Multiple Sclerosis

Women with multiple sclerosis can be reassured that should they choose to become pregnant, they are generally not at any greater risk of adverse pregnancy or birth outcomes than are similar women without the disease, according to a retrospective cohort study.

The findings should have important clinical implications for this group of patients, because about three-quarters of people with MS are women and the clinical onset of the disease most often occurs in early adulthood, just when many are considering starting a family, Mia L. van der Kop and her coauthors wrote.

Studies have shown that one-fifth to one-third of women with MS bear children after disease onset.

Ms. van der Kop and her coinvestigators at the University of British Columbia, Vancouver, linked clinical data from the British Columbia (BC) MS clinics' database with outcomes data from the BC Perinatal Database Registry (BCPDR) to examine whether maternal MS was associated with adverse neonatal and delivery outcomes and what factors, if any, were associated with risk (Ann. Neurol. 2011 June 27 [doi: 10.1002/ana.22483]).

Of 7,056 female patients who were registered at one of the four MS clinics in BC from 1980 through 2008, the investigators found links for 321 women (432 births) with laboratory-supported or clinically definite MS whose with births occurred between April 1998 and March 2009 in the BCPDR. These births were compared with 2,975 births from a random sample of 2,958 women in the general population who were frequency-matched for age, local health authority, and delivery year. The clinics' database is estimated to capture 80% of the MS population in BC. Patients' names and dates of birth were used to confirm the accuracy of linkage.

A greater proportion of births in the MS group were to women who were nulliparous, primigravid, hypertensive, or had smoked during pregnancy. A greater proportion of births in the comparison group were to mothers with diabetes during pregnancy and a history of multiple therapeutic abortions.

Maternal MS was not associated with assisted vaginal delivery (odds ratio, 0.78) or cesarean section (OR, 0.94). The proportion of elective cesarean sections was similar in both the MS and comparison groups (18.6% vs. 16.1%, respectively), and the indication for cesarean delivery did not differ between groups. Delivery outcomes were not associated with either an older age at MS onset or longer duration.

The degree of disability in MS mothers was not significantly associated with higher odds of a cesarean section or an assisted vaginal delivery, compared with women with a normal neurologic exam.

Among nulliparous women, there was no significant difference in the median duration of the second stage of labor between those with MS and those in the comparison group. Duration of the second stage of labor was not associated with age at MS onset.

This study was supported by the Canadian Institutes of Health Research. All of the authors reported having significant ties to disease advocacy- or government-based groups, research groups, or pharmaceutical companies.

Women with multiple sclerosis can be reassured that should they choose to become pregnant, they are generally not at any greater risk of adverse pregnancy or birth outcomes than are similar women without the disease, according to a retrospective cohort study.

The findings should have important clinical implications for this group of patients, because about three-quarters of people with MS are women and the clinical onset of the disease most often occurs in early adulthood, just when many are considering starting a family, Mia L. van der Kop and her coauthors wrote.

Studies have shown that one-fifth to one-third of women with MS bear children after disease onset.

Ms. van der Kop and her coinvestigators at the University of British Columbia, Vancouver, linked clinical data from the British Columbia (BC) MS clinics' database with outcomes data from the BC Perinatal Database Registry (BCPDR) to examine whether maternal MS was associated with adverse neonatal and delivery outcomes and what factors, if any, were associated with risk (Ann. Neurol. 2011 June 27 [doi: 10.1002/ana.22483]).

Of 7,056 female patients who were registered at one of the four MS clinics in BC from 1980 through 2008, the investigators found links for 321 women (432 births) with laboratory-supported or clinically definite MS whose with births occurred between April 1998 and March 2009 in the BCPDR. These births were compared with 2,975 births from a random sample of 2,958 women in the general population who were frequency-matched for age, local health authority, and delivery year. The clinics' database is estimated to capture 80% of the MS population in BC. Patients' names and dates of birth were used to confirm the accuracy of linkage.

A greater proportion of births in the MS group were to women who were nulliparous, primigravid, hypertensive, or had smoked during pregnancy. A greater proportion of births in the comparison group were to mothers with diabetes during pregnancy and a history of multiple therapeutic abortions.

Maternal MS was not associated with assisted vaginal delivery (odds ratio, 0.78) or cesarean section (OR, 0.94). The proportion of elective cesarean sections was similar in both the MS and comparison groups (18.6% vs. 16.1%, respectively), and the indication for cesarean delivery did not differ between groups. Delivery outcomes were not associated with either an older age at MS onset or longer duration.

The degree of disability in MS mothers was not significantly associated with higher odds of a cesarean section or an assisted vaginal delivery, compared with women with a normal neurologic exam.

Among nulliparous women, there was no significant difference in the median duration of the second stage of labor between those with MS and those in the comparison group. Duration of the second stage of labor was not associated with age at MS onset.

This study was supported by the Canadian Institutes of Health Research. All of the authors reported having significant ties to disease advocacy- or government-based groups, research groups, or pharmaceutical companies.

Women with multiple sclerosis can be reassured that should they choose to become pregnant, they are generally not at any greater risk of adverse pregnancy or birth outcomes than are similar women without the disease, according to a retrospective cohort study.

The findings should have important clinical implications for this group of patients, because about three-quarters of people with MS are women and the clinical onset of the disease most often occurs in early adulthood, just when many are considering starting a family, Mia L. van der Kop and her coauthors wrote.

Studies have shown that one-fifth to one-third of women with MS bear children after disease onset.

Ms. van der Kop and her coinvestigators at the University of British Columbia, Vancouver, linked clinical data from the British Columbia (BC) MS clinics' database with outcomes data from the BC Perinatal Database Registry (BCPDR) to examine whether maternal MS was associated with adverse neonatal and delivery outcomes and what factors, if any, were associated with risk (Ann. Neurol. 2011 June 27 [doi: 10.1002/ana.22483]).

Of 7,056 female patients who were registered at one of the four MS clinics in BC from 1980 through 2008, the investigators found links for 321 women (432 births) with laboratory-supported or clinically definite MS whose with births occurred between April 1998 and March 2009 in the BCPDR. These births were compared with 2,975 births from a random sample of 2,958 women in the general population who were frequency-matched for age, local health authority, and delivery year. The clinics' database is estimated to capture 80% of the MS population in BC. Patients' names and dates of birth were used to confirm the accuracy of linkage.

