Multiple Sclerosis Hub

More than 20% of patients with multiple sclerosis experience moderate to high trait anxiety—a psychological symptom whose role in the disease course has not been well-defined.

MONTREAL—State and trait anxiety are prevalent in patients with multiple sclerosis (MS), and that increased anxiety correlates strongly with lower mental quality of life and higher depression and fatigue, according to research that was presented at the 25th Annual Meeting of the Consortium of Multiple Sclerosis Centers.
 “MS patients have an increased rate of psychological symptoms beyond those found in controls and even in other chronic diseases,” reported Line E. Hviid, a research assistant and study coordinator at the Brigham and Women’s Hospital at Harvard Medical School in Boston. “While depression in the MS population has been studied in great detail, there has been little study of anxiety in MS, despite evidence of a nearly equally high prevalence.”
Ms. Hviid and colleagues enrolled 303 patients (mean age, 47.2) with clinically isolated syndrome or MS and administered questionnaires regarding state and trait anxiety, quality of life and health status, fatigue, social support, and depression to examine the role of anxiety in MS disease course. The patients also completed cognitive screening tests and were annually evaluated using the Expanded Disability Status Scale (EDSS).
A Significant Number of Patients With MS Experience Anxiety
“Using the published normal ranges, 14.5% of our subjects reported moderate to high state anxiety and 21.9% reported moderate to high trait anxiety,” the investigators stated. “Only 3.0% of our subjects reported high state anxiety, and 9.3% reported high trait anxiety.”
The researchers found statistically significant correlations when comparing measures of state and trait anxiety and all patient-reported outcomes; the highest correlations were recorded between anxiety and depression, the mental health scale, and the mental components summary score.
The team of investigators also observed mild but statistically significant associations between anxiety and both EDSS scores and the number of recent attacks. “No significant differences were found due to cognitive functioning, disease duration, disease course, or treatment status,” they reported.
The weak but significant correlation observed between anxiety and physical functioning—as measured by EDSS scores—and the stronger relationship between anxiety and role-physical subscale of the health status questionnaire—which measures the impact of physical functioning on daily life—suggest that the impact of physical disability on anxiety may be more profound than the physical disability itself, according to the researchers.
Comorbidities of MS-Associated Anxiety
“A striking comorbidity was found between depression and anxiety,” the authors stated. Increased anxiety was also correlated with a lower mental quality of life, as well as with increased fatigue, depression, and lower levels of social support.
“Anxiety is an important feature of MS,” the researchers concluded. “These findings highlight the need for identification and treatment of patients with anxiety, particularly in patients who experience depression.”

More than 20% of patients with multiple sclerosis experience moderate to high trait anxiety—a psychological symptom whose role in the disease course has not been well-defined.

MONTREAL—State and trait anxiety are prevalent in patients with multiple sclerosis (MS), and that increased anxiety correlates strongly with lower mental quality of life and higher depression and fatigue, according to research that was presented at the 25th Annual Meeting of the Consortium of Multiple Sclerosis Centers.
 “MS patients have an increased rate of psychological symptoms beyond those found in controls and even in other chronic diseases,” reported Line E. Hviid, a research assistant and study coordinator at the Brigham and Women’s Hospital at Harvard Medical School in Boston. “While depression in the MS population has been studied in great detail, there has been little study of anxiety in MS, despite evidence of a nearly equally high prevalence.”
Ms. Hviid and colleagues enrolled 303 patients (mean age, 47.2) with clinically isolated syndrome or MS and administered questionnaires regarding state and trait anxiety, quality of life and health status, fatigue, social support, and depression to examine the role of anxiety in MS disease course. The patients also completed cognitive screening tests and were annually evaluated using the Expanded Disability Status Scale (EDSS).
A Significant Number of Patients With MS Experience Anxiety
“Using the published normal ranges, 14.5% of our subjects reported moderate to high state anxiety and 21.9% reported moderate to high trait anxiety,” the investigators stated. “Only 3.0% of our subjects reported high state anxiety, and 9.3% reported high trait anxiety.”
The researchers found statistically significant correlations when comparing measures of state and trait anxiety and all patient-reported outcomes; the highest correlations were recorded between anxiety and depression, the mental health scale, and the mental components summary score.
The team of investigators also observed mild but statistically significant associations between anxiety and both EDSS scores and the number of recent attacks. “No significant differences were found due to cognitive functioning, disease duration, disease course, or treatment status,” they reported.
The weak but significant correlation observed between anxiety and physical functioning—as measured by EDSS scores—and the stronger relationship between anxiety and role-physical subscale of the health status questionnaire—which measures the impact of physical functioning on daily life—suggest that the impact of physical disability on anxiety may be more profound than the physical disability itself, according to the researchers.
Comorbidities of MS-Associated Anxiety
“A striking comorbidity was found between depression and anxiety,” the authors stated. Increased anxiety was also correlated with a lower mental quality of life, as well as with increased fatigue, depression, and lower levels of social support.
“Anxiety is an important feature of MS,” the researchers concluded. “These findings highlight the need for identification and treatment of patients with anxiety, particularly in patients who experience depression.”

More than 20% of patients with multiple sclerosis experience moderate to high trait anxiety—a psychological symptom whose role in the disease course has not been well-defined.

MONTREAL—State and trait anxiety are prevalent in patients with multiple sclerosis (MS), and that increased anxiety correlates strongly with lower mental quality of life and higher depression and fatigue, according to research that was presented at the 25th Annual Meeting of the Consortium of Multiple Sclerosis Centers.
 “MS patients have an increased rate of psychological symptoms beyond those found in controls and even in other chronic diseases,” reported Line E. Hviid, a research assistant and study coordinator at the Brigham and Women’s Hospital at Harvard Medical School in Boston. “While depression in the MS population has been studied in great detail, there has been little study of anxiety in MS, despite evidence of a nearly equally high prevalence.”
Ms. Hviid and colleagues enrolled 303 patients (mean age, 47.2) with clinically isolated syndrome or MS and administered questionnaires regarding state and trait anxiety, quality of life and health status, fatigue, social support, and depression to examine the role of anxiety in MS disease course. The patients also completed cognitive screening tests and were annually evaluated using the Expanded Disability Status Scale (EDSS).
A Significant Number of Patients With MS Experience Anxiety
“Using the published normal ranges, 14.5% of our subjects reported moderate to high state anxiety and 21.9% reported moderate to high trait anxiety,” the investigators stated. “Only 3.0% of our subjects reported high state anxiety, and 9.3% reported high trait anxiety.”
The researchers found statistically significant correlations when comparing measures of state and trait anxiety and all patient-reported outcomes; the highest correlations were recorded between anxiety and depression, the mental health scale, and the mental components summary score.
The team of investigators also observed mild but statistically significant associations between anxiety and both EDSS scores and the number of recent attacks. “No significant differences were found due to cognitive functioning, disease duration, disease course, or treatment status,” they reported.
The weak but significant correlation observed between anxiety and physical functioning—as measured by EDSS scores—and the stronger relationship between anxiety and role-physical subscale of the health status questionnaire—which measures the impact of physical functioning on daily life—suggest that the impact of physical disability on anxiety may be more profound than the physical disability itself, according to the researchers.
Comorbidities of MS-Associated Anxiety
“A striking comorbidity was found between depression and anxiety,” the authors stated. Increased anxiety was also correlated with a lower mental quality of life, as well as with increased fatigue, depression, and lower levels of social support.
“Anxiety is an important feature of MS,” the researchers concluded. “These findings highlight the need for identification and treatment of patients with anxiety, particularly in patients who experience depression.”

Researchers identify clinical and MRI biomarkers that may help predict outcomes in patients with relapsing-remitting MS up to eight years after starting therapy.

HONOLULU—Higher brain volume at baseline and a greater medication possession ratio predicted improved long-term clinical outcomes among patients with relapsing-remitting multiple sclerosis (MS), according to research presented at the 63rd Annual Meeting of the American Academy of Neurology. In addition, a higher baseline Expanded Disability Status Scale (EDSS) score and a greater early increase in EDSS score predicted worse outcomes, researchers reported.

“Given the heterogeneous nature of MS, it is important to identify prognostic factors that may predict outcomes as long as eight years after starting therapy,” stated Anthony Traboulsee, MD, Assistant Professor of Neurology at the University of British Columbia in Vancouver, and colleagues. “Assessing baseline brain volume and closely monitoring early disability status may be important to consider in monitoring and treatment decisions.”

Long-Term Follow-Up After Treatment Initiation
Dr. Traboulsee’s group conducted the Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) long-term follow-up (LTFU) study to analyze early clinical and MRI variables as predictors of long-term outcomes in patients with relapsing-remitting MS. The PRISMS LTFU cohort was followed prospectively for as long as eight years, with a 68% patient return rate in the follow-up. “Assessment protocols remained consistent through the course of the PRISMS study, thereby providing one of the most complete datasets of its type available,” noted the investigators.

A total of 382 patients were included in the LTFU follow-up to PRISMS, in which 560 patients were originally randomized. Among the 382 patients in the LTFU, 136 patients had been initially randomized to receive interferon beta-1a 44 µg; 123 patients had received interferon beta-1a 22 µg subcutaneously three times per week; and 123 participants had received placebo. Post-hoc exploratory analyses were conducted on data collected from all LTFU patients and in the subcohort originally randomized to receive subcutaneous interferon beta-1a, who were referred to as early-start patients (n = 259).

Baseline variables and medication possession ratio, as an indicator of subcutaneous interferon beta-1a treatment exposure, were explored as candidate prognostic factors for outcomes measured from baseline to LTFU (for up to eight years). The authors also investigated indicators of early clinical and MRI activity from baseline to month 24 as candidate prognostic factors for outcomes measured from month 24 to LTFU.
Predicting Favorable and Unfavorable Outcomes in MS
The researchers found that age, duration of MS, baseline EDSS score, baseline log (T2 disease of burden), and baseline brain volume were univariate predictors for nearly all long-term outcomes as measured from baseline to LTFU among all patients and early-start patients. Medication possession ratio predicted most of the long-term outcomes measured from baseline to LTFU in all patients and was a predictor for several outcomes in early-start patients.

Early change in EDSS score up to two years was a univariate predictor for virtually all outcomes measured from month 24 to LTFU in all patients and early-start patients, according to the investigators. In addition, EDSS progression and the number of EDSS progressions during the first 24 months were  frequent predictors for clinical outcomes as measured from month 24 to LTFU in all patients and early-start patients.

“The early MRI activity indicators were significant univariate predictors of several long-term disability outcomes, but not as frequently as seen with early EDSS progression,” reported Dr. Traboulsee and colleagues. “Brain volumes at baseline continued to be a predictor in all final multivariate models for all long-term clinical outcomes in both patient groups measured from baseline to LTFU. EDSS score at baseline continued to be a predictor in most multivariate models in both patient groups measured from baseline to LTFU.”

In several multivariate models, medication possession ratio continued to be a predictor for all long-term clinical outcomes in the all-patient cohort measured from baseline to LTFU, noted the investigators. The change in EDSS score from baseline to month 24 continued to be a predictor in nearly all final multivariate models for long-term clinical outcomes in all patients, and in all final multivariate models for all long-term clinical outcomes in early-start patients. Also, short-term MRI activity was predictive of some of the long-term clinical outcomes.

“These data suggest that a good early clinical response—no EDSS progression—can be predictive of a favorable long-term outcome,” Dr. Traboulsee and colleagues concluded. “However, patients who show worrisome signs of early disease progression may require earlier therapeutic review."

Researchers identify clinical and MRI biomarkers that may help predict outcomes in patients with relapsing-remitting MS up to eight years after starting therapy.

HONOLULU—Higher brain volume at baseline and a greater medication possession ratio predicted improved long-term clinical outcomes among patients with relapsing-remitting multiple sclerosis (MS), according to research presented at the 63rd Annual Meeting of the American Academy of Neurology. In addition, a higher baseline Expanded Disability Status Scale (EDSS) score and a greater early increase in EDSS score predicted worse outcomes, researchers reported.

“Given the heterogeneous nature of MS, it is important to identify prognostic factors that may predict outcomes as long as eight years after starting therapy,” stated Anthony Traboulsee, MD, Assistant Professor of Neurology at the University of British Columbia in Vancouver, and colleagues. “Assessing baseline brain volume and closely monitoring early disability status may be important to consider in monitoring and treatment decisions.”

Long-Term Follow-Up After Treatment Initiation
Dr. Traboulsee’s group conducted the Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) long-term follow-up (LTFU) study to analyze early clinical and MRI variables as predictors of long-term outcomes in patients with relapsing-remitting MS. The PRISMS LTFU cohort was followed prospectively for as long as eight years, with a 68% patient return rate in the follow-up. “Assessment protocols remained consistent through the course of the PRISMS study, thereby providing one of the most complete datasets of its type available,” noted the investigators.

A total of 382 patients were included in the LTFU follow-up to PRISMS, in which 560 patients were originally randomized. Among the 382 patients in the LTFU, 136 patients had been initially randomized to receive interferon beta-1a 44 µg; 123 patients had received interferon beta-1a 22 µg subcutaneously three times per week; and 123 participants had received placebo. Post-hoc exploratory analyses were conducted on data collected from all LTFU patients and in the subcohort originally randomized to receive subcutaneous interferon beta-1a, who were referred to as early-start patients (n = 259).

Baseline variables and medication possession ratio, as an indicator of subcutaneous interferon beta-1a treatment exposure, were explored as candidate prognostic factors for outcomes measured from baseline to LTFU (for up to eight years). The authors also investigated indicators of early clinical and MRI activity from baseline to month 24 as candidate prognostic factors for outcomes measured from month 24 to LTFU.
Predicting Favorable and Unfavorable Outcomes in MS
The researchers found that age, duration of MS, baseline EDSS score, baseline log (T2 disease of burden), and baseline brain volume were univariate predictors for nearly all long-term outcomes as measured from baseline to LTFU among all patients and early-start patients. Medication possession ratio predicted most of the long-term outcomes measured from baseline to LTFU in all patients and was a predictor for several outcomes in early-start patients.

Early change in EDSS score up to two years was a univariate predictor for virtually all outcomes measured from month 24 to LTFU in all patients and early-start patients, according to the investigators. In addition, EDSS progression and the number of EDSS progressions during the first 24 months were  frequent predictors for clinical outcomes as measured from month 24 to LTFU in all patients and early-start patients.

“The early MRI activity indicators were significant univariate predictors of several long-term disability outcomes, but not as frequently as seen with early EDSS progression,” reported Dr. Traboulsee and colleagues. “Brain volumes at baseline continued to be a predictor in all final multivariate models for all long-term clinical outcomes in both patient groups measured from baseline to LTFU. EDSS score at baseline continued to be a predictor in most multivariate models in both patient groups measured from baseline to LTFU.”

