Corticospinal output and loss of force during motor fatigue.

The objective of this study was to analyze central motor output changes in relation to contraction force during motor fatigue. The triple stimulation technique (TST, Magistris et al. in Brain 121(Pt 3):437-450, 1998) was used to quantify a central conduction index (CCI = amplitude ratio of central conduction response and peripheral nerve response, obtained simultaneously by the TST). The CCI removes effects of peripheral fatigue from the quantification. It allows a quantification of the percentage of the entire target muscle motor unit pool driven to discharge by a transcranial magnetic stimulus. Subjects (n = 23) performed repetitive maximal voluntary contractions (MVC) of abductor digiti minimi (duration 1 s, frequency 0.5 Hz) during 2 min. TST recordings were obtained every 15 s, using stimulation intensities sufficient to stimulate all cortical motor neurons (MNs) leading to the target muscle, and during voluntary contractions of 20% of the MVC to facilitate the responses. TST was also repetitively recorded during recovery. This basic exercise protocol was modified in a number of experiments to further characterize influences on CCI of motor fatigue (4 min exercise at 50% MVC; delayed fatigue recovery during local hemostasis, "stimulated exercise" by 20 Hz trains of 1 s duration at 0.5 Hz during 2 min). In addition, the cortical silent period was measured during the basic exercise protocol. Force fatigued to approximately 40% of MVC in all experiments and in all subjects. In all subjects, CCI decreased during exercise, but this decrease varied markedly between subjects. On average, CCI reductions preceded force reductions during exercise, and CCI recovery preceded force recovery. Exercising at 50% for 4 min reduced muscle force more markedly than CCI. Hemostasis induced by a cuff delayed muscle force recovery, but not CCI recovery. Stimulated exercise reduced force markedly, but CCI decreased only marginally. Summarized, force reduction and reduction of the CCI related poorly quantitatively and in time, and voluntary drive was particularly critical to reduce the CCI. The fatigue induced reduction of CCI may result from a central inhibitory phenomenon. Voluntary muscle activation is critical for the CCI reduction, suggesting a primarily supraspinal mechanism.

[Clinical findings, electroneuromyography and MRI in trauma of the brachial plexus]. / Aspects cliniques, électroneuromyographiques et IRM des traumatismes du plexus brachial.

OBJECTIVES: Management of traumatic lesions of the brachial plexus mainly depends on whether the injury is pre- (nerve root avulsion) or postganglionic (trunks and cords). The aim of this study was to assess the diagnostic and prognostic value of MRI in such lesions, and to determine any correlations among radiological, clinical and electroneuromyographical (EMG) data from both the initial and follow-up studies. MATERIAL AND METHODS: Nine patients with acute traumatic lesions of the brachial plexus were investigated by MRI and EMG. Five further patients served as controls. The MRI protocol included fast spin-echo (FSE) T2-weighted and STIR sequencing. These scans were independently interpreted by two senior radiologists. Their findings were then validated during consensus meetings of surgeons, radiologists and neurologists to identify the exact localization and mechanism of each lesion, and to determine the advantages and drawbacks of each technique. RESULTS: Among the nine patients, MRI scans were judged as normal in three whereas EMG showed distal lesions in two of them. In a further three patients, STIR MRI sequences demonstrated high signal intensities from the trunks and cords of C5 to T1. Among these three patients, MRI at three months showed persistence of these signal anomalies in one patient, and partial regression in the two others. In the remaining three patients, three-dimensional T2-weighted sequences showed nerve root avulsion, consistent with the initial EMG findings. CONCLUSION: MRI is the best technique to demonstrate nerve root avulsion. However, unlike EMG, MRI does not allow visualization of distal lesions of the brachial plexus. Differentiation between edema (reversible) and demyelination (irreversible) of trunk and cord lesions remains difficult, and requires EMG or late MRI.

[Amyotrophic lateral sclerosis: differential diagnosis and frontier forms]. / Sclérose latérale amyotrophique: diagnostic différentiel et formes frontières.

Amyotrophic lateral sclerosis (ALS) may be mimicked by disorders affecting the different levels of the motor system from cortex to muscle. Clinical heterogeneity is a feature of both ALS and related syndromes allowing for a large differential diagnosis. During the initial stage of a motor disorder false positive and false negative diagnoses of ALS are possible. Examples of disorders that should not be misdiagnosed as ALS, because their prognosis and treatment differ, are multifocal motor neuropathy, Kennedy's bulbospinal atrophy, cervical myelopathy, hyperthyroidism and hyperparathyroidism. Syndromes remote from polio and radiation treatments should be recognised. Eventually, frontier forms of ALS with signs restricted to either the upper or lower motor neurons deserve particular attention. Electrodiagnosis is pivotal to disclose signs and extension of the peripheral motor neuron, to detect and quantify cortico-spinal involvement, to search for specific signs of conditions that mimic ALS. Until specific markers become available, clinical evaluation supported by electrodiagnosis and other ancillary tests are crucial to provide with the correct diagnosis, prognosis and treatment.