A greater proportion of births in the MS group were to women who were nulliparous, primigravid, hypertensive, or had smoked during pregnancy. A greater proportion of births in the comparison group were to mothers with diabetes during pregnancy and a history of multiple therapeutic abortions.

Maternal MS was not associated with assisted vaginal delivery (odds ratio, 0.78) or cesarean section (OR, 0.94). The proportion of elective cesarean sections was similar in both the MS and comparison groups (18.6% vs. 16.1%, respectively), and the indication for cesarean delivery did not differ between groups. Delivery outcomes were not associated with either an older age at MS onset or longer duration.

The degree of disability in MS mothers was not significantly associated with higher odds of a cesarean section or an assisted vaginal delivery, compared with women with a normal neurologic exam.

Among nulliparous women, there was no significant difference in the median duration of the second stage of labor between those with MS and those in the comparison group. Duration of the second stage of labor was not associated with age at MS onset.

This study was supported by the Canadian Institutes of Health Research. All of the authors reported having significant ties to disease advocacy- or government-based groups, research groups, or pharmaceutical companies.

Serum levels of interleukin-7 helped determine which patients with relapsing-remitting multiple sclerosis would benefit from treatment with interferon-beta in a series of experiments involving human sera and mice with experimental autoimmune encephalo-myelitis.

Patients with high IL-7 levels had a T helper cell type 1 (T_H1) form of MS that has been shown to respond better to interferon-beta therapy than does the T_H17 form of MS.

“These results not only help to clarify our understanding of a genetic risk factor associated with MS but also suggest new predictive, mechanism-based measurements for MS patient stratification,” wrote Li-Fen Lee, Ph.D., of Pfizer, and her colleagues (Sci. Transl. Med.2011;3:93ra68).

The study brings together findings from earlier reports that in totality suggested that IL-7 and its receptor, IL-7R-alpha, may be involved the pathogenesis of MS. Several genome-wide association studies have pointed to a single nucleotide polymorphism in the gene encoding IL-7R-alpha that confers increased susceptibility to MS. In another study, patients with MS had higher levels of both IL-7R and IL-7 mRNA in cerebrospinal fluid than did patients with noninflammatory neurological diseases. And other studies have shown that IL-7/IL-7R-alpha signaling is necessary for the survival of T lymphocytes in humans and animal models.

Using cells from 26 patients with relapsing-remitting MS and mice with experimental autoimmune encephalomyelitis (EAE), Dr. Lee and coauthors found that in both cases, IL-7 promotes the differentiation of naive T cells into T_H1 cells, but not T_H17 cells. Mice that were given IL-7 after EAE was established and paralysis had begun experienced worsened symptoms, whereas those that were given an antagonist IL-7R-alpha antibody had reduced disease severity.

Previous studies have suggested that interferon-beta (IFN-beta) treatment prevents EAE in mice with pathogenic T_H1 cells before symptom onset, yet it exacerbates the disease when given to mice with the T_H17 form of EAE.

The investigators examined the relationship between MS type and response to IFN-beta treatment in the 26 patients.

The level of IL-7 in serum was significantly associated with the rate of relapse. In the 2 years after treatment with IFN-beta, there were no relapses in 5 of 5 patients with an IL-7 level greater than 150 pg/mL, compared with no relapses in 7 of 21 patients with an IL-7 level less than 150 pg/mL.

“Our finding of a role for IL-7 in directing and promoting the generation of human T_H1 cells … is entirely consistent with the elevated IL-7 levels seen in patients with the IFN-beta-responsive form of MS,” the investigators wrote.

They concluded that “it is possible that serum IL-7 level may be useful for predicting clinical benefit from IFN-beta treatment in [relapsing remitting MS] patients. It is conceivable that patients with high levels of serum IL-7 might directly benefit from potential new therapies targeting either IL-7 or its receptor.”

The study was funded by grants from the National Institutes of Health and a National Multiple Sclerosis Society fellowship. Dr. Lee and eight other authors are employees of Pfizer, which has filed a patent application titled, “Antagonist Anti-IL-7 Receptor Antibodies and Methods” with three of the authors. Stanford University and two of the authors have filed a separate patent application for “Markers for Determination of Patient Responsiveness.” The remaining seven authors declared having no competing interests.

Adviser's Viewpoint

Validation, Additional Data Needed

This manuscript explores the role of IL-7 in MS and experimental autoimmune encephalomyelitis (EAE) in mice. The authors present data showing that high serum levels of IL-7, especially in association with low levels of IL-17F, predict a good clinical response to interferon-beta (IFN-beta) therapy in MS. They also show that IL-7 can induce T_H1, but not T_H17, cell differentiation in both humans and mice. They postulate a “T_H1-driven” form of MS responsive to IFN-beta and a “T_H17-driven” form of MS not responsive to IFN-beta. Use of IL-7R-alpha-blocking antibodies in EAE before or after onset of paralysis resulted in reduced severity of EAE, reductions in peripheral naive and activated T cells, and reduced lymphocyte infiltration into the central nervous system.

The authors propose that such IL-7R-alpha-blocking antibodies may be effective in treatment of MS. These results are exciting, and suggest that we may be able to predict an individual's response to treatment with IFN-beta or other MS therapies by looking at induction of specific cytokines. This would be a major advance in a field where we treat patients with a variety of disease-modifying therapies with very little knowledge of how individual responses to therapy may vary.

However, there are a few cautions to keep in mind when reviewing these results. The results are preliminary, and based on a retrospective sample of 26 patients treated with IFN-beta for at least 12 months. Two blinded neurologists classified the patients as responders or nonresponders based on historical data on the number of relapses and steroid treatments in the 2 years before initiation of therapy, compared with 2 years after starting therapy. No MRI data were reported to assess for subclinical disease activity, and neutralizing antibody status to IFN-beta was also not reported. The “high IL-7, low IL-17F” group comprised only five patients, who had an average of two relapses in the 2 years preceding treatment and no relapses in the 2 years during treatment with IFN-beta.

