Chronic fatigue syndrome: Abnormally fast muscle fiber conduction in the membranes of motor units at low static force load.

OBJECTIVE: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are disorders of unknown etiology and unclear pathophysiology, with overlapping symptoms of - especially muscular -fatigue and pain. Studies have shown increased muscle fiber conduction velocity (CV) in the non-painful muscles of FM patients. We investigated whether CFS patients also show CV abnormalities. METHODS: Females with CFS (n = 25), with FM (n = 22), and healthy controls (n = 21) underwent surface electromyography of the biceps brachii, loaded up to 20% of maximum strength, during short static contractions. The mean CV and motor unit potential (MUP) velocities with their statistical distribution were measured. RESULTS: The CV changes with force differed between CFS-group and both FM-group and controls (P = 0.01). The CV of the CFS-group increased excessively with force (P < 0.001), whereas that of the controls increased only slightly and non-significantly, and that of the FM-group did not increase at all. In the CFS-group, the number of MUPs conveying very high conduction velocities increased abundantly with force and the MUPs narrowed. CONCLUSION: Our results suggest disturbed muscle membrane function in CFS patients, in their motor units involved in low force generation. Central neural deregulation may contribute to this disturbance. SIGNIFICANCE: These findings help to detangle the underlying mechanisms of CFS.

Fibromyalgia: Increased reactivity of the muscle membrane and a role of central regulation.

OBJECTIVE: Fibromyalgia (FM) is characterized by widespread muscle pain and central neural deregulation. Previous studies showed increased muscle fiber conduction velocity (CV) in non-painful muscles of FM patients. This study investigates the relationship between central activation and the CV in FM. METHODS: Twenty-two females with primary FM and 21 controls underwent surface electromyography of the non-painful biceps brachii. Mean CVs were calculated from the motor unit potential velocities (CV-MUPs), and the CV-MUPs' statistical distributions were presented as histograms. The amount of muscle activity (average rectified voltage, ARV) was measured. RESULTS: The CV was higher in the FM-group than in the controls (P = 0.021), with CV-MUPs generally shifted to higher values, indicative of increased muscle membrane propagation speeds. The largest increase in the CV of the FM-group occurred when adopting and maintaining a limb position at only 5% of maximum strength (P < 0.001); the CV did not, as normal, increase with greater force. However, the ARV in both groups similarly increased with force. CONCLUSIONS: In fibromyalgia patients, the muscle membrane propagation speed increases independently of the force load or amount of muscle activity produced. When adopting a limb position, the patients show an augmented muscle membrane reaction, suggesting deregulation from higher neural centers. SIGNIFICANCE: These findings contribute to understanding fibromyalgia.

Effects of vibration-induced fatigue on the H-reflex.

Vibration exercise (VE) has been suggested as an effective training for improving muscle strength and coordination. However, the underlying physiological adaptation processes are not yet fully understood, limiting the development of safe and effective exercise protocols. To better understand the neuromuscular responses elicited by VE, we aimed at investigating the acute effects of superimposed vibration on the Hoffmann reflex (H-reflex), measured after fatiguing exercise. Twenty-five volunteers performed four isometric contractions of the right Flexor Carpi Radialis (FCR) with baseline load at 80% of their maximal voluntary contraction (MVC), both with no vibration and with superimposed vibration at 15, 30, and 45 Hz. Fatigue was estimated by MVC test and estimation of electromyographic spectral compression. H-reflex suppression was estimated as the relative decrease after exercise. Our results show that fatiguing exercise determined a decrease in H-reflex amplitude compared to rest condition while vibration determined a lower H-reflex suppression as compared to no vibration. The superimposition of 30-Hz vibration determined the largest acute reduction in force generating capacity (36 N, p < 0.05) and the lowest H-reflex suppression (20%, p < 0.05). These results suggest VE to be particularly suitable in rehabilitation programs for rapid restoration of muscle form and function after immobilization periods.

Loss of motor unit size and quadriceps strength over 10 years in post-polio syndrome.

OBJECTIVE: To investigate whether strength decline in post-polio syndrome (PPS) results from excessive distal axonal degeneration of enlarged motor units. METHODS: We assessed changes over 10 years in isometric quadriceps strength, mean motor unit action potential (MUAP) size, root mean squared (RMS) amplitude, and level of interference (LOI) in 47 patients with PPS and 12 healthy controls, using high density surface EMG. At baseline, all patients had symptomatic quadriceps dysfunction, evidenced by transmission defects on single-fibre EMG. RESULTS: MU size and strength declined significantly by 20% and 15%, respectively in patients with PPS. Those with the largest initial MU sizes exhibited the greatest losses of mean MU size (27%) and proportional decreases in quadriceps strength (23%). Initial strength, change in LOI and change in RMS amplitude together explained 35% of the variability in strength changes in patients. MU size of controls did not change, although they lost 29% strength. CONCLUSIONS: MU size and strength declined concomitantly in a homogeneous cohort of patients with PPS and quadriceps dysfunction. SIGNIFICANCE: This long term follow-up study provides evidence that size diminution of enlarged MUs combined with a reduced number of active MUs contributes to the gradual strength decline in PPS.

