Multiple Sclerosis Hub

Several factors associated with worsening in timed 25-foot walk (T25FW) scores and other clinical indicators may be used to predict clinically significant change in patients with multiple sclerosis, according to an analysis of 1,544 patients.

Investigators reviewed patients who experienced a 20% or greater worsening in T25FW, and found the following factors related to disease progression:

• lower baseline Multiple Sclerosis Performance Scales (MSPS) scores

• sex, baseline T25FW, and time since diagnosis

• Patient Health Questionaire-9 (PHQ9) scores

The disease course time to worsening was significantly shorter for secondary progressive compared to relapsing-remitting disease.

Citation: Miller DM, Thompson NR, Cohen JA, et al. Factors associated with clinically significant increased walking time in multiple sclerosis: results of a survival analysis of short-term follow-up data from a clinical database. Mult Scler. 2015;21(4):457-465. doi: 10.1177/1352458514544536.

Several factors associated with worsening in timed 25-foot walk (T25FW) scores and other clinical indicators may be used to predict clinically significant change in patients with multiple sclerosis, according to an analysis of 1,544 patients.

Investigators reviewed patients who experienced a 20% or greater worsening in T25FW, and found the following factors related to disease progression:

• lower baseline Multiple Sclerosis Performance Scales (MSPS) scores

• sex, baseline T25FW, and time since diagnosis

• Patient Health Questionaire-9 (PHQ9) scores

The disease course time to worsening was significantly shorter for secondary progressive compared to relapsing-remitting disease.

Citation: Miller DM, Thompson NR, Cohen JA, et al. Factors associated with clinically significant increased walking time in multiple sclerosis: results of a survival analysis of short-term follow-up data from a clinical database. Mult Scler. 2015;21(4):457-465. doi: 10.1177/1352458514544536.

Several factors associated with worsening in timed 25-foot walk (T25FW) scores and other clinical indicators may be used to predict clinically significant change in patients with multiple sclerosis, according to an analysis of 1,544 patients.

Investigators reviewed patients who experienced a 20% or greater worsening in T25FW, and found the following factors related to disease progression:

• lower baseline Multiple Sclerosis Performance Scales (MSPS) scores

• sex, baseline T25FW, and time since diagnosis

• Patient Health Questionaire-9 (PHQ9) scores

The disease course time to worsening was significantly shorter for secondary progressive compared to relapsing-remitting disease.

Citation: Miller DM, Thompson NR, Cohen JA, et al. Factors associated with clinically significant increased walking time in multiple sclerosis: results of a survival analysis of short-term follow-up data from a clinical database. Mult Scler. 2015;21(4):457-465. doi: 10.1177/1352458514544536.

WASHINGTON, DC—Women with multiple sclerosis (MS) may have lower levels of important antioxidant and anti-inflammatory nutrients, such as folate from food and vitamin E, than healthy people, according to a study presented at the American Academy of Neurology’s 67th Annual Meeting.

For the study, researchers identified 27 Caucasian women with MS and compared them to 30 healthy Caucasian women between the ages of 18 and 60 and with BMI of less than or equal to 30 kg/m2. Participants reported on their diet and nutrition over the previous year prior to starting vitamin D supplementation.

On average, the women who had MS had lower levels of the following five nutrients with antioxidant or anti-inflammatory properties: food folate, vitamin E, magnesium, lutein-zeaxanthin, and quercetin. For food folate, the women with MS had average intake of 244 mg, while the healthy women had an average intake of 321 mg. The recommended daily allowance is 400 mg.

For magnesium, the women with MS had average intake of 254 mg, while the healthy women met the recommended daily allowance of 320 mg with an average of 321 mg. The women with MS also had a lower average percentage of their calories from fat than the healthy participants.

“Since MS is a chronic inflammatory disorder, having enough nutrients with anti-inflammatory properties may help prevent the disease or reduce the risk of attacks for those who already have MS,” said study author Sandra D. Cassard, ScD, of Johns Hopkins University in Baltimore. “Antioxidants are also critical to good health and help reduce the effects of other types of damage that can occur on a cellular level and contribute to neurologic diseases like MS. Whether the nutritional differences that we identified in the study are a cause of MS or a result of having it is not yet clear.”

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

WASHINGTON, DC—Women with multiple sclerosis (MS) may have lower levels of important antioxidant and anti-inflammatory nutrients, such as folate from food and vitamin E, than healthy people, according to a study presented at the American Academy of Neurology’s 67th Annual Meeting.

For the study, researchers identified 27 Caucasian women with MS and compared them to 30 healthy Caucasian women between the ages of 18 and 60 and with BMI of less than or equal to 30 kg/m2. Participants reported on their diet and nutrition over the previous year prior to starting vitamin D supplementation.

On average, the women who had MS had lower levels of the following five nutrients with antioxidant or anti-inflammatory properties: food folate, vitamin E, magnesium, lutein-zeaxanthin, and quercetin. For food folate, the women with MS had average intake of 244 mg, while the healthy women had an average intake of 321 mg. The recommended daily allowance is 400 mg.

For magnesium, the women with MS had average intake of 254 mg, while the healthy women met the recommended daily allowance of 320 mg with an average of 321 mg. The women with MS also had a lower average percentage of their calories from fat than the healthy participants.

“Since MS is a chronic inflammatory disorder, having enough nutrients with anti-inflammatory properties may help prevent the disease or reduce the risk of attacks for those who already have MS,” said study author Sandra D. Cassard, ScD, of Johns Hopkins University in Baltimore. “Antioxidants are also critical to good health and help reduce the effects of other types of damage that can occur on a cellular level and contribute to neurologic diseases like MS. Whether the nutritional differences that we identified in the study are a cause of MS or a result of having it is not yet clear.”

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

WASHINGTON, DC—Women with multiple sclerosis (MS) may have lower levels of important antioxidant and anti-inflammatory nutrients, such as folate from food and vitamin E, than healthy people, according to a study presented at the American Academy of Neurology’s 67th Annual Meeting.

For the study, researchers identified 27 Caucasian women with MS and compared them to 30 healthy Caucasian women between the ages of 18 and 60 and with BMI of less than or equal to 30 kg/m2. Participants reported on their diet and nutrition over the previous year prior to starting vitamin D supplementation.

On average, the women who had MS had lower levels of the following five nutrients with antioxidant or anti-inflammatory properties: food folate, vitamin E, magnesium, lutein-zeaxanthin, and quercetin. For food folate, the women with MS had average intake of 244 mg, while the healthy women had an average intake of 321 mg. The recommended daily allowance is 400 mg.

For magnesium, the women with MS had average intake of 254 mg, while the healthy women met the recommended daily allowance of 320 mg with an average of 321 mg. The women with MS also had a lower average percentage of their calories from fat than the healthy participants.

“Since MS is a chronic inflammatory disorder, having enough nutrients with anti-inflammatory properties may help prevent the disease or reduce the risk of attacks for those who already have MS,” said study author Sandra D. Cassard, ScD, of Johns Hopkins University in Baltimore. “Antioxidants are also critical to good health and help reduce the effects of other types of damage that can occur on a cellular level and contribute to neurologic diseases like MS. Whether the nutritional differences that we identified in the study are a cause of MS or a result of having it is not yet clear.”

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

Using computerized cognitive training can help to improve processing speed and working memory in patients with multiple sclerosis, according to a pilot study.

Investigators randomized subjects into 6 weeks of training in either an active or sham group, and found the active training group improved on measures of processing speed and attention, with significant improvements on measures of other domains.

The study authors noted the results provide preliminary evidence that cognitive training in multiple sclerosis patients may produce moderate improvements in select areas of cognitive functioning.

Citation: Hancock LM, Bruce JM, Bruce AS, Lynch SG. Processing speed and working memory training in multiple sclerosis: a double-blind randomized controlled pilot study. J Clin Exp Neuropsychol. 2015:1-15.

