Exercise-induced Muscle Weakness Research Articles

Exercise induced muscle weakness in a young adult: McArdle’s disease unusual presentation

McArdle’s disease (Glycogen storage disease type V) is a rare inherited autosomal recessive disease involving defect in enzyme, glycogen phosphorylase (PYGM) which results in accumulation of glycogen mainly affecting skeletal muscles. It commonly presents in childhood and rarely in adults with symptoms like exercise intolerance, muscle weakness, cramps and fatigue. Herein, we report an unusual case of a 22 years old male in Pakistan with probable McArdle’s Disease presenting with repeated episodes of generalized cramping muscle pain, exercise intolerance and haematuria. The diagnostic approach to identifying this disease as well as the differentials of other rare types of skeletal muscle disorders that should be kept in mind while dealing with a similar clinical picture, irrespective of the age of presentation, have been discussed. Keywords: Glycogen Storage Disease Type V, Myoglobinuria.

A new family with a case of severe early-onset muscle fatigue and a peculiar maternally inherited painful swelling in chewing muscles associated with homoplasmic m.15992A>T mutation in mitochondrial tRNAPro

A 16-year-old boy was evaluated for a history of exercise-induced fatigability associated with nausea even after minimal effort, lower limbs muscle hypotrophy, and swelling of the masseter muscles after chewing. Laboratory tests were remarkable for hyperlactatemia and metabolic acidosis after short physical activity. The muscle biopsy showed non-specific mitochondrial alterations and an increase in intrafibral lipids. Biochemical analysis showed reduced activity of the respiratory chain complexes. Mitochondrial DNA sequencing revealed the presence of a homoplasmic variant m.15992A>T in the MT-TP gene, coding for the mt-tRNAPro in the patient, in his mother and in his brother. Pathogenic or likely pathogenic variants in MT-TP gene are rare. They are responsible for different clinical presentation, almost ever involving the muscle tissue. We report the first family with exercise-induced muscle weakness and swelling of the chewing muscles due to m.15992A>T variant in absence of J1c10 haplogroup, confirming its pathogenicity.

Brody myopathy associated with novel compound heterozygous ATP2A1 mutations (P6-8.015)

<h3>Objective:</h3> To describe a case of presumed Brody myopathy associated with novel compound heterozygous ATP2A1 mutations. <h3>Background:</h3> Brody myopathy is a rare autosomal recessive skeletal muscle disease characterized by exertional muscle cramps, weakness, and/or rhabdomyolysis associated with clinical myotonia. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 19-year-old man with normal development and motor milestones presented to neuromuscular clinic after two episodes of exercise-induced muscle weakness and rhabdomyolysis in the past 6-months. Peak creatinine phosphokinase (CPK) was &gt;63,000 units/L and he quickly returned to baseline after each episode with intravenous fluids and supportive care. Remaining initial testing including serum total carnitine and acylcarnitine levels, and urine organic acid levels, were normal. He provided additional history of progressive difficulty relaxing leg and handgrip muscles after exertion since childhood, and multiple episodes of asymptomatic dark-colored urine provoked by strenuous exercise over the past two years. Physical examination showed bilateral grip and percussion myotonia with otherwise normal muscle bulk, strength, and remaining neurologic examination. Electromyography was normal. Genetic testing including myotonic dystrophy types 1 and 2, Pompe disease, and non-dystrophic myotonic disorders was notable for compound heterozygous ATP2A1 gene c.2032C&gt;T (p.Arg678Cys) and c.2176G&gt;A (p.Val726Met) variants of uncertain significance. Separate pathogenic mutations in this gene cause Brody myopathy, a non-dystrophic myotonic disorder characterized by exertional rhabdomyolysis. The patient is presumed to have Brody myopathy due to novel compound heterozygous ATP2A1 mutations. <h3>Conclusions:</h3> Brody myopathy should be considered in individuals presenting with muscle cramps, clinical myotonia, and exertional rhabdomyolysis. Clinical features and electromyographic findings are milder than myotonic dystrophies, Pompe disease, and typical non-dystrophic myotonic disorders. Genetic testing including ATP2A1 gene sequencing aids diagnosis. Management is supportive, although individuals should be aware of a 5% association with malignant hyperthermia-like episodes after exposure to volatile anesthetics. <b>Disclosure:</b> Dr. Walia has nothing to disclose. Dr. Su has nothing to disclose.

