Contractile speed and fatigue of adductor pollicis muscle in multiple sclerosis

The purpose of the study was to investigate differences in contractile speed, force, and fatigability of the adductor pollicis muscle between 12 patients with multiple sclerosis (MS) and 8 sedentary control subjects matched for age and gender. There were no differences between the patients with MS and control subjects with respect to the percentage of maximal muscle force that could be recruited during voluntary effort (95.5 +/- 3.9% and 98.2 +/- 2.0%, respectively, P = 0.10), the stimulation frequency/force and force/velocity relationships, the rates of force development and relaxation, fatigue resistance, and the recovery rate of adductor pollicis muscle. However, previous results from the same group of MS patients showed that quadriceps femoris muscle force and resistance to fatigue were reduced. Therefore, our data support the clinical experience that, in patients with MS, lower limb muscle function is more or earlier affected than upper limb muscle function.     

Fatigue of muscles weakened by death of motoneurons

Weakness is a characteristic of muscles influenced by the postpolio syndrome (PPS), amyotrophic lateral sclerosis (ALS), and spinal cord injury (SCI). The strength deficits relate to changes in muscle use and to the chronic denervation that can follow the spinal motoneuron death common to these disorders. PPS, ALS, and SCI also involve variable amounts of supraspinal neuron death, the effects of which on muscle weakness remains unclear. Nevertheless, weakness of muscle itself defines the functional consequences of these disorders. A weaker muscle requires an individual to work that muscle at higher than usual intensities relative to its maximal capacity, inducing progressive fatigue and an increased sense of effort. Little evidence is available to suggest that the fatigue commonly experienced by individuals with these disorders relates to an increase in the intrinsic fatigability of the muscle fibers. The only exception is when SCI induces chronic muscle paralysis. To reduce long-term functional deficits in these disorders, studies must identify the signaling pathways that influence neuron survival and determine the factors that encourage and limit sprouting of motor axons. This may ensure that a greater proportion of the fibers in each muscle remain innervated and available for use.     

Quadriceps muscle strength and voluntary activation after polio

Quadriceps strength, maximal anatomical cross-sectional area (CSA), maximal voluntary activation (MVA), and maximal relaxation rate (MRR) were studied in 48 subjects with a past history of polio, 26 with and 22 without postpoliomyelitis syndrome (PPS), and in 13 control subjects. It was also investigated whether, apart from CSA, MVA and MRR were determinants of muscle strength. Polio subjects had significantly less strength, CSA, and MRR in the more-affected quadriceps than control subjects. MVA was reduced in 18 polio subjects and normal in all controls. PPS subjects differed from non-PPS subjects only in that the MVA of the more-affected quadriceps was significantly lower. Both CSA and MVA were found to be associated with muscle strength. Quadriceps strength in polio subjects was dependent not only on muscle mass, but also on the ability to activate the muscles. Since impaired activation was more pronounced in PPS subjects, the new muscle weakness and functional decline in PPS may be due not only to a gradual loss of muscle fibers, but also to an increasing inability to activate the muscles.     

Fatigue of lateral rectus and retractor bulbi motor units in cat

The fatigue properties of lateral rectus, retractor bulbi and split lateral rectus-retractor bulbi motor units were studied in the cat. Lateral rectus motor units showed a range in resistance to fatigue while retractor bulbi motor units were all fatigable. Within the abducens nucleus, axons of split lateral rectus-retractor bulbi motor units are found. These motor units are unique in that one motoneuron projects to two separate muscles. Split motor units were studied to determine if both the lateral rectus and retractor bulbi muscle fibers of split units would show uniform fatigue properties. The results showed that the fatigue resistance of the separate muscle components of these motor units are different, suggesting that the muscle fibers of a motor unit may be physiologically dissimilar.     