Commentary: Cognitive impairment in MS is common and can impact employment, driving, and quality of life. So often treatments require costly medications and expensive treatments. The few clinical trials to evaluate medications to improve memory in patients with MS have not demonstrated great efficacy. Information processing speed and attention are 2 cognitive domains commonly affected in MS. Computerized cognitive training might be a great opportunity and option to provide an effective treatment approach for those impacted and be delivered in a manner that could be inexpensive, easily made available, and accessible. This pilot study might provide great promise for those in need. —Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY.

Using computerized cognitive training can help to improve processing speed and working memory in patients with multiple sclerosis, according to a pilot study.

Investigators randomized subjects into 6 weeks of training in either an active or sham group, and found the active training group improved on measures of processing speed and attention, with significant improvements on measures of other domains.

The study authors noted the results provide preliminary evidence that cognitive training in multiple sclerosis patients may produce moderate improvements in select areas of cognitive functioning.

Citation: Hancock LM, Bruce JM, Bruce AS, Lynch SG. Processing speed and working memory training in multiple sclerosis: a double-blind randomized controlled pilot study. J Clin Exp Neuropsychol. 2015:1-15.

Commentary: Cognitive impairment in MS is common and can impact employment, driving, and quality of life. So often treatments require costly medications and expensive treatments. The few clinical trials to evaluate medications to improve memory in patients with MS have not demonstrated great efficacy. Information processing speed and attention are 2 cognitive domains commonly affected in MS. Computerized cognitive training might be a great opportunity and option to provide an effective treatment approach for those impacted and be delivered in a manner that could be inexpensive, easily made available, and accessible. This pilot study might provide great promise for those in need. —Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY.

Using computerized cognitive training can help to improve processing speed and working memory in patients with multiple sclerosis, according to a pilot study.

Investigators randomized subjects into 6 weeks of training in either an active or sham group, and found the active training group improved on measures of processing speed and attention, with significant improvements on measures of other domains.

The study authors noted the results provide preliminary evidence that cognitive training in multiple sclerosis patients may produce moderate improvements in select areas of cognitive functioning.

Citation: Hancock LM, Bruce JM, Bruce AS, Lynch SG. Processing speed and working memory training in multiple sclerosis: a double-blind randomized controlled pilot study. J Clin Exp Neuropsychol. 2015:1-15.

Commentary: Cognitive impairment in MS is common and can impact employment, driving, and quality of life. So often treatments require costly medications and expensive treatments. The few clinical trials to evaluate medications to improve memory in patients with MS have not demonstrated great efficacy. Information processing speed and attention are 2 cognitive domains commonly affected in MS. Computerized cognitive training might be a great opportunity and option to provide an effective treatment approach for those impacted and be delivered in a manner that could be inexpensive, easily made available, and accessible. This pilot study might provide great promise for those in need. —Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY.

Postmenopausal patients with multiple sclerosis report worsening disease severity on the Multiple Sclerosis Rating Scale (MSRS), according to an online cohort study on the PatientsLikeMe (PLM) platform.

Participants filled out a detailed reproductive history survey and linked to PLM’s prospectively collected patient-reported severity score. Of the 513 respondents:

• 55% were post-menopausal

• 54% of post-menopausal respondents reported induced menopause and were more likely to be treated with hormone replacement therapy

• median age at natural menopause was 51

Postmenopausal status, surgical menopause, and earlier age at menopause were associated with worse MSRS scores.

Citation: Bove R, Healy BC, Secor E, et al. Patients report worse MS symptoms after menopause: findings from an online cohort. Mult Scler Relat Disord. 2015;4(1):18-24. doi: 10.1016/j.msard.2014.11.009.

Postmenopausal patients with multiple sclerosis report worsening disease severity on the Multiple Sclerosis Rating Scale (MSRS), according to an online cohort study on the PatientsLikeMe (PLM) platform.

Participants filled out a detailed reproductive history survey and linked to PLM’s prospectively collected patient-reported severity score. Of the 513 respondents:

• 55% were post-menopausal

• 54% of post-menopausal respondents reported induced menopause and were more likely to be treated with hormone replacement therapy

• median age at natural menopause was 51

Postmenopausal status, surgical menopause, and earlier age at menopause were associated with worse MSRS scores.

Citation: Bove R, Healy BC, Secor E, et al. Patients report worse MS symptoms after menopause: findings from an online cohort. Mult Scler Relat Disord. 2015;4(1):18-24. doi: 10.1016/j.msard.2014.11.009.

Postmenopausal patients with multiple sclerosis report worsening disease severity on the Multiple Sclerosis Rating Scale (MSRS), according to an online cohort study on the PatientsLikeMe (PLM) platform.

Participants filled out a detailed reproductive history survey and linked to PLM’s prospectively collected patient-reported severity score. Of the 513 respondents:

• 55% were post-menopausal

• 54% of post-menopausal respondents reported induced menopause and were more likely to be treated with hormone replacement therapy

• median age at natural menopause was 51

Postmenopausal status, surgical menopause, and earlier age at menopause were associated with worse MSRS scores.

Citation: Bove R, Healy BC, Secor E, et al. Patients report worse MS symptoms after menopause: findings from an online cohort. Mult Scler Relat Disord. 2015;4(1):18-24. doi: 10.1016/j.msard.2014.11.009.

A biosocial approach including psychoeducational wellness programs for treating patients with multiple sclerosis may help to improve a patient’s overall quality of life and well-being, according to a 10-week study of the group sessions.

At baseline, 54 MS patients completed a series of self-reported questionnaires, then either attended 10, 90-minute weekly psychoeducational wellness group sessions or no interventions. The intervention was aimed at improving patients’ awareness of social, intellectual, emotional, and spiritual factors that can affect their overall well-being.

After 10 weeks study, subjects repeated the questionnaire and showed improvements in depression, anxiety, overall mental health, perceived stress, and pain, compared to the controls. No significant improvements were noted regarding social support, cognitive complaints, or fatigue.

Citation: McGuire KB, Stojanovic-Radic J, Strober L, Chiaravalloti ND, DeLuca J. Development and effectiveness of a psychoeducational wellness program for people with multiple sclerosis: description and outcomes. Int J MS Care. 2015;17(1):1-8. doi: 10.7224/1537-2073.2013-045.

A biosocial approach including psychoeducational wellness programs for treating patients with multiple sclerosis may help to improve a patient’s overall quality of life and well-being, according to a 10-week study of the group sessions.

At baseline, 54 MS patients completed a series of self-reported questionnaires, then either attended 10, 90-minute weekly psychoeducational wellness group sessions or no interventions. The intervention was aimed at improving patients’ awareness of social, intellectual, emotional, and spiritual factors that can affect their overall well-being.

After 10 weeks study, subjects repeated the questionnaire and showed improvements in depression, anxiety, overall mental health, perceived stress, and pain, compared to the controls. No significant improvements were noted regarding social support, cognitive complaints, or fatigue.

Citation: McGuire KB, Stojanovic-Radic J, Strober L, Chiaravalloti ND, DeLuca J. Development and effectiveness of a psychoeducational wellness program for people with multiple sclerosis: description and outcomes. Int J MS Care. 2015;17(1):1-8. doi: 10.7224/1537-2073.2013-045.

A biosocial approach including psychoeducational wellness programs for treating patients with multiple sclerosis may help to improve a patient’s overall quality of life and well-being, according to a 10-week study of the group sessions.

At baseline, 54 MS patients completed a series of self-reported questionnaires, then either attended 10, 90-minute weekly psychoeducational wellness group sessions or no interventions. The intervention was aimed at improving patients’ awareness of social, intellectual, emotional, and spiritual factors that can affect their overall well-being.

After 10 weeks study, subjects repeated the questionnaire and showed improvements in depression, anxiety, overall mental health, perceived stress, and pain, compared to the controls. No significant improvements were noted regarding social support, cognitive complaints, or fatigue.

Citation: McGuire KB, Stojanovic-Radic J, Strober L, Chiaravalloti ND, DeLuca J. Development and effectiveness of a psychoeducational wellness program for people with multiple sclerosis: description and outcomes. Int J MS Care. 2015;17(1):1-8. doi: 10.7224/1537-2073.2013-045.

