Multiple Sclerosis

PHILADELPHIA—Alemtuzumab may prevent disease activity for as long as three years in patients with active relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology.

The drug appears to suppress gadolinium-enhancing activity and new or enlarging T2 lesions efficiently among treatment-naïve patients and patients who have relapsed on previous therapy. In addition, alemtuzumab reduces brain volume loss to a rate similar to that associated with normal aging, said Douglas Arnold, MD, a neurologist at the Montreal Neurological Institute and Hospital.

Dr. Arnold and colleagues presented three-year MRI outcomes from the Comparison of Alemtuzumab and Rebif Efficacy in MS (CARE-MS) I and II trials, which lasted for two years. CARE-MS I included treatment-naïve participants, and CARE-MS II included participants who had relapsed on prior therapy. In both trials, patients with MS were randomized to alemtuzumab or interferon beta-1a. Patients randomized to alemtuzumab received 12 mg at baseline and at one year. In CARE-MS I, alemtuzumab reduced relapse rates, compared with interferon beta-1a. In CARE-MS II, alemtuzumab reduced relapse rates and sustained accumulation of disability, compared with interferon beta-1a.

Alemtuzumab Slowed the Rate of Brain Atrophy
A total of 349 participants in CARE-MS I and 393 participants in CARE-MS II entered the extension trial. At year three, the researchers administered alemtuzumab again to patients with recurrence of disease activity. Approximately 18% of patients in CARE-MS I and 20% of patients in CARE-MS II had recurrence. Fewer than 3% of patients had taken any other therapy at year three.

“At year three, patients maintained approximately 90% suppression of gadolinium-enhancing activity and about 75% suppression of new or enlarging T2 lesion formation,” said Dr. Arnold. Similar proportions of patients had new or active gadolinium-enhancing lesions at year three and at year two (9.6% and 7.1%, respectively). Also, similar proportions of patients had new and enlarging T2 lesions at year three and at year two (27.4% and 23.1%, respectively). Approximately 75% of patients in both trials had no MRI activity.

The rate of change in brain volume slowed progressively from year one to year three. At year three, the rate of change was 0.19% per year in CARE-MS I and 0.1% per year in CARE-MS II.

Positive Outcomes Despite Two-Year Lack of Treatment
“These findings provide strong support for the efficacy of alemtuzumab in treatment-naïve patients and patients who have relapsed on prior therapy,” said Dr. Arnold. “It is important to note that the majority of patients in this three-year follow-up received no treatment for two years, since they received their second course of alemtuzumab at the beginning of year two. Despite being treatment-free for two years, they had these remarkable outcomes on MRI.”

—Erik Greb

PHILADELPHIA—Alemtuzumab may prevent disease activity for as long as three years in patients with active relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology.

The drug appears to suppress gadolinium-enhancing activity and new or enlarging T2 lesions efficiently among treatment-naïve patients and patients who have relapsed on previous therapy. In addition, alemtuzumab reduces brain volume loss to a rate similar to that associated with normal aging, said Douglas Arnold, MD, a neurologist at the Montreal Neurological Institute and Hospital.

Dr. Arnold and colleagues presented three-year MRI outcomes from the Comparison of Alemtuzumab and Rebif Efficacy in MS (CARE-MS) I and II trials, which lasted for two years. CARE-MS I included treatment-naïve participants, and CARE-MS II included participants who had relapsed on prior therapy. In both trials, patients with MS were randomized to alemtuzumab or interferon beta-1a. Patients randomized to alemtuzumab received 12 mg at baseline and at one year. In CARE-MS I, alemtuzumab reduced relapse rates, compared with interferon beta-1a. In CARE-MS II, alemtuzumab reduced relapse rates and sustained accumulation of disability, compared with interferon beta-1a.

Alemtuzumab Slowed the Rate of Brain Atrophy
A total of 349 participants in CARE-MS I and 393 participants in CARE-MS II entered the extension trial. At year three, the researchers administered alemtuzumab again to patients with recurrence of disease activity. Approximately 18% of patients in CARE-MS I and 20% of patients in CARE-MS II had recurrence. Fewer than 3% of patients had taken any other therapy at year three.

“At year three, patients maintained approximately 90% suppression of gadolinium-enhancing activity and about 75% suppression of new or enlarging T2 lesion formation,” said Dr. Arnold. Similar proportions of patients had new or active gadolinium-enhancing lesions at year three and at year two (9.6% and 7.1%, respectively). Also, similar proportions of patients had new and enlarging T2 lesions at year three and at year two (27.4% and 23.1%, respectively). Approximately 75% of patients in both trials had no MRI activity.

The rate of change in brain volume slowed progressively from year one to year three. At year three, the rate of change was 0.19% per year in CARE-MS I and 0.1% per year in CARE-MS II.

Positive Outcomes Despite Two-Year Lack of Treatment
“These findings provide strong support for the efficacy of alemtuzumab in treatment-naïve patients and patients who have relapsed on prior therapy,” said Dr. Arnold. “It is important to note that the majority of patients in this three-year follow-up received no treatment for two years, since they received their second course of alemtuzumab at the beginning of year two. Despite being treatment-free for two years, they had these remarkable outcomes on MRI.”

—Erik Greb

PHILADELPHIA—Alemtuzumab may prevent disease activity for as long as three years in patients with active relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology.

The drug appears to suppress gadolinium-enhancing activity and new or enlarging T2 lesions efficiently among treatment-naïve patients and patients who have relapsed on previous therapy. In addition, alemtuzumab reduces brain volume loss to a rate similar to that associated with normal aging, said Douglas Arnold, MD, a neurologist at the Montreal Neurological Institute and Hospital.

Dr. Arnold and colleagues presented three-year MRI outcomes from the Comparison of Alemtuzumab and Rebif Efficacy in MS (CARE-MS) I and II trials, which lasted for two years. CARE-MS I included treatment-naïve participants, and CARE-MS II included participants who had relapsed on prior therapy. In both trials, patients with MS were randomized to alemtuzumab or interferon beta-1a. Patients randomized to alemtuzumab received 12 mg at baseline and at one year. In CARE-MS I, alemtuzumab reduced relapse rates, compared with interferon beta-1a. In CARE-MS II, alemtuzumab reduced relapse rates and sustained accumulation of disability, compared with interferon beta-1a.

Alemtuzumab Slowed the Rate of Brain Atrophy
A total of 349 participants in CARE-MS I and 393 participants in CARE-MS II entered the extension trial. At year three, the researchers administered alemtuzumab again to patients with recurrence of disease activity. Approximately 18% of patients in CARE-MS I and 20% of patients in CARE-MS II had recurrence. Fewer than 3% of patients had taken any other therapy at year three.

“At year three, patients maintained approximately 90% suppression of gadolinium-enhancing activity and about 75% suppression of new or enlarging T2 lesion formation,” said Dr. Arnold. Similar proportions of patients had new or active gadolinium-enhancing lesions at year three and at year two (9.6% and 7.1%, respectively). Also, similar proportions of patients had new and enlarging T2 lesions at year three and at year two (27.4% and 23.1%, respectively). Approximately 75% of patients in both trials had no MRI activity.

The rate of change in brain volume slowed progressively from year one to year three. At year three, the rate of change was 0.19% per year in CARE-MS I and 0.1% per year in CARE-MS II.

Positive Outcomes Despite Two-Year Lack of Treatment
“These findings provide strong support for the efficacy of alemtuzumab in treatment-naïve patients and patients who have relapsed on prior therapy,” said Dr. Arnold. “It is important to note that the majority of patients in this three-year follow-up received no treatment for two years, since they received their second course of alemtuzumab at the beginning of year two. Despite being treatment-free for two years, they had these remarkable outcomes on MRI.”

—Erik Greb

PHILADELPHIA—After a patient with relapsing-remitting multiple sclerosis (MS) has been on a first-line drug for two years, the factors that most influence neurologists’ decision to consider changing therapies are clinical measures such as relapse rate and Expanded Disability Status Scale (EDSS) score and subclinical measures such as MRI, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. In contrast, quality-of-life measures do not contribute significantly to treatment decisions, the researchers said.