Quantitative muscle ultrasound and quadriceps strength in patients with post‐polio syndrome

Introduction: We investigated whether muscle ultrasound can distinguish muscles affected by post‐polio syndrome (PPS) from healthy muscles and whether severity of ultrasound abnormalities is associated with muscle strength. Methods: Echo intensity, muscle thickness, and isometric strength of the quadriceps muscles were measured in 48 patients with PPS and 12 healthy controls. Results: Patients with PPS had significantly higher echo intensity and lower muscle thickness than healthy controls. In patients, both echo intensity and muscle thickness were associated independently with muscle strength. A combined measure of echo intensity and muscle thickness was more strongly related to muscle strength than either parameter alone. Conclusions: Quantitative ultrasound distinguishes healthy muscles from those affected by PPS, and measures of muscle quality and quantity are associated with muscle strength. Hence, ultrasound could be a useful tool for assessing disease severity and monitoring changes resulting from disease progression or clinical intervention in patients with PPS. Muscle Nerve 51 : 24–29, 2015     

Lactate metabolism during exercise in patients with mitochondrial myopathy

Patients with mitochondrial DNA mutations often have elevated plasma lactate at rest and during exercise, but it is unknown whether the high lactate levels are caused by a high production, an impaired oxidation or a combination. We studied lactate kinetics in 10 patients with mtDNA mutations and 10 matched healthy control subjects at rest and during cycle exercise with a combination of femoral arterio-venous differences of lactate, and lactate tracer dilution methodology. During exercise, lactate concentration and production rates were several-fold higher in patients, but despite mitochondrial dysfunction, lactate was oxidized in muscle to the same extent as in healthy control subjects. This surprisingly high ability to burn lactate in working muscle with defective mitochondria, probably relates to the variability of oxidative capacity among muscle fibers. The data suggests that lactate is not solely an indicator of impaired oxidative capacity, but an important fuel for oxidative metabolism, even in muscle with severely impaired mitochondrial function.     

Elevated serum inflammatory markers in post-poliomyelitis syndrome

OBJECTIVES: To determine (i) whether serum inflammatory markers TNFalpha, IL-1beta. IL-6, and leptin are increased in post-poliomyelitis syndrome (PPS) compared to healthy controls; and (ii) whether an association exists between elevated inflammatory markers and clinical parameters in PPS. The cause of PPS is unknown, but abnormal inflammatory responses have been implicated in several small studies. METHODS: Serum inflammatory markers were measured (by Luminex) in 51 PPS patients and 26 normal controls. Clinical parameters assessed included disease duration, muscle strength (Medical Research Council sumscore), fatigue (Fatigue Severity Scale and Multidimensional Fatigue Inventory), and pain (visual analog scale scores). RESULTS: In PPS, TNFalpha levels, as well as IL-6 and leptin were significantly increased compared to controls (Wilcoxon rank-sum test, p=0.03 for TNFalpha, p=0.03 for IL-6, p=0.01 for leptin). The elevated TNFalpha levels in PPS were associated with increased pain due to illness (Spearman correlation coefficient r=0.36, 95% C.I. 0.09 to 0.57) and specifically, with muscle pain (r=0.38, 95% C.I. 0.11 to 0.59). There were no correlations between inflammatory markers in PPS and joint pain, muscle strength, fatigue, or disease duration. CONCLUSIONS: Serum TNFalpha, IL-6 and leptin levels are abnormally increased in PPS patients. Elevated TNFalpha levels appear to be specifically associated with increased muscle pain.     