Lower urinary tract symptoms (LUTS) are common among patients with multiple sclerosis, however they remain largely untreated, according to an online, cross-sectional survey of 1,052 individuals with MS.

One or more lower urinary tract symptoms were present in 92% of subjects with the most common as follows:

• Post-micturition dribble (64.9%)

• Urinary urgency (61.7%)

• Feeling of incomplete emptying (60.7%)

• Some type of UTI (79%)

Of those with symptoms, 70% previously discussed it with a health care provider, however, only 32% had seen a health care provider in the past year. Patients were more likely to seek treatment for urgency, intermittent urine stream, and urgency urinary incontinence.

Citation: Khalaf KM, Coyne KS, Globe DR, Armstrong EP, Malone DC, Burks J. Lower urinary tract symptom prevalence and management among patients with multiple sclerosis. Int J MS Care. 2015;17(1):14-25. doi: 10.7224/1537-2073.2013-040.

Lower urinary tract symptoms (LUTS) are common among patients with multiple sclerosis, however they remain largely untreated, according to an online, cross-sectional survey of 1,052 individuals with MS.

One or more lower urinary tract symptoms were present in 92% of subjects with the most common as follows:

• Post-micturition dribble (64.9%)

• Urinary urgency (61.7%)

• Feeling of incomplete emptying (60.7%)

• Some type of UTI (79%)

Of those with symptoms, 70% previously discussed it with a health care provider, however, only 32% had seen a health care provider in the past year. Patients were more likely to seek treatment for urgency, intermittent urine stream, and urgency urinary incontinence.

Citation: Khalaf KM, Coyne KS, Globe DR, Armstrong EP, Malone DC, Burks J. Lower urinary tract symptom prevalence and management among patients with multiple sclerosis. Int J MS Care. 2015;17(1):14-25. doi: 10.7224/1537-2073.2013-040.

Lower urinary tract symptoms (LUTS) are common among patients with multiple sclerosis, however they remain largely untreated, according to an online, cross-sectional survey of 1,052 individuals with MS.

One or more lower urinary tract symptoms were present in 92% of subjects with the most common as follows:

• Post-micturition dribble (64.9%)

• Urinary urgency (61.7%)

• Feeling of incomplete emptying (60.7%)

• Some type of UTI (79%)

Of those with symptoms, 70% previously discussed it with a health care provider, however, only 32% had seen a health care provider in the past year. Patients were more likely to seek treatment for urgency, intermittent urine stream, and urgency urinary incontinence.

Citation: Khalaf KM, Coyne KS, Globe DR, Armstrong EP, Malone DC, Burks J. Lower urinary tract symptom prevalence and management among patients with multiple sclerosis. Int J MS Care. 2015;17(1):14-25. doi: 10.7224/1537-2073.2013-040.

The modified Story Memory Technique (mSMT), a behavioral intervention aimed at improving new learning and memory in patients with multiple sclerosis, may help with processing speed and other cognitive markers, according to the double-blind, placebo-controlled, MEMREHAB trial of patients with clinically definite multiple sclerosis.

Participants were randomized to either mSMT or a placebo group, and underwent baseline and follow-up neuropsychological assessment. Compared to the control group, the treatment group showed significant improvements on California Verbal Learning Test (CVLT).

Investigators also note that performance on the Symbol Digit Modalities Test (SDMT) was a significant predictor of benefit from mSMT therapy, suggesting SDMT scores may serve as a proxy for overall cognitive impairment.

Citation: Chiaravalloti ND, DeLuca J. The influence of cognitive dysfunction on benefit from learning and memory rehabilitation in MS: a sub-analysis of the MEMREHAB trial. Mult Scler. 2015. pii: 1352458514567726.

The modified Story Memory Technique (mSMT), a behavioral intervention aimed at improving new learning and memory in patients with multiple sclerosis, may help with processing speed and other cognitive markers, according to the double-blind, placebo-controlled, MEMREHAB trial of patients with clinically definite multiple sclerosis.

Participants were randomized to either mSMT or a placebo group, and underwent baseline and follow-up neuropsychological assessment. Compared to the control group, the treatment group showed significant improvements on California Verbal Learning Test (CVLT).

Investigators also note that performance on the Symbol Digit Modalities Test (SDMT) was a significant predictor of benefit from mSMT therapy, suggesting SDMT scores may serve as a proxy for overall cognitive impairment.

Citation: Chiaravalloti ND, DeLuca J. The influence of cognitive dysfunction on benefit from learning and memory rehabilitation in MS: a sub-analysis of the MEMREHAB trial. Mult Scler. 2015. pii: 1352458514567726.

The modified Story Memory Technique (mSMT), a behavioral intervention aimed at improving new learning and memory in patients with multiple sclerosis, may help with processing speed and other cognitive markers, according to the double-blind, placebo-controlled, MEMREHAB trial of patients with clinically definite multiple sclerosis.

Participants were randomized to either mSMT or a placebo group, and underwent baseline and follow-up neuropsychological assessment. Compared to the control group, the treatment group showed significant improvements on California Verbal Learning Test (CVLT).

Investigators also note that performance on the Symbol Digit Modalities Test (SDMT) was a significant predictor of benefit from mSMT therapy, suggesting SDMT scores may serve as a proxy for overall cognitive impairment.

Citation: Chiaravalloti ND, DeLuca J. The influence of cognitive dysfunction on benefit from learning and memory rehabilitation in MS: a sub-analysis of the MEMREHAB trial. Mult Scler. 2015. pii: 1352458514567726.

Researchers have identified a genetic variation that significantly increases women’s risk of developing multiple sclerosis (MS). The variant, a single nucleotide polymorphism (SNP) in the gene serine-threonine-kinase 11 (STK11), occurs approximately 1.7 times more often in women with MS than in women without the disease, according to a study published February 18 in ASN Neuro.

Researchers zeroed in on the STK11 SNP after a woman told study coordinator and lead author Anne I. Boullerne, PhD, Research Assistant Professor of Anesthesiology at the University of Illinois at Chicago, that she and her four siblings all had MS or clinically isolated syndrome. The five siblings—four sisters, including twins, and a brother—were between ages 23 and 26.

The woman, who was participating in another medical study at the university, also described a prevalence of diseases associated with Peutz–Jeghers syndrome, a rare genetic disease caused by mutations in the STK11 gene, on her mother’s side of the family. The syndrome is characterized by an increased risk for certain cancers, including breast, ovary, and colon cancers.

Gene Tied to Loss of Myelin in Mice
A literature search by senior author Douglas L. Feinstein, PhD, Professor of Anesthesiology at the University of Illinois at Chicago and Research Biologist at the Jesse Brown VA Medical Center, uncovered an article that described how mice with a disabled STK11 gene had a higher incidence of loss of myelin from the nerves of the CNS, a defining characteristic of MS.

The woman consented to a complete DNA sequencing of her genome, and Dr. Boullerne examined the STK11 gene, where she discovered the SNP. Dr. Boullerne then obtained consent to sequence the genomes of two of the woman’s sisters and found that they carried the same SNP. Researchers do not know whether the other two siblings have the same variation.

The authors then screened DNA samples from approximately 1,400 people, including 754 people with MS. They found that the SNP was 1.66 times as prevalent in women with MS as in women without the disease. That makes the variant “one of the strongest genetic risk factors for MS discovered to date,” Dr. Feinstein said.

Researchers compared DNA samples from 654 patients with relapsing-remitting MS (RRMS), 100 patients with primary progressive MS (PPMS), and 661 controls.

While the STK11 SNP is present in about 7% of the general population, the variant was present in approximately 11% of the women with MS. In men, the risk of RRMS was only modestly increased by the STK11 SNP, and none of the male patients with PPMS had the variant.

Variant Associated With Reduced Disease Severity
The STK11 SNP was not associated with disease duration or onset. However, it was significantly associated with reduced disease severity, with the lowest MS severity scores in patients who also harbored the HLA-DRB1*1501 allele, the strongest known genetic risk factor for MS.

