Search

Purpose of review Skeletal muscle dysfunction contributes to exercise intolerance, which manifests as dyspnea and fatiguability in patients with heart failure with preserved ejection fraction (HFpEF). This review aims to summarize the current understanding of skeletal muscle dysfunction in HFpEF. Recent findings Animal and human studies in HFpEF provide insights into the pathophysiological alterations in skeletal muscle structure and function with the identification of several molecular mechanisms. Exercise training and novel pharmacological therapies that target skeletal muscle are proposed as therapeutic interventions to treat HFpEF. Summary There is evidence that skeletal muscle dysfunction plays a pathophysiological role in HFpEF. However, precise mechanistic insights are needed to understand the contribution of skeletal muscle dysfunction in HFpEF.

Background: Acute fatigue is hypothesized to alter lower extremity injury risk profiles by affecting intrinsic risk factors (i.e. single leg postural control, hamstring strength). However, no systematic overview exists that merges the insights into prospective lower extremity injury risk profiling with the effect of acute fatigue on functional test performance. Objective: The objective of this review is to identify the influence of acute fatigue on prospectively determined modifiable intrinsic risk factors for lower extremity injuries. Design: Systematic review. Methods: PubMed (MEDLINE), Web of Science, PEDro, and Cochrane Library were searched until 29 May 2019. Studies were eligible when the study outcomes encompassed intrinsic modifiable risk factors for lower extremity injury, an acute fatigue intervention, and included healthy athletes or physically active people. Intrinsic modifiable risk factors were identified through recent systematic reviews and meta-analyses, and the referenced original research papers were used to determine outcome measures associated with increased injury risk. Results: Forty-three studies reported acute fatigue effects on modifiable risk factors, with eight studies matching all criteria for data-extraction. Acute fatigue can decrease single leg postural control, decrease ankle joint position sense, decrease isokinetic strength of hamstring and quadriceps muscles and can affect isokinetic hamstring:quadriceps ratios. Conclusion: Acute fatigue affects prospective intrinsic modifiable risk factors for lower extremity injury, indicating an altered injury risk profile for lateral ankle sprain, patellofemoral pain syndrome and hamstring injuries. Future research should allow for individual fatiguability as a relevant outcome, and merge insights from athlete-centred injury risk profiling and fatigue.

A 54-year-old man presented with easy fatiguability, dyspnoea on exertion and dyspeptic symptoms. On evaluation, he was found to have an ulcero-proliferative growth in the gastric fundus, the biopsy of which was malignant melanoma of the stomach. Further evaluation with 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) scan showed operable disease with no focus of disease elsewhere. He was diagnosed as primary gastric melanoma and underwent radical total gastrectomy with adequate margins. His postoperative period was uneventful. Further adjuvant therapy was refused by the patient. At 6-month follow-up, an 18F-FDG PET-CT scan was done, which showed no evidence of disease. On follow-up at 1-year, he was alive and asymptomatic.

A 34-year-old woman was admitted with symptoms of easy fatiguability, decreased urine output and jaundice for 1 week. She had similar history of weakness and jaundice 3 months ago that lasted for a week for which she consumed herbal medicines. Laboratory evaluation revealed anaemia with

Exercise intolerance and early fatiguability are hallmark symptoms of chronic heart failure. While the malfunction of the heart is certainly the leading cause of chronic heart failure, the patho-physiological mechanisms of exercise intolerance in these patients are more complex, multifactorial and only partially understood. Some evidence points towards a potential role of an exaggerated afferent feedback from group III/IV muscle afferents in the genesis of these symptoms. Overactivity of feedback from these muscle afferents may cause exercise intolerance with a double action: by inducing cardiovascular dysregulation, by reducing motor output and by facilitating the development of central and peripheral fatigue during exercise. Importantly, physical inactivity appears to affect the progression of the syndrome negatively, while physical training can partially counteract this condition. In the present review, the role played by group III/IV afferent feedback in cardiovascular regulation during exercise and exercise-induced muscle fatigue of healthy people and their potential role in inducing exercise intolerance in chronic heart failure patients will be summarised.

Background: Impairment of peripheral skeletal muscle function is a common phenomenon in patients with cystic fibrosis (CF) in addition to great clinical connotations, such as lack of exercise tolerance and decrease of health-related quality of life. There is very limited data on the effects of maximal exercise on muscle fatiguability and exercise capacity in children with cystic fibrosis. Objectives: The aim of this study was to evaluate the effect of progressive maximal exercise training of the lower extremities on exercise capacity and muscle fatiguability in children with cystic fibrosis.Study design: Between June and September 2017, eighteen children aged 8-12 years were recruited in this study. This study had two groups of children; the CF group consisted of nine children (6 males and 3 females) with cystic fibrosis and the control group consisted of nine healthy age matched children (6 males and 3 females). The children underwent a progressive maximal cardiopulmonary exercise cycling test (CPET), muscle fatigue test, and magnetic resonance imaging (MRI) to measure a muscle cross-section area (CSA). Also, pulmonary functions were assessed.Results: The findings of this study showed that the CF children had less pulmonary functions, had a less exercise capacity, and had a higher breathing reserve index and oxygen desaturation when compared with healthy children (p0.05). Conclusion: This study indicates that progressive maximal exercise doesn’t affect muscle fatiguability, muscle cross-section area, and maximal voluntary contraction in CF children with moderate respiratory diseases but includes lower exercise capacity. CF children and healthy age matched children have similar responses to maximal exercise in muscle fatiguability, muscle cross-section area, and maximal voluntary contractions but lower exercise capacity in the CF group.Keywords: Cystic fibrosis, children, lower extremities, exercise capacity, muscle fatiguability.

A 32-year-old male presented with shortness of breath and easy fatiguability for the past six months. There was no history of chest pain, fever, or palpitations. His renal function parameters were ...