Stephan Schmidt, MD, PhD, a neurologist at Neurologische Gemeinschaftspraxis in Bonn, Germany, and colleagues performed an interim analysis of data from EPIDEM, an ongoing retrospective, noninterventional study that collects cross-sectional data for 5,000 patients at 150 sites in Germany. Eligible patients had received immunomodulatory treatment (ie, interferon beta or glatiramer acetate) continuously during the two years before enrollment. The researchers collected information about demographics, immunomodulatory treatment, EDSS score, MRI, John Cunningham virus (JCV) status, and quality of life (using MSQoL-54).

During the study, the participants’ neurologists were asked whether they were considering a switch to a second-line therapy, and the researchers performed χ² homogeneity analysis to identify factors that influenced this treatment decision. The study did not document whether patients switched to a second-line therapy, however.

Most Patients Had No Relapses or MRI Activity
The interim analysis included 2,500 patients from October 2011 to April 2013. Patients’ mean EDSS score was 2.2 at the beginning of the period and remained stable. Approximately 65% of patients had been relapse-free during the previous 24 months, and about 35% of patients had had at least one relapse.

MRI data were available for two-thirds of the participants. The mean duration between the documentation visit and the last MRI was 9.4 months. Approximately 74% of patients had neither increased T2 lesion load nor new gadolinium-enhancing T1 lesions, compared with the last MRI. About 23% of patients had increased MRI activity, compared with the last MRI.

The STRATIFY-JCV assay to determine JCV antibody status became available in Germany in May 2011. Neurologists determined the JCV antibody status of 6.1% of participants, and 56.9% of reported test results were positive.

Most Patients Reported Good Health
A total of 2,018 patients underwent MSQoL-54, and 74% of patients rated their general state of health as good to excellent. In addition, 21% of participants rated their overall health as fair, and 2% rated their health as poor.

Neurologists described the course of disease as stable in 81% of patients, improved in 3% of patients, and worse in 15% of patients. In contrast, 57% of patients described their course of disease as stable, 17% as improved, and 24% as worse.

Neurologists considered changing the current treatment regimen for 11% of the patients. The availability of JCV-antibody test results, relapse rate, EDSS score, and MRI activity had the strongest influence when considering second-line therapies. Quality-of-life parameters, treatment duration, disease duration, and number of previous disease-modifying therapies had little or no influence on therapeutic considerations.

—Erik Greb

PHILADELPHIA—After a patient with relapsing-remitting multiple sclerosis (MS) has been on a first-line drug for two years, the factors that most influence neurologists’ decision to consider changing therapies are clinical measures such as relapse rate and Expanded Disability Status Scale (EDSS) score and subclinical measures such as MRI, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. In contrast, quality-of-life measures do not contribute significantly to treatment decisions, the researchers said.

Stephan Schmidt, MD, PhD, a neurologist at Neurologische Gemeinschaftspraxis in Bonn, Germany, and colleagues performed an interim analysis of data from EPIDEM, an ongoing retrospective, noninterventional study that collects cross-sectional data for 5,000 patients at 150 sites in Germany. Eligible patients had received immunomodulatory treatment (ie, interferon beta or glatiramer acetate) continuously during the two years before enrollment. The researchers collected information about demographics, immunomodulatory treatment, EDSS score, MRI, John Cunningham virus (JCV) status, and quality of life (using MSQoL-54).

During the study, the participants’ neurologists were asked whether they were considering a switch to a second-line therapy, and the researchers performed χ² homogeneity analysis to identify factors that influenced this treatment decision. The study did not document whether patients switched to a second-line therapy, however.

Most Patients Had No Relapses or MRI Activity
The interim analysis included 2,500 patients from October 2011 to April 2013. Patients’ mean EDSS score was 2.2 at the beginning of the period and remained stable. Approximately 65% of patients had been relapse-free during the previous 24 months, and about 35% of patients had had at least one relapse.

MRI data were available for two-thirds of the participants. The mean duration between the documentation visit and the last MRI was 9.4 months. Approximately 74% of patients had neither increased T2 lesion load nor new gadolinium-enhancing T1 lesions, compared with the last MRI. About 23% of patients had increased MRI activity, compared with the last MRI.

The STRATIFY-JCV assay to determine JCV antibody status became available in Germany in May 2011. Neurologists determined the JCV antibody status of 6.1% of participants, and 56.9% of reported test results were positive.

Most Patients Reported Good Health
A total of 2,018 patients underwent MSQoL-54, and 74% of patients rated their general state of health as good to excellent. In addition, 21% of participants rated their overall health as fair, and 2% rated their health as poor.

Neurologists described the course of disease as stable in 81% of patients, improved in 3% of patients, and worse in 15% of patients. In contrast, 57% of patients described their course of disease as stable, 17% as improved, and 24% as worse.

Neurologists considered changing the current treatment regimen for 11% of the patients. The availability of JCV-antibody test results, relapse rate, EDSS score, and MRI activity had the strongest influence when considering second-line therapies. Quality-of-life parameters, treatment duration, disease duration, and number of previous disease-modifying therapies had little or no influence on therapeutic considerations.

—Erik Greb

PHILADELPHIA—After a patient with relapsing-remitting multiple sclerosis (MS) has been on a first-line drug for two years, the factors that most influence neurologists’ decision to consider changing therapies are clinical measures such as relapse rate and Expanded Disability Status Scale (EDSS) score and subclinical measures such as MRI, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. In contrast, quality-of-life measures do not contribute significantly to treatment decisions, the researchers said.

Stephan Schmidt, MD, PhD, a neurologist at Neurologische Gemeinschaftspraxis in Bonn, Germany, and colleagues performed an interim analysis of data from EPIDEM, an ongoing retrospective, noninterventional study that collects cross-sectional data for 5,000 patients at 150 sites in Germany. Eligible patients had received immunomodulatory treatment (ie, interferon beta or glatiramer acetate) continuously during the two years before enrollment. The researchers collected information about demographics, immunomodulatory treatment, EDSS score, MRI, John Cunningham virus (JCV) status, and quality of life (using MSQoL-54).

During the study, the participants’ neurologists were asked whether they were considering a switch to a second-line therapy, and the researchers performed χ² homogeneity analysis to identify factors that influenced this treatment decision. The study did not document whether patients switched to a second-line therapy, however.

Most Patients Had No Relapses or MRI Activity
The interim analysis included 2,500 patients from October 2011 to April 2013. Patients’ mean EDSS score was 2.2 at the beginning of the period and remained stable. Approximately 65% of patients had been relapse-free during the previous 24 months, and about 35% of patients had had at least one relapse.

MRI data were available for two-thirds of the participants. The mean duration between the documentation visit and the last MRI was 9.4 months. Approximately 74% of patients had neither increased T2 lesion load nor new gadolinium-enhancing T1 lesions, compared with the last MRI. About 23% of patients had increased MRI activity, compared with the last MRI.

The STRATIFY-JCV assay to determine JCV antibody status became available in Germany in May 2011. Neurologists determined the JCV antibody status of 6.1% of participants, and 56.9% of reported test results were positive.

Most Patients Reported Good Health
A total of 2,018 patients underwent MSQoL-54, and 74% of patients rated their general state of health as good to excellent. In addition, 21% of participants rated their overall health as fair, and 2% rated their health as poor.

Neurologists described the course of disease as stable in 81% of patients, improved in 3% of patients, and worse in 15% of patients. In contrast, 57% of patients described their course of disease as stable, 17% as improved, and 24% as worse.

Neurologists considered changing the current treatment regimen for 11% of the patients. The availability of JCV-antibody test results, relapse rate, EDSS score, and MRI activity had the strongest influence when considering second-line therapies. Quality-of-life parameters, treatment duration, disease duration, and number of previous disease-modifying therapies had little or no influence on therapeutic considerations.

—Erik Greb

Peginterferon beta-1a has been approved by the Food and Drug Administration for treating relapsing forms of multiple sclerosis, based on the results of the ADVANCE trial, the manufacturer, Biogen Idec, announced on August 15.

