title: Cortical hyperexcitability in patients with C9ORF72 mutations: Relationship to phenotype.
abstract: Patients with mutations in C9orf72 can have amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or ALS-FTD. The goals were to establish whether cortical hyperexcitability occurs in C9orf72 patients with different clinical presentations.
  
  
  
  Cortical thresholds and silent periods were measured in thenar muscles in 19 participants with C9orf72 expansions and 21 healthy controls using transcranial magnetic stimulation (TMS). El Escorial and Rascovsky criteria were used to diagnose ALS and FTD. Fourteen participants with C9orf72 expansions were re-tested 6 months later. Correlations with finger-tapping speed, timed peg test, the ALS functional rating scale, and Dementia Rating Scale were examined.
  
  
  
  Most participants with C9orf72 expansions had normal or low cortical thresholds. Among them, ALS patients had the lowest thresholds and significantly shorter silent periods. Thresholds correlated with timed peg-test scores. TMS did not correlate with the Dementia Rating Scale.
  
  
  
  TMS measures of cortical excitability may serve as noninvasive biomarkers of ALS disease activity. Muscle Nerve, 2016 Muscle Nerve 54: 264-269, 2016.
authors.affiliation: Motor Neuron Disorders Unit, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Schanz
authors.affiliation: Motor Neuron Disorders Unit, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Bageac
authors.affiliation: Motor Neuron Disorders Unit, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Braun
authors.affiliation: Neurogenetics of Neuromuscular Disease Section, National Institute of Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.affiliation: EMG section, National Institute of Neurological Disorders, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Tanya J
authors.initials: TJ
authors.lastname: Lehky
authors.affiliation: Motor Neuron Disorders Unit, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Floeter
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology*; D000073885:C9orf72 Protein; D002540:Cerebral Cortex / Q000503:physiopathology*; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000235:genetics / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D057180:Frontotemporal Dementia / Q000235:genetics / Q000473:pathology; D007839:Functional Laterality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D018709:Statistics, Nonparametric; D050781:Transcranial Magnetic Stimulation
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins
keywords: ALS; C9orf72; amyotrophic lateral sclerosis; cortical hyperexcitability; cortical silent period; frontotemporal dementia; transcranial magnetic stimulation