Multiple Sclerosis Hub

Patients with multiple sclerosis (MS) have a decreased overall cancer risk but have a higher risk of brain tumors and urinary organ cancer, according to a study published in the March 31 issue of Neurology. The lack of cancer risk among patients with MS likely does not result from an inherited characteristic, but rather from a behavioral change, treatment, or immunologic characteristic that improves antitumor surveillance, researchers reported.

Shahram Bahmanyar, MD, PhD, of the Clinical Epidemiology Unit in the Department of Medicine at Karolinska Institute in Karolinska Hospital in Stockholm, and colleagues estimated the disease risk among 20,276 patients with MS and 203,951 controls using data from the Swedish general population register. Similar analyses were completed among 11,284 fathers and 12,006 mothers of patients with MS, and also 123,158 fathers and 129,409 mothers of controls. The average length of follow-up was 35 years.

Overall, there was a decreased risk of cancer among patients with MS (hazard ratio [HR], 0.91). The risk for women was especially low. Follow-up beginning at the time of MS diagnosis showed little change (HR, 0.88). The risk was lower when, to ensure diagnostic accuracy, the analysis was restricted to MS register subjects and the relevant comparisons population (HR, 0.63). However, increased risks were observed for brain tumors (HR, 1.44) and urinary organ cancer (HR, 1.27). The average age of brain tumor diagnosis among patients with MS was 51.4, compared with 53.2 in the comparison group. An overall lower risk was observed among those who were diagnosed at earlier ages. Those diagnosed at age 20, between 20 and 34, and older than 34 had HRs of 0.32, 0.64, and 0.92, respectively. This effect was more pronounced among women, and an interaction test of age by gender produced a statistically significant HR of 0.974.

The overall cancer risk among parents of those with MS was not notably increased or decreased. Analysis of specific cancer sites did not show a protective or risk pattern. A modest increase for cancers of bone, kidney, and lymphoma among fathers was observed, along with an increase of endocrine cancers among mothers. “The lack of association among parents indicates that a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS,” Dr. Bahmanyar and colleagues stated.

“The lower cancer risk among patients with MS could be associated with lifestyle changes, treatment, disease-related activity, or a combination of these factors,” Dr. Bahmanyar and the study group suggested. Patients with MS often have a lower body mass index, which is a risk factor for some types of cancer. The researchers also speculated that cancer protection may result in part from the increase in systemic autoimmune responses against myelin antigens observed among patients.

“If autoimmune cells such as these react specifically against tumor autoantigens, this could represent an effective tumor defense mechanism,” the authors reported.

Patients with multiple sclerosis (MS) have a decreased overall cancer risk but have a higher risk of brain tumors and urinary organ cancer, according to a study published in the March 31 issue of Neurology. The lack of cancer risk among patients with MS likely does not result from an inherited characteristic, but rather from a behavioral change, treatment, or immunologic characteristic that improves antitumor surveillance, researchers reported.

Shahram Bahmanyar, MD, PhD, of the Clinical Epidemiology Unit in the Department of Medicine at Karolinska Institute in Karolinska Hospital in Stockholm, and colleagues estimated the disease risk among 20,276 patients with MS and 203,951 controls using data from the Swedish general population register. Similar analyses were completed among 11,284 fathers and 12,006 mothers of patients with MS, and also 123,158 fathers and 129,409 mothers of controls. The average length of follow-up was 35 years.

Overall, there was a decreased risk of cancer among patients with MS (hazard ratio [HR], 0.91). The risk for women was especially low. Follow-up beginning at the time of MS diagnosis showed little change (HR, 0.88). The risk was lower when, to ensure diagnostic accuracy, the analysis was restricted to MS register subjects and the relevant comparisons population (HR, 0.63). However, increased risks were observed for brain tumors (HR, 1.44) and urinary organ cancer (HR, 1.27). The average age of brain tumor diagnosis among patients with MS was 51.4, compared with 53.2 in the comparison group. An overall lower risk was observed among those who were diagnosed at earlier ages. Those diagnosed at age 20, between 20 and 34, and older than 34 had HRs of 0.32, 0.64, and 0.92, respectively. This effect was more pronounced among women, and an interaction test of age by gender produced a statistically significant HR of 0.974.

The overall cancer risk among parents of those with MS was not notably increased or decreased. Analysis of specific cancer sites did not show a protective or risk pattern. A modest increase for cancers of bone, kidney, and lymphoma among fathers was observed, along with an increase of endocrine cancers among mothers. “The lack of association among parents indicates that a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS,” Dr. Bahmanyar and colleagues stated.

“The lower cancer risk among patients with MS could be associated with lifestyle changes, treatment, disease-related activity, or a combination of these factors,” Dr. Bahmanyar and the study group suggested. Patients with MS often have a lower body mass index, which is a risk factor for some types of cancer. The researchers also speculated that cancer protection may result in part from the increase in systemic autoimmune responses against myelin antigens observed among patients.

“If autoimmune cells such as these react specifically against tumor autoantigens, this could represent an effective tumor defense mechanism,” the authors reported.

Patients with multiple sclerosis (MS) have a decreased overall cancer risk but have a higher risk of brain tumors and urinary organ cancer, according to a study published in the March 31 issue of Neurology. The lack of cancer risk among patients with MS likely does not result from an inherited characteristic, but rather from a behavioral change, treatment, or immunologic characteristic that improves antitumor surveillance, researchers reported.

Shahram Bahmanyar, MD, PhD, of the Clinical Epidemiology Unit in the Department of Medicine at Karolinska Institute in Karolinska Hospital in Stockholm, and colleagues estimated the disease risk among 20,276 patients with MS and 203,951 controls using data from the Swedish general population register. Similar analyses were completed among 11,284 fathers and 12,006 mothers of patients with MS, and also 123,158 fathers and 129,409 mothers of controls. The average length of follow-up was 35 years.

Overall, there was a decreased risk of cancer among patients with MS (hazard ratio [HR], 0.91). The risk for women was especially low. Follow-up beginning at the time of MS diagnosis showed little change (HR, 0.88). The risk was lower when, to ensure diagnostic accuracy, the analysis was restricted to MS register subjects and the relevant comparisons population (HR, 0.63). However, increased risks were observed for brain tumors (HR, 1.44) and urinary organ cancer (HR, 1.27). The average age of brain tumor diagnosis among patients with MS was 51.4, compared with 53.2 in the comparison group. An overall lower risk was observed among those who were diagnosed at earlier ages. Those diagnosed at age 20, between 20 and 34, and older than 34 had HRs of 0.32, 0.64, and 0.92, respectively. This effect was more pronounced among women, and an interaction test of age by gender produced a statistically significant HR of 0.974.

The overall cancer risk among parents of those with MS was not notably increased or decreased. Analysis of specific cancer sites did not show a protective or risk pattern. A modest increase for cancers of bone, kidney, and lymphoma among fathers was observed, along with an increase of endocrine cancers among mothers. “The lack of association among parents indicates that a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS,” Dr. Bahmanyar and colleagues stated.

“The lower cancer risk among patients with MS could be associated with lifestyle changes, treatment, disease-related activity, or a combination of these factors,” Dr. Bahmanyar and the study group suggested. Patients with MS often have a lower body mass index, which is a risk factor for some types of cancer. The researchers also speculated that cancer protection may result in part from the increase in systemic autoimmune responses against myelin antigens observed among patients.

“If autoimmune cells such as these react specifically against tumor autoantigens, this could represent an effective tumor defense mechanism,” the authors reported.

Urgent Treatment of Minor Strokes Improves Outcomes
NEW YORK, February 4 (Reuters Health)—Urgent evaluation and treatment of patients with minor strokes and transient ischemic attacks (TIAs) in a specialist outpatient clinic can reduce future hospital bed-days, costs, and disability at six months, new research shows.

In the initial analysis of the Early use of eXisting PREventive Strategies for Stroke (EXPRESS) study, urgent assessment and treatment cut the 90-day risk of repeat stroke by roughly 80%. In the current analysis, Dr. Peter M. Rothwell, from John Radcliffe Hospital, Oxford, UK, and colleagues looked at the impact on hospital admission, costs, and disability.

EXPRESS involved a comparison of stroke outcomes between April 2002 and September 2004, before the set-up of specialist outpatient clinics designed to expedite stroke treatment and assessment, and afterwards during the period October 2004 to March 2007. Unlike the standard clinics, these clinics did not require an appointment, and primary care doctors were advised to send all patients with suspected stroke or TIA to them immediately.

As reported in the March issue of the Lancet Neurology, the urgent stroke clinics were associated with significant reductions in the 90-day risk of fatal or disabling stroke and hospital admissions for recurrent stroke. Reductions in the overall and vascular-related number of hospital bed days also occurred, from 1957 to 672 bed days after the clinics began. For each patient referred to an urgent stroke clinic, a cost savings of £624 ($887) was realized, the report indicated.

Further studies are needed to assess the long-term benefits of urgent assessment and treatment of strokes in specialist clinics, the authors concluded.

In a related editorial, Dr. Naeem Dean and Dr. Ashfaq Shuaib, from Royal Alexandra Hospital and the University of Alberta, Edmonton, Canada, commented that “the care of patients with stroke and the prevention of further events in patients who present with TIA, will, unfortunately, always be suboptimum as long as we fail to equate TIA and stroke care in line with the way we manage patients with acute coronary disorders.”

They added, “We hope that the research work emanating from several stroke centers ... will bring awareness to this underrecognized and poorly treated but common condition.”

Lancet Neurol. 2009;8(3):218-219, 235-243.

Both Cortical and Subcortical Atrophy Involved in Amnesia of MS
NEW YORK, February 6 (Reuters Health)—Memory impairment in multiple sclerosis (MS) correlates with both mesial temporal (MTL) and deep grey matter (DGM) atrophy, researchers from the State University of New York at Buffalo have observed.

“We have compared the relative clinical significance of MTL and DGM atrophy and found evidence supporting significant and distinct contributions of each region to MS-associated memory disorder,” Dr. Ralph H. B. Benedict and colleagues reported in the February issue of the Journal of Neurology, Neurosurgery, and Psychiatry.

In the study, 50 patients with MS underwent structural brain MRI and neuropsychologic testing. The results suggest that DGM atrophy is the primary predictor of impairment in new learning and acquisition, whereas MTL atrophy plays a more critical role in the retention of recently learned information, as measured by 20- to 25-minute delayed recall and recognition tasks.

“This paper makes an important conceptual point—that the dementia of MS includes clinical features that are related to frontal-subcortical circuitry and MTL cortex pathology,” Dr. Benedict noted in comments to Reuters Health. “Understanding that MS patients can present with either or both helps doctors correctly describe and explain the cognitive presentation of MS patients, and in turn, provide better management of this aspect of the illness,” he added.

The current findings, the investigators said, “support a rationale for therapies directed at both the encoding and consolidation aspects of memory in MS.”

J Neurol Neurosurg Psychiatry. 2009;80(2):201-206.

Urgent Treatment of Minor Strokes Improves Outcomes
NEW YORK, February 4 (Reuters Health)—Urgent evaluation and treatment of patients with minor strokes and transient ischemic attacks (TIAs) in a specialist outpatient clinic can reduce future hospital bed-days, costs, and disability at six months, new research shows.

In the initial analysis of the Early use of eXisting PREventive Strategies for Stroke (EXPRESS) study, urgent assessment and treatment cut the 90-day risk of repeat stroke by roughly 80%. In the current analysis, Dr. Peter M. Rothwell, from John Radcliffe Hospital, Oxford, UK, and colleagues looked at the impact on hospital admission, costs, and disability.

EXPRESS involved a comparison of stroke outcomes between April 2002 and September 2004, before the set-up of specialist outpatient clinics designed to expedite stroke treatment and assessment, and afterwards during the period October 2004 to March 2007. Unlike the standard clinics, these clinics did not require an appointment, and primary care doctors were advised to send all patients with suspected stroke or TIA to them immediately.

As reported in the March issue of the Lancet Neurology, the urgent stroke clinics were associated with significant reductions in the 90-day risk of fatal or disabling stroke and hospital admissions for recurrent stroke. Reductions in the overall and vascular-related number of hospital bed days also occurred, from 1957 to 672 bed days after the clinics began. For each patient referred to an urgent stroke clinic, a cost savings of £624 ($887) was realized, the report indicated.

Further studies are needed to assess the long-term benefits of urgent assessment and treatment of strokes in specialist clinics, the authors concluded.

In a related editorial, Dr. Naeem Dean and Dr. Ashfaq Shuaib, from Royal Alexandra Hospital and the University of Alberta, Edmonton, Canada, commented that “the care of patients with stroke and the prevention of further events in patients who present with TIA, will, unfortunately, always be suboptimum as long as we fail to equate TIA and stroke care in line with the way we manage patients with acute coronary disorders.”

They added, “We hope that the research work emanating from several stroke centers ... will bring awareness to this underrecognized and poorly treated but common condition.”

Lancet Neurol. 2009;8(3):218-219, 235-243.

Both Cortical and Subcortical Atrophy Involved in Amnesia of MS
NEW YORK, February 6 (Reuters Health)—Memory impairment in multiple sclerosis (MS) correlates with both mesial temporal (MTL) and deep grey matter (DGM) atrophy, researchers from the State University of New York at Buffalo have observed.