These results obviously need to be validated in a larger, prospectively determined cohort with appropriate MRI monitoring for subclinical MS disease activity. Past experience with MS clinical trials and our evolving knowledge of the complexity of the immune alterations in MS suggest that focusing on changes in one or two cytokines and concepts such at “T_H1-driven” and “T_H17-driven” forms of the disease are likely oversimplifications, although they may serve as useful constructs for future investigation.

JONATHAN L. CARTER, M.D., is an associate professor of neurology at the Mayo Clinic in Scottsdale, Ariz. He specializes in multiple sclerosis, optic neuritis, transverse myelitis, and neuroimmunology. He has no relevant disclosures.

Serum levels of interleukin-7 helped determine which patients with relapsing-remitting multiple sclerosis would benefit from treatment with interferon-beta in a series of experiments involving human sera and mice with experimental autoimmune encephalo-myelitis.

Patients with high IL-7 levels had a T helper cell type 1 (T_H1) form of MS that has been shown to respond better to interferon-beta therapy than does the T_H17 form of MS.

“These results not only help to clarify our understanding of a genetic risk factor associated with MS but also suggest new predictive, mechanism-based measurements for MS patient stratification,” wrote Li-Fen Lee, Ph.D., of Pfizer, and her colleagues (Sci. Transl. Med.2011;3:93ra68).

The study brings together findings from earlier reports that in totality suggested that IL-7 and its receptor, IL-7R-alpha, may be involved the pathogenesis of MS. Several genome-wide association studies have pointed to a single nucleotide polymorphism in the gene encoding IL-7R-alpha that confers increased susceptibility to MS. In another study, patients with MS had higher levels of both IL-7R and IL-7 mRNA in cerebrospinal fluid than did patients with noninflammatory neurological diseases. And other studies have shown that IL-7/IL-7R-alpha signaling is necessary for the survival of T lymphocytes in humans and animal models.

Using cells from 26 patients with relapsing-remitting MS and mice with experimental autoimmune encephalomyelitis (EAE), Dr. Lee and coauthors found that in both cases, IL-7 promotes the differentiation of naive T cells into T_H1 cells, but not T_H17 cells. Mice that were given IL-7 after EAE was established and paralysis had begun experienced worsened symptoms, whereas those that were given an antagonist IL-7R-alpha antibody had reduced disease severity.

Previous studies have suggested that interferon-beta (IFN-beta) treatment prevents EAE in mice with pathogenic T_H1 cells before symptom onset, yet it exacerbates the disease when given to mice with the T_H17 form of EAE.

The investigators examined the relationship between MS type and response to IFN-beta treatment in the 26 patients.

The level of IL-7 in serum was significantly associated with the rate of relapse. In the 2 years after treatment with IFN-beta, there were no relapses in 5 of 5 patients with an IL-7 level greater than 150 pg/mL, compared with no relapses in 7 of 21 patients with an IL-7 level less than 150 pg/mL.

“Our finding of a role for IL-7 in directing and promoting the generation of human T_H1 cells … is entirely consistent with the elevated IL-7 levels seen in patients with the IFN-beta-responsive form of MS,” the investigators wrote.

They concluded that “it is possible that serum IL-7 level may be useful for predicting clinical benefit from IFN-beta treatment in [relapsing remitting MS] patients. It is conceivable that patients with high levels of serum IL-7 might directly benefit from potential new therapies targeting either IL-7 or its receptor.”

The study was funded by grants from the National Institutes of Health and a National Multiple Sclerosis Society fellowship. Dr. Lee and eight other authors are employees of Pfizer, which has filed a patent application titled, “Antagonist Anti-IL-7 Receptor Antibodies and Methods” with three of the authors. Stanford University and two of the authors have filed a separate patent application for “Markers for Determination of Patient Responsiveness.” The remaining seven authors declared having no competing interests.

Adviser's Viewpoint

Validation, Additional Data Needed

This manuscript explores the role of IL-7 in MS and experimental autoimmune encephalomyelitis (EAE) in mice. The authors present data showing that high serum levels of IL-7, especially in association with low levels of IL-17F, predict a good clinical response to interferon-beta (IFN-beta) therapy in MS. They also show that IL-7 can induce T_H1, but not T_H17, cell differentiation in both humans and mice. They postulate a “T_H1-driven” form of MS responsive to IFN-beta and a “T_H17-driven” form of MS not responsive to IFN-beta. Use of IL-7R-alpha-blocking antibodies in EAE before or after onset of paralysis resulted in reduced severity of EAE, reductions in peripheral naive and activated T cells, and reduced lymphocyte infiltration into the central nervous system.

The authors propose that such IL-7R-alpha-blocking antibodies may be effective in treatment of MS. These results are exciting, and suggest that we may be able to predict an individual's response to treatment with IFN-beta or other MS therapies by looking at induction of specific cytokines. This would be a major advance in a field where we treat patients with a variety of disease-modifying therapies with very little knowledge of how individual responses to therapy may vary.

However, there are a few cautions to keep in mind when reviewing these results. The results are preliminary, and based on a retrospective sample of 26 patients treated with IFN-beta for at least 12 months. Two blinded neurologists classified the patients as responders or nonresponders based on historical data on the number of relapses and steroid treatments in the 2 years before initiation of therapy, compared with 2 years after starting therapy. No MRI data were reported to assess for subclinical disease activity, and neutralizing antibody status to IFN-beta was also not reported. The “high IL-7, low IL-17F” group comprised only five patients, who had an average of two relapses in the 2 years preceding treatment and no relapses in the 2 years during treatment with IFN-beta.

These results obviously need to be validated in a larger, prospectively determined cohort with appropriate MRI monitoring for subclinical MS disease activity. Past experience with MS clinical trials and our evolving knowledge of the complexity of the immune alterations in MS suggest that focusing on changes in one or two cytokines and concepts such at “T_H1-driven” and “T_H17-driven” forms of the disease are likely oversimplifications, although they may serve as useful constructs for future investigation.