A 42-year-old man presented with easy fatiguability, pain and swelling in the upper limbs of 6-month duration associated with progressive difficulty in bearing weights ([figure 1][1]). Imaging revealed extensive ill-defined osteolytic lesions of both humerus which are permeative, with a wide zone of

A 57-year-old woman presented to the emergency department with melena, easy fatiguability and dizziness for 2 days. She did not have haematemesis, abdominal pain, ascites or jaundice. Her routine master health check-up done 4 years previously revealed a diagnosis of Bernard-Soulier syndrome (BSS

Introduction/Hypothesis The purpose of this study is to determine the mid/long term shoulder function in patients with complete deltoid paralysis and intact rotator cuff. 27 patients with at least 2-years FU were included. Materials and methods Outcome measures included pain, range of motion (including the swallowtail test STT), deltoid extension lag test DELT and Bertelli test), subjective fatigability using the injured shoulder and postoperative modified Neer ratings. Results At an average 68 months FU, mean shoulder abduction was 131°, flexion 153°, external rotation with the arm at the side 58° and 58° with the arm abducted. All patients reported quick fatiguability with repetitive use of the injured arm which did not change over time. Average pain score was 2. Eighteen patients had positive STT and DELT tests and all patients had positive Bertelli test. Discussion This study demonstrates that patients with deltoid paralysis and intact rotator cuff do maintain most of their shoulder function and this is sustained over time. Level of evidence Level IV; prognostic Study: case series.

Examination of the oral cavity provides valuable clues to a large number of systemic disorders. Gum hypertrophy is usually associated with myelomonocytic and monocytic subtypes of acute myeloid leukaemia.1 Its occurrence in a case of acute promyelocytic leukaemia (APL) is unusual.1 We describe a 28-year-old man from India who presented to our hospital with a 2-week history of easy fatiguability and gum bleeding. Examination revealed pallor and marked gum hypertrophy (figure 1). Blood investigations showed haemoglobin 50 g/L, white cell count 5.4×109/L, differential counts 95% promyelocytes, 3% myelocytes, 1% metamyelocytes and 1% …

A 14-year-old boy of Asian origin presented with a history of bluish discolouration of the finger and toenail bed with associated mild fatiguability on exertion since early childhood. Clinical examination revealed bilaterally symmetric uniform central cyanosis with no associated clubbing. Cardiovascular and respiratory system examination was normal. Pulse oximetry revealed an oxygen saturation of 87% in all four limbs. Transthoracic and transoesophageal echocardiography showed no evidence of shunt lesions. In view of the past diagnosis of pulmonary arteriovenous fistulae made at 4 years of age, a repeat cardiac catheterisation study was done, which revealed no shunt at any level. Interestingly, arterial oxygen tension of the chocolate-brown blood was normal in all the samples, suggesting the possibility of methaemoglobinaemia. Co-oximetry revealed methaemoglobin levels of 36%, confirming the diagnosis. Secondary causes were ruled out. The family was counselled about the hereditary nature of the condition.

This systematic literature review aimed at examining the validity and applicability in everyday clinical rehabilitation practise of methods for the assessment of back muscle fatiguability in patients with chronic non-specific low back pain (CNSLBP).Extensive research was performed in MEDLINE, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Embase, Physiotherapy Evidence Database (PEDro) and Cochrane Central Register of Controlled Trials (CENTRAL) databases from their inception to September 2014. Potentially relevant articles were also manually looked for in the reference lists of the identified publications. Studies examining lumbar muscle fatigue in people with CNSLBP were selected. Two reviewers independently selected the articles, carried out the study quality assessment and extracted the results. A modified Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) scale was used to evaluate the scientific rigour of the selected works.Twenty-four studies fulfilled the selection criteria and were included in the systematic review. We found conflicting data regarding the validity of methods used to examine back muscle fatigue. The Biering-Sorensen test, performed in conjunction with surface electromyography spectral analysis, turned out to be the most widely used and comparatively, the most optimal modality currently available to assess objective back muscle fatigue in daily clinical practise, even though critical limitations are discussed.Future research should address the identification of an advanced method for lower back fatigue assessment in patients with CNSLBP which, eventually, might provide physical therapists with an objective and reliable test usable in everyday clinical practise. Implications for Rehabilitation Despite its limitations, the Biering-Sorensen test is currently the most used, convenient and easily available fatiguing test for lumbar muscles. To increase validity and reliability of the Biering-Sorensen test, concomitant activation of synergistic muscles should be taken into account. Pooled mean frequency and half-width of the spectrum are currently the most valid electromyographic parameters to assess fatigue in chronic non-specific low back pain. Body mass index, grading of pain and level of disability of the study population should be reported to enhance research quality.

The purpose of this study was to identify potential gender discrepancies in adaptation to low-volume high-intensity interval training (HIT). Active, young men (n = 11, age = 25.3 ± 5.5 years) and women (n = 9, age = 25.2 ± 3.1 years) matched for age, physical activity, and VO(2max) completed six sessions of HIT separated by 48 h over a 2-3 week period. Subjects completed four Wingate tests on days 1 and 2, five on days 3 and 4, and six on days 5 and 6. A control group of five men and four women (age = 22.8 ± 2.8 years) completed all testing, but did not perform HIT. Changes in VO(2max), oxygen (O(2)) pulse, peak/mean power output, fatiguability, substrate oxidation, and voluntary force production of the knee flexors and extensors were examined pre- and post-training with repeated measures ANOVA, with gender and group as between-subjects variables. Results showed significant (p0.05) improvements in VCO(2max) and peak/mean power output in response to HIT, as well as reduced respiratory exchange ratio and heart rate during submaximal exercise. The magnitude of change in VO(2max) (5.9 vs. 6.8%), power output (10.4-14.9% vs. 9.1-10.9%), and substrate oxidation was similar (p0.05) between men and women. Data show that adaptations to 6 days of low-volume HIT are similar in men and women matched for VO(2max) and physical activity.