This is the only pegylated interferon approved for treating relapsing MS, according to a statement from the company.

Biogen Idec will be marketing the drug as Plegridy. The recommended dose is 125 mcg administered subcutaneously every 14 days. It can be administered with a prefilled syringe or a new autoinjector the company is marketing as the Plegridy Pen, according to the statement.

The approval is based on the results of the ADVANCE study, a randomized, double-blind, phase III, 2-year study of about 1,516 patients with relapsing MS, which was placebo-controlled during the first year. The annualized relapse rate, the primary outcome, was reduced by 36% among those treated with peginterferon beta-1a, compared with those on placebo, a statistically significant difference.

Secondary outcomes including the proportion of patients who relapsed, which was reduced by 19%, compared with placebo; the mean number of new or newly enlarging T2 hyperintense lesions, which was reduced by 67%, compared with placebo; and the mean number of new gadolinium-enhancing lesions, which was reduced by 86%, compared with placebo.

Injection-site erythema, influenzalike illness, fever, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia were the most common adverse events associated with treatment, affecting at least 10% of treated patients and occurring at a rate that was at least 2% greater than among those on placebo, according to the prescribing information.

Postmarketing studies that the company will be required to conduct include a pediatric study and a registry study in the United States that will compare the maternal, fetal, and infant outcomes, including birth defects, of women with MS who are treated with peginterferon beta-1a during pregnancy against women with MS who are not treated with the drug during pregnancy and women who do not have MS.

The product has already been approved in Europe.

Serious adverse events associated with this product should be reported to the FDA at 800-332-1088 or www. fda.gov/medwatch.

emechcatie@frontlinemedcom.com

Peginterferon beta-1a has been approved by the Food and Drug Administration for treating relapsing forms of multiple sclerosis, based on the results of the ADVANCE trial, the manufacturer, Biogen Idec, announced on August 15.

This is the only pegylated interferon approved for treating relapsing MS, according to a statement from the company.

Biogen Idec will be marketing the drug as Plegridy. The recommended dose is 125 mcg administered subcutaneously every 14 days. It can be administered with a prefilled syringe or a new autoinjector the company is marketing as the Plegridy Pen, according to the statement.

The approval is based on the results of the ADVANCE study, a randomized, double-blind, phase III, 2-year study of about 1,516 patients with relapsing MS, which was placebo-controlled during the first year. The annualized relapse rate, the primary outcome, was reduced by 36% among those treated with peginterferon beta-1a, compared with those on placebo, a statistically significant difference.

Secondary outcomes including the proportion of patients who relapsed, which was reduced by 19%, compared with placebo; the mean number of new or newly enlarging T2 hyperintense lesions, which was reduced by 67%, compared with placebo; and the mean number of new gadolinium-enhancing lesions, which was reduced by 86%, compared with placebo.

Injection-site erythema, influenzalike illness, fever, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia were the most common adverse events associated with treatment, affecting at least 10% of treated patients and occurring at a rate that was at least 2% greater than among those on placebo, according to the prescribing information.

Postmarketing studies that the company will be required to conduct include a pediatric study and a registry study in the United States that will compare the maternal, fetal, and infant outcomes, including birth defects, of women with MS who are treated with peginterferon beta-1a during pregnancy against women with MS who are not treated with the drug during pregnancy and women who do not have MS.

The product has already been approved in Europe.

Serious adverse events associated with this product should be reported to the FDA at 800-332-1088 or www. fda.gov/medwatch.

emechcatie@frontlinemedcom.com

Peginterferon beta-1a has been approved by the Food and Drug Administration for treating relapsing forms of multiple sclerosis, based on the results of the ADVANCE trial, the manufacturer, Biogen Idec, announced on August 15.

This is the only pegylated interferon approved for treating relapsing MS, according to a statement from the company.

Biogen Idec will be marketing the drug as Plegridy. The recommended dose is 125 mcg administered subcutaneously every 14 days. It can be administered with a prefilled syringe or a new autoinjector the company is marketing as the Plegridy Pen, according to the statement.

The approval is based on the results of the ADVANCE study, a randomized, double-blind, phase III, 2-year study of about 1,516 patients with relapsing MS, which was placebo-controlled during the first year. The annualized relapse rate, the primary outcome, was reduced by 36% among those treated with peginterferon beta-1a, compared with those on placebo, a statistically significant difference.

Secondary outcomes including the proportion of patients who relapsed, which was reduced by 19%, compared with placebo; the mean number of new or newly enlarging T2 hyperintense lesions, which was reduced by 67%, compared with placebo; and the mean number of new gadolinium-enhancing lesions, which was reduced by 86%, compared with placebo.

Injection-site erythema, influenzalike illness, fever, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia were the most common adverse events associated with treatment, affecting at least 10% of treated patients and occurring at a rate that was at least 2% greater than among those on placebo, according to the prescribing information.

Postmarketing studies that the company will be required to conduct include a pediatric study and a registry study in the United States that will compare the maternal, fetal, and infant outcomes, including birth defects, of women with MS who are treated with peginterferon beta-1a during pregnancy against women with MS who are not treated with the drug during pregnancy and women who do not have MS.

The product has already been approved in Europe.

Serious adverse events associated with this product should be reported to the FDA at 800-332-1088 or www. fda.gov/medwatch.

emechcatie@frontlinemedcom.com

Disability in patients with multiple sclerosis was independently linked to microstructural abnormalities of spinal cord grey matter on diffusion tensor imaging study in a prospective study of healthy controls and patients at various stages of disease.

Spinal cord atrophy and abnormal grey matter radial diffusivity explained 77% of variance in scores on the Expanded Disability Status Scale (EDSS), said Dr. Hugh Kearney of the Queen Square MS Centre at the University College London Institute of Neurology and his associates. Grey matter involvement was already present in patients with relapsing-remitting multiple sclerosis (MS) but was more pronounced in those with secondary progressive disease, the investigators said.

The researchers performed 3 T spinal cord magnetic resonance imaging and diffusion tensor imaging on 113 subjects – 30 healthy controls, 21 individuals with a clinically isolated syndrome, 33 who had relapsing-remitting MS and 29 who had secondary progressive MS (J. Neurol. Neurosurg. Psychiatry 2014 Aug. 5 [doi:10.1136/jnnp-2014-308241]).

Compared with controls and subjects with relapsing-remitting MS, those with secondary progressive disease had significantly worse abnormalities in measures of spinal cord radial diffusivity, fractional anisotropy, and mean diffusivity in the grey matter and posterior columns, the investigators said.

Furthermore, spinal cord grey matter radial diffusivity and cord area were independently associated with EDSS disability scores (beta = 0.33 and P less than .01; beta = –0.45 and P less than .01, respectively), and radial diffusivity was independently linked to scores on a 9-hole peg test (beta = –0.33; P less than .01) and timed walk (beta = –0.20, P = .04), the researchers said.

Based on the findings, grey matter pathology in the spinal cord may underlie physical disability in MS, including the irreversible disability that characterizes secondary progressive disease, Dr. Kearney and his associates said. Investigators should next examine longitudinal changes in diffusion tensor imaging measures of spinal cord grey matter and how these changes relate to clinical progression, they said.

The research was funded by the MS Society of Great Britain and Northern Ireland, UCLH-UCL Biomedical Research Centre, the International Spinal Research Trust, and the Engineering and Physical Sciences Research Council. The authors reported no competing interests.

Disability in patients with multiple sclerosis was independently linked to microstructural abnormalities of spinal cord grey matter on diffusion tensor imaging study in a prospective study of healthy controls and patients at various stages of disease.

Spinal cord atrophy and abnormal grey matter radial diffusivity explained 77% of variance in scores on the Expanded Disability Status Scale (EDSS), said Dr. Hugh Kearney of the Queen Square MS Centre at the University College London Institute of Neurology and his associates. Grey matter involvement was already present in patients with relapsing-remitting multiple sclerosis (MS) but was more pronounced in those with secondary progressive disease, the investigators said.