In several multivariate models, medication possession ratio continued to be a predictor for all long-term clinical outcomes in the all-patient cohort measured from baseline to LTFU, noted the investigators. The change in EDSS score from baseline to month 24 continued to be a predictor in nearly all final multivariate models for long-term clinical outcomes in all patients, and in all final multivariate models for all long-term clinical outcomes in early-start patients. Also, short-term MRI activity was predictive of some of the long-term clinical outcomes.

“These data suggest that a good early clinical response—no EDSS progression—can be predictive of a favorable long-term outcome,” Dr. Traboulsee and colleagues concluded. “However, patients who show worrisome signs of early disease progression may require earlier therapeutic review."

Researchers identify clinical and MRI biomarkers that may help predict outcomes in patients with relapsing-remitting MS up to eight years after starting therapy.

HONOLULU—Higher brain volume at baseline and a greater medication possession ratio predicted improved long-term clinical outcomes among patients with relapsing-remitting multiple sclerosis (MS), according to research presented at the 63rd Annual Meeting of the American Academy of Neurology. In addition, a higher baseline Expanded Disability Status Scale (EDSS) score and a greater early increase in EDSS score predicted worse outcomes, researchers reported.

“Given the heterogeneous nature of MS, it is important to identify prognostic factors that may predict outcomes as long as eight years after starting therapy,” stated Anthony Traboulsee, MD, Assistant Professor of Neurology at the University of British Columbia in Vancouver, and colleagues. “Assessing baseline brain volume and closely monitoring early disability status may be important to consider in monitoring and treatment decisions.”

Long-Term Follow-Up After Treatment Initiation
Dr. Traboulsee’s group conducted the Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) long-term follow-up (LTFU) study to analyze early clinical and MRI variables as predictors of long-term outcomes in patients with relapsing-remitting MS. The PRISMS LTFU cohort was followed prospectively for as long as eight years, with a 68% patient return rate in the follow-up. “Assessment protocols remained consistent through the course of the PRISMS study, thereby providing one of the most complete datasets of its type available,” noted the investigators.

A total of 382 patients were included in the LTFU follow-up to PRISMS, in which 560 patients were originally randomized. Among the 382 patients in the LTFU, 136 patients had been initially randomized to receive interferon beta-1a 44 µg; 123 patients had received interferon beta-1a 22 µg subcutaneously three times per week; and 123 participants had received placebo. Post-hoc exploratory analyses were conducted on data collected from all LTFU patients and in the subcohort originally randomized to receive subcutaneous interferon beta-1a, who were referred to as early-start patients (n = 259).

Baseline variables and medication possession ratio, as an indicator of subcutaneous interferon beta-1a treatment exposure, were explored as candidate prognostic factors for outcomes measured from baseline to LTFU (for up to eight years). The authors also investigated indicators of early clinical and MRI activity from baseline to month 24 as candidate prognostic factors for outcomes measured from month 24 to LTFU.
Predicting Favorable and Unfavorable Outcomes in MS
The researchers found that age, duration of MS, baseline EDSS score, baseline log (T2 disease of burden), and baseline brain volume were univariate predictors for nearly all long-term outcomes as measured from baseline to LTFU among all patients and early-start patients. Medication possession ratio predicted most of the long-term outcomes measured from baseline to LTFU in all patients and was a predictor for several outcomes in early-start patients.

Early change in EDSS score up to two years was a univariate predictor for virtually all outcomes measured from month 24 to LTFU in all patients and early-start patients, according to the investigators. In addition, EDSS progression and the number of EDSS progressions during the first 24 months were  frequent predictors for clinical outcomes as measured from month 24 to LTFU in all patients and early-start patients.

“The early MRI activity indicators were significant univariate predictors of several long-term disability outcomes, but not as frequently as seen with early EDSS progression,” reported Dr. Traboulsee and colleagues. “Brain volumes at baseline continued to be a predictor in all final multivariate models for all long-term clinical outcomes in both patient groups measured from baseline to LTFU. EDSS score at baseline continued to be a predictor in most multivariate models in both patient groups measured from baseline to LTFU.”

In several multivariate models, medication possession ratio continued to be a predictor for all long-term clinical outcomes in the all-patient cohort measured from baseline to LTFU, noted the investigators. The change in EDSS score from baseline to month 24 continued to be a predictor in nearly all final multivariate models for long-term clinical outcomes in all patients, and in all final multivariate models for all long-term clinical outcomes in early-start patients. Also, short-term MRI activity was predictive of some of the long-term clinical outcomes.

“These data suggest that a good early clinical response—no EDSS progression—can be predictive of a favorable long-term outcome,” Dr. Traboulsee and colleagues concluded. “However, patients who show worrisome signs of early disease progression may require earlier therapeutic review."

A majority of patients with neuromyelitis optica also experience disease-specific brain lesions that could help distinguish neuromyelitis optica from multiple sclerosis.

MONTREAL—Imaging studies of patients with neuromyelitis optica (NMO)–spectrum disorders reveal that effects of the aquaporin-4 (AQP4) autoantibody, a marker of the disease, may extend beyond the spinal cord and optic nerve, according to researchers. MRI findings of these disease-specific lesions may make it possible to differentiate between NMO and multiple sclerosis (MS).
Jose A. Cabrera-Gomez, MD, PhD, of the Multiple Sclerosis Clinic International Neurologic Restoration Center and Cuban Multiple Sclerosis Society in Havana, and Ilya Kister, MD, from the New York University School of Medicine, presented their findings at the 25th Annual Meeting of the Consortium of Multiple Sclerosis Centers.
“Antibody to aquaporin-4 (AQP4) is a marker of relapsing NMO with specificity that approaches 100%,” the authors wrote. “Since AQP4 is distributed widely throughout the brain, especially in the ependyma and microvessels, one might expect that NMO would affect not only spinal cord and optic nerves, but brain as well.”
Frequency of Brain Abnormalities in Patients With NMO
To examine the extent of brain involvement in NMO, the researchers reviewed 18 case series (involving approximately 500 patients) that used MRI to document brain abnormalities in patients with NMO-spectrum disorders. The cases were divided into three groups: adult NMO (10), pediatric NMO (5), and anti-AQP4–positive patients (4).
“The frequency of brain abnormalities ranged from 43% to 100%,” Drs. Cabrera-Gomez and Kister reported. Differences in disease expression across ethnic groups, varying time from symptom onset to brain MRI, and methodological differences could contribute to this wide range of findings, they noted.
The authors reported finding striking convergent findings across multiple research groups. “Brain lesions on MRI are very common in NMO and are seen in the majority of patients with prolonged disease duration,” Dr. Lister told Neurology Reviews. “Certain lesion types appear to be typical for NMO and atypical for MS and these could potentially be useful to differentiate NMO from MS.” Lesion types that were typical of NMO included callosal/septal interface lesions, Balo-like lesions in the pons, and cavitary lesions in the occipital lobe. The researchers also noted that AQP4-seropositive patients were more likely to have brain lesions.
Can MRI Findings Differentiate Between NMO and MS?
“Brain lesions are seen in many NMO patients at onset of the disease, and in the majority of NMO patients on follow-up imaging,” the investigators wrote. This study’s findings and the discovery of NMO-specific lesions could lead to the development of diagnostic criteria for the disease.
“We advocate for systematic, prospective, multicenter studies to further characterize evolution of brain lesions in NMO and development of consensus criteria of brain MRI findings that could assist in differentiating NMO from MS,” the authors stated. This entails developing criteria that incorporate both positive brain MRI findings (“typical NMO lesions/high positive predictive value”) and negative brain MRI findings (“atypical in NMO/high negative predictive value”). “Studies are needed to determine sensitivity and specificity of various brain MRI findings for diagnosis of NMO,” said Dr. Lister. “A substantial minority of NMO patients have brain abnormalities that fulfill Barkhoff criteria for dissemination in space in MS. Thus, current MRI criteria for MS cannot be used to definitively differentiate MS from NMO.”

A majority of patients with neuromyelitis optica also experience disease-specific brain lesions that could help distinguish neuromyelitis optica from multiple sclerosis.

MONTREAL—Imaging studies of patients with neuromyelitis optica (NMO)–spectrum disorders reveal that effects of the aquaporin-4 (AQP4) autoantibody, a marker of the disease, may extend beyond the spinal cord and optic nerve, according to researchers. MRI findings of these disease-specific lesions may make it possible to differentiate between NMO and multiple sclerosis (MS).
Jose A. Cabrera-Gomez, MD, PhD, of the Multiple Sclerosis Clinic International Neurologic Restoration Center and Cuban Multiple Sclerosis Society in Havana, and Ilya Kister, MD, from the New York University School of Medicine, presented their findings at the 25th Annual Meeting of the Consortium of Multiple Sclerosis Centers.
“Antibody to aquaporin-4 (AQP4) is a marker of relapsing NMO with specificity that approaches 100%,” the authors wrote. “Since AQP4 is distributed widely throughout the brain, especially in the ependyma and microvessels, one might expect that NMO would affect not only spinal cord and optic nerves, but brain as well.”
Frequency of Brain Abnormalities in Patients With NMO
To examine the extent of brain involvement in NMO, the researchers reviewed 18 case series (involving approximately 500 patients) that used MRI to document brain abnormalities in patients with NMO-spectrum disorders. The cases were divided into three groups: adult NMO (10), pediatric NMO (5), and anti-AQP4–positive patients (4).
“The frequency of brain abnormalities ranged from 43% to 100%,” Drs. Cabrera-Gomez and Kister reported. Differences in disease expression across ethnic groups, varying time from symptom onset to brain MRI, and methodological differences could contribute to this wide range of findings, they noted.
The authors reported finding striking convergent findings across multiple research groups. “Brain lesions on MRI are very common in NMO and are seen in the majority of patients with prolonged disease duration,” Dr. Lister told Neurology Reviews. “Certain lesion types appear to be typical for NMO and atypical for MS and these could potentially be useful to differentiate NMO from MS.” Lesion types that were typical of NMO included callosal/septal interface lesions, Balo-like lesions in the pons, and cavitary lesions in the occipital lobe. The researchers also noted that AQP4-seropositive patients were more likely to have brain lesions.
Can MRI Findings Differentiate Between NMO and MS?
“Brain lesions are seen in many NMO patients at onset of the disease, and in the majority of NMO patients on follow-up imaging,” the investigators wrote. This study’s findings and the discovery of NMO-specific lesions could lead to the development of diagnostic criteria for the disease.
“We advocate for systematic, prospective, multicenter studies to further characterize evolution of brain lesions in NMO and development of consensus criteria of brain MRI findings that could assist in differentiating NMO from MS,” the authors stated. This entails developing criteria that incorporate both positive brain MRI findings (“typical NMO lesions/high positive predictive value”) and negative brain MRI findings (“atypical in NMO/high negative predictive value”). “Studies are needed to determine sensitivity and specificity of various brain MRI findings for diagnosis of NMO,” said Dr. Lister. “A substantial minority of NMO patients have brain abnormalities that fulfill Barkhoff criteria for dissemination in space in MS. Thus, current MRI criteria for MS cannot be used to definitively differentiate MS from NMO.”

A majority of patients with neuromyelitis optica also experience disease-specific brain lesions that could help distinguish neuromyelitis optica from multiple sclerosis.

MONTREAL—Imaging studies of patients with neuromyelitis optica (NMO)–spectrum disorders reveal that effects of the aquaporin-4 (AQP4) autoantibody, a marker of the disease, may extend beyond the spinal cord and optic nerve, according to researchers. MRI findings of these disease-specific lesions may make it possible to differentiate between NMO and multiple sclerosis (MS).
Jose A. Cabrera-Gomez, MD, PhD, of the Multiple Sclerosis Clinic International Neurologic Restoration Center and Cuban Multiple Sclerosis Society in Havana, and Ilya Kister, MD, from the New York University School of Medicine, presented their findings at the 25th Annual Meeting of the Consortium of Multiple Sclerosis Centers.
“Antibody to aquaporin-4 (AQP4) is a marker of relapsing NMO with specificity that approaches 100%,” the authors wrote. “Since AQP4 is distributed widely throughout the brain, especially in the ependyma and microvessels, one might expect that NMO would affect not only spinal cord and optic nerves, but brain as well.”
Frequency of Brain Abnormalities in Patients With NMO
To examine the extent of brain involvement in NMO, the researchers reviewed 18 case series (involving approximately 500 patients) that used MRI to document brain abnormalities in patients with NMO-spectrum disorders. The cases were divided into three groups: adult NMO (10), pediatric NMO (5), and anti-AQP4–positive patients (4).
“The frequency of brain abnormalities ranged from 43% to 100%,” Drs. Cabrera-Gomez and Kister reported. Differences in disease expression across ethnic groups, varying time from symptom onset to brain MRI, and methodological differences could contribute to this wide range of findings, they noted.
The authors reported finding striking convergent findings across multiple research groups. “Brain lesions on MRI are very common in NMO and are seen in the majority of patients with prolonged disease duration,” Dr. Lister told Neurology Reviews. “Certain lesion types appear to be typical for NMO and atypical for MS and these could potentially be useful to differentiate NMO from MS.” Lesion types that were typical of NMO included callosal/septal interface lesions, Balo-like lesions in the pons, and cavitary lesions in the occipital lobe. The researchers also noted that AQP4-seropositive patients were more likely to have brain lesions.
Can MRI Findings Differentiate Between NMO and MS?
“Brain lesions are seen in many NMO patients at onset of the disease, and in the majority of NMO patients on follow-up imaging,” the investigators wrote. This study’s findings and the discovery of NMO-specific lesions could lead to the development of diagnostic criteria for the disease.
“We advocate for systematic, prospective, multicenter studies to further characterize evolution of brain lesions in NMO and development of consensus criteria of brain MRI findings that could assist in differentiating NMO from MS,” the authors stated. This entails developing criteria that incorporate both positive brain MRI findings (“typical NMO lesions/high positive predictive value”) and negative brain MRI findings (“atypical in NMO/high negative predictive value”). “Studies are needed to determine sensitivity and specificity of various brain MRI findings for diagnosis of NMO,” said Dr. Lister. “A substantial minority of NMO patients have brain abnormalities that fulfill Barkhoff criteria for dissemination in space in MS. Thus, current MRI criteria for MS cannot be used to definitively differentiate MS from NMO.”