The researchers plan to continue looking for other genetic risk factors for MS among the five siblings and possibly their parents. Dr. Boullerne found no published studies that identified five siblings with MS. Identifying the five siblings with MS and suspected MS is an opportunity to pinpoint genes related to the disease, she said.

“I was immediately interested in the possibility of a genetic study of the family because all five siblings—an entire generation—are affected by MS, and so we could have a very good chance of discovering key genes related to inheritance of the disease,” Dr. Boullerne said.

Researchers also will investigate the function of the STK11 gene in the laboratory, which could reveal molecular pathways involved in MS. Their findings raise the possibility that cells harboring the STK11 SNP could be targeted by drugs that increase metabolic stress.

Rarity of Cases Has Limited Analyses
Genetic factors are known to influence the risk of developing MS, but the rarity of multigenerational cases of MS, or families with four or more affected members, has limited further analyses, said the authors.

Several studies have identified the HLA-DRB1*1501 allele as a variant associated with increased risk, with an odds ratio of approximately 3 across various ethnic groups.

The STK11 SNP had odds ratios for females of 1.63 in RRMS, 1.88 in PPMS, and 1.66 for both MS forms.

The different ratios for women with RRMS and PPMS could result from the different group sizes used in the study (ie, 56 female patients with PPMS, compared with 396 female patients with RRMS) or because of differences in the development and evolution of PPMS and RRMS, said the authors.

—Jake Remaly

Researchers have identified a genetic variation that significantly increases women’s risk of developing multiple sclerosis (MS). The variant, a single nucleotide polymorphism (SNP) in the gene serine-threonine-kinase 11 (STK11), occurs approximately 1.7 times more often in women with MS than in women without the disease, according to a study published February 18 in ASN Neuro.

Researchers zeroed in on the STK11 SNP after a woman told study coordinator and lead author Anne I. Boullerne, PhD, Research Assistant Professor of Anesthesiology at the University of Illinois at Chicago, that she and her four siblings all had MS or clinically isolated syndrome. The five siblings—four sisters, including twins, and a brother—were between ages 23 and 26.

The woman, who was participating in another medical study at the university, also described a prevalence of diseases associated with Peutz–Jeghers syndrome, a rare genetic disease caused by mutations in the STK11 gene, on her mother’s side of the family. The syndrome is characterized by an increased risk for certain cancers, including breast, ovary, and colon cancers.

Gene Tied to Loss of Myelin in Mice
A literature search by senior author Douglas L. Feinstein, PhD, Professor of Anesthesiology at the University of Illinois at Chicago and Research Biologist at the Jesse Brown VA Medical Center, uncovered an article that described how mice with a disabled STK11 gene had a higher incidence of loss of myelin from the nerves of the CNS, a defining characteristic of MS.

The woman consented to a complete DNA sequencing of her genome, and Dr. Boullerne examined the STK11 gene, where she discovered the SNP. Dr. Boullerne then obtained consent to sequence the genomes of two of the woman’s sisters and found that they carried the same SNP. Researchers do not know whether the other two siblings have the same variation.

The authors then screened DNA samples from approximately 1,400 people, including 754 people with MS. They found that the SNP was 1.66 times as prevalent in women with MS as in women without the disease. That makes the variant “one of the strongest genetic risk factors for MS discovered to date,” Dr. Feinstein said.

Researchers compared DNA samples from 654 patients with relapsing-remitting MS (RRMS), 100 patients with primary progressive MS (PPMS), and 661 controls.

While the STK11 SNP is present in about 7% of the general population, the variant was present in approximately 11% of the women with MS. In men, the risk of RRMS was only modestly increased by the STK11 SNP, and none of the male patients with PPMS had the variant.

Variant Associated With Reduced Disease Severity
The STK11 SNP was not associated with disease duration or onset. However, it was significantly associated with reduced disease severity, with the lowest MS severity scores in patients who also harbored the HLA-DRB1*1501 allele, the strongest known genetic risk factor for MS.

The researchers plan to continue looking for other genetic risk factors for MS among the five siblings and possibly their parents. Dr. Boullerne found no published studies that identified five siblings with MS. Identifying the five siblings with MS and suspected MS is an opportunity to pinpoint genes related to the disease, she said.

“I was immediately interested in the possibility of a genetic study of the family because all five siblings—an entire generation—are affected by MS, and so we could have a very good chance of discovering key genes related to inheritance of the disease,” Dr. Boullerne said.

Researchers also will investigate the function of the STK11 gene in the laboratory, which could reveal molecular pathways involved in MS. Their findings raise the possibility that cells harboring the STK11 SNP could be targeted by drugs that increase metabolic stress.

Rarity of Cases Has Limited Analyses
Genetic factors are known to influence the risk of developing MS, but the rarity of multigenerational cases of MS, or families with four or more affected members, has limited further analyses, said the authors.

Several studies have identified the HLA-DRB1*1501 allele as a variant associated with increased risk, with an odds ratio of approximately 3 across various ethnic groups.

The STK11 SNP had odds ratios for females of 1.63 in RRMS, 1.88 in PPMS, and 1.66 for both MS forms.

The different ratios for women with RRMS and PPMS could result from the different group sizes used in the study (ie, 56 female patients with PPMS, compared with 396 female patients with RRMS) or because of differences in the development and evolution of PPMS and RRMS, said the authors.

—Jake Remaly

Researchers have identified a genetic variation that significantly increases women’s risk of developing multiple sclerosis (MS). The variant, a single nucleotide polymorphism (SNP) in the gene serine-threonine-kinase 11 (STK11), occurs approximately 1.7 times more often in women with MS than in women without the disease, according to a study published February 18 in ASN Neuro.

Researchers zeroed in on the STK11 SNP after a woman told study coordinator and lead author Anne I. Boullerne, PhD, Research Assistant Professor of Anesthesiology at the University of Illinois at Chicago, that she and her four siblings all had MS or clinically isolated syndrome. The five siblings—four sisters, including twins, and a brother—were between ages 23 and 26.

The woman, who was participating in another medical study at the university, also described a prevalence of diseases associated with Peutz–Jeghers syndrome, a rare genetic disease caused by mutations in the STK11 gene, on her mother’s side of the family. The syndrome is characterized by an increased risk for certain cancers, including breast, ovary, and colon cancers.

Gene Tied to Loss of Myelin in Mice
A literature search by senior author Douglas L. Feinstein, PhD, Professor of Anesthesiology at the University of Illinois at Chicago and Research Biologist at the Jesse Brown VA Medical Center, uncovered an article that described how mice with a disabled STK11 gene had a higher incidence of loss of myelin from the nerves of the CNS, a defining characteristic of MS.

The woman consented to a complete DNA sequencing of her genome, and Dr. Boullerne examined the STK11 gene, where she discovered the SNP. Dr. Boullerne then obtained consent to sequence the genomes of two of the woman’s sisters and found that they carried the same SNP. Researchers do not know whether the other two siblings have the same variation.

The authors then screened DNA samples from approximately 1,400 people, including 754 people with MS. They found that the SNP was 1.66 times as prevalent in women with MS as in women without the disease. That makes the variant “one of the strongest genetic risk factors for MS discovered to date,” Dr. Feinstein said.

Researchers compared DNA samples from 654 patients with relapsing-remitting MS (RRMS), 100 patients with primary progressive MS (PPMS), and 661 controls.

While the STK11 SNP is present in about 7% of the general population, the variant was present in approximately 11% of the women with MS. In men, the risk of RRMS was only modestly increased by the STK11 SNP, and none of the male patients with PPMS had the variant.

Variant Associated With Reduced Disease Severity
The STK11 SNP was not associated with disease duration or onset. However, it was significantly associated with reduced disease severity, with the lowest MS severity scores in patients who also harbored the HLA-DRB1*1501 allele, the strongest known genetic risk factor for MS.

The researchers plan to continue looking for other genetic risk factors for MS among the five siblings and possibly their parents. Dr. Boullerne found no published studies that identified five siblings with MS. Identifying the five siblings with MS and suspected MS is an opportunity to pinpoint genes related to the disease, she said.