JONATHAN L. CARTER, M.D., is an associate professor of neurology at the Mayo Clinic in Scottsdale, Ariz. He specializes in multiple sclerosis, optic neuritis, transverse myelitis, and neuroimmunology. He has no relevant disclosures.

Serum levels of interleukin-7 helped determine which patients with relapsing-remitting multiple sclerosis would benefit from treatment with interferon-beta in a series of experiments involving human sera and mice with experimental autoimmune encephalo-myelitis.

Patients with high IL-7 levels had a T helper cell type 1 (T_H1) form of MS that has been shown to respond better to interferon-beta therapy than does the T_H17 form of MS.

“These results not only help to clarify our understanding of a genetic risk factor associated with MS but also suggest new predictive, mechanism-based measurements for MS patient stratification,” wrote Li-Fen Lee, Ph.D., of Pfizer, and her colleagues (Sci. Transl. Med.2011;3:93ra68).

The study brings together findings from earlier reports that in totality suggested that IL-7 and its receptor, IL-7R-alpha, may be involved the pathogenesis of MS. Several genome-wide association studies have pointed to a single nucleotide polymorphism in the gene encoding IL-7R-alpha that confers increased susceptibility to MS. In another study, patients with MS had higher levels of both IL-7R and IL-7 mRNA in cerebrospinal fluid than did patients with noninflammatory neurological diseases. And other studies have shown that IL-7/IL-7R-alpha signaling is necessary for the survival of T lymphocytes in humans and animal models.

Using cells from 26 patients with relapsing-remitting MS and mice with experimental autoimmune encephalomyelitis (EAE), Dr. Lee and coauthors found that in both cases, IL-7 promotes the differentiation of naive T cells into T_H1 cells, but not T_H17 cells. Mice that were given IL-7 after EAE was established and paralysis had begun experienced worsened symptoms, whereas those that were given an antagonist IL-7R-alpha antibody had reduced disease severity.

Previous studies have suggested that interferon-beta (IFN-beta) treatment prevents EAE in mice with pathogenic T_H1 cells before symptom onset, yet it exacerbates the disease when given to mice with the T_H17 form of EAE.

The investigators examined the relationship between MS type and response to IFN-beta treatment in the 26 patients.

The level of IL-7 in serum was significantly associated with the rate of relapse. In the 2 years after treatment with IFN-beta, there were no relapses in 5 of 5 patients with an IL-7 level greater than 150 pg/mL, compared with no relapses in 7 of 21 patients with an IL-7 level less than 150 pg/mL.

“Our finding of a role for IL-7 in directing and promoting the generation of human T_H1 cells … is entirely consistent with the elevated IL-7 levels seen in patients with the IFN-beta-responsive form of MS,” the investigators wrote.

They concluded that “it is possible that serum IL-7 level may be useful for predicting clinical benefit from IFN-beta treatment in [relapsing remitting MS] patients. It is conceivable that patients with high levels of serum IL-7 might directly benefit from potential new therapies targeting either IL-7 or its receptor.”

The study was funded by grants from the National Institutes of Health and a National Multiple Sclerosis Society fellowship. Dr. Lee and eight other authors are employees of Pfizer, which has filed a patent application titled, “Antagonist Anti-IL-7 Receptor Antibodies and Methods” with three of the authors. Stanford University and two of the authors have filed a separate patent application for “Markers for Determination of Patient Responsiveness.” The remaining seven authors declared having no competing interests.

Adviser's Viewpoint

Validation, Additional Data Needed

This manuscript explores the role of IL-7 in MS and experimental autoimmune encephalomyelitis (EAE) in mice. The authors present data showing that high serum levels of IL-7, especially in association with low levels of IL-17F, predict a good clinical response to interferon-beta (IFN-beta) therapy in MS. They also show that IL-7 can induce T_H1, but not T_H17, cell differentiation in both humans and mice. They postulate a “T_H1-driven” form of MS responsive to IFN-beta and a “T_H17-driven” form of MS not responsive to IFN-beta. Use of IL-7R-alpha-blocking antibodies in EAE before or after onset of paralysis resulted in reduced severity of EAE, reductions in peripheral naive and activated T cells, and reduced lymphocyte infiltration into the central nervous system.

The authors propose that such IL-7R-alpha-blocking antibodies may be effective in treatment of MS. These results are exciting, and suggest that we may be able to predict an individual's response to treatment with IFN-beta or other MS therapies by looking at induction of specific cytokines. This would be a major advance in a field where we treat patients with a variety of disease-modifying therapies with very little knowledge of how individual responses to therapy may vary.

However, there are a few cautions to keep in mind when reviewing these results. The results are preliminary, and based on a retrospective sample of 26 patients treated with IFN-beta for at least 12 months. Two blinded neurologists classified the patients as responders or nonresponders based on historical data on the number of relapses and steroid treatments in the 2 years before initiation of therapy, compared with 2 years after starting therapy. No MRI data were reported to assess for subclinical disease activity, and neutralizing antibody status to IFN-beta was also not reported. The “high IL-7, low IL-17F” group comprised only five patients, who had an average of two relapses in the 2 years preceding treatment and no relapses in the 2 years during treatment with IFN-beta.

These results obviously need to be validated in a larger, prospectively determined cohort with appropriate MRI monitoring for subclinical MS disease activity. Past experience with MS clinical trials and our evolving knowledge of the complexity of the immune alterations in MS suggest that focusing on changes in one or two cytokines and concepts such at “T_H1-driven” and “T_H17-driven” forms of the disease are likely oversimplifications, although they may serve as useful constructs for future investigation.

JONATHAN L. CARTER, M.D., is an associate professor of neurology at the Mayo Clinic in Scottsdale, Ariz. He specializes in multiple sclerosis, optic neuritis, transverse myelitis, and neuroimmunology. He has no relevant disclosures.