Vascular conditions, including atherosclerosis, may play an important role in the development of cognitive impairment and dementia, according to a report published online in the July 21 Stroke. The authors used previously published guidelines and literature, as well as personal experience, to summarize existing evidence, indicate gaps in current knowledge, and formulate recommendations regarding vascular contributions to cognitive decline late in life. Observed vascular risk factors included atrial fibrillation, hypertension, diabetes mellitus, and hypercholesterolemia, all of which, the researchers noted, were also risk factors for stroke and Alzheimer’s disease. “The neuropathology of cognitive impairment later in life is often a mixture of Alzheimer’s disease and microvascular brain damage,” the authors wrote. “Detection and control of the traditional risk factors for stroke and cardiovascular disease may be effective in the prevention of vascular cognitive impairment, even in older people.”
Women with epilepsy experience greater seizure frequency during anovulatory cycles than during cycles when ovulation occurs, according to results of a study published July 14 online ahead of print in Epilepsia. Almost 300 women with epilepsy were enrolled in the study; 92 had completed both cycles during the study period. Their average daily seizure frequency, seizure type, and progesterone/estradiol serum level ratios were recorded. “Average daily seizure frequency was 29.5% greater for secondary generalized tonic-clonic seizures during anovulatory than during ovulatory cycles,” the researchers wrote. Frequency did not differ significantly for complex or simple partial seizures, or for all seizure types combined. “Because the proportional increases in secondary generalized tonic-clonic seizure frequency during anovulatory cycles correlate with the proportional increases in estradiol/progesterone serum level ratios, these findings support a possible role for reproductive steroids in [seizure] occurrence.”
Researchers have identified a new genetic risk factor for restless legs syndrome (RLS), as reported in the July 14 PLoS Genetics. The authors conducted a genome-wide association study of 922 patients with RLS, and compared the results with 1,526 controls. The researchers included 301,406 single nucleotide polymorphisms (SNPs) in the study, followed by a replication of 76 candidate SNPs in 3,935 patients and 5,754 controls. “We identified six RLS susceptibility loci of genome-wide significance, two of them novel: an intergenic region on chromosome 2p14 (rs6747972) and a locus on 16q12.1 (rs3104767) in a linkage disequilibrium block of 40 kb containing the 5´-end of TOX3 and the adjacent noncoding RNA BC034767,” the investigators reported. They concluded, “The physiologic role of TOX3 and BC034767 in the CNS and a possible involvement of these two genes in RLS pathogenesis remain to be established.”
Breastfeeding does not significantly provide protection against postpartum relapses in women with multiple sclerosis (MS), a finding that contradicts results from previous studies, researchers reported in the July 12 Neurology. The investigators prospectively followed up pregnancies in 298 women with MS and gathered data on breastfeeding; they monitored relapse rates for up to one year after delivery. “The time-dependent profile of the relapse rate before, during, and after pregnancy did not differ between patients who breastfed and patients who did not,” the authors reported. The only significant predictors of postpartum relapses were relapses before and during pregnancy. “Therefore, the reported association between breastfeeding and a lower risk of postpartum relapses may simply reflect different patient behavior, biased by the disease activity,” the investigators concluded.
Low bone density and osteoporosis commonly appear in the early stages of multiple sclerosis (MS), according to a study published in the July 12 Neurology. “If vitamin D exerts a major effect on MS risk,” the investigators hypothesized, “skeletal consequences of hypovitaminosis D could be apparent shortly after the onset of MS.” To test their hypothesis, the researchers measured the bone mineral density of 99 patients in the early stages of the disease with no or minor disability; these results were compared with the densities of 159 healthy controls. Half of the patients had either osteopenia or osteoporosis, compared with 37.1% of the controls. “[This finding is] compatible with shared etiologic or pathogenic factors in MS and osteoporosis, and calls for an active approach to optimize bone health in early stages of MS,” the authors concluded.
According to a study published in the July 12 online BMJ, there is no significant link between adjuvanted vaccines used during the 2009 swine flu pandemic and Guillain-Barré syndrome. The investigators performed a case-control study in five European countries of 104 patients with the syndrome and age-, sex-, and location-matched controls. The initial, unadjusted pooled risk estimate for all countries was 2.8, and case recruitment and vaccine coverage varied considerably between countries. “After adjustment for influenza-like illness/upper respiratory tract infection and seasonal influenza vaccination, receipt of pandemic influenza vaccine was not associated with an increased risk of Guillain-Barré syndrome,” the investigators reported. They did note, however, “the upper limit does not exclude a potential increase in risk up to 2.7-fold or three excess cases per one million vaccinated people.”
A team of researchers has found a genetic determinant of late-onset Parkinson’s disease, according to a study published in the July 9 issue of American Journal of Human Genetics. “To identify rare causal variants in late-onset Parkinson’s disease, we investigated an Austrian family with 16 affected individuals by exome sequencing,” the investigators explained. “We found a missense mutation, c.1858G>A, in the VPS35 gene in all seven affected family members who are alive.” Screening the entire VPS35 coding sequence in additional Parkinson’s disease cases and controls revealed six other missense variants; three were only present in patients, two were only present in controls, and one was present in both groups. The investigators also noted, “VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer’s disease.”
Researchers have found that African-American patients with ischemic stroke are significantly less likely to be treated with IV t-PA, due to delayed presentation and stroke severity, according to a study published in the June 30 online Stroke. The investigators performed a systematic chart review on patients admitted to seven Washington, DC–area hospitals; of 1,044 patients with ischemic stroke, 74% were black and 5% received t-PA. African-American patients were one-third less likely than white patients to receive IV t-PA, were less likely to present at the hospital within three hours of symptom onset, and were less likely to be eligible for t-PA treatment. African-American patients also had a greater rate of contraindications to t-PA treatment, including hypertension, recent stroke, or use of blood thinners.
People with a history of traumatic brain injury (TBI) are more likely to develop long-term neurodegeneration than those who have never experienced a brain injury, according to research appearing in the June 29 online Brain Pathology. Investigators examined postmortem brains from 39 survivors of a single TBI and 47 brains of uninjured, age-matched controls using immunochemistry and thioflavin-S staining. “Neurofibrillary tangles were exceptionally rare in young, uninjured controls, yet were abundant and widely distributed in approximately one-third of TBI cases,” the researchers reported. In addition, patients with TBI had a greater density of amyloid-beta plaques than controls. “These data demonstrate widespread neurofibrillary tangles and amyloid-beta plaque pathologies are present in a proportion of patients following a single TBI, suggesting that some individuals who experience a single TBI may develop long-term neuropathological changes akin to those found in neurodegenerative disease,” the authors concluded.
A group of researchers presented a new set of practice guidelines regarding genetic counseling, as reported in the June Genetics in Medicine. The guidelines, developed through a joint effort by the American College of Medical Genetics and the National Society of Genetic Counselors, seek to provide medical professionals with guidance in the complex area of genetic testing. “Despite its limited utility, patients express concern over their risk and, in some instances, request testing,” the authors wrote. “This practice guideline provides clinicians with a framework for assessing their patients’ genetic risk for Alzheimer’s disease, identifying which individuals may benefit from genetic testing, and providing the key elements of genetic counseling for Alzheimer’s disease,” they concluded.
Regions important for cognitive and motor control are smaller in the brains of children with attention-deficit hyperactivity disorder (ADHD) than in typically developing children, researchers reported in the June 9 online Clinical Neuropsychologist. To understand the neurobiologic development of ADHD, the investigators examined high-resolution anatomic images of 13 children with ADHD and 13 controls (ages 4 to 5). “Children with ADHD showed significantly reduced caudate volumes bilaterally; in contrast there were no significant group differences in cortical volume or thickness in this range,” the authors observed. Left caudate volume was a significant predictor of hyperactive and impulsive symptom severity, but not inattention. “Anomalous basal ganglia, particularly caudate, development appears to play an important role among children presenting with early onset symptoms of ADHD,” the researchers concluded.
A diet low in saturated fat and simple carbohydrates may modulate the risk of developing dementia that precedes Alzheimer’s disease, researchers reported in the June Archives of Neurology. To compare the effects of different diets on insulin and lipid metabolism, CSF markers of Alzheimer’s disease, and cognition, the investigators randomized 20 healthy adults and 29 adults with amnestic mild cognitive impairment to either a high- or low-fat and glycemic index diet. In the cognitively impaired group, the “low” diet increased CSF amyloid-beta 42 concentrations; the opposite was true for healthy patients on this diet. For both groups, the “low” diet improved visual memory. “Diet may be a powerful environmental factor that modulates Alzheimer’s disease risk through its effects on CNS concentrations of amyloid-beta 42, lipoproteins, oxidative stress, and insulin,” the investigators concluded.
A study in the June Headache found that prophylactic medications and behavioral interventions for migraine are cost-competitive and cost-efficient options during the early phases of treatment. Researchers distributed surveys to physicians and behavioral specialists to gather data about costs of prototypical regimens for preventive pharmacologic treatment, clinic-based behavioral treatment, minimal contact behavioral treatment, and group behavioral treatment. During the initial months of treatment, pharmacologic treatment with inexpensive medications was the least costly option (

Vascular conditions, including atherosclerosis, may play an important role in the development of cognitive impairment and dementia, according to a report published online in the July 21 Stroke. The authors used previously published guidelines and literature, as well as personal experience, to summarize existing evidence, indicate gaps in current knowledge, and formulate recommendations regarding vascular contributions to cognitive decline late in life. Observed vascular risk factors included atrial fibrillation, hypertension, diabetes mellitus, and hypercholesterolemia, all of which, the researchers noted, were also risk factors for stroke and Alzheimer’s disease. “The neuropathology of cognitive impairment later in life is often a mixture of Alzheimer’s disease and microvascular brain damage,” the authors wrote. “Detection and control of the traditional risk factors for stroke and cardiovascular disease may be effective in the prevention of vascular cognitive impairment, even in older people.”
Women with epilepsy experience greater seizure frequency during anovulatory cycles than during cycles when ovulation occurs, according to results of a study published July 14 online ahead of print in Epilepsia. Almost 300 women with epilepsy were enrolled in the study; 92 had completed both cycles during the study period. Their average daily seizure frequency, seizure type, and progesterone/estradiol serum level ratios were recorded. “Average daily seizure frequency was 29.5% greater for secondary generalized tonic-clonic seizures during anovulatory than during ovulatory cycles,” the researchers wrote. Frequency did not differ significantly for complex or simple partial seizures, or for all seizure types combined. “Because the proportional increases in secondary generalized tonic-clonic seizure frequency during anovulatory cycles correlate with the proportional increases in estradiol/progesterone serum level ratios, these findings support a possible role for reproductive steroids in [seizure] occurrence.”
Researchers have identified a new genetic risk factor for restless legs syndrome (RLS), as reported in the July 14 PLoS Genetics. The authors conducted a genome-wide association study of 922 patients with RLS, and compared the results with 1,526 controls. The researchers included 301,406 single nucleotide polymorphisms (SNPs) in the study, followed by a replication of 76 candidate SNPs in 3,935 patients and 5,754 controls. “We identified six RLS susceptibility loci of genome-wide significance, two of them novel: an intergenic region on chromosome 2p14 (rs6747972) and a locus on 16q12.1 (rs3104767) in a linkage disequilibrium block of 40 kb containing the 5´-end of TOX3 and the adjacent noncoding RNA BC034767,” the investigators reported. They concluded, “The physiologic role of TOX3 and BC034767 in the CNS and a possible involvement of these two genes in RLS pathogenesis remain to be established.”
Breastfeeding does not significantly provide protection against postpartum relapses in women with multiple sclerosis (MS), a finding that contradicts results from previous studies, researchers reported in the July 12 Neurology. The investigators prospectively followed up pregnancies in 298 women with MS and gathered data on breastfeeding; they monitored relapse rates for up to one year after delivery. “The time-dependent profile of the relapse rate before, during, and after pregnancy did not differ between patients who breastfed and patients who did not,” the authors reported. The only significant predictors of postpartum relapses were relapses before and during pregnancy. “Therefore, the reported association between breastfeeding and a lower risk of postpartum relapses may simply reflect different patient behavior, biased by the disease activity,” the investigators concluded.
Low bone density and osteoporosis commonly appear in the early stages of multiple sclerosis (MS), according to a study published in the July 12 Neurology. “If vitamin D exerts a major effect on MS risk,” the investigators hypothesized, “skeletal consequences of hypovitaminosis D could be apparent shortly after the onset of MS.” To test their hypothesis, the researchers measured the bone mineral density of 99 patients in the early stages of the disease with no or minor disability; these results were compared with the densities of 159 healthy controls. Half of the patients had either osteopenia or osteoporosis, compared with 37.1% of the controls. “[This finding is] compatible with shared etiologic or pathogenic factors in MS and osteoporosis, and calls for an active approach to optimize bone health in early stages of MS,” the authors concluded.
According to a study published in the July 12 online BMJ, there is no significant link between adjuvanted vaccines used during the 2009 swine flu pandemic and Guillain-Barré syndrome. The investigators performed a case-control study in five European countries of 104 patients with the syndrome and age-, sex-, and location-matched controls. The initial, unadjusted pooled risk estimate for all countries was 2.8, and case recruitment and vaccine coverage varied considerably between countries. “After adjustment for influenza-like illness/upper respiratory tract infection and seasonal influenza vaccination, receipt of pandemic influenza vaccine was not associated with an increased risk of Guillain-Barré syndrome,” the investigators reported. They did note, however, “the upper limit does not exclude a potential increase in risk up to 2.7-fold or three excess cases per one million vaccinated people.”
A team of researchers has found a genetic determinant of late-onset Parkinson’s disease, according to a study published in the July 9 issue of American Journal of Human Genetics. “To identify rare causal variants in late-onset Parkinson’s disease, we investigated an Austrian family with 16 affected individuals by exome sequencing,” the investigators explained. “We found a missense mutation, c.1858G>A, in the VPS35 gene in all seven affected family members who are alive.” Screening the entire VPS35 coding sequence in additional Parkinson’s disease cases and controls revealed six other missense variants; three were only present in patients, two were only present in controls, and one was present in both groups. The investigators also noted, “VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer’s disease.”
Researchers have found that African-American patients with ischemic stroke are significantly less likely to be treated with IV t-PA, due to delayed presentation and stroke severity, according to a study published in the June 30 online Stroke. The investigators performed a systematic chart review on patients admitted to seven Washington, DC–area hospitals; of 1,044 patients with ischemic stroke, 74% were black and 5% received t-PA. African-American patients were one-third less likely than white patients to receive IV t-PA, were less likely to present at the hospital within three hours of symptom onset, and were less likely to be eligible for t-PA treatment. African-American patients also had a greater rate of contraindications to t-PA treatment, including hypertension, recent stroke, or use of blood thinners.
People with a history of traumatic brain injury (TBI) are more likely to develop long-term neurodegeneration than those who have never experienced a brain injury, according to research appearing in the June 29 online Brain Pathology. Investigators examined postmortem brains from 39 survivors of a single TBI and 47 brains of uninjured, age-matched controls using immunochemistry and thioflavin-S staining. “Neurofibrillary tangles were exceptionally rare in young, uninjured controls, yet were abundant and widely distributed in approximately one-third of TBI cases,” the researchers reported. In addition, patients with TBI had a greater density of amyloid-beta plaques than controls. “These data demonstrate widespread neurofibrillary tangles and amyloid-beta plaque pathologies are present in a proportion of patients following a single TBI, suggesting that some individuals who experience a single TBI may develop long-term neuropathological changes akin to those found in neurodegenerative disease,” the authors concluded.
A group of researchers presented a new set of practice guidelines regarding genetic counseling, as reported in the June Genetics in Medicine. The guidelines, developed through a joint effort by the American College of Medical Genetics and the National Society of Genetic Counselors, seek to provide medical professionals with guidance in the complex area of genetic testing. “Despite its limited utility, patients express concern over their risk and, in some instances, request testing,” the authors wrote. “This practice guideline provides clinicians with a framework for assessing their patients’ genetic risk for Alzheimer’s disease, identifying which individuals may benefit from genetic testing, and providing the key elements of genetic counseling for Alzheimer’s disease,” they concluded.
Regions important for cognitive and motor control are smaller in the brains of children with attention-deficit hyperactivity disorder (ADHD) than in typically developing children, researchers reported in the June 9 online Clinical Neuropsychologist. To understand the neurobiologic development of ADHD, the investigators examined high-resolution anatomic images of 13 children with ADHD and 13 controls (ages 4 to 5). “Children with ADHD showed significantly reduced caudate volumes bilaterally; in contrast there were no significant group differences in cortical volume or thickness in this range,” the authors observed. Left caudate volume was a significant predictor of hyperactive and impulsive symptom severity, but not inattention. “Anomalous basal ganglia, particularly caudate, development appears to play an important role among children presenting with early onset symptoms of ADHD,” the researchers concluded.
A diet low in saturated fat and simple carbohydrates may modulate the risk of developing dementia that precedes Alzheimer’s disease, researchers reported in the June Archives of Neurology. To compare the effects of different diets on insulin and lipid metabolism, CSF markers of Alzheimer’s disease, and cognition, the investigators randomized 20 healthy adults and 29 adults with amnestic mild cognitive impairment to either a high- or low-fat and glycemic index diet. In the cognitively impaired group, the “low” diet increased CSF amyloid-beta 42 concentrations; the opposite was true for healthy patients on this diet. For both groups, the “low” diet improved visual memory. “Diet may be a powerful environmental factor that modulates Alzheimer’s disease risk through its effects on CNS concentrations of amyloid-beta 42, lipoproteins, oxidative stress, and insulin,” the investigators concluded.
A study in the June Headache found that prophylactic medications and behavioral interventions for migraine are cost-competitive and cost-efficient options during the early phases of treatment. Researchers distributed surveys to physicians and behavioral specialists to gather data about costs of prototypical regimens for preventive pharmacologic treatment, clinic-based behavioral treatment, minimal contact behavioral treatment, and group behavioral treatment. During the initial months of treatment, pharmacologic treatment with inexpensive medications was the least costly option (

