The cortico-diaphragmatic pathway involvement in amyotrophic lateral sclerosis: Neurophysiological, respiratory and clinical considerations

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Abstract

Cortico-diaphragmatic pathway was investigated by means of transcranial magnetic stimulation (TMS), in 14 patients affected by definite amyotrophic lateral sclerosis (ALS) without clinical signs of respiratory impairment. Spirometry, gas analysis, and measurement of static inspiratory and expiratory pressures were performed in all patients.

Forced vital capacity, forced expiratory volume at the first and second peak expiratory flow, sniff effort from FRC level (SNIP), maximal inspiratory and expiratory pressure at mouth (MIP/MEP), maximal transdiaphragmatic pressure (Pdimx) were considered. TMS was performed, recording by surface electrodes from hemidiaphragm, bilaterally. Latency of cortical and spinal motor-evoked potentials (Cx-MEP/Sp-MEP) and central motor conduction time (CMCT) were measured.

None of the patients showed altered spirometry and gas levels. Seven patients showed decreased Pdimx and eight of MEP values. Four patients showed a delayed Sp-MEP. In one patient the Cx-MEP was abolished while the mean values of both Cx-MEP and CMCT were significantly increased (19.2 ± 4.1 ms, P < 0.0001; 10.8 ± 4.8 ms, P < 0.0001). Cx-MEP and CMCT did not show significant correlations with any of the respiratory measures. The patients with prolonged Sp-MEP, showed longer disease duration, lower Norris score, lower Pdimx and MEP values. In conclusion, cortico-diaphragmatic study is a sensitive measure to reveal subclinical diaphragmatic impairment although not correlated to respiratory measures.

Introduction

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive disease characterised by signs of lower motor neurone involvement variably combined with those of upper motor neurone lesion, leading inexorably to death. The fatal event, in most cases, is due to ventilatory failure caused by respiratory muscle weakness [1].

An impaired diaphragmatic strength is a major factor for the respiratory failure in the ALS patients, and its accurate and reliable measurement, a major concern in the management of the ALS patient.

The measure of the transdiaphragmatic pressure has been considered a more reliable and accurate assessment of the diaphragmatic strength [2], [3]. Nevertheless the use of such measure can be questionable in a large population of ALS patients, who may frequently present severe bulbar signs and deglutition impairment.

More recently, transcranial magnetic stimulation has been demonstrated to be highly informative of the upper motor neurone impairment in the respiratory drive in several neurological disorders [4], [5], [6], [7], [8], with great advantage as to being non-invasive, well tolerated by the patients, and non-volitional, and hence independent by their compliance. Nevertheless, this technique has been scantly employed in the study of the respiratory function of ALS patients [9], [10].

In a recent paper [9], transcranial magnetic stimulation recording from diaphragm was applied to a group of ALS patients, according to the presence or absence of dyspnea. Cortico-diaphragmatic abnormalities were common in ALS patients and more pronounced in those reporting dyspnea. Such dysfunction could stem from upper motor neurone abnormalities and was linked to dyspnea. However, the clinical relevance of the use of central motor conduction time (CMCT) from diaphragm remains to be investigated. For this reason we performed the present study aimed at investigating the respiratory function in a sample of ALS patients without severe bulbar signs and clinical respiratory symptoms, to evaluate the role of the cortico-diaphragmatic involvement in the respiratory dynamic of these patients and its relationship with either invasive or non-invasive conventional respiratory tests.

Section snippets

Materials and methods

Fourteen ALS patients (1 female and 13 males; mean age 51.9 ± 11.2 years, range 31–60 years) without dyspnoea were selected for the study. The diagnosis of motor neurone disease was based on the patient's history, clinical examination and neurophysiological tests. All the patients had “definite” forms of ALS according to the El Escorial diagnostic criteria [11]. The mean disease duration was 28.7 ± 10.1 months (range 13–46 months). The severity of the disease was measured by the Norris score [12].

Respiratory tests

The mean values of spirometric and gas analysis for the whole population of patients were in the normal range. None of the patients showed PCO2 and PO2 alterations. Only two patients (14.3%) showed decreased PEF values. Four and three out of fourteen patients (28.5% and 21.4%) showed pathological values of MIP and SNIP, respectively; these percentages markedly increased at Pdimx and MEP tests: in fact seven and eight patients (50% and 57.1%), respectively, presented altered values. The detailed

Discussion

The present study investigated the cortico-diaphragmatic pathway by means of magnetic stimulation in a sample of ALS patients without signs and symptoms of respiratory failure, and without severe bulbar involvement, and it combined the non-invasive and non-volitional neurophysiological technique of magnetic stimulation, with validated non-invasive/invasive, volitional respiratory tests.

Magnetic stimulation of the motor cortex seems particularly indicated to investigate the neurophysiological

Acknowledgements

We are grateful to Dr. Lorenzo Appendini for the measurement of the respiratory pressures.

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