H-reflex changes in the course of amyotrophic lateral sclerosis

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Abstract

In this study the H-reflex and M-wave were evoked in a group of ALS patients, to correlate the findings with the clinical state, and to investigate whether a statistical approach for assessing H-reflex changes in the presence of a constant M-wave could be reproducible and helpful in monitoring the course of amyotrophic lateral sclerosis (ALS). The H-reflex and M-wave from the soleus muscle were evoked at different stimulus strengths in 35 patients with definite ALS during the course of their illness. The mean amplitude of the H-reflexes (H-mean) obtained in different sessions within an established range of mean M-response amplitude (M-mean) was calculated. For each patient, M-mean was made constant across sessions. H-mean showed high reproducibility and two different trends of changes which emerged in a 1 year follow-up within the population: a significant progressive increase and a steady decrease. When grouped on the basis of their H-mean trend, the patients did not differ in terms of any clinical variables considered. However, the group with progressive increase of H-mean showed a better prognosis. This study has shown that H-mean is effective in assessing the clinical course of ALS and could be useful in monitoring drug effects during clinical trials.

Introduction

Changes in the amplitude of the H-reflex or in the shape of its recruitment curve, or both, have been widely used to study the excitability of the alpha-motorneurons (MNs) and its relationship to clinical signs of upper MN syndrome (Schieppati, 1987). However, the H-reflex has been rarely investigated in amyotrophic lateral sclerosis (ALS) (Raynor and Shefner, 1994; Soliven and Maselli, 1992) and little is known about its modifications in the course of the disease or its relationship with the clinical state. The reason is probably related to the various methodological problems involved such as the site of fixation of the stimulating electrodes, the determination of the motor threshold under conditions in which the structure of the nerve and muscle is continuously changing, and the reproducibility of the method given the decline in the number of motorneurons as the disease progresses. However, the procedure for evoking the H-reflex is reasonably quick and painless and the reflex response is easily quantified. Hence, its evaluation might still offer some advantage in the assessment of the course of the disease and in the monitoring of clinical trials. Therefore, we decided (1) to evoke the H-reflex and M-wave in a group of ALS patients and correlate the findings with the clinical state, and (2) to investigate whether a statistical approach for assessing H-reflex changes in the presence of a constant M-wave could be helpful in monitoring the course of ALS.

Section snippets

Patients and methods

We investigated 35 patients with definite ALS according to the criteria developed by the World Federation of Neurology(WFN Subcommittee on Motor Neuron Disease, 1994). Our analysis excluded cases with pure progressive muscular atrophy or primary lateral sclerosis. Patients were categorised as Spinal or Bulbar based upon the presenting symptoms. The duration of the disease was defined as the time span in months between the date of appearance of the first symptom (assumed to correspond to the

Reproducibility of the tests

Fig. 1 shows an example of the recruitment curves obtained over 3 consecutive days in one patient. The mean amplitude of the H-reflex values (H-mean) corresponding to M-waves ranging from 1.5 to 7.5 mV (same range for the 3 sessions), and the mean amplitudes of the M-waves falling in that range were calculated. Both values were not statistically different across the 3 sessions, with a P value>0.7 in all cases.

Table 1 shows the results of the reproducibility study concerning the selected

Discussion

The first finding in this study is that H-mean is an effective parameter for evaluating the progression of the excitability of a motorneuron pool in the course of amyotrophic lateral sclerosis. Basically, it is well reproducible, the variability within a single patient is much smaller than the total variability among all patients and the intraclass correlation coefficient is 0.96, which represents a high reproducibility. The correlation coefficient between successive recordings is also 0.95.

Acknowledgements

We thank Professor Marco Schieppati for his helpful suggestions and critical reading of the manuscript, and Ms. Rosemary Allpress for revising the English text.

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