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Microglia, the resident inflammatory cells of the CNS, are the only CNS cells that express the fractalkine receptor (CX3CR1). Using three different in vivo models, we show that CX3CR1 deficiency dysregulates microglial responses, resulting in neurotoxicity. Following peripheral lipopolysaccharide injections, Cx3cr1-/- mice showed cell-autonomous microglial(More)
We performed magnetic resonance imaging and magnetic resonance spectroscopic imaging on 28 patients with multiple sclerosis stratified for disability and clinical course (relapsing with at least partial remissions or secondary progressive disease). Lesions were segmented on the conventional proton density and T2-weighted magnetic resonance images, and(More)
The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in(More)
OBJECTIVE In familial amyotrophic lateral sclerosis (fALS) harboring superoxide dismutase (SOD1) mutations (fALS1), SOD1 toxicity has been linked to its propensity to misfold and aggregate. It has recently been proposed that misfolded SOD1 may be causative of all types of ALS, including sporadic cases (sALS). In the present study, we have used a specific(More)
PURPOSE To study whether inconsistent findings in voxel-based morphometry (VBM) in amyotrophic lateral sclerosis (ALS) brain are due to use of different data preprocessing and statistical methods in two software packages. MATERIALS AND METHODS T1-weighted magnetic resonance imaging (MRI) was obtained during routine clinical imaging at 1.5T in ALS patients(More)
The multisubunit Golgi-associated retrograde protein (GARP) complex is required for tethering and fusion of endosome-derived transport vesicles to the trans-Golgi network. Mutation of leucine-967 to glutamine in the Vps54 subunit of GARP is responsible for spinal muscular atrophy in the wobbler mouse, an animal model of amyotrophic lateral sclerosis. The(More)
OBJECTIVE Since the discovery of mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) ten years ago, testing for SOD1 gene mutations has become a part of the investigation of patients with suspected motor neuron disease. We searched for novel SOD1 mutations and for clinical characteristics of patients with these mutations. METHODS Analysis was(More)
OBJECTIVE To evaluate dextromethorphan combined with ultra low-dose quinidine (DMq) for treating pseudobulbar affect (PBA) in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). METHODS In a 12-week randomized, double-blind trial, ALS and MS patients with clinically significant PBA (a baseline score ≥13 on the Center for(More)
BACKGROUND Mitochondrial dysfunction occurs early in the course of ALS, and the mitochondria may be an important site for therapeutic intervention. Creatine stabilizes the mitochondrial transition pore, and is important in mitochondrial ATP production. In a transgenic mouse model of ALS, administration of creatine prolongs survival and preserves motor(More)
OBJECTIVE Amyotrophic lateral sclerosis (ALS) is a devastating, and currently incurable, neuromuscular disease in which oxidative stress and mitochondrial impairment are contributing to neuronal loss. Coenzyme Q10 (CoQ10), an antioxidant and mitochondrial cofactor, has shown promise in ALS transgenic mice, and in clinical trials for neurodegenerative(More)