“I was immediately interested in the possibility of a genetic study of the family because all five siblings—an entire generation—are affected by MS, and so we could have a very good chance of discovering key genes related to inheritance of the disease,” Dr. Boullerne said.

Researchers also will investigate the function of the STK11 gene in the laboratory, which could reveal molecular pathways involved in MS. Their findings raise the possibility that cells harboring the STK11 SNP could be targeted by drugs that increase metabolic stress.

Rarity of Cases Has Limited Analyses
Genetic factors are known to influence the risk of developing MS, but the rarity of multigenerational cases of MS, or families with four or more affected members, has limited further analyses, said the authors.

Several studies have identified the HLA-DRB1*1501 allele as a variant associated with increased risk, with an odds ratio of approximately 3 across various ethnic groups.

The STK11 SNP had odds ratios for females of 1.63 in RRMS, 1.88 in PPMS, and 1.66 for both MS forms.

The different ratios for women with RRMS and PPMS could result from the different group sizes used in the study (ie, 56 female patients with PPMS, compared with 396 female patients with RRMS) or because of differences in the development and evolution of PPMS and RRMS, said the authors.

—Jake Remaly

A new research initiative for multiple sclerosis (MS) is seeking to recruit 20,000 people with MS—about 5% of the estimated US population with the disease—by this September, and aims to change the way MS research is conducted.

The web-based initiative, called iConquerMS, was formed with the help of a nearly $1-million contract from the Patient-Centered Outcomes Research Institute set up under the Affordable Care Act of 2010. iConquerMS is led by the Accelerated Cure Project for MS, a nonprofit research organization based in Waltham, Massachusetts.

Among the group’s initiatives is OPT-UP, a five-year, clinic-based study designed to compare patient outcomes from all the approved MS treatments and develop the evidence base for personalized medicine for MS. iConquerMS grew out of Accelerated Cure’s large-scale biospecimen and data repository, as well as the planning phase of OPT-UP, said Robert McBurney, PhD, the CEO of Accelerated Cure and the principal investigator for iConquerMS.

“Patients recruited into OPT-UP could become part of iConquerMS. But OPT-UP seeks only 2,500 patients,” Dr. McBurney said, “while iConquerMS is soliciting participation from a much larger number of MS patients, along with other participants, such as friends and relatives of people with MS, who want to contribute their data.”

The combination of the registry and OPT-UP “gives us the pathway to start a very long-term study of MS,” Dr. McBurney said. “Perhaps the children of people with MS will sign up as well. OPT-UP plus iConquerMS really has the possibility of becoming the Framingham of MS.” To date, iConquerMS has enrolled about 1,000 participants who are encouraged to contribute their health information through surveys and electronic health records.

New Registry Joins Several Existing MS Patient Registries
iConquerMS joins a handful of existing MS patient registries, including the 20-year-old North American Research Committee on MS (NARCOMS), a nonprofit registry with more than 36,000 patients, and the newly established North American Registry for Care and Research in MS (NARCRMS). Patients Like Me, a for-profit registry founded in 2004 for people with chronic diseases, now counts about 38,000 members with MS.

June Halper, CEO of the Hackensack, New Jersey-based Consortium of MS Centers (CMSC), which administers NARCOMS and NARCRMS, said that while there is some sense of competition among the MS registries, there should be no dearth of patients to enroll and many opportunities to collaborate.

“We hope that not too far into this picture we will be able to work with iConquerMS,” she said, “because the more we know about MS from the patient’s perspective, the better it’s going to be. One of the things we don’t have is any kind of comparative study comparing outcomes of one disease-modifying drug to another, and OPT-UP is seeking to do that, which is very important,” she added.

Ms. Halper said that in 1995, when the NARCOMS registry was established, “all we could do was symptomatic management, and we could treat relapses, but there were no disease-modifying therapies. We didn’t have MRI. We had rehab but we didn’t know much about it. People with MS were told to rest a lot by their neurologists.”

The NARCOMS surveys—now mostly online—were conducted then as mailed questionnaires. Deidentified patient-reported data from NARCOMS have since generated dozens of papers with findings on smoking, vitamin D, reproduction, depression, fatigue, comorbidities, and other subjects.

Dr. McBurney noted that the patient-centric approach is consistent with broader trends in MS clinical research favoring more nuanced measures of patient outcomes “well beyond MRI and the 25-foot walk,” he said. “These don’t capture the whole experience, and it’s important to incorporate the patient voice in outcome measures.”

NARCOMS relies exclusively on patient-reported information. The registry does not draw on medical records or validation of disease status, though one study found that virtually all NARCOMS participants have an MS diagnosis, Ms. Halper said. Patients Like Me is similarly reliant on patient-reported data.

Patient- and Physician-Reported Information
The two new initiatives, iConquerMS and NARCRMS, differ from prior registries in that they add a significant component of physician-reported data to complement the patient portal. iConquerMS, for example, requests submission of electronic health records. “The anchor of the electronic health record is helpful to confirm some of the information contributed by the patient, but the most important part is patient-reported health information,” Dr. McBurney said.

NARCRMS—launched as a complement to NARCOMS—focuses as much on physician reports as patient reports to create “a concurrent longitudinal database that simultaneously captures both patient-based and physician-based information,” according to its website. The site, which also will incorporate imaging data, is modeled closely after an open-access Alzheimer’s disease database—the Alzheimer’s Disease Neuroimaging Initiative. Participating patients will be able to access the database to see how they compare with others.

Industry participation varies among the registries. NARCOMS does not receive money from industry except for use in selected studies, while Patients Like Me sells deidentified patient data to pharmaceutical and device manufacturers. NARCRMS allows its industry sponsors full access to its data, and iConquerMS has also received industry support.

More Data Yield More Answers
The proliferation of registries should bring MS research closer to that seen with other chronic diseases, said Ms. Halper. While people are being diagnosed more quickly, and more treatments are available, there is still a lot of work to be done, she said. “We don’t know a heck of a lot about MS, and everybody wants to know more. We need data.”

Dr. McBurney concurred. “We’re making an impact on the early relapsing-remitting phase of the disorder, but to date, no drugs have been approved for progressive MS. Maybe they’re not even the same disease. We still have very little idea which patient is going to benefit from any particular treatment strategy without experiencing troubling side effects,” he said. Registry data may help answer these and other questions.

—Jennie Smith

A new research initiative for multiple sclerosis (MS) is seeking to recruit 20,000 people with MS—about 5% of the estimated US population with the disease—by this September, and aims to change the way MS research is conducted.

The web-based initiative, called iConquerMS, was formed with the help of a nearly $1-million contract from the Patient-Centered Outcomes Research Institute set up under the Affordable Care Act of 2010. iConquerMS is led by the Accelerated Cure Project for MS, a nonprofit research organization based in Waltham, Massachusetts.

Among the group’s initiatives is OPT-UP, a five-year, clinic-based study designed to compare patient outcomes from all the approved MS treatments and develop the evidence base for personalized medicine for MS. iConquerMS grew out of Accelerated Cure’s large-scale biospecimen and data repository, as well as the planning phase of OPT-UP, said Robert McBurney, PhD, the CEO of Accelerated Cure and the principal investigator for iConquerMS.

“Patients recruited into OPT-UP could become part of iConquerMS. But OPT-UP seeks only 2,500 patients,” Dr. McBurney said, “while iConquerMS is soliciting participation from a much larger number of MS patients, along with other participants, such as friends and relatives of people with MS, who want to contribute their data.”

The combination of the registry and OPT-UP “gives us the pathway to start a very long-term study of MS,” Dr. McBurney said. “Perhaps the children of people with MS will sign up as well. OPT-UP plus iConquerMS really has the possibility of becoming the Framingham of MS.” To date, iConquerMS has enrolled about 1,000 participants who are encouraged to contribute their health information through surveys and electronic health records.