During constant-load exercise above the lactate threshold, oxygen-uptake kinetics deviate from the pattern seen below the threshold, with an additional, delayed component superimposed on the monoexponential pattern. It was hypothesised that this slow component is due to the progressive recruitment of type II muscle fibres. Oxygen uptake was measured for six male power athletes (group P) and six male endurance athletes (group E) during constant-load knee extension exercise tests in order to determine slow component amplitude. In addition, an electrical stimulation protocol was employed in order to assess the functional contractile profile and fatiguability of the knee extensors. The amplitude of the slow component during exercise was significantly ( P0.05) greater in group P than in group E when expressed as an absolute value [mean (SEM)=77 (17) ml min(-1) and 24 (16) ml min(-1)] and when normalised to end-exercise oxygen uptake, VO(2) [8.2 (0.5)% and 2.6 (1.8)%]. Group differences were observed for percentage force loss during the electrical stimulation protocol [50.0 (3.4)% and 31.5 (3.7)% for groups P and E, respectively], increase in relaxation time from start to end of the fatigue test [87.9 (15.5)% and 31.1 (11.9)%], and relaxation time for fresh muscle [32.4 (1.0) ms and 40.6 (2.1) ms]. These contractile parameters may indicate a higher proportion of type II fibres in group P compared with group E. These experiments have shown evidence of a relationship between the amplitude of the slow component and muscle contractile properties, indicating that the origin of the slow component may lie in the pattern of different muscle fibre types.

Background Chronic fatigue syndrome (CFS) patients frequently complain of muscle fatigue and abnormally slow recovery, especially of the upper limb muscles during and after activities of daily living. Furthermore, disease heterogeneity has not yet been studied in relation to recovery of muscle function in CFS. Here, we examine recovery of upper limb muscle function from a fatiguing exercise in CFS patients with (CFS+FM) and without (CFS-only) comorbid fibromyalgia and compare their results with a matched inactive control group. Design In this case–control study, 18 CFS-only patients, 30 CFS+FM patients and 30 healthy inactive controls performed a fatiguing upper limb exercise test with subsequent recovery measures. Results There was no significant difference among the three groups for maximal handgrip strength of the non-dominant hand. A significant worse recovery of upper limb muscle function was found in the CFS+FM, but not in de CFS-only group compared with the controls (P

Objective Myofascial trigger points contribute significantly to musculoskeletal pain and motor dysfunction and may be associated with accelerated muscle fatiguability. The aim of this study was to investigate the electrically induced force and fatigue characteristics of muscle taut bands in rats. Methods Muscle taut bands were dissected out and subjected to trains of electrical stimulation. The electrical threshold intensity for muscle contraction and maximum contraction force (MCF), electrical intensity dependent fatigue and electrical frequency dependent fatigue characteristics were assessed in three different sessions (n=10 each) and compared with non-taut bands in the biceps femoris muscle. Results The threshold intensity for muscle contraction and MCF at the 10th, 15th and 20th intensity dependent fatigue stimuli of taut bands were significantly lower than those of non-taut bands (all pConclusions The present study demonstrates that the muscle taut band itself was more excitable to electrical stimulation and significantly less fatigue resistant than normal muscle fibres.

We have recently shown that patients with chronic obstructive pulmonary disease (COPD) develop contractile fatigue of their quadriceps muscle following endurance exercise. Pulmonary rehabilitation can produce physiological adaptations in patients with COPD. We hypothesized that if pulmonary rehabilitation induces physiological adaptations in the exercising muscle, it should become more fatigue resistant. Twenty one patients with COPD, mean age 69.9 +/- 1.9 yr, FEV(1) 45 +/- 4% predicted, participated in an 8-wk outpatient, supervised pulmonary rehabilitation exercise program. Quadriceps contractile fatigue was detected by a fall in quadriceps twitch force postexercise. Twitch force was measured during magnetic stimulation of the femoral nerve. Because potentiated twitches may be more sensitive at detecting fatigue, both unpotentiated (TwQu) and potentiated (TwQp) twitches were obtained before and 10, 30, and 60 min after constant load cycle exercise. Prerehabilitation, during constant load exercise, patients exercised at 37 +/- 4 W for 11.2 +/- 1.8 min. Prerehabilitation, TwQu fell significantly postexercise down to a minimum value of 82.5 +/- 3.1% of the baseline preexercise value (p < 0.001). Similarly, prerehabilitation, TwQp fell significantly postexercise down to a minimum value of 73.9 +/- 3.9% of baseline (p < 0.001). Postrehabilitation, for the same intensity and duration of exercise, TwQu was not significantly different from baseline at any time postexercise. Postrehabilitation, TwQp fell significantly postexercise but the fall in TwQp with exercise was significantly less postrehabilitation compared with prerehabilitation (p < 0.001). In conclusion, pulmonary rehabilitation resulted in increased fatigue resistance of the quadriceps muscle in patients with COPD.

This patient presented with progressive eating difficulties, having been originally investigated for mechanical gastroenterological problems. Fruitless examinations led to referral to a tertiary oral medicine unit and a detailed review of his history, where the significance of progressive fatiguability during and after mastication became apparent in his dysphagia. The insidious onset contrasted with his more rapid decline in function between the initial examination and specialist electromyographic investigations, neurological admission and management. The dangers of fatigue and pharyngeal incompetence are of particular relevance to oral and maxillofacial clinicians.

