Central and peripheral components of exercise-related fatigability in myotonic dystrophy type 1.

BACKGROUND: Fatigue frequently occurs in myotonic dystrophy type 1 (DM1), but its pathophysiology remains unclear. This study assessed central and peripheral components of exercise-related fatigability in patients with DM1, compared to controls. METHODS: Examinations were performed before and after a contraction of the abductor digiti minimi (ADM) muscle sustained for 45 s at 60% of maximal voluntary contraction (MVC). Myoelectric activity was recorded using high spatial resolution surface EMG during twitch stimulations and MVC and was characterized by root mean square, mean power frequency (MPF), and muscle fiber conduction velocity (MFCV). Peripheral nerve excitability was assessed by stimulating the ulnar nerve at the wrist with ADM recordings. Motor cortex excitability testing to transcranial magnetic stimulation included measures of intracortical facilitation and inhibition of motor evoked potentials (MEPs) in ADM muscle. RESULTS: At baseline, patients with DM1 showed altered peripheral nerve and cortical excitability (reduced intracortical facilitation) associated with impaired myoelectric properties. During the fatiguing exercise, the force remained stable, while MPF and MFCV decreased in both DM1 and control groups. After exercise, only refractoriness was reduced in patients with DM1, whereas controls showed marked neuromuscular and cortical changes. CONCLUSION: Patients with DM1 showed altered excitability of various cortical and neuromuscular components at baseline. However, most of excitability parameters did not vary after exercise in patients with DM1, in contrast to controls. This suggests that excitability properties, frankly altered at baseline, were not prone to be affected further after exercise in patients with DM1.

Stimulus-response curve of human motor nerves: multicenter assessment of various indexes.

The value of various indexes to characterize the stimulus-response curve of human motor nerves was assessed in 40 healthy subjects recruited from four European centers of investigation (Créteil, Lausanne, Liège, Marseille). Stimulus-response curves were established by stimulating the right median and ulnar motor nerves at the wrist, with stimulus durations of 0.05 and 0.5 ms. The following parameters were studied: the threshold intensity of stimulation to obtain 10% (I 10), 50% (I 50), and 90% (I 90) of the maximal compound muscle action potential, the ratios I 10/I 50, I 90/I 50, (I 90 - I 10)/I 10, (I 90-I 50)/I 50, and (I 50 - I 10)/I 10, and the slopes of the stimulus-response curves with or without normalization to I 50. For each parameter, within-center variability and reproducibility (in a test-retest study) were assessed and between-center comparisons were made. For most of the parameters, the results varied significantly within and between the centers. Within the centers, only the ratios I 10/I 50 and I 90/I 50 were found constant and reproducible. Between the centers, the absolute intensity thresholds (I 10, I 50, I 90) and the ratio I 90/I 50 did not show significant differences at stimulus duration of 0.5 ms, whatever the stimulated nerve. The reduced variability and good reproducibility of the ratios I 10/I 50 and I 90/I 50 open perspectives in neurophysiological practice for the use of these indexes of the stimulus-response curve, a rapid and noninvasive test.

Walking capacities in multiple sclerosis measured by global positioning system odometer.

We used a global positioning satellite technology odometer to determine the maximum objective walking distance capacity (MOWD) of patients with multiple sclerosis (MS). The MOWD correlated with Expanded Disability Status Scale (EDSS) score (r(2) =0.41; P <0.0001), the MSWS-12 scale (r(2) =0.46; P <0.0001), time to walk 10 m (r(2) =0.51; P <0.02) and walking speed (r(2) =0.75; P <0.001). Limitation of walking capacities was measurable up to 4550 m, strikingly above the 500-m limit of the EDSS. This objective odometer is a promising tool for evaluation and follow-up of patients with MS.

[Nerve excitability studies in the assessment of dysimmune neuropathies]. / Etude de l'excitabilité nerveuse dans l'exploration des neuropathies dysimmunitaires.

INTRODUCTION: Various changes in axonal membrane excitability might explain negative symptoms in dysimmune neuropathies, e.g., acute or chronic inflammatory demyelinating neuropathies or multifocal neuropathies with persistent conduction blocks. Several electrophysiological methods have recently been designed to specifically assess such axonal membrane excitability changes. STATE OF ART: Resting and action potentials are related to ionic movements through the axonal membrane, mainly involving various types of sodium and potassium channels, as well as the ATP-dependent Na+/K+ pump. The functional status of these channels and pumps can be assessed in man, by studying the excitability recovery cycle after a single impulse, the strength-duration and stimulus-response curves, and the effects of hyperpolarization and depolarization depending on activity (voluntary contraction), ischemia or application of prolonged subthreshold currents. Various features of altered axonal membrane excitability might characterize dysimmune neuropathies, according to the course of the disease and its treatment. PERSPECTIVES: This electrophysiological approach allowed changes in axonal membrane properties to be objectively determined. In particular, some results obtained with these methods could explain the rapid action of intravenous immunoglobulins, and various pathophysiological mechanisms of conduction block or axonal degeneration. CONCLUSIONS: Nerve excitability studies appeared to be useful for the diagnosis and the follow-up of dysimmune neuropathies. New therapeutical strategies for such neuropathies will be probably developed in the future intending to improve nerve function by acting on axonal membrane excitability.

