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.

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.

Long-lasting conduction block in hereditary neuropathy with liability to pressure palsies.

We detected 29 conduction blocks in 12 patients with hereditary neuropathy and liability to pressure palsies. The blocks occurred at entrapment sites, most often the ulnar nerve at the elbow. Some had lasted for several years. This kind of block seems to be characteristic of the neuropathy, and may be related to the localized thickening of myelin ("tomacula"). In one patient with two permanent and severe blocks, neurolysis was beneficial.

Contraction response to muscle percussion is increased in peripheral nerve conduction block.

We studied the contraction of skeletal muscle upon direct percussion in 119 patients presenting with palsies related to focal peripheral nerve disorders. We compared the response of the paralyzed muscles with the response obtained on the contralateral normal side. The cause of the palsy was subsequently assessed by electrophysiological testing which disclosed: conduction block (CB), axonal, or mixed lesions (when both CB and denervation existed in similar proportions). Most of the time, the muscle response to percussion was increased in patients with CB (37/47), decreased in axonal lesions (44/53), and symmetric in mixed lesions (12/19). We conclude that distinction between CB and denervation is often possible on the basis of this simple bedside test.

Predictive value of anti-GM1 ganglioside antibodies in neuromuscular diseases: a study of 180 sera.

The incidence of anti-GM1 antibodies in the serum of 104 patients with neurological diseases, 35 patients with non-neurological diseases (NND) and 41 normal controls was determined by enzyme-linked immunosorbent assay (ELISA). Anti-GM1 antibodies were found in 90% of patients presenting with a motor neuropathy (all except one had multifocal conduction blocks). A large proportion (60%) of these patients displayed high antibody titer ranging from 101 to 788. A low incidence of anti-GM1 antibodies was found in the other groups of patients, i.e. 21% of amyotrophic lateral sclerosis (ALS), 26% of other neurological diseases (OND) and 23% of NND. High antibody titers ranging from 106 to 260 were found in two (5%) ALS patients, one (2%) OND patient (myasthenia gravis), and one (3%) NND patient (Waldenström's disease). This study shows that high titers of anti-GM1 antibodies are found in a large proportion of patients with motor neuropathy with multifocal conduction blocks. This argues for a possible autoimmune origin of this neuropathy. We suggest that anti-GM1 antibody determination should be included systematically in the evaluation of all patients with motor neuron diseases and predominantly motor neuropathies.

Neuromuscular disorder in intensive care unit patients treated with pancuronium bromide. Occurrence in a cluster group of seven patients and two sporadic cases, with electrophysiologic and histologic examination.

During six consecutive months, seven patients admitted to our ICU (15 beds, general ICU, approximately 300 intubated patients per year) for acute respiratory failure requiring intubation and mechanical ventilation presented with a peculiar neuromuscular disorder. After the occurrence of this cluster group of patients, we detected two more similar but isolated cases in the following 18 months, ie, altogether 9 patients in 2 years of observation, or 1.55 percent of all intubated patients in our ICU. Sedation was achieved using midazolam, curarization was effected with the neuromuscular non-depolarizing agent pancuronium bromide (PB), and corticosteroids were administered to eight patients. Shortly after discontinuation of sedation and curarization, we observed a persistent tetraparetic syndrome and/or peroneal palsy with a concomitant increase of serum creatine kinase (CK). None of the patients was septic or had the multisystem organ failure. A strong association between CK increase and PB administration was found, whereas no patient suffered severe liver or kidney failure. The duration of the neurologic deficit ranged from 4 to 52 weeks, with only partial recovery for some patients; the duration of dysfunction was apparently related to the total dose of corticosteroids received. Two patients had difficulty being weaned from the respirator and required tracheostomy. Electrophysiologic studies showed signs of axonal neuropathy and myopathic changes, ie, motor units of brief duration, small amplitude, overly abundant for the voluntary effort being exerted. Muscle biopsies showed significant myopathic alterations, with foci of muscle necrosis in most patients and minimal lymphocytic inflammation in one patient. The neurologic complication described differs from the polyneuropathy in critically ill patients. Furthermore, PB or corticosteroids or both appear to be the causal agents. The duration of the neuromuscular dysfunction may be related to concomitant steroid therapy. The CK enzyme seems to be a marker of the disorder. This disorder is associated with myopathic alterations and axonal degeneration in some patients. Pancuronium bromide should be used with caution, particularly when associated with steroids therapy, and it may cause difficulty in weaning patients from the respirator.