“We have compared the relative clinical significance of MTL and DGM atrophy and found evidence supporting significant and distinct contributions of each region to MS-associated memory disorder,” Dr. Ralph H. B. Benedict and colleagues reported in the February issue of the Journal of Neurology, Neurosurgery, and Psychiatry.

In the study, 50 patients with MS underwent structural brain MRI and neuropsychologic testing. The results suggest that DGM atrophy is the primary predictor of impairment in new learning and acquisition, whereas MTL atrophy plays a more critical role in the retention of recently learned information, as measured by 20- to 25-minute delayed recall and recognition tasks.

“This paper makes an important conceptual point—that the dementia of MS includes clinical features that are related to frontal-subcortical circuitry and MTL cortex pathology,” Dr. Benedict noted in comments to Reuters Health. “Understanding that MS patients can present with either or both helps doctors correctly describe and explain the cognitive presentation of MS patients, and in turn, provide better management of this aspect of the illness,” he added.

The current findings, the investigators said, “support a rationale for therapies directed at both the encoding and consolidation aspects of memory in MS.”

J Neurol Neurosurg Psychiatry. 2009;80(2):201-206.

Urgent Treatment of Minor Strokes Improves Outcomes
NEW YORK, February 4 (Reuters Health)—Urgent evaluation and treatment of patients with minor strokes and transient ischemic attacks (TIAs) in a specialist outpatient clinic can reduce future hospital bed-days, costs, and disability at six months, new research shows.

In the initial analysis of the Early use of eXisting PREventive Strategies for Stroke (EXPRESS) study, urgent assessment and treatment cut the 90-day risk of repeat stroke by roughly 80%. In the current analysis, Dr. Peter M. Rothwell, from John Radcliffe Hospital, Oxford, UK, and colleagues looked at the impact on hospital admission, costs, and disability.

EXPRESS involved a comparison of stroke outcomes between April 2002 and September 2004, before the set-up of specialist outpatient clinics designed to expedite stroke treatment and assessment, and afterwards during the period October 2004 to March 2007. Unlike the standard clinics, these clinics did not require an appointment, and primary care doctors were advised to send all patients with suspected stroke or TIA to them immediately.

As reported in the March issue of the Lancet Neurology, the urgent stroke clinics were associated with significant reductions in the 90-day risk of fatal or disabling stroke and hospital admissions for recurrent stroke. Reductions in the overall and vascular-related number of hospital bed days also occurred, from 1957 to 672 bed days after the clinics began. For each patient referred to an urgent stroke clinic, a cost savings of £624 ($887) was realized, the report indicated.

Further studies are needed to assess the long-term benefits of urgent assessment and treatment of strokes in specialist clinics, the authors concluded.

In a related editorial, Dr. Naeem Dean and Dr. Ashfaq Shuaib, from Royal Alexandra Hospital and the University of Alberta, Edmonton, Canada, commented that “the care of patients with stroke and the prevention of further events in patients who present with TIA, will, unfortunately, always be suboptimum as long as we fail to equate TIA and stroke care in line with the way we manage patients with acute coronary disorders.”

They added, “We hope that the research work emanating from several stroke centers ... will bring awareness to this underrecognized and poorly treated but common condition.”

Lancet Neurol. 2009;8(3):218-219, 235-243.

Both Cortical and Subcortical Atrophy Involved in Amnesia of MS
NEW YORK, February 6 (Reuters Health)—Memory impairment in multiple sclerosis (MS) correlates with both mesial temporal (MTL) and deep grey matter (DGM) atrophy, researchers from the State University of New York at Buffalo have observed.

“We have compared the relative clinical significance of MTL and DGM atrophy and found evidence supporting significant and distinct contributions of each region to MS-associated memory disorder,” Dr. Ralph H. B. Benedict and colleagues reported in the February issue of the Journal of Neurology, Neurosurgery, and Psychiatry.

In the study, 50 patients with MS underwent structural brain MRI and neuropsychologic testing. The results suggest that DGM atrophy is the primary predictor of impairment in new learning and acquisition, whereas MTL atrophy plays a more critical role in the retention of recently learned information, as measured by 20- to 25-minute delayed recall and recognition tasks.

“This paper makes an important conceptual point—that the dementia of MS includes clinical features that are related to frontal-subcortical circuitry and MTL cortex pathology,” Dr. Benedict noted in comments to Reuters Health. “Understanding that MS patients can present with either or both helps doctors correctly describe and explain the cognitive presentation of MS patients, and in turn, provide better management of this aspect of the illness,” he added.

The current findings, the investigators said, “support a rationale for therapies directed at both the encoding and consolidation aspects of memory in MS.”

J Neurol Neurosurg Psychiatry. 2009;80(2):201-206.

SALT LAKE CITY—ST8SIA1 is a susceptibility gene for multiple sclerosis (MS) and is transmitted primarily paternally, according to research presented at the 133rd Annual Meeting of the American Neurological Association. The finding may lead to new approaches for understanding the molecular pathophysiology of MS, reported Seema Husain, PhD, Research Associate at the Institute of Genomic Medicine, University of Medicine and Dentistry of New Jersey in Newark, and colleagues.

Two independent studies involving single-nucleotide polymorphism (SNP) analysis and gene sequence were conducted. The allelic association of MS with polymorphisms in the ST8SIA1 gene, located on chromosome 12p12, was first found in a single three-generation Pennsylvania Dutch family, in which the rs4762896 SNP was segregated along with the HLA DR15/DQ6 haplotype in patients with MS. Similar observations were made in a study of 274 Australian family trios that had an affected child and unaffected parents. Within this sample, researchers reported evidence of transmission disequilibrium of the paternal alleles for three more SNPs—rs704219, rs2041906, and rs1558793.

In the Pennsylvania Dutch family, six members were diagnosed with clinically definite MS and one had clinically probable MS. The investigators found only rs4762896 segregate along with the HLA DR15/DQ6 haplotype in the seven affected individuals.

An examination of the Australian sample of 209 trios showed significantly increased transmission of paternal alleles for rs704219, rs2041906, and rs1558793. An additional 65 trios from Tasmania were also genotyped for these three SNPs, and the same trend was observed.

In an analysis of interaction between the SNPs typed in the extended Australian cohorts (rs704219, rs2041906, and rs1558793) and HLA DR15/DQ6, the trios were divided into DR15-positive (n = 145) and DR15-negative (n = 128) groups. Transmission disequilibrium test analysis was completed separately. Results were similar but less significant than those in the previous analysis. In addition, the Australian cohort partially shared one haplotype with the Pennsylvania Dutch family—the T allele of rs1558793 and the A allele of rs2041906.

“Our results suggest that ST8SIA1 may be an MS susceptibility gene possibly regulated by genomic imprinting,” said Dr. Husain and colleagues. “Outside of the immunoregulatory system, this is the first gene extensively involved in neuronal function and membrane structure to be implicated with MS.”

SALT LAKE CITY—ST8SIA1 is a susceptibility gene for multiple sclerosis (MS) and is transmitted primarily paternally, according to research presented at the 133rd Annual Meeting of the American Neurological Association. The finding may lead to new approaches for understanding the molecular pathophysiology of MS, reported Seema Husain, PhD, Research Associate at the Institute of Genomic Medicine, University of Medicine and Dentistry of New Jersey in Newark, and colleagues.

Two independent studies involving single-nucleotide polymorphism (SNP) analysis and gene sequence were conducted. The allelic association of MS with polymorphisms in the ST8SIA1 gene, located on chromosome 12p12, was first found in a single three-generation Pennsylvania Dutch family, in which the rs4762896 SNP was segregated along with the HLA DR15/DQ6 haplotype in patients with MS. Similar observations were made in a study of 274 Australian family trios that had an affected child and unaffected parents. Within this sample, researchers reported evidence of transmission disequilibrium of the paternal alleles for three more SNPs—rs704219, rs2041906, and rs1558793.

In the Pennsylvania Dutch family, six members were diagnosed with clinically definite MS and one had clinically probable MS. The investigators found only rs4762896 segregate along with the HLA DR15/DQ6 haplotype in the seven affected individuals.

An examination of the Australian sample of 209 trios showed significantly increased transmission of paternal alleles for rs704219, rs2041906, and rs1558793. An additional 65 trios from Tasmania were also genotyped for these three SNPs, and the same trend was observed.

In an analysis of interaction between the SNPs typed in the extended Australian cohorts (rs704219, rs2041906, and rs1558793) and HLA DR15/DQ6, the trios were divided into DR15-positive (n = 145) and DR15-negative (n = 128) groups. Transmission disequilibrium test analysis was completed separately. Results were similar but less significant than those in the previous analysis. In addition, the Australian cohort partially shared one haplotype with the Pennsylvania Dutch family—the T allele of rs1558793 and the A allele of rs2041906.

“Our results suggest that ST8SIA1 may be an MS susceptibility gene possibly regulated by genomic imprinting,” said Dr. Husain and colleagues. “Outside of the immunoregulatory system, this is the first gene extensively involved in neuronal function and membrane structure to be implicated with MS.”

SALT LAKE CITY—ST8SIA1 is a susceptibility gene for multiple sclerosis (MS) and is transmitted primarily paternally, according to research presented at the 133rd Annual Meeting of the American Neurological Association. The finding may lead to new approaches for understanding the molecular pathophysiology of MS, reported Seema Husain, PhD, Research Associate at the Institute of Genomic Medicine, University of Medicine and Dentistry of New Jersey in Newark, and colleagues.

Two independent studies involving single-nucleotide polymorphism (SNP) analysis and gene sequence were conducted. The allelic association of MS with polymorphisms in the ST8SIA1 gene, located on chromosome 12p12, was first found in a single three-generation Pennsylvania Dutch family, in which the rs4762896 SNP was segregated along with the HLA DR15/DQ6 haplotype in patients with MS. Similar observations were made in a study of 274 Australian family trios that had an affected child and unaffected parents. Within this sample, researchers reported evidence of transmission disequilibrium of the paternal alleles for three more SNPs—rs704219, rs2041906, and rs1558793.

In the Pennsylvania Dutch family, six members were diagnosed with clinically definite MS and one had clinically probable MS. The investigators found only rs4762896 segregate along with the HLA DR15/DQ6 haplotype in the seven affected individuals.

An examination of the Australian sample of 209 trios showed significantly increased transmission of paternal alleles for rs704219, rs2041906, and rs1558793. An additional 65 trios from Tasmania were also genotyped for these three SNPs, and the same trend was observed.

In an analysis of interaction between the SNPs typed in the extended Australian cohorts (rs704219, rs2041906, and rs1558793) and HLA DR15/DQ6, the trios were divided into DR15-positive (n = 145) and DR15-negative (n = 128) groups. Transmission disequilibrium test analysis was completed separately. Results were similar but less significant than those in the previous analysis. In addition, the Australian cohort partially shared one haplotype with the Pennsylvania Dutch family—the T allele of rs1558793 and the A allele of rs2041906.

“Our results suggest that ST8SIA1 may be an MS susceptibility gene possibly regulated by genomic imprinting,” said Dr. Husain and colleagues. “Outside of the immunoregulatory system, this is the first gene extensively involved in neuronal function and membrane structure to be implicated with MS.”

SALT LAKE CITY—Patients with multiple sclerosis (MS) who use glatiramer acetate have significantly fewer relapses and lower medical costs, compared with those who use interferon beta-1b, reported researchers at the 133rd Annual Meeting of the American Neurological Association.

A Retrospective Analysis
Kenneth P. Johnson, MD, Professor Emeritus of Neurology at the University of Maryland and Director of the Maryland Center for Multiple Sclerosis in Baltimore, and Maureen J. Lage, PhD, Managing Member of HealthMetrics Outcomes Research in Groton, Connecticut, retrospectively studied data from the i3 LabRx Database. This health claims database includes laboratory test results, hospitalization data, pharmacy data, and demographic information for more than 20 million individuals from a major US managed care organization. Data were collected from July 2001 through June 2006.

Patients were included in the continuous use cohort (n = 418) if they used either interferon beta-1b or glatiramer acetate continuously for at least 24 months.

Costs were calculated as direct medical costs, which included inpatient, outpatient, and prescription drug services. These were based on paid amounts (eg, insurer and health plan payments, copayments, and deductibles). All costs were converted to 2006 values using the medical component of the Consumer Price Index.

Relapse was defined as either a hospitalization with a primary diagnosis of MS or an outpatient visit with a diagnosis of MS accompanied by a prescription for steroids within seven days after the outpatient visit.

One hundred ten patients received interferon beta-1b (mean age, 43.96; 76% female) and 308 patients received glatiramer acetate (mean age, 44.23; 82% female). The mean number of outpatient prescription medications totaled 4.18 and 4.42, respectively. Approximately 98% of patients in both groups had commercial insurance.

Hypertension was the most frequent comorbidity, occurring in 19 patients in the interferon beta-1b group and 39 patients in the glatiramer acetate group. Other comorbidities included anxiety, depression, diabetes, and high cholesterol. Concomitant medication uses included adrenal, anticholinergic, anticonvulsant, antiviral, cerebral stimulant, genitourinary, and skeletal muscle agents.

Eleven patients from the interferon beta-1b group and 23 from the glatiramer acetate group had a preperiod hospitalization with MS diagnosis (ie, six months before the date of first use of interferon beta-1b or glatiramer acetate).