Vascular conditions, including atherosclerosis, may play an important role in the development of cognitive impairment and dementia, according to a report published online in the July 21 Stroke. The authors used previously published guidelines and literature, as well as personal experience, to summarize existing evidence, indicate gaps in current knowledge, and formulate recommendations regarding vascular contributions to cognitive decline late in life. Observed vascular risk factors included atrial fibrillation, hypertension, diabetes mellitus, and hypercholesterolemia, all of which, the researchers noted, were also risk factors for stroke and Alzheimer’s disease. “The neuropathology of cognitive impairment later in life is often a mixture of Alzheimer’s disease and microvascular brain damage,” the authors wrote. “Detection and control of the traditional risk factors for stroke and cardiovascular disease may be effective in the prevention of vascular cognitive impairment, even in older people.”
Women with epilepsy experience greater seizure frequency during anovulatory cycles than during cycles when ovulation occurs, according to results of a study published July 14 online ahead of print in Epilepsia. Almost 300 women with epilepsy were enrolled in the study; 92 had completed both cycles during the study period. Their average daily seizure frequency, seizure type, and progesterone/estradiol serum level ratios were recorded. “Average daily seizure frequency was 29.5% greater for secondary generalized tonic-clonic seizures during anovulatory than during ovulatory cycles,” the researchers wrote. Frequency did not differ significantly for complex or simple partial seizures, or for all seizure types combined. “Because the proportional increases in secondary generalized tonic-clonic seizure frequency during anovulatory cycles correlate with the proportional increases in estradiol/progesterone serum level ratios, these findings support a possible role for reproductive steroids in [seizure] occurrence.”
Researchers have identified a new genetic risk factor for restless legs syndrome (RLS), as reported in the July 14 PLoS Genetics. The authors conducted a genome-wide association study of 922 patients with RLS, and compared the results with 1,526 controls. The researchers included 301,406 single nucleotide polymorphisms (SNPs) in the study, followed by a replication of 76 candidate SNPs in 3,935 patients and 5,754 controls. “We identified six RLS susceptibility loci of genome-wide significance, two of them novel: an intergenic region on chromosome 2p14 (rs6747972) and a locus on 16q12.1 (rs3104767) in a linkage disequilibrium block of 40 kb containing the 5´-end of TOX3 and the adjacent noncoding RNA BC034767,” the investigators reported. They concluded, “The physiologic role of TOX3 and BC034767 in the CNS and a possible involvement of these two genes in RLS pathogenesis remain to be established.”
Breastfeeding does not significantly provide protection against postpartum relapses in women with multiple sclerosis (MS), a finding that contradicts results from previous studies, researchers reported in the July 12 Neurology. The investigators prospectively followed up pregnancies in 298 women with MS and gathered data on breastfeeding; they monitored relapse rates for up to one year after delivery. “The time-dependent profile of the relapse rate before, during, and after pregnancy did not differ between patients who breastfed and patients who did not,” the authors reported. The only significant predictors of postpartum relapses were relapses before and during pregnancy. “Therefore, the reported association between breastfeeding and a lower risk of postpartum relapses may simply reflect different patient behavior, biased by the disease activity,” the investigators concluded.
Low bone density and osteoporosis commonly appear in the early stages of multiple sclerosis (MS), according to a study published in the July 12 Neurology. “If vitamin D exerts a major effect on MS risk,” the investigators hypothesized, “skeletal consequences of hypovitaminosis D could be apparent shortly after the onset of MS.” To test their hypothesis, the researchers measured the bone mineral density of 99 patients in the early stages of the disease with no or minor disability; these results were compared with the densities of 159 healthy controls. Half of the patients had either osteopenia or osteoporosis, compared with 37.1% of the controls. “[This finding is] compatible with shared etiologic or pathogenic factors in MS and osteoporosis, and calls for an active approach to optimize bone health in early stages of MS,” the authors concluded.
According to a study published in the July 12 online BMJ, there is no significant link between adjuvanted vaccines used during the 2009 swine flu pandemic and Guillain-Barré syndrome. The investigators performed a case-control study in five European countries of 104 patients with the syndrome and age-, sex-, and location-matched controls. The initial, unadjusted pooled risk estimate for all countries was 2.8, and case recruitment and vaccine coverage varied considerably between countries. “After adjustment for influenza-like illness/upper respiratory tract infection and seasonal influenza vaccination, receipt of pandemic influenza vaccine was not associated with an increased risk of Guillain-Barré syndrome,” the investigators reported. They did note, however, “the upper limit does not exclude a potential increase in risk up to 2.7-fold or three excess cases per one million vaccinated people.”
A team of researchers has found a genetic determinant of late-onset Parkinson’s disease, according to a study published in the July 9 issue of American Journal of Human Genetics. “To identify rare causal variants in late-onset Parkinson’s disease, we investigated an Austrian family with 16 affected individuals by exome sequencing,” the investigators explained. “We found a missense mutation, c.1858G>A, in the VPS35 gene in all seven affected family members who are alive.” Screening the entire VPS35 coding sequence in additional Parkinson’s disease cases and controls revealed six other missense variants; three were only present in patients, two were only present in controls, and one was present in both groups. The investigators also noted, “VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer’s disease.”
Researchers have found that African-American patients with ischemic stroke are significantly less likely to be treated with IV t-PA, due to delayed presentation and stroke severity, according to a study published in the June 30 online Stroke. The investigators performed a systematic chart review on patients admitted to seven Washington, DC–area hospitals; of 1,044 patients with ischemic stroke, 74% were black and 5% received t-PA. African-American patients were one-third less likely than white patients to receive IV t-PA, were less likely to present at the hospital within three hours of symptom onset, and were less likely to be eligible for t-PA treatment. African-American patients also had a greater rate of contraindications to t-PA treatment, including hypertension, recent stroke, or use of blood thinners.
People with a history of traumatic brain injury (TBI) are more likely to develop long-term neurodegeneration than those who have never experienced a brain injury, according to research appearing in the June 29 online Brain Pathology. Investigators examined postmortem brains from 39 survivors of a single TBI and 47 brains of uninjured, age-matched controls using immunochemistry and thioflavin-S staining. “Neurofibrillary tangles were exceptionally rare in young, uninjured controls, yet were abundant and widely distributed in approximately one-third of TBI cases,” the researchers reported. In addition, patients with TBI had a greater density of amyloid-beta plaques than controls. “These data demonstrate widespread neurofibrillary tangles and amyloid-beta plaque pathologies are present in a proportion of patients following a single TBI, suggesting that some individuals who experience a single TBI may develop long-term neuropathological changes akin to those found in neurodegenerative disease,” the authors concluded.
A group of researchers presented a new set of practice guidelines regarding genetic counseling, as reported in the June Genetics in Medicine. The guidelines, developed through a joint effort by the American College of Medical Genetics and the National Society of Genetic Counselors, seek to provide medical professionals with guidance in the complex area of genetic testing. “Despite its limited utility, patients express concern over their risk and, in some instances, request testing,” the authors wrote. “This practice guideline provides clinicians with a framework for assessing their patients’ genetic risk for Alzheimer’s disease, identifying which individuals may benefit from genetic testing, and providing the key elements of genetic counseling for Alzheimer’s disease,” they concluded.
Regions important for cognitive and motor control are smaller in the brains of children with attention-deficit hyperactivity disorder (ADHD) than in typically developing children, researchers reported in the June 9 online Clinical Neuropsychologist. To understand the neurobiologic development of ADHD, the investigators examined high-resolution anatomic images of 13 children with ADHD and 13 controls (ages 4 to 5). “Children with ADHD showed significantly reduced caudate volumes bilaterally; in contrast there were no significant group differences in cortical volume or thickness in this range,” the authors observed. Left caudate volume was a significant predictor of hyperactive and impulsive symptom severity, but not inattention. “Anomalous basal ganglia, particularly caudate, development appears to play an important role among children presenting with early onset symptoms of ADHD,” the researchers concluded.
A diet low in saturated fat and simple carbohydrates may modulate the risk of developing dementia that precedes Alzheimer’s disease, researchers reported in the June Archives of Neurology. To compare the effects of different diets on insulin and lipid metabolism, CSF markers of Alzheimer’s disease, and cognition, the investigators randomized 20 healthy adults and 29 adults with amnestic mild cognitive impairment to either a high- or low-fat and glycemic index diet. In the cognitively impaired group, the “low” diet increased CSF amyloid-beta 42 concentrations; the opposite was true for healthy patients on this diet. For both groups, the “low” diet improved visual memory. “Diet may be a powerful environmental factor that modulates Alzheimer’s disease risk through its effects on CNS concentrations of amyloid-beta 42, lipoproteins, oxidative stress, and insulin,” the investigators concluded.
A study in the June Headache found that prophylactic medications and behavioral interventions for migraine are cost-competitive and cost-efficient options during the early phases of treatment. Researchers distributed surveys to physicians and behavioral specialists to gather data about costs of prototypical regimens for preventive pharmacologic treatment, clinic-based behavioral treatment, minimal contact behavioral treatment, and group behavioral treatment. During the initial months of treatment, pharmacologic treatment with inexpensive medications was the least costly option (

Statin Treatment Does Not Lower Risk for Recurrent Stroke in Patients With Type 2 Diabetes or Metabolic Syndrome
Patients with type 2 diabetes or metabolic syndrome did not benefit from treatment with atorvastatin, when compared with patients without either metabolic disorder, according to a study published in the June 13 online Archives of Neurology.
Alfred Callahan, MD, from the Vanderbilt University School of Medicine in Nashville, and colleagues conducted a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial to determine whether the effect of treatment on the primary end point (risk for stroke) and secondary end points (occurrence of coronary and cardiovascular events and procedures) varied based on the presence of type 2 diabetes or metabolic syndrome.
“The SPARCL trial found that statin treatment reduced stroke risk in patients with recent stroke or TIA and no known coronary heart disease (CHD),” Dr. Callahan’s group wrote. “No information is available, however, on the effect of statins on secondary stroke prevention in diabetic patients or in those with metabolic syndrome.”
Of the 4,731 subjects enrolled in the trial, 794 had diabetes and 642 had metabolic syndrome; 3,295 had neither condition and were included as the reference group. All patients were adults who had an ischemic or hemorrhagic stroke or TIA one to six months prior to randomization.
“The risk of stroke was 11.0% in the reference group, 18.1% in subjects with type 2 diabetes, and 10.7% in those with metabolic syndrome,” the investigators reported. “Subjects with type 2 diabetes mellitus were more likely to have any of the primary and secondary end points, including death.” Patients with metabolic syndrome had no increase in the risk of major cardiovascular events or major coronary events, but they were more likely to have any CHD event or revascularization procedure.
“In this post hoc analysis, we found that SPARCL subjects with type 2 diabetes mellitus were at higher risk for recurrent stroke and cardiovascular events but that there was no difference in the effect of statin treatment in reducing these events in subjects with or without type 2 diabetes or metabolic syndrome,” the authors concluded. They also noted that the possibility of variation on the benefit of statin treatment in subjects with or without type 2 diabetes or metabolic syndrome cannot be excluded by their analysis.
Callahan A, Amarenco P, Goldstein LB, et al. Risk of stroke and cardiovascular events after ischemic stroke or transient ischemic attack in patients with type 2 diabetes or metabolic syndrome: Secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Arch Neurol. 2011 Jun 13; [Epub ahead of print].