The researchers performed 3 T spinal cord magnetic resonance imaging and diffusion tensor imaging on 113 subjects – 30 healthy controls, 21 individuals with a clinically isolated syndrome, 33 who had relapsing-remitting MS and 29 who had secondary progressive MS (J. Neurol. Neurosurg. Psychiatry 2014 Aug. 5 [doi:10.1136/jnnp-2014-308241]).

Compared with controls and subjects with relapsing-remitting MS, those with secondary progressive disease had significantly worse abnormalities in measures of spinal cord radial diffusivity, fractional anisotropy, and mean diffusivity in the grey matter and posterior columns, the investigators said.

Furthermore, spinal cord grey matter radial diffusivity and cord area were independently associated with EDSS disability scores (beta = 0.33 and P less than .01; beta = –0.45 and P less than .01, respectively), and radial diffusivity was independently linked to scores on a 9-hole peg test (beta = –0.33; P less than .01) and timed walk (beta = –0.20, P = .04), the researchers said.

Based on the findings, grey matter pathology in the spinal cord may underlie physical disability in MS, including the irreversible disability that characterizes secondary progressive disease, Dr. Kearney and his associates said. Investigators should next examine longitudinal changes in diffusion tensor imaging measures of spinal cord grey matter and how these changes relate to clinical progression, they said.

The research was funded by the MS Society of Great Britain and Northern Ireland, UCLH-UCL Biomedical Research Centre, the International Spinal Research Trust, and the Engineering and Physical Sciences Research Council. The authors reported no competing interests.

Disability in patients with multiple sclerosis was independently linked to microstructural abnormalities of spinal cord grey matter on diffusion tensor imaging study in a prospective study of healthy controls and patients at various stages of disease.

Spinal cord atrophy and abnormal grey matter radial diffusivity explained 77% of variance in scores on the Expanded Disability Status Scale (EDSS), said Dr. Hugh Kearney of the Queen Square MS Centre at the University College London Institute of Neurology and his associates. Grey matter involvement was already present in patients with relapsing-remitting multiple sclerosis (MS) but was more pronounced in those with secondary progressive disease, the investigators said.

The researchers performed 3 T spinal cord magnetic resonance imaging and diffusion tensor imaging on 113 subjects – 30 healthy controls, 21 individuals with a clinically isolated syndrome, 33 who had relapsing-remitting MS and 29 who had secondary progressive MS (J. Neurol. Neurosurg. Psychiatry 2014 Aug. 5 [doi:10.1136/jnnp-2014-308241]).

Compared with controls and subjects with relapsing-remitting MS, those with secondary progressive disease had significantly worse abnormalities in measures of spinal cord radial diffusivity, fractional anisotropy, and mean diffusivity in the grey matter and posterior columns, the investigators said.

Furthermore, spinal cord grey matter radial diffusivity and cord area were independently associated with EDSS disability scores (beta = 0.33 and P less than .01; beta = –0.45 and P less than .01, respectively), and radial diffusivity was independently linked to scores on a 9-hole peg test (beta = –0.33; P less than .01) and timed walk (beta = –0.20, P = .04), the researchers said.

Based on the findings, grey matter pathology in the spinal cord may underlie physical disability in MS, including the irreversible disability that characterizes secondary progressive disease, Dr. Kearney and his associates said. Investigators should next examine longitudinal changes in diffusion tensor imaging measures of spinal cord grey matter and how these changes relate to clinical progression, they said.

The research was funded by the MS Society of Great Britain and Northern Ireland, UCLH-UCL Biomedical Research Centre, the International Spinal Research Trust, and the Engineering and Physical Sciences Research Council. The authors reported no competing interests.

In patients with primary progressive multiple sclerosis, older age and bilateral motor symptoms at disease onset predicted faster disability progression in a retrospective analysis of prospectively collected data.

Age was the most important predictor, but both factors seemed to affect disability accumulation throughout the course of primary progressive multiple sclerosis (PPMS), in contrast to the distinct stages and risk factors that characterize relapsing-remitting disease, said Dr. Marcus W. Koch and his associates at the University of Calgary (Alta.).

Primary progressive disease affects about 10%-20% of MS patients. To study its natural history, the investigators analyzed data on 446 patients with PPMS who were followed for a median of 14 years from disease onset (J. Neurol. Neurosurg. Psychiatry 2014 Aug. 4 [doi:10.1136/jnnp-2014-307948]).

Patients reached Expanded Disability Status Scale (EDSS) scores of 4 and 6 a median of 5 and 9 years after disease onset, the researchers said. Median age at EDSS = 4 was 51 years, and median age at EDSS = 6 was 55 years, they added. For each 1-year increase in age at disease onset, time to progression to EDSS = 4 decreased by 3% (hazard ratio per 1-year increase, 1.03; 95% confidence interval, 1.02-1.04), and time from onset to EDSS = 6 decreased by 4% (HR, 1.04; 95% CI, 1.02-1.05), the researchers reported.

Patients with bilateral motor onset symptoms also progressed to EDSS scores of 4 and 6 significantly faster than did patients with unilateral onset motor symptoms (P = .005 and .03, respectively), the investigators reported.

The researchers excluded some patients from analyses because of missing data, and these patients were significantly more likely to be female and to have a younger age at onset than were the patients who were included in analyses. They also did not subgroup PPMS patients by disease course because the criteria for these subcategories were not published until after the study began, they said (Neurology 2014;83:278-86).

Funding information for the study was not available. The authors reported no conflicts of interest.

In patients with primary progressive multiple sclerosis, older age and bilateral motor symptoms at disease onset predicted faster disability progression in a retrospective analysis of prospectively collected data.

Age was the most important predictor, but both factors seemed to affect disability accumulation throughout the course of primary progressive multiple sclerosis (PPMS), in contrast to the distinct stages and risk factors that characterize relapsing-remitting disease, said Dr. Marcus W. Koch and his associates at the University of Calgary (Alta.).

Primary progressive disease affects about 10%-20% of MS patients. To study its natural history, the investigators analyzed data on 446 patients with PPMS who were followed for a median of 14 years from disease onset (J. Neurol. Neurosurg. Psychiatry 2014 Aug. 4 [doi:10.1136/jnnp-2014-307948]).

Patients reached Expanded Disability Status Scale (EDSS) scores of 4 and 6 a median of 5 and 9 years after disease onset, the researchers said. Median age at EDSS = 4 was 51 years, and median age at EDSS = 6 was 55 years, they added. For each 1-year increase in age at disease onset, time to progression to EDSS = 4 decreased by 3% (hazard ratio per 1-year increase, 1.03; 95% confidence interval, 1.02-1.04), and time from onset to EDSS = 6 decreased by 4% (HR, 1.04; 95% CI, 1.02-1.05), the researchers reported.

Patients with bilateral motor onset symptoms also progressed to EDSS scores of 4 and 6 significantly faster than did patients with unilateral onset motor symptoms (P = .005 and .03, respectively), the investigators reported.

The researchers excluded some patients from analyses because of missing data, and these patients were significantly more likely to be female and to have a younger age at onset than were the patients who were included in analyses. They also did not subgroup PPMS patients by disease course because the criteria for these subcategories were not published until after the study began, they said (Neurology 2014;83:278-86).

Funding information for the study was not available. The authors reported no conflicts of interest.

In patients with primary progressive multiple sclerosis, older age and bilateral motor symptoms at disease onset predicted faster disability progression in a retrospective analysis of prospectively collected data.

Age was the most important predictor, but both factors seemed to affect disability accumulation throughout the course of primary progressive multiple sclerosis (PPMS), in contrast to the distinct stages and risk factors that characterize relapsing-remitting disease, said Dr. Marcus W. Koch and his associates at the University of Calgary (Alta.).

Primary progressive disease affects about 10%-20% of MS patients. To study its natural history, the investigators analyzed data on 446 patients with PPMS who were followed for a median of 14 years from disease onset (J. Neurol. Neurosurg. Psychiatry 2014 Aug. 4 [doi:10.1136/jnnp-2014-307948]).