Interferon Beta-1b: Costlier, With More MS Relapses
According to Drs. Johnson and Lage, in the two years following initiation of therapy, subjects who received interferon beta-1b had a 10.92% chance of relapse, while those taking glatiramer acetate had a 2.09% risk. The two-year total direct medical costs associated with the use of interferon beta-1b was $53,185; this amount was greatly reduced for subjects taking glatiramer acetate, with a direct two-year cost of $48,130.

This study was limited by the use of an administrative claims database that included only patients with medical and prescription benefit coverage. The medical claims data precluded the use of physician- or patient-reported functioning. In addition, the study used a different method for defining relapses than those used in traditional clinical studies; however, the algorithm was applied equally to both groups. The authors also stated that the study focused only on direct medical costs, despite other research that has indicated that the indirect costs of MS are also large.

Results Depict “Real Life” Data
Despite these limitations, the results are consistent with prior research. “Based on all of the currently available published data, glatiramer acetate is not only better tolerated but also shows significantly better clinical efficacy than interferon beta-1b for relapsing MS and is less costly,” Dr. Johnson commented in an interview with Neurology Reviews.

“While this is a direct comparison of the two drugs, it differs from the recent head-to-head trial data. This analysis was of the outcomes over two years of MS patients [in the US] who were not rigidly defined, as is required in a clinical trial, but depended on personal treatment decisions of US physicians, mainly neurologists practicing in all regions of the US,” concluded Dr. Johnson. “In my view, this analysis comes closer to the ‘real life’ situation in the US.

SALT LAKE CITY—Patients with multiple sclerosis (MS) who use glatiramer acetate have significantly fewer relapses and lower medical costs, compared with those who use interferon beta-1b, reported researchers at the 133rd Annual Meeting of the American Neurological Association.

A Retrospective Analysis
Kenneth P. Johnson, MD, Professor Emeritus of Neurology at the University of Maryland and Director of the Maryland Center for Multiple Sclerosis in Baltimore, and Maureen J. Lage, PhD, Managing Member of HealthMetrics Outcomes Research in Groton, Connecticut, retrospectively studied data from the i3 LabRx Database. This health claims database includes laboratory test results, hospitalization data, pharmacy data, and demographic information for more than 20 million individuals from a major US managed care organization. Data were collected from July 2001 through June 2006.

Patients were included in the continuous use cohort (n = 418) if they used either interferon beta-1b or glatiramer acetate continuously for at least 24 months.

Costs were calculated as direct medical costs, which included inpatient, outpatient, and prescription drug services. These were based on paid amounts (eg, insurer and health plan payments, copayments, and deductibles). All costs were converted to 2006 values using the medical component of the Consumer Price Index.

Relapse was defined as either a hospitalization with a primary diagnosis of MS or an outpatient visit with a diagnosis of MS accompanied by a prescription for steroids within seven days after the outpatient visit.

One hundred ten patients received interferon beta-1b (mean age, 43.96; 76% female) and 308 patients received glatiramer acetate (mean age, 44.23; 82% female). The mean number of outpatient prescription medications totaled 4.18 and 4.42, respectively. Approximately 98% of patients in both groups had commercial insurance.

Hypertension was the most frequent comorbidity, occurring in 19 patients in the interferon beta-1b group and 39 patients in the glatiramer acetate group. Other comorbidities included anxiety, depression, diabetes, and high cholesterol. Concomitant medication uses included adrenal, anticholinergic, anticonvulsant, antiviral, cerebral stimulant, genitourinary, and skeletal muscle agents.

Eleven patients from the interferon beta-1b group and 23 from the glatiramer acetate group had a preperiod hospitalization with MS diagnosis (ie, six months before the date of first use of interferon beta-1b or glatiramer acetate).

Interferon Beta-1b: Costlier, With More MS Relapses
According to Drs. Johnson and Lage, in the two years following initiation of therapy, subjects who received interferon beta-1b had a 10.92% chance of relapse, while those taking glatiramer acetate had a 2.09% risk. The two-year total direct medical costs associated with the use of interferon beta-1b was $53,185; this amount was greatly reduced for subjects taking glatiramer acetate, with a direct two-year cost of $48,130.

This study was limited by the use of an administrative claims database that included only patients with medical and prescription benefit coverage. The medical claims data precluded the use of physician- or patient-reported functioning. In addition, the study used a different method for defining relapses than those used in traditional clinical studies; however, the algorithm was applied equally to both groups. The authors also stated that the study focused only on direct medical costs, despite other research that has indicated that the indirect costs of MS are also large.

Results Depict “Real Life” Data
Despite these limitations, the results are consistent with prior research. “Based on all of the currently available published data, glatiramer acetate is not only better tolerated but also shows significantly better clinical efficacy than interferon beta-1b for relapsing MS and is less costly,” Dr. Johnson commented in an interview with Neurology Reviews.

“While this is a direct comparison of the two drugs, it differs from the recent head-to-head trial data. This analysis was of the outcomes over two years of MS patients [in the US] who were not rigidly defined, as is required in a clinical trial, but depended on personal treatment decisions of US physicians, mainly neurologists practicing in all regions of the US,” concluded Dr. Johnson. “In my view, this analysis comes closer to the ‘real life’ situation in the US.

SALT LAKE CITY—Patients with multiple sclerosis (MS) who use glatiramer acetate have significantly fewer relapses and lower medical costs, compared with those who use interferon beta-1b, reported researchers at the 133rd Annual Meeting of the American Neurological Association.

A Retrospective Analysis
Kenneth P. Johnson, MD, Professor Emeritus of Neurology at the University of Maryland and Director of the Maryland Center for Multiple Sclerosis in Baltimore, and Maureen J. Lage, PhD, Managing Member of HealthMetrics Outcomes Research in Groton, Connecticut, retrospectively studied data from the i3 LabRx Database. This health claims database includes laboratory test results, hospitalization data, pharmacy data, and demographic information for more than 20 million individuals from a major US managed care organization. Data were collected from July 2001 through June 2006.

Patients were included in the continuous use cohort (n = 418) if they used either interferon beta-1b or glatiramer acetate continuously for at least 24 months.

Costs were calculated as direct medical costs, which included inpatient, outpatient, and prescription drug services. These were based on paid amounts (eg, insurer and health plan payments, copayments, and deductibles). All costs were converted to 2006 values using the medical component of the Consumer Price Index.

Relapse was defined as either a hospitalization with a primary diagnosis of MS or an outpatient visit with a diagnosis of MS accompanied by a prescription for steroids within seven days after the outpatient visit.

One hundred ten patients received interferon beta-1b (mean age, 43.96; 76% female) and 308 patients received glatiramer acetate (mean age, 44.23; 82% female). The mean number of outpatient prescription medications totaled 4.18 and 4.42, respectively. Approximately 98% of patients in both groups had commercial insurance.

Hypertension was the most frequent comorbidity, occurring in 19 patients in the interferon beta-1b group and 39 patients in the glatiramer acetate group. Other comorbidities included anxiety, depression, diabetes, and high cholesterol. Concomitant medication uses included adrenal, anticholinergic, anticonvulsant, antiviral, cerebral stimulant, genitourinary, and skeletal muscle agents.

Eleven patients from the interferon beta-1b group and 23 from the glatiramer acetate group had a preperiod hospitalization with MS diagnosis (ie, six months before the date of first use of interferon beta-1b or glatiramer acetate).

Interferon Beta-1b: Costlier, With More MS Relapses
According to Drs. Johnson and Lage, in the two years following initiation of therapy, subjects who received interferon beta-1b had a 10.92% chance of relapse, while those taking glatiramer acetate had a 2.09% risk. The two-year total direct medical costs associated with the use of interferon beta-1b was $53,185; this amount was greatly reduced for subjects taking glatiramer acetate, with a direct two-year cost of $48,130.

This study was limited by the use of an administrative claims database that included only patients with medical and prescription benefit coverage. The medical claims data precluded the use of physician- or patient-reported functioning. In addition, the study used a different method for defining relapses than those used in traditional clinical studies; however, the algorithm was applied equally to both groups. The authors also stated that the study focused only on direct medical costs, despite other research that has indicated that the indirect costs of MS are also large.

Results Depict “Real Life” Data
Despite these limitations, the results are consistent with prior research. “Based on all of the currently available published data, glatiramer acetate is not only better tolerated but also shows significantly better clinical efficacy than interferon beta-1b for relapsing MS and is less costly,” Dr. Johnson commented in an interview with Neurology Reviews.

“While this is a direct comparison of the two drugs, it differs from the recent head-to-head trial data. This analysis was of the outcomes over two years of MS patients [in the US] who were not rigidly defined, as is required in a clinical trial, but depended on personal treatment decisions of US physicians, mainly neurologists practicing in all regions of the US,” concluded Dr. Johnson. “In my view, this analysis comes closer to the ‘real life’ situation in the US.

MONTREAL—Treating patients with multiple sclerosis (MS) who have breakthrough disease activity despite the use of disease-modifying drug therapy requires identification of suboptimal responders, a monitoring strategy, and consideration of largely unproven treatment approaches, said Richard A. Rudick, MD, at the 2008 World Congress on Treatment and Research in Multiple Sclerosis.

“A large proportion of patients with relapsing-remitting MS will show signs of disease activity within one to two years,” said Dr. Rudick. “This is not necessarily a poor response to therapy; this is expected.”

In published phase III trials, 62% to 75% of patients with relapsing-remitting MS had one or more relapses within two years while on disease-modifying drug therapy, about one fourth had a sustained increase in Expanded Disability Status Scale score, about one fourth had one or more gadolinium (Gd)-enhancing lesions, and more than half had one or more new T2 lesions.

Identifying nonresponders, therefore, is the first consideration in managing true breakthrough disease, said Dr. Rudick, Director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic. Patient self-report and the physician’s global impression of change are usually the initial approaches, although the validity of these approaches has not been studied.

Relapses do not appear to be a reliable marker for response to a disease-modifying drug, according to Dr. Rudick. In placebo-controlled clinical studies, many patients who remain on placebo will have fewer relapses in year 2 than in year 1—a regression to the mean phenomenon. Reliance on relapse data—especially from studies in which patients are crossed over from placebo to treatment after a length of time—to justify a switch of therapy is therefore misleading, said Dr. Rudick, who is also Vice Chairman of Research and Development in the Neurological Institute at Cleveland Clinic and Professor of Medicine in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.

“MRI findings are considerably more promising,” he said. Several studies suggest that Gd-enhancing lesions or T2 lesions developing while on treatment are reliable indicators of suboptimal response or nonresponse to interferon treatment.

Dr. Rudick cited a study in which 383 patients with clinically isolated syndrome underwent MRI scans every six months for up to 18 months. Among patients treated with interferon beta-1a, those who developed at least one Gd-enhancing lesion, or two or more T2 lesions, at six months had nearly four times the risk of converting to clinically definite MS within 30 months (hazard ratio, 3.94), compared with treated patients who had no Gd-enhancing lesions and/or less than two T2 lesions at six months.

MRI activity “appears to be a marker at six months that identifies progression over the subsequent 18 months and is predominantly seen in the treated groups, so this appears to be a treatment response marker,” said Dr. Rudick. “We may not need to wait for one or two years.” The same predictor has not been studied in groups treated with glatiramer acetate, he noted.

At this point, there is no reliable biomarker for response or nonresponse to interferon or glatiramer acetate. However, “multiple studies by groups worldwide have documented a blunted or absent biologic and clinical response to interferon in patients with high titer neutralizing antibodies,” he said.

Managing patients with breakthrough disease starts with a monitoring strategy, asserted Dr. Rudick. “I see patients semiannually for a history and physical. I do an annual MRI scan, and I always consider the possibility of noncompliance. Patients don’t volunteer that they’re not taking their medication,” he said.

Next, he recommends deciding how much disease activity is tolerable. “I believe this has to be individualized,” he said. “In many patients, an occasional relapse is not only anticipated, but it may be okay. You need to consider how well the individual patient recovers from relapses.”

More aggressive management would be warranted in those patients who recover poorly from relapses. “For patients on interferon, I check neutralizing antibodies if I’m in doubt, and some argue that all patients on interferon should have antibodies tested,” he said.

For patients with unacceptable levels of disease activity, clinicians should consider changing therapy “probably earlier rather than later,” Dr. Rudick advised. Switching between interferon products and glatiramer acetate is a common practice for patients with breakthrough disease, but there are no randomized controlled trials to support this practice. Regression to the mean will drive the appearance of switching toward benefit. Dr. Rudick recommended that treatment should only be switched when a patient develops neutralizing antibodies while on interferon, in which case the patient should be switched to glatiramer acetate.

Combination therapy for suboptimal responders is also common but not supported by strong evidence. Combination therapy has had “disappointing” results in randomized clinical trials, he said, and may increase the incidence of side effects, compared with monotherapy.

Dr. Rudick noted that his treatment of choice in patients with disease activity while on disease-modifying drug therapy is natalizumab. Symptomatic therapy and rehabilitation should not be forgotten for patients during the process of monitoring and managing patients with disease-modifying drugs.

“I think we need realistic expectations,” he said. “There are no drugs labeled for progressive MS, because there is no established efficacy in this category of patient.” He added that caution should be exercised when considering off-label use of drugs that are in phase II studies.

