| This week in Neurology(R) |
this week in neurology(r): highlights of the february 9 issue.
Pages: 445
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| Editorials |
does immigration to canada prevent stroke, eh?.
- Jacobs, Bradley, MD, MS. Pages: 446-447
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visual input is critical for postural control in patients with chronic right hemisphere infarcts.
- Rundek, Tatjana, Lalit, Kalra. Pages: 448-449
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| In Memoriam |
stanley van den noort, md (1930-2009).
- Frohman, Elliot, MD, PhD. Pages: 450
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| Articles |
risk of premature stroke in recent immigrants (presario): population-based matched cohort study .
- Saposnik, G., MD, MSc, Redelmeier, D., MD, MA, Lu, H., Lonn, E., MD, MSc, Fuller-Thomson, E., Ray, J., MD, MSc. Pages: 451-457
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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.
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altered control of postural sway following cerebral infarction: a cross-sectional analysis.
- Manor, B., Hu, K., Zhao, P., Selim, M., MD, PhD, Alsop, D., Novak, P., MD, PhD, Lipsitz, L., Novak, V., MD, PhD. Pages: 458-464
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Objective: Balance impairment is common following cerebral infarction. However, the effects of lesion hemisphere on postural control are largely unknown. We examined dependence upon vision and noninfarcted regional brain tissue volumes for postural control in individuals with right and left hemisphere middle cerebral artery (MCA) infarcts.Methods: Subjects with right MCA infarct (n = 17, age = 65 +/- 8 years, 7 +/- 6 years poststroke), left MCA infarct (n = 20, age = 65 +/- 8 years, 7 +/- 6 years poststroke), and controls (n = 55, age = 65 +/- 8 years) were studied. Postural control was defined by average velocity and the range and variability of mediolateral (ML) and anteroposterior (AP) sway during eyes-open and eyes-closed standing. Regional brain volumes were quantified using anatomic MRI at 3 Tesla.Results: Right and left hemisphere stroke groups had similar infarct volumes and outcomes. Subjects with right hemisphere infarcts demonstrated greater sway velocity, ML range, and ML variability with eyes closed compared to eyes open. In this group, smaller occipital lobe volumes were associated with greater eyes-open sway velocity (R = -0.64, p = 0.012) and ML range (R = -0.82, p = 0.001). Smaller cerebellar volumes were associated with greater eyes-closed sway velocity (R = -0.60, p = 0.015), ML range (R = -0.70, p = 0.007), and ML variability (R = -0.85, p < 0.001). These associations were not observed in left hemisphere infarct subjects or controls. AP sway was unaffected by infarct hemisphere or visual condition and did not correlate with regional brain volumes.Conclusions: Right hemisphere middle cerebral artery infarcts are associated with increased dependence on vision and noninfarcted brain regions (i.e., occipital lobes, cerebellum) to control postural sway. Strategies emphasizing postural tasks under reduced visual conditions may enhance functional recovery in these individuals.(C)2010AAN Enterprises, Inc.
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the rising prevalence and changing age distribution of multiple sclerosis in manitoba.
- Marrie, R., MD, PhD, Yu, N., Blanchard, J., MD, PhD, Leung, S., Elliott, L., MD, MSc. Pages: 465-471
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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.
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how preserved is episodic memory in behavioral variant frontotemporal dementia?
- Hornberger, M., Piguet, O., Graham, A., PhD, MRCP, Nestor, P., MD, FRACP, Hodges, J., MD, FRCP. Pages: 472-479
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Objective: Studies have shown variable memory performance in patients with behavioral variant frontotemporal dementia (bvFTD). Our study investigated whether this variability is due to the admixture of patients with true bvFTD and phenocopy patients. We also sought to compare performance of patients with bvFTD and patients with Alzheimer disease (AD).Methods: We analyzed neuropsychological memory performance in patients with a clinical diagnosis of bvFTD divided into those who progressed (n = 50) and those who remained stable (n = 39), patients with AD (n = 64), and healthy controls (n = 64).Results: Patients with progressive bvFTD were impaired on most memory tests to a similar level to that of patients with early AD. Findings from a subset of patients with progressive bvFTD with confirmed FTLD pathology (n = 10) corroborated these findings. By contrast, patients with phenocopy bvFTD performed significantly better than progressors and patients with AD. Logistic regression revealed that patients with bvFTD can be distinguished to a high degree (85%) on the immediate recall score of a word list learning test (Rey Auditory Verbal Learning Test).Conclusions: Our results provide evidence for an underlying memory deficit in "real" or progressive behavioral variant frontotemporal dementia (bvFTD) similar to Alzheimer disease, though the groups differ in orientation scores, with patients with bvFTD being intact. Exclusion solely based on impaired neuropsychological memory performance can potentially lead to an underdiagnosis of FTD.(C)2010AAN Enterprises, Inc.
