Learn More
BACKGROUND The progranulin gene (GRN) is mutated in 5-10% of patients with frontotemporal lobar degeneration (FTLD) and in about 20% of patients with familial FTLD. The most common mutation in GRN is Arg493X. We aimed to establish the contribution of this mutation to FTLD and related disorders. METHODS We measured the frequency of Arg493X in 3405(More)
The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were(More)
The authors sought to determine trends in the incidence of ALS in Olmsted County from 1925 to 1998. Seventy-seven cases of ALS were identified during the period studied. The incidence rate remained stable at 1.7 cases per 100,000 people per year. Mean age at onset was 63 years. Mean survival was 23 months from diagnosis. Mean survival for patients <60 years(More)
BACKGROUND Preclinical and clinical studies of gabapentin in patients with ALS led the authors to undertake a phase III randomized clinical trial. METHODS Patients were randomly assigned, in a double-blinded fashion, to receive oral gabapentin 3,600 mg or placebo daily for 9 months. The primary outcome measure was the average rate of decline in isometric(More)
BACKGROUND Frontotemporal dementia and amyotrophic lateral sclerosis are neurodegenerative diseases associated with TAR DNA-binding protein 43- and ubiquitin-immunoreactive pathologic lesions. OBJECTIVE To determine whether survival is influenced by symptom of onset in patients with frontotemporal dementia and amyotrophic lateral sclerosis. DESIGN,(More)
BACKGROUND We recently described a genomic pathway approach to study complex diseases. We demonstrated that models constructed using single nucleotide polymorphisms (SNPs) within axon guidance pathway genes were highly predictive of Parkinson disease (PD) susceptibility, survival free of PD, and age at onset of PD within two independent whole-genome(More)
BACKGROUND A small proportion of patients with amyotrophic lateral sclerosis (ALS) survive more than 5 years. The frequency of 5-year or longer survival with ALS in a USA population is unknown but may provide a baseline for studies that employ survival as a primary endpoint of analysis. METHODS All persons diagnosed as having ALS in Olmsted County between(More)
BACKGROUND Although spinal-bulbar muscular atrophy (SBMA) is generally believed to be associated with better survival and function compared to other motor neuron diseases, no systematic study of long-term functional status or survival has been reported. METHODS We report the results a retrospective review of 39 patients with genetically confirmed(More)
Combining agents with different mechanisms of action may be necessary for meaningful results in treating ALS. The combinations of minocycline-creatine and celecoxib-creatine have additive effects in the murine model. New trial designs are needed to efficiently screen the growing number of potential neuroprotective agents. Our objective was to assess two(More)