Patients reached Expanded Disability Status Scale (EDSS) scores of 4 and 6 a median of 5 and 9 years after disease onset, the researchers said. Median age at EDSS = 4 was 51 years, and median age at EDSS = 6 was 55 years, they added. For each 1-year increase in age at disease onset, time to progression to EDSS = 4 decreased by 3% (hazard ratio per 1-year increase, 1.03; 95% confidence interval, 1.02-1.04), and time from onset to EDSS = 6 decreased by 4% (HR, 1.04; 95% CI, 1.02-1.05), the researchers reported.

Patients with bilateral motor onset symptoms also progressed to EDSS scores of 4 and 6 significantly faster than did patients with unilateral onset motor symptoms (P = .005 and .03, respectively), the investigators reported.

The researchers excluded some patients from analyses because of missing data, and these patients were significantly more likely to be female and to have a younger age at onset than were the patients who were included in analyses. They also did not subgroup PPMS patients by disease course because the criteria for these subcategories were not published until after the study began, they said (Neurology 2014;83:278-86).

Funding information for the study was not available. The authors reported no conflicts of interest.

PHILADELPHIA—Cannabis is used by 8.6% of patients with multiple sclerosis (MS), making it the second most commonly used alternative therapy in this patient population, according to research reported at the 66th Annual Meeting of the American Academy of Neurology.

Patients with MS most frequently used marijuana for such symptoms as fatigue, heat sensitivity, and numbness, tingling, and pain. Massage was the leading alternative therapy used by patients with MS, reported by 12% of this group, said Stanley Cohan, MD, PhD, and his research colleagues.

The researchers sent surveys with questions related to demographics, symptoms of MS, disability status, quality of life, use of MS medications, and alternative therapies to patients with MS (ages 18 and older) who were enrolled in the Pacific Northwest MS Registry. Oregon and Washington are among the 20 states that allow the use of marijuana for medicinal purposes, and Washington is one of two states that have legalized marijuana for recreational use.

The investigators conducted analyses to determine the percentage of responders who reported cannabis use for MS symptoms and compared the data with those of nonusers according to demographic characteristics, score on the MS Impact Scale, responses on the Patient Determined Disease Steps questionnaire, and current symptoms using χ² and t-tests.

A total of 1,701 surveys (70%) were returned by patients in the registry; 8.6% of respondents reported current use of medical marijuana for their MS symptoms. The investigators found that patients who had used marijuana for MS were more likely to be younger, have more progressive disease or greater disability, be male, be unable to work due to MS, and smoke tobacco.

“There were no significant differences between cannabis users and nonusers in the use of MS medications, mean disease duration, or seeing a neurologist for treatment of MS,” stated Dr. Cohan, who is a neurologist and Medical Director of the Providence MS Center in Portland, Oregon.

Other complementary or alternative therapies used for MS included “other” (reported by 7.5% of survey responders), chiropractic (7.1%), acupuncture or acupressure (6.9%), naturopathy (3.8%), and biofeedback (0.6%). Regarding which MS symptoms were targeted by marijuana users, 82.2% used marijuana for fatigue, 76% for heat sensitivity, 74.7% for numbness, tingling, or pain, 68.5% for problems with thinking or memory, 67.1% for stiffness, spasms, or tremors in limbs, 62.3% for difficulty walking or maintaining balance, 58.2% for pain related to MS, 47.9% for impaired coordination, and 47.3% for depression and for problems with urination.

“Participants who used cannabis for their symptom management also reported higher unemployment due to MS, a higher impact of MS on quality of life, and greater disability,” Dr. Cohan commented. “The results highlight the need for in-depth studies on the impact of medical marijuana for management of MS symptoms. Follow-up studies will investigate the patient-reported impact of cannabis on symptom management.”

—Colby Stong

PHILADELPHIA—Cannabis is used by 8.6% of patients with multiple sclerosis (MS), making it the second most commonly used alternative therapy in this patient population, according to research reported at the 66th Annual Meeting of the American Academy of Neurology.

Patients with MS most frequently used marijuana for such symptoms as fatigue, heat sensitivity, and numbness, tingling, and pain. Massage was the leading alternative therapy used by patients with MS, reported by 12% of this group, said Stanley Cohan, MD, PhD, and his research colleagues.

The researchers sent surveys with questions related to demographics, symptoms of MS, disability status, quality of life, use of MS medications, and alternative therapies to patients with MS (ages 18 and older) who were enrolled in the Pacific Northwest MS Registry. Oregon and Washington are among the 20 states that allow the use of marijuana for medicinal purposes, and Washington is one of two states that have legalized marijuana for recreational use.

The investigators conducted analyses to determine the percentage of responders who reported cannabis use for MS symptoms and compared the data with those of nonusers according to demographic characteristics, score on the MS Impact Scale, responses on the Patient Determined Disease Steps questionnaire, and current symptoms using χ² and t-tests.

A total of 1,701 surveys (70%) were returned by patients in the registry; 8.6% of respondents reported current use of medical marijuana for their MS symptoms. The investigators found that patients who had used marijuana for MS were more likely to be younger, have more progressive disease or greater disability, be male, be unable to work due to MS, and smoke tobacco.

“There were no significant differences between cannabis users and nonusers in the use of MS medications, mean disease duration, or seeing a neurologist for treatment of MS,” stated Dr. Cohan, who is a neurologist and Medical Director of the Providence MS Center in Portland, Oregon.

Other complementary or alternative therapies used for MS included “other” (reported by 7.5% of survey responders), chiropractic (7.1%), acupuncture or acupressure (6.9%), naturopathy (3.8%), and biofeedback (0.6%). Regarding which MS symptoms were targeted by marijuana users, 82.2% used marijuana for fatigue, 76% for heat sensitivity, 74.7% for numbness, tingling, or pain, 68.5% for problems with thinking or memory, 67.1% for stiffness, spasms, or tremors in limbs, 62.3% for difficulty walking or maintaining balance, 58.2% for pain related to MS, 47.9% for impaired coordination, and 47.3% for depression and for problems with urination.

“Participants who used cannabis for their symptom management also reported higher unemployment due to MS, a higher impact of MS on quality of life, and greater disability,” Dr. Cohan commented. “The results highlight the need for in-depth studies on the impact of medical marijuana for management of MS symptoms. Follow-up studies will investigate the patient-reported impact of cannabis on symptom management.”

—Colby Stong

PHILADELPHIA—Cannabis is used by 8.6% of patients with multiple sclerosis (MS), making it the second most commonly used alternative therapy in this patient population, according to research reported at the 66th Annual Meeting of the American Academy of Neurology.

Patients with MS most frequently used marijuana for such symptoms as fatigue, heat sensitivity, and numbness, tingling, and pain. Massage was the leading alternative therapy used by patients with MS, reported by 12% of this group, said Stanley Cohan, MD, PhD, and his research colleagues.

The researchers sent surveys with questions related to demographics, symptoms of MS, disability status, quality of life, use of MS medications, and alternative therapies to patients with MS (ages 18 and older) who were enrolled in the Pacific Northwest MS Registry. Oregon and Washington are among the 20 states that allow the use of marijuana for medicinal purposes, and Washington is one of two states that have legalized marijuana for recreational use.

The investigators conducted analyses to determine the percentage of responders who reported cannabis use for MS symptoms and compared the data with those of nonusers according to demographic characteristics, score on the MS Impact Scale, responses on the Patient Determined Disease Steps questionnaire, and current symptoms using χ² and t-tests.

A total of 1,701 surveys (70%) were returned by patients in the registry; 8.6% of respondents reported current use of medical marijuana for their MS symptoms. The investigators found that patients who had used marijuana for MS were more likely to be younger, have more progressive disease or greater disability, be male, be unable to work due to MS, and smoke tobacco.

“There were no significant differences between cannabis users and nonusers in the use of MS medications, mean disease duration, or seeing a neurologist for treatment of MS,” stated Dr. Cohan, who is a neurologist and Medical Director of the Providence MS Center in Portland, Oregon.