Rapid cortical motor output map changes assessed by the triple stimulation technique.

The amplitudes of motor evoked potentials (MEPs) were mapped by transcranial magnetic stimulation (TMS) using the triple stimulation technique (TST) in 11 normal individuals. Stimuli were given while the subjects were (a) distracted, (b) concentrating on their target (recorded) hand, and (c) concentrating on their contralateral hand. Within seconds, the proportion of excited motor units increased, similarly in all subjects, by an average of 70% from (a) to (b), and by 48% from (a) to (c). At the optimal stimulation site, results obtained with the TST were compared to those of conventional MEPs. The TST proved superior in detecting the rapid changes of the motor output caused by the non-specific mental tasks studied.

Cerebrospinal fluid in acute peripheral facial palsy.

Cerebrospinal fluid (CSF) is rarely analyzed in peripheral facial palsy, and reports in the literature are scarce. We report the CSF findings in 265 patients with acute isolated peripheral facial palsy. The CSF findings were abnormal in 11% of 230 patients with idiopathic peripheral facial palsy, in 60% of 17 patients with Ramsay Hunt syndrome (pleocytosis), in 25% of 8 patients with Lyme disease, in all of 8 patients with HIV infection, and in 2 other patients (sarcoidosis and herpes simplex). We conclude from this large series that the CSF is usually normal in idiopathic peripheral facial palsy. If the CSF is abnormal, a specific cause should be sought.

Amyotrophic lateral sclerosis versus cervical spondylotic myelopathy: a study using transcranial magnetic stimulation with recordings from the trapezius and limb muscles.

OBJECTIVE: We report an electrophysiological method to differentiate amyotrophic lateral sclerosis (ALS) from cervical spondylotic myelopathy (CSM). METHODS: Motor evoked potentials (MEPs) by transcranial magnetic stimulation were investigated in patients with ALS (n=10) and CSM (n=9). In addition to limb MEPs using the triple stimulation technique (TST) at upper limbs, MEPs recorded from trapezius muscles were compared with those obtained from 23 normal subjects. The parameters studied were: central motor conduction time, amplitude ratio and, for the trapezius, the interside asymmetry. RESULTS: Whereas limb MEPs were abnormal in most ALS and CSM patients (17/19), trapezius MEPs were abnormal in all ALS patients, and normal in 8 out of 9 CSM patients. CONCLUSION: Recording of trapezius MEPs is a valuable addition to the limb MEPs study, since it distinguishes ALS from SCM in most patients.

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.

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.

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.

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.

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.

Positive giant potentials: an electromyographic investigation.

Positive giant potentials (PGPs) consist of a peculiar EMG activity which is observed mostly in the large lower limb muscles, and mainly in men, either during the insertion of the needle electrode or during muscle contraction. PGPs have a shape similar to that of positive sharp waves, but with a larger amplitude (up to 25 mV). Their firing rate may reach 200 c/s. PGPs probably have no diagnostic significance since they are frequently observed in healthy individuals. They correspond to an insertional activity and should be recognized as such because they may be mistaken for giant motor unit potentials and thus be the source of diagnostic errors. The mechanism involved in the genesis of PGPs remains a matter of speculation.

[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.

Identification of motor conduction block despite desynchronisation. A method.

Identification of incomplete motor conduction block (CB) by the usual single stimulation method is problematic when impaired conduction velocity of the axons spared by the block exists at the site of the presumed CB, leading to desynchronisation. Indeed, the area of the compound muscle action potential (MAP) evoked by stimulation applied above this site may be reduced by the phase cancellation related to desynchronisation. A triple stimulation method with double collisions allows virtual displacement of the CB distally to the site where desynchronisation occurs. A first stimulus applied on the nerve above the site of the CB is followed--after a delay--by a stimulation applied distally on the nerve where a collision occurs. This collision, however, does not concern the antidromic wave of the blocked axons which travels towards the block. A third stimulus is then applied--after a second delay--below the site of the CB, where a second collision occurs in the blocked axons. Thus, the third stimulus evokes a MAP that concerns only the unblocked axons, as would the stimulus applied above the site of the CB. In this manner, desynchronisation occurring at the CB site is avoided. The method was developed on simulated CBs of the ulnar nerve at the elbow of 33 normal subjects and compared with the usual single stimulation method. Subsequently, it was evaluated on 8 pathological CBs of the ulnar nerve at the elbow and of the peroneal nerve at the fibular head. The method detects CBs of 5% or more despite the occurrence of desynchronisation.