Dr. Rudick concluded that randomized controlled trials of alternative monotherapies or combination therapies are needed for patients with breakthrough disease, as are methods to stratify patients for treatment selection and biomarkers to predict individual response to therapy.

MONTREAL—Treating patients with multiple sclerosis (MS) who have breakthrough disease activity despite the use of disease-modifying drug therapy requires identification of suboptimal responders, a monitoring strategy, and consideration of largely unproven treatment approaches, said Richard A. Rudick, MD, at the 2008 World Congress on Treatment and Research in Multiple Sclerosis.

“A large proportion of patients with relapsing-remitting MS will show signs of disease activity within one to two years,” said Dr. Rudick. “This is not necessarily a poor response to therapy; this is expected.”

In published phase III trials, 62% to 75% of patients with relapsing-remitting MS had one or more relapses within two years while on disease-modifying drug therapy, about one fourth had a sustained increase in Expanded Disability Status Scale score, about one fourth had one or more gadolinium (Gd)-enhancing lesions, and more than half had one or more new T2 lesions.

Identifying nonresponders, therefore, is the first consideration in managing true breakthrough disease, said Dr. Rudick, Director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic. Patient self-report and the physician’s global impression of change are usually the initial approaches, although the validity of these approaches has not been studied.

Relapses do not appear to be a reliable marker for response to a disease-modifying drug, according to Dr. Rudick. In placebo-controlled clinical studies, many patients who remain on placebo will have fewer relapses in year 2 than in year 1—a regression to the mean phenomenon. Reliance on relapse data—especially from studies in which patients are crossed over from placebo to treatment after a length of time—to justify a switch of therapy is therefore misleading, said Dr. Rudick, who is also Vice Chairman of Research and Development in the Neurological Institute at Cleveland Clinic and Professor of Medicine in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.

“MRI findings are considerably more promising,” he said. Several studies suggest that Gd-enhancing lesions or T2 lesions developing while on treatment are reliable indicators of suboptimal response or nonresponse to interferon treatment.

Dr. Rudick cited a study in which 383 patients with clinically isolated syndrome underwent MRI scans every six months for up to 18 months. Among patients treated with interferon beta-1a, those who developed at least one Gd-enhancing lesion, or two or more T2 lesions, at six months had nearly four times the risk of converting to clinically definite MS within 30 months (hazard ratio, 3.94), compared with treated patients who had no Gd-enhancing lesions and/or less than two T2 lesions at six months.

MRI activity “appears to be a marker at six months that identifies progression over the subsequent 18 months and is predominantly seen in the treated groups, so this appears to be a treatment response marker,” said Dr. Rudick. “We may not need to wait for one or two years.” The same predictor has not been studied in groups treated with glatiramer acetate, he noted.

At this point, there is no reliable biomarker for response or nonresponse to interferon or glatiramer acetate. However, “multiple studies by groups worldwide have documented a blunted or absent biologic and clinical response to interferon in patients with high titer neutralizing antibodies,” he said.

Managing patients with breakthrough disease starts with a monitoring strategy, asserted Dr. Rudick. “I see patients semiannually for a history and physical. I do an annual MRI scan, and I always consider the possibility of noncompliance. Patients don’t volunteer that they’re not taking their medication,” he said.

Next, he recommends deciding how much disease activity is tolerable. “I believe this has to be individualized,” he said. “In many patients, an occasional relapse is not only anticipated, but it may be okay. You need to consider how well the individual patient recovers from relapses.”

More aggressive management would be warranted in those patients who recover poorly from relapses. “For patients on interferon, I check neutralizing antibodies if I’m in doubt, and some argue that all patients on interferon should have antibodies tested,” he said.

For patients with unacceptable levels of disease activity, clinicians should consider changing therapy “probably earlier rather than later,” Dr. Rudick advised. Switching between interferon products and glatiramer acetate is a common practice for patients with breakthrough disease, but there are no randomized controlled trials to support this practice. Regression to the mean will drive the appearance of switching toward benefit. Dr. Rudick recommended that treatment should only be switched when a patient develops neutralizing antibodies while on interferon, in which case the patient should be switched to glatiramer acetate.

Combination therapy for suboptimal responders is also common but not supported by strong evidence. Combination therapy has had “disappointing” results in randomized clinical trials, he said, and may increase the incidence of side effects, compared with monotherapy.

Dr. Rudick noted that his treatment of choice in patients with disease activity while on disease-modifying drug therapy is natalizumab. Symptomatic therapy and rehabilitation should not be forgotten for patients during the process of monitoring and managing patients with disease-modifying drugs.

“I think we need realistic expectations,” he said. “There are no drugs labeled for progressive MS, because there is no established efficacy in this category of patient.” He added that caution should be exercised when considering off-label use of drugs that are in phase II studies.

Dr. Rudick concluded that randomized controlled trials of alternative monotherapies or combination therapies are needed for patients with breakthrough disease, as are methods to stratify patients for treatment selection and biomarkers to predict individual response to therapy.

MONTREAL—Treating patients with multiple sclerosis (MS) who have breakthrough disease activity despite the use of disease-modifying drug therapy requires identification of suboptimal responders, a monitoring strategy, and consideration of largely unproven treatment approaches, said Richard A. Rudick, MD, at the 2008 World Congress on Treatment and Research in Multiple Sclerosis.

“A large proportion of patients with relapsing-remitting MS will show signs of disease activity within one to two years,” said Dr. Rudick. “This is not necessarily a poor response to therapy; this is expected.”

In published phase III trials, 62% to 75% of patients with relapsing-remitting MS had one or more relapses within two years while on disease-modifying drug therapy, about one fourth had a sustained increase in Expanded Disability Status Scale score, about one fourth had one or more gadolinium (Gd)-enhancing lesions, and more than half had one or more new T2 lesions.

Identifying nonresponders, therefore, is the first consideration in managing true breakthrough disease, said Dr. Rudick, Director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic. Patient self-report and the physician’s global impression of change are usually the initial approaches, although the validity of these approaches has not been studied.

Relapses do not appear to be a reliable marker for response to a disease-modifying drug, according to Dr. Rudick. In placebo-controlled clinical studies, many patients who remain on placebo will have fewer relapses in year 2 than in year 1—a regression to the mean phenomenon. Reliance on relapse data—especially from studies in which patients are crossed over from placebo to treatment after a length of time—to justify a switch of therapy is therefore misleading, said Dr. Rudick, who is also Vice Chairman of Research and Development in the Neurological Institute at Cleveland Clinic and Professor of Medicine in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.

“MRI findings are considerably more promising,” he said. Several studies suggest that Gd-enhancing lesions or T2 lesions developing while on treatment are reliable indicators of suboptimal response or nonresponse to interferon treatment.

Dr. Rudick cited a study in which 383 patients with clinically isolated syndrome underwent MRI scans every six months for up to 18 months. Among patients treated with interferon beta-1a, those who developed at least one Gd-enhancing lesion, or two or more T2 lesions, at six months had nearly four times the risk of converting to clinically definite MS within 30 months (hazard ratio, 3.94), compared with treated patients who had no Gd-enhancing lesions and/or less than two T2 lesions at six months.

MRI activity “appears to be a marker at six months that identifies progression over the subsequent 18 months and is predominantly seen in the treated groups, so this appears to be a treatment response marker,” said Dr. Rudick. “We may not need to wait for one or two years.” The same predictor has not been studied in groups treated with glatiramer acetate, he noted.

At this point, there is no reliable biomarker for response or nonresponse to interferon or glatiramer acetate. However, “multiple studies by groups worldwide have documented a blunted or absent biologic and clinical response to interferon in patients with high titer neutralizing antibodies,” he said.

Managing patients with breakthrough disease starts with a monitoring strategy, asserted Dr. Rudick. “I see patients semiannually for a history and physical. I do an annual MRI scan, and I always consider the possibility of noncompliance. Patients don’t volunteer that they’re not taking their medication,” he said.

Next, he recommends deciding how much disease activity is tolerable. “I believe this has to be individualized,” he said. “In many patients, an occasional relapse is not only anticipated, but it may be okay. You need to consider how well the individual patient recovers from relapses.”

More aggressive management would be warranted in those patients who recover poorly from relapses. “For patients on interferon, I check neutralizing antibodies if I’m in doubt, and some argue that all patients on interferon should have antibodies tested,” he said.

For patients with unacceptable levels of disease activity, clinicians should consider changing therapy “probably earlier rather than later,” Dr. Rudick advised. Switching between interferon products and glatiramer acetate is a common practice for patients with breakthrough disease, but there are no randomized controlled trials to support this practice. Regression to the mean will drive the appearance of switching toward benefit. Dr. Rudick recommended that treatment should only be switched when a patient develops neutralizing antibodies while on interferon, in which case the patient should be switched to glatiramer acetate.

Combination therapy for suboptimal responders is also common but not supported by strong evidence. Combination therapy has had “disappointing” results in randomized clinical trials, he said, and may increase the incidence of side effects, compared with monotherapy.

Dr. Rudick noted that his treatment of choice in patients with disease activity while on disease-modifying drug therapy is natalizumab. Symptomatic therapy and rehabilitation should not be forgotten for patients during the process of monitoring and managing patients with disease-modifying drugs.

“I think we need realistic expectations,” he said. “There are no drugs labeled for progressive MS, because there is no established efficacy in this category of patient.” He added that caution should be exercised when considering off-label use of drugs that are in phase II studies.

Dr. Rudick concluded that randomized controlled trials of alternative monotherapies or combination therapies are needed for patients with breakthrough disease, as are methods to stratify patients for treatment selection and biomarkers to predict individual response to therapy.

MONTREAL—Pediatric-onset acute demyelination provides a unique window for studying environmental exposure and disease mechanisms involved in multiple sclerosis (MS), said Brenda Banwell, MD, at the 2008 World Congress on Treatment and Research in Multiple Sclerosis. Some of the triggers being studied in children include viral exposure (eg, Epstein-Barr virus [EBV]) and vitamin D deficiency.

“Pediatric acute demyelination provides an opportunity to look at a population of individuals presenting at a time when they have had a relatively limited environmental experience, when the immune attack may be directed at the primary target involved in the MS disease process with a reduced possibility of secondary immune responses to injured tissue,” said Dr. Banwell, Associate Professor of Pediatrics (Neurology) and Director of the Pediatric Multiple Sclerosis and Demyelinating Disease Program at the Hospital for Sick Children, University of Toronto. In pediatric MS, the targets become available to the immune system potentially at a time when the environmental exposures, or triggers of the disease, are still operative.

Dr. Banwell and colleagues obtained data from the Canadian National Pediatric Demyelinating Disease Study, a prospective study involving 23 sites across Canada. Children with a first demyelinating event were enrolled at presentation and underwent a comprehensive clinical, genetic, pathobiologic, and neuroimaging assessment, which was performed at three, six, and 12 months, and then annually thereafter.

EBV as a Possible Trigger
A viral pathogen of interest as a potential trigger of MS is EBV. “EBV has a very powerful effect on our immune system; when you acquire EBV infection, you never really lose it,” she said. “It becomes part of our B-cell repertoire, and it’s a part of our repertoire that we have to tightly control.”

She described a study of 137 children with MS and 96 controls matched by age and geographic region who underwent standardized assays for immunoglobulin G antibodies directed against EBV, cytomegalovirus, parvovirus B19, varicella zoster virus, and herpes simplex virus.

“We found that when you compare children with MS to non-MS participants, the MS children do indeed have higher titer reactions to the EBV protein,” she said. A greater percentage of children with MS were in the high-titer group (area under the curve > 195), compared with age-matched, EBV-positive healthy controls (40% vs 18%).

Serial samples demonstrated that “high titers persist,” she said. “It’s not a transient phenomenon.”

Is Vitamin D Insufficiency Linked to MS?
More than 80% of the children with MS were seropositive for EBV infection, a significantly higher rate than that observed in controls. Children with MS did not differ from controls in seroprevalence of the other viruses studied.

The high rate of MS in Canada may be related to vitamin D insufficiency, said Dr. Banwell. Canada has one of the highest rates of MS in the world, and distance from the equator is one variable that has been shown to be associated with MS prevalence. One of the more popular theories is that suboptimal vitamin D synthesis in the skin may play a role in the pathobiology of MS.

Therefore, Dr. Banwell and colleagues evaluated vitamin D status in 117 children with a first attack of demyelination who were enrolled in the Canadian National Pediatric Demyelinating Disease Study; 98 had monophasic acquired demyelination syndrome (ADS) at the time of the study, and 19 were diagnosed with MS.

The mean serum level of 25-hydroxyvitamin D was 61.3 nmol/L at presentation in the children with monophasic ADS, which was significantly greater than the 44.2-nmol/L mean level at presentation in the children who were later diagnosed with MS. The mean level of serum 25-hydroxyvitamin D value for the entire group of 117 children was 58.5 nmol/L, “well below what is considered to be a reasonable vitamin D level in serum, which is 75 nmol/L,” said Dr. Banwell.

More than 75% of the entire cohort were vitamin D–insufficient. Of the children in the lowest quartile of serum 25-hydroxyvitamin D level (≤ 34.8 nmol/L), 28% were diagnosed with MS, compared with 7% of children with serum 25-hydroxyvitamin D levels in the highest quartile (> 76.3 nmol/L).