New Risk Factors for Alzheimer’s Disease?
Vision and hearing deficits, poorly fitting dentures, and increased serum proinflammatory cytokines all may be risk factors for Alzheimer’s disease, according to three studies published in the July 12 online issue of Neurology.
Alzheimer’s disease and dementia risk were associated with health deficits that are usually seen in the elderly but were not previously known to predict dementia, according to a study by Xiaowei Song, PhD, of Dalhousie University, Halifax, Canada, and colleagues.
The investigators created an index combining 19 such deficits—including problems with vision, hearing, denture fit, chest or skin, stomach or bladder, sinuses, broken bones, and feet or ankles—and applied it to 7,239 participants who were age 65 or older and free of dementia at baseline. After adjustment for age, sex, education, and baseline cognition, participants’ index scores were significantly associated with Alzheimer’s disease and dementia of all types at five and 10 years. In addition, their risk of dementia increased by 3.2% with each deficit included in the index.
Both lower and higher levels of hemoglobin were associated with Alzheimer’s disease and cognitive decline in a study by Raj C. Shah, MD, of Rush University Medical Center in Chicago, and colleagues. They gave annual cognitive assessments and clinical evaluations for Alzheimer’s disease to 881 community-dwelling, elderly participants for a mean of 3.3 years.
With adjustment for age, sex, and education, higher and lower levels of hemoglobin were associated with Alzheimer’s disease risk, with a hazard ratio of 1.06 for the quadratic of hemoglobin. Participants who had anemia or clinically high hemoglobin had a 60% increased risk of Alzheimer’s disease dementia, compared with participants who had clinically normal hemoglobin.
Increased serum proinflammatory cytokines predicted such “sickness behaviors” as increased anxiety, depression, and apathy in patients with Alzheimer’s disease, according to a study by Clive Holmes, PhD, of the University of Southampton, Southampton, UK, and colleagues. The investigators took blood samples from and performed cognitive assessments on 300 patients with mild to severe Alzheimer’s disease at baseline and two, four, and six months. Increased levels of serum tumor necrosis factor and IL-6 at baseline were associated with an approximately twofold increased frequency of neuropsychiatric symptoms characteristic of sickness behavior, independent of a history of delirium, at six months.
Despite these findings, “much uncertainty remains” about the value of nontraditional Alzheimer’s disease risk factors, emphasized Jean François Dartigues, MD, PhD, and Catherine Féart, PhD, both of the University of Victor Segalen of Bordeaux, Bordeaux, France, in an accompanying editorial. They suggested that “the studied factors could be a nonspecific consequence of aging phenomenon” and that health-related behaviors, nutritional factors, physical activities, or leisure activities could have affected the studies’ results.
Nevertheless, they added, the studies “suggest a new vision of preventive or curative treatments which, instead of targeting specific etiologic mechanisms, would aim at improving general health. Perhaps increasing adaptation to age-related changes would reduce the risk of Alzheimer’s disease dementia or its impact on the patient, caregivers, and society.”
Holmes C, Cunningham C, Zotova E, et al. Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology. 2011;77(3):212-218.
Shah RC, Buchman AS, Wilson RS, et al. Hemoglobin level in older persons and incident Alzheimer disease: prospective cohort analysis. Neurology. 2011;77(3):219-226.
Song X, Mitnitski A, Rockwood K. Nontraditional risk factors combine to predict Alzheimer disease and dementia. Neurology. 2011;77(3):227-234.
Dartigues JF, Féart C. Risk factors for Alzheimer disease: aging beyond age? Neurology. 2011;77(3):206-207.

Reducing Tonic-Clonic Seizures Can Minimize Risk of SUDEP
Clinicians can minimize the risk of sudden unexpected death in epilepsy (SUDEP) through such measures as reducing tonic-clonic seizures, choosing drugs carefully, changing treatments gradually, acting on ictal warning signs, and supervising and counseling patients, according to a seminar published online July 6 in Lancet. The seminar, by Simon Shorvon, FRCP, of the UCL Institute of Neurology in London, and Torbjorn Tomson, MD, of the Karolinska Institute in Stockholm, reviewed current research on and provided advice about minimizing SUDEP risk.
Almost all studies indicate that this risk is high in patients with a high number of tonic-clonic seizures, the authors noted. They suggested reducing these seizures through optimum treatment, good drug compliance, and advice on such lifestyle choices as alcohol intake and sleep. Ictal warning signs for tonic-clonic seizures include prolonged seizures that are associated with marked cyanosis, severe bradycardia or apnea, and postictal EEG suppression; complex partial seizures with marked atonia; and seizures in patients with pre-existing cardiac or respiratory impairment.
Patients who experience tonic-clonic seizures require supervision, the authors noted. They recommended attending to these patients continuously until the full restoration of consciousness, contacting emergency services for high-risk seizures, and supervising high-risk patients at night through attendance and use of alarms.
Clinicians should be cautious in using antiepileptic drugs (AEDs) with potential cardiorespiratory adverse effects, according to the researchers. When clinicians switch AEDs, they should introduce the new drug before withdrawing the old one and provide patients with “access to immediate advice in the event of worsening seizures,” the investigators stated.
Although some clinicians believe that informing all patients with epilepsy about the risk of SUDEP will cause unnecessary stress and anxiety, the authors recommended informing most patients about the risk to facilitate its minimization. However, they further suggested putting the risk in perspective—for example, by pointing out that, on an annual basis, it is similar to that of dying in a motor vehicle accident.
SUDEP probably has several mechanisms, and “most research has focused on seizure-related respiratory depression, cardiac arrhythmia, cerebral depression, and autonomic dysfunction,” the authors noted. Along with tonic-clonic seizures, risk factors for the event include male sex, long-duration epilepsy, and antiepileptic polytherapy.
Shorvon S, Tomson T. Sudden unexpected death in epilepsy. Lancet. 2011 Jul 5; [Epub ahead of print].