We previously reported that patients with spinal muscular atrophy do not lose muscle strength over time as measured quantitatively. However, we noted that many patients with spinal muscular atrophy suffer from what they called fatigue. We wondered if we could measure fatigue during a single maximal voluntary contraction, whether fatigue might increase with time, independent of muscle strength, and whether increasing fatigue might correlate with loss of function in some patients. We measured fatigue during a single maximal voluntary contraction in a cohort of patients having spinal muscular atrophy using quantitative strength testing. We included only patients with spinal muscular atrophy aged 5 years or older, so they could follow instructions regarding muscle contraction, and who were followed for at least 2 years. Seventy-six children with spinal muscular atrophy and 24 untrained individuals, aged 5 to 57 years (mean, 16.8 years), were studied. There was no discernible abnormal fatigue in patients with spinal muscular atrophy compared to untrained controls using our methodology. Thus, spinal muscular atrophy may not be associated with fatiguability. Moreover, spinal muscular atrophy does not appear to cause progressive muscle fatigue with age or loss of function. It is possible that fatigue was undetectable by our methods. An alternative explanation is that what patients describe as fatigue may be caused by factors outside the neuromuscular system. Such factors may include chronic respiratory insufficiency with hypoventilation and carbon dioxide retention as well as chronic malnutrition and negative nitrogen balance. ( J Child Neurol 1997;12:321-326).

1. To investigate the effect of the female reproductive hormones on muscle function, patients undergoing in vitro fertilization were tested during two phases of treatment. The first was following the downregulation of pituitary gonadotrophin releasing hormone (GnRH) receptors and the second after 9 days of gonadotrophin injections. 2. Maximal strength and fatiguability of the first dorsal interosseus muscle were assessed when oestrogen and progesterone were low, and less than 2 weeks later when oestrogen production reached supraphysiological levels. 3. There were no significant changes in either strength or fatigue resistance during acute, massive fluctuations in oestrogen. These results occurred at a time when progesterone levels remained relatively low. 4. Contrary to previous work, the present results suggest that oestrogen does not affect muscle strength.

The isokinetic forces, produced by a single as well as repetitive maximal knee extensions, and cross-sectional area (CSA) of the quadriceps femoris muscles were measured in 36 young adult males aged from 18 to 24 years: strength-trained (weight resistance-trained subjects, WT, N = 8), endurance-trained (middle distance runners, RUN, N = 13), and age-matched untrained subjects (UNT, N = 15). The CSA was measured using a B-mode ultrasound technique at the midpoint of the thigh length. The isokinetic forces at three velocities (1.05, 3.14 and 5.24 rad.s-1) were significantly correlated to CSA in all subjects (r = 0.01-0.849, p < 0.05). The absolute values in force development at three test velocities were significantly higher in WT than in RUN and UNT. While average values of force output per unit CSA were almost the same among the subject groups at test velocities of 3.14 and 5.24 rad.s-1, it was significantly higher in WT than in UNT at 1.05 rad.s-1. The repetitive maximal task consisted of 50 consecutive maximal knee extensions with constant velocity of 3.14 rad.s-1. The mean value of force (MF) of every 5 consecutive and all trials, respectively, was significantly correlated to CSA in all subjects (r = 0.448-0.885, p < 0.05). The average percentage of decline of MF with 50 maximal contractions was significantly lower in RUN (36 +/- 5%, mean +/- SE) than in WT (59 +/- 2%) and UNT (47 +/- 3%), and in UNT than in WT. The average values of MF per unit CSA for RUN became significantly higher than those for WT and UNT on and after the 36th-40th trial. Thus, force output during a single as well as repetitive maximal contractions was significantly correlated to muscle CSA. In terms of force per unit muscle CSA, however, WT and RUN showed specific force-velocity relation and fatiguability during repetitive maximal contractions, respectively, which could be considered as a result of muscle adaptation to their own training regimens.

The hair-on-end sign is a finding seen in the diploic space on skull radiographs and has the appearance of long, thin vertical striations of calcified spicules perpendicular to bone surface that look like hair standing on end. It is classically seen in children/adolescents with haemolytic anaemias, in particular, thalassemia major. A 24-year-oldman, born out of consanguinous marriage with history of splenectomy done at the age of four and history of requiring frequent blood transfusions, that is, every 5–6 months, came with complaints of breathlessness on exertion, generalised fatiguability and weakness. …

Three patients (two of them siblings) presented with easy fatiguability and prominent postexercise pain. Muscle biopsy showed that large areas of about one third of the type II fibers were completely devoid of mitochondria. The remaining mitochondria were unusually large in size, but otherwise normal ultrastructurally. In two patients, 31P in vivo MRS showed low phosphocreatine (PCr), high ADP, low phosphorylation potential at rest and slow ADP and PCr recovery after aerobic exercise. This appears to be a pathologically unique form of metabolic myopathy. The cause of the focal mitochondrial depletion is not known. It should be distinguished from the mtDNA depletion syndrome in which muscle mitochondria are not reduced, but proliferate.

Fibromyalgia is common in hospital practice. It is rarely reported in children, and most patients are in their 40s or 50s. In all settings there is a strong female preponderance (about 90%). It is well reported in the United States, Canada, and Europe, but racial and social predisposition have not been adequately addressed. Symptoms are variable. Pain and fatiguability are usually prominent and associated with considerable disability and handicap. Although patients can usually dress and wash independently, they cannot cope with a job or ordinary household activities. Pain is predominently axial and diffuse but can affect any region and may at times be felt all over. Characteristically, analgesics, non-steroidal anti-inflammatory drugs, and local physical treatments are ineffective and may even worsen symptoms. Patients often have a poor sleep pattern with considerable latency and frequent arousal. Typically they awake exhausted and feel more tired in the morning than later in the day. Unexplained headache, urinary frequency, and abdominal symptoms are common and may have been extensively investigated with no cause found. Patients usually score highly on measures of anxiety and depression. Although the term fibromyalgia syndrome is not ideal, it does not imply causation and describes the commonest symptom. Idiopathic diffuse pain syndrome, generalised rheumatism, and non-restorative sleep disorder are terms that are increasingly preferred by some. Typical hyperalgesic withdrawal response by patient with fibromyalgia. (Picture reproduced with patient's permission.) View this table: Prevalence of fibromyalgia Principal symptoms of fibromyalgia Pain Predominantly axial (neck and back), but may be all over Often aggravated by stress, cold, and activity Often associated with generalised morning stiffness Often with subjective swelling of extremities Paraesthesiae and dysaesthesiae of hands and feet Fatiguability Often extreme, occurring after minimal exertion Non-restorative sleep Waking unrefreshed Poor concentration and forgetfulness Low affect, irritable, and weepy Headache …

