Motor unit firing in amyotrophic lateral sclerosis and other upper and lower motor neurone disorders
Highlights
► Testing the same target muscle by a conventional electromyographic (EMG) setting, with normal strength on clinical examination, could provide a tool to evaluate upper motor neuron dysfunction on firing rate. ► We observed that inter-individual firing rate variability in patients with upper motor neuron (UMN) lesion is decreased, as compared with patient with pure lower motor neuron dysfunction. ► We propose that this observation should be further explored in detail to find a sensitive method to identify UMN dysfunction in routine EMG investigation.
Introduction
Motor unit recruitment and firing is fundamental to voluntary movement and motor control. However, this aspect of the pathophysiology of human motor disorders has received little attention, although it has potential in categorizing different motor system disorders, for example lower and upper motor neurone disorders. The detection and quantification of upper motor neurone (UMN) disorder in amyotrophic lateral sclerosis (ALS) is a long-standing problem both in clinical practice and in research, despite assiduous but essentially subjective clinical testing and the advent of more complex methods, utilizing cortical magnetic stimulation and diffusion tensor magnetic resonance (MR) tractography. Both of the latter can detect cerebral motor system degeneration, including corticospinal tract involvement, although with undetermined sensitivity (Turner et al., 2009).
We considered that to be useful any method of studying motor unit firing should be applicable in the context of ordinary EMG practice. We have therefore studied this phenomenon by using standard concentric needle electromyography on slight voluntary contraction. This technique imposes limitations, principally that only the first-detected motor units can be studied, necessarily therefore at low discharge rates. However, motor unit firing in EMG recordings is not usually specifically evaluated in any detailed, quantitative fashion, although motor unit morphology and other parameters of the EMG discharge at low firing rates can be evaluated quantitatively using the standard inbuilt software provided in modern EMG equipment. Our objective was to analyze firing rates of motor units during slight voluntary activation in normal subjects and to compare these data with information from similar recordings made in patients with the three major clinical forms of motor neurone disease. i.e., amyotrophic lateral sclerosis, progressive muscular atrophy and primary lateral sclerosis, and also in patients with polyneuropathy and UMN syndromes associated with various spinal lesions. We set out to define the pattern of motor unit firing in these different disorders, and to discover any specific features associated with UMN compared to lower motor neurone (LMN) disease, and with ALS or other motor neurone syndromes. Off-line analysis of data from large numbers of patients enables such studies to be attempted in a manner not available to the pioneering investigators of a previous era.
Section snippets
Patients
We have studied normal subjects (n = 45) and five groups of patients with amyotrophic lateral sclerosis (ALS) (n = 36), primary lateral sclerosis (PLS) (n = 21), various upper motor neurone lesions (n = 16), progressive muscular atrophy (PMA) (n = 14), and other lower motor neurone lesions i.e., polyneuropathy (n = 42). Demographic and clinical details of these 174 patients and control subjects are given in Table 1.
Control subjects
The 45 control subjects were recruited from two sources. Twenty came for neurophysiological
Effect of age
In the control subjects the mean motor unit firing rate was 7.3 Hz (SD ± 0.86; CV 23.28% ± 7.13). There was no correlation between the coefficients of variation of amplitude, area, duration or firing rate with age in these normal subjects.
Firing rate
The data analysis is summarized in Table 2. Notably, the mean amplitude, area and duration of motor units was significantly greater in the groups of patients with PNP, ALS, PMA and PLS as compared with normal subjects. In addition the amplitude, area and duration
Discussion
Motor unit activation in normal human subjects was first studied by Adrian and Bronk (1929), in recordings from muscles using the concentric needle electrode. They noted that “force exerted by a muscle during a voluntary contraction was the result of the concurrent recruitment of motor units and modulation of the rate at which they discharged action potentials”. Denny-Brown and Pennybacker (1938) observed that in the process of recruitment of motor units in EMG recordings the first recruited
Acknowledgements
The first author acknowledges funding from the “Fundação para a Ciência e a Tecnologia”, SFRH/BD/30714/2006. This work was supported by “Fundação para a Ciência e Tecnologia” – PIC/IC/82765/2007.
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