How Cost-Effective Are Disease-Modifying Therapies in MS?
Disease-modifying therapies (DMTs) for relapsing-remitting or secondary progressive multiple sclerosis (MS) do not appear to be cost-effective in the United States, according to findings published online July 20 by Neurology.
Katia Noyes, PhD, MPH, of the University of Rochester, New York, and colleagues calculated the cost-effectiveness of four DMTs in a  nationally representative cohort of 1,121 patients with MS. The investigators generated 10-year disease progression paths for this cohort; looked at data on drug effectiveness, patient health preferences, health care use, lost productivity, and medical costs; measured health gains in quality-adjusted life-years (QALYs) and relapse-free years; and calculated incremental cost-effectiveness ratios (ICERs). The DMTs studied were glatiramer acetate, intramuscular interferon beta-1a, subcutaneous interferon beta-1a, and interferon beta-1b.
DMT therapy for 10 years resulted in modest QALY gains (0.082 for glatiramer acetate and 0.126 to 0.192 for the interferons), compared with basic supportive therapy. In addition, DMT therapy resulted in more relapse-free years throughout the course of a decade; patients on basic therapy averaged 5.051 relapse-free years, compared with 5.879 relapse-free years for glatiramer acetate and 5.620 to 6.074 relapse-free years for the interferons.
However, the ICERs of all four DMTs far exceeded $800,000 per QALY gained. The interferons had similar ICERs, at $901,319/QALY for intramuscular interferon beta-1a, $1,487,306/QALY for subcutaneous interferon beta-1a, and $1,123,162/QALY for interferon beta-1b. The ICER for glatiramer acetate was significantly higher, at $2,178,555/QALY. “While there is no formal cost-effectiveness threshold in the US, these estimates are an order of magnitude greater than the cost-effectiveness of many commonly accepted therapies for chronic illness,” the researchers commented.
The researchers added that cutting DMT costs by two-thirds would make the therapies’ cost-effectiveness comparable to that of other accepted interventions, however. In addition, the investigators noted that starting DMT earlier was associated with a more favorable ICER, compared with initiating treatment at any disease state, and that early treatment “may defer the substantial costs associated with late-stage MS and disability.”
Noyes K, Bajorska A, Chappel A, et al. Cost-effectiveness of disease-modifying therapy for multiple sclerosis: a population-based study. Neurology. 2011 Jul 20; [Epub ahead of print]. 

New Risk Factors for Alzheimer’s Disease?
Vision and hearing deficits, poorly fitting dentures, and increased serum proinflammatory cytokines all may be risk factors for Alzheimer’s disease, according to three studies published in the July 12 online issue of Neurology.
Alzheimer’s disease and dementia risk were associated with health deficits that are usually seen in the elderly but were not previously known to predict dementia, according to a study by Xiaowei Song, PhD, of Dalhousie University, Halifax, Canada, and colleagues.
The investigators created an index combining 19 such deficits—including problems with vision, hearing, denture fit, chest or skin, stomach or bladder, sinuses, broken bones, and feet or ankles—and applied it to 7,239 participants who were age 65 or older and free of dementia at baseline. After adjustment for age, sex, education, and baseline cognition, participants’ index scores were significantly associated with Alzheimer’s disease and dementia of all types at five and 10 years. In addition, their risk of dementia increased by 3.2% with each deficit included in the index.
Both lower and higher levels of hemoglobin were associated with Alzheimer’s disease and cognitive decline in a study by Raj C. Shah, MD, of Rush University Medical Center in Chicago, and colleagues. They gave annual cognitive assessments and clinical evaluations for Alzheimer’s disease to 881 community-dwelling, elderly participants for a mean of 3.3 years.
With adjustment for age, sex, and education, higher and lower levels of hemoglobin were associated with Alzheimer’s disease risk, with a hazard ratio of 1.06 for the quadratic of hemoglobin. Participants who had anemia or clinically high hemoglobin had a 60% increased risk of Alzheimer’s disease dementia, compared with participants who had clinically normal hemoglobin.
Increased serum proinflammatory cytokines predicted such “sickness behaviors” as increased anxiety, depression, and apathy in patients with Alzheimer’s disease, according to a study by Clive Holmes, PhD, of the University of Southampton, Southampton, UK, and colleagues. The investigators took blood samples from and performed cognitive assessments on 300 patients with mild to severe Alzheimer’s disease at baseline and two, four, and six months. Increased levels of serum tumor necrosis factor and IL-6 at baseline were associated with an approximately twofold increased frequency of neuropsychiatric symptoms characteristic of sickness behavior, independent of a history of delirium, at six months.
Despite these findings, “much uncertainty remains” about the value of nontraditional Alzheimer’s disease risk factors, emphasized Jean François Dartigues, MD, PhD, and Catherine Féart, PhD, both of the University of Victor Segalen of Bordeaux, Bordeaux, France, in an accompanying editorial. They suggested that “the studied factors could be a nonspecific consequence of aging phenomenon” and that health-related behaviors, nutritional factors, physical activities, or leisure activities could have affected the studies’ results.
Nevertheless, they added, the studies “suggest a new vision of preventive or curative treatments which, instead of targeting specific etiologic mechanisms, would aim at improving general health. Perhaps increasing adaptation to age-related changes would reduce the risk of Alzheimer’s disease dementia or its impact on the patient, caregivers, and society.”
Holmes C, Cunningham C, Zotova E, et al. Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology. 2011;77(3):212-218.
Shah RC, Buchman AS, Wilson RS, et al. Hemoglobin level in older persons and incident Alzheimer disease: prospective cohort analysis. Neurology. 2011;77(3):219-226.
Song X, Mitnitski A, Rockwood K. Nontraditional risk factors combine to predict Alzheimer disease and dementia. Neurology. 2011;77(3):227-234.
Dartigues JF, Féart C. Risk factors for Alzheimer disease: aging beyond age? Neurology. 2011;77(3):206-207.