Other complementary or alternative therapies used for MS included “other” (reported by 7.5% of survey responders), chiropractic (7.1%), acupuncture or acupressure (6.9%), naturopathy (3.8%), and biofeedback (0.6%). Regarding which MS symptoms were targeted by marijuana users, 82.2% used marijuana for fatigue, 76% for heat sensitivity, 74.7% for numbness, tingling, or pain, 68.5% for problems with thinking or memory, 67.1% for stiffness, spasms, or tremors in limbs, 62.3% for difficulty walking or maintaining balance, 58.2% for pain related to MS, 47.9% for impaired coordination, and 47.3% for depression and for problems with urination.

“Participants who used cannabis for their symptom management also reported higher unemployment due to MS, a higher impact of MS on quality of life, and greater disability,” Dr. Cohan commented. “The results highlight the need for in-depth studies on the impact of medical marijuana for management of MS symptoms. Follow-up studies will investigate the patient-reported impact of cannabis on symptom management.”

—Colby Stong

PHILADELPHIA—A new study suggests that targeting B cells may be associated with reduced disease activity for people with multiple sclerosis (MS). The study was presented at the 66th Annual Meeting of the American Academy of Neurology.

A total of 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of ofatumumab, an anti-B cell antibody, for 24 weeks, the first 12 of which were the placebo-controlled period.

The main objective was to determine the effects of ofatumumab dosing regimens, compared with placebo, on the total number of new brain lesions assessed every four weeks during a 12-week period.

All dose groups, including placebo, showed lesion activity in the first four weeks. Lesion suppression occurred in all ofatumumab dose groups from weeks four to 12. Researchers measured the amount of B cells in participants and compared it with the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.

When B cells were reduced to below a threshold of 64 cells/µL, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells/µL, compared with 16 lesions without treatment.

The most common side effects, defined as those occurring in at least 5% of participants and at a rate twice that of placebo for weeks zero to 12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection, and nerve pain.

Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, said that the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.

“These results need to be validated, of course, but the findings are interesting,” Dr. Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.”

Ofatumumab is not approved anywhere in the world for use in the treatment of MS.

NR Narrowing of Carotid Artery Without Warning May Signal Memory and Cognitive Decline
Narrowing of the carotid artery without any symptoms may be linked to problems in learning, memory, thinking, and decision-making, compared with people with similar risk factors but no narrowing of the carotid artery, according to a study presented by Moira Dux, PhD.

“To date, the focus of diagnosis and management of carotid artery blockages has been prevention of stroke, since that was the only harm that these blockages were thought to cause to patients,” said principal investigator Brajesh K. Lal, MD, of the VA Maryland Health Care System’s Baltimore VA Medical Center and the University of Maryland School of Medicine in Baltimore. “These results underscore the importance of assessing the status of memory and thinking in people with carotid artery narrowing.”

The study involved 67 people with asymptomatic carotid stenosis (ACS) and a 50% reduction in the diameter of the artery and 60 people with vascular risk factors but without the condition. Risk factors included diabetes, high blood pressure, high blood cholesterol, and coronary artery disease. The participants underwent extensive testing for overall thinking abilities and for specific aspects of thinking, such as processing speed, learning, memory, decision-making, and language.

Patients with ACS performed significantly worse on the overall memory and thinking tests. On testing of specific aspects of thinking, they performed worse on tests for motor and processing speed and tests for learning and memory. Language scores did not differ between the two groups.

“If these findings are confirmed in larger studies, they [will] hold significant implications for new treatment targets and open the door for more questions such as: should these patients be treated more aggressively with medications, cognitive rehabilitation, or even surgery to open up the artery,” said Dr. Lal. “I anticipate a large number of follow-up studies searching for causes and the best treatment option for this newly identified morbidity associated with carotid narrowing.”

Study Examines Risk of Early Death for People With Mild Cognitive Impairment
One of the first studies to look at a relationship between death and the two types of mild cognitive impairment (MCI) suggests that people who have cognitive problems but no memory problems might have a higher death rate in a period of six years, compared with people who have no cognitive or memory problems. The same increased death rate was suggested in the study for individuals who have MCI with memory decline. Patients with MCI and no memory loss had the highest death rate, however.

“Currently, there is little information about death and the types of memory loss that affect many millions of Americans,” said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minnesota. “Exploring how memory may or may not be linked with the length of life a person has is of tremendous significance as the population ages.” For the study, 862 people with thinking problems and 1,292 with no thinking problems between the ages of 70 and 89 were followed for nearly six years. Participants were from Olmsted County, Minnesota, and were given tests at the start of the study and every 15 months to assess their thinking abilities.

After six years, 331 of the group with MCI and 224 of the group without MCI died. Those who had MCI had an 80% higher death rate during the study than those without MCI. People with MCI and no memory loss had more than twice the death rate during the study than those without MCI, while people with MCI with memory loss had a 68% higher death rate during the study than those without MCI.

Low Tolerance for Pain? The Reason May Be Genetic
Researchers may have identified genes that affect individuals’ tolerance for pain. “Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, who is affiliated with Proove Biosciences. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for the genes COMT, DRD2, DRD1, and OPRK1. Participants, all of whom were taking prescription opioid pain medications, were asked to rate their perception of pain on a scale from 0 to 10. People who rated their pain as 0 were excluded from further study. Low pain perception was defined as a score of 1, 2, or 3; moderate pain perception as a score of 4, 5, or 6; and high pain perception as a score of 7 or higher. Approximately 9% of the participants had low pain perception, 46% had moderate pain perception, and 45% had high pain perception. The researchers found that the DRD1 gene variant was 33% more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were found 25% and 19% more often, respectively, than in individuals with a high pain perception. The DRD2 variant was 25% more common among people with a high pain perception, compared with people with moderate pain.

“Chronic pain can affect every other part of life,” said Dr. Onojjighofia. “Finding genes that may play a role in pain perception could provide a target for developing new therapies.

PHILADELPHIA—A new study suggests that targeting B cells may be associated with reduced disease activity for people with multiple sclerosis (MS). The study was presented at the 66th Annual Meeting of the American Academy of Neurology.

A total of 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of ofatumumab, an anti-B cell antibody, for 24 weeks, the first 12 of which were the placebo-controlled period.

The main objective was to determine the effects of ofatumumab dosing regimens, compared with placebo, on the total number of new brain lesions assessed every four weeks during a 12-week period.

All dose groups, including placebo, showed lesion activity in the first four weeks. Lesion suppression occurred in all ofatumumab dose groups from weeks four to 12. Researchers measured the amount of B cells in participants and compared it with the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.

When B cells were reduced to below a threshold of 64 cells/µL, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells/µL, compared with 16 lesions without treatment.

The most common side effects, defined as those occurring in at least 5% of participants and at a rate twice that of placebo for weeks zero to 12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection, and nerve pain.

Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, said that the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.

“These results need to be validated, of course, but the findings are interesting,” Dr. Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.”

Ofatumumab is not approved anywhere in the world for use in the treatment of MS.

NR Narrowing of Carotid Artery Without Warning May Signal Memory and Cognitive Decline
Narrowing of the carotid artery without any symptoms may be linked to problems in learning, memory, thinking, and decision-making, compared with people with similar risk factors but no narrowing of the carotid artery, according to a study presented by Moira Dux, PhD.

“To date, the focus of diagnosis and management of carotid artery blockages has been prevention of stroke, since that was the only harm that these blockages were thought to cause to patients,” said principal investigator Brajesh K. Lal, MD, of the VA Maryland Health Care System’s Baltimore VA Medical Center and the University of Maryland School of Medicine in Baltimore. “These results underscore the importance of assessing the status of memory and thinking in people with carotid artery narrowing.”

The study involved 67 people with asymptomatic carotid stenosis (ACS) and a 50% reduction in the diameter of the artery and 60 people with vascular risk factors but without the condition. Risk factors included diabetes, high blood pressure, high blood cholesterol, and coronary artery disease. The participants underwent extensive testing for overall thinking abilities and for specific aspects of thinking, such as processing speed, learning, memory, decision-making, and language.

Patients with ACS performed significantly worse on the overall memory and thinking tests. On testing of specific aspects of thinking, they performed worse on tests for motor and processing speed and tests for learning and memory. Language scores did not differ between the two groups.