[Pathophysiology and treatment of fatigue in multiple sclerosis]. / Physiopathologie et traitement de la fatigue dans la sclérose en plaques.

Patients suffering from multiple sclerosis (MS) frequently complain of fatigue (53 to 92 percent depending on studies). Fatigue can be one of the most disabling symptoms of MS and presents as physical or mental fatigue in daily living activities. Besides this permanent feeling of exhaustion, MS patients can suffer from an abnormal tiredness and lack of energy after a given motor or mental task, which defines fatigability. A number of studies explored the origins of fatigue and fatigability by means of subjective and objective tools. The implication of central nervous system dysfunctions has been established in several studies; however the contribution of peripheral nervous system factors and systemic abnormalities associated with inflammatory and immunological parameters was also suggested. The aim of this review is to present the different types of fatigue and fatigability occurring in MS patients, their origins, the investigation tools which allow the quantification of fatigue and fatigability and characterization of their mechanisms. The currently available therapeutic strategies that have been proposed to relieve this disabling symptom are presented.

Central and peripheral fatigue of the knee extensor muscles induced by electromyostimulation.

The main purpose of this study was to characterise neuromuscular fatigue induced by 30 contractions of the knee extensor muscles evoked by electromyostimulation (EMS). Twelve healthy subjects were tested before and after a typical EMS session (frequency: 75 Hz, on-off ratio: 6.25 s on-20 s off) used for quadriceps femoris muscle strengthening. Surface electromyographic (EMG) activity and torque obtained during maximal voluntary and electrically evoked contractions were analysed to distinguish peripheral from central fatigue. Maximal voluntary torque of the knee extensor muscles decreased approximately 20 % (p < 0.001) following EMS. In the same way, peak torque associated to single (p < 0.05) and paired (p < 0.001) stimuli as well as M-wave amplitude (p < 0.05) significantly decreased as a result of EMS. The raw EMG activity of both vastus lateralis and rectus femoris muscle recorded during maximal voluntary isometric contraction significantly decreased after the session (-17.3 and -14.5 %, respectively) whereas no changes were observed when EMG signals were normalised to respective M-wave amplitudes. Similarly, voluntary activation estimated by using the twitch interpolation technique was unchanged following EMS. In conclusion, a typical session of EMS of the knee extensor muscles mainly induced neuromuscular propagation failure while excitation-contraction coupling and neural mechanisms were not significantly affected. It is recommended to interpret surface EMG data together with the corresponding M wave, at least for the knee extensor muscles, in order to distinguish peripheral from central causes of fatigue.

[Methods and clinical value of peripheral nerve refractory period measurement in man]. / Méthodes et intérêt clinique de la mesure de la période réfractaire nerveuse périphérique chez l'homme.

Immediately after action potential occurrence, owing to transient sodium channel inactivation, axon excitability is reduced for a short period of time, including the absolute refractory period, a first period of total inexcitability, followed by the relative refractory period. There are basically two different stimulation protocols to estimate axonal refractoriness, i.e. "paired-pulse" and "collision" techniques. Refractory period has been assessed in various conditions and appeared to depend on several physiological or methodological factors, featuring the type of nerve or the characteristics of the subject, but also the technique of stimulation or the method of data analysis. In addition, refractory periods can be altered by pathological conditions. Several studies showed prolonged refractory periods in patients suffering from alcoholic, diabetic or toxic neuropathies. Refractory period abnormality is a sensitive marker of axonal dysfunction as observed in Guillain-Barré syndrome, carpal tunnel syndrome or multiple sclerosis. Thus, the measurement of the refractory periods is a valuable tool to study the pathophysiology of peripheral nerves, complementary to standard nerve conduction studies. However, the application of these techniques in the routine practice of clinical neurophysiology remains limited.

Vaccination of leukemic mice with viable drug-altered leukemic cells.

The treatment in vivo with anti-tumour drugs can induce an antigenic alteration of L1210 leukemia resulting in the rejection of an inoculum of 10 X 10(6) viable cells in syngeneic mice. As drug-induced antigens appeared in excess of any pre-existing tumour-associated transplantation antigens (TATA), viable altered cells have been used to sensitize syngeneic animals. Experiments showed that viable altered cells elicited stronger anti-TATA reaction than X-inactivated parental cells, as measured by host survival to a challenge of L1210 leukemia. TATA immunogenicity of parental cells has been preminent, in the strain of animals used, to determine the sensitizing effectiveness of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) cells. Host protection to an inoculum of parental tumours has been more proficient with the DTIC subline derived from highly immunogenic L1210Ha cells than from poorly immunogenic L1210Cr cells. Immunoprophylactic inocula, proper chemotherapeutic treatments and adoptive transfer of immune lymphocytes used in combination exerted a synergic host protection.