Assessing Immunologic Biomarkers
Several immunologic biomarkers and their association with pediatric MS have also been studied. Dr. Banwell’s research team conducted one such study of serum biomarkers in children with clinically isolated syndrome and age- and gender-matched healthy children. In this study, children with demyelination had higher levels of matrix metalloproteinase (a marker of potential immune cell entry into the CNS), reduced levels of tumor necrosis factor–related apoptosis-inducing ligand, which is a potential biomarker of reduced apoptosis of inflammatory cells, and reduced levels of interleukin 10 (indicating a reduction in anti-inflammatory activity), compared with healthy controls.

MONTREAL—Pediatric-onset acute demyelination provides a unique window for studying environmental exposure and disease mechanisms involved in multiple sclerosis (MS), said Brenda Banwell, MD, at the 2008 World Congress on Treatment and Research in Multiple Sclerosis. Some of the triggers being studied in children include viral exposure (eg, Epstein-Barr virus [EBV]) and vitamin D deficiency.

“Pediatric acute demyelination provides an opportunity to look at a population of individuals presenting at a time when they have had a relatively limited environmental experience, when the immune attack may be directed at the primary target involved in the MS disease process with a reduced possibility of secondary immune responses to injured tissue,” said Dr. Banwell, Associate Professor of Pediatrics (Neurology) and Director of the Pediatric Multiple Sclerosis and Demyelinating Disease Program at the Hospital for Sick Children, University of Toronto. In pediatric MS, the targets become available to the immune system potentially at a time when the environmental exposures, or triggers of the disease, are still operative.

Dr. Banwell and colleagues obtained data from the Canadian National Pediatric Demyelinating Disease Study, a prospective study involving 23 sites across Canada. Children with a first demyelinating event were enrolled at presentation and underwent a comprehensive clinical, genetic, pathobiologic, and neuroimaging assessment, which was performed at three, six, and 12 months, and then annually thereafter.

EBV as a Possible Trigger
A viral pathogen of interest as a potential trigger of MS is EBV. “EBV has a very powerful effect on our immune system; when you acquire EBV infection, you never really lose it,” she said. “It becomes part of our B-cell repertoire, and it’s a part of our repertoire that we have to tightly control.”

She described a study of 137 children with MS and 96 controls matched by age and geographic region who underwent standardized assays for immunoglobulin G antibodies directed against EBV, cytomegalovirus, parvovirus B19, varicella zoster virus, and herpes simplex virus.

“We found that when you compare children with MS to non-MS participants, the MS children do indeed have higher titer reactions to the EBV protein,” she said. A greater percentage of children with MS were in the high-titer group (area under the curve > 195), compared with age-matched, EBV-positive healthy controls (40% vs 18%).

Serial samples demonstrated that “high titers persist,” she said. “It’s not a transient phenomenon.”

Is Vitamin D Insufficiency Linked to MS?
More than 80% of the children with MS were seropositive for EBV infection, a significantly higher rate than that observed in controls. Children with MS did not differ from controls in seroprevalence of the other viruses studied.

The high rate of MS in Canada may be related to vitamin D insufficiency, said Dr. Banwell. Canada has one of the highest rates of MS in the world, and distance from the equator is one variable that has been shown to be associated with MS prevalence. One of the more popular theories is that suboptimal vitamin D synthesis in the skin may play a role in the pathobiology of MS.

Therefore, Dr. Banwell and colleagues evaluated vitamin D status in 117 children with a first attack of demyelination who were enrolled in the Canadian National Pediatric Demyelinating Disease Study; 98 had monophasic acquired demyelination syndrome (ADS) at the time of the study, and 19 were diagnosed with MS.

The mean serum level of 25-hydroxyvitamin D was 61.3 nmol/L at presentation in the children with monophasic ADS, which was significantly greater than the 44.2-nmol/L mean level at presentation in the children who were later diagnosed with MS. The mean level of serum 25-hydroxyvitamin D value for the entire group of 117 children was 58.5 nmol/L, “well below what is considered to be a reasonable vitamin D level in serum, which is 75 nmol/L,” said Dr. Banwell.

More than 75% of the entire cohort were vitamin D–insufficient. Of the children in the lowest quartile of serum 25-hydroxyvitamin D level (≤ 34.8 nmol/L), 28% were diagnosed with MS, compared with 7% of children with serum 25-hydroxyvitamin D levels in the highest quartile (> 76.3 nmol/L).

Assessing Immunologic Biomarkers
Several immunologic biomarkers and their association with pediatric MS have also been studied. Dr. Banwell’s research team conducted one such study of serum biomarkers in children with clinically isolated syndrome and age- and gender-matched healthy children. In this study, children with demyelination had higher levels of matrix metalloproteinase (a marker of potential immune cell entry into the CNS), reduced levels of tumor necrosis factor–related apoptosis-inducing ligand, which is a potential biomarker of reduced apoptosis of inflammatory cells, and reduced levels of interleukin 10 (indicating a reduction in anti-inflammatory activity), compared with healthy controls.

MONTREAL—Pediatric-onset acute demyelination provides a unique window for studying environmental exposure and disease mechanisms involved in multiple sclerosis (MS), said Brenda Banwell, MD, at the 2008 World Congress on Treatment and Research in Multiple Sclerosis. Some of the triggers being studied in children include viral exposure (eg, Epstein-Barr virus [EBV]) and vitamin D deficiency.

“Pediatric acute demyelination provides an opportunity to look at a population of individuals presenting at a time when they have had a relatively limited environmental experience, when the immune attack may be directed at the primary target involved in the MS disease process with a reduced possibility of secondary immune responses to injured tissue,” said Dr. Banwell, Associate Professor of Pediatrics (Neurology) and Director of the Pediatric Multiple Sclerosis and Demyelinating Disease Program at the Hospital for Sick Children, University of Toronto. In pediatric MS, the targets become available to the immune system potentially at a time when the environmental exposures, or triggers of the disease, are still operative.

Dr. Banwell and colleagues obtained data from the Canadian National Pediatric Demyelinating Disease Study, a prospective study involving 23 sites across Canada. Children with a first demyelinating event were enrolled at presentation and underwent a comprehensive clinical, genetic, pathobiologic, and neuroimaging assessment, which was performed at three, six, and 12 months, and then annually thereafter.

EBV as a Possible Trigger
A viral pathogen of interest as a potential trigger of MS is EBV. “EBV has a very powerful effect on our immune system; when you acquire EBV infection, you never really lose it,” she said. “It becomes part of our B-cell repertoire, and it’s a part of our repertoire that we have to tightly control.”

She described a study of 137 children with MS and 96 controls matched by age and geographic region who underwent standardized assays for immunoglobulin G antibodies directed against EBV, cytomegalovirus, parvovirus B19, varicella zoster virus, and herpes simplex virus.

“We found that when you compare children with MS to non-MS participants, the MS children do indeed have higher titer reactions to the EBV protein,” she said. A greater percentage of children with MS were in the high-titer group (area under the curve > 195), compared with age-matched, EBV-positive healthy controls (40% vs 18%).

Serial samples demonstrated that “high titers persist,” she said. “It’s not a transient phenomenon.”

Is Vitamin D Insufficiency Linked to MS?
More than 80% of the children with MS were seropositive for EBV infection, a significantly higher rate than that observed in controls. Children with MS did not differ from controls in seroprevalence of the other viruses studied.

The high rate of MS in Canada may be related to vitamin D insufficiency, said Dr. Banwell. Canada has one of the highest rates of MS in the world, and distance from the equator is one variable that has been shown to be associated with MS prevalence. One of the more popular theories is that suboptimal vitamin D synthesis in the skin may play a role in the pathobiology of MS.

Therefore, Dr. Banwell and colleagues evaluated vitamin D status in 117 children with a first attack of demyelination who were enrolled in the Canadian National Pediatric Demyelinating Disease Study; 98 had monophasic acquired demyelination syndrome (ADS) at the time of the study, and 19 were diagnosed with MS.

The mean serum level of 25-hydroxyvitamin D was 61.3 nmol/L at presentation in the children with monophasic ADS, which was significantly greater than the 44.2-nmol/L mean level at presentation in the children who were later diagnosed with MS. The mean level of serum 25-hydroxyvitamin D value for the entire group of 117 children was 58.5 nmol/L, “well below what is considered to be a reasonable vitamin D level in serum, which is 75 nmol/L,” said Dr. Banwell.

More than 75% of the entire cohort were vitamin D–insufficient. Of the children in the lowest quartile of serum 25-hydroxyvitamin D level (≤ 34.8 nmol/L), 28% were diagnosed with MS, compared with 7% of children with serum 25-hydroxyvitamin D levels in the highest quartile (> 76.3 nmol/L).

Assessing Immunologic Biomarkers
Several immunologic biomarkers and their association with pediatric MS have also been studied. Dr. Banwell’s research team conducted one such study of serum biomarkers in children with clinically isolated syndrome and age- and gender-matched healthy children. In this study, children with demyelination had higher levels of matrix metalloproteinase (a marker of potential immune cell entry into the CNS), reduced levels of tumor necrosis factor–related apoptosis-inducing ligand, which is a potential biomarker of reduced apoptosis of inflammatory cells, and reduced levels of interleukin 10 (indicating a reduction in anti-inflammatory activity), compared with healthy controls.

MONTREAL—Macrophages and microglia represent rational targets in the treatment of patients with multiple sclerosis (MS), given that these cells are key effectors for tissue injury in inflammatory conditions in the CNS, said Samia J. Khoury, MD, at the 2008 World Congress on Treatment and Research in Multiple Sclerosis.
Therapies that inhibit microglial activation may be beneficial in chronic inflammatory diseases of the central nervous system such as MS. Potential inhibitors of microglia activation are peroxisome proliferator-activated receptor γ (PPAR-γ) agonists, anti-CD200 antibodies, and minocycline. Dr. Khoury discussed the role of reactive microglia in the initiation and propagation of immune responses as inflammatory mediators during inflammation in the CNS.

The acute MS lesion has been classically defined based on the presence of microglia ingesting myelin components and a lymphocyte inflammatory response. The chronic MS lesion, characteristic of the progressive phase of the disease, is dominated by the presence of activated microglia/macrophages without a prominent lymphocytic infiltrate. Human adult microglia can phagocytose myelin vesicles and secrete proinflammatory cytokines such as interleukin 1 (IL‑1), IL-6, and tumor necrosis factor α (TNF-α), and they are also known to undergo oxidative bursts. Diffuse injury of the normal-appearing white matter and cortical demyelination are classic hallmarks of primary and secondary progressive MS. The inflammation consists of mononuclear cells and diffuse infiltration of the tissue by T lymphocytes associated with profound activation of microglia.

Similar to patients with MS, the peak of disease activity in mice with experimental autoimmune encephalomyelitis (EAE)—a widely used animal model in MS—is characterized by T-cell infiltrates that decline during extended follow-up, whereas the microglia are activated persistently throughout the chronic phases. “This activation correlates well with the presence of cortical lesions, alteration of synaptic function, and axonal transport, each indicative of neuronal dysfunction,” said Dr. Khoury, Professor of Neurology at Brigham and Women’s Hospital in Boston. These data suggest that inflammation is sustained by microglia during the chronic phase of EAE.

The contribution of microglia to the progression of MS is evident in the following:
• Progressive MS correlates with the presence of diffuse axonal injury and activated microglia in the cortex and nonlesioned white matter.
• Increased expression of the major histocompatibility complex class II (MHC II) gene is found on microglia in nonlesioned white matter in the brains of patients with MS.
• Proinflammatory mediators released by microglia appear to be important contributors in blocking neurogenesis.
• Activation of microglia results in secretion of nitric oxide and proinflammatory cytokines such as IL-1, IL-6, IL-8, macrophage inflammatory protein 1-α, monocyte chemotactic protein 1, and TNF-α.
• Microglia in the subventricular zone proliferate and closely contact the neural stem cells.
Compounds that inhibit microglia activation include PPAR-γ agonists, anti-CD200 antibodies, and minocycline. PPAR-γ is a nuclear receptor that controls reproduction, metabolism, development, and immune responses. Natural and synthetic PPAR-γ agonists may control brain inflammation by inhibiting microglial activation, noted Dr. Khoury.

CD200 is expressed on neurons, and CD200R is expressed on macrophages/microglia. CD200-null mice experience an earlier onset of EAE, accompanied by an increased number and accumulation of activated macrophages and microglia in the CNS. After facial nerve transection, CD200-null mice have shown accelerated microglial response around neurons. Slow Wallerian degeneration mice have up-regulated CD200 and protection from EAE.

Minocycline has been shown to ameliorate EAE by peripheral immunomodulatory properties. Its mechanisms of action include inhibition of matrix metalloproteinase 2 activity and inhibition of inducible nitric oxide synthase, prostaglandin-E2, caspase-1, caspase-3, and cyclo-oxygenase–2 expressions, as well as the impairment of cytokine production. Some of these mechanisms are manifested, at least in part, by inhibition of mitogen-activated protein kinases. Minocycline also inhibits protein kinase C activation and decreases MHC II expression.