Does Stress Increase the Risk for Multiple Sclerosis?
Daily life- and work-related stress and childhood trauma have no significant impact on increasing the risk of developing multiple sclerosis (MS), according to a study published in the May 31 issue of Neurology.
“Several studies have shown that stressful life events are associated with a subsequent significant increase in risk of MS exacerbations,” the authors wrote. “We wanted to study prospectively whether stress can increase the risk of developing the disease itself.”
Trond Riise, PhD, from the Department of Public Health and Primary Health Care at the University of Bergen in Norway, and colleagues analyzed questionnaires regarding stress at work and home and the effects of physical and sexual abuse in childhood and adolescence completed by women in the Nurses’ Health Study and Nurses’ Health Study II who developed MS during the study period. They then conducted separate analyses by levels of stress and by severity of childhood abuse to calculate incidence rates and hazard ratios of MS.
“Stress measurements were available for 77 of the 94 women who had developed MS,” the researchers reported. “Adjusting for age, ethnicity, latitude at birth, BMI at age 18, and biannually updated smoking status, there were no significant differences in the risk of MS between any of the levels of stress at home or at work.” Of the 292 women from the Nurses’ Health Study II who responded to questions about childhood trauma, 7% reported severe abuse; there was no significant increased risk.
The lack of a significant relationship between stress and trauma and the risk for MS could potentially be caused by the study’s retrospective design. “A major challenge when studying this relation is to achieve unbiased measurement of stress,” the authors explained. “The possibility that these assessments were not sensitive to the stressors and stress mechanisms that might increase risk of developing MS cannot be ruled out.
“These results do not support a major role of stress [for developing MS], but repeated and more focused measures of stress are needed to firmly exclude stress as a potential risk factor for MS,” the investigators concluded.
Riise T, Mohr DC, Munger KL, et al. Stress and the risk of multiple sclerosis. Neurology. 2011;76(22);1866-1871.

Statin Treatment Does Not Lower Risk for Recurrent Stroke in Patients With Type 2 Diabetes or Metabolic Syndrome
Patients with type 2 diabetes or metabolic syndrome did not benefit from treatment with atorvastatin, when compared with patients without either metabolic disorder, according to a study published in the June 13 online Archives of Neurology.
Alfred Callahan, MD, from the Vanderbilt University School of Medicine in Nashville, and colleagues conducted a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial to determine whether the effect of treatment on the primary end point (risk for stroke) and secondary end points (occurrence of coronary and cardiovascular events and procedures) varied based on the presence of type 2 diabetes or metabolic syndrome.
“The SPARCL trial found that statin treatment reduced stroke risk in patients with recent stroke or TIA and no known coronary heart disease (CHD),” Dr. Callahan’s group wrote. “No information is available, however, on the effect of statins on secondary stroke prevention in diabetic patients or in those with metabolic syndrome.”
Of the 4,731 subjects enrolled in the trial, 794 had diabetes and 642 had metabolic syndrome; 3,295 had neither condition and were included as the reference group. All patients were adults who had an ischemic or hemorrhagic stroke or TIA one to six months prior to randomization.
“The risk of stroke was 11.0% in the reference group, 18.1% in subjects with type 2 diabetes, and 10.7% in those with metabolic syndrome,” the investigators reported. “Subjects with type 2 diabetes mellitus were more likely to have any of the primary and secondary end points, including death.” Patients with metabolic syndrome had no increase in the risk of major cardiovascular events or major coronary events, but they were more likely to have any CHD event or revascularization procedure.
“In this post hoc analysis, we found that SPARCL subjects with type 2 diabetes mellitus were at higher risk for recurrent stroke and cardiovascular events but that there was no difference in the effect of statin treatment in reducing these events in subjects with or without type 2 diabetes or metabolic syndrome,” the authors concluded. They also noted that the possibility of variation on the benefit of statin treatment in subjects with or without type 2 diabetes or metabolic syndrome cannot be excluded by their analysis.
Callahan A, Amarenco P, Goldstein LB, et al. Risk of stroke and cardiovascular events after ischemic stroke or transient ischemic attack in patients with type 2 diabetes or metabolic syndrome: Secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Arch Neurol. 2011 Jun 13; [Epub ahead of print].

Does Stress Increase the Risk for Multiple Sclerosis?
Daily life- and work-related stress and childhood trauma have no significant impact on increasing the risk of developing multiple sclerosis (MS), according to a study published in the May 31 issue of Neurology.
“Several studies have shown that stressful life events are associated with a subsequent significant increase in risk of MS exacerbations,” the authors wrote. “We wanted to study prospectively whether stress can increase the risk of developing the disease itself.”
Trond Riise, PhD, from the Department of Public Health and Primary Health Care at the University of Bergen in Norway, and colleagues analyzed questionnaires regarding stress at work and home and the effects of physical and sexual abuse in childhood and adolescence completed by women in the Nurses’ Health Study and Nurses’ Health Study II who developed MS during the study period. They then conducted separate analyses by levels of stress and by severity of childhood abuse to calculate incidence rates and hazard ratios of MS.
“Stress measurements were available for 77 of the 94 women who had developed MS,” the researchers reported. “Adjusting for age, ethnicity, latitude at birth, BMI at age 18, and biannually updated smoking status, there were no significant differences in the risk of MS between any of the levels of stress at home or at work.” Of the 292 women from the Nurses’ Health Study II who responded to questions about childhood trauma, 7% reported severe abuse; there was no significant increased risk.
The lack of a significant relationship between stress and trauma and the risk for MS could potentially be caused by the study’s retrospective design. “A major challenge when studying this relation is to achieve unbiased measurement of stress,” the authors explained. “The possibility that these assessments were not sensitive to the stressors and stress mechanisms that might increase risk of developing MS cannot be ruled out.
“These results do not support a major role of stress [for developing MS], but repeated and more focused measures of stress are needed to firmly exclude stress as a potential risk factor for MS,” the investigators concluded.
Riise T, Mohr DC, Munger KL, et al. Stress and the risk of multiple sclerosis. Neurology. 2011;76(22);1866-1871.

Statin Treatment Does Not Lower Risk for Recurrent Stroke in Patients With Type 2 Diabetes or Metabolic Syndrome
Patients with type 2 diabetes or metabolic syndrome did not benefit from treatment with atorvastatin, when compared with patients without either metabolic disorder, according to a study published in the June 13 online Archives of Neurology.
Alfred Callahan, MD, from the Vanderbilt University School of Medicine in Nashville, and colleagues conducted a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial to determine whether the effect of treatment on the primary end point (risk for stroke) and secondary end points (occurrence of coronary and cardiovascular events and procedures) varied based on the presence of type 2 diabetes or metabolic syndrome.
“The SPARCL trial found that statin treatment reduced stroke risk in patients with recent stroke or TIA and no known coronary heart disease (CHD),” Dr. Callahan’s group wrote. “No information is available, however, on the effect of statins on secondary stroke prevention in diabetic patients or in those with metabolic syndrome.”
Of the 4,731 subjects enrolled in the trial, 794 had diabetes and 642 had metabolic syndrome; 3,295 had neither condition and were included as the reference group. All patients were adults who had an ischemic or hemorrhagic stroke or TIA one to six months prior to randomization.
“The risk of stroke was 11.0% in the reference group, 18.1% in subjects with type 2 diabetes, and 10.7% in those with metabolic syndrome,” the investigators reported. “Subjects with type 2 diabetes mellitus were more likely to have any of the primary and secondary end points, including death.” Patients with metabolic syndrome had no increase in the risk of major cardiovascular events or major coronary events, but they were more likely to have any CHD event or revascularization procedure.
“In this post hoc analysis, we found that SPARCL subjects with type 2 diabetes mellitus were at higher risk for recurrent stroke and cardiovascular events but that there was no difference in the effect of statin treatment in reducing these events in subjects with or without type 2 diabetes or metabolic syndrome,” the authors concluded. They also noted that the possibility of variation on the benefit of statin treatment in subjects with or without type 2 diabetes or metabolic syndrome cannot be excluded by their analysis.
Callahan A, Amarenco P, Goldstein LB, et al. Risk of stroke and cardiovascular events after ischemic stroke or transient ischemic attack in patients with type 2 diabetes or metabolic syndrome: Secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Arch Neurol. 2011 Jun 13; [Epub ahead of print].

Does Stress Increase the Risk for Multiple Sclerosis?
Daily life- and work-related stress and childhood trauma have no significant impact on increasing the risk of developing multiple sclerosis (MS), according to a study published in the May 31 issue of Neurology.
“Several studies have shown that stressful life events are associated with a subsequent significant increase in risk of MS exacerbations,” the authors wrote. “We wanted to study prospectively whether stress can increase the risk of developing the disease itself.”
Trond Riise, PhD, from the Department of Public Health and Primary Health Care at the University of Bergen in Norway, and colleagues analyzed questionnaires regarding stress at work and home and the effects of physical and sexual abuse in childhood and adolescence completed by women in the Nurses’ Health Study and Nurses’ Health Study II who developed MS during the study period. They then conducted separate analyses by levels of stress and by severity of childhood abuse to calculate incidence rates and hazard ratios of MS.
“Stress measurements were available for 77 of the 94 women who had developed MS,” the researchers reported. “Adjusting for age, ethnicity, latitude at birth, BMI at age 18, and biannually updated smoking status, there were no significant differences in the risk of MS between any of the levels of stress at home or at work.” Of the 292 women from the Nurses’ Health Study II who responded to questions about childhood trauma, 7% reported severe abuse; there was no significant increased risk.
The lack of a significant relationship between stress and trauma and the risk for MS could potentially be caused by the study’s retrospective design. “A major challenge when studying this relation is to achieve unbiased measurement of stress,” the authors explained. “The possibility that these assessments were not sensitive to the stressors and stress mechanisms that might increase risk of developing MS cannot be ruled out.
“These results do not support a major role of stress [for developing MS], but repeated and more focused measures of stress are needed to firmly exclude stress as a potential risk factor for MS,” the investigators concluded.
Riise T, Mohr DC, Munger KL, et al. Stress and the risk of multiple sclerosis. Neurology. 2011;76(22);1866-1871.

Olfactory bulb and brain volume may provide valuable information about olfactory dysfunction in patients with MS.

HONOLULU—A correlation between decreased olfactory bulb and brain volume and multiple sclerosis (MS) lesions may help to explain olfactory dysfunction among patients with MS, according to research presented at the American Academy of Neurology’s 63rd Annual Meeting.

Noting that olfactory dysfunction can occur in patients with MS, Felix Alexander Schmidt, a medical student at the Department of Neurology, University Hospitals Charité in Berlin, and colleagues investigated the reasons for the problem and the best ways of detecting it. They determined and compared objective olfactometry, olfactory bulb volume, olfactory brain volume, and number and volume of lesions in the olfactory brain in patients with MS.

Their study, which was also published in the May 17 online PLoS One, included 34 patients (24 women), ages 22 to 64, with MS and 30 healthy controls matched by age, sex, and smoking habits. Participants’ olfactory bulb volume, olfactory brain volume, and plaque load were assessed with use of MRI. The researchers performed orthonasal olfactory testing using the Threshold-Discrimination-Identification test, and they determined objective olfactometry by measuring Olfactory-Evoked-Potentials. Participants also were given the Expanded Disability Status Scale (EDSS) test.

Olfactory dysfunction was present in 41% of patients with MS and 8% of the control group. The researchers found hyposmia in 71% of patients with a decreased olfactory bulb volume (<100 mm3) and 83% of patients with a decreased olfactory brain volume (<30,000 mm3). Decreased olfactory bulb volume was correlated with objective olfactometry, as well as with the number and volume of MS lesions in the olfactory brain. In addition, decreased olfactory brain volume was correlated with the volume of lesions in the olfactory brain and EDSS scores. Patients’ scores on the Identification subtest of the Threshold-Discrimination-Identification test were correlated with their EDSS scores, latest relapsing phase, and disease duration.

“The correlation between a higher number and volume of lesions in the olfactory brain with a decreased olfactory bulb and olfactory brain volume could help to explain olfactory dysfunction in MS patients,” the researchers concluded. “The correlation between volumetric measurements and objective olfactometry results shows that olfactory bulb and olfactory brain volume may provide valuable information about olfactory function in MS patients. Hyposmia seems to appear more frequently in an early stage of disease. The Identification subtest was especially sensitive in detecting olfactory changes in MS patients.”

Olfactory bulb and brain volume may provide valuable information about olfactory dysfunction in patients with MS.

HONOLULU—A correlation between decreased olfactory bulb and brain volume and multiple sclerosis (MS) lesions may help to explain olfactory dysfunction among patients with MS, according to research presented at the American Academy of Neurology’s 63rd Annual Meeting.

Noting that olfactory dysfunction can occur in patients with MS, Felix Alexander Schmidt, a medical student at the Department of Neurology, University Hospitals Charité in Berlin, and colleagues investigated the reasons for the problem and the best ways of detecting it. They determined and compared objective olfactometry, olfactory bulb volume, olfactory brain volume, and number and volume of lesions in the olfactory brain in patients with MS.

Their study, which was also published in the May 17 online PLoS One, included 34 patients (24 women), ages 22 to 64, with MS and 30 healthy controls matched by age, sex, and smoking habits. Participants’ olfactory bulb volume, olfactory brain volume, and plaque load were assessed with use of MRI. The researchers performed orthonasal olfactory testing using the Threshold-Discrimination-Identification test, and they determined objective olfactometry by measuring Olfactory-Evoked-Potentials. Participants also were given the Expanded Disability Status Scale (EDSS) test.

Olfactory dysfunction was present in 41% of patients with MS and 8% of the control group. The researchers found hyposmia in 71% of patients with a decreased olfactory bulb volume (<100 mm3) and 83% of patients with a decreased olfactory brain volume (<30,000 mm3). Decreased olfactory bulb volume was correlated with objective olfactometry, as well as with the number and volume of MS lesions in the olfactory brain. In addition, decreased olfactory brain volume was correlated with the volume of lesions in the olfactory brain and EDSS scores. Patients’ scores on the Identification subtest of the Threshold-Discrimination-Identification test were correlated with their EDSS scores, latest relapsing phase, and disease duration.

“The correlation between a higher number and volume of lesions in the olfactory brain with a decreased olfactory bulb and olfactory brain volume could help to explain olfactory dysfunction in MS patients,” the researchers concluded. “The correlation between volumetric measurements and objective olfactometry results shows that olfactory bulb and olfactory brain volume may provide valuable information about olfactory function in MS patients. Hyposmia seems to appear more frequently in an early stage of disease. The Identification subtest was especially sensitive in detecting olfactory changes in MS patients.”

Olfactory bulb and brain volume may provide valuable information about olfactory dysfunction in patients with MS.