Blood Pressure Responses to Postexercise Circulatory Occlusion Are Attenuated After Exercise-Induced Muscle Weakness.

Exercise blood pressure (BP) responses are thought to be determined by relative exercise intensity (percent maximal voluntary contraction (MVC) strength). However, cross-sectional studies report that during a static contraction, higher absolute force is associated with greater BP responses to relative intensity exercise and subsequent muscle metaboreflex activation with postexercise circulatory occlusion (PECO). We hypothesized that a bout of unaccustomed eccentric exercise would reduce knee extensor MVC and subsequently attenuate BP responses to PECO. Continuous BP, heart rate, muscle oxygenation, and knee extensor electromyography were recorded in 21 young healthy individuals (female, n = 10) during 2 min of 20% MVC static knee extension exercise and 2 min of PECO, performed before and 24 h after 300 maximal knee extensor eccentric contractions to cause exercise-induced muscle weakness. As a control, 14 participants repeated the eccentric exercise 4 wks later to test whether BP responses were altered when exercise-induced muscle weakness was attenuated via the protective effects of the repeated bout effect. Eccentric exercise reduced MVC in all participants (144 ± 43 vs 110 ± 34 N·m, P < 0.0001). BP responses to matched relative intensity static exercise (lower absolute force) were unchanged after eccentric exercise ( P > 0.99) but were attenuated during PECO (systolic BP: 18 ± 10 vs 12 ± 9 mm Hg, P = 0.02). Exercise-induced muscle weakness modulated the deoxygenated hemoglobin response to static exercise (64% ± 22% vs 46% ± 22%, P = 0.04). When repeated after 4 wks, exercise-induced weakness after eccentric exercise was attenuated (-21.6% ± 14.3% vs -9.3 ± 9.7, P = 0.0002) and BP responses to PECO were not different from control values (all, P > 0.96). BP responses to muscle metaboreflex activation, but not exercise, are attenuated by exercise-induced muscle weakness, indicating a contribution of absolute exercise intensity on muscle metaboreflex activation.

Eccentric exercise-induced muscle weakness abolishes sex differences in fatigability during sustained submaximal isometric contractions

BackgroundFemales are typically less fatigable than males during sustained isometric contractions at lower isometric contraction intensities. This sex difference in fatigability becomes more variable during higher intensity isometric and dynamic contractions. While less fatiguing than isometric or concentric contractions, eccentric contractions induce greater and longer lasting impairments in force production. However, it is not clear how muscle weakness influences fatigability in males and females during sustained isometric contractions. MethodsWe investigated the effects of eccentric exercise-induced muscle weakness on time to task failure (TTF) during a sustained submaximal isometric contraction in young (18–30 years) healthy males (n = 9) and females (n = 10). Participants performed a sustained isometric contraction of the dorsiflexors at 35° plantar flexion by matching a 30% maximal voluntary contraction (MVC) torque target until task failure (i.e., falling below 5% of their target torque for ≥2 s). The same sustained isometric contraction was repeated 30 min after 150 maximal eccentric contractions. Agonist and antagonist activation were assessed using surface electromyography over the tibialis anterior and soleus muscles, respectively. ResultsMales were ∼41% stronger than females. Following eccentric exercise both males and females experienced an ∼20% decline in maximal voluntary contraction torque. TTF was ∼34% longer in females than males prior to eccentric exercise-induced muscle weakness. However, following eccentric exercise-induced muscle weakness, this sex-related difference was abolished, with both groups having an ∼45% shorter TTF. Notably, there was ∼100% greater antagonist activation in the female group during the sustained isometric contraction following exercise-induced weakness as compared to the males. ConclusionThis increase in antagonist activation disadvantaged females by decreasing their TTF, resulting in a blunting of their typical fatigability advantage over males.

Eccentric exercise-induced muscle weakness amplifies the history dependence of force.

