Transcranial magnetic stimulation in lower motor neuron diseases

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Abstract

Objective

To study the diagnostic value of transcranial magnetic stimulation (TMS) in a group of patients with lower motor neuron disease (LMND). Among LMND, several chronic immune mediate motor neuropathies may simulate amyotrophic lateral sclerosis (ALS).

Methods

Forty patients with LMND were included TMS was performed at the first visit. The patients were seen prospectively every 3 months for a period of 1–4 years.

Results

Three different groups were distinguished at the end of follow-up: (1) ALS group with 7 patients, (2) Pure motor neuropathy with 14 patients and (3) Other LMND including 12 patients with hereditary spinal amyotrophy, 3 patients with Kennedy's disease and 4 patients with post-poliomyelitis. On the basis of the results of TMS variables, 6 out of 7 ALS patients had abnormality of silent period (SP) associated or not with abnormality of excitatory threshold or amplitude ratio. Patients with pure motor neuropathy had normal SP and amplitude ratio. Four out of 14 patients had increased central motor conduction time (CMCT), one had increased CMCT and excitatory threshold, and one patient had a slightly increased excitatory threshold. Considering the abnormality of TMS variables in the groups, SP, excitatory threshold, and amplitude ratio were chosen in a post-hoc attempt to select variables yielding high sensitivity and specificity. The overall sensitivity of TMS for diagnosis of ALS among LMND was 85.7%, its specificity was 93.9%. When only the abnormality of SP was taken into account, the sensitivity was unchanged. But the specificity was improved to 100%.

Conclusions

TMS helped to distinguish suspected ALS from pure motor neuropathy.

Introduction

Among the lower motor neuron diseases (LMND) are several chronic motor neuropathies that have been suggested to be immune mediated. This group includes multifocal motor neuropathy with conduction block (Parry et al., 1986, Roth et al., 1986), proximal motor neuropathy associated with paraproteinemia (Parry et al., 1986, Rowland et al., 1982) or elevated GM1 antibodies (Pestronk, 1991), multifocal motor neuropathy without conduction block (Kornberg and Pestronk, 1995, Pakiam and Parry, 1998), and chronic motor axonal neuropathy (Attarian et al., 2004, Gorson et al., 1999, Katz et al., 2002, Kornberg and Pestronk, 1995, van den Berg-Vos et al., 2003). The clinical distinction between motor neuropathies and amyotrophic lateral sclerosis (ALS) without clinical upper motor neuron signs can be particularly difficult if conduction block or other electrodignostic features of demyelination are absent. However, it is essential to distinguish ALS from motor neuropathies since prognosis and treatment are totally different. Demonstration of subclinical involvement of corticospinal tract may allow suspected ALS to be distinguished from motor neuropathies. Studies have shown that transcranial magnetic stimulation (TMS) is a sensitive tool for the identification of upper motor neuron dysfunction in ALS patients (Desiato and Caramia, 1997, Di Lazzaro et al., 1999, Eisen and Swash, 2001, Eisen et al., 1990, Eisen et al., 1993, Magistris et al., 1999, Mills and Nithi, 1997, Pouget et al., 2000, Triggs et al., 1999, Urban et al., 1998).

The present study was undertaken prospectively in patients presenting clinical lower motor neuron involvement in order to determine the diagnostic value of TMS for distinguishing suspected ALS from pure motor neuropathies.

Section snippets

Patients

A group of 40 patients with LMND were included in this study. They were selected among 300 patients with motor neuron diseases, the majority of whom had possible, probable or definite forms of ALS. The final diagnosis was based on clinical signs, electrophysiological data and biological markers when available. For 19 patients a definite diagnosis was obtained rapidly (see Section 3). These patients formed the pathological control group in this study. The other 21 patients were followed in our

Results

At the end of the follow-up 3 different patient groups could be distinguished and the results of TMS study performed at the first visit were analyzed for each group:

Discussion

The main finding here is that in the LMND group, TMS revealed early subclinical abnormalities in patients who later developed obvious clinical upper motor neuron signs. TMS thus provides early clues for the diagnosis of ALS at the early stage of disease and helps to distinguish it from pure motor neuropathy. This is crucial since the prognosis and the treatment are quite different.

The main clinical diagnostic criterion was appearance of upper motor neuron signs during follow-up. These signs

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