Peripheral and central motor conduction in amyotrophic lateral sclerosis
Introduction
The neurophysiological examination remains an essential investigation in confirming or refuting a clinical diagnosis of amyotrophic lateral sclerosis (ALS). Although the clinical features in advanced cases may leave little room for diagnostic doubt, at earlier stages in the disease clinical examination is rarely sufficient to differentiate between other potentially treatable conditions such as cervical spondylosis and multifocal motor neuropathy with conduction block (MMN) [10].
The classic electrodiagnostic criteria were defined by Lambert [19], while more recently they were revised in the El Escorial criteria [6]. Both sets of criteria require, in neurophysiological terms, signs of lower motor neurone (LMN) degeneration on needle electrode examination-fibrillation and fasciculation potentials, large motor unit action potentials and reduced recruitment. Sensory nerve conduction and motor conduction velocity (MCV) are expected to be normal, although mild motor slowing is allowed in the presence of small amplitude compound muscle action potentials (CMAPs). The El Escorial criteria allow mild abnormalities in F wave latency and central motor conduction time (CMCT), but neither set of criteria comment specifically on distal motor latency (DML).
A review of reported neurophysiological studies in ALS 3, 5, 9, 13, 17, 18, 28, shows that most patients meet the primary requirements of signs of LMN degeneration together with normal peripheral, sensory and motor nerve conduction. However abnormalities in DML, CMCT and to a lesser extent F waves and MCV, are seen in a number of patients.
Specifically, with respect to peripheral conduction, a prolonged DML is found in a number of patients in all studies. Behnia and Kelly [3]also found additional abnormalities of MCV and F wave latencies in a small number of patients.
With respect to CMCT measured by transcranial magnetic stimulation (TMS), there is considerable variation in the results obtained. Barker et al. [2], studying five patients, found normal CMCT to both cervical and lumbar regions. Berardelli et al. [4]found delayed responses in 15% of patients and Schriefer et al. [26]found prolonged CMCT in 12 sides from 22 patients. Claus [8]found an abnormal CMCT in 51% to upper or lower limbs of 63 patients, while Hugon et al. [16]studying 13 patients found an abnormal CMCT to lower limbs in all of them. Eisen et al. [11]reported that almost all of a group of 40 patients had abnormal responses to TMS due to prolonged CMCT or small amplitude or absent responses. This latter finding of small or absent responses to TMS is reported, to a varying degree, in all of these studies. The variation in the magnitude and prevalence of these abnormalities between studies is considerable and is probably a reflection of differences in both the clinical features of the patients studied, and neurophysiological methodology.
The aim of this study was to look specifically at peripheral and central motor conduction studies of ALS patients when they were first referred for neurophysiological evaluation, and to correlate the results with clinical features.
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Patients
All patients referred to the department for neurophysiological diagnosis of ALS over a 2-year-period from July 1995 onwards were eligible for inclusion in the study. Only patients fulfilling the primary requirements of the El Escorial criteria for definite or probable ALS, at their first or subsequent clinical and neurophysiological assessments were included in the final analysis. In total 65 patients met these criteria. The study had approval from the Local Ethics Committee.
The age, sex and
Results
Patients ranged between 32 and 85 years of age, and 40 of the 65 patients were male. The median duration of symptoms before the first neurophysiological examination was 356 days (range 64–2885). Fifteen patients died within the time period of the study. With respect to site of onset of symptoms, 25 were lower limb, 20 upper limb and 19 bulbar.
Of the 65 patients included in the study, recordings were made from 58 pairs of hands. Classification of hands according to physical findings yielded, 35,
Discussion
Although it is needle electromyography that provides the essential positive neurophysiological confirmation for a diagnosis of ALS, nerve conduction studies are necessary for differentiation from other neuropathies. The findings in our study, show abnormalities in both peripheral and central motor conduction in a significant number of patients.
The most prevalent abnormalities in peripheral studies were low amplitude CMAPs. As expected these correlated with hands showing signs of LMN involvement
Acknowledgements
This work was in part supported by the Motor Neurone Disease Association, UK, and a Wellcome Trust Fellowship (KN).
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