“If these findings are confirmed in larger studies, they [will] hold significant implications for new treatment targets and open the door for more questions such as: should these patients be treated more aggressively with medications, cognitive rehabilitation, or even surgery to open up the artery,” said Dr. Lal. “I anticipate a large number of follow-up studies searching for causes and the best treatment option for this newly identified morbidity associated with carotid narrowing.”

Study Examines Risk of Early Death for People With Mild Cognitive Impairment
One of the first studies to look at a relationship between death and the two types of mild cognitive impairment (MCI) suggests that people who have cognitive problems but no memory problems might have a higher death rate in a period of six years, compared with people who have no cognitive or memory problems. The same increased death rate was suggested in the study for individuals who have MCI with memory decline. Patients with MCI and no memory loss had the highest death rate, however.

“Currently, there is little information about death and the types of memory loss that affect many millions of Americans,” said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minnesota. “Exploring how memory may or may not be linked with the length of life a person has is of tremendous significance as the population ages.” For the study, 862 people with thinking problems and 1,292 with no thinking problems between the ages of 70 and 89 were followed for nearly six years. Participants were from Olmsted County, Minnesota, and were given tests at the start of the study and every 15 months to assess their thinking abilities.

After six years, 331 of the group with MCI and 224 of the group without MCI died. Those who had MCI had an 80% higher death rate during the study than those without MCI. People with MCI and no memory loss had more than twice the death rate during the study than those without MCI, while people with MCI with memory loss had a 68% higher death rate during the study than those without MCI.

Low Tolerance for Pain? The Reason May Be Genetic
Researchers may have identified genes that affect individuals’ tolerance for pain. “Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, who is affiliated with Proove Biosciences. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for the genes COMT, DRD2, DRD1, and OPRK1. Participants, all of whom were taking prescription opioid pain medications, were asked to rate their perception of pain on a scale from 0 to 10. People who rated their pain as 0 were excluded from further study. Low pain perception was defined as a score of 1, 2, or 3; moderate pain perception as a score of 4, 5, or 6; and high pain perception as a score of 7 or higher. Approximately 9% of the participants had low pain perception, 46% had moderate pain perception, and 45% had high pain perception. The researchers found that the DRD1 gene variant was 33% more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were found 25% and 19% more often, respectively, than in individuals with a high pain perception. The DRD2 variant was 25% more common among people with a high pain perception, compared with people with moderate pain.

“Chronic pain can affect every other part of life,” said Dr. Onojjighofia. “Finding genes that may play a role in pain perception could provide a target for developing new therapies.

PHILADELPHIA—A new study suggests that targeting B cells may be associated with reduced disease activity for people with multiple sclerosis (MS). The study was presented at the 66th Annual Meeting of the American Academy of Neurology.

A total of 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of ofatumumab, an anti-B cell antibody, for 24 weeks, the first 12 of which were the placebo-controlled period.

The main objective was to determine the effects of ofatumumab dosing regimens, compared with placebo, on the total number of new brain lesions assessed every four weeks during a 12-week period.

All dose groups, including placebo, showed lesion activity in the first four weeks. Lesion suppression occurred in all ofatumumab dose groups from weeks four to 12. Researchers measured the amount of B cells in participants and compared it with the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.

When B cells were reduced to below a threshold of 64 cells/µL, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells/µL, compared with 16 lesions without treatment.

The most common side effects, defined as those occurring in at least 5% of participants and at a rate twice that of placebo for weeks zero to 12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection, and nerve pain.

Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, said that the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.

“These results need to be validated, of course, but the findings are interesting,” Dr. Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.”

Ofatumumab is not approved anywhere in the world for use in the treatment of MS.

NR Narrowing of Carotid Artery Without Warning May Signal Memory and Cognitive Decline
Narrowing of the carotid artery without any symptoms may be linked to problems in learning, memory, thinking, and decision-making, compared with people with similar risk factors but no narrowing of the carotid artery, according to a study presented by Moira Dux, PhD.

“To date, the focus of diagnosis and management of carotid artery blockages has been prevention of stroke, since that was the only harm that these blockages were thought to cause to patients,” said principal investigator Brajesh K. Lal, MD, of the VA Maryland Health Care System’s Baltimore VA Medical Center and the University of Maryland School of Medicine in Baltimore. “These results underscore the importance of assessing the status of memory and thinking in people with carotid artery narrowing.”

The study involved 67 people with asymptomatic carotid stenosis (ACS) and a 50% reduction in the diameter of the artery and 60 people with vascular risk factors but without the condition. Risk factors included diabetes, high blood pressure, high blood cholesterol, and coronary artery disease. The participants underwent extensive testing for overall thinking abilities and for specific aspects of thinking, such as processing speed, learning, memory, decision-making, and language.

Patients with ACS performed significantly worse on the overall memory and thinking tests. On testing of specific aspects of thinking, they performed worse on tests for motor and processing speed and tests for learning and memory. Language scores did not differ between the two groups.

“If these findings are confirmed in larger studies, they [will] hold significant implications for new treatment targets and open the door for more questions such as: should these patients be treated more aggressively with medications, cognitive rehabilitation, or even surgery to open up the artery,” said Dr. Lal. “I anticipate a large number of follow-up studies searching for causes and the best treatment option for this newly identified morbidity associated with carotid narrowing.”

Study Examines Risk of Early Death for People With Mild Cognitive Impairment
One of the first studies to look at a relationship between death and the two types of mild cognitive impairment (MCI) suggests that people who have cognitive problems but no memory problems might have a higher death rate in a period of six years, compared with people who have no cognitive or memory problems. The same increased death rate was suggested in the study for individuals who have MCI with memory decline. Patients with MCI and no memory loss had the highest death rate, however.

“Currently, there is little information about death and the types of memory loss that affect many millions of Americans,” said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minnesota. “Exploring how memory may or may not be linked with the length of life a person has is of tremendous significance as the population ages.” For the study, 862 people with thinking problems and 1,292 with no thinking problems between the ages of 70 and 89 were followed for nearly six years. Participants were from Olmsted County, Minnesota, and were given tests at the start of the study and every 15 months to assess their thinking abilities.

After six years, 331 of the group with MCI and 224 of the group without MCI died. Those who had MCI had an 80% higher death rate during the study than those without MCI. People with MCI and no memory loss had more than twice the death rate during the study than those without MCI, while people with MCI with memory loss had a 68% higher death rate during the study than those without MCI.

Low Tolerance for Pain? The Reason May Be Genetic
Researchers may have identified genes that affect individuals’ tolerance for pain. “Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, who is affiliated with Proove Biosciences. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for the genes COMT, DRD2, DRD1, and OPRK1. Participants, all of whom were taking prescription opioid pain medications, were asked to rate their perception of pain on a scale from 0 to 10. People who rated their pain as 0 were excluded from further study. Low pain perception was defined as a score of 1, 2, or 3; moderate pain perception as a score of 4, 5, or 6; and high pain perception as a score of 7 or higher. Approximately 9% of the participants had low pain perception, 46% had moderate pain perception, and 45% had high pain perception. The researchers found that the DRD1 gene variant was 33% more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were found 25% and 19% more often, respectively, than in individuals with a high pain perception. The DRD2 variant was 25% more common among people with a high pain perception, compared with people with moderate pain.

“Chronic pain can affect every other part of life,” said Dr. Onojjighofia. “Finding genes that may play a role in pain perception could provide a target for developing new therapies.

Conventional MRI brain images of patients with multiple sclerosis are "indistinguishable to the expert eye" from those of patients who have an MS-like disease associated with Leber’s hereditary optic neuropathy, according to a retrospective, case-control study.

Leber’s hereditary optic neuropathy (LHON), a mitochondrial abnormality inherited through the maternal line, is characterized by painless, subacute bilateral loss of vision that usually occurs in early adulthood. Very rarely, it is associated with a coexisting MS-like disease, which is often referred to as Harding’s disease. If the brain-imaging traits of these two disorders were found to be similar, it would suggest that they share a common pathophysiologic mechanism, said Dr. Lucy Matthews of the Nuffield Department of Clinical Neurosciences at Oxford (England) University, and her associates.