[Pathogenic mechanisms of neurodegenerative diseases: amyotrophic lateral sclerosis]. / Mécanismes pathogéniques des maladies neurodégénératives: l'exemple de la sclérose latérale amyotrophique.

Since its description by Charcot in 1869, the mechanism underlying the characteristic selective degeneration and death of motor neurons in amyotrophic lateral sclerosis (ALS) has remained a mystery. There is no effective remedy for this progressive, fatal disorder. Modern genetics have now identified two genes, SODI and ALS2 as primary causes of the disease and has implicated others as potential contributors. These insights have enabled development of model systems to test hypotheses of disease mechanism and potential therapies. Along with errors in the handling of synaptic glutamate and the potential excitotoxic response that it provokes, these model systems underscore the involvement of non-neuronal cells in disease progression and provide new therapeutic strategies.

Quantification of central motor conduction deficits in multiple sclerosis patients before and after treatment of acute exacerbation by methylprednisolone.

OBJECTIVE: To compare the effects of intravenous methylprednisolone (IVMP) in patients with relapsing-remitting (RR-MS), secondary progressive (SP-MS), and primary progressive multiple sclerosis (PP-MS). METHODS: Clinical and neurophysiological follow up was undertaken in 24 RR-MS, eight SP-MS, and nine PP-MS patients receiving Solu-Medrol 500 mg/d over five days for exacerbations involving the motor system. Motor evoked potentials (MEPs) were used to measure central motor conduction time (CMCT) and the triple stimulation technique (TST) was applied to assess conduction deficits. The TST allows accurate quantification of the number of conducting central motor neurones, expressed by the TST amplitude ratio. RESULTS: There was a significant increase in TST amplitude ratio in RR-MS (p<0.001) and SP-MS patients (p<0.02) at day 5, paralleling an increase in muscle force. TST amplitude ratio and muscle force remained stable at two months. In PP-MS, TST amplitude ratio and muscle force did not change. CMCT did not change significantly in any of the three groups. CONCLUSIONS: In RR-MS and SP-MS, IVMP is followed by a prompt increase in conducting central motor neurones paralleled by improvement in muscle force, which most probably reflects partial resolution of central conduction block. The lack of similar clinical and neurophysiological changes in PP-MS corroborates previous clinical reports on limited IVMP efficacy in this patient group and points to pathophysiological differences underlying exacerbations in PP-MS.

Repetitive spinal motor neuron discharges following single transcranial magnetic stimuli: a quantitative study.

OBJECTIVE: To quantify repetitive discharges of spinal motor neurons (repMNDs) in response to single transcranial magnetic stimuli (TMS). To assess their contribution to the size of motor evoked potentials (MEPs). METHODS: We combined the triple stimulation technique (TST) with an additional nerve stimulus in the periphery (= quadruple stimulation; QuadS). The QuadS eliminates the first action potential descending on each axon after TMS, and eliminates effects on response size induced by desynchronization of these discharges, thereby allowing a quantification of motor neurons (MNs) discharging twice. In some instances, a quintuple stimulation (QuintS) was used, to quantify the number of MNs discharging three times. Recordings were from the abductor digiti minimi of 14 healthy subjects, using two different stimulation intensities and three different levels of facilitatory muscle pre-contractions. RESULTS: The threshold to obtain repMNDs was high. Their maximal size differed markedly between subjects, ranging from 8 to 52% of all MNs. Stimulation intensity and facilitatory muscle contraction, but not resting motor threshold, correlated with the amount of repMNDs. QuintS never yielded discernible responses, hence all observed repMNDs were double discharges. RepMNDs contributed to the MEP areas, but did not influence MEP amplitudes. CONCLUSIONS: QuadS and QuintS allow precise quantification of repMNDs. The threshold of repMNDs is high and varies considerably between subjects. SIGNIFICANCE: repMNDs have to be considered when MEP areas are measured. Their analysis may be of interest in neurological disorders, but standardized stimulation parameters appear essential.

Quantification of Uhthoff's phenomenon in multiple sclerosis: a magnetic stimulation study.