The role of physical activity and physical fitness in postcancer fatigue: a randomized controlled trial.

PURPOSE: Patients suffering from postcancer fatigue have both an inferior physical activity and physical fitness compared to non-fatigued cancer survivors. The aims of this study were (1) to examine the effect of cognitive behavior therapy, an effective treatment for postcancer fatigue, on physical activity and physical fitness and (2) to examine whether the effect of cognitive behavior therapy on postcancer fatigue is mediated by physical activity and/or physical fitness. METHODS: Severely fatigued cancer survivors were randomly assigned to either the intervention (cognitive behavior therapy) or the waiting list condition. After assigning 23 patients in the intervention condition and 14 patients in the waiting list condition, they were assessed both at baseline and 6 months later. Physical activity was assessed via actigraphy and physical fitness was assessed by a maximal exercise test. A nonparametric bootstrap approach was used to test the statistical significance of the mediation effects. RESULTS: A significant increase in physical activity was observed in the intervention group from baseline to follow-up, whereas physical activity did not change from baseline to follow-up in the waiting list group. Physical fitness did not significantly change after cognitive behavior therapy or after 6 months of waiting for therapy. Fatigue decreased more significantly in the intervention group than in the waiting list group. The mediation hypotheses were rejected. CONCLUSIONS: Cognitive behavior therapy effectively reduced postcancer fatigue and increased physical activity but did not change physical fitness. The effect of cognitive behavior therapy on postcancer fatigue is not mediated by a change in physical activity or physical fitness.

Maximal exercise performance in patients with postcancer fatigue.

PURPOSE: The aim of this study is to examine whether physical fitness of severely fatigued and non-fatigued cancer survivors, as measured by maximal exercise performance, is different between both groups and, if so, whether this difference can be explained by differences in physical activity, self-efficacy regarding the exercise test, and/or social support. METHODS: Severely fatigued (n = 20) and sex- and age-matched non-fatigued (n = 20) disease-free cancer survivors, who completed treatment for a malignant, solid tumor at least 1 year earlier, participated in this case-control study. Maximal oxygen consumption was measured during an incremental cycling exercise test. Physical activity was assessed via actigraphy. Self-efficacy regarding the test and social support were assessed via questionnaires to study its relationship with physical fitness. RESULTS: Maximal oxygen consumption was significantly lower in fatigued compared to non-fatigued participants. Actual physical activity, self-efficacy regarding the test, and negative interactions of social support were significantly different between both groups. However, after inclusion of these three variables in linear regression analyses, the difference in physical fitness between fatigued and non-fatigued cancer survivors persisted. CONCLUSIONS: Maximal oxygen consumption, a measure for physical fitness, was reduced in severely fatigued compared to non-fatigued cancer survivors. The inferior maximal exercise performance cannot fully be explained by differences in physical activity, self-efficacy, or social support between both groups. Other currently still unknown factors, such as a disturbance in the cardiopulmonary circuit, may play a role.

Botulinum toxin has an increased effect when targeted toward the muscle's endplate zone: a high-density surface EMG guided study.

OBJECTIVES: To compare the effect of endplate-targeted injections of a low Botulinum neurotoxin type A (BoNT-A) dose with that of injections at defined distances from the motor endplate zone. METHODS: In eight healthy volunteers, the main endplate zones of the right and left extensor digitorum brevis (EDB) muscles were localized using high-density surface EMG. On the study side BoNT-A was injected at fixed distances from the endplate zone. On the control side, BoNT-A was administered into the endplate zone. Compound muscle action potential (CMAP) prior to the injection and 2, 12, and 24 weeks later were recorded. RESULTS: On the control side, the mean CMAP reduction 2 weeks after BoNT-A injection was 79.3%. The difference in CMAP reduction between both EDB muscles was significantly related to the injection distance from the endplate zone. Increasing the injection distance by 1cm reduced the effect of BoNT-A by 46%. CONCLUSIONS: Guided injection of a reduced BoNT-A dose into the muscle's endplate zone(s) is a promising strategy for optimizing the therapeutic effectiveness of BoNT-A and for minimizing side-effects such as unwanted weakness of adjacent muscles. SIGNIFICANCE: Precise endplate-targeted injections increase the effect of BoNT-A and may thus prove to reduce required dosage and treatment costs.