Contractile properties and fatigue of quadriceps muscles in multiple sclerosis

Functional characteristics of electrically stimulated quadriceps muscles of patients with multiple sclerosis (MS) were determined to investigate whether adaptations in muscle properties contribute to the higher fatigability of these patients. The estimated maximal isometric force generating capacity of MS patients was only 11.2% (P < 0.05) lower than control subjects. However, the patients were only able to voluntarily exert 75 +/- 22% (n = 12) of their maximal capacity, against 94 +/- 6% (n = 7) for the control subjects. There were no differences in muscle speed, suggesting that muscle fiber distribution was not different in the MS patients due to reduced muscle usage. During a series of repeated contractions, greater decrements occurred in isometric force and in maximal rate of force rise in the MS patients (by 31.3 +/- 10.3% and 50.1 +/- 10.0%, respectively; n = 13) than control subjects (23.8 +/- 6.6% and 39.0 +/- 8.1%, n = 15), suggesting a lower oxidative capacity. The results indicate that increasing the mass of their muscles by training may help to reduce the excessive muscle fatigue of MS patients.     

Exercise performance and fatiguability in patients with chronic fatigue syndrome.

To examine the role of delay in recovery of peripheral muscle function following exercise in the fatigue experienced by patients with the chronic fatigue syndrome (CFS) and to examine the influence of effort perception in limiting exercise performance in these patients, a study was carried out on a group of twelve patients with chronic fatigue syndrome and 12 sex and age-matched sedentary control subjects. Symptom limited incremental cycle exercise tests including measurements of perceived exertion were performed followed by examination of the contractile properties of the quadriceps muscle group for up to 48 hours. Muscle function was assessed by percutaneous electrical stimulation and maximum voluntary contractions. Muscle function at rest and during recovery was normal in CFS patients as assessed by maximum isometric voluntary contraction, 20:50 Hz tetanic force ratio and maximum relaxation rate. Exercise duration and the relationship between heart rate and work rate during exercise were similar in both groups. CFS patients had higher perceived exertion scores in relation to heart rate during exercise representing a reduced effort sensation threshold of 3.2 units on an unmodified Borg scale in CFS patients. Patients with chronic fatigue syndrome show normal muscle physiology before and after exercise. Raised perceived exertion scores during exercise suggest that central factors are limiting exercise capacity in these patients.     

Slower conduction velocity and motor unit discharge frequency are associated with muscle fatigue during isometric exercise in type 1 diabetes mellitus

Type 1 diabetes mellitus (T1DM) is associated with a peripheral neuropathy that reduces nerve conduction velocity. This may impair high motor-unit discharge frequencies (MUDF), decrease muscle activation, and curtail the ability to sustain repetitive contractile tasks. We examined (1) whether MUDF, the contractile properties of the knee extensors, and the conduction velocity of persons with T1DM differed from controls; (2) whether persons with T1DM can maintain adequate MUDF during a fatigue protocol; and (3) the relationship between these parameters and impaired glycemic control. We studied male and female subjects with T1DM and controls matched for age, height, weight, and gender. Single motor unit recordings were made from vastus lateralis during maximal and submaximal contractions and during a fatigue protocol. Glycemic control was assessed from blood glucose concentration and glycosylated hemoglobin (HbA1c). Control femoral conduction velocities were comparable to literature values and those of the T1DM subjects were slower. These values correlated with plasma glucose and HbA1c. T1DM subjects fatigued 45% sooner than controls, and time to fatigue and conduction velocity were correlated (r = 0.54, P < 0.05). Discharge frequencies tended to be slower during 50% maximal voluntary contractile force in the T1DM subjects at task failure. Persons with T1DM had slower conduction velocities and lower MUDF than their controls, which apparently leads to impaired activation of muscle and decreased endurance during isometric fatigue.     

Muscle after spinal cord injury

The morphological and contractile changes of muscles below the level of the lesion after spinal cord injury (SCI) are dramatic. In humans with SCI, a fiber‐type transformation away from type I begins 4–7 months post‐SCI and reaches a new steady state with predominantly fast glycolytic IIX fibers years after the injury. There is a progressive drop in the proportion of slow myosin heavy chain (MHC) isoform fibers and a rise in the proportion of fibers that coexpress both the fast and slow MHC isoforms. The oxidative enzymatic activity starts to decline after the first few months post‐SCI. Muscles from individuals with chronic SCI show less resistance to fatigue, and the speed‐related contractile properties change, becoming faster. These findings are also present in animals. Future studies should longitudinally examine changes in muscles from early SCI until steady state is reached in order to determine optimal training protocols for maintaining skeletal muscle after paralysis. Muscle Nerve, 2009     

