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Cortical excitability in hereditary motor neuronopathy with pyramidal signs: comparison with ALS
  1. S Vucic1,2,
  2. G A Nicholson3,
  3. M C Kiernan2
  1. 1
    Department of Neurology, Westmead Hospital, Western Clinical School, University of Sydney, Sydney, Australia
  2. 2
    Prince of Wales Medical Research Institute and Prince of Wales Clinical School, University of New South Wales, Sydney, Australia
  3. 3
    Molecular Medicine and Neurobiology Laboratories, ANZAC Medical Research Institute, University of Sydney, Concord Hospital NSW, Sydney, Australia
  1. Correspondence to Dr M C Kiernan, Prince of Wales Medical Research Institute, Barker Street, Randwick, Sydney, NSW 2031, Australia; m.kiernan{at}


Background: Distal hereditary motor neuronopathy with pyramidal features (dHMNP) is a hereditary neurodegenerative disorder characterised by the presence of upper and lower motor neuron signs. The pathophysiological mechanisms underlying these clinical findings remain elusive. Given that cortical hyperexcitability appears to underlie neurodegeneration in amyotrophic lateral sclerosis (ALS), a disorder that may clinically resemble dHMNP, the present study applied novel cortical excitability studies to further investigate the pathophysiological mechanisms in dHMNP.

Methods: Threshold tracking transcranial magnetic stimulation (TMS) studies were undertaken using a 90 mm circular coil. Peripheral nerve excitability was performed by stimulating the median nerve at the wrist, with recording made over the abductor pollicis brevis muscle. Studies were undertaken in six dHMNP and 52 ALS patients, and compared with 55 normal controls.

Results: Central motor conduction time (CMCT) was significantly prolonged in dHMNP (dHMNP 7.7 (SEM 0.7) ms; ALS 4.9 (0.3) ms; controls 5.1 (0.2) ms, p<0.01). Short interval intacortical inhibition (SICI) was significantly reduced in ALS patients (0.8 (0.8)%) when compared with dHMNP (6.4 (0.7)%, p<0.0001) and controls (8.6 (1.1)%, p<0.0001). Reduction in SICI was accompanied by significant increases in the magnetic stimulus–response curve gradient and intracortical facilitation, and reduction in cortical silent period duration in ALS, while all these parameters of cortical excitability were normal in dHMNP.

Conclusions: The present study has established a prolonged CMCT and normal cortical excitability in dHMNP, thereby providing further support for the hypothesis that cortical hyperexcitability underlies neurodegeneration in ALS.

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  • SV had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding Motor Neuron Disease Research Institute of Australia (MNDRIA) and National Health and Medical Research Council of Australia (Project grant number 510233).

  • Competing interests None.

  • Ethics approval Ethics approval was provided by South East Sydney Area Health Service Human Research Ethics Committee.

  • Patient consent Obtained.

  • SV had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Provenance and Peer review Not commissioned; externally peer reviewed.