MONTREAL—Macrophages and microglia represent rational targets in the treatment of patients with multiple sclerosis (MS), given that these cells are key effectors for tissue injury in inflammatory conditions in the CNS, said Samia J. Khoury, MD, at the 2008 World Congress on Treatment and Research in Multiple Sclerosis.
Therapies that inhibit microglial activation may be beneficial in chronic inflammatory diseases of the central nervous system such as MS. Potential inhibitors of microglia activation are peroxisome proliferator-activated receptor γ (PPAR-γ) agonists, anti-CD200 antibodies, and minocycline. Dr. Khoury discussed the role of reactive microglia in the initiation and propagation of immune responses as inflammatory mediators during inflammation in the CNS.

The acute MS lesion has been classically defined based on the presence of microglia ingesting myelin components and a lymphocyte inflammatory response. The chronic MS lesion, characteristic of the progressive phase of the disease, is dominated by the presence of activated microglia/macrophages without a prominent lymphocytic infiltrate. Human adult microglia can phagocytose myelin vesicles and secrete proinflammatory cytokines such as interleukin 1 (IL‑1), IL-6, and tumor necrosis factor α (TNF-α), and they are also known to undergo oxidative bursts. Diffuse injury of the normal-appearing white matter and cortical demyelination are classic hallmarks of primary and secondary progressive MS. The inflammation consists of mononuclear cells and diffuse infiltration of the tissue by T lymphocytes associated with profound activation of microglia.

Similar to patients with MS, the peak of disease activity in mice with experimental autoimmune encephalomyelitis (EAE)—a widely used animal model in MS—is characterized by T-cell infiltrates that decline during extended follow-up, whereas the microglia are activated persistently throughout the chronic phases. “This activation correlates well with the presence of cortical lesions, alteration of synaptic function, and axonal transport, each indicative of neuronal dysfunction,” said Dr. Khoury, Professor of Neurology at Brigham and Women’s Hospital in Boston. These data suggest that inflammation is sustained by microglia during the chronic phase of EAE.

The contribution of microglia to the progression of MS is evident in the following:
• Progressive MS correlates with the presence of diffuse axonal injury and activated microglia in the cortex and nonlesioned white matter.
• Increased expression of the major histocompatibility complex class II (MHC II) gene is found on microglia in nonlesioned white matter in the brains of patients with MS.
• Proinflammatory mediators released by microglia appear to be important contributors in blocking neurogenesis.
• Activation of microglia results in secretion of nitric oxide and proinflammatory cytokines such as IL-1, IL-6, IL-8, macrophage inflammatory protein 1-α, monocyte chemotactic protein 1, and TNF-α.
• Microglia in the subventricular zone proliferate and closely contact the neural stem cells.
Compounds that inhibit microglia activation include PPAR-γ agonists, anti-CD200 antibodies, and minocycline. PPAR-γ is a nuclear receptor that controls reproduction, metabolism, development, and immune responses. Natural and synthetic PPAR-γ agonists may control brain inflammation by inhibiting microglial activation, noted Dr. Khoury.

CD200 is expressed on neurons, and CD200R is expressed on macrophages/microglia. CD200-null mice experience an earlier onset of EAE, accompanied by an increased number and accumulation of activated macrophages and microglia in the CNS. After facial nerve transection, CD200-null mice have shown accelerated microglial response around neurons. Slow Wallerian degeneration mice have up-regulated CD200 and protection from EAE.

Minocycline has been shown to ameliorate EAE by peripheral immunomodulatory properties. Its mechanisms of action include inhibition of matrix metalloproteinase 2 activity and inhibition of inducible nitric oxide synthase, prostaglandin-E2, caspase-1, caspase-3, and cyclo-oxygenase–2 expressions, as well as the impairment of cytokine production. Some of these mechanisms are manifested, at least in part, by inhibition of mitogen-activated protein kinases. Minocycline also inhibits protein kinase C activation and decreases MHC II expression.

MONTREAL—Macrophages and microglia represent rational targets in the treatment of patients with multiple sclerosis (MS), given that these cells are key effectors for tissue injury in inflammatory conditions in the CNS, said Samia J. Khoury, MD, at the 2008 World Congress on Treatment and Research in Multiple Sclerosis.
Therapies that inhibit microglial activation may be beneficial in chronic inflammatory diseases of the central nervous system such as MS. Potential inhibitors of microglia activation are peroxisome proliferator-activated receptor γ (PPAR-γ) agonists, anti-CD200 antibodies, and minocycline. Dr. Khoury discussed the role of reactive microglia in the initiation and propagation of immune responses as inflammatory mediators during inflammation in the CNS.

The acute MS lesion has been classically defined based on the presence of microglia ingesting myelin components and a lymphocyte inflammatory response. The chronic MS lesion, characteristic of the progressive phase of the disease, is dominated by the presence of activated microglia/macrophages without a prominent lymphocytic infiltrate. Human adult microglia can phagocytose myelin vesicles and secrete proinflammatory cytokines such as interleukin 1 (IL‑1), IL-6, and tumor necrosis factor α (TNF-α), and they are also known to undergo oxidative bursts. Diffuse injury of the normal-appearing white matter and cortical demyelination are classic hallmarks of primary and secondary progressive MS. The inflammation consists of mononuclear cells and diffuse infiltration of the tissue by T lymphocytes associated with profound activation of microglia.

Similar to patients with MS, the peak of disease activity in mice with experimental autoimmune encephalomyelitis (EAE)—a widely used animal model in MS—is characterized by T-cell infiltrates that decline during extended follow-up, whereas the microglia are activated persistently throughout the chronic phases. “This activation correlates well with the presence of cortical lesions, alteration of synaptic function, and axonal transport, each indicative of neuronal dysfunction,” said Dr. Khoury, Professor of Neurology at Brigham and Women’s Hospital in Boston. These data suggest that inflammation is sustained by microglia during the chronic phase of EAE.

The contribution of microglia to the progression of MS is evident in the following:
• Progressive MS correlates with the presence of diffuse axonal injury and activated microglia in the cortex and nonlesioned white matter.
• Increased expression of the major histocompatibility complex class II (MHC II) gene is found on microglia in nonlesioned white matter in the brains of patients with MS.
• Proinflammatory mediators released by microglia appear to be important contributors in blocking neurogenesis.
• Activation of microglia results in secretion of nitric oxide and proinflammatory cytokines such as IL-1, IL-6, IL-8, macrophage inflammatory protein 1-α, monocyte chemotactic protein 1, and TNF-α.
• Microglia in the subventricular zone proliferate and closely contact the neural stem cells.
Compounds that inhibit microglia activation include PPAR-γ agonists, anti-CD200 antibodies, and minocycline. PPAR-γ is a nuclear receptor that controls reproduction, metabolism, development, and immune responses. Natural and synthetic PPAR-γ agonists may control brain inflammation by inhibiting microglial activation, noted Dr. Khoury.

CD200 is expressed on neurons, and CD200R is expressed on macrophages/microglia. CD200-null mice experience an earlier onset of EAE, accompanied by an increased number and accumulation of activated macrophages and microglia in the CNS. After facial nerve transection, CD200-null mice have shown accelerated microglial response around neurons. Slow Wallerian degeneration mice have up-regulated CD200 and protection from EAE.

Minocycline has been shown to ameliorate EAE by peripheral immunomodulatory properties. Its mechanisms of action include inhibition of matrix metalloproteinase 2 activity and inhibition of inducible nitric oxide synthase, prostaglandin-E2, caspase-1, caspase-3, and cyclo-oxygenase–2 expressions, as well as the impairment of cytokine production. Some of these mechanisms are manifested, at least in part, by inhibition of mitogen-activated protein kinases. Minocycline also inhibits protein kinase C activation and decreases MHC II expression.

Alzheimer’s Pathology Reduced With Combined Diabetes Therapy
NEW YORK, September 9 (Reuters Health)—In a postmortem study of patients with Alzheimer’s disease, diabetic subjects treated with both insulin and oral hypoglycemic agents had lower neuritic plaque densities than did other diabetics and nondiabetics, new research shows.
In several studies, type 2 diabetes has been identified as a risk factor for Alzheimer’s disease. The link between diabetes and Alzheimer’s neuropathology, by contrast, is less clear, according to the report in the September 2 issue of Neurology.
The current study, conducted by Dr. M. S. Beeri, from Mount Sinai School of Medicine in New York City, and colleagues, involved an analysis of neuritic plaques and neurofibrillary tangles in brain specimens from 124 diabetics and 124 nondiabetics.
The diabetic group consisted of 29 patients who had never used antidiabetic agents, 49 who had received insulin only, 28 treated with agents other than insulin, and 18 treated with both insulin and oral antidiabetic medications.
The overall neuritic plaque rating, the rating in the entorhinal cortex and amygdala, and the neuritic plaque count in all regions examined differed significantly among the groups. In all of the analyses, the combined medication group had fewer neuritic plaques than did the other groups.
By contrast, the authors found no significant difference in neurofibrillary tangles between the groups.
The findings provide “evidence of substantially lower neuritic plaque density in diabetic subjects taking both insulin and hypoglycemic medication consistent with the effects of both on the neurobiology of insulin,” the researchers concluded. “These pathways should be considered as potentially mechanistically important in the etiology of β amyloid–associated neuropathology and deposition of neuritic plaques.”
Neurology. 2008;71(10):750-757.
Antiepileptic Drug Use May Contribute to Bone Loss in Older Men
NEW YORK, September 19 (Reuters Health)—Use of non–enzyme-inducing antiepileptic drugs (AEDs) independently raises the risk of bone loss at the hip in older men, results of a prospective study suggest.
In the September 2 issue of Neurology, Dr. Kristine E. Ensrud, from the Veterans Affairs Medical Center in Minneapolis, and colleagues pointed out, “AED use may be associated with higher rates of bone loss because [the drugs] may have adverse effects on bone metabolism. On the other hand, AED use may be a marker of factors such as poor health ... that are associated with greater rates of bone loss.”
In 4,222 older community-dwelling participants in the Osteoporosis Fractures in Men study, the researchers analyzed use of non–enzyme-inducing and enzyme-inducing AEDs. They also measured subjects’ hip bone mineral density (BMD) at baseline and at an average of 4.6 years later.
Among men who didn’t use AEDs at all, the average rate of decline in total hip BMD per year was -0.35%, compared with -0.46% among enzyme-inducing AED users and -0.53% among non–enzyme-inducing AED users.
The rate of loss per year was -0.60% among men who were taking non–enzyme-inducing AEDs at both examinations, -0.51% among men taking non–enzyme-inducing AEDs at one examination only, and -0.35% among nonusers.
The researchers pointed out that these findings were achieved after adjustment for a myriad of potential confounders not accounted for in past studies, including age, race, health status, baseline BMD, physical activity, smoking, alcohol intake, total calcium intake, diabetes, kidney disease, bisphosphonate or SSRI use, and BMI.
“Our results suggest that non–enzyme-inducing AED use is associated in a graded manner with rates of hip bone loss in older men, with lower rates of loss among nonusers of AEDs, intermediate rates of loss among intermittent users, and high rates of loss among continuous users,” the authors wrote.
They added, “These findings are supported by prior studies reporting higher fracture rates among non–enzyme-inducing AED users compared with nonusers of AEDs or a similar fracture risk between patients taking non–enzyme-inducing AEDs versus those taking enzyme-inducing AEDs.”
In particular, the results suggest that men who take gabapentin have a 1.4- to 1.8-fold higher adjusted rate of bone loss at the hip compared with nonusers of AEDs.
Neurology. 2008;71(10):723-730.
Relatives of Patients With Brain Tumors Seem to Be at Increased Risk
NEW YORK, September 22 (Reu­ters Health)—By linking a Utah genealogy database to statewide cancer records, researchers have uncovered evidence of a familial contribution to primary brain cancer risk.
“There has been landmark work done previously using the Utah Population Database resource, in discovering hereditary associations and specific genes for breast cancer, colon cancer, and other nonneoplastic diseases,” Dr. Deborah T. Blumenthal told Reuters Health. “We sought to utilize this unique resource to search for familial relationships in primary brain tumors.”
The database includes more than two million persons with up to 10 generations of genealogic data. Dr. Blumenthal, currently at Tel-Aviv Sourasky Medical Center, and Dr. Lisa A. Cannon-Albright, at the University of Utah in Salt Lake City, examined the risk of brain tumors in the relatives of 744 individuals with astrocytoma, 658 patients with glioblastoma, and one patient with both.
According to their report in the September 23 issue of Neurology, significant excess risk exists among first-degree relatives of patients with astrocytoma or glioblastoma, compared with the rate of disease in the general population.
There was also significantly increased risk among second-degree relatives of patients with astrocytoma.
Noting that cancers with a genetic contribution often occur at an earlier age than sporadic cases, the researchers report that first-degree relatives of patients diagnosed before age 20 were at higher risk. Risk was also elevated for family members of cases with astrocytoma diagnosed before age 15.
“These findings, which remained significant beyond first-degree relations, support the hypothesis of familiality—a common gene or group of genes that may predispose individuals to brain tumors,” Dr. Blumenthal said.
“It needs to be stressed that we are still considering a very small minority (less than 5%) of an already small group of patients (less than 20,000/year in the US) who may have a familial risk for being affected with these tumors,” she added. “However, clinicians should be aware of this association and carefully query family history in their patients. If other family members have neurologic symptoms, the threshold for screening them for a brain tumor should be lower.”
Such symptoms, she explained, may include “new, progressive headaches, nausea or vomiting, seizures (which may be motor or sensory phenomenon, or even episodes of odd smells/tastes or déjà vu, when the temporal lobe is involved), changes in vision, changes in speech or language ability (word-finding difficulty), changes in personality (including apathy or apparent depression), and imbalance or incoordination.”