HONOLULU—A correlation between decreased olfactory bulb and brain volume and multiple sclerosis (MS) lesions may help to explain olfactory dysfunction among patients with MS, according to research presented at the American Academy of Neurology’s 63rd Annual Meeting.

Noting that olfactory dysfunction can occur in patients with MS, Felix Alexander Schmidt, a medical student at the Department of Neurology, University Hospitals Charité in Berlin, and colleagues investigated the reasons for the problem and the best ways of detecting it. They determined and compared objective olfactometry, olfactory bulb volume, olfactory brain volume, and number and volume of lesions in the olfactory brain in patients with MS.

Their study, which was also published in the May 17 online PLoS One, included 34 patients (24 women), ages 22 to 64, with MS and 30 healthy controls matched by age, sex, and smoking habits. Participants’ olfactory bulb volume, olfactory brain volume, and plaque load were assessed with use of MRI. The researchers performed orthonasal olfactory testing using the Threshold-Discrimination-Identification test, and they determined objective olfactometry by measuring Olfactory-Evoked-Potentials. Participants also were given the Expanded Disability Status Scale (EDSS) test.

Olfactory dysfunction was present in 41% of patients with MS and 8% of the control group. The researchers found hyposmia in 71% of patients with a decreased olfactory bulb volume (<100 mm3) and 83% of patients with a decreased olfactory brain volume (<30,000 mm3). Decreased olfactory bulb volume was correlated with objective olfactometry, as well as with the number and volume of MS lesions in the olfactory brain. In addition, decreased olfactory brain volume was correlated with the volume of lesions in the olfactory brain and EDSS scores. Patients’ scores on the Identification subtest of the Threshold-Discrimination-Identification test were correlated with their EDSS scores, latest relapsing phase, and disease duration.

“The correlation between a higher number and volume of lesions in the olfactory brain with a decreased olfactory bulb and olfactory brain volume could help to explain olfactory dysfunction in MS patients,” the researchers concluded. “The correlation between volumetric measurements and objective olfactometry results shows that olfactory bulb and olfactory brain volume may provide valuable information about olfactory function in MS patients. Hyposmia seems to appear more frequently in an early stage of disease. The Identification subtest was especially sensitive in detecting olfactory changes in MS patients.”

Neurologic and psychiatric comorbidities pose additional challenges for treating patients with MS.

HONOLULU—A survey comparing adults with multiple sclerosis (MS) and healthy controls revealed that persons with the disease have a higher prevalence of comorbid neurologic, psychiatric, and cardiovascular symptoms and conditions, all of which may complicate disease management. The research was presented at the 63rd Annual Meeting of the American Academy of Neurology.

“A better understanding of the nature and prevalence of comorbid illness in MS may guide development of treatment protocols to improve outcomes in individuals with MS with comorbidities,” reported Michelle Stewart, PhD, from Pfizer Global Research and Development in New London, Connecticut, and colleagues.

The researchers collected data from the National Health and Wellness Survey, an internet-based annual study of health care attitudes in the United States. Dr. Stewart’s group analyzed responses from 549 patients with MS (mean age, 48.6) and 74,451 healthy controls (mean age, 47.9). Respondents’ demographics, health status information, and comorbid symptoms and conditions were recorded.

“Compared with controls, a greater proportion of individuals with MS reported being female and white,” the researchers reported. Although patients with MS were more likely to be poor and unemployed, they were also more likely to have health insurance. Regarding health status, “individuals with MS were less likely to use alcohol, less likely to exercise, and more likely to smoke.”

Common Neurologic, Psychiatric, and Cardiovascular Comorbidities
When the researchers compared data from patients with MS and healthy controls, they found statistically significant differences for several neurologic, psychiatric, and cardiovascular symptoms and conditions.

Pain, headache, migraine, restless legs syndrome, stroke, epilepsy, dementia, Parkinson’s disease, and Alzheimer’s disease were all more prevalent in patients with MS than in persons without the disorder. More than 50% of the MS cohort reported pain and headache as neurologic symptoms; Parkinson’s disease (2.0%) and Alzheimer’s disease (1.9%) were the least commonly reported conditions.

Among psychiatric comorbidities that were recorded, sleep difficulties, depression, and anxiety were the most commonly reported symptoms in both populations. Statistically significant differences were also found between patients with MS and controls in the following conditions and symptoms: insomnia, panic disorder, bipolar disorder, generalized anxiety disorder, obsessive compulsive disorder, posttraumatic stress disorder, and narcolepsy.

Patients with MS had a higher prevalence of cardiovascular symptoms, including angina, arrhythmia, transient ischemic stroke, and deep vein thrombosis, compared with controls. However, the investigators reported, “rates for hypertension, high cholesterol, ever had a heart attack, congestive heart failure, and atrial fibrillation were similar for individuals with and without MS.”

Impact of Comorbid Illness on MS Treatment
“An increasing amount of evidence suggests that physical and mental comorbidities, and adverse health factors such as smoking and obesity, are common in MS,” the authors stated. “These comorbidities and lifestyle factors may affect the diagnostic delay between symptom onset and diagnosis, disability progression, and health-related quality of life.”

In this study, persons with MS had significant comorbid illness, compared with controls, as the researchers expected. “Neurologic and psychiatric comorbid conditions and symptoms are common and typically more prevalent in MS,” the authors explained. “Cardiovascular risk factors in individuals with MS are similar to risk factors in controls, although some conditions have a higher association.

“The presence of comorbidities in individuals with MS merits attention as they may present challenges in managing this chronic and progressive disorder,” the researchers concluded.

Neurologic and psychiatric comorbidities pose additional challenges for treating patients with MS.

HONOLULU—A survey comparing adults with multiple sclerosis (MS) and healthy controls revealed that persons with the disease have a higher prevalence of comorbid neurologic, psychiatric, and cardiovascular symptoms and conditions, all of which may complicate disease management. The research was presented at the 63rd Annual Meeting of the American Academy of Neurology.

“A better understanding of the nature and prevalence of comorbid illness in MS may guide development of treatment protocols to improve outcomes in individuals with MS with comorbidities,” reported Michelle Stewart, PhD, from Pfizer Global Research and Development in New London, Connecticut, and colleagues.

The researchers collected data from the National Health and Wellness Survey, an internet-based annual study of health care attitudes in the United States. Dr. Stewart’s group analyzed responses from 549 patients with MS (mean age, 48.6) and 74,451 healthy controls (mean age, 47.9). Respondents’ demographics, health status information, and comorbid symptoms and conditions were recorded.

“Compared with controls, a greater proportion of individuals with MS reported being female and white,” the researchers reported. Although patients with MS were more likely to be poor and unemployed, they were also more likely to have health insurance. Regarding health status, “individuals with MS were less likely to use alcohol, less likely to exercise, and more likely to smoke.”

Common Neurologic, Psychiatric, and Cardiovascular Comorbidities
When the researchers compared data from patients with MS and healthy controls, they found statistically significant differences for several neurologic, psychiatric, and cardiovascular symptoms and conditions.

Pain, headache, migraine, restless legs syndrome, stroke, epilepsy, dementia, Parkinson’s disease, and Alzheimer’s disease were all more prevalent in patients with MS than in persons without the disorder. More than 50% of the MS cohort reported pain and headache as neurologic symptoms; Parkinson’s disease (2.0%) and Alzheimer’s disease (1.9%) were the least commonly reported conditions.

Among psychiatric comorbidities that were recorded, sleep difficulties, depression, and anxiety were the most commonly reported symptoms in both populations. Statistically significant differences were also found between patients with MS and controls in the following conditions and symptoms: insomnia, panic disorder, bipolar disorder, generalized anxiety disorder, obsessive compulsive disorder, posttraumatic stress disorder, and narcolepsy.

Patients with MS had a higher prevalence of cardiovascular symptoms, including angina, arrhythmia, transient ischemic stroke, and deep vein thrombosis, compared with controls. However, the investigators reported, “rates for hypertension, high cholesterol, ever had a heart attack, congestive heart failure, and atrial fibrillation were similar for individuals with and without MS.”

Impact of Comorbid Illness on MS Treatment
“An increasing amount of evidence suggests that physical and mental comorbidities, and adverse health factors such as smoking and obesity, are common in MS,” the authors stated. “These comorbidities and lifestyle factors may affect the diagnostic delay between symptom onset and diagnosis, disability progression, and health-related quality of life.”

In this study, persons with MS had significant comorbid illness, compared with controls, as the researchers expected. “Neurologic and psychiatric comorbid conditions and symptoms are common and typically more prevalent in MS,” the authors explained. “Cardiovascular risk factors in individuals with MS are similar to risk factors in controls, although some conditions have a higher association.

“The presence of comorbidities in individuals with MS merits attention as they may present challenges in managing this chronic and progressive disorder,” the researchers concluded.

Neurologic and psychiatric comorbidities pose additional challenges for treating patients with MS.

HONOLULU—A survey comparing adults with multiple sclerosis (MS) and healthy controls revealed that persons with the disease have a higher prevalence of comorbid neurologic, psychiatric, and cardiovascular symptoms and conditions, all of which may complicate disease management. The research was presented at the 63rd Annual Meeting of the American Academy of Neurology.

“A better understanding of the nature and prevalence of comorbid illness in MS may guide development of treatment protocols to improve outcomes in individuals with MS with comorbidities,” reported Michelle Stewart, PhD, from Pfizer Global Research and Development in New London, Connecticut, and colleagues.

The researchers collected data from the National Health and Wellness Survey, an internet-based annual study of health care attitudes in the United States. Dr. Stewart’s group analyzed responses from 549 patients with MS (mean age, 48.6) and 74,451 healthy controls (mean age, 47.9). Respondents’ demographics, health status information, and comorbid symptoms and conditions were recorded.

“Compared with controls, a greater proportion of individuals with MS reported being female and white,” the researchers reported. Although patients with MS were more likely to be poor and unemployed, they were also more likely to have health insurance. Regarding health status, “individuals with MS were less likely to use alcohol, less likely to exercise, and more likely to smoke.”

Common Neurologic, Psychiatric, and Cardiovascular Comorbidities
When the researchers compared data from patients with MS and healthy controls, they found statistically significant differences for several neurologic, psychiatric, and cardiovascular symptoms and conditions.

Pain, headache, migraine, restless legs syndrome, stroke, epilepsy, dementia, Parkinson’s disease, and Alzheimer’s disease were all more prevalent in patients with MS than in persons without the disorder. More than 50% of the MS cohort reported pain and headache as neurologic symptoms; Parkinson’s disease (2.0%) and Alzheimer’s disease (1.9%) were the least commonly reported conditions.

Among psychiatric comorbidities that were recorded, sleep difficulties, depression, and anxiety were the most commonly reported symptoms in both populations. Statistically significant differences were also found between patients with MS and controls in the following conditions and symptoms: insomnia, panic disorder, bipolar disorder, generalized anxiety disorder, obsessive compulsive disorder, posttraumatic stress disorder, and narcolepsy.

Patients with MS had a higher prevalence of cardiovascular symptoms, including angina, arrhythmia, transient ischemic stroke, and deep vein thrombosis, compared with controls. However, the investigators reported, “rates for hypertension, high cholesterol, ever had a heart attack, congestive heart failure, and atrial fibrillation were similar for individuals with and without MS.”

Impact of Comorbid Illness on MS Treatment
“An increasing amount of evidence suggests that physical and mental comorbidities, and adverse health factors such as smoking and obesity, are common in MS,” the authors stated. “These comorbidities and lifestyle factors may affect the diagnostic delay between symptom onset and diagnosis, disability progression, and health-related quality of life.”

In this study, persons with MS had significant comorbid illness, compared with controls, as the researchers expected. “Neurologic and psychiatric comorbid conditions and symptoms are common and typically more prevalent in MS,” the authors explained. “Cardiovascular risk factors in individuals with MS are similar to risk factors in controls, although some conditions have a higher association.

“The presence of comorbidities in individuals with MS merits attention as they may present challenges in managing this chronic and progressive disorder,” the researchers concluded.

One third of patients with pathologically confirmed early-onset Alzheimer’s disease presented with atypical symptoms, and 53% of patients with nonamnestic presentations were initially misdiagnosed, according to a study in the May 17 Neurology. Researchers conducted a retrospective review of clinical data from patients with confirmed early-onset Alzheimer’s disease to determine the frequency and types of incorrect diagnoses. The majority of these cases were diagnosed with other types of dementia, including pseudodementia with depression, semantic dementia, and primary progressive aphasia. “Early-onset Alzheimer’s disease diagnosis often represents a challenge because of the high frequency of atypical presentations,” the study authors wrote. More than one-third (37.5%) of patients presented with atypical symptoms other than memory problems; the most prevalent of these was behavioral/executive dysfunction.

Neuronal activity may be a potential mechanism for vulnerability to amyloid-β deposition in certain areas of the brain, researchers reported in the May 1 online Nature Neuroscience. The investigators examined endogenous neuronal activity in mice with Alzheimer’s disease and determined that this activity regulates the regional concentration of interstitial fluid amyloid-β, which drives local aggregation of amyloid-β. Using unilateral vibrissal stimulation in the contralateral barrel cortex, they found that activity increased interstitial fluid amyloid-β. Unilateral vibrissal deprivation decreased interstitial fluid amyloid-β deposition; long-term deprivation also decreased amyloid plaque formation and growth. “Our results suggest a mechanism to account for the vulnerability of specific brain regions to amyloid-β deposition in Alzheimer’s disease,” the authors concluded.

A newly confirmed genetic risk allele of the clusterin gene contributes to white matter degeneration in young adults and may increase the risk for Alzheimer’s disease later in life, according to results published in the May 4 Journal of Neuroscience. Investigators used diffusion-tensor MRI to scan the brains of 398 healthy young adults (mean age, 23.6) and to evaluate whether the C-allele clusterin risk variant was associated with lower white matter integrity. “Each C-allele copy of the clusterin variant was associated with lower fractional anisotropy—a widely accepted measure of white matter integrity—in multiple brain regions,” the authors wrote. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. “Young healthy carriers of the clusterin gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing Alzheimer’s disease later in life,” the researchers concluded.

A higher BMI may improve survival in patients with amyotrophic lateral sclerosis (ALS). As published in the May 23 online Muscle & Nerve, investigators aimed to determine whether cholesterol levels are an independent predictor of ALS survival. They measured cholesterol levels in 427 people with ALS from three clinical trial databases and found that the low-density and high-density lipoprotein level ratio did not decrease over time, even though BMI significantly declined. “After adjusting for BMI, forced vital capacity, and age, the lipid ratio was not associated with survival,” the investigators wrote. The highest survival rate, though, was found among patients with a BMI between 30 and 35, or mild obesity. “We found that dyslipidemia is not an independent predictor of survival in ALS,” the researchers concluded, whereas, “BMI is an independent prognostic factor for survival after adjusting for markers of disease severity.”

