Novel threshold tracking techniques suggest that cortical hyperexcitability is an early feature of motor neuron disease.

Full Abstract

The dying forward hypothesis of motor neuron disease (MND) suggests that corticomotoneurons induce excitotoxic anterior horn cell death, with involvement of the glutamatergic neurotransmitter system. The aim of the present study was to apply novel threshold tracking transcranial magnetic stimulation (TMS) techniques in conjunction with peripheral nerve excitability studies in MND patients to further investigate the dying forward hypothesis and possibly determine the site of disease onset. Studies were undertaken in 23 MND patients using a 90-mm circular coil connected to a BiStim magnetic stimulator for cortical studies and electrical stimulation for peripheral nerve excitability studies. Motor-evoked potentials and compound muscle action potentials (CMAPs) were recorded from the right abductor pollicis brevis in the same setting. Measures of cortical and peripheral nerve excitability were correlated with clinical and neurophysiological parameters of disease severity. Short-interval intracortical inhibition (SICI) was significantly reduced in MND patients compared with controls (MND group = 3.6 +/- 0.8%; controls = 8.5 +/- 1.0%, P < 0.001), most prominently in MND patients with limb-onset disease. Changes in intracortical inhibition were accompanied by alterations in the magnetic stimulus-response curve, cortical silent period duration and resting motor threshold, all indicative of cortical hyperexcitability. Although the reduction in SICI was more pronounced in MND patients with less severe disease, as assessed by the CMAP amplitude, it remained evident even in MND patients with advanced disease. Measures of peripheral disease burden, namely the CMAP amplitude (r = -0.6) and neurophysiological index (r = -0.6), correlated with cortical hyperexcitability changes, as did the strength-duration time constant (r = -0.6), a peripheral marker of axonal excitability. Simultaneous assessment of central and peripheral nerve excitability has established the presence of co-existent upper and lower motor neuron dysfunction, with cortical hyperexcitability an early feature in MND.

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Author information

Author/s: Vucic, Steve (S); Kiernan, Matthew C (MC);

Affiliation: Prince of Wales Medical Research Institute and Prince of Wales Clinical School, University of New South Wales, Prince of Wales Hospital, Randwick, Sydney, Australia.

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: Brain : a journal of neurology (Brain), published in England. (Language: eng)

Reference: 2006-Sep; vol 129 (issue Pt 9) : pp 2436-46

Dates: Created 2006/08/22; Completed 2006/10/04; Revised 2006/11/15;

PMID: 16835248, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Action Potentials - physiology
Adult
Aged
Axons - physiology
Cell Death - physiology
Electric Stimulation - methods
Evoked Potentials, Motor - physiology
Female
Humans
Male

Male
Median Nerve - physiopathology
Middle Aged
Motor Cortex - physiopathology
Motor Neuron Disease - physiopathology
Motor Neurons - physiology
Muscle Contraction - physiology
Muscle, Skeletal - physiopathology
Neural Inhibition
Transcranial Magnetic Stimulation - methods

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