The researchers now plan prospective follow-up of these high-risk pedigrees.
“If genes or loci responsible for brain tumors could be identified, they could have relevance not only for familial tumors, but for the larger population as well,” Dr. Blumenthal concluded. “Ultimately, with such information, screening and even preventive therapy for malignant brain tumors might be possible in the future.”
Neurology. 2008;71(13):1015-1020.
Engerix B Vaccine May Increase the Risk of Multiple Sclerosis in Children
NEW YORK, September 26 (Reuters Health)—Although most hepatitis B vaccines do not seem to increase the risk of multiple sclerosis (MS) in children, use of one particular brand—Engerix B (GlaxoSmithKline)—may, according to findings from a study conducted in France.
In the study reported in the October 8 online issue of Neurology, the odds ratio (OR) for Engerix B exposure was 2.77 among children with MS, compared with an unaffected control group.
Prior reports have suggested a link between hepatitis B vaccine exposure and CNS inflammatory demyelination, including MS as well as acute disseminated encephalomyelitis and transverse myelitis. In general, however, findings from epidemiologic studies have not supported an association.
The focus of the current case-control study was on the neurologic effects of hepatitis B vaccination in children, since most of the prior investigations involved adults only, lead author Dr. Yann Mikaeloff, from Assistance Publique-Hôpitaux de Paris, and colleagues noted.
Case patients included 349 children with a first episode of CNS inflammatory demyelination between 1994 and 2003. Each subject was matched to up to 12 controls by age, gender, and geographic location.
In the overall analysis, hepatitis B vaccination did not increase the risk of CNS inflammatory demyelination.
However, when the analysis was confined to vaccine-compliant subjects, vaccine exposure more than three years prior to the index date was linked to an elevated risk (OR, 1.50). Further analysis showed that this association was mostly driven by the risk seen with Engerix B use (OR, 1.74).
Vaccine exposure more than three years before the index date was tied to a 2.12-fold increased risk of confirmed MS. Once again, however, this was mostly accounted for by Engerix B use (OR,  2.77).
As to why one brand of hepatitis B vaccine is safe while another may not be, the authors offer two possible explanations: “(1) each vaccine uses a different section of the hepatitis B antigen, and some protein fragments produced by yeasts may induce molecular mimicry, while others do not; (2) the production process varies by brand, and differences in yeast protein content may be crucial if yeast protein may trigger autoimmune reactions.”
The packaging insert (December 2006) for Engerix B mentions reports of patients with MS who experience exacerbations following use of the vaccine, but it points out that causality has not been established. The insert also notes new cases of MS and transverse myelitis that occurred after vaccination and were identified during postmarketing surveillance.
Neurology. 2008 Oct 8; [Epub ahead of print].

Alzheimer’s Pathology Reduced With Combined Diabetes Therapy
NEW YORK, September 9 (Reuters Health)—In a postmortem study of patients with Alzheimer’s disease, diabetic subjects treated with both insulin and oral hypoglycemic agents had lower neuritic plaque densities than did other diabetics and nondiabetics, new research shows.
In several studies, type 2 diabetes has been identified as a risk factor for Alzheimer’s disease. The link between diabetes and Alzheimer’s neuropathology, by contrast, is less clear, according to the report in the September 2 issue of Neurology.
The current study, conducted by Dr. M. S. Beeri, from Mount Sinai School of Medicine in New York City, and colleagues, involved an analysis of neuritic plaques and neurofibrillary tangles in brain specimens from 124 diabetics and 124 nondiabetics.
The diabetic group consisted of 29 patients who had never used antidiabetic agents, 49 who had received insulin only, 28 treated with agents other than insulin, and 18 treated with both insulin and oral antidiabetic medications.
The overall neuritic plaque rating, the rating in the entorhinal cortex and amygdala, and the neuritic plaque count in all regions examined differed significantly among the groups. In all of the analyses, the combined medication group had fewer neuritic plaques than did the other groups.
By contrast, the authors found no significant difference in neurofibrillary tangles between the groups.
The findings provide “evidence of substantially lower neuritic plaque density in diabetic subjects taking both insulin and hypoglycemic medication consistent with the effects of both on the neurobiology of insulin,” the researchers concluded. “These pathways should be considered as potentially mechanistically important in the etiology of β amyloid–associated neuropathology and deposition of neuritic plaques.”
Neurology. 2008;71(10):750-757.
Antiepileptic Drug Use May Contribute to Bone Loss in Older Men
NEW YORK, September 19 (Reuters Health)—Use of non–enzyme-inducing antiepileptic drugs (AEDs) independently raises the risk of bone loss at the hip in older men, results of a prospective study suggest.
In the September 2 issue of Neurology, Dr. Kristine E. Ensrud, from the Veterans Affairs Medical Center in Minneapolis, and colleagues pointed out, “AED use may be associated with higher rates of bone loss because [the drugs] may have adverse effects on bone metabolism. On the other hand, AED use may be a marker of factors such as poor health ... that are associated with greater rates of bone loss.”
In 4,222 older community-dwelling participants in the Osteoporosis Fractures in Men study, the researchers analyzed use of non–enzyme-inducing and enzyme-inducing AEDs. They also measured subjects’ hip bone mineral density (BMD) at baseline and at an average of 4.6 years later.
Among men who didn’t use AEDs at all, the average rate of decline in total hip BMD per year was -0.35%, compared with -0.46% among enzyme-inducing AED users and -0.53% among non–enzyme-inducing AED users.
The rate of loss per year was -0.60% among men who were taking non–enzyme-inducing AEDs at both examinations, -0.51% among men taking non–enzyme-inducing AEDs at one examination only, and -0.35% among nonusers.
The researchers pointed out that these findings were achieved after adjustment for a myriad of potential confounders not accounted for in past studies, including age, race, health status, baseline BMD, physical activity, smoking, alcohol intake, total calcium intake, diabetes, kidney disease, bisphosphonate or SSRI use, and BMI.
“Our results suggest that non–enzyme-inducing AED use is associated in a graded manner with rates of hip bone loss in older men, with lower rates of loss among nonusers of AEDs, intermediate rates of loss among intermittent users, and high rates of loss among continuous users,” the authors wrote.
They added, “These findings are supported by prior studies reporting higher fracture rates among non–enzyme-inducing AED users compared with nonusers of AEDs or a similar fracture risk between patients taking non–enzyme-inducing AEDs versus those taking enzyme-inducing AEDs.”
In particular, the results suggest that men who take gabapentin have a 1.4- to 1.8-fold higher adjusted rate of bone loss at the hip compared with nonusers of AEDs.
Neurology. 2008;71(10):723-730.
Relatives of Patients With Brain Tumors Seem to Be at Increased Risk
NEW YORK, September 22 (Reu­ters Health)—By linking a Utah genealogy database to statewide cancer records, researchers have uncovered evidence of a familial contribution to primary brain cancer risk.
“There has been landmark work done previously using the Utah Population Database resource, in discovering hereditary associations and specific genes for breast cancer, colon cancer, and other nonneoplastic diseases,” Dr. Deborah T. Blumenthal told Reuters Health. “We sought to utilize this unique resource to search for familial relationships in primary brain tumors.”
The database includes more than two million persons with up to 10 generations of genealogic data. Dr. Blumenthal, currently at Tel-Aviv Sourasky Medical Center, and Dr. Lisa A. Cannon-Albright, at the University of Utah in Salt Lake City, examined the risk of brain tumors in the relatives of 744 individuals with astrocytoma, 658 patients with glioblastoma, and one patient with both.
According to their report in the September 23 issue of Neurology, significant excess risk exists among first-degree relatives of patients with astrocytoma or glioblastoma, compared with the rate of disease in the general population.
There was also significantly increased risk among second-degree relatives of patients with astrocytoma.
Noting that cancers with a genetic contribution often occur at an earlier age than sporadic cases, the researchers report that first-degree relatives of patients diagnosed before age 20 were at higher risk. Risk was also elevated for family members of cases with astrocytoma diagnosed before age 15.
“These findings, which remained significant beyond first-degree relations, support the hypothesis of familiality—a common gene or group of genes that may predispose individuals to brain tumors,” Dr. Blumenthal said.
“It needs to be stressed that we are still considering a very small minority (less than 5%) of an already small group of patients (less than 20,000/year in the US) who may have a familial risk for being affected with these tumors,” she added. “However, clinicians should be aware of this association and carefully query family history in their patients. If other family members have neurologic symptoms, the threshold for screening them for a brain tumor should be lower.”
Such symptoms, she explained, may include “new, progressive headaches, nausea or vomiting, seizures (which may be motor or sensory phenomenon, or even episodes of odd smells/tastes or déjà vu, when the temporal lobe is involved), changes in vision, changes in speech or language ability (word-finding difficulty), changes in personality (including apathy or apparent depression), and imbalance or incoordination.”

The researchers now plan prospective follow-up of these high-risk pedigrees.
“If genes or loci responsible for brain tumors could be identified, they could have relevance not only for familial tumors, but for the larger population as well,” Dr. Blumenthal concluded. “Ultimately, with such information, screening and even preventive therapy for malignant brain tumors might be possible in the future.”
Neurology. 2008;71(13):1015-1020.
Engerix B Vaccine May Increase the Risk of Multiple Sclerosis in Children
NEW YORK, September 26 (Reuters Health)—Although most hepatitis B vaccines do not seem to increase the risk of multiple sclerosis (MS) in children, use of one particular brand—Engerix B (GlaxoSmithKline)—may, according to findings from a study conducted in France.
In the study reported in the October 8 online issue of Neurology, the odds ratio (OR) for Engerix B exposure was 2.77 among children with MS, compared with an unaffected control group.
Prior reports have suggested a link between hepatitis B vaccine exposure and CNS inflammatory demyelination, including MS as well as acute disseminated encephalomyelitis and transverse myelitis. In general, however, findings from epidemiologic studies have not supported an association.
The focus of the current case-control study was on the neurologic effects of hepatitis B vaccination in children, since most of the prior investigations involved adults only, lead author Dr. Yann Mikaeloff, from Assistance Publique-Hôpitaux de Paris, and colleagues noted.
Case patients included 349 children with a first episode of CNS inflammatory demyelination between 1994 and 2003. Each subject was matched to up to 12 controls by age, gender, and geographic location.
In the overall analysis, hepatitis B vaccination did not increase the risk of CNS inflammatory demyelination.
However, when the analysis was confined to vaccine-compliant subjects, vaccine exposure more than three years prior to the index date was linked to an elevated risk (OR, 1.50). Further analysis showed that this association was mostly driven by the risk seen with Engerix B use (OR, 1.74).
Vaccine exposure more than three years before the index date was tied to a 2.12-fold increased risk of confirmed MS. Once again, however, this was mostly accounted for by Engerix B use (OR,  2.77).
As to why one brand of hepatitis B vaccine is safe while another may not be, the authors offer two possible explanations: “(1) each vaccine uses a different section of the hepatitis B antigen, and some protein fragments produced by yeasts may induce molecular mimicry, while others do not; (2) the production process varies by brand, and differences in yeast protein content may be crucial if yeast protein may trigger autoimmune reactions.”
The packaging insert (December 2006) for Engerix B mentions reports of patients with MS who experience exacerbations following use of the vaccine, but it points out that causality has not been established. The insert also notes new cases of MS and transverse myelitis that occurred after vaccination and were identified during postmarketing surveillance.
Neurology. 2008 Oct 8; [Epub ahead of print].