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gene expression levels as endophenotypes in genome-wide association studies of alzheimer disease.
- Zou, F., Carrasquillo, M., Pankratz, V., Belbin, O., Morgan, K., Allen, M., Wilcox, S., Ma, L., Walker, L., Kouri, N., Burgess, J., Younkin, L., Younkin, Samuel, Younkin, C., Bisceglio, G., Crook, J., Dickson, D., Petersen, R., MD, PhD, Graff-Radford, N., Younkin, Steven, MD, PhD, Ertekin-Taner, N., MD, PhD. Pages: 480-486
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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.
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11c-pib binding is increased in patients with cerebral amyloid angiopathy-related hemorrhage.
- Ly, J., Donnan, G., Villemagne, V., Zavala, J., Ma, H., O'Keefe, G., Gong, S., Gunawan, R., Saunder, T., Ackerman, U., Tochon-Danguy, H., Churilov, L., Phan, T., Rowe, C.. Pages: 487-493
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Background: The in vivo diagnosis of cerebral amyloid angiopathy (CAA) is inferred from clinical and structural imaging features. 11C-Pittsburgh compound B (PIB) is a PET ligand that binds to [beta]-amyloid in extracellular plaques and vessel walls. We hypothesized that patients with a clinical diagnosis of CAA-related hemorrhage (CAAH) have increased 11C-PIB uptake and that the pattern differs from Alzheimer disease (AD).Methodology: Patients with CAAH based on established clinical criteria were studied using 11C-PIB PET and were compared with age-matched controls and patients with AD. Distribution volume ratio (DVR) parametric maps were created using the cerebellar cortex as a reference region.Results: Twelve patients with CAAH of mean age 73.9 (range 58-93) years were compared with 22 normal controls and 13 patients with AD of mean age 71.8 (59-83) and 73.8 (56-90) years, respectively. CAAH PIB median DVR binding was higher in cortical regions (1.69, interquartile range 1.44-1.97) compared with controls (1.32, 1.21-1.44, p = 0.002) but lower than AD (2.04, 1.93-2.26, p = 0.004). The occipital-global uptake ratio was lower among patients with AD than among patients with CAAH (p = 0.008), and the frontal-global uptake ratio was higher (p = 0.012).Conclusion: 11C-Pittsburgh compound B (PIB) binding is moderately increased in most patients with probable cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage. The distribution may differ from that seen in Alzheimer disease. 11C-PIB PET may assist in the in vivo diagnosis of CAA and serve as a surrogate marker for future therapeutic studies.(C)2010AAN Enterprises, Inc.
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intracerebral and subarachnoid hemorrhage in patients with cancer.
- Navi, B., Reichman, J., Berlin, D., Reiner, A., Panageas, K., Segal, A., DeAngelis, L.. Pages: 494-501
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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.
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mutant small heat shock protein b3 causes motor neuropathy: utility of a candidate gene approach.
- Kolb, S., MD, PhD, Snyder, P., Poi, E., Renard, E., Bartlett, A., Gu, S., Sutton, S., Arnold, W., Freimer, M., Lawson, V., Kissel, J., Prior, T.. Pages: 502-506
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Objective: Idiopathic peripheral neuropathy is common and likely due to genetic factors that are not detectable using standard linkage analysis. We initiated a candidate gene approach to study the genetic influence of the small heat shock protein (sHSP) gene family on an axonal motor and motor/sensory neuropathy patient population.Methods: The promoter region and all exonic and intronic sequences of the 10 sHSP genes (HSPB1-HSPB10) were screened in a cohort of presumed nonacquired, axonal motor and motor/sensory neuropathy patients seen at the Ohio State University Neuromuscular Clinic.Results: A missense mutation in the gene encoding small heat shock protein B3 (HSPB3, also called HSP27, protein 3) was discovered in 2 siblings with an asymmetric axonal motor neuropathy. Electrophysiologic studies revealed an axonal, predominantly motor, length-dependent neuropathy. The mutation, HSPB3(R7S), is located in the N-terminal domain and involves the loss of a conserved arginine.Conclusions: The discovery of an HSPB3 mutation associated with an axonal motor neuropathy using a candidate gene approach supports the notion that the small heat shock protein gene family coordinately plays an important role in motor neuron viability.(C)2010AAN Enterprises, Inc.
