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This Month in Archives of Neurology
June 2010

This Month in Archives of Neurology

Arch Neurol. 2010;67(6):659-660. doi:10.1001/archneurol.2010.106

Stem Cells and Spinal Muscular Atrophy

Ebert and SvendsenArticle address the generation of induced pluripotent stem cells from skin fibroblasts taken from various patient populations, with a specific focus on spinal muscular atrophy. These patient-derived cells may help devise more appropriate therapies through greater understanding of the molecular mechanisms that underlie neuron dysfunction and death in a number of diseases. Furthermore, they provide an ideal platform for small-molecule screening and subsequent drug development.

Nonmotor Symptoms in Genetic Parkinson Disease

Kasten and colleaguesArticle review current knowledge of nonmotor symptoms, particularly psychiatric features, in genetic Parkinson disease (PD) and provide original data for genetic and idiopathic PD. Nonmotor symptoms have a high impact on patients' quality of life and caregiver burden and should be considered as important and often treatable concomitant features of genetic PD.

Genetic Variation and Neuroimaging in Alzheimer Disease

Biffi et alArticle provide a multicenter case-control study of genetic and neuroimaging data from the Alzheimer Disease Neuroimaging Initiative. Genome-wide association studies–validated variants at the CR1 and PICALM loci and markers at 2 novel loci (BIN1 and CNTN5) showed association with multiple magnetic resonance imaging characteristics (false discovery rate P < .05). Loci associated with Alzheimer disease also influence neuroimaging correlates of this disease. Neuroimaging analysis identified 2 additional loci of high interest for further study. John Hardy, PhD, and Julie Williams, PhD, provide editorial perspective.Article

Cerebrospinal Fluid Abnormalities Across the Dementia Spectrum: Normal Aging, Mild Cognitive Impairment, and Alzheimer Disease

Okonkwo and colleaguesArticle investigate the effect of cerebrospinal fluid (CSF) abnormalities on rate of decline in everyday function in normal aging, mild cognitive impairment, and mild Alzheimer disease (AD). Total tau, tau phosphorylated at threonine 181, and β-amyloid 1-42 were immunoassayed in CSF obtained from participants in the AD Neuroimaging Initiative. Abnormalities in CSF are associated with functional decline, and thus with future development of AD in controls and patients with mild cognitive impairment.

Food Combination and Alzheimer Disease Risk: a Protective Diet

Gu and colleaguesArticle assess the association between food combination and Alzheimer disease risk. Because foods are not consumed in isolation, dietary pattern analysis of food combination that takes into account the interactions among food components may offer methodological advantages. This dietary pattern was characterized by higher intake of salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, and dark and green leafy vegetables, and lower intake of high-fat dairy products, red meat, organ meat, and butter.

Survival curves based on Cox analysis comparing cumulative Alzheimer disease incidence in subjects belonging to each dietary pattern (DP) score 2 tertile (P for trend <.001). Lowest tertile (black line) corresponds to the lowest adherence to DP 2; median tertile (dark-gray line), to median adherence; and highest tertile (light-gray line), to the highest adherence. The Figure was derived from a crude model that used all subjects (N = 2148).

Survival curves based on Cox analysis comparing cumulative Alzheimer disease incidence in subjects belonging to each dietary pattern (DP) score 2 tertile (P for trend <.001). Lowest tertile (black line) corresponds to the lowest adherence to DP 2; median tertile (dark-gray line), to median adherence; and highest tertile (light-gray line), to the highest adherence. The Figure was derived from a crude model that used all subjects (N = 2148).

B and T Lymphocytes and Chemokines With Rituximab Treatment in Multiple Sclerosis

Piccio et alArticle note that B cells are implicated in the pathogenesis of multiple sclerosis. A beneficial effect of B-cell depletion using rituximab has been shown, but the complete mechanism of action for the drug is unclear. They have determined the relationship between T cells, B cells, and changes in cerebrospinal fluid chemokines with rituximab, a monoclonal antibody that targets CD20. They report that B cells are critical for T-cell trafficking into the central nervous system in patients with multiple sclerosis.

Multiple Sclerosis After Allogeneic Hematopoietic Stem Cell Transplantation

Lu and colleaguesArticle indicate that allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be a therapeutic option in multiple sclerosis. Its effect on the brains of subjects with or without multiple sclerosis is evaluated by postmortem histopathological examination. They report that allo-HSCT fails to halt demyelination and inflammation in multiple sclerosis.

Outcome Predictors in First-Ever Acute Myelitis: A Retrospective Study of 53 Cases

Gajofatto et alArticle identified predictors of acute myelitis with short- and long-term outcomes. Patients with a first episode of acute myelitis were retrospectively identified from a neurological department database. Information regarding demographics, clinical status, laboratory evaluation, magnetic resonance imaging of the spine and brain, and electrophysiological assessment was collected. Tau, 14-3-3 protein, and cystatin C levels were assessed de novo in stored cerebrospinal fluid samples. They find that, in patients with first-ever acute myelitis, the conversion rate to multiple sclerosis was considerably high.

Predictors of Parkin Mutations

Marder and colleaguesArticle determined risk factors associated with carrying mutations in the parkin gene in a cross-sectional observational study from 13 movement disorders centers. They find that age at onset, Hispanic ethnicity, and family history of Parkinson disease are associated with carrying any parkin mutation. They emphasize that the increased odds of carrying a parkin mutation in Hispanic individuals warrants further study.

Professional Exposure to Organochlorine Insecticides in Parkinson Disease

Dutheil et alArticle note that the ABCB1 gene encodes the P-glycoprotein (P-gp), which acts as an efflux pump of endogenous compounds and xenobiotics to limit their cerebral penetration. Several pesticides, including organochlorines, are substrates and/or inhibitors of P-gp. They studied the association between Parkinson disease and 2 polymorphisms in the ABCB1 gene among subjects enrolled in the French health system for agricultural workers (Mutualité Sociale Agricole) as well as the interaction between ABCB1 and organochlorine insecticides. They find that the ABCB1 gene and exposure to organochlorine insecticides interact to increase Parkinson disease risk.

Clinical Dementia Rating Scale Sum of Boxes Score in the National Alzheimer Coordinating Center Database

O’Bryant et alArticle indicate that the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score can be used to accurately stage the severity of Alzheimer dementia and mild cognitive impairment. However, to date, the utility of these interpretive guidelines has not been cross-validated or applied to a heterogeneous sample of dementia cases. This study sought to cross-validate the staging guidelines utilizing the National Alzheimer Coordinating Center database. Their findings cross-validate the previously published CDR-SB interpretative guidelines for staging dementia severity and extend those findings to a large heterogeneous sample of patients with dementia.