapses or gadolinium-enhancing lesions, but are not receiving any therapy. Such patients should be strongly encouraged to participate in a clinical trial if they are eligible. “It’s important to try to help enroll in those studies,” said Dr. Bourdette.

The patient cannot make an informed decision about treatment unless he or she understands that the goal of the therapy would be to prevent relapses and the formation of new lesions, not to stop disease progression. For some patients, an occasional small gadolinium-enhancing lesion without relapses would not justify the initiation of a therapy. If the neurologist and patient decide to begin treatment, the neurologist should recommend the safest medicine available, most likely one of the injectable drugs, said Dr. Bourdette.

 

Other patients present with progressive disease, but without evidence of active inflammatory disease, and are not taking any medication. These patients also can be encouraged to participate in a clinical trial if they are eligible. “It’s important to explain the status of the evidence, which basically does not justify putting them on a disease-modifying therapy,” said Dr. Bourdette. If, after a discussion with the neurologist, a patient decides to try a drug, the patient should use the safest medication available and understand that the treatment is off label, he concluded.

—Erik Greb

INDIANAPOLIS—Disease-modifying therapies approved for relapsing-remitting multiple sclerosis (MS) do not slow clinical worsening in progressive MS, according to research reviewed at the 2015 CMSC Annual Meeting. These anti-inflammatory medicines can decrease the risk of relapses and the formation of new T2 lesions, however. They therefore may benefit patients with active progressive MS.

Mitoxantrone is the only medicine that is FDA-approved for the treatment of secondary progressive MS. Few neurologists recommend this chemotherapy drug because it has limited efficacy in progressive MS, is highly cardiotoxic, and increases the risk of leukemia, said Dennis Bourdette, MD, Roy and Eulalia Swank Family Research Professor and Chairman of the Department of Neurology at Oregon Health & Science University School of Medicine in Portland.

No Effect on EDSS Worsening
Researchers have studied the efficacy of several therapies for relapsing-remitting MS among patients with secondary progressive MS. A European trial found that interferon beta-1b delayed worsening of Expanded Disability Status Scale (EDSS) score in people with progressive disease. A subsequent North American trial had opposite results, although investigators observed that the drug decreased relapses and the formation of new T2 lesions.

In another study, researchers administered 60 µg of intramuscular interferon beta-1a once per week to patients with secondary progressive MS. The standard dose of interferon beta-1a for treating relapsing-remitting MS is 30 µg. Although the treatment delayed worsening on the MS Functional Composite, it did not delay worsening of EDSS score, and the FDA did not approve it for secondary progressive MS. Interferon beta-1a decreased relapses and the formation of new T2 lesions in patients with secondary progressive MS, however.

Trials of medicines approved for relapsing-remitting MS in patients with primary progressive MS have yielded similar results. Studies suggest that glatiramer acetate, rituximab, and fingolimod do not delay worsening of EDSS score among these patients, but do decrease the number of new T2 lesions.

Researchers are examining several other therapies, including natalizu­mab and ibudilast, in patients with progressive MS. “I’m not particularly optimistic that agents such as natalizumab that are anti-inflammatory therapies are going to be effective in altering the progressive component of MS,” said Dr. Bourdette.

A Joint Decision Between Doctors and Patients
Despite the failures of these medicines in progressive MS in clinical trials, neurologists should not give their patients the impression that nothing can be done, he continued. Much can be done with symptomatic therapies to improve the quality of life of patients with progressive MS. In addition, current disease-modifying therapies might be appropriate for some patients with progressive MS, but physicians must counsel these patients about the pros and cons of taking a disease-modifying therapy.

Some patients begin treatment after receiving a diagnosis of relapsing-remitting MS and later present with evidence of progressive myelopathy. These patients no longer have relapses or new T2 lesions and have developed secondary progressive MS. “We don’t have strong evidence to guide us about whether we should continue the therapy or not” for these patients, said Dr. Bourdette. One small study suggested that some of these patients do well after they stop taking their current therapies, but “we need better evidence.”