The purpose of this study is to determine the stability of symptoms of hypomania and depression across repeated affective episodes in patients with rapid-cycling bipolar disorder. Nine patients had a total of 30 depressive episodes and 31 hypomanic episodes during the period of observation. Standardized observer ratings indicated that the three symptoms most consistently reported during depressive episodes were fatiguability, decreased work activities and hypersomnia. These results as well as those from the standardized observer ratings of hypomania indicate that depression in this population consists of a lethargic, hypoactive state while hypomania may be a heightened state of activation. The clinical and theoretical implications of these findings are discussed.

Disabling generalized fatigue and muscle fatiguability are common features of post-poliomyelitis syndrome (PPS). In 17 fatigued PPS patients, we measured jitter on stimulation single-fiber electromyography (S-SFEMG) for at least 3.5 min before and after i.v. injection of 10 mg edrophonium. We observed reduction in jitter (defined as a significant difference in jitter means before and after edrophonium, unpaired t-test P < 0.05) in 7 patients, no change in 8, and a significant increase in 2 patients. Blinded to their edrophonium results, the 17 patients were treated with pyridostigmine 180 mg/day for 1 month, with a subjective improvement of fatigue in 9 patients, and with a significant reduction in mean Hare fatigue scores in the entire group of 17 patients (pre = 2.71, and post = 1.71; Wilcoxan signed rank sum test, P < 0.05). Edrophonium-induced reduction of jitter on S-SFEMG was significantly associated with pyridostigmine-induced subjective improvement of fatigue (Fisher's exact test, P < 0.04). A significant reduction in fatigue with pyridostigmine was observed only in the 7 patients who experienced a significant reduction in jitter with edrophonium (Wilcoxan signed rank sum test, P = 0.03). In addition, the 9 pyridostigmine responders experienced a significant reduction in jitter means pre- and post-edrophonium (100% vs. 88%, Bonferroni corrected, P < 0.01). We conclude that neuromuscular transmission as measured by jitter on S-SFEMG can improve with edrophonium in a proportion of PPS patients, and that generalized fatigue and muscle fatiguability in some patients with PPS may be due to anticholinesterase-responsive NMJ transmission defects.

The study design used is cross-sectional.The aim of this study is to examine muscle contractile and excitability characteristics during fatigue of the tibialis anterior in six individuals with chronic spinal cord injury (SCI) and matched able-bodied (AB) controls.McMaster University, Hamilton, ON, Canada.Muscle compound action potential (M-wave) characteristics, muscle twitch properties, and summated force were examined during a 2 min fatigue protocol of intermittent bursts at 30 Hz (4 s tetanus, 2 s rest) or maximal voluntary contraction (MVC). Evoked twitch responses were followed during a recovery period.M-wave amplitude was smaller in SCI (2.5 ± 1.6 mV in SCI, 5.7 ± 3.2 mV in AB) at baseline, but there was no change in M-wave amplitude or area during fatigue in either group. There was an increase in M-wave duration toward the end of recovery in the SCI group. Peak torque (PT) was not different between groups at baseline (3.8 ± 1.8 Nm in SCI, 3.7 ± 0.6 Nm in AB); PT potentiated significantly during fatigue in the AB, but not SCI group. There was significantly greater fatigue of both PT (43% decline) and summated force (57% decline) in the SCI group compared with the AB group (13% increase and 22% decline for PT and MVC, respectively).The dorsiflexor muscles in people with SCI are significantly more fatiguable than those in AB controls, but decreases in muscle excitability do not seem to be an important contributor to the increased fatiguability. The mechanisms behind the increased fatigue must lie distal to the muscle membrane.

1. In a multicenter, placebo-controlled, double-blind clinical trial in 156 elderly patients with psychopathologic symptoms, glycosaminoglycan polysulfate was found to be a therapeutlcally effective agent in the treatment of the earliest manifestations of a dementing process. 2. Treatment with glycosaminoglycan polysulfate in the daily dosage of 600 LRU, administered on the basis of a divided dosage schedule for 24 weeks, was significantly superior to an inactive placebo on several several outcome measures including the SCAG Total and factor scores (i.e., Cognitive Dysfunction, Withdrawal, Agitation/Irritability and Depression), the NOHLIS Total and Fatiguability factor scores, the MMSE, the HAM-D Total and Vegetative Symptoms factor score and the CGI Severity of Illness and Global Improvement. 3. The drug was well tolerated; vital signs and laboratory measures did not show clinically significant changes within the experimental period.

Quadriceps isometric strength, activation and fatiguability were measured in 11 patients with symptoms of fatigue three months after glandular fever or a glandular fever-like illness. Predicted normal and lower limits of normal muscle strength were calculated from height and age. These measures and the fatigue index were compared with a group of healthy students of similar age. Two of the patients were unable to activate fully their muscles. After allowing for this inhibition the group mean (SD) strength was 104 (22%) of predicted. Although there was no significant difference in the fatigue index between the patients and the control group, there was a trend for the patients to show less fatigue than controls. There was no difference in the muscle results for those patients who were found to have Epstein-Barr virus infections and those who did not. The feelings of weakness and fatigue experienced by the patients could not be explained by either physiological muscle fatigue or lack of effort.