Following active lengthening or shortening contractions, isometric steady-state torque is increased (residual force enhancement; rFE) or decreased (residual force depression; rFD), respectively, compared to fixed-end isometric contractions at the same muscle length and level of activation. Though the mechanisms underlying this history dependence of force have been investigated extensively, little is known about the influence of exercise-induced muscle weakness on rFE and rFD. Assess rFE and rFD in the dorsiflexors at 20%, 60%, and 100% maximal voluntary torque (MVC) and activation matching, and electrically stimulated at 20% MVC, prior to, 1h following, and 24h following 150 maximal eccentric dorsiflexion contractions. Twenty-six participants (13 male, 24.7 ± 2.0y; 13 female, 22.5 ± 3.6y) were seated in a dynamometer with their right hip and knee angle set to 110° and 140°, respectively, with an ankle excursion set between 0° and 40° plantar flexion (PF). MVC torque, peak twitch torque, and prolonged low frequency force depression were used to assess eccentric exercise-induced neuromuscular impairments. History-dependent contractions consisted of a 1s isometric (40°PF or 0°PF) phase, a 1s shortening or lengthening phase (40°/s), and an 8s isometric (0°PF or 40°PF) phase. Following eccentric exercise; MVC torque was decreased, prolonged low frequency force depression was present, and both rFE and rFD increased for all maximal and submaximal conditions. The history dependence of force during voluntary torque and activation matching, and electrically stimulated contractions is amplified following eccentric exercise. It appears that a weakened neuromuscular system amplifies the magnitude of the history-dependence of force.

Respiratory muscle fatigability in patients with spinal muscular atrophy.

Respiratory failure is a major cause of morbidity and mortality in patients with Spinal Muscular Atrophy (SMA). Lack of endurance, or "fatigability," is an important symptom of SMA. In addition to respiratory muscle weakness, respiratory function in SMA may be affected by Respiratory Muscle Fatigability (RMF). The purpose of this study was to explore RMF in patients with SMA. We assessed a Respiratory Endurance Test (RET) in 19 children (median age [years]: 11) and 36 adults (median age [years]: 34) with SMA types 2 and 3. Participants were instructed to breath against an inspiratory threshold load at either 20%, 35%, 45%, 55%, or 70% of their individual maximal inspiratory mouth pressure (PImax). RMF was defined as the inability to complete 60 consecutive breaths. Respiratory fatigability response was determined by change in maximal inspiratory mouth pressure (ΔPImax) and perceived fatigue (∆perceived fatigue). The probability of RMF during the RET increased by 59%-69% over 60 breaths with every 10% increase in inspiratory threshold load (%PImax). Fatigability response was characterized by a large variability in ΔPImax (-21% to +16%) and a small increase in perceived fatigue (p = 0.041, range 0 to +3). Patients with SMA demonstrate a dose-dependent increase in RMF without severe increase in exercise-induced muscle weakness or perceived fatigue. Inspiratory muscle loading in patients with SMA seems feasible and its potential to stabilize or improve respiratory function in patients with SMA needs to be determined in further research.

The vestibulomyogenic balance response is elevated following high-intensity lengthening contractions of the lower limb

The purpose was to investigate whether exercise-induced muscle weakness of the plantar and dorsiflexors through high-intensity lengthening contractions increases the vestibulomyogenic balance response. Nine males (∼25 years) participated in three experimental testing days to evaluate the vestibular control of standing balance and neuromuscular function of the plantar and dorsiflexors pre- and post (30 min, and 1 and 7 days) high-intensity lengthening plantar and dorsiflexions. To evaluate the vestibular-evoked balance response, participants stood quietly on a force plate while exposed to continuous, random electrical vestibular stimulation (EVS) for two 90-s trials. Relationships between EVS-antero-posterior (AP) forces and EVS-medial gastrocnemius electromyography (EMG) were estimated in the frequency domain (i.e., coherence). Weakness of the right plantar and dorsiflexors were assessed using maximal voluntary contraction (MVC) torque. The lengthening contractions induced a 13 and 24% reduction in plantar and dorsiflexor MVC torque, respectively (p < 0.05) of the exercised leg, which did not recover by 1 day post. The EVS-EMG coherence increased over a range of frequencies up to 7 days post compared to pre-lengthening contractions. Conversely, EVS-AP forces coherence exhibited limited changes. The greater EVS-EMG coherence post exercise-induced muscle weakness may be a compensatory mechanism to maintain the whole-body vestibular-evoked balance response when muscle strength is reduced.