New Registry Joins Several Existing MS Patient Registries
iConquerMS joins a handful of existing MS patient registries, including the 20-year-old North American Research Committee on MS (NARCOMS), a nonprofit registry with more than 36,000 patients, and the newly established North American Registry for Care and Research in MS (NARCRMS). Patients Like Me, a for-profit registry founded in 2004 for people with chronic diseases, now counts about 38,000 members with MS.

June Halper, CEO of the Hackensack, New Jersey-based Consortium of MS Centers (CMSC), which administers NARCOMS and NARCRMS, said that while there is some sense of competition among the MS registries, there should be no dearth of patients to enroll and many opportunities to collaborate.

“We hope that not too far into this picture we will be able to work with iConquerMS,” she said, “because the more we know about MS from the patient’s perspective, the better it’s going to be. One of the things we don’t have is any kind of comparative study comparing outcomes of one disease-modifying drug to another, and OPT-UP is seeking to do that, which is very important,” she added.

Ms. Halper said that in 1995, when the NARCOMS registry was established, “all we could do was symptomatic management, and we could treat relapses, but there were no disease-modifying therapies. We didn’t have MRI. We had rehab but we didn’t know much about it. People with MS were told to rest a lot by their neurologists.”

The NARCOMS surveys—now mostly online—were conducted then as mailed questionnaires. Deidentified patient-reported data from NARCOMS have since generated dozens of papers with findings on smoking, vitamin D, reproduction, depression, fatigue, comorbidities, and other subjects.

Dr. McBurney noted that the patient-centric approach is consistent with broader trends in MS clinical research favoring more nuanced measures of patient outcomes “well beyond MRI and the 25-foot walk,” he said. “These don’t capture the whole experience, and it’s important to incorporate the patient voice in outcome measures.”

NARCOMS relies exclusively on patient-reported information. The registry does not draw on medical records or validation of disease status, though one study found that virtually all NARCOMS participants have an MS diagnosis, Ms. Halper said. Patients Like Me is similarly reliant on patient-reported data.

Patient- and Physician-Reported Information
The two new initiatives, iConquerMS and NARCRMS, differ from prior registries in that they add a significant component of physician-reported data to complement the patient portal. iConquerMS, for example, requests submission of electronic health records. “The anchor of the electronic health record is helpful to confirm some of the information contributed by the patient, but the most important part is patient-reported health information,” Dr. McBurney said.

NARCRMS—launched as a complement to NARCOMS—focuses as much on physician reports as patient reports to create “a concurrent longitudinal database that simultaneously captures both patient-based and physician-based information,” according to its website. The site, which also will incorporate imaging data, is modeled closely after an open-access Alzheimer’s disease database—the Alzheimer’s Disease Neuroimaging Initiative. Participating patients will be able to access the database to see how they compare with others.

Industry participation varies among the registries. NARCOMS does not receive money from industry except for use in selected studies, while Patients Like Me sells deidentified patient data to pharmaceutical and device manufacturers. NARCRMS allows its industry sponsors full access to its data, and iConquerMS has also received industry support.

More Data Yield More Answers
The proliferation of registries should bring MS research closer to that seen with other chronic diseases, said Ms. Halper. While people are being diagnosed more quickly, and more treatments are available, there is still a lot of work to be done, she said. “We don’t know a heck of a lot about MS, and everybody wants to know more. We need data.”

Dr. McBurney concurred. “We’re making an impact on the early relapsing-remitting phase of the disorder, but to date, no drugs have been approved for progressive MS. Maybe they’re not even the same disease. We still have very little idea which patient is going to benefit from any particular treatment strategy without experiencing troubling side effects,” he said. Registry data may help answer these and other questions.

—Jennie Smith

A new research initiative for multiple sclerosis (MS) is seeking to recruit 20,000 people with MS—about 5% of the estimated US population with the disease—by this September, and aims to change the way MS research is conducted.

The web-based initiative, called iConquerMS, was formed with the help of a nearly $1-million contract from the Patient-Centered Outcomes Research Institute set up under the Affordable Care Act of 2010. iConquerMS is led by the Accelerated Cure Project for MS, a nonprofit research organization based in Waltham, Massachusetts.

Among the group’s initiatives is OPT-UP, a five-year, clinic-based study designed to compare patient outcomes from all the approved MS treatments and develop the evidence base for personalized medicine for MS. iConquerMS grew out of Accelerated Cure’s large-scale biospecimen and data repository, as well as the planning phase of OPT-UP, said Robert McBurney, PhD, the CEO of Accelerated Cure and the principal investigator for iConquerMS.

“Patients recruited into OPT-UP could become part of iConquerMS. But OPT-UP seeks only 2,500 patients,” Dr. McBurney said, “while iConquerMS is soliciting participation from a much larger number of MS patients, along with other participants, such as friends and relatives of people with MS, who want to contribute their data.”

The combination of the registry and OPT-UP “gives us the pathway to start a very long-term study of MS,” Dr. McBurney said. “Perhaps the children of people with MS will sign up as well. OPT-UP plus iConquerMS really has the possibility of becoming the Framingham of MS.” To date, iConquerMS has enrolled about 1,000 participants who are encouraged to contribute their health information through surveys and electronic health records.

New Registry Joins Several Existing MS Patient Registries
iConquerMS joins a handful of existing MS patient registries, including the 20-year-old North American Research Committee on MS (NARCOMS), a nonprofit registry with more than 36,000 patients, and the newly established North American Registry for Care and Research in MS (NARCRMS). Patients Like Me, a for-profit registry founded in 2004 for people with chronic diseases, now counts about 38,000 members with MS.

June Halper, CEO of the Hackensack, New Jersey-based Consortium of MS Centers (CMSC), which administers NARCOMS and NARCRMS, said that while there is some sense of competition among the MS registries, there should be no dearth of patients to enroll and many opportunities to collaborate.

“We hope that not too far into this picture we will be able to work with iConquerMS,” she said, “because the more we know about MS from the patient’s perspective, the better it’s going to be. One of the things we don’t have is any kind of comparative study comparing outcomes of one disease-modifying drug to another, and OPT-UP is seeking to do that, which is very important,” she added.

Ms. Halper said that in 1995, when the NARCOMS registry was established, “all we could do was symptomatic management, and we could treat relapses, but there were no disease-modifying therapies. We didn’t have MRI. We had rehab but we didn’t know much about it. People with MS were told to rest a lot by their neurologists.”

The NARCOMS surveys—now mostly online—were conducted then as mailed questionnaires. Deidentified patient-reported data from NARCOMS have since generated dozens of papers with findings on smoking, vitamin D, reproduction, depression, fatigue, comorbidities, and other subjects.

Dr. McBurney noted that the patient-centric approach is consistent with broader trends in MS clinical research favoring more nuanced measures of patient outcomes “well beyond MRI and the 25-foot walk,” he said. “These don’t capture the whole experience, and it’s important to incorporate the patient voice in outcome measures.”

NARCOMS relies exclusively on patient-reported information. The registry does not draw on medical records or validation of disease status, though one study found that virtually all NARCOMS participants have an MS diagnosis, Ms. Halper said. Patients Like Me is similarly reliant on patient-reported data.

Patient- and Physician-Reported Information
The two new initiatives, iConquerMS and NARCRMS, differ from prior registries in that they add a significant component of physician-reported data to complement the patient portal. iConquerMS, for example, requests submission of electronic health records. “The anchor of the electronic health record is helpful to confirm some of the information contributed by the patient, but the most important part is patient-reported health information,” Dr. McBurney said.

NARCRMS—launched as a complement to NARCOMS—focuses as much on physician reports as patient reports to create “a concurrent longitudinal database that simultaneously captures both patient-based and physician-based information,” according to its website. The site, which also will incorporate imaging data, is modeled closely after an open-access Alzheimer’s disease database—the Alzheimer’s Disease Neuroimaging Initiative. Participating patients will be able to access the database to see how they compare with others.