Reducing Tonic-Clonic Seizures Can Minimize Risk of SUDEP
Clinicians can minimize the risk of sudden unexpected death in epilepsy (SUDEP) through such measures as reducing tonic-clonic seizures, choosing drugs carefully, changing treatments gradually, acting on ictal warning signs, and supervising and counseling patients, according to a seminar published online July 6 in Lancet. The seminar, by Simon Shorvon, FRCP, of the UCL Institute of Neurology in London, and Torbjorn Tomson, MD, of the Karolinska Institute in Stockholm, reviewed current research on and provided advice about minimizing SUDEP risk.
Almost all studies indicate that this risk is high in patients with a high number of tonic-clonic seizures, the authors noted. They suggested reducing these seizures through optimum treatment, good drug compliance, and advice on such lifestyle choices as alcohol intake and sleep. Ictal warning signs for tonic-clonic seizures include prolonged seizures that are associated with marked cyanosis, severe bradycardia or apnea, and postictal EEG suppression; complex partial seizures with marked atonia; and seizures in patients with pre-existing cardiac or respiratory impairment.
Patients who experience tonic-clonic seizures require supervision, the authors noted. They recommended attending to these patients continuously until the full restoration of consciousness, contacting emergency services for high-risk seizures, and supervising high-risk patients at night through attendance and use of alarms.
Clinicians should be cautious in using antiepileptic drugs (AEDs) with potential cardiorespiratory adverse effects, according to the researchers. When clinicians switch AEDs, they should introduce the new drug before withdrawing the old one and provide patients with “access to immediate advice in the event of worsening seizures,” the investigators stated.
Although some clinicians believe that informing all patients with epilepsy about the risk of SUDEP will cause unnecessary stress and anxiety, the authors recommended informing most patients about the risk to facilitate its minimization. However, they further suggested putting the risk in perspective—for example, by pointing out that, on an annual basis, it is similar to that of dying in a motor vehicle accident.
SUDEP probably has several mechanisms, and “most research has focused on seizure-related respiratory depression, cardiac arrhythmia, cerebral depression, and autonomic dysfunction,” the authors noted. Along with tonic-clonic seizures, risk factors for the event include male sex, long-duration epilepsy, and antiepileptic polytherapy.
Shorvon S, Tomson T. Sudden unexpected death in epilepsy. Lancet. 2011 Jul 5; [Epub ahead of print].

How Cost-Effective Are Disease-Modifying Therapies in MS?
Disease-modifying therapies (DMTs) for relapsing-remitting or secondary progressive multiple sclerosis (MS) do not appear to be cost-effective in the United States, according to findings published online July 20 by Neurology.
Katia Noyes, PhD, MPH, of the University of Rochester, New York, and colleagues calculated the cost-effectiveness of four DMTs in a  nationally representative cohort of 1,121 patients with MS. The investigators generated 10-year disease progression paths for this cohort; looked at data on drug effectiveness, patient health preferences, health care use, lost productivity, and medical costs; measured health gains in quality-adjusted life-years (QALYs) and relapse-free years; and calculated incremental cost-effectiveness ratios (ICERs). The DMTs studied were glatiramer acetate, intramuscular interferon beta-1a, subcutaneous interferon beta-1a, and interferon beta-1b.
DMT therapy for 10 years resulted in modest QALY gains (0.082 for glatiramer acetate and 0.126 to 0.192 for the interferons), compared with basic supportive therapy. In addition, DMT therapy resulted in more relapse-free years throughout the course of a decade; patients on basic therapy averaged 5.051 relapse-free years, compared with 5.879 relapse-free years for glatiramer acetate and 5.620 to 6.074 relapse-free years for the interferons.
However, the ICERs of all four DMTs far exceeded $800,000 per QALY gained. The interferons had similar ICERs, at $901,319/QALY for intramuscular interferon beta-1a, $1,487,306/QALY for subcutaneous interferon beta-1a, and $1,123,162/QALY for interferon beta-1b. The ICER for glatiramer acetate was significantly higher, at $2,178,555/QALY. “While there is no formal cost-effectiveness threshold in the US, these estimates are an order of magnitude greater than the cost-effectiveness of many commonly accepted therapies for chronic illness,” the researchers commented.
The researchers added that cutting DMT costs by two-thirds would make the therapies’ cost-effectiveness comparable to that of other accepted interventions, however. In addition, the investigators noted that starting DMT earlier was associated with a more favorable ICER, compared with initiating treatment at any disease state, and that early treatment “may defer the substantial costs associated with late-stage MS and disability.”
Noyes K, Bajorska A, Chappel A, et al. Cost-effectiveness of disease-modifying therapy for multiple sclerosis: a population-based study. Neurology. 2011 Jul 20; [Epub ahead of print]. 

New Risk Factors for Alzheimer’s Disease?
Vision and hearing deficits, poorly fitting dentures, and increased serum proinflammatory cytokines all may be risk factors for Alzheimer’s disease, according to three studies published in the July 12 online issue of Neurology.
Alzheimer’s disease and dementia risk were associated with health deficits that are usually seen in the elderly but were not previously known to predict dementia, according to a study by Xiaowei Song, PhD, of Dalhousie University, Halifax, Canada, and colleagues.
The investigators created an index combining 19 such deficits—including problems with vision, hearing, denture fit, chest or skin, stomach or bladder, sinuses, broken bones, and feet or ankles—and applied it to 7,239 participants who were age 65 or older and free of dementia at baseline. After adjustment for age, sex, education, and baseline cognition, participants’ index scores were significantly associated with Alzheimer’s disease and dementia of all types at five and 10 years. In addition, their risk of dementia increased by 3.2% with each deficit included in the index.
Both lower and higher levels of hemoglobin were associated with Alzheimer’s disease and cognitive decline in a study by Raj C. Shah, MD, of Rush University Medical Center in Chicago, and colleagues. They gave annual cognitive assessments and clinical evaluations for Alzheimer’s disease to 881 community-dwelling, elderly participants for a mean of 3.3 years.
With adjustment for age, sex, and education, higher and lower levels of hemoglobin were associated with Alzheimer’s disease risk, with a hazard ratio of 1.06 for the quadratic of hemoglobin. Participants who had anemia or clinically high hemoglobin had a 60% increased risk of Alzheimer’s disease dementia, compared with participants who had clinically normal hemoglobin.
Increased serum proinflammatory cytokines predicted such “sickness behaviors” as increased anxiety, depression, and apathy in patients with Alzheimer’s disease, according to a study by Clive Holmes, PhD, of the University of Southampton, Southampton, UK, and colleagues. The investigators took blood samples from and performed cognitive assessments on 300 patients with mild to severe Alzheimer’s disease at baseline and two, four, and six months. Increased levels of serum tumor necrosis factor and IL-6 at baseline were associated with an approximately twofold increased frequency of neuropsychiatric symptoms characteristic of sickness behavior, independent of a history of delirium, at six months.
Despite these findings, “much uncertainty remains” about the value of nontraditional Alzheimer’s disease risk factors, emphasized Jean François Dartigues, MD, PhD, and Catherine Féart, PhD, both of the University of Victor Segalen of Bordeaux, Bordeaux, France, in an accompanying editorial. They suggested that “the studied factors could be a nonspecific consequence of aging phenomenon” and that health-related behaviors, nutritional factors, physical activities, or leisure activities could have affected the studies’ results.
Nevertheless, they added, the studies “suggest a new vision of preventive or curative treatments which, instead of targeting specific etiologic mechanisms, would aim at improving general health. Perhaps increasing adaptation to age-related changes would reduce the risk of Alzheimer’s disease dementia or its impact on the patient, caregivers, and society.”
Holmes C, Cunningham C, Zotova E, et al. Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology. 2011;77(3):212-218.
Shah RC, Buchman AS, Wilson RS, et al. Hemoglobin level in older persons and incident Alzheimer disease: prospective cohort analysis. Neurology. 2011;77(3):219-226.
Song X, Mitnitski A, Rockwood K. Nontraditional risk factors combine to predict Alzheimer disease and dementia. Neurology. 2011;77(3):227-234.
Dartigues JF, Féart C. Risk factors for Alzheimer disease: aging beyond age? Neurology. 2011;77(3):206-207.