Intragenic DOK7 deletion detected by whole-genome sequencing in congenital myasthenic syndromes.

Objective:To identify the genetic cause in a patient affected by ptosis and exercise-induced muscle weakness and diagnosed with congenital myasthenic syndromes (CMS) using whole-genome sequencing (WGS).Methods:Candidate gene screening and WGS analysis were performed in the case. Allele-specific PCR was subsequently performed to confirm the copy number variation (CNV) that was suspected from the WGS results.Results:In addition to the previously reported frameshift mutation c.1124_1127dup, an intragenic 6,261 bp deletion spanning from the 5′ untranslated region to intron 2 of the DOK7 gene was identified by WGS in the patient with CMS. The heterozygous deletion was suspected based on reduced coverage on WGS and confirmed by allele-specific PCR. The breakpoints had microhomology and an inverted repeat, which may have led to the development of the deletion during DNA replication.Conclusions:We report a CMS case with identification of the breakpoints of the intragenic DOK7 deletion using WGS analysis. This case illustrates that CNVs undetected by Sanger sequencing may be identified by WGS and highlights their relevance in the molecular diagnosis of a treatable neurologic condition such as CMS.

Neural Correlates of Effort during Exercise

Changes in movement-related cortical potentials (MRCPs) with increasing workload and muscle weakness could be related to effort. However, there is a lack of MRCP studies that have experimentally manipulated effort and correlated MRCP components with subjective effort ratings. PURPOSE: To determine whether the MRCP is a neurophysiological correlate of effort by experimentally manipulating effort during a weightlifting task with exercise induced muscle weakness. METHODS: Ten right-handed participants had one arm (randomly counterbalanced) eccentrically pre-fatigued. Participants performed four blocks of 50 quasi isometric elbow flexions (± 2 s each) in a randomized order. They lifted a light weight (20% of one-repetition maximum (1RM)) and a heavy weight (35% 1RM) with the fatigued (FAT) and the non-fatigued (NF) arm with 6 s rest between lifts. Ratings of perceived effort, biceps brachii electromyogram (EMG) and 62-channel electroencephalogram (EEG) were recorded. EEG was segmented and time-locked to EMG onset (0 ms), and artefact free trials were averaged within each block. Comparisons between blocks were made using two-way ANOVA with repeated measures. Means and standard deviations and p-levels of paired differences are reported. RESULTS: The fatigued arm was on average 29% weaker than the non-fatigued arm (p = 0.001). Effort ratings were significantly higher for the fatigued arm compared to the non-fatigued arm for both weights (Light FAT 3.1 ± 1.2 vs. NF 1.9 ± 0.7, p = 0.003; Heavy FAT 6.0 ± 1.5 vs. NF 3.9 ± 1.2, p < 0.001). Similar effects were found for biceps EMG amplitude (Light FAT 282 ± 222 vs. NF 139 ± 108 μV, p = 0.012; Heavy FAT 422 ± 332 vs. NF 192 ± 136 μV, p = 0.008). Effects of fatigue on MRCPs were found during and after the movement at selected electrode sites (e.g. Cz 0-1000 ms: Heavy FAT -12.9 ± 5.9 vs. NF -10.5 ± 4.4 μV, p = 0.038; C1' 1000-2000 ms: Heavy FAT -5.7 ± 3.4 vs. NF -7.0 ± 3.2 μV, p = 0.013; Pz 2000-3000 ms: Heavy FAT 5.6 ± 5.2 vs. NF 4.3 ± 4.9 μV, p = 0.023). CONCLUSION: Certain MRCP components reflect experimentally induced changes in effort during weightlifting exercise. No effects of fatigue were found before EMG onset in Cz, C1', and Pz. The supplementary motor area, primary motor cortex and parietal cortex might be involved in the perception of effort.

