J Neurol Neurosurg Psychiatry doi:10.1136/jnnp-2012-304019
  • Neuromuscular
  • Review

Transcranial magnetic stimulation and amyotrophic lateral sclerosis: pathophysiological insights

  1. Matthew C Kiernan2,6
  1. 1Sydney Medical School Westmead, University of Sydney, Sydney, New South Wales, Australia
  2. 2Neuroscience Research Australia, Sydney, New South Wales, Australia
  3. 3Department of Neurology and Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls University, Tübingen, Germany
  4. 4Division of Neurology, The University of British Columbia, Vancouver, British Columbia, Canada
  5. 5Human Motor Control Section, NINDS, NIH, Bethesda, Maryland, USA
  6. 6Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia
  1. Correspondence to Associate Professor Steve Vucic, Sydney Medical School Westmead, University of Sydney, Darcy and Hawkesbury Rd, Wentworthville, Sydney, NSW 2045, Australia; s.vucic{at}
  • Received 20 September 2012
  • Revised 20 November 2012
  • Accepted 25 November 2012
  • Published Online First 21 December 2012


Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the motor neurons in the motor cortex, brainstem and spinal cord. A combination of upper and lower motor neuron dysfunction comprises the clinical ALS phenotype. Although the ALS phenotype was first observed by Charcot over 100 years ago, the site of ALS onset and the pathophysiological mechanisms underlying the development of motor neuron degeneration remain to be elucidated. Transcranial magnetic stimulation (TMS) enables non-invasive assessment of the functional integrity of the motor cortex and its corticomotoneuronal projections. To date, TMS studies have established motor cortical and corticospinal dysfunction in ALS, with cortical hyperexcitability being an early feature in sporadic forms of ALS and preceding the clinical onset of familial ALS. Taken together, a central origin of ALS is supported by TMS studies, with an anterograde transsynaptic mechanism implicated in ALS pathogenesis. Of further relevance, TMS techniques reliably distinguish ALS from mimic disorders, despite a compatible peripheral disease burden, thereby suggesting a potential diagnostic utility of TMS in ALS. This review will focus on the mechanisms underlying the generation of TMS measures used in assessment of cortical excitability, the contribution of TMS in enhancing the understanding of ALS pathophysiology and the potential diagnostic utility of TMS techniques in ALS.

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