Preservation of in vitro muscle fiber function in dermatomyositis and inclusion body myositis: a single fiber study

Five patients with untreated dermatomyositis, five with inclusion body myositis, and 16 healthy elderly volunteer subjects (controls) underwent open (dermatomyositis and inclusion body myositis) or percutaneous (controls) muscle biopsy. Biopsied muscles included deltoid, biceps and vastus lateralis. Chemically skinned single muscle fibers were activated with Ca(+2); the slack test was performed to determine maximal unloaded shortening velocity (Vo). Parameters measured include single fiber cross sectional area, maximal force, specific force and Vo. 429 Type I and 94 Type IIA fibers were studied. Cross sectional area and maximal force were greater in inclusion body myositis than dermatomyositis or control for Type I and IIA fibers. Specific force of Type I fibers was similar in inclusion body myositis and dermatomyositis but greater than in controls. Vo was greater in Type I, but not IIA, fibers in dermatomyositis compared with inclusion body myositis and controls. The force and velocity generating capacity of single muscle fibers is preserved in patients with dermatomyositis and inclusion body myositis suggesting that dysfunction of the contractile proteins does not contribute to clinical muscle weakness.     

Quantitative assessment of motor fatigue and strength in MS.

OBJECTIVE: To determine the test-retest reliability of strength and fatigue measurements in patients with MS and in healthy control subjects, and to examine associations among motor fatigue, strength, and ambulatory impairment in MS patients. BACKGROUND: Motor fatigue, defined as the loss of the maximal capacity to generate force during exercise, and weakness are common in patients with MS. METHOD: Twenty ambulatory MS patients and 20 age- and sex-matched healthy control subjects participated in the study. Test-retest reliability was assessed in two identical testing sessions, separated by 3 to 5 days. Maximal voluntary isometric strength was determined by fixed myometry of seven muscle groups on each side. Motor fatigue was assessed using three exercise protocols: sustained maximal contractions (static fatigue), repetitive maximal contractions, and walking as far as 500 m. Four analysis models for static fatigue were examined for their test-retest reliability and their ability to discriminate between normal fatigue and pathologic fatigue from MS. RESULTS: Test-retest reliability in MS patients was excellent for isometric strength and very good for static fatigue. Test-retest reliability was lower for exercise protocols that involved repetitive contractions or ambulation. Compared with healthy control subjects, MS patients were weak in lower extremity muscles, but upper extremity strength was relatively preserved. Fatigue was greater in MS patients, even in muscles that were not clearly weak. There were no significant associations between strength and fatigue in any of the muscles tested. A fatigue analysis model based on the area under the force-versus-time curve gave the best combination of reliability and sensitivity to detect differences between MS patients and healthy control subjects. CONCLUSIONS: Strength and motor fatigue can be measured reliably in patients with MS. MS patients experience more fatigue than healthy control subjects during sustained contractions, repetitive contractions, and ambulation. Motor fatigue appears to be distinct from weakness because the degree of fatigue was not associated with the degree of weakness in individual muscles. Quantitative assessment of strength and fatigue may be useful to monitor changes in motor function over time in MS patients.     