OBJECTIVE: To quantify temperature induced changes (=Uhthoff phenomenon) in central motor conduction and their relation to clinical motor deficits in 20 multiple sclerosis (MS) patients. METHODS: Self-assessment of vulnerability to temperature and clinical examination were performed. We used motor evoked potentials to measure central motor conduction time (CMCT) and applied the triple stimulation technique (TST) to assess conduction failure. The TST allows an accurate quantification of the proportion of conducting central motor neurons, expressed by the TST amplitude ratio (TST-AR). RESULTS: Temperature induced changes of TST-AR were significantly more marked in patients with prolonged CMCT (P=0.037). There was a significant linear correlation between changes of TST-AR and walking velocity (P=0.0002). Relationships were found between pronounced subjective vulnerability to temperature and (i) abnormal CMCT (P=0.02), (ii) temperature induced changes in TST-AR (P=0.04) and (iii) temperature induced changes in walking velocity (P=0.04). CMCT remained virtually unchanged by temperature modification. CONCLUSIONS: Uhthoff phenomena in the motor system are due to varying degrees of conduction block and associated with prolonged CMCT. In contrast to conduction block, CMCT is not importantly affected by temperature. SIGNIFICANCE: This is the first study quantifying the Uhthoff phenomenon in the pyramidal tract of MS patients. The results suggest that patients with central conduction slowing are particularly vulnerable to develop temperature-dependent central motor conduction blocks.

Assessment of central motor conduction to intrinsic hand muscles using the triple stimulation technique: normal values and repeatability.

OBJECTIVE: To establish the triple stimulation technique (TST) for recordings from the first dorsal interosseus (FDI) and the abductor pollicis brevis muscles (APB), and to analyse the test-retest repeatability of the TST measurements in APB. METHODS: The recently developed TST was slightly modified for recordings from small hand muscles to account for volume conducted activity from surrounding muscles. The TST combines transcranial magnetic stimulation (TMS) with a peripheral collision technique [Magistris et al. Brain 121 (1998) 437]. In contrast to conventional motor-evoked potentials (MEPs), it quantifies the number of conducting central motor neurons (expressed by the TST amplitude ratio, TST-AR). MEPs and TST were performed in 30 sides of 25 healthy subjects (target muscle FDI), and in 29 sides of 21 healthy subjects (target muscle APB). All APB recordings were repeated after 25+/-5.9 days. RESULTS: The TST-AR averaged 97.4+/-2.5% in FDI and 95.9+/-4.7% in APB. There was a mean difference of the TST-AR ratio of 2.9+/-3.1% between the repeated APB recordings (95% limits of agreement+/-6.3%). CONCLUSIONS: TMS allows activation of virtually all motor neurons supplying FDI and APB, when effects of volume conduction are eliminated. Its test-retest repeatability is excellent. SIGNIFICANCE: The TST is well suited for follow-up examinations of central motor conduction failures. The greater number of established target muscles widens its clinical applicability.

[Strategies to interpret late waves in routine neurophysiology]. / Stratégies d'interprétation des ondes tardives en neurophysiologie de routine.

A number of late waves other than F and H spinal waves are commonly observed during motor nerve conduction studies. Simple criteria are available that allow an understanding of their origin and significance. A late wave can be characterized by 1) its origin, proximal or distal to the stimulator, 2) its position with reference to the spinal waves, 3) its latency, stable or not, 4) its appearance in response to all (constant) or not to all stimuli (inconstant), 5) its persistence or not to intense stimuli, 6) its relative threshold, 7) its behavior to paired stimuli (namely if it is or not evoked twice by paired stimuli). By use of these criteria, one may distinguish the late waves that are evoked proximal to the stimulator (indirect late waves), such as the spinal responses (H and F), the motor axon reflex and the indirect double discharge, from those late waves that originate distally to the stimulator (direct late waves) such as the late potential, the myo-axonal ephaptic response and the direct double discharge. Signification of these late waves in relation to peripheral nerve disorders is discussed. Late potentials, motor axon reflex and ephaptic myo-axonal responses are signs of a prior axonal lesions, whereas indirect double discharges relate to an ongoing demyelinating process.

[Neuropathy versus neuronopathy: distinctive features]. / Comment distinguer une neuropathie d'une neuronopathie?