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severe epilepsy as the major symptom of new mutations in the mitochondrial trnaphe gene.
- Zsurka, G., MD, PhD, Hampel, K., Nelson, I., Jardel, C., PharmD, PhD, Mirandola, S., Sassen, R., Kornblum, C., Marcorelles, P., Lavoue, S., Lombes, A., MD, PhD, Kunz, W.. Pages: 507-512
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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.
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availability of brain serotonin transporters in patients with restless legs syndrome.
- Jhoo, J., MD, PhD, Yoon, I., MD, PhD, Kim, Y., Chung, S., MD, PhD, Kim, J., MD, PhD, Lee, S., Kim, T., Moon, S., Kim, S., MD, PhD, Kim, K., MD, PhD. Pages: 513-518
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Background: Selective serotonin reuptake inhibitors have been associated with the risk of restless legs syndrome (RLS), suggesting that dysregulation of serotonergic neurotransmission may provoke or exacerbate RLS.Methods: We compared the availability of serotonin transporter (SERT) between 16 drug-naive patients with RLS and 16 healthy controls. SERT was measured in the pons and medulla via [123I]-2[beta]-carbomethoxy-3[beta]-(4-iodophenyl) tropane ([beta]-CIT) SPECT. A ratio of specific to nonspecific brain uptake (V3") was used for all comparisons. RLS was diagnosed according to the criteria proposed by the National Institute of Health, and its severity was measured using the International RLS Study Group (IRLSSG) Severity Scale.Results: The availability of SERT was similar in the RLS group and the control group with regards to the pons (1.24 +/- 0.31 vs 1.24 +/- 0.25, p > 0.1) and the medulla (0.99 +/- 0.25 vs 1.00 +/- 0.23, p > 0.1). However, IRLSSG Severity Scale scores increased with decrease of SERT availability in both the pons ([beta] = -0.50, t = -3.19, p = 0.009) and the medulla ([beta] = -0.42, t = -2.44, p = 0.03).Conclusions: Although serotonin transporter (SERT) availability in pons and medulla was similar in the restless legs syndrome (RLS) group and the control group, the severity of RLS symptoms increased as the availability of SERT decreased. These data partially support the hypothesis that an increase of serotonergic neurotransmission in the brainstem may exacerbate RLS, possibly via dual modulations on striatal dopaminergic neurotransmission and on the activities of spinal motor and sensory neurons.(C)2010AAN Enterprises, Inc.
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| Clinical/Scientific Notes |
phenotype of a patient with recessive centronuclear myopathy and a novel bin1 mutation.
- Claeys, K., MD, PhD, Maisonobe, T., Bohm, J., Laporte, J., Hezode, M., Romero, N., MD, PhD, Brochier, G., Bitoun, M., Carlier, R., Stojkovic, T.. Pages: 519-521
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severe cutaneous candida infection during natalizumab therapy in multiple sclerosis.
- Gutwinski, S., Erbe, S., Munch, C., Janke, O., Muller, U., Haas, J.. Pages: 521-523
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| Reflections: Neurology and the Humanities |
reflections for february: an economy of words.
- Jones, Lyell. Pages: 524-525
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| Resident & Fellow Section |
child neurology: past, present, and future: part 2: present training structure.
- Maski, Kiran, Jeste, Shafali, Darras, Basil. Pages: e17-e19
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teaching neuroimages: mri in fibrodysplasia ossificans progressiva.
- Shiva Kumar, R., Keerthiraj, B., Kesavadas, Chandrasekhran. Pages: e20
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| Correspondence |
prior antiplatelet use does not affect hemorrhage growth or outcome after ich 2.
- Naidech, Andrew, Bernstein, Richard, Alberts, Mark, Bleck, Thomas. Pages: 526-527
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teaching neuroimages: the full-blown neuroimaging of wernicke encephalopathy.
- Zuccoli, Giulio, Vaughan, Kevin. Pages: 527-528
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| Departments: Book Review |
clinical neurophysiology, 3rd edition.
- Kincaid, John, MD, FAAN. Pages: 529
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| Departments: Calendar |
calendar.
Pages: 530
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| Future Issues |
in the next issue of neurology(r): volume 74, number 7, february 16, 2010.
Pages: A32
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