Neurologists should discuss openly with patients with secondary progressive MS the advantages and disadvantages of stopping therapy. Although cessation of treatment may have advantages, it could reveal a previously hidden relapsing component of the disease. A decision about treatment should be made jointly after a discussion of the patient’s goals and concerns, said Dr. Bourdette. If the decision is to stop treatment, the neurologist should develop a monitoring plan that includes periodic MRIs.

Rather than treatment cessation, some patients may ask about escalation. Clinical experience and current clinical trial evidence, however, suggest that more aggressive immunosuppression only increases these patients’ risk of complications without providing benefit. “I don’t think escalation without any evidence of active inflammatory disease is a good idea,” said Dr. Bourdette.

Other patients present with progressive MS and evidence of active inflammatory disease, such as a history of recent relapses or gadolinium-enhancing lesions, but are not receiving any therapy. Such patients should be strongly encouraged to participate in a clinical trial if they are eligible. “It’s important to try to help enroll in those studies,” said Dr. Bourdette.

The patient cannot make an informed decision about treatment unless he or she understands that the goal of the therapy would be to prevent relapses and the formation of new lesions, not to stop disease progression. For some patients, an occasional small gadolinium-enhancing lesion without relapses would not justify the initiation of a therapy. If the neurologist and patient decide to begin treatment, the neurologist should recommend the safest medicine available, most likely one of the injectable drugs, said Dr. Bourdette.

 

Other patients present with progressive disease, but without evidence of active inflammatory disease, and are not taking any medication. These patients also can be encouraged to participate in a clinical trial if they are eligible. “It’s important to explain the status of the evidence, which basically does not justify putting them on a disease-modifying therapy,” said Dr. Bourdette. If, after a discussion with the neurologist, a patient decides to try a drug, the patient should use the safest medication available and understand that the treatment is off label, he concluded.

—Erik Greb

INDIANAPOLIS—In August 2014, approximately 16% of patients with multiple sclerosis (MS) reported currently using marijuana to treat their disease, according to survey results presented at the 2015 CMSC Annual Meeting. People with moderate disability and those with high spasticity are more likely to use marijuana than other patients.

Approximately 82% of respondents reported that they would consider using marijuana if it became legal where they live, said Stacey Cofield, PhD, Associate Professor of Biostatistics at the University of Alabama at Birmingham. More than one-third of respondents already had spoken to their physician about using marijuana, regardless of whether they were current marijuana users.

Survey Not Linked With NARCOMS Data
In 2014, the North American Research Committee on MS (NARCOMS) created a brief online survey to characterize marijuana use among people with MS, determine whether participants had spoken to their doctors about marijuana use, and investigate the disease status of marijuana users and nonusers. The survey did not distinguish between various forms (eg, smoked, ingested, or sprayed) of marijuana. To ensure that participants’ personal health information was not associated with their marijuana status, NARCOMS initiated the survey outside of the organization’s website and kept all responses anonymous. One of the survey’s limitations is that the responses are not linked with the NARCOMS longitudinal data, said Dr. Cofield.

In August 2014, more than 12,000 active participants in the NARCOMS database received invitations to participate in the survey, and more than 5,600 people responded. About 50% of participants live in a place where marijuana is legal in some form, and this result is consistent with the characteristics of the general US population. Also, 1.1% of respondents live in a place outside of the US where marijuana is legal.

Approximately 10% of participants described their disease as progressive MS with no history of relapses, and about 90% of participants had a history of relapses. Respondents with progressive MS were older at diagnosis, older at the time of the survey, and less likely to be female, compared with respondents with relapsing-remitting MS. These results are consistent with the characteristics of the larger population of Americans with MS, said Dr. Cofield.

Respondents’ median score on the Patient Determined Disease Steps (PDDS), a self-reported measure of disability, was 3, which represents early gait disability. People with stable relapsing-remitting MS (ie, with no relapse in the previous two years) had moderate disability, and patients with active relapsing-remitting MS had a higher level of disability. People with progressive MS had the highest levels of disability.

Respondents’ median score on the spasticity performance scale was 2, which represents mild spasticity. People with active MS had slightly more spasticity than respondents with stable MS. Patients with progressive MS and relapses had more spasticity than patients with primary progressive MS.

