Annals of neurology
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Annals of neurology · Nov 2016
Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's.
We hypothesized that specific mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non-neuropathic GD mutations confer intermediate progression rates. ⋯ Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into "high gear." These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674-685.
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Annals of neurology · Nov 2016
Case ReportsTherapy with eculizumab for patients with CD59 p.Cys89Tyr mutation.
The objective of this work was to report on the outcome of eculizumab treatment in pediatric patients with recurrent acute predominantly motor, demyelinating neuropathy with conduction block, and chronic hemolysis attributed to p.Cys89Tyr mutation in the CD59 gene. ⋯ Eculizumab was safely administered to these patients. Marked clinical improvement suggests that eculizumab may be a life-saving treatment for patients with acute predominantly motor, demyelinating neuropathy with conduction block, and secondary axonal damage attributed to primary p.Cys89Tyr mutation in the CD59 gene. Ann Neurol 2016;80:708-717.
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Annals of neurology · Nov 2016
Neuroinflammatory component of gray matter pathology in multiple sclerosis.
In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with 11 C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation. ⋯ In MS, neuroinflammation is present in the cortex, cortical lesions, deep GM, and NAWM, is closely linked to poor clinical outcome, and is at least partly linked to neurodegeneration. Distinct inflammatory-mediated factors may underlie accumulation of cortical and WM lesions. Quantification of TSPO levels in MS could prove to be a sensitive tool for evaluating in vivo the inflammatory component of GM pathology, particularly in cortical lesions. Ann Neurol 2016;80:776-790.