New cases of adult-onset Sandhoff disease with a cerebellar or lower motor neuron phenotype.

Sandhoff disease is a lipid-storage disorder caused by a defect in ganglioside metabolism. It is caused by a lack of functional N-acetyl-beta-d-glucosaminidase A and B due to mutations in the HEXB gene. Typical, early-onset Sandhoff disease presents before 9 months of age with progressive psychomotor retardation and early death. A late-onset form of Sandhoff disease is rare, and its symptoms are heterogeneous. As drug trials that aim to intervene in the disease mechanism are emerging, the recognition and identification of Sandhoff disease patients-particularly those with atypical phenotypes-are becoming more important. The authors describe six new late-onset Sandhoff cases demonstrating cerebellar ataxia or lower motor neuron (LMN) involvement combined with, mostly subclinical, neuropathy. Two different mutations were found: IVS 12-26 G/A and c.1514G-->A. In patients with either progressive cerebellar ataxia or LMN disease in the setting of a possibly recessive disorder, Sandhoff disease should be suspected, even when the onset age is over 45 years.

Age-related changes in motor unit number estimates in adult patients with Charcot-Marie-Tooth type 1A.

BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is known as a demyelinating hereditary neuropathy. Secondary axonal dysfunction is the most important determinant of disease severity. In adult patients, clinical progression may be because of further axonal deterioration as was shown with compound muscle action potential (CMAP) amplitude reductions over time. The motor unit number estimation (MUNE) technique may be more accurate to determine the number of axons as it is not disturbed by the effect of reinnervation. The purpose of this study was to investigate the number and size of motor units in relation to age in patients and controls. METHODS: In a cross-sectional design, we assessed arm and hand strength and performed electrophysiological examinations, including CMAP amplitudes and MUNE of the thenar muscles using high-density surface EMG in 69 adult patients with CMT1A and 55 age-matched healthy controls. RESULTS: In patients, lower CMAP amplitudes and MUNE values were related to hand weakness. The CMAP amplitude and MUNE value of the thenar muscles were significantly lower in patients than in controls. CMAP amplitudes declined with age in controls, but not in patients. MUNE values declined with age in both patients and controls. CONCLUSIONS: The age-dependent decrease in the number of motor units was not significantly different between patients with CMT1A and controls, indicating that loss of motor units in adult patients is limited.

Neuromuscular features in Marfan syndrome.

Marfan syndrome is a clinically and allelic heterogeneous, heritable connective tissue disorder with infrequently reported neuromuscular features. This study is the first to delineate these symptoms in a non-selected population. Neuromuscular involvement was evaluated in 10 Marfan patients through a standardized questionnaire, physical examination, nerve conduction study (NCS), needle electromyography (EMG), muscle ultrasound, laboratory investigation, and muscle biopsy. Existing neuroimages were screened for dural ectasia and spinal meningeal cysts. Twenty healthy controls with similar age distribution completed the questionnaire. The results showed that various neuromuscular symptoms occur more frequently in the patients. Four older patients reported muscle weakness, five patients had a mild-to-moderate reduction in vibration sense, and all older patients mentioned mild functional impairments. NCS showed axonal polyneuropathy in four and EMG myopathic and neurogenic changes in all patients. Increased echo intensity and atrophy on muscle ultrasound was found in more than half of the patients. Muscle biopsies obtained in two patients showed myopathic changes in the older, female patient. In conclusion, the majority of Marfan patients exhibited neuromuscular symptoms characterized as myopathy or polyneuropathy or both, and signs of lumbosacral radiculopathy, with symptoms being most pronounced in the older patients. Although meriting corroboration, these findings indicate a need to further the awareness of neuromuscular involvement in this population.

Muscle ultrasound measurements and functional muscle parameters in non-dystrophic myotonias suggest structural muscle changes.

Patients with non-dystrophic myotonias, including chloride (myotonia congenita) and sodium channelopathies (paramyotonia congenita/potassium aggravated myotonias), may show muscular hypertrophy in combination with some histopathological abnormalities. However, the extent of muscle changes has never been assessed objectively in a large group genetically confirmed patients. This study quantitatively determines echo intensities, thicknesses, ranges-of-motion and force of four skeletal muscles in 63 genetically confirmed patients. The main findings revealed elevated echo intensities in all muscles except the rectus femoris (+1.3-2.2SD, p<0.0001), and hypertrophy in the arms (+0.5-0.9SD, p<0.01). Muscle echo intensities were inversely correlated to the corresponding ranges-of-motion (biceps brachii: r= -0.43; p<0.001, forearm flexors: r= -0.47; p<0.001, rectus femoris: r= -0.40; p=0.001, and tibial anterior: r= -0.27; p=0.04) and correlated positively to age (r=0.22; p=0.05). The echo intensity of the forearm flexors was inversely correlated to their muscles' force (r= -0.30; p=0.02). Together, these data suggest that non-dystrophic myotonias may lead to structural muscle changes.