In what they described as "the first blinded observational study of the MRI features of LHON and LHON-associated MS," Dr. Matthews and her colleagues reviewed brain MRIs from patients treated at six clinical sites in Oxford; Milan and Siena, Italy; London; Bochum, Germany; and Copenhagen. A total of 31 patients had LHON, including 11 with LHON-associated MS. Their MRIs were compared with those from 30 age-matched control subjects who had MS alone (J. Neurol. Neurosurg. Psychiatry 2014 July 22 [doi:10.1136/jnnp-2014-308186]).

Three experts in the field of MRI and MS who were blinded to patients’ clinical and demographic data independently reviewed these MRIs. They found that the morphology and location of cerebral lesions were identical in LHON-associated MS and MS. Brain atrophy and hypointense T1 lesions were observed in both disorders.

In contrast, patients who had LHON alone showed T2 hyperintense white matter lesions, notably fewer oval lesions, and no Dawson’s fingers or diffuse-type lesions. Most of their lesions were 2-5 mm in size, while most of the lesions in the MS and LHON-associated MS patients were larger, some as big as 25 mm.

In addition, T2 lesions showed a similar distribution between patients with MS and patients with LHON-associated MS, while T2 lesions in the LHON-only group were uncommon in the corpus callosum and nonexistent in the cerebellum.

A total of 90% of the patients with MS and 73% of those with LHON-associated MS fulfilled McDonald’s criterion for the spatial dissemination of brain lesions, compared with only 6.7% of the patients who had LHON alone.

These findings support the idea that "MRI changes in LHON-associated MS are due to MS pathology and not a separate Leber’s mitochondrial-related process." They also suggest that mitochondrial pathways may be important in the development of MS, the investigators said.

The researchers also observed an "intriguing" influence of gender in these disorders. "The penetrance of LHON in women is much lower than in men. However, it appears that once a woman develops LHON clinically, she has a very high risk of developing either radiological or clinical MS. It is [neither] clear whether those with asymptomatic lesions at the time of MRI will develop clinical features in the future, nor what the risk is in asymptomatic female carriers of Leber’s mutation," they added.

This study was supported in part by the U.K. Medical Research Council. Dr. Matthews’s associates reported numerous ties to industry sources.

Conventional MRI brain images of patients with multiple sclerosis are "indistinguishable to the expert eye" from those of patients who have an MS-like disease associated with Leber’s hereditary optic neuropathy, according to a retrospective, case-control study.

Leber’s hereditary optic neuropathy (LHON), a mitochondrial abnormality inherited through the maternal line, is characterized by painless, subacute bilateral loss of vision that usually occurs in early adulthood. Very rarely, it is associated with a coexisting MS-like disease, which is often referred to as Harding’s disease. If the brain-imaging traits of these two disorders were found to be similar, it would suggest that they share a common pathophysiologic mechanism, said Dr. Lucy Matthews of the Nuffield Department of Clinical Neurosciences at Oxford (England) University, and her associates.

In what they described as "the first blinded observational study of the MRI features of LHON and LHON-associated MS," Dr. Matthews and her colleagues reviewed brain MRIs from patients treated at six clinical sites in Oxford; Milan and Siena, Italy; London; Bochum, Germany; and Copenhagen. A total of 31 patients had LHON, including 11 with LHON-associated MS. Their MRIs were compared with those from 30 age-matched control subjects who had MS alone (J. Neurol. Neurosurg. Psychiatry 2014 July 22 [doi:10.1136/jnnp-2014-308186]).

Three experts in the field of MRI and MS who were blinded to patients’ clinical and demographic data independently reviewed these MRIs. They found that the morphology and location of cerebral lesions were identical in LHON-associated MS and MS. Brain atrophy and hypointense T1 lesions were observed in both disorders.

In contrast, patients who had LHON alone showed T2 hyperintense white matter lesions, notably fewer oval lesions, and no Dawson’s fingers or diffuse-type lesions. Most of their lesions were 2-5 mm in size, while most of the lesions in the MS and LHON-associated MS patients were larger, some as big as 25 mm.

In addition, T2 lesions showed a similar distribution between patients with MS and patients with LHON-associated MS, while T2 lesions in the LHON-only group were uncommon in the corpus callosum and nonexistent in the cerebellum.

A total of 90% of the patients with MS and 73% of those with LHON-associated MS fulfilled McDonald’s criterion for the spatial dissemination of brain lesions, compared with only 6.7% of the patients who had LHON alone.

These findings support the idea that "MRI changes in LHON-associated MS are due to MS pathology and not a separate Leber’s mitochondrial-related process." They also suggest that mitochondrial pathways may be important in the development of MS, the investigators said.

The researchers also observed an "intriguing" influence of gender in these disorders. "The penetrance of LHON in women is much lower than in men. However, it appears that once a woman develops LHON clinically, she has a very high risk of developing either radiological or clinical MS. It is [neither] clear whether those with asymptomatic lesions at the time of MRI will develop clinical features in the future, nor what the risk is in asymptomatic female carriers of Leber’s mutation," they added.

This study was supported in part by the U.K. Medical Research Council. Dr. Matthews’s associates reported numerous ties to industry sources.

Conventional MRI brain images of patients with multiple sclerosis are "indistinguishable to the expert eye" from those of patients who have an MS-like disease associated with Leber’s hereditary optic neuropathy, according to a retrospective, case-control study.

Leber’s hereditary optic neuropathy (LHON), a mitochondrial abnormality inherited through the maternal line, is characterized by painless, subacute bilateral loss of vision that usually occurs in early adulthood. Very rarely, it is associated with a coexisting MS-like disease, which is often referred to as Harding’s disease. If the brain-imaging traits of these two disorders were found to be similar, it would suggest that they share a common pathophysiologic mechanism, said Dr. Lucy Matthews of the Nuffield Department of Clinical Neurosciences at Oxford (England) University, and her associates.

In what they described as "the first blinded observational study of the MRI features of LHON and LHON-associated MS," Dr. Matthews and her colleagues reviewed brain MRIs from patients treated at six clinical sites in Oxford; Milan and Siena, Italy; London; Bochum, Germany; and Copenhagen. A total of 31 patients had LHON, including 11 with LHON-associated MS. Their MRIs were compared with those from 30 age-matched control subjects who had MS alone (J. Neurol. Neurosurg. Psychiatry 2014 July 22 [doi:10.1136/jnnp-2014-308186]).

Three experts in the field of MRI and MS who were blinded to patients’ clinical and demographic data independently reviewed these MRIs. They found that the morphology and location of cerebral lesions were identical in LHON-associated MS and MS. Brain atrophy and hypointense T1 lesions were observed in both disorders.

In contrast, patients who had LHON alone showed T2 hyperintense white matter lesions, notably fewer oval lesions, and no Dawson’s fingers or diffuse-type lesions. Most of their lesions were 2-5 mm in size, while most of the lesions in the MS and LHON-associated MS patients were larger, some as big as 25 mm.

In addition, T2 lesions showed a similar distribution between patients with MS and patients with LHON-associated MS, while T2 lesions in the LHON-only group were uncommon in the corpus callosum and nonexistent in the cerebellum.

A total of 90% of the patients with MS and 73% of those with LHON-associated MS fulfilled McDonald’s criterion for the spatial dissemination of brain lesions, compared with only 6.7% of the patients who had LHON alone.

These findings support the idea that "MRI changes in LHON-associated MS are due to MS pathology and not a separate Leber’s mitochondrial-related process." They also suggest that mitochondrial pathways may be important in the development of MS, the investigators said.

The researchers also observed an "intriguing" influence of gender in these disorders. "The penetrance of LHON in women is much lower than in men. However, it appears that once a woman develops LHON clinically, she has a very high risk of developing either radiological or clinical MS. It is [neither] clear whether those with asymptomatic lesions at the time of MRI will develop clinical features in the future, nor what the risk is in asymptomatic female carriers of Leber’s mutation," they added.

This study was supported in part by the U.K. Medical Research Council. Dr. Matthews’s associates reported numerous ties to industry sources.