The term “myasthenia” comes from the Latin “myos” meaning muscle, and the Greek asthenes, meaning a- (without) + sthenos (strength), and so it literally means muscle weakness, not fatiguable weakness. In common parlance, however, the term “myasthenic weakness” is used to describe the fatiguability which is a cardinal feature of myasthenia gravis, an acquired, autoimmune, post-synaptic disorder. In 1956 Lambert, Eaton and Rooke described a novel acquired pre-synaptic neuromuscular transmission disorder which has become referred to as the Lambert–Eaton myasthenic syndrome or LEMS. Indeed, it is described as a “myasthenic” syndrome in textbooks alongside myasthenia gravis but, potentially confusingly, it is not usually characterised by prominent complaints of fatiguable weakness and the clinical picture is unlike conventional myasthenia gravis. This commonly leads to diagnostic delay in a treatable disorder. A woman presented at the age of 32 years. She gave a four-year history of bilateral knee pain and had thought this was the explanation for her decreasing mobility requiring her to resort to sticks to walk, and for the past six months the use of a wheelchair out of doors. She had a past history of chondromalacia patellae and presumed this to be the cause of her pain. She did not give any story of variability in muscle strength or fatiguability. There was no upper limb weakness, or bulbar features. She had difficulty rising from a chair and was unable to get out of a bath. There were no sensory symptoms. She was referred from …

It is 60 years since malnutrition was first recognized as contributing significantly to the development of postoperative complications.’ This observation has since been confirmed in many studies. The attractiveness of this association has been the suggestion that, in contrast to many other surgical risk factors, impaired nutritional status can be treated. Nutritional support has indeed been shown to reduce weight loss and improve nitrogen balance and serum protein parameters.*J Furthermore, clinical evidence indicates that nutritional support restores tissue function, reflected by improved skeletal muscle force, decreased fatiguability, improvement of ventilatory function4 and the reversal of skin anergy, presumably equivalent to improved immune function. These observations have led to high expectations with regard to the ability of nutritional intervention to decrease morbidity and mortality from surgical therapy. However, it has been difficult to demonstrate a positive effect on clinical outcome since this is influenced by so many other factors, including the quality of anesthesia and surgery, age, and cardiorespiratory disease. Furthermore, a large number of studies investigating the effects of

The prognosis for patients who have mixed connective tissue disease (MCTD) varies from a benign course to severe progressive disease. In approximately one third of patients the clinical symptoms go into long-term remission and the anti-U1 small nuclear ribonucleoprotein antibodies disappear. One third of patients have a severe, progressive disease course. Persistent morbidity often is attributable to arthritis, easy fatiguability, and dyspnea on exertion. The most severe clinical manifestation is pulmonary hypertension which contributes to premature death in patients who have MCTD. Pulmonary hypertension is associated with proliferative vascular abnormalities that involve small pulmonary vessels, rather than interstitial lung disease.

The sleep apnoea/hypopnoea syndrome (SAHS) is characterized by retroglossal or retropalatal narrowing. The site of obstruction, and the fact that negative pressure in the upper airway increases retroglossal airway size, suggests that tongue muscles may play a role in the maintenance of upper airway patency. We therefore hypothesized that tongue protrusion strength and fatiguability may be predictors of apnoea/hypopnoea index, vary with age and may be different in SAHS patients and normal subjects. Maximal strength (Fmax) and fatiguability (measured as the total time subjects were able to maintain 50% Fmax on three consecutive occasions separated by 30 s) were assessed using a force transducer in 98 consecutive apnoeic/hypopnoeic male patients referred to our laboratory for sleep studies [apnoea/hypopnoea index (AHI) range 3–130/h, age range 30–74 y]. Fmax and fatiguability were also compared in 15 male SAHS patients (mean AHI 20/h) and 15 nonsnoring male subjects matched for age, body mass index and fat free mass. A further 26 SAHS patients had tongue protrusion strength/fatiguability measured before, during and after a night’s sleep. Log AHI was only weakly correlated with Fmax (r=− 0.21; P=0.03) and age (r=0.23; P=0.025), but not to fatiguability (P > 0.05). Comparison between SAHS and nonsnoring subjects did not demonstrate significant differences in Fmax (P=0.1) or fatiguability (P=0.1). There was no evidence of a change in muscle strength (P > 0.05) or fatigue (P > 0.05) during the course of a night’s sleep. We conclude that tongue protrusion strength and fatiguability are unlikely to be important factors in the pathogenesis of SAHS.

The mechanisms of senescence remain to be fully defined. This review focuses on recent advances in our understanding of body protein turnover, which is essential for the remodeling of tissues and production of specific proteins in time of need. Recent advances in technology make it possible to measure the synthesis rate of muscle myosin heavy chain, mitochondrial proteins and sarcoplasmic proteins, providing insight into the mechanisms of the sarcopenia of aging. A reduced synthesis rate of myosin heavy chain and mitochondrial protein may explain muscle weakness and fatiguability that occurs with aging. Aging also seems to affect selected liver proteins such as fibrinogen. The potential roles of exercise and hormone replacement in slowing the age-related decline in protein turnover is discussed.