Active Disease Increased Likelihood of Use
The lowest prevalence of marijuana use (12.2%) was among respondents with stable relapsing-remitting MS. Approximately 19.9% of respondents with active relapsing-remitting MS and 19.2% of respondents with progressive MS and a history of relapses reported marijuana use. About 15.0% of respondents with primary progressive MS currently used marijuana. Between 60% and 70% of people reported using marijuana at least once in the past, and about 50% of people had considered using marijuana for their MS since their diagnosis.

Respondents with a moderate level of disability, as measured by PDDS, reported the highest percentage of current marijuana use, compared with those with mild disability and those with severe disability. The low level of marijuana use among NARCOMS participants with severe disability (ie, bedridden status) may result from the small sample size or the limited mobility among these patients who completed the survey, said Dr. Cofield. Marijuana use increased with increasing spasticity. The proportion of respondents who had never used marijuana was highest among people reporting no spasticity.

People with progressive MS and relapses, progressive MS without relapses, and active relapsing-remitting MS were more likely to be current marijuana users than respondents with stable relapsing-remitting MS. In addition, people with more severe disability, as measured by PDDS score, were more likely to be current marijuana users than respondents with no disability. “This holds true for every level higher than normal [ie, no disability],” said Dr. Cofield. Among respondents with moderate disability, people with higher PDDS scores were more likely to be current marijuana users than people with lower PDDS scores.

Survey May Inform Clinical Trials
Among the goals of the survey were to see which patients with MS were talking about using marijuana “and to bring the participants into the discussion,” said Dr. Cofield. “It’s clear from … the responses that we’ve gotten that patients are willing to talk about it—even the patients who aren’t taking it.”

 

Approximately 5% of respondents said that they did not think that marijuana helped their symptoms. All other respondents reported that they thought that marijuana might be helpful in at least one domain. “Knowing these types of numbers, that a large proportion have tried it and a large proportion of people are willing to talk about it, can advance the conversation and perhaps assist with people who would be willing to be enrolled in clinical trials,” Dr. Cofield concluded.

—Erik Greb

INDIANAPOLIS—In August 2014, approximately 16% of patients with multiple sclerosis (MS) reported currently using marijuana to treat their disease, according to survey results presented at the 2015 CMSC Annual Meeting. People with moderate disability and those with high spasticity are more likely to use marijuana than other patients.

Approximately 82% of respondents reported that they would consider using marijuana if it became legal where they live, said Stacey Cofield, PhD, Associate Professor of Biostatistics at the University of Alabama at Birmingham. More than one-third of respondents already had spoken to their physician about using marijuana, regardless of whether they were current marijuana users.

Survey Not Linked With NARCOMS Data
In 2014, the North American Research Committee on MS (NARCOMS) created a brief online survey to characterize marijuana use among people with MS, determine whether participants had spoken to their doctors about marijuana use, and investigate the disease status of marijuana users and nonusers. The survey did not distinguish between various forms (eg, smoked, ingested, or sprayed) of marijuana. To ensure that participants’ personal health information was not associated with their marijuana status, NARCOMS initiated the survey outside of the organization’s website and kept all responses anonymous. One of the survey’s limitations is that the responses are not linked with the NARCOMS longitudinal data, said Dr. Cofield.

In August 2014, more than 12,000 active participants in the NARCOMS database received invitations to participate in the survey, and more than 5,600 people responded. About 50% of participants live in a place where marijuana is legal in some form, and this result is consistent with the characteristics of the general US population. Also, 1.1% of respondents live in a place outside of the US where marijuana is legal.

Approximately 10% of participants described their disease as progressive MS with no history of relapses, and about 90% of participants had a history of relapses. Respondents with progressive MS were older at diagnosis, older at the time of the survey, and less likely to be female, compared with respondents with relapsing-remitting MS. These results are consistent with the characteristics of the larger population of Americans with MS, said Dr. Cofield.

Respondents’ median score on the Patient Determined Disease Steps (PDDS), a self-reported measure of disability, was 3, which represents early gait disability. People with stable relapsing-remitting MS (ie, with no relapse in the previous two years) had moderate disability, and patients with active relapsing-remitting MS had a higher level of disability. People with progressive MS had the highest levels of disability.

