title: Cortical hyperexcitability precedes lower motor neuron dysfunction in ALS.
abstract: OBJECTIVE
  To determine whether cortical hyperexcitability preceded the development of lower motor neuron (LMN) dysfunction in sporadic amyotrophic lateral sclerosis (ALS).
  
  
  METHODS
  Cortical excitability studies were undertaken in 24 ALS patients with motor evoked potential (MEP) recorded over the abductor pollicis brevis (APB) muscle. In the same sitting, LMN function of the target APB muscle was assessed utilising qualitative and quantitative electromyography techniques along with axonal excitability studies.
  
  
  RESULTS
  At time of assessment, the anatomical and functional integrity of the lower motor neuronal circuits innervating the target APB muscle was preserved in all patients, confirmed by a normal CMAP amplitude (P=0.37), absence of fasciculations, or features of neurogenic change. Despite this apparent 'normality' cortical dysfunction was evident, with significant reduction of short interval intracortical inhibition (P<0.01), resting motor threshold (P<0.05) and cortical silent period duration (P<0.001), along with increases in MEP amplitude (P<0.05) and intracortical facilitation (P<0.05).
  
  
  CONCLUSIONS
  The findings in the present study suggest that cortical hyperexcitability occurs upstream to a seemingly intact lower motor neuronal system.
  
  
  CONCLUSIONS
  Corticomotoneuronal dysfunction appears to be a primary event in ALS, suggesting a cortical origin of the disease.
authors.affiliation: Sydney Medical School Westmead, University of Sydney, Australia.
authors.forename: Parvathi
authors.initials: P
authors.lastname: Menon
authors.affiliation: Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
authors.affiliation: Sydney Medical School Westmead, University of Sydney, Australia. Electronic address: s.vucic@neura.edu.au.
authors.forename: Steve
authors.initials: S
authors.lastname: Vucic
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000503:physiopathology*; D015331:Cohort Studies; D004576:Electromyography / Q000379:methods; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009046:Motor Neurons / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology; D011446:Prospective Studies; D050781:Transcranial Magnetic Stimulation / Q000379:methods
keywords: Amyotrophic lateral sclerosis; Cortical hyperexcitability; Dying forward; Motor neuron