Limb and respiratory muscle (diaphragm) strength and fatiguability have been extensively studied in man and are known to vary with age and sex. However, in contrast to limb muscles and the diaphragm, force and fatiguability characteristics have not been studied in upper airway muscles. This study examines the hypotheses that tongue protrusion strength or fatiguability, determined by the properties of the intrinsic muscles and genioglossus, may change with age and may be reduced in males compared to females. A force transducer was used to compare maximal tongue protrusion force (Fmax) and fatiguability in 81 males and 86 females matched for age (mean+/-SD, 43+/-19 yrs, 42+/-19 yrs, respectively). Fatiguability indices were based on the time that subjects could maintain 50% of Fmax. Fmax declined with age in both males (r=-0.57, p

Hyperventilation during phonation is one of the causes of fatigue in patients with vocal cord disorders. Transcutaneous (TC) PCO2 and PO2 were analyzed during phonation in patients with known recurrent nerve paralyses (RNP). There was no significant change in TCPCO2 in eight normal subjects. In cases with unilateral RNP and incomplete glottic closure, TCPCO2 decreased during phonation. This decrease in TCPCO2 resulted from hyperventilation during phonation. The TCPCO2 did not decrease in one case with RNP and complete glottic closure. In one case with incomplete glottic closure, the decrease in TCPCO2 and fatigue disappeared after treatment. These results suggest that hyperventilation is one of the causes for easy fatiguability during phonation in patients with RNP. Findings also show that measurements of TCPCO2 during phonation are useful for evaluating the cause of fatigue in patients with vocal disorders.

Patients with fibromyalgia complain of muscle pain, increased fatiguability and low physical endurance. However, no signs of specific muscle pathology have been determined in fibromyalgia. Alterations in muscle function may reflect effects of deconditioning or inhibition of contraction due to spinal or supraspinal mechanisms.

1. Given the importance of the ventilatory 'pump' muscles, it would not be surprising if they were endowed with both sensory and motor specializations. The present review focuses on some unexpected properties of the respiratory muscle system in human subjects. 2. Although changes in blood gas tension were long held not to influence sensation directly, studies in subjects who are completely paralysed show that increases in arterial CO2 levels elicit strong sensations of respiratory discomfort. 3. Stretch reflexes in human limb muscles contain a monosynaptic spinal excitation and a long-latency excitation. However, inspiratory muscles show an initial inhibition when tested with brief airway occlusions during inspiration. This inhibition does not depend critically on input from pulmonary or upper airway receptors. 4. Human inspiratory muscles (including the diaphragm) have been considered to fatigue during inspiratory resistive loading. However, recent studies using phrenic nerve stimulation to test the force produced by the diaphragm show that carbon dioxide retention (hypoventilation) and voluntary cessation of loading occur before the muscles become overtly fatigued.

Twelve outpatients, all women, who fulfilled the criteria for both fibromyalgia and chronic fatigue syndrome were rated on 15 items of the Comprehensive Psychopathological Rating Scale (CPRS-15). These items were chosen to constitute a proper neurasthenic subscale. Blood laboratory levels were generally normal. The most obvious finding was that, in all the patients, the homocysteine (HCY) levels were increased in the cerebrospinal fluid (CSF). There was a significant positive correlation between CSF-HCY levels and fatiguability, and the levels of CSF-B12 correlated significantly with the item of fatiguability and with CPRS-15. The correlations between vitamin B12 and clinical variables of the CPRS-scale in this study indicate that low CSF-B12 values are of clinical importance. Vitamin B12 deficiency causes a deficient remethylation of HCY and is therefore probably contributing to the increased homocysteine levels found in our patient group. We conclude that increased homocysteine levels in the central nervous system characterize patients fulfilling the criteria for both fibromyalgia and chronic fatigue syndrome.

A 50-year-old woman presented with complaints of progressive breathlessness and easy fatiguability over the past 2 years. Jugular venous pressure was raised with absence of a wave. Cardiac auscultation revealed two distinct mid-diastolic murmurs at the apex and a left lower sternal border with an ejection systolic murmur at the right second intercostal space. The ECG performed showed atrial fibrillation with a fast ventricular rate. Rate control was achieved with amiodarone infusion and intravenous diuretic therapy was instituted. Chest radiograph (figure 1 …

1. The effect of the different phases of the menstrual cycle on skeletal muscle strength, contractile properties and fatiguability was investigated in ten young, healthy females. Results were compared with a similar group on the combined (non-phasic) oral contraceptive pill (OC). Cycle phases were divided into the early and mid-follicular, mid-cycle (ovulatory) and mid- and late luteal. Cycle phases were estimated from the first day of the menstrual bleed. 2. Subjects were studied weekly through two complete cycles. Measurements included quadriceps and handgrip maximum voluntary isometric force and the relaxation times, force-frequency relationship and fatigue index of the quadriceps during percutaneous stimulation at a range of frequencies from 1 to 100 Hz. 3. In the women not taking the OC there was a significant increase of about 11% in quadriceps and handgrip strength at mid-cycle compared with both the follicular and luteal phases. Accompanying the increases in strength there was a significant slowing of relaxation and increase in fatiguability at mid-cycle. No changes in any parameter were found in the women taking the OC. 4. The changes in muscle function at mid-cycle may be due to the increase in oestrogen that occurs prior to ovulation.

To clarify the relationship between metabolic energy expenditure and fatiguability in paraplegic persons fitted with orthoses, we measured energy consumption in six thoracic paraplegic patients ambulating by means of reciprocating gait orthosis (RGO) used with and without functional electrical stimulation (FES). The data obtained from persons using both RGO and FES were adjusted to allow for the effects of fatiguability so as to obtain an approximate value for upper-body consumption. The data obtained from persons using RGO only were not adjusted, because no energy consumption occurred in the lower portion of the body. The data, expressed in kcal/kg-min and kcal/kg-m, were plotted against walking speed attained using RGO, and RGO with FES. The results were compared with those from persons fitted with long leg braces (LLB), hip guidance orthoses (HGO) and an FES walking aid (data obtained from available literature). We found that the lowest energy expenditure in kcal/kg-m across the full range of walking speeds occurred when both RGO and FES were used together, followed by RGO only, HGO, LLB, and FES only, respectively. The lowest energy expenditure in kcal/kg-min, for walking speeds, below 0-28 m/s, also occurred when both RGO and FES were used together, followed by RGO only, HGO, LLB, and FES only. The results suggest that, although the use of FES with RGO may increase oxygen uptake, it decreases energy expenditure in the upper extremities, thereby reducing patient fatigue. They also suggest that mechanical orthosis giving passive support to the hip, knee and ankle in combination with FES may provide the most efficient walking aid for paraplegic persons.