Respondents’ median score on the spasticity performance scale was 2, which represents mild spasticity. People with active MS had slightly more spasticity than respondents with stable MS. Patients with progressive MS and relapses had more spasticity than patients with primary progressive MS.

Active Disease Increased Likelihood of Use
The lowest prevalence of marijuana use (12.2%) was among respondents with stable relapsing-remitting MS. Approximately 19.9% of respondents with active relapsing-remitting MS and 19.2% of respondents with progressive MS and a history of relapses reported marijuana use. About 15.0% of respondents with primary progressive MS currently used marijuana. Between 60% and 70% of people reported using marijuana at least once in the past, and about 50% of people had considered using marijuana for their MS since their diagnosis.

Respondents with a moderate level of disability, as measured by PDDS, reported the highest percentage of current marijuana use, compared with those with mild disability and those with severe disability. The low level of marijuana use among NARCOMS participants with severe disability (ie, bedridden status) may result from the small sample size or the limited mobility among these patients who completed the survey, said Dr. Cofield. Marijuana use increased with increasing spasticity. The proportion of respondents who had never used marijuana was highest among people reporting no spasticity.

People with progressive MS and relapses, progressive MS without relapses, and active relapsing-remitting MS were more likely to be current marijuana users than respondents with stable relapsing-remitting MS. In addition, people with more severe disability, as measured by PDDS score, were more likely to be current marijuana users than respondents with no disability. “This holds true for every level higher than normal [ie, no disability],” said Dr. Cofield. Among respondents with moderate disability, people with higher PDDS scores were more likely to be current marijuana users than people with lower PDDS scores.

Survey May Inform Clinical Trials
Among the goals of the survey were to see which patients with MS were talking about using marijuana “and to bring the participants into the discussion,” said Dr. Cofield. “It’s clear from … the responses that we’ve gotten that patients are willing to talk about it—even the patients who aren’t taking it.”

 

Approximately 5% of respondents said that they did not think that marijuana helped their symptoms. All other respondents reported that they thought that marijuana might be helpful in at least one domain. “Knowing these types of numbers, that a large proportion have tried it and a large proportion of people are willing to talk about it, can advance the conversation and perhaps assist with people who would be willing to be enrolled in clinical trials,” Dr. Cofield concluded.

—Erik Greb

INDIANAPOLIS—In August 2014, approximately 16% of patients with multiple sclerosis (MS) reported currently using marijuana to treat their disease, according to survey results presented at the 2015 CMSC Annual Meeting. People with moderate disability and those with high spasticity are more likely to use marijuana than other patients.

Approximately 82% of respondents reported that they would consider using marijuana if it became legal where they live, said Stacey Cofield, PhD, Associate Professor of Biostatistics at the University of Alabama at Birmingham. More than one-third of respondents already had spoken to their physician about using marijuana, regardless of whether they were current marijuana users.

Survey Not Linked With NARCOMS Data
In 2014, the North American Research Committee on MS (NARCOMS) created a brief online survey to characterize marijuana use among people with MS, determine whether participants had spoken to their doctors about marijuana use, and investigate the disease status of marijuana users and nonusers. The survey did not distinguish between various forms (eg, smoked, ingested, or sprayed) of marijuana. To ensure that participants’ personal health information was not associated with their marijuana status, NARCOMS initiated the survey outside of the organization’s website and kept all responses anonymous. One of the survey’s limitations is that the responses are not linked with the NARCOMS longitudinal data, said Dr. Cofield.

In August 2014, more than 12,000 active participants in the NARCOMS database received invitations to participate in the survey, and more than 5,600 people responded. About 50% of participants live in a place where marijuana is legal in some form, and this result is consistent with the characteristics of the general US population. Also, 1.1% of respondents live in a place outside of the US where marijuana is legal.

Approximately 10% of participants described their disease as progressive MS with no history of relapses, and about 90% of participants had a history of relapses. Respondents with progressive MS were older at diagnosis, older at the time of the survey, and less likely to be female, compared with respondents with relapsing-remitting MS. These results are consistent with the characteristics of the larger population of Americans with MS, said Dr. Cofield.

Respondents’ median score on the Patient Determined Disease Steps (PDDS), a self-reported measure of disability, was 3, which represents early gait disability. People with stable relapsing-remitting MS (ie, with no relapse in the previous two years) had moderate disability, and patients with active relapsing-remitting MS had a higher level of disability. People with progressive MS had the highest levels of disability.