Risk factors for post-polio syndrome among an Italian population: a case–control study

Post-polio syndrome (PPS) is a clinical syndrome of new weakness, fatigue and musculoskeletal pain occurring in a variable proportion of polio survivors decades after acute disease. To date, several risk factors for PPS development have been reported, although the etiology of this disorder remains elusive. Using a case–control design, we aimed to assess risk indicators for PPS in a group of Italian polio survivors. Subjects with prior poliomyelitis attending the rehabilitation hospital of Malcesine, Italy, were the target population. Patients with PPS, diagnosed according to the European Federation of Neurological Societies criteria, served as cases, while patients not meeting diagnostic criteria for PPS were used as controls. All subjects were assessed through a structured questionnaire made of 82 questions and neurological examination. The association with investigated risk factors (sex, age at polio onset, age at onset of symptoms, extension and severity of polio, employment) was analyzed by the calculation of the odds ratio. A total of 161 out of 391 eligible patients met the adopted diagnostic criteria for PPS, giving a frequency of 41.2%. Symptoms most frequently complained by PPS patients were loss of muscle strength, loss of resistance, loss of muscle volume and generalized fatigue. Female gender, the presence of respiratory disturbance during the acute phase of polio and the use of orthoses and aids during the recovery and stabilization represented independent risk factors for PPS in the studied population.     

Acute hypoxia limits endurance but does not affect muscle contractile properties

Acute hypoxia causes skeletal muscle dysfunction in vitro, but little is known about its effect on muscle function in vivo. In 10 healthy male subjects, isometric contractile properties and fatigue resistance of the quadriceps muscle were determined during normoxia and hypoxia using electrically evoked and voluntary contractions. The oxygen saturation (SaO(2); 96.9 +/- 0.7 vs. 79.9 +/- 3.0%; P < 0.001) was reduced during hypoxia. The maximal voluntary contraction (MVC), force-frequency relation, and contraction and relaxation times were unaffected by hypoxia. The endurance time of a sustained 30% MVC was reduced in hypoxia (248 +/- 104 vs. 217 +/- 76 s; P < 0.05), but not that of a sustained 70% MVC. Fatigue induced by electrically evoked intermittent contractions was unaltered. Thus, acute hypoxia has no significant impact on contractile properties of skeletal muscle in vivo but causes reduced endurance during low-level sustained voluntary contractions. This indicates that skeletal muscle dysfunction during conditions associated with prolonged hypoxemia, except for limited endurance, is not due to acute effects of hypoxemia.     

Mechanisms of force failure during repetitive maximal efforts in a human upper airway muscle

The upper airway respiratory muscles play an important role in the regulation of airway resistance, but surprisingly little is known about their contractile properties and endurance performance. We developed a technique that allows measurement of force and the electromyogram (EMG) of human nasal dilator muscles (NDMs). Endurance performance was quantified by measuring NDM "flaring" force and EMG activity as healthy human subjects performed 10 s maximal voluntary contractions (MVCs), separated by 10 s rest, until the area under the force curve fell to 50% MVC (the time limit of the fatigue task, Tlim), which was reached in 34.2 +/- 3.1 contractions (685.0 +/- 62.3 s). EMG activity was unchanged except at Tlim, where it averaged 78.7 +/- 3.6% of pretest activity (P < 0.01). M-wave amplitude did not change, suggesting that neuromuscular propagation was not impaired. MVC force increased to 80% of the pretest level within 10 min of recovery but twitch force failed to recover, suggesting low-frequency fatigue. The data suggest that a failure of the nervous system to excite muscle could explain at most only a small fraction of the NDM force loss during an intermittent fatigue task, and then only at Tlim. Thus, the majority of the force failure during this task is due to impairment of mechanisms that reside within the muscle fibers.     

Effect of hind-limb suspension on young and adult skeletal muscle. II. Dystrophic mice