Patients with a history of intracerebral hemorrhage (ICH) should avoid using statins for prevention of ischemic cardiac and cerebrovascular disease, according to a study in the May Archives of Neurology. Statins are widely prescribed for disease prevention, the authors noted, and “although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of ICH associated with statin use.” To determine if statin therapy should be avoided in patients with a baseline elevated risk of ICH, investigators evaluated the risks and benefits of the therapy in patients with prior ICH using clinical parameters such as hemorrhage location (deep or lobar). For survivors of ICH both with and without prior cardiovascular events, the benefits of statin therapy were not strong enough to offset the increased risk for hemorrhage recurrence.

Adverse changes in sleep duration are associated with poorer cognitive function in middle-aged adults, per a study in the May 1 Sleep. Researchers conducted cross-sectional studies of women and men (age range, 45 to 69) to examine the effect of changes in sleep duration on cognitive function. Participants’ cognitive function was assessed at baseline, and their sleep duration on an average weeknight was measured once at baseline and again an average of 5.4 years later. After adjustment for age, gender, education, and occupation, the authors reported that “firm evidence remained for an association between an increase from seven or eight hours sleep and lower cognitive function for all tests, except memory, and between a decrease from six or eight hours sleep and poorer reasoning, vocabulary, and Mini-Mental State Examination score.” These adverse changes in duration were equivalent to a four- to seven-year increase in age.

African Americans with multiple sclerosis (MS) have lower vitamin D levels than their healthy counterparts, according to a study published in the May 24 Neurology. Researchers conducted a cross-sectional study of 339 African-American patients with MS and 342 without MS to determine if vitamin D levels were associated with MS disease severity. Between 71% and 77% of all participants were vitamin D–deficient and 93% to 94% were vitamin D–insufficient, the authors reported. Overall, vitamin D levels were lower in patients with MS, but this was due to differences in climate and geography and did not have an impact on disease severity. “These results are consistent with observations in other populations that lower [vitamin D level] is associated with having MS,” the investigators concluded, “but also highlight the importance of climate and ancestry in determining vitamin D status.”

Protein-based human-induced pluripotent stem cells (hiPSCs) and those derived from human embryonic stem cells (hESCs) may be effective in the treatment of Parkinson’s disease, according to a study in the May 16 Journal of Clinical Investigation. Results showed that neuronal precursors cells derived from hESCs and protein-based hiPSCs reversed disease when transplanted into the brains of rats modeling Parkinson’s disease. The researchers attempted to use neuronal cells derived from virus-based hiPSCs but were unable to do so because these virus-based cells exhibited apoptotic cell death. “[hiPSCs] are a potentially unlimited source of patient-specific cells for transplantation…. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of Parkinson’s disease,” the investigators concluded.

Women may have a greater risk than men for adverse events following certain stroke prevention procedures, as reported in the May 6 online Lancet Neurology. A total of 2,502 patients with symptomatic and asymptomatic stenosis were randomized to undergo carotid endarterectomy or carotid artery stenting. The rates of periprocedural stroke, myocardial infarction, and death were similar in men who underwent endarterectomy (4.9%) and stenting (4.3%). In women, however, a significant difference in rates of adverse events was observed—3.8% for endarterectomy versus 6.8% for stenting. “Periprocedural risk of events seems to be higher in women who have carotid artery stenting than those who have carotid endarterectomy, whereas there is little difference in men,” the authors concluded. “Additional data are needed to confirm whether this differential risk should be taken into account in decisions for treatment of carotid disease in women.”

About 14% of ischemic strokes presented at emergency departments are wake-up strokes, researchers reported in the May 10 Neurology. Wake-up strokes, according to the authors, cannot be distinguished from other types of stroke based on clinical features or outcome, making them difficult to treat with effective clot-busting therapies. The researchers analyzed data from patients presenting at emergency departments with ischemic stroke; they identified 1,854 ischemic stroke cases, 273 of which were wake-up strokes. “There were no differences between wake-up strokes and all other strokes with regard to clinical features or outcomes except for minor differences in age and baseline retrospective NIH Stroke Scale score,” the authors reported. “Of the wake-up strokes, at least 98 (35.9%) would have been eligible for thrombolysis if arrival time were not a factor.”

The annual rate of coronary artery bypass graft surgeries decreased 30% between 2001 and 2008, while rates of other percutaneous coronary interventions remained stable, according to an examination of national trends published in the May 4 JAMA. Investigators conducted a serial cross-sectional study to examine time trends of patients undergoing revascularization procedures, and determined that the annual surgery rate decreased from 1,742 to 1,081 per million adults in 2008. “Between 2001 and 2008, the number of hospitals … providing [coronary artery bypass graft surgery] increased by 12%, and the number of [percutaneous coronary interventions] hospitals increased by 26%,” the authors reported. They noted that new revascularization technologies, new clinical evidence from trials, and updated clinical guidelines may have affected the volume and distribution of coronary revascularizations.

Patients with traumatic brain injury (TBI) and refractory intracranial hypertension may benefit from decompressive craniectomy, but they may also experience unfavorable outcomes, according to a study in the April 21 New England Journal of Medicine. Researchers randomly assigned 155 adults with TBI and intracranial hypertension to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The results revealed that the standard-care group had higher levels of intracranial pressure and longer stays in the intensive care unit. “However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care,” the authors noted. Patients with craniectomy were also more than twice as likely to experience an unfavorable outcome, including death, vegetative state, or severe disability.

One third of patients with pathologically confirmed early-onset Alzheimer’s disease presented with atypical symptoms, and 53% of patients with nonamnestic presentations were initially misdiagnosed, according to a study in the May 17 Neurology. Researchers conducted a retrospective review of clinical data from patients with confirmed early-onset Alzheimer’s disease to determine the frequency and types of incorrect diagnoses. The majority of these cases were diagnosed with other types of dementia, including pseudodementia with depression, semantic dementia, and primary progressive aphasia. “Early-onset Alzheimer’s disease diagnosis often represents a challenge because of the high frequency of atypical presentations,” the study authors wrote. More than one-third (37.5%) of patients presented with atypical symptoms other than memory problems; the most prevalent of these was behavioral/executive dysfunction.

Neuronal activity may be a potential mechanism for vulnerability to amyloid-β deposition in certain areas of the brain, researchers reported in the May 1 online Nature Neuroscience. The investigators examined endogenous neuronal activity in mice with Alzheimer’s disease and determined that this activity regulates the regional concentration of interstitial fluid amyloid-β, which drives local aggregation of amyloid-β. Using unilateral vibrissal stimulation in the contralateral barrel cortex, they found that activity increased interstitial fluid amyloid-β. Unilateral vibrissal deprivation decreased interstitial fluid amyloid-β deposition; long-term deprivation also decreased amyloid plaque formation and growth. “Our results suggest a mechanism to account for the vulnerability of specific brain regions to amyloid-β deposition in Alzheimer’s disease,” the authors concluded.

A newly confirmed genetic risk allele of the clusterin gene contributes to white matter degeneration in young adults and may increase the risk for Alzheimer’s disease later in life, according to results published in the May 4 Journal of Neuroscience. Investigators used diffusion-tensor MRI to scan the brains of 398 healthy young adults (mean age, 23.6) and to evaluate whether the C-allele clusterin risk variant was associated with lower white matter integrity. “Each C-allele copy of the clusterin variant was associated with lower fractional anisotropy—a widely accepted measure of white matter integrity—in multiple brain regions,” the authors wrote. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. “Young healthy carriers of the clusterin gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing Alzheimer’s disease later in life,” the researchers concluded.

A higher BMI may improve survival in patients with amyotrophic lateral sclerosis (ALS). As published in the May 23 online Muscle & Nerve, investigators aimed to determine whether cholesterol levels are an independent predictor of ALS survival. They measured cholesterol levels in 427 people with ALS from three clinical trial databases and found that the low-density and high-density lipoprotein level ratio did not decrease over time, even though BMI significantly declined. “After adjusting for BMI, forced vital capacity, and age, the lipid ratio was not associated with survival,” the investigators wrote. The highest survival rate, though, was found among patients with a BMI between 30 and 35, or mild obesity. “We found that dyslipidemia is not an independent predictor of survival in ALS,” the researchers concluded, whereas, “BMI is an independent prognostic factor for survival after adjusting for markers of disease severity.”

Patients with a history of intracerebral hemorrhage (ICH) should avoid using statins for prevention of ischemic cardiac and cerebrovascular disease, according to a study in the May Archives of Neurology. Statins are widely prescribed for disease prevention, the authors noted, and “although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of ICH associated with statin use.” To determine if statin therapy should be avoided in patients with a baseline elevated risk of ICH, investigators evaluated the risks and benefits of the therapy in patients with prior ICH using clinical parameters such as hemorrhage location (deep or lobar). For survivors of ICH both with and without prior cardiovascular events, the benefits of statin therapy were not strong enough to offset the increased risk for hemorrhage recurrence.

Adverse changes in sleep duration are associated with poorer cognitive function in middle-aged adults, per a study in the May 1 Sleep. Researchers conducted cross-sectional studies of women and men (age range, 45 to 69) to examine the effect of changes in sleep duration on cognitive function. Participants’ cognitive function was assessed at baseline, and their sleep duration on an average weeknight was measured once at baseline and again an average of 5.4 years later. After adjustment for age, gender, education, and occupation, the authors reported that “firm evidence remained for an association between an increase from seven or eight hours sleep and lower cognitive function for all tests, except memory, and between a decrease from six or eight hours sleep and poorer reasoning, vocabulary, and Mini-Mental State Examination score.” These adverse changes in duration were equivalent to a four- to seven-year increase in age.

African Americans with multiple sclerosis (MS) have lower vitamin D levels than their healthy counterparts, according to a study published in the May 24 Neurology. Researchers conducted a cross-sectional study of 339 African-American patients with MS and 342 without MS to determine if vitamin D levels were associated with MS disease severity. Between 71% and 77% of all participants were vitamin D–deficient and 93% to 94% were vitamin D–insufficient, the authors reported. Overall, vitamin D levels were lower in patients with MS, but this was due to differences in climate and geography and did not have an impact on disease severity. “These results are consistent with observations in other populations that lower [vitamin D level] is associated with having MS,” the investigators concluded, “but also highlight the importance of climate and ancestry in determining vitamin D status.”

Protein-based human-induced pluripotent stem cells (hiPSCs) and those derived from human embryonic stem cells (hESCs) may be effective in the treatment of Parkinson’s disease, according to a study in the May 16 Journal of Clinical Investigation. Results showed that neuronal precursors cells derived from hESCs and protein-based hiPSCs reversed disease when transplanted into the brains of rats modeling Parkinson’s disease. The researchers attempted to use neuronal cells derived from virus-based hiPSCs but were unable to do so because these virus-based cells exhibited apoptotic cell death. “[hiPSCs] are a potentially unlimited source of patient-specific cells for transplantation…. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of Parkinson’s disease,” the investigators concluded.

Women may have a greater risk than men for adverse events following certain stroke prevention procedures, as reported in the May 6 online Lancet Neurology. A total of 2,502 patients with symptomatic and asymptomatic stenosis were randomized to undergo carotid endarterectomy or carotid artery stenting. The rates of periprocedural stroke, myocardial infarction, and death were similar in men who underwent endarterectomy (4.9%) and stenting (4.3%). In women, however, a significant difference in rates of adverse events was observed—3.8% for endarterectomy versus 6.8% for stenting. “Periprocedural risk of events seems to be higher in women who have carotid artery stenting than those who have carotid endarterectomy, whereas there is little difference in men,” the authors concluded. “Additional data are needed to confirm whether this differential risk should be taken into account in decisions for treatment of carotid disease in women.”

About 14% of ischemic strokes presented at emergency departments are wake-up strokes, researchers reported in the May 10 Neurology. Wake-up strokes, according to the authors, cannot be distinguished from other types of stroke based on clinical features or outcome, making them difficult to treat with effective clot-busting therapies. The researchers analyzed data from patients presenting at emergency departments with ischemic stroke; they identified 1,854 ischemic stroke cases, 273 of which were wake-up strokes. “There were no differences between wake-up strokes and all other strokes with regard to clinical features or outcomes except for minor differences in age and baseline retrospective NIH Stroke Scale score,” the authors reported. “Of the wake-up strokes, at least 98 (35.9%) would have been eligible for thrombolysis if arrival time were not a factor.”

The annual rate of coronary artery bypass graft surgeries decreased 30% between 2001 and 2008, while rates of other percutaneous coronary interventions remained stable, according to an examination of national trends published in the May 4 JAMA. Investigators conducted a serial cross-sectional study to examine time trends of patients undergoing revascularization procedures, and determined that the annual surgery rate decreased from 1,742 to 1,081 per million adults in 2008. “Between 2001 and 2008, the number of hospitals … providing [coronary artery bypass graft surgery] increased by 12%, and the number of [percutaneous coronary interventions] hospitals increased by 26%,” the authors reported. They noted that new revascularization technologies, new clinical evidence from trials, and updated clinical guidelines may have affected the volume and distribution of coronary revascularizations.

Patients with traumatic brain injury (TBI) and refractory intracranial hypertension may benefit from decompressive craniectomy, but they may also experience unfavorable outcomes, according to a study in the April 21 New England Journal of Medicine. Researchers randomly assigned 155 adults with TBI and intracranial hypertension to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The results revealed that the standard-care group had higher levels of intracranial pressure and longer stays in the intensive care unit. “However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care,” the authors noted. Patients with craniectomy were also more than twice as likely to experience an unfavorable outcome, including death, vegetative state, or severe disability.

One third of patients with pathologically confirmed early-onset Alzheimer’s disease presented with atypical symptoms, and 53% of patients with nonamnestic presentations were initially misdiagnosed, according to a study in the May 17 Neurology. Researchers conducted a retrospective review of clinical data from patients with confirmed early-onset Alzheimer’s disease to determine the frequency and types of incorrect diagnoses. The majority of these cases were diagnosed with other types of dementia, including pseudodementia with depression, semantic dementia, and primary progressive aphasia. “Early-onset Alzheimer’s disease diagnosis often represents a challenge because of the high frequency of atypical presentations,” the study authors wrote. More than one-third (37.5%) of patients presented with atypical symptoms other than memory problems; the most prevalent of these was behavioral/executive dysfunction.