BackgroundOne of the major symptoms of postpoliomyelitis syndrome (PPS) is disabling generalized fatigue. Subjects with PPS also report muscle fatiguability and display electrophysiologic evidence of anticholinesterase-responsive neuromuscular junction transmission defects, suggesting that anticholinesterase therapy may be useful in the management of disabling fatigue.MethodsWe initiated an open trial of the oral anticholinesterase pyridostigmine, up to 180 mg per day, in 27 PPS patients with generalized fatigue and muscle fatiguability. Response to pyridostigmine was assessed with the Hare fatigue scale, the modified Barthel index for activities of daily living, and a modified Klingman mobility index.ResultsTwo patients could not tolerate the medication. After one month of therapy, 16 patients (64%) reported a reduction in fatigue on the Hare fatigue scale; three of 16 showed improvement on the modified Barthel index for activities of daily living, and two of 16 experienced improvement on a modified Klingman mobility index. Pyridostigmine responders were significantly more fatigued than non-responders on the pre-treatment Hare score, but were not significantly different with regard to age, sex, age at acute poliomyelitis, or severity of acute poliomyelitis.ConclusionsPyridostigmine may be useful in the management of fatigue in selected patients with PPS. Response to pyridostigmine may be predicted by severity of pre-treatment fatigue.

A 27-year-old woman presented to the medicine outpatient clinic with easy fatiguability and breathlessness on exertion since 2 months. She also complained of sore oral mucosa and was unable to swallow large morsels of food. Physical examination revealed angular cheilitis and pigmentation of the oral mucosa, severe pallor, koilonychias (figure 1), large volume pulse and a haemic murmur in the left parasternal area. Investigations revealed hypochromic microcytic anaemia with haemoglobin of 5.6 g%. Serum iron studies, showed an …

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.

Generalized fatigue and muscle fatiguability are major symptoms of post-poliomyelitis syndrome (PPS), and may be due to neuromuscular junction transmission defects, as suggested by increased jitter on single fiber electromyography (SFEMG). To determine the etiology of this defect, we studied jitter at low (1, 5 Hz) and high (10, 15, 20 Hz) frequency stimulation with stimulation SFEMG in 17 post-polio patients with muscle fatiguability, and in 9 normal controls. In 5 of 17 PPS patients and in 1 of 9 controls, jitter was significantly higher (unpaired t-test, P < 0.05) at high frequency stimulation (HFS). In the remaining PPS patients and controls there was no significant difference in jitter at high and low stimulation frequencies. PPS patients with increased jitter at HFS had a significantly longer time interval since acute polio (mean 48.5 years) than PPS patients without increased jitter at HFS (mean 40 years; P < 0.05), but were not distinguished by other historical or clinical criteria. We conclude that the neuromuscular junction defect in post-polio patients is similar to that observed in amyotrophic lateral sclerosis, and is probably due to ineffective conduction along immature nerve sprouts and exhaustion of acetylcholine stores. The appearance of an increase in jitter with HFS in post-polio patients may be dependent upon time after acute polio.

Subjective impairment of memory and concentration is a frequent complaint in sufferers from chronic fatigue. To study this, 65 general practice attenders identified as having chronic fatigue were administered a structured psychiatric interview and a brief screening battery of cognitive tests. Subjective cognitive impairment was strongly related to psychiatric disorder, especially depressed mood, but not fatigue, anxiety, or objective performance. Simple tests of attention and concentration showed some impairment but this was influenced by both fatigue and depression. Subjects with high levels of fatigue performed less well on a memory task requiring cognitive effort, even in the absence of depression. There was no evidence for mental fatiguability. The relationship between depression, fatigue, and cognitive function requires further research.

Answers on p 279. A 35 year old man was referred for acromegaly by primary physicians. He complained of mild diffuse headache and easy fatiguability. Clinically he had somatic features of acromegaly and his visual acuity was reduced (6/30: left eye, 6/36 right eye) with a bitemporal superior quadrantanopia. Fundi were normal. He was …

Muscle function tests of the triceps brachii muscle were performed before operation and on the third postoperative day in ten patients undergoing elective cholecystectomy. Electromyograms (EMGs) were recorded by surface electrodes during sustained isotonic and isometric muscle contraction with a constant force of 20 per cent of the preoperative maximal voluntary contraction. Root-mean-square of the EMG was calculated together with the neuromuscular efficiency and measures of the fatiguability. These parameters were compared with changes in the simultaneously measured serum phosphate concentrations. Mean(s.e.m.) neuromuscular efficiency measured after 32–40 s of muscle contraction decreased 14(5) per cent after operation (P < 0·01), whereas the mean fatiguability of the muscle was unchanged. Mean serum phosphate concentration was 0·87(0·06) mmol/l before operation and 0·79(0·06) mmol/l 3 days after the operation (P > 0·05). Two patients developed severe postoperative hypophosphataemia (serum phosphate concentration < 0·50 mmol/l). Postoperative muscle function deterioration was not associated with changes in the serum phosphate level (P > 0·10; r = 0·03). We conclude that patients undergoing cholecystectomy develop postoperative deterioration in skeletal muscle function, which is not associated with serum phosphate concentration.