Neurology Journal

Background: New immigrants to North America, most of whom are under age 50 years, exhibit fewer risk factors for cardiovascular disease than their native-born counterparts, yet the stress of resettlement may conceivably place them at higher risk of stroke. We determined the risk of acute stroke associated with recency of immigration.Methods: We completed a population-based matched cohort study in Ontario, the largest province in Canada, from April 1, 1995, to March 31, 2007. Overall, 965,829 new immigrants were matched to 3,272,393 long-term residents by year of birth, sex, and location. New immigrants were identified as new recipients of universally available public health insurance, and long-term residents were those insured for 5 years or longer.Results: The mean age of the participants at study entry was about 34 years and the total number of observed strokes was 6,216 after a median duration of follow-up of about 6 years. The incidence rate of acute stroke was 1.69 per 10,000 person-years among new immigrants and 2.56 per 10,000 person-years among long-term residents (crude hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.62-0.71). After adjusting for age, income quintile, urban vs rural residence, history of hypertension, diabetes mellitus and smoking, and number of health insurance claims, the HR for stroke was 0.69 (95% CI 0.64-0.74). Similar risk estimates were seen for both ischemic and hemorrhagic stroke subtypes.Conclusion: New immigrants appear to be at lower risk of premature acute stroke than long-term residents. This finding does not appear to be explained by the availability of health care services or income level.(C)2010AAN Enterprises, Inc.

Objective: Several studies suggest an increasing prevalence of multiple sclerosis (MS) in Canada. We aimed to validate a case definition for MS using administrative health insurance data, and to describe the incidence and prevalence of MS in Manitoba, Canada.Methods: We used provincial administrative claims data to identify persons with demyelinating disease using International Classification of Diseases 9/10 codes and prescription claims. To validate the case definition, questionnaires were mailed to 2,000 randomly selected persons with an encounter for demyelinating disease, requesting permission for medical records review. We used diagnoses abstracted from medical records as the gold standard to evaluate candidate case definitions using administrative data.Results: From 1984 to 1997, cases of MS using claims data were defined as persons with >=7 medical contacts for MS. From 1998 onward, cases were defined as persons with >=3 medical contacts. As compared to medical records, this definition had a positive predictive value of 80.5% and negative predictive value of 75.5%. From 1998 to 2006, the average age- and sex-adjusted annual incidence of MS per 100,000 population was 11.4 (95% confidence interval [CI] 10.7-12.0). The age-adjusted prevalence of MS per 100,000 population increased from 32.6 (95% CI 29.4-35.8) in 1984 to 226.7 (95% CI 218.1-235.3) in 2006, with the peak prevalence shifting to older age groups.Conclusion: The prevalence of multiple sclerosis (MS) in Manitoba is among the highest in the world. The rising prevalence with minimally changing incidence suggests improving survival. This study supports the use of administrative data to develop case definitions and further define the epidemiology of MS.(C)2010AAN Enterprises, Inc.

Background: Late-onset Alzheimer disease (LOAD) is a common disorder with a substantial genetic component. We postulate that many disease susceptibility variants act by altering gene expression levels.Methods: We measured messenger RNA (mRNA) expression levels of 12 LOAD candidate genes in the cerebella of 200 subjects with LOAD. Using the genotypes from our LOAD genome-wide association study for the cis-single nucleotide polymorphisms (SNPs) (n = 619) of these 12 LOAD candidate genes, we tested for associations with expression levels as endophenotypes. The strongest expression cis-SNP was tested for AD association in 7 independent case-control series (2,280 AD and 2,396 controls).Results: We identified 3 SNPs that associated significantly with IDE (insulin degrading enzyme) expression levels. A single copy of the minor allele for each significant SNP was associated with ~twofold higher IDE expression levels. The most significant SNP, rs7910977, is 4.2 kb beyond the 3' end of IDE. The association observed with this SNP was significant even at the genome-wide level (p = 2.7 x 10-8). Furthermore, the minor allele of rs7910977 associated significantly (p = 0.0046) with reduced LOAD risk (OR = 0.81 with a 95% CI of 0.70-0.94), as expected biologically from its association with elevated IDE expression.Conclusions: These results provide strong evidence that IDE is a late-onset Alzheimer disease (LOAD) gene with variants that modify risk of LOAD by influencing IDE expression. They also suggest that the use of expression levels as endophenotypes in genome-wide association studies may provide a powerful approach for the identification of disease susceptibility alleles.(C)2010AAN Enterprises, Inc.

Objective: To analyze the risk factors, presentation, etiologies, and outcomes of adult cancer patients with intracranial hemorrhage (IH).Methods: We analyzed 208 patients retrospectively with the diagnosis of IH from the Memorial Sloan-Kettering neurology database from January 2000 through December 2007. Charts were examined for clinical and radiographic data. Survival was calculated using the Kaplan-Meier method. Survival between groups was compared via the log-rank test. Logistic regression models were used to assess for prognostic indicators of 30- and 90-day mortality.Results: There were 181 intracerebral and 46 subarachnoid hemorrhages. Sixty-eight percent of patients had solid tumors, 16% had primary brain tumors, and 16% had hematopoietic tumors. Hemiparesis and headache were the most common symptoms. Intratumoral hemorrhage (61%) and coagulopathy (46%) accounted for the majority of hemorrhages, whereas hypertension (5%) was rare. Median survival was 3 months (95% confidence interval [CI] 2-4), and 30-day mortality was 31%. However, nearly one-half of patients were completely or partially independent at the time of discharge. Patients with primary brain tumors had the longest median survival (5.9 months, 95% CI 2.9-11.8, p = 0.05). Independent predictors of 30-day mortality were not having a primary brain tumor, impaired consciousness, multiple foci of hemorrhage, hydrocephalus, no ventriculostomy, and treatment of increased intracranial pressure.Conclusions: Intracranial hemorrhage in patients with cancer is often due to unique mechanisms. Prognosis is poor, but comparable to intracranial hemorrhage in the general population. Aggressive care is recommended despite high mortality, because many patients have good functional outcomes.(C)2010AAN Enterprises, Inc.

Objective: To present 2 families with maternally inherited severe epilepsy as the main symptom of mitochondrial disease due to point mutations at position 616 in the mitochondrial tRNAPhe (MT-TF) gene.Methods: Histologic stainings were performed on skeletal muscle slices from the 2 index patients. Oxidative phosphorylation activity was measured by oxygraphic and spectrophotometric methods. The patients' complete mitochondrial DNA (mtDNA) and the relevant mtDNA region in maternal relatives were sequenced.Results: Muscle histology showed only decreased overall COX staining, while a combined respiratory chain defect, most severely affecting complex IV, was noted in both patients' skeletal muscle. Sequencing of the mtDNA revealed in both patients a mutation at position 616 in the MT-TF gene (T>C or T>G). These mutations disrupt a base pair in the anticodon stem at a highly conserved position. They were apparently homoplasmic in both patients, and had different heteroplasmy levels in the investigated maternal relatives.Conclusions: Deleterious mutations in the mitochondrial tRNAPhe may solely manifest with epilepsy when segregating to homoplasmy. They may be overlooked in the absence of lactate accumulation and typical mosaic mitochondrial defects in muscle.(C)2010AAN Enterprises, Inc.