Sensory nerve conduction studies in neuralgic amyotrophy.

Neuralgic amyotrophy is a painful, episodic peripheral nerve disorder localized to the brachial plexus. Sensory symptoms occur in 80% of the patients. We assessed the frequency of abnormalities in sensory nerve conduction studies of the lateral and medial antebrachial cutaneous, radial sensory, median sensory, and ulnar sensory nerves in 112 patients. Sensory nerve conduction studies showed abnormalities in <20% of nerves, even when the nerve was clinically affected. The lateral and medial antebrachial cutaneous nerves were most often abnormal, in 15% and 17% of nerves. No correlation with the presence or localization of clinical deficits was found. Brachial plexus sensory nerve conduction studies seem to be of little diagnostic value in neuralgic amyotrophy. Our findings also indicate that some sensory lesions may be in the nerve roots instead of the plexus. An examination of normal sensory nerve conduction studies does not preclude neuralgic amyotrophy as a diagnosis.

Clinical neurophysiology of fatigue.

Fatigue is a multidimensional concept covering both physiological and psychological aspects. Chronic fatigue is a typical symptom of diseases such as cancer, multiple sclerosis (MS), Parkinson's disease (PD) and cerebrovascular disorders but is also presented by people in whom no defined somatic disease has been established. If certain criteria are met, chronic fatigue syndrome can be diagnosed. The 4-item Abbreviated Fatigue Questionnaire allows the extent of the experienced fatigue to be assessed with a high degree of reliability and validity. Physiological fatigue has been well defined and originates in both the peripheral and central nervous system. The condition can be assessed by combining force and surface-EMG measurements (including frequency analyses and muscle-fibre conduction estimations), twitch interpolation, magnetic stimulation of the motor cortex and analysis of changes in the readiness potential. Fatigue is a well-known phenomenon in both central and peripheral neurological disorders. Examples of the former conditions are multiple sclerosis, Parkinson's disease and stroke. Although it seems to be a universal symptom of many brain disorders, the unique characteristics of the concomitant fatigue also point to a specific relationship with several of these syndromes. As regards neuromuscular disorders, fatigue has been reported in patients with post-polio syndrome, myasthenia gravis, Guillain-Barré syndrome, facioscapulohumeral dystrophy, myotonic dystrophy and hereditary motor and sensory neuropathy type-I. More than 60% of all neuromuscular patients suffer from severe fatigue, a prevalence resembling that of patients with MS. Except for several rare myopathies with specific metabolic derangements leading to exercise-induced muscle fatigue, most studies have not identified a prominent peripheral cause for the fatigue in this population. In contrast, the central activation of the diseased neuromuscular system is generally found to be suboptimal. The reliability of the psychological and clinical neurophysiological assessment techniques available today allows a multidisciplinary approach to fatigue in neurological patients, which may contribute to the elucidation of the pathophysiological mechanisms of chronic fatigue, with the ultimate goal to develop tailored treatments for fatigue in neurological patients. The present report discusses the different manifestations of fatigue and the available tools to assess peripheral and central fatigue.

Distribution of motor unit potential velocities in short static and prolonged dynamic contractions at low forces: use of the within-subject's skewness and standard deviation variables.

Behaviour of motor unit potential (MUP) velocities in relation to (low) force and duration was investigated in biceps brachii muscle using a surface electrode array. Short static tests of 3.8 s (41 subjects) and prolonged dynamic tests (prolonged tests) of 4 min (30 subjects) were performed as position tasks, applying forces up to 20% of maximal voluntary contraction (MVC). Four variables, derived from the inter-peak latency technique, were used to describe changes in the surface electromyography signal: the mean muscle fibre conduction velocity (CV), the proportion between slow and fast MUPs expressed as the within-subject skewness of MUP velocities, the within-subject standard deviation of MUP velocities [SD-peak velocity (PV)], and the amount of MUPs per second (peak frequency=PF). In short static tests and the initial phase of prolonged tests, larger forces induced an increase of the CV and PF, accompanied with the shift of MUP velocities towards higher values, whereas the SD-PV did not change. During the first 1.5-2 min of the prolonged lower force levels tests (unloaded, and loaded 5 and 10% MVC) the CV and SD-PV slightly decreased and the MUP velocities shifted towards lower values; then the three variables stabilized. The PF values did not change in these tests. However, during the prolonged higher force (20% MVC) test, the CV decreased and MUP velocities shifted towards lower values without stabilization, while the SD-PV broadened and the PF decreased progressively. It is argued that these combined results reflect changes in both neural regulatory strategies and muscle membrane state.