Industry participation varies among the registries. NARCOMS does not receive money from industry except for use in selected studies, while Patients Like Me sells deidentified patient data to pharmaceutical and device manufacturers. NARCRMS allows its industry sponsors full access to its data, and iConquerMS has also received industry support.

More Data Yield More Answers
The proliferation of registries should bring MS research closer to that seen with other chronic diseases, said Ms. Halper. While people are being diagnosed more quickly, and more treatments are available, there is still a lot of work to be done, she said. “We don’t know a heck of a lot about MS, and everybody wants to know more. We need data.”

Dr. McBurney concurred. “We’re making an impact on the early relapsing-remitting phase of the disorder, but to date, no drugs have been approved for progressive MS. Maybe they’re not even the same disease. We still have very little idea which patient is going to benefit from any particular treatment strategy without experiencing troubling side effects,” he said. Registry data may help answer these and other questions.

—Jennie Smith

NAPLES, FLORIDA—Psychiatric comorbidities, particularly depression, worsen the course of major neurologic conditions, according to research described at the 42nd Annual Meeting of the Southern Clinical Neurological Society. Among individuals with neurologic diseases, depression is associated with greater cognitive deficits, greater impairments in activities of daily living, and lower quality of life.

“Intuitively, we would think that if we treat those comorbid depressive disorders, patients’ course would get better,” said Andres M. Kanner, MD, Professor of Clinical Neurology at the University of Miami Miller School of Medicine. “The problem is that there’s been such apathy about paying attention to comorbid depressive disorders in neurologic conditions that there are no good data on their treatment.” This lack of data needs to be addressed, he added.

A Bidirectional Relationship
The pathogenic mechanisms operant in the development of mood disorders include environmental factors (eg, stressful events), genetic predispositions, and neurotransmitter and neuroendocrine disturbances, which, in turn, can result in structural and functional changes in the CNS. These changes could explain why the course of a neurologic condition is worse among patients with depression than among patients without depression.

Various studies have suggested that depression and some neurologic disorders share common pathogenic mechanisms. For example, data indicate that decreased binding of the serotonin 1A receptor in the hippocampus, insula, amygdala, cingulate gyrus, and Raphe nuclei occurs in temporal lobe epilepsy and depression. Depression also is associated with low platelet serotonin concentration, which can yield a higher platelet adhesivity, and increased secretion of cytokines, which may be associated with vasculitic processes. These factors may heighten the risk of stroke. Likewise, glutamate, one of the neurotransmitters implicated in epileptogenesis, is present at high levels in the CSF, plasma, and cortex of patients with depression.

Depression is common among patients with neurologic disorders. Population-based studies suggest that one in every three patients who develop stroke, epilepsy, migraine, or Parkinson’s disease will develop depression. Between 27% and 54% of patients with multiple sclerosis (MS) have had an episode of major depressive disorder. And between 30% and 50% of patients with dementia have depression.

Depression and neurologic disorders appear to have a bidirectional relationship. “Not only are people with some of the major neurologic conditions more likely to develop depression, but a history of depression is associated with a higher risk of developing several of the neurologic conditions, such as epilepsy, migraine, stroke, Parkinson’s disease, and dementia,” said Dr. Kanner. This complex interaction also affects clinical treatment. A patient’s family psychiatric history, psychiatric comorbidity, and stressful life events can influence his or her response to pharmacotherapy, as well as the development of psychiatric adverse events to pharmacologic and surgical treatment.

Depression’s Effects in Neurologic Diseases
The negative effects of mood disorders vary according to the patient’s neurologic disease. Researchers at Johns Hopkins University found that patients with stroke and major poststroke depression had significantly more cognitive deficits than patients with stroke who did not have depression. In a follow-up study, the same researchers found that major poststroke depression was associated with greater cognitive impairment at two years after stroke onset. A separate investigation indicated that in-hospital poststroke depression was the most important predictor of poor recovery in activities of daily living after two years. Other data suggested that mortality risk was 50% higher for patients with stroke and poststroke depression than for patients with stroke without poststroke depression.

Among people with MS, depression significantly and independently affects quality of life. In one trial, depression was a stronger predictor of poor quality of life than disease severity, as measured by the Expanded Disability Status Scale. A study of 136 patients with MS found that depression decreased quality of life by reducing energy, mental health, sexual function, and cognitive function.

Among people with Alzheimer’s dementia, depression is a predictor of cognitive decline and is associated with greater impairment in activities of daily living. For this population, depression also is associated with an earlier need for placement in a nursing home, an earlier need for transfer from an assisted-living facility to a higher-level health care facility, and increased caregiver depression and burden.

In addition, depression is the factor most closely related to poor quality of life among patients with Parkinson’s disease. “Depression in Parkinson’s disease has been associated with a more rapid deterioration of motor and cognitive function, especially executive function, and a greater likelihood of displaying psychotic symptoms and physical disability,” said Dr. Kanner. In people with Parkinson’s disease, depression is associated with impairment in set shifting and concept formation.

Depression Complicates Epilepsy Treatment
Several studies describe the various negative effects that depression has among people with epilepsy. Investigators in the United Kingdom concluded that people with a lifetime history of depression before epilepsy onset were twice as likely to develop treatment-resistant epilepsy than people without depression before epilepsy onset.

In an Australian study of people with new-onset epilepsy, comorbid symptoms of depression and anxiety at epilepsy diagnosis were associated with a lower likelihood of being seizure-free at 52 weeks of treatment. Research by Dr. Kanner and colleagues found that among patients who became seizure-free after temporal lobectomy, 12% had had a lifetime history of depression. Approximately 80% of people who had resistant seizures after surgery had had a lifetime history of depression.

A multicenter study of people with epilepsy indicated that patients with depression or anxiety were significantly more likely to have a greater number and severity of adverse events from antiepileptic drugs. Other data indicate a high correlation between severity of depression and poor quality of life among individuals with treatment-resistant temporal lobe epilepsy. This investigation also found no correlation between seizure frequency and quality of life.

—Erik Greb

NAPLES, FLORIDA—Psychiatric comorbidities, particularly depression, worsen the course of major neurologic conditions, according to research described at the 42nd Annual Meeting of the Southern Clinical Neurological Society. Among individuals with neurologic diseases, depression is associated with greater cognitive deficits, greater impairments in activities of daily living, and lower quality of life.

“Intuitively, we would think that if we treat those comorbid depressive disorders, patients’ course would get better,” said Andres M. Kanner, MD, Professor of Clinical Neurology at the University of Miami Miller School of Medicine. “The problem is that there’s been such apathy about paying attention to comorbid depressive disorders in neurologic conditions that there are no good data on their treatment.” This lack of data needs to be addressed, he added.

A Bidirectional Relationship
The pathogenic mechanisms operant in the development of mood disorders include environmental factors (eg, stressful events), genetic predispositions, and neurotransmitter and neuroendocrine disturbances, which, in turn, can result in structural and functional changes in the CNS. These changes could explain why the course of a neurologic condition is worse among patients with depression than among patients without depression.

Various studies have suggested that depression and some neurologic disorders share common pathogenic mechanisms. For example, data indicate that decreased binding of the serotonin 1A receptor in the hippocampus, insula, amygdala, cingulate gyrus, and Raphe nuclei occurs in temporal lobe epilepsy and depression. Depression also is associated with low platelet serotonin concentration, which can yield a higher platelet adhesivity, and increased secretion of cytokines, which may be associated with vasculitic processes. These factors may heighten the risk of stroke. Likewise, glutamate, one of the neurotransmitters implicated in epileptogenesis, is present at high levels in the CSF, plasma, and cortex of patients with depression.

Depression is common among patients with neurologic disorders. Population-based studies suggest that one in every three patients who develop stroke, epilepsy, migraine, or Parkinson’s disease will develop depression. Between 27% and 54% of patients with multiple sclerosis (MS) have had an episode of major depressive disorder. And between 30% and 50% of patients with dementia have depression.