Neuropathy may be difficult to distinguish from neuronopathy, on both motor and sensory sides. A number of disorders that present with characteristic electro-clinical features are readily recognized. Except for those, distinction of the lesions that concern the peripheral nerve cell or the axon may require support of clinical, electrophysiological and other ancillary tests. Distinction between motor neuropathy and neuronopathy can be based on the abnormalities of nerve conduction and on the signs that relate to the reinnervation process. Signs of terminal axonal reinnervation, such as motor axon reflex, may be observed in axonal neuronopathies, whereas only collateral reinnervation occurs in motor neuronopathies. Sensory axonopathies are usually characterized by clinical and electrophysiological findings that are axon length-dependent, by the course of the disorder that is most often chronic, and by possible reversibility. Sensory neuronopathies are usually subacute and induce clinical deficits that are more or less widespread to the whole body surface rather than distal. Follow-up studies disclose limited or absent recovery. A better knowledge of the structural differences of motor and sensory neurons and axons will improve our understanding and lead to the development of specific tests. Meanwhile, although some parameters and techniques should still be improved, electrophysiological and additional tests are useful to detect and to distinguish the peripheral nerve disorders that affect the nerve cell bodies and their axons.

[Lombosacral radiculopathy (L3-S1) and specificity of multifidus EMG]. / Radiculopathies lombosacrées (L3-S1) et spécificité de l'EMG du muscle multifidus.

AIMS OF THE STUDY: This prospective study tried to establish, in a group of patients with lombosacral radiculopathy, whether the electromyography of the multifidus muscles following the "Paraspinal Mapping" described by Haig and colleagues (1991, 1993, 1995, 1997) allows to specify the exact level of the radiculopathy. MATERIAL AND METHODS: Twenty-three patients with symptoms of mono or pluriradiculopathy were submitted to an EMG of the lower limbs and multifidus muscles at different levels in accordance to the "Paraspinal Mapping" cartography. RESULTS AND CONCLUSION: No patient had signs of acute denervation in the multifidus muscles that corresponded exclusively to the suspected levels as determined by clinical and radiological examinations. No patient had signs of acute denervation in the multifidus muscles without associated signs in the lower limb muscles. Conversely, four patients had signs of acute denervation in the lower limb muscles without any signs in the multifidus muscles. In our small series, the EMG of the multifidus muscles was neither sensitive nor specific and did not allow by itself topographical diagnosis.

Central motor conduction differs between acute relapsing-remitting and chronic progressive multiple sclerosis.

OBJECTIVE: To characterize central motor conduction in relation to the clinical deficits and to the disease duration in 90 patients with acute relapsing-remitting MS (RR-MS) and in 51 patients with chronic primary or secondary progressive MS (P-MS). METHODS: The triple stimulation technique (TST) was used to quantify the central motor conduction failure (expressed by the TST amplitude ratio) and conventional motor evoked potentials (MEPs) were used to measure the central motor conduction time (CMCT). RESULTS: The TST amplitude ratio was reduced in presence of a clinical motor deficit (p=0.02 for RR-MS, p<0.01 for P-MS), but did not significantly differ in RR-MS and P-MS (p>0.05) when patients with similar clinical motor deficit were compared. The CMCT was not related to the clinical motor deficit in both RR-MS and P-MS. However, the CMCT was markedly prolonged in P-MS, when patients with similar clinical motor deficit and with similar disease duration were compared (p<0.01). The differences were not attributable to differential involvement of the spinal cord, which was similar in RR-MS and P-MS. CONCLUSIONS: Our results disclose differences between the central motor conduction in RR-MS and P-MS that are not related to disease severity, spinal cord involvement or disease duration.

Endplate dysfunction causing respiratory failure in a patient with prior paralytic poliomyelitis.

A 56-year-old man with late amyotrophic sequelae from poliomyelitis experienced progressive dyspnoea requiring intubation and artificial ventilation in the intensive care unit. Repetitive stimulation studies showed a marked decrement of the trapezius muscle response reversible with edrophonium. Ventilatory function considerably and lastingly improved under anticholinesterase treatment. In the absence of biological evidence for autoimmune myasthenia gravis, it is suggested that a mechanism implying endplate dysfunction related to postpolio syndrome. Repetitive stimulation procedure should be considered in postpolio syndrome patients as some of them may benefit from anticholinesterase treatment.

[Critical illness neuropathies]. / Neuropathies de réanimation.