Alzheimer’s Pathology Reduced With Combined Diabetes Therapy
NEW YORK, September 9 (Reuters Health)—In a postmortem study of patients with Alzheimer’s disease, diabetic subjects treated with both insulin and oral hypoglycemic agents had lower neuritic plaque densities than did other diabetics and nondiabetics, new research shows.
In several studies, type 2 diabetes has been identified as a risk factor for Alzheimer’s disease. The link between diabetes and Alzheimer’s neuropathology, by contrast, is less clear, according to the report in the September 2 issue of Neurology.
The current study, conducted by Dr. M. S. Beeri, from Mount Sinai School of Medicine in New York City, and colleagues, involved an analysis of neuritic plaques and neurofibrillary tangles in brain specimens from 124 diabetics and 124 nondiabetics.
The diabetic group consisted of 29 patients who had never used antidiabetic agents, 49 who had received insulin only, 28 treated with agents other than insulin, and 18 treated with both insulin and oral antidiabetic medications.
The overall neuritic plaque rating, the rating in the entorhinal cortex and amygdala, and the neuritic plaque count in all regions examined differed significantly among the groups. In all of the analyses, the combined medication group had fewer neuritic plaques than did the other groups.
By contrast, the authors found no significant difference in neurofibrillary tangles between the groups.
The findings provide “evidence of substantially lower neuritic plaque density in diabetic subjects taking both insulin and hypoglycemic medication consistent with the effects of both on the neurobiology of insulin,” the researchers concluded. “These pathways should be considered as potentially mechanistically important in the etiology of β amyloid–associated neuropathology and deposition of neuritic plaques.”
Neurology. 2008;71(10):750-757.
Antiepileptic Drug Use May Contribute to Bone Loss in Older Men
NEW YORK, September 19 (Reuters Health)—Use of non–enzyme-inducing antiepileptic drugs (AEDs) independently raises the risk of bone loss at the hip in older men, results of a prospective study suggest.
In the September 2 issue of Neurology, Dr. Kristine E. Ensrud, from the Veterans Affairs Medical Center in Minneapolis, and colleagues pointed out, “AED use may be associated with higher rates of bone loss because [the drugs] may have adverse effects on bone metabolism. On the other hand, AED use may be a marker of factors such as poor health ... that are associated with greater rates of bone loss.”
In 4,222 older community-dwelling participants in the Osteoporosis Fractures in Men study, the researchers analyzed use of non–enzyme-inducing and enzyme-inducing AEDs. They also measured subjects’ hip bone mineral density (BMD) at baseline and at an average of 4.6 years later.
Among men who didn’t use AEDs at all, the average rate of decline in total hip BMD per year was -0.35%, compared with -0.46% among enzyme-inducing AED users and -0.53% among non–enzyme-inducing AED users.
The rate of loss per year was -0.60% among men who were taking non–enzyme-inducing AEDs at both examinations, -0.51% among men taking non–enzyme-inducing AEDs at one examination only, and -0.35% among nonusers.
The researchers pointed out that these findings were achieved after adjustment for a myriad of potential confounders not accounted for in past studies, including age, race, health status, baseline BMD, physical activity, smoking, alcohol intake, total calcium intake, diabetes, kidney disease, bisphosphonate or SSRI use, and BMI.
“Our results suggest that non–enzyme-inducing AED use is associated in a graded manner with rates of hip bone loss in older men, with lower rates of loss among nonusers of AEDs, intermediate rates of loss among intermittent users, and high rates of loss among continuous users,” the authors wrote.
They added, “These findings are supported by prior studies reporting higher fracture rates among non–enzyme-inducing AED users compared with nonusers of AEDs or a similar fracture risk between patients taking non–enzyme-inducing AEDs versus those taking enzyme-inducing AEDs.”
In particular, the results suggest that men who take gabapentin have a 1.4- to 1.8-fold higher adjusted rate of bone loss at the hip compared with nonusers of AEDs.
Neurology. 2008;71(10):723-730.
Relatives of Patients With Brain Tumors Seem to Be at Increased Risk
NEW YORK, September 22 (Reu­ters Health)—By linking a Utah genealogy database to statewide cancer records, researchers have uncovered evidence of a familial contribution to primary brain cancer risk.
“There has been landmark work done previously using the Utah Population Database resource, in discovering hereditary associations and specific genes for breast cancer, colon cancer, and other nonneoplastic diseases,” Dr. Deborah T. Blumenthal told Reuters Health. “We sought to utilize this unique resource to search for familial relationships in primary brain tumors.”
The database includes more than two million persons with up to 10 generations of genealogic data. Dr. Blumenthal, currently at Tel-Aviv Sourasky Medical Center, and Dr. Lisa A. Cannon-Albright, at the University of Utah in Salt Lake City, examined the risk of brain tumors in the relatives of 744 individuals with astrocytoma, 658 patients with glioblastoma, and one patient with both.
According to their report in the September 23 issue of Neurology, significant excess risk exists among first-degree relatives of patients with astrocytoma or glioblastoma, compared with the rate of disease in the general population.
There was also significantly increased risk among second-degree relatives of patients with astrocytoma.
Noting that cancers with a genetic contribution often occur at an earlier age than sporadic cases, the researchers report that first-degree relatives of patients diagnosed before age 20 were at higher risk. Risk was also elevated for family members of cases with astrocytoma diagnosed before age 15.
“These findings, which remained significant beyond first-degree relations, support the hypothesis of familiality—a common gene or group of genes that may predispose individuals to brain tumors,” Dr. Blumenthal said.
“It needs to be stressed that we are still considering a very small minority (less than 5%) of an already small group of patients (less than 20,000/year in the US) who may have a familial risk for being affected with these tumors,” she added. “However, clinicians should be aware of this association and carefully query family history in their patients. If other family members have neurologic symptoms, the threshold for screening them for a brain tumor should be lower.”
Such symptoms, she explained, may include “new, progressive headaches, nausea or vomiting, seizures (which may be motor or sensory phenomenon, or even episodes of odd smells/tastes or déjà vu, when the temporal lobe is involved), changes in vision, changes in speech or language ability (word-finding difficulty), changes in personality (including apathy or apparent depression), and imbalance or incoordination.”

The researchers now plan prospective follow-up of these high-risk pedigrees.
“If genes or loci responsible for brain tumors could be identified, they could have relevance not only for familial tumors, but for the larger population as well,” Dr. Blumenthal concluded. “Ultimately, with such information, screening and even preventive therapy for malignant brain tumors might be possible in the future.”
Neurology. 2008;71(13):1015-1020.
Engerix B Vaccine May Increase the Risk of Multiple Sclerosis in Children
NEW YORK, September 26 (Reuters Health)—Although most hepatitis B vaccines do not seem to increase the risk of multiple sclerosis (MS) in children, use of one particular brand—Engerix B (GlaxoSmithKline)—may, according to findings from a study conducted in France.
In the study reported in the October 8 online issue of Neurology, the odds ratio (OR) for Engerix B exposure was 2.77 among children with MS, compared with an unaffected control group.
Prior reports have suggested a link between hepatitis B vaccine exposure and CNS inflammatory demyelination, including MS as well as acute disseminated encephalomyelitis and transverse myelitis. In general, however, findings from epidemiologic studies have not supported an association.
The focus of the current case-control study was on the neurologic effects of hepatitis B vaccination in children, since most of the prior investigations involved adults only, lead author Dr. Yann Mikaeloff, from Assistance Publique-Hôpitaux de Paris, and colleagues noted.
Case patients included 349 children with a first episode of CNS inflammatory demyelination between 1994 and 2003. Each subject was matched to up to 12 controls by age, gender, and geographic location.
In the overall analysis, hepatitis B vaccination did not increase the risk of CNS inflammatory demyelination.
However, when the analysis was confined to vaccine-compliant subjects, vaccine exposure more than three years prior to the index date was linked to an elevated risk (OR, 1.50). Further analysis showed that this association was mostly driven by the risk seen with Engerix B use (OR, 1.74).
Vaccine exposure more than three years before the index date was tied to a 2.12-fold increased risk of confirmed MS. Once again, however, this was mostly accounted for by Engerix B use (OR,  2.77).
As to why one brand of hepatitis B vaccine is safe while another may not be, the authors offer two possible explanations: “(1) each vaccine uses a different section of the hepatitis B antigen, and some protein fragments produced by yeasts may induce molecular mimicry, while others do not; (2) the production process varies by brand, and differences in yeast protein content may be crucial if yeast protein may trigger autoimmune reactions.”
The packaging insert (December 2006) for Engerix B mentions reports of patients with MS who experience exacerbations following use of the vaccine, but it points out that causality has not been established. The insert also notes new cases of MS and transverse myelitis that occurred after vaccination and were identified during postmarketing surveillance.
Neurology. 2008 Oct 8; [Epub ahead of print].

CHICAGO—Many of the neuropsychologic tests that target cognitive domains affected in patients with multiple sclerosis (MS) do not appear to be predictive of neuropsychiatric symptoms in these patients, as has been previously hypothesized, reported Jesus Lovera, PhD, and colleagues. Neuropsychiatric symptoms occur in 80% of patients with MS, and depression is the most common of these symptoms, the researchers stated at the 60th Annual Meeting of the American Academy of Neurology.

The investigators studied 109 patients (mean age, 51) who were enrolled in clinical trials of memantine for cognitive impairment in MS. Among the inclusion criteria were significant cognitive complaints, a score 1 SD below the normal population average on the Paced Auditory Serial Addition Test (PASAT) or the California Verbal Learning Test-II (CVLT-II), and a Beck Depression Inventory–IA score of less than 19.

Neuropsychologic tests included a three-second version of the PASAT, the CVLT-II, the Symbol Digits Modalities Test, the Delis-Kaplan Executive Function System (D-KEFS) sorting test, the Controlled Oral Word Association Test (COWAT), and the Victoria version of the Stroop test. Neuropsychiatric symptoms were assessed using the Modified Neuropsychiatric Inventory.

According to Dr. Lovera, who is an Instructor in the Department of Neurology at Oregon Health and Science University in Portland, and colleagues, 55 patients had one or more neuropsychiatric symptoms: 42 had irritability, 31 anxiety, 24 agitation/aggression, 23 apathy, 18 disinhibition, and 11 euphoria. Tests of attention and processing speed (PASAT), verbal fluency (COWAT), sorting (D-KEFS), and verbal learning and recall (CVLT-II) were not predictive of neuropsychiatric symptoms.

Perseveration and intrusions, as measured by the Stroop test and the CVLT-II, were highly predictive of neuropsychiatric symptoms.

Physicians should consider screening for neuropsychiatric symptoms in patients with MS, particularly in those with cognitive complaints, commented the researchers. They also advised that patients with MS who have impairment on the Stroop test or intrusions or repetitions on the CVLT-II be screened for neuropsychiatric symptoms.

CHICAGO—Many of the neuropsychologic tests that target cognitive domains affected in patients with multiple sclerosis (MS) do not appear to be predictive of neuropsychiatric symptoms in these patients, as has been previously hypothesized, reported Jesus Lovera, PhD, and colleagues. Neuropsychiatric symptoms occur in 80% of patients with MS, and depression is the most common of these symptoms, the researchers stated at the 60th Annual Meeting of the American Academy of Neurology.

The investigators studied 109 patients (mean age, 51) who were enrolled in clinical trials of memantine for cognitive impairment in MS. Among the inclusion criteria were significant cognitive complaints, a score 1 SD below the normal population average on the Paced Auditory Serial Addition Test (PASAT) or the California Verbal Learning Test-II (CVLT-II), and a Beck Depression Inventory–IA score of less than 19.

Neuropsychologic tests included a three-second version of the PASAT, the CVLT-II, the Symbol Digits Modalities Test, the Delis-Kaplan Executive Function System (D-KEFS) sorting test, the Controlled Oral Word Association Test (COWAT), and the Victoria version of the Stroop test. Neuropsychiatric symptoms were assessed using the Modified Neuropsychiatric Inventory.

According to Dr. Lovera, who is an Instructor in the Department of Neurology at Oregon Health and Science University in Portland, and colleagues, 55 patients had one or more neuropsychiatric symptoms: 42 had irritability, 31 anxiety, 24 agitation/aggression, 23 apathy, 18 disinhibition, and 11 euphoria. Tests of attention and processing speed (PASAT), verbal fluency (COWAT), sorting (D-KEFS), and verbal learning and recall (CVLT-II) were not predictive of neuropsychiatric symptoms.

Perseveration and intrusions, as measured by the Stroop test and the CVLT-II, were highly predictive of neuropsychiatric symptoms.

Physicians should consider screening for neuropsychiatric symptoms in patients with MS, particularly in those with cognitive complaints, commented the researchers. They also advised that patients with MS who have impairment on the Stroop test or intrusions or repetitions on the CVLT-II be screened for neuropsychiatric symptoms.

CHICAGO—Many of the neuropsychologic tests that target cognitive domains affected in patients with multiple sclerosis (MS) do not appear to be predictive of neuropsychiatric symptoms in these patients, as has been previously hypothesized, reported Jesus Lovera, PhD, and colleagues. Neuropsychiatric symptoms occur in 80% of patients with MS, and depression is the most common of these symptoms, the researchers stated at the 60th Annual Meeting of the American Academy of Neurology.

The investigators studied 109 patients (mean age, 51) who were enrolled in clinical trials of memantine for cognitive impairment in MS. Among the inclusion criteria were significant cognitive complaints, a score 1 SD below the normal population average on the Paced Auditory Serial Addition Test (PASAT) or the California Verbal Learning Test-II (CVLT-II), and a Beck Depression Inventory–IA score of less than 19.

Neuropsychologic tests included a three-second version of the PASAT, the CVLT-II, the Symbol Digits Modalities Test, the Delis-Kaplan Executive Function System (D-KEFS) sorting test, the Controlled Oral Word Association Test (COWAT), and the Victoria version of the Stroop test. Neuropsychiatric symptoms were assessed using the Modified Neuropsychiatric Inventory.

According to Dr. Lovera, who is an Instructor in the Department of Neurology at Oregon Health and Science University in Portland, and colleagues, 55 patients had one or more neuropsychiatric symptoms: 42 had irritability, 31 anxiety, 24 agitation/aggression, 23 apathy, 18 disinhibition, and 11 euphoria. Tests of attention and processing speed (PASAT), verbal fluency (COWAT), sorting (D-KEFS), and verbal learning and recall (CVLT-II) were not predictive of neuropsychiatric symptoms.

Perseveration and intrusions, as measured by the Stroop test and the CVLT-II, were highly predictive of neuropsychiatric symptoms.

Physicians should consider screening for neuropsychiatric symptoms in patients with MS, particularly in those with cognitive complaints, commented the researchers. They also advised that patients with MS who have impairment on the Stroop test or intrusions or repetitions on the CVLT-II be screened for neuropsychiatric symptoms.