Exercise-Induced Muscle Weakness And Soreness Are Attenuated In Resistance-Trained Individuals By Pomegranate Juice Supplementation

Exercise-Induced Muscle Weakness And Soreness Are Attenuated In Resistance-Trained Individuals By Pomegranate Juice Supplementation

Myogenic differentiation induces taurine transporter in association with taurine-mediated cytoprotection in skeletal muscles

Skeletal muscle homoeostasis is maintained by a variety of cytoprotective mechanisms. Since ablation of the TauT (taurine transporter) gene results in susceptibility to exercise-induced muscle weakness in vivo, it has been suggested that TauT is essential for skeletal muscle function. However, the regulatory mechanisms of TauT expression remain to be elucidated. In the present study, we demonstrated that TauT was up-regulated during myogenesis in C2C12 cells. Treatment with bFGF (basic fibroblast growth factor), which inhibited muscle differentiation, abrogated myogenic induction of TauT. The promoter activities of TauT were up-regulated during muscle differentiation in C2C12 cells. Database analyses identified an MEF2 (myocyte enhancer binding factor 2) consensus sequence at -844 in the rat TauT gene. Truncation of the promoter region containing the MEF2 site significantly reduced the promoter activity, demonstrating the functional importance of the MEF2 site. Electrophoretic mobility-shift assays confirmed that MEF2 bound to the MEF2 consensus sequence and that DNA-protein complex levels were increased during differentiation. Promoter analyses using mutated promoter-reporter plasmids demonstrated that this site was functional. Importantly, transfection with a MyoD expression vector markedly enhanced TauT promoter activity in the (non-myogenic) 10T1/2 cells. Moreover, co-transfection with an MEF2 expression vector augmented MyoD-induced TauT promoter activity, suggesting that MEF2 is required for full activation of TauT expression. Finally, we examined the effects of taurine on myotube atrophy to clarify the biological significance of the up-regulation of TauT, and demonstrated that taurine attenuated muscle atrophy induced by dexamethasone. TauT expression is regulated under the control of the myogenic programme, and we propose that this is the mechanism for taurine-mediated resistance to muscle atrophy.

MOLECULAR BASIS OF MITOCHONDRIAL MYOPATHIES: POLYPEPTIDE ANALYSIS IN COMPLEX-1 DEFICIENCY

Clinical and biochemical data are reported for three patients with mitochondrial myopathy. One patient presented only with exercise-induced muscle weakness, whereas the other two showed signs of multisystem disease. Polarographic determination of oxygen uptake in skeletal muscle mitochondria suggested complex-I (nicotinamide adenine dinucleotide [reduced] ubiquinone oxidoreductase) deficiency. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and immunoblotting with antibody to the holoenzyme of complex-I and specific antibodies to certain of the Fe-S subunits of complex-I showed a relatively normal profile in the least affected patient and a generalised reduction in the intensities of all crossreacting bands in the other two patients. The most severely affected patient also showed a disproportionate and pronounced reduction in the 24 K Fe-S subunit. Clinical severity of muscle involvement correlated with the biochemical deficiency as determined polarographically and with the immunoblot appearances.

Effect of diet on human muscle weakness following prolonged exercise.

The effect of altering muscle glycogen on the ability of skeletal muscle to generate voluntary and electrically evoked isometric force following prolonged exercise has been investigated in five healthy male subjects. Measurements from the triceps surae were made at rest, and before and after prolonged exercise (uphill walking) at approximately 75% VO2 max in low muscle glycogen (low CHO) and high muscle glycogen (high CHO) conditions. The results showed that before exercise there was no change in maximal twitch tension (Pto), maximal tetanic tension at frequencies of 10 (Po10), 20 (Po20) and 50 HZ (Po50), and maximal voluntary contraction (MVC) in low and high CHO compared with normal. The loss of force during a 2 min electrically evoked "fatigue test" at rest was found to be higher (p less than 0.05) in low CHO and lower (p less than 0.05) in high CHO than normal. Following the prolonged exercise, muscle weakness was produced in both low and high CHO conditions, but was found to be significantly greater in the low CHO condition for the measurements of Po10 (P less than 0.01), Po20 (p less than 0.05) and MVC (p less than 0.05). It is concluded that changes in muscle glycogen alone do not alter the isometric force generating capacity of human muscle, but when combined with prolonged exercise low muscle glycogen enhances exercise-induced muscle weakness.