title: Cortical excitability changes distinguish the motor neuron disease phenotypes from hereditary spastic paraplegia.
abstract: OBJECTIVE
  Cortical hyperexcitability has been identified as an important pathogenic mechanism in motor neuron disease (MND). The issue as to whether cortical hyperexcitability is a common process across the MND phenotypes, including amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), remains unresolved. Separately, the clinical distinction between PLS and 'mimic disorders' such as hereditary spastic paraparesis (HSP) may be difficult, potentially delaying diagnosis. Consequently, the aim of the present study was to determine the nature and spectrum of cortical excitability changes across the MND phenotypes, and to determine whether the presence of cortical dysfunction distinguishes PLS from HSP.
  
  
  METHODS
  Cortical excitability studies were undertaken on a cohort of 14 PLS, 82 ALS and 13 HSP patients with mutations in the spastin gene.
  
  
  RESULTS
  Cortical hyperexcitability, as heralded by reduction of short interval intracortical inhibition (PLS 0.26%, -3.8% to 1.4%; ALS -0.15%, -3.6% to 7.0%; P < 0.01) and cortical silent period duration (CSPPLS 172.2 ± 5.4 ms; CSPALS 178.1 ± 5.1 ms; P < 0.001), along with an increase in intracortical facilitation was evident in ALS and PLS phenotypes, although appeared more frequently in ALS. Inexcitability of the motor cortex was more frequent in PLS (PLS 71%, ALS 24%, P < 0.0001). Cortical excitability was preserved in HSP.
  
  
  CONCLUSIONS
  Cortical dysfunction appears to be an intrinsic process across the MND phenotypes, with cortical inexcitability predominating in PLS and cortical hyperexcitability predominating in ALS. Importantly, cortical excitability was preserved in HSP, thereby suggesting that the presence of cortical dysfunction could help differentiate PLS from HSP in a clinical setting.
authors: Westmead Clinical School, University of Sydney, Sydney, NSW, Australia.
authors: N
authors: N
authors: Geevasinga
authors: P
authors: P
authors: Menon
authors: C M
authors: CM
authors: Sue
authors: K R
authors: KR
authors: Kumar
authors: K
authors: K
authors: Ng
authors: C
authors: C
authors: Yiannikas
authors: M C
authors: MC
authors: Kiernan
authors: S
authors: S
authors: Vucic
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000503:physiopathology*; D055724:Electrophysiological Phenomena / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology; D016472:Motor Neuron Disease / Q000503:physiopathology*; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000503:physiopathology*; D000074181:Spastin; D055815:Young Adult
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human
keywords: hereditary spastic paraplegia; motor neuron disease; neurological disorders; neuromuscular diseases; primary lateral sclerosis