Respondents’ median score on the spasticity performance scale was 2, which represents mild spasticity. People with active MS had slightly more spasticity than respondents with stable MS. Patients with progressive MS and relapses had more spasticity than patients with primary progressive MS.

Active Disease Increased Likelihood of Use
The lowest prevalence of marijuana use (12.2%) was among respondents with stable relapsing-remitting MS. Approximately 19.9% of respondents with active relapsing-remitting MS and 19.2% of respondents with progressive MS and a history of relapses reported marijuana use. About 15.0% of respondents with primary progressive MS currently used marijuana. Between 60% and 70% of people reported using marijuana at least once in the past, and about 50% of people had considered using marijuana for their MS since their diagnosis.

Respondents with a moderate level of disability, as measured by PDDS, reported the highest percentage of current marijuana use, compared with those with mild disability and those with severe disability. The low level of marijuana use among NARCOMS participants with severe disability (ie, bedridden status) may result from the small sample size or the limited mobility among these patients who completed the survey, said Dr. Cofield. Marijuana use increased with increasing spasticity. The proportion of respondents who had never used marijuana was highest among people reporting no spasticity.

People with progressive MS and relapses, progressive MS without relapses, and active relapsing-remitting MS were more likely to be current marijuana users than respondents with stable relapsing-remitting MS. In addition, people with more severe disability, as measured by PDDS score, were more likely to be current marijuana users than respondents with no disability. “This holds true for every level higher than normal [ie, no disability],” said Dr. Cofield. Among respondents with moderate disability, people with higher PDDS scores were more likely to be current marijuana users than people with lower PDDS scores.

Survey May Inform Clinical Trials
Among the goals of the survey were to see which patients with MS were talking about using marijuana “and to bring the participants into the discussion,” said Dr. Cofield. “It’s clear from … the responses that we’ve gotten that patients are willing to talk about it—even the patients who aren’t taking it.”

 

Approximately 5% of respondents said that they did not think that marijuana helped their symptoms. All other respondents reported that they thought that marijuana might be helpful in at least one domain. “Knowing these types of numbers, that a large proportion have tried it and a large proportion of people are willing to talk about it, can advance the conversation and perhaps assist with people who would be willing to be enrolled in clinical trials,” Dr. Cofield concluded.

—Erik Greb

The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is a promising screening tool to predict actual functional performance in patients with multiple sclerosis (MS), according to a study of 41 individuals with MS and 32 healthy controls.

Investigators administered BICAMS and Actual Reality (AR) tests to participants, which included using the internet to purchase a flight ticket or cookies. Subjects with MS performed significantly worse on both BICAMS and AR than controls. In addition, better BICAMS performance was associated with more independent AR performance.

Citation: Goverover Y, Chiaravalloti N, DeLuca J. Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and performance of everyday life tasks: Actual Reality. Mult Scler. 2015. pii: 1352458515593637.  

The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is a promising screening tool to predict actual functional performance in patients with multiple sclerosis (MS), according to a study of 41 individuals with MS and 32 healthy controls.

Investigators administered BICAMS and Actual Reality (AR) tests to participants, which included using the internet to purchase a flight ticket or cookies. Subjects with MS performed significantly worse on both BICAMS and AR than controls. In addition, better BICAMS performance was associated with more independent AR performance.

Citation: Goverover Y, Chiaravalloti N, DeLuca J. Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and performance of everyday life tasks: Actual Reality. Mult Scler. 2015. pii: 1352458515593637.  

The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is a promising screening tool to predict actual functional performance in patients with multiple sclerosis (MS), according to a study of 41 individuals with MS and 32 healthy controls.

Investigators administered BICAMS and Actual Reality (AR) tests to participants, which included using the internet to purchase a flight ticket or cookies. Subjects with MS performed significantly worse on both BICAMS and AR than controls. In addition, better BICAMS performance was associated with more independent AR performance.

Citation: Goverover Y, Chiaravalloti N, DeLuca J. Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and performance of everyday life tasks: Actual Reality. Mult Scler. 2015. pii: 1352458515593637.