Reducing Tonic-Clonic Seizures Can Minimize Risk of SUDEP
Clinicians can minimize the risk of sudden unexpected death in epilepsy (SUDEP) through such measures as reducing tonic-clonic seizures, choosing drugs carefully, changing treatments gradually, acting on ictal warning signs, and supervising and counseling patients, according to a seminar published online July 6 in Lancet. The seminar, by Simon Shorvon, FRCP, of the UCL Institute of Neurology in London, and Torbjorn Tomson, MD, of the Karolinska Institute in Stockholm, reviewed current research on and provided advice about minimizing SUDEP risk.
Almost all studies indicate that this risk is high in patients with a high number of tonic-clonic seizures, the authors noted. They suggested reducing these seizures through optimum treatment, good drug compliance, and advice on such lifestyle choices as alcohol intake and sleep. Ictal warning signs for tonic-clonic seizures include prolonged seizures that are associated with marked cyanosis, severe bradycardia or apnea, and postictal EEG suppression; complex partial seizures with marked atonia; and seizures in patients with pre-existing cardiac or respiratory impairment.
Patients who experience tonic-clonic seizures require supervision, the authors noted. They recommended attending to these patients continuously until the full restoration of consciousness, contacting emergency services for high-risk seizures, and supervising high-risk patients at night through attendance and use of alarms.
Clinicians should be cautious in using antiepileptic drugs (AEDs) with potential cardiorespiratory adverse effects, according to the researchers. When clinicians switch AEDs, they should introduce the new drug before withdrawing the old one and provide patients with “access to immediate advice in the event of worsening seizures,” the investigators stated.
Although some clinicians believe that informing all patients with epilepsy about the risk of SUDEP will cause unnecessary stress and anxiety, the authors recommended informing most patients about the risk to facilitate its minimization. However, they further suggested putting the risk in perspective—for example, by pointing out that, on an annual basis, it is similar to that of dying in a motor vehicle accident.
SUDEP probably has several mechanisms, and “most research has focused on seizure-related respiratory depression, cardiac arrhythmia, cerebral depression, and autonomic dysfunction,” the authors noted. Along with tonic-clonic seizures, risk factors for the event include male sex, long-duration epilepsy, and antiepileptic polytherapy.
Shorvon S, Tomson T. Sudden unexpected death in epilepsy. Lancet. 2011 Jul 5; [Epub ahead of print].

How Cost-Effective Are Disease-Modifying Therapies in MS?
Disease-modifying therapies (DMTs) for relapsing-remitting or secondary progressive multiple sclerosis (MS) do not appear to be cost-effective in the United States, according to findings published online July 20 by Neurology.
Katia Noyes, PhD, MPH, of the University of Rochester, New York, and colleagues calculated the cost-effectiveness of four DMTs in a  nationally representative cohort of 1,121 patients with MS. The investigators generated 10-year disease progression paths for this cohort; looked at data on drug effectiveness, patient health preferences, health care use, lost productivity, and medical costs; measured health gains in quality-adjusted life-years (QALYs) and relapse-free years; and calculated incremental cost-effectiveness ratios (ICERs). The DMTs studied were glatiramer acetate, intramuscular interferon beta-1a, subcutaneous interferon beta-1a, and interferon beta-1b.
DMT therapy for 10 years resulted in modest QALY gains (0.082 for glatiramer acetate and 0.126 to 0.192 for the interferons), compared with basic supportive therapy. In addition, DMT therapy resulted in more relapse-free years throughout the course of a decade; patients on basic therapy averaged 5.051 relapse-free years, compared with 5.879 relapse-free years for glatiramer acetate and 5.620 to 6.074 relapse-free years for the interferons.
However, the ICERs of all four DMTs far exceeded $800,000 per QALY gained. The interferons had similar ICERs, at $901,319/QALY for intramuscular interferon beta-1a, $1,487,306/QALY for subcutaneous interferon beta-1a, and $1,123,162/QALY for interferon beta-1b. The ICER for glatiramer acetate was significantly higher, at $2,178,555/QALY. “While there is no formal cost-effectiveness threshold in the US, these estimates are an order of magnitude greater than the cost-effectiveness of many commonly accepted therapies for chronic illness,” the researchers commented.
The researchers added that cutting DMT costs by two-thirds would make the therapies’ cost-effectiveness comparable to that of other accepted interventions, however. In addition, the investigators noted that starting DMT earlier was associated with a more favorable ICER, compared with initiating treatment at any disease state, and that early treatment “may defer the substantial costs associated with late-stage MS and disability.”
Noyes K, Bajorska A, Chappel A, et al. Cost-effectiveness of disease-modifying therapy for multiple sclerosis: a population-based study. Neurology. 2011 Jul 20; [Epub ahead of print]. 

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.”