Disuse atrophy induced by limb immobilization reportedly protects dystrophic mouse muscle from histopathological changes. This study was conducted to determine whether disuse atrophy induced by hind-limb suspension (HS) limits the histopathology and contractile abnormalities typically observed in the dystrophic mouse. Two weeks of hind-limb suspension were applied to dystrophic mice (line 129B6F1) at two ages, 4 weeks (6 mice) and 12 weeks (8 mice). Thirty-one untreated dystrophics served as controls. In general, HS exaggerated the dystrophic signs, especially in the younger mice; it reduced animal weight, muscle weight, maximum tetanic and twitch tensions, and rates of tetanic and twitch tension development. HS further slowed the contractile properties of soleus (SOL) and extensor digitorum longus (EDL) muscles, and increased their fatigue resistance. HS reduced the size of type I and IIA fibers in the 6-week SOL and EDL, but not in the 14-week muscles. HS produced a preferential atrophy of SOL type I fibers, with a parallel increase in type IIA fibers. However, it did not alleviate the fiber size variability, degree of necrosis, central nucleation, inflammation, or muscle fibrosis in dystrophic muscles. These data demonstrate that disuse by hind-limb suspension does not prevent the histopathological deterioration or loss of muscle function in 6- and 14-week dystrophic mice.     

Isotonic fatigue in laminin alpha2-deficient dy/dy dystrophic mouse diaphragm

Laminin alpha2 deficiency causes approximately 50% of human congenital muscular dystrophies. Muscle in the corresponding dy/dy mouse model has reduced force but increased fatigue resistance during isometric contractions. To determine whether a similar pattern of alterations is present during isotonic contractions, dy/dy diaphragm was studied in vitro. During 20% load, dystrophic diaphragm had significantly reduced shortening, shortening velocity, work and power deficits, which persisted during the fatigue-inducing stimulation. In contrast, during 40% load, isotonic contractile performance of diseased muscle was impaired only mildly and only for some contractile parameters. At both loads, rate of isotonic fatigue when expressed relative to initial contractile values was similar for dystrophic and normal muscle, or in some instances slightly higher for dystrophic muscle. Therefore, fatigue resistance is considerably impaired during isotonic contractions relative to that reported previously for isometric contractions. This has important implications for increased susceptibility to respiratory failure in laminin alpha2-deficient muscular dystrophy.     

Contractile properties of adjacent segments of single human muscle fibers

A comparison of the contractile properties of adjacent segments of single human muscle fibers may help to explain the interaction among nuclear domains within the myofiber. Biopsy samples were obtained from the vastus lateralis muscle of 20 healthy untrained women (age 18-79 years). Single fibers (n = 38) were dissected and cut into halves (segments A and B). Segment diameter and depth were measured using an image analysis system. Maximal force (Po) was recorded during activation with calcium (pCa 4.5). Maximal unloaded shortening velocity (Vo) was calculated using the slack test. Myosin heavy chain (MyHC) expression was determined using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). A significant difference ( approximately 7%) in Po was seen between adjacent segments expressing type I MyHC that could not be attributed to differences in fiber size. Significant differences were observed in Vo even after adjusting for fiber type. A positive correlation was seen in Po (concordance coefficient Rho_C = 0.803) and Vo (Rho_C = 0.690) between segments, but concordance was less than perfect in both cases. Possible explanations for nonuniformity of contractile properties include random variations in physiological systems or variability of protein expression among nuclear domains.     

Skeletal muscle fiber function and rate of disease progression in amyotrophic lateral sclerosis

The contractile properties of single muscle fibers reflect the functional status of muscle at the cellular level and have not been described in amyotrophic lateral sclerosis (ALS). Chemically skinned single muscle fibers (n = 173), obtained by needle biopsy from six men with ALS, were activated with Ca(2+), allowing maximal force measurements and specific force (SF) estimates. Maximum unloaded shortening velocity (V(o)) was determined using the slack test. The results were compared with muscle from healthy controls. Markers of disease progression included rate of change of ALS functional rating scale score, rate of change of forced vital capacity, and disease duration. Compared with controls, ALS patients had decreased whole muscle SF (measured by a combination of computerized tomography and isokinetic testing) but normal single fiber SF. The V(o) was greater for type I fibers in ALS. Patients with slower disease progression had increased single fiber size and a high percentage of hybrid fibers (expressing multiple myosin heavy chain isoforms). A needle biopsy obtained at the time of ALS diagnosis may assist with predicting rate of disease progression.