Neuronal activity may be a potential mechanism for vulnerability to amyloid-β deposition in certain areas of the brain, researchers reported in the May 1 online Nature Neuroscience. The investigators examined endogenous neuronal activity in mice with Alzheimer’s disease and determined that this activity regulates the regional concentration of interstitial fluid amyloid-β, which drives local aggregation of amyloid-β. Using unilateral vibrissal stimulation in the contralateral barrel cortex, they found that activity increased interstitial fluid amyloid-β. Unilateral vibrissal deprivation decreased interstitial fluid amyloid-β deposition; long-term deprivation also decreased amyloid plaque formation and growth. “Our results suggest a mechanism to account for the vulnerability of specific brain regions to amyloid-β deposition in Alzheimer’s disease,” the authors concluded.

A newly confirmed genetic risk allele of the clusterin gene contributes to white matter degeneration in young adults and may increase the risk for Alzheimer’s disease later in life, according to results published in the May 4 Journal of Neuroscience. Investigators used diffusion-tensor MRI to scan the brains of 398 healthy young adults (mean age, 23.6) and to evaluate whether the C-allele clusterin risk variant was associated with lower white matter integrity. “Each C-allele copy of the clusterin variant was associated with lower fractional anisotropy—a widely accepted measure of white matter integrity—in multiple brain regions,” the authors wrote. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. “Young healthy carriers of the clusterin gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing Alzheimer’s disease later in life,” the researchers concluded.

A higher BMI may improve survival in patients with amyotrophic lateral sclerosis (ALS). As published in the May 23 online Muscle & Nerve, investigators aimed to determine whether cholesterol levels are an independent predictor of ALS survival. They measured cholesterol levels in 427 people with ALS from three clinical trial databases and found that the low-density and high-density lipoprotein level ratio did not decrease over time, even though BMI significantly declined. “After adjusting for BMI, forced vital capacity, and age, the lipid ratio was not associated with survival,” the investigators wrote. The highest survival rate, though, was found among patients with a BMI between 30 and 35, or mild obesity. “We found that dyslipidemia is not an independent predictor of survival in ALS,” the researchers concluded, whereas, “BMI is an independent prognostic factor for survival after adjusting for markers of disease severity.”

Patients with a history of intracerebral hemorrhage (ICH) should avoid using statins for prevention of ischemic cardiac and cerebrovascular disease, according to a study in the May Archives of Neurology. Statins are widely prescribed for disease prevention, the authors noted, and “although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of ICH associated with statin use.” To determine if statin therapy should be avoided in patients with a baseline elevated risk of ICH, investigators evaluated the risks and benefits of the therapy in patients with prior ICH using clinical parameters such as hemorrhage location (deep or lobar). For survivors of ICH both with and without prior cardiovascular events, the benefits of statin therapy were not strong enough to offset the increased risk for hemorrhage recurrence.

Adverse changes in sleep duration are associated with poorer cognitive function in middle-aged adults, per a study in the May 1 Sleep. Researchers conducted cross-sectional studies of women and men (age range, 45 to 69) to examine the effect of changes in sleep duration on cognitive function. Participants’ cognitive function was assessed at baseline, and their sleep duration on an average weeknight was measured once at baseline and again an average of 5.4 years later. After adjustment for age, gender, education, and occupation, the authors reported that “firm evidence remained for an association between an increase from seven or eight hours sleep and lower cognitive function for all tests, except memory, and between a decrease from six or eight hours sleep and poorer reasoning, vocabulary, and Mini-Mental State Examination score.” These adverse changes in duration were equivalent to a four- to seven-year increase in age.

African Americans with multiple sclerosis (MS) have lower vitamin D levels than their healthy counterparts, according to a study published in the May 24 Neurology. Researchers conducted a cross-sectional study of 339 African-American patients with MS and 342 without MS to determine if vitamin D levels were associated with MS disease severity. Between 71% and 77% of all participants were vitamin D–deficient and 93% to 94% were vitamin D–insufficient, the authors reported. Overall, vitamin D levels were lower in patients with MS, but this was due to differences in climate and geography and did not have an impact on disease severity. “These results are consistent with observations in other populations that lower [vitamin D level] is associated with having MS,” the investigators concluded, “but also highlight the importance of climate and ancestry in determining vitamin D status.”

Protein-based human-induced pluripotent stem cells (hiPSCs) and those derived from human embryonic stem cells (hESCs) may be effective in the treatment of Parkinson’s disease, according to a study in the May 16 Journal of Clinical Investigation. Results showed that neuronal precursors cells derived from hESCs and protein-based hiPSCs reversed disease when transplanted into the brains of rats modeling Parkinson’s disease. The researchers attempted to use neuronal cells derived from virus-based hiPSCs but were unable to do so because these virus-based cells exhibited apoptotic cell death. “[hiPSCs] are a potentially unlimited source of patient-specific cells for transplantation…. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of Parkinson’s disease,” the investigators concluded.

Women may have a greater risk than men for adverse events following certain stroke prevention procedures, as reported in the May 6 online Lancet Neurology. A total of 2,502 patients with symptomatic and asymptomatic stenosis were randomized to undergo carotid endarterectomy or carotid artery stenting. The rates of periprocedural stroke, myocardial infarction, and death were similar in men who underwent endarterectomy (4.9%) and stenting (4.3%). In women, however, a significant difference in rates of adverse events was observed—3.8% for endarterectomy versus 6.8% for stenting. “Periprocedural risk of events seems to be higher in women who have carotid artery stenting than those who have carotid endarterectomy, whereas there is little difference in men,” the authors concluded. “Additional data are needed to confirm whether this differential risk should be taken into account in decisions for treatment of carotid disease in women.”

About 14% of ischemic strokes presented at emergency departments are wake-up strokes, researchers reported in the May 10 Neurology. Wake-up strokes, according to the authors, cannot be distinguished from other types of stroke based on clinical features or outcome, making them difficult to treat with effective clot-busting therapies. The researchers analyzed data from patients presenting at emergency departments with ischemic stroke; they identified 1,854 ischemic stroke cases, 273 of which were wake-up strokes. “There were no differences between wake-up strokes and all other strokes with regard to clinical features or outcomes except for minor differences in age and baseline retrospective NIH Stroke Scale score,” the authors reported. “Of the wake-up strokes, at least 98 (35.9%) would have been eligible for thrombolysis if arrival time were not a factor.”

The annual rate of coronary artery bypass graft surgeries decreased 30% between 2001 and 2008, while rates of other percutaneous coronary interventions remained stable, according to an examination of national trends published in the May 4 JAMA. Investigators conducted a serial cross-sectional study to examine time trends of patients undergoing revascularization procedures, and determined that the annual surgery rate decreased from 1,742 to 1,081 per million adults in 2008. “Between 2001 and 2008, the number of hospitals … providing [coronary artery bypass graft surgery] increased by 12%, and the number of [percutaneous coronary interventions] hospitals increased by 26%,” the authors reported. They noted that new revascularization technologies, new clinical evidence from trials, and updated clinical guidelines may have affected the volume and distribution of coronary revascularizations.

Patients with traumatic brain injury (TBI) and refractory intracranial hypertension may benefit from decompressive craniectomy, but they may also experience unfavorable outcomes, according to a study in the April 21 New England Journal of Medicine. Researchers randomly assigned 155 adults with TBI and intracranial hypertension to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The results revealed that the standard-care group had higher levels of intracranial pressure and longer stays in the intensive care unit. “However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care,” the authors noted. Patients with craniectomy were also more than twice as likely to experience an unfavorable outcome, including death, vegetative state, or severe disability.

Vitamin D metabolism is associated with disability and lower brain parenchymal fraction in patients with MS.

Vitamin D metabolites have protective associations with disability and brain atrophy in patients with multiple sclerosis (MS), according to a study in the February issue of the Journal of Neurology, Neurosurgery, and Psychiatry. In particular, the results indicate strong associations for the 24, 25(OH)2VD3 metabolite, which has not been extensively investigated in patients with MS, reported Bianca Weinstock-Guttman, MD, of the Department of Neurology, State University of New York, Buffalo, and colleagues.

Dr. Weinstock-Guttman and colleagues evaluated the significance of vitamin D and its active metabolites in brain tissue injury and clinical disability in 193 patients with MS (152 women; mean age, 46.1; disease duration, 13.8 years). Serum levels of 25-hydroxyvitamin D3 (25(OH)VD3), 25-hydroxyvitamin D2 (25(OH)VD2), 1α, 25-dihydroxyvitamin D3 (1, 25(OH)2VD3), and 24(R),25-dihydroxyvitamin D3 (24, 25(OH)2VD3) were measured using a novel capillary liquid—chromatography—mass spectrometry method.

The investigators used the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS) to assess disability. MRI measures included T2 lesion volume, T1 lesion volume, and brain parenchymal fraction. The associations between deseasonalized levels of vitamin D metabolites and clinical and MRI measurements were assessed using regression analyses.

Dr. Weinstock-Guttman’s group found that lower deseasonalized levels of total 25(OH)VD, 25(OH)VD3, and 24, 25(OH)2VD3 were associated with a higher MSSS score. Similarly, lower deseasonalized levels of 24, 25(OH)2VD3 were associated with a higher EDSS score. Higher values of the 25(OH)VD3 to 24, 25(OH)2VD3 ratio were associated with a higher MSSS score and lower brain parenchymal fraction.

“Our µLC/MS/MS assay was important for enabling the systems pharmacology approach, which to our knowledge has not been used to investigate vitamin D metabolism in MS disease progression,” stated the researchers. “The low serum concentration of 1, 25 (OH)2VD3, low ionization efficiency and fragmentation patterns of vitamin D metabolites precluded sensitive detection by selected reactions monitoring. To obtain higher sensitivity, samples were derivatized with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD), which is specific for vitamin D metabolites, and the solid phase extraction step enabled loading of analytes extracted from a relatively high volume of sample into the µLC separation step. The method achieved sensitive and selective quantification of vitamin D metabolites in 0.2 ml of serum.”

Vitamin D metabolism is associated with disability and lower brain parenchymal fraction in patients with MS.

Vitamin D metabolites have protective associations with disability and brain atrophy in patients with multiple sclerosis (MS), according to a study in the February issue of the Journal of Neurology, Neurosurgery, and Psychiatry. In particular, the results indicate strong associations for the 24, 25(OH)2VD3 metabolite, which has not been extensively investigated in patients with MS, reported Bianca Weinstock-Guttman, MD, of the Department of Neurology, State University of New York, Buffalo, and colleagues.

Dr. Weinstock-Guttman and colleagues evaluated the significance of vitamin D and its active metabolites in brain tissue injury and clinical disability in 193 patients with MS (152 women; mean age, 46.1; disease duration, 13.8 years). Serum levels of 25-hydroxyvitamin D3 (25(OH)VD3), 25-hydroxyvitamin D2 (25(OH)VD2), 1α, 25-dihydroxyvitamin D3 (1, 25(OH)2VD3), and 24(R),25-dihydroxyvitamin D3 (24, 25(OH)2VD3) were measured using a novel capillary liquid—chromatography—mass spectrometry method.

The investigators used the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS) to assess disability. MRI measures included T2 lesion volume, T1 lesion volume, and brain parenchymal fraction. The associations between deseasonalized levels of vitamin D metabolites and clinical and MRI measurements were assessed using regression analyses.

Dr. Weinstock-Guttman’s group found that lower deseasonalized levels of total 25(OH)VD, 25(OH)VD3, and 24, 25(OH)2VD3 were associated with a higher MSSS score. Similarly, lower deseasonalized levels of 24, 25(OH)2VD3 were associated with a higher EDSS score. Higher values of the 25(OH)VD3 to 24, 25(OH)2VD3 ratio were associated with a higher MSSS score and lower brain parenchymal fraction.

“Our µLC/MS/MS assay was important for enabling the systems pharmacology approach, which to our knowledge has not been used to investigate vitamin D metabolism in MS disease progression,” stated the researchers. “The low serum concentration of 1, 25 (OH)2VD3, low ionization efficiency and fragmentation patterns of vitamin D metabolites precluded sensitive detection by selected reactions monitoring. To obtain higher sensitivity, samples were derivatized with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD), which is specific for vitamin D metabolites, and the solid phase extraction step enabled loading of analytes extracted from a relatively high volume of sample into the µLC separation step. The method achieved sensitive and selective quantification of vitamin D metabolites in 0.2 ml of serum.”

Vitamin D metabolism is associated with disability and lower brain parenchymal fraction in patients with MS.

Vitamin D metabolites have protective associations with disability and brain atrophy in patients with multiple sclerosis (MS), according to a study in the February issue of the Journal of Neurology, Neurosurgery, and Psychiatry. In particular, the results indicate strong associations for the 24, 25(OH)2VD3 metabolite, which has not been extensively investigated in patients with MS, reported Bianca Weinstock-Guttman, MD, of the Department of Neurology, State University of New York, Buffalo, and colleagues.

Dr. Weinstock-Guttman and colleagues evaluated the significance of vitamin D and its active metabolites in brain tissue injury and clinical disability in 193 patients with MS (152 women; mean age, 46.1; disease duration, 13.8 years). Serum levels of 25-hydroxyvitamin D3 (25(OH)VD3), 25-hydroxyvitamin D2 (25(OH)VD2), 1α, 25-dihydroxyvitamin D3 (1, 25(OH)2VD3), and 24(R),25-dihydroxyvitamin D3 (24, 25(OH)2VD3) were measured using a novel capillary liquid—chromatography—mass spectrometry method.

The investigators used the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS) to assess disability. MRI measures included T2 lesion volume, T1 lesion volume, and brain parenchymal fraction. The associations between deseasonalized levels of vitamin D metabolites and clinical and MRI measurements were assessed using regression analyses.

Dr. Weinstock-Guttman’s group found that lower deseasonalized levels of total 25(OH)VD, 25(OH)VD3, and 24, 25(OH)2VD3 were associated with a higher MSSS score. Similarly, lower deseasonalized levels of 24, 25(OH)2VD3 were associated with a higher EDSS score. Higher values of the 25(OH)VD3 to 24, 25(OH)2VD3 ratio were associated with a higher MSSS score and lower brain parenchymal fraction.

“Our µLC/MS/MS assay was important for enabling the systems pharmacology approach, which to our knowledge has not been used to investigate vitamin D metabolism in MS disease progression,” stated the researchers. “The low serum concentration of 1, 25 (OH)2VD3, low ionization efficiency and fragmentation patterns of vitamin D metabolites precluded sensitive detection by selected reactions monitoring. To obtain higher sensitivity, samples were derivatized with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD), which is specific for vitamin D metabolites, and the solid phase extraction step enabled loading of analytes extracted from a relatively high volume of sample into the µLC separation step. The method achieved sensitive and selective quantification of vitamin D metabolites in 0.2 ml of serum.”