Depression and neurologic disorders appear to have a bidirectional relationship. “Not only are people with some of the major neurologic conditions more likely to develop depression, but a history of depression is associated with a higher risk of developing several of the neurologic conditions, such as epilepsy, migraine, stroke, Parkinson’s disease, and dementia,” said Dr. Kanner. This complex interaction also affects clinical treatment. A patient’s family psychiatric history, psychiatric comorbidity, and stressful life events can influence his or her response to pharmacotherapy, as well as the development of psychiatric adverse events to pharmacologic and surgical treatment.

Depression’s Effects in Neurologic Diseases
The negative effects of mood disorders vary according to the patient’s neurologic disease. Researchers at Johns Hopkins University found that patients with stroke and major poststroke depression had significantly more cognitive deficits than patients with stroke who did not have depression. In a follow-up study, the same researchers found that major poststroke depression was associated with greater cognitive impairment at two years after stroke onset. A separate investigation indicated that in-hospital poststroke depression was the most important predictor of poor recovery in activities of daily living after two years. Other data suggested that mortality risk was 50% higher for patients with stroke and poststroke depression than for patients with stroke without poststroke depression.

Among people with MS, depression significantly and independently affects quality of life. In one trial, depression was a stronger predictor of poor quality of life than disease severity, as measured by the Expanded Disability Status Scale. A study of 136 patients with MS found that depression decreased quality of life by reducing energy, mental health, sexual function, and cognitive function.

Among people with Alzheimer’s dementia, depression is a predictor of cognitive decline and is associated with greater impairment in activities of daily living. For this population, depression also is associated with an earlier need for placement in a nursing home, an earlier need for transfer from an assisted-living facility to a higher-level health care facility, and increased caregiver depression and burden.

In addition, depression is the factor most closely related to poor quality of life among patients with Parkinson’s disease. “Depression in Parkinson’s disease has been associated with a more rapid deterioration of motor and cognitive function, especially executive function, and a greater likelihood of displaying psychotic symptoms and physical disability,” said Dr. Kanner. In people with Parkinson’s disease, depression is associated with impairment in set shifting and concept formation.

Depression Complicates Epilepsy Treatment
Several studies describe the various negative effects that depression has among people with epilepsy. Investigators in the United Kingdom concluded that people with a lifetime history of depression before epilepsy onset were twice as likely to develop treatment-resistant epilepsy than people without depression before epilepsy onset.

In an Australian study of people with new-onset epilepsy, comorbid symptoms of depression and anxiety at epilepsy diagnosis were associated with a lower likelihood of being seizure-free at 52 weeks of treatment. Research by Dr. Kanner and colleagues found that among patients who became seizure-free after temporal lobectomy, 12% had had a lifetime history of depression. Approximately 80% of people who had resistant seizures after surgery had had a lifetime history of depression.

A multicenter study of people with epilepsy indicated that patients with depression or anxiety were significantly more likely to have a greater number and severity of adverse events from antiepileptic drugs. Other data indicate a high correlation between severity of depression and poor quality of life among individuals with treatment-resistant temporal lobe epilepsy. This investigation also found no correlation between seizure frequency and quality of life.

—Erik Greb

NAPLES, FLORIDA—Psychiatric comorbidities, particularly depression, worsen the course of major neurologic conditions, according to research described at the 42nd Annual Meeting of the Southern Clinical Neurological Society. Among individuals with neurologic diseases, depression is associated with greater cognitive deficits, greater impairments in activities of daily living, and lower quality of life.

“Intuitively, we would think that if we treat those comorbid depressive disorders, patients’ course would get better,” said Andres M. Kanner, MD, Professor of Clinical Neurology at the University of Miami Miller School of Medicine. “The problem is that there’s been such apathy about paying attention to comorbid depressive disorders in neurologic conditions that there are no good data on their treatment.” This lack of data needs to be addressed, he added.

A Bidirectional Relationship
The pathogenic mechanisms operant in the development of mood disorders include environmental factors (eg, stressful events), genetic predispositions, and neurotransmitter and neuroendocrine disturbances, which, in turn, can result in structural and functional changes in the CNS. These changes could explain why the course of a neurologic condition is worse among patients with depression than among patients without depression.

Various studies have suggested that depression and some neurologic disorders share common pathogenic mechanisms. For example, data indicate that decreased binding of the serotonin 1A receptor in the hippocampus, insula, amygdala, cingulate gyrus, and Raphe nuclei occurs in temporal lobe epilepsy and depression. Depression also is associated with low platelet serotonin concentration, which can yield a higher platelet adhesivity, and increased secretion of cytokines, which may be associated with vasculitic processes. These factors may heighten the risk of stroke. Likewise, glutamate, one of the neurotransmitters implicated in epileptogenesis, is present at high levels in the CSF, plasma, and cortex of patients with depression.

Depression is common among patients with neurologic disorders. Population-based studies suggest that one in every three patients who develop stroke, epilepsy, migraine, or Parkinson’s disease will develop depression. Between 27% and 54% of patients with multiple sclerosis (MS) have had an episode of major depressive disorder. And between 30% and 50% of patients with dementia have depression.

Depression and neurologic disorders appear to have a bidirectional relationship. “Not only are people with some of the major neurologic conditions more likely to develop depression, but a history of depression is associated with a higher risk of developing several of the neurologic conditions, such as epilepsy, migraine, stroke, Parkinson’s disease, and dementia,” said Dr. Kanner. This complex interaction also affects clinical treatment. A patient’s family psychiatric history, psychiatric comorbidity, and stressful life events can influence his or her response to pharmacotherapy, as well as the development of psychiatric adverse events to pharmacologic and surgical treatment.

Depression’s Effects in Neurologic Diseases
The negative effects of mood disorders vary according to the patient’s neurologic disease. Researchers at Johns Hopkins University found that patients with stroke and major poststroke depression had significantly more cognitive deficits than patients with stroke who did not have depression. In a follow-up study, the same researchers found that major poststroke depression was associated with greater cognitive impairment at two years after stroke onset. A separate investigation indicated that in-hospital poststroke depression was the most important predictor of poor recovery in activities of daily living after two years. Other data suggested that mortality risk was 50% higher for patients with stroke and poststroke depression than for patients with stroke without poststroke depression.

Among people with MS, depression significantly and independently affects quality of life. In one trial, depression was a stronger predictor of poor quality of life than disease severity, as measured by the Expanded Disability Status Scale. A study of 136 patients with MS found that depression decreased quality of life by reducing energy, mental health, sexual function, and cognitive function.

Among people with Alzheimer’s dementia, depression is a predictor of cognitive decline and is associated with greater impairment in activities of daily living. For this population, depression also is associated with an earlier need for placement in a nursing home, an earlier need for transfer from an assisted-living facility to a higher-level health care facility, and increased caregiver depression and burden.

In addition, depression is the factor most closely related to poor quality of life among patients with Parkinson’s disease. “Depression in Parkinson’s disease has been associated with a more rapid deterioration of motor and cognitive function, especially executive function, and a greater likelihood of displaying psychotic symptoms and physical disability,” said Dr. Kanner. In people with Parkinson’s disease, depression is associated with impairment in set shifting and concept formation.

Depression Complicates Epilepsy Treatment
Several studies describe the various negative effects that depression has among people with epilepsy. Investigators in the United Kingdom concluded that people with a lifetime history of depression before epilepsy onset were twice as likely to develop treatment-resistant epilepsy than people without depression before epilepsy onset.

In an Australian study of people with new-onset epilepsy, comorbid symptoms of depression and anxiety at epilepsy diagnosis were associated with a lower likelihood of being seizure-free at 52 weeks of treatment. Research by Dr. Kanner and colleagues found that among patients who became seizure-free after temporal lobectomy, 12% had had a lifetime history of depression. Approximately 80% of people who had resistant seizures after surgery had had a lifetime history of depression.

A multicenter study of people with epilepsy indicated that patients with depression or anxiety were significantly more likely to have a greater number and severity of adverse events from antiepileptic drugs. Other data indicate a high correlation between severity of depression and poor quality of life among individuals with treatment-resistant temporal lobe epilepsy. This investigation also found no correlation between seizure frequency and quality of life.

—Erik Greb