A number of patients admitted to intensive care units for non-neurological disorders develop neuromuscular complications. These patients present with an acute flaccid generalized weakness that may or may not be accompanied by sensory symptoms. There are two main conditions, namely critical illness polyneuropathy and neuromuscular disorder related to the use of neuromuscular blocking agents. These conditions differ in several ways. Critical illness polyneuropathy occurs usually after long stays (weeks) in intensive care units. It concerns patients presenting with a multiple organ dysfunction syndrome, and often sepsis. The polyneuropathy is axonal and implies both sensory and motor fibres. Its pathophysiology remains unclear. Mortality is as high as 60 p.cent and relates to the medical, rather than to the neurological condition. In survivors recovery may be complete, although over a period of months. Neuromuscular disorder related to the use of neuromuscular blocking agents occurs on average after 10 days. It most often concerns patients admitted to intensive care units for acute respiratory failure, mainly asthma or adult respiratory distress syndrome, that may require mechanical ventilation, use of neuromuscular blocking agents and steroids. A purely motor deficit is usually first noticed when curarisation is discontinued. Electromyography discloses fibrillation potentials in all muscles, as well as myopathic changes. Muscle biopsy demonstrates necrosis and a deficit in myosin filaments. In severe cases, injury to distal motor axons probably occurs. Recovery is usually excellent over a few weeks. Recently, replacement of neuromuscular blocking agents by sedatives has notably reduced the occurrence of this disorder. Critical illness neuropathies often cause difficulty in weaning patients from the respirator. They prolong the stay in the intensive care unit, thereby increasing the risks of complications for the patients. Course of these neuromuscular disorders is usually favorable, however sometimes with sequelae.

The triple stimulation technique to study central motor conduction to the lower limbs.

OBJECTIVE: To quantify the percentage of motor units of a foot muscle that can be activated by transcranial magnetic stimulation (TMS) in normal subjects and patients. METHODS: We adapted the recently described triple stimulation technique (TST) for recordings from abductor hallucis (AH). Conventional motor evoked potentials (MEPs) of this muscle are usually small and variable in shape, because of an important temporal desynchronization of the TMS induced spinal motor neuron discharges. The TST allows 'resynchronization' of these discharges and thereby a quantification of the proportion of motor units activated by TMS. The lower limb (LL-) TST was applied to 33 sides of 18 normal subjects and 51 sides of 46 patients with multiple sclerosis, amyotrophic lateral sclerosis, or spinal cord disorders. RESULTS: In healthy subjects, the LL-TST demonstrated that TMS achieves activation of virtually all motor neurons supplying the AH. In 33 of 51 patient sides, abnormal LL-TST responses suggested corticospinal conduction failures of various degrees. The LL-TST was 2.54 times more sensitive to detect central conduction failures than the conventional LL-MEPs. Combining the LL-TST with TST of the upper limbs further increased the sensitivity to detect a conduction failure by 1.50 times. CONCLUSION: The LL-TST markedly improves the examination of corticospinal pathways.

[Treatment of recurrent luxation of the temporomandibular joint with botulinum toxin]. / Traitement de la luxation temporo-mandibulaire récidivante par toxine botulique.

We report the case of a 70-year-old man who suffered recurrent dislocations of the temporomandibular joint secondary to severe Parkinson syndrome. The patient was given repeated injections of botulinum toxin. After 3 injections over a 9-month period, no further dislocation occurred. Botulinum toxin may be an alternative to surgery.

Quantification of upper motor neuron loss in amyotrophic lateral sclerosis.

OBJECTIVE: To quantitatively estimate upper motor neuron (UMN) loss in ALS. METHODS: We used the recently developed triple stimulation technique (TST) to study corticospinal conduction to 86 abductor digiti minimi muscles of 48 ALS patients. This method employs a collision technique to estimate the proportion of motor units activated by a transcranial magnetic stimulus. At the same time, it yields an estimate of lower motor neuron (LMN) integrity. RESULTS: The TST disclosed and quantified central conduction failures attributable to UMN loss in 38 sides of 24 patients (subclinical in 15 sides), whereas conventional motor evoked potentials detected abnormalities in only 18 sides of 12 patients (subclinical in two sides). The increased sensitivity of the TST to detect UMN dysfunction was particularly observed in early cases. Increased central motor conduction times (CMCT) occurred exclusively in sides with conduction failure. In sides with clinical UMN syndromes, the TST response size (but not the CMCT) correlated with the muscle weakness. In sides with clinical LMN syndromes, the size of the peripherally evoked compound muscle action potentials correlated with the muscle weakness. CONCLUSION: The TST is a sensitive method to detect UMN dysfunction in ALS. It allows a quantitative estimate of the UMN loss, which is related to the functional deficit. Therefore, the TST has a considerable impact on diagnostic certainty in many patients. It will be suited to follow the disease progression and therapeutic trials.