Muscle Weakness and Atrophy—Clinical and Laboratory Evaluation

A thorough family history, the age at the time of onset and detailed information regarding the rate, mode of progression and distribution of weakness is needed for evaluation of patients with weakness and atrophy. Associated findings such as dermal lesions, tenderness, myotonia and fasciculations should also be noted.The major diagnostically useful laboratory tests are electromyography, nerve conduction, serum enzyme levels and muscle biopsy.Each clinical and laboratory finding should be categorized in terms of its neuro-anatomical origin, since weakness may result from disturbances in the corticospinal pathways, the lower motor neuron, the myoneural junction and the muscle.     

Rhabdomyolysis happened after the start of dabigatran etexilate treatment: A case report

There are few reports of rhabdomyolysis caused by anticoagulants, and it is extremely rare for it to be caused by dabigatran etexilate. An 86-year-old female experienced sudden muscle weakness and pain, a significant increase in Creatine kinase, and renal impairment after oral administration of dabigatran etexilate for 3 weeks. The enhanced thigh MRI showed abnormal signal in multiple thigh muscle groups, indicating that the lesions should be considered inflammatory diseases. In conclusion, the possibility of rhabdomyolysis should be ruled out when muscle weakness and myalgia occur at the beginning of dabigatran etexilate treatment.     

The skeletal muscle phenotype of children with Neurofibromatosis Type 1 – A clinical perspective

Neurofibromatosis type 1 (NF1) can affect multiple systems in the body. An under recognised phenotype is one of muscle weakness. Clinical studies using dynamometry and jumping mechanography have demonstrated that children with NF1 are more likely to have reduced muscle force and power. Many children with NF1 are unable to undertake physical activities to the same level as their peers, and report leg pains on physical activity and aching hands on writing. Children and adolescents with NF1 reporting symptoms of muscle weakness should have a focused assessment to exclude alternative causes of muscle weakness. Assessments of muscle strength and fine motor skills by physiotherapists and occupational therapists can provide objective evidence of muscle function and deficits, allowing supporting systems in education and at home to be implemented. In the absence of an evidence base for management of NF1-related muscle weakness, we recommend muscle-strengthening exercises and generic strategies for pain and fatigue management. Currently, trials are underway involving whole-body vibration therapy and carnitine supplementation as potential future management options.     

Acromegaly as An Endocrine Form of Myopathy: Case Report and Review of Literature

ObjectiveTo describe a case of muscle weakness in a patient with acromegaly and to review the pathophysiologic features of this disorder.MethodsWe present the clinical, laboratory, electromyographic, and muscle biopsy findings in our patient and review related reports in the literature.ResultsA 58-year-old woman with acromegaly presented with complaints of bilateral hip pain, weakness, and instability 8 months after transsphenoidal resection of a growth hormone (GH)-secreting pituitary macroadenoma. She had biochemically normal thyroid and adrenal function and no evidence of any neuropathy, inflammatory myopathy, or rheumatologic disorder to explain her symptoms. Investigations revealed increased levels of GH, insulin-like growth factor-I, serum creatine kinase (CK), and the MB fraction of CK, normal results of nerve conduction studies, and nonspecific findings on electromyography and muscle biopsy. A review of the literature revealed that although muscle weakness is a well-recognized feature of acromegaly, only a few cases similar to ours have been reported since acromegaly was first described in the late 1800s. Little is known about the natural history, best diagnostic approach, and optimal therapy for this debilitating complication.ConclusionMuscle weakness in acromegaly is common and may result from a combination of the direct effect of GH excess on muscle and other metabolic derangements (hypothyroidism, hypoadrenalism, or diabetes). Mechanical factors may also contribute, such as joint laxity in conjunction with hypermobility. Affected patients may benefit from a reduction in GH levels and physiotherapy for adaptive training. Persistently increased serum CK levels in a patient with diabetes, for whom no other cause is found, should prompt an investigation for acromegaly. More research into this aspect of acromegaly is needed for enhancement of our understanding of, and therapy for, this debilitating condition. (Endocr Pract. 2005;11:18-22)     

Piriform Syndrome

Among a variety of deep muscle trigger points, the piriform muscle trigger point is selected for individual scrutiny. This seems fully justified by the great potential for confusing this entity with discogenic disease and consequently having unnecessary surgical procedures carried out.The diagnosis can be made from findings on simple physical diagnostic tests and an appropriate history. Low back and hip pain with pain radiating down the back of the leg should suggest piriform syndrome as part of the differential diagnosis. This is especially true if a female patient has complaint of dyspareunia.Pain and weakness on resisted abduction-external rotation of the thigh is a sign of piriform syndrome. This is confirmed by tenderness and reproduction of the patient''s complaints by digital pressure over the belly of the piriform muscle, completing the diagnostic criteria.Local injection of the muscle belly is curative. There are no laboratory or x-ray findings leading to a diagnosis.     

Gluteus maximus and soleus compensate for simulated quadriceps atrophy and activation failure during walking

Important activities of daily living, like walking and stair climbing, may be impaired by muscle weakness. In particular, quadriceps weakness is common in populations such as those with knee osteoarthritis (OA) and following ACL injury and may be a result of muscle atrophy or reduced voluntary muscle activation. While weak quadriceps have been strongly correlated with functional limitations in these populations, the important cause–effect relationships between abnormal lower extremity muscle function and patient function remain unknown. As a first step towards determining those relationships, the purpose of this study was to estimate changes in muscle forces and contributions to support and progression to maintain normal gait in response to two sources of quadriceps weakness: atrophy and activation failure. We used muscle-driven simulations to track normal gait kinematics in healthy subjects and applied simulated quadriceps weakness as atrophy and activation failure to evaluate compensation patterns associated with the individual sources of weakness. We found that the gluteus maximus and soleus muscles display the greatest ability to compensate for simulated quadriceps weakness. Also, by simulating two different causes of muscle weakness, this model suggested different compensation strategies by the lower extremity musculature in response to atrophy and activation deficits. Estimating the compensation strategies that are necessary to maintain normal gait will enable investigations of the role of muscle weakness in abnormal gait and inform potential rehabilitation strategies to improve such conditions.     

Increase in glucose 1,6-bisphosphate levels, activation of phosphofructokinase and phosphoglucomutase, and inhibition of glucose 1,6-bisphosphatase in muscle induced by trifluoperazine

Injection of trifluoperazine (TFP) to rats induced a significant rise in the level of glucose 1,6-bisphosphate (Glc-1,6-P2) in muscle. This increase in Glc-1,6-P2, the potent activator of phosphofructokinase and phosphoglucomutase, was accompanied by a marked activation of both enzymes, when assayed in the absence of exogenous Glc-1,6-P2 under conditions in which these enzymes are sensitive to regulation by endogenous Glc-1,6-P2. Glucose-1,6-bisphosphatase (the enzyme that degrades Glc-1,6-P2) was markedly inhibited following the injection of TFP, which may account for the rise in the Glc-1,6-P2 level. Previous results from this laboratory have revealed that muscle damage or weakness is characterized by a decrease in Glc-1,6-P2 levels, leading to a marked reduction in the activities of phosphoglucomutase and phosphofructokinase (the rate-limiting enzyme in glycolysis). The present results suggest that TFP treatment may have a beneficial effect on the depressed glycolysis in muscle weakness or damage.     

Botox produces functional weakness in non-injected muscles adjacent to the target muscle

Botulinum type-A (BTX-A) neurotoxin exerts a paralytic effect on muscles and is used increasingly to treat a variety of muscle spasticity disorders. While its pathogenesis for muscle-induced weakness has been well elucidated, the functional effects of BTX-A administration are incomplete. Specifically, weakness as a function of muscle length and stimulation frequency has only been investigated qualitatively in a few muscles and the possible effect of the toxin on non-target muscles, although considered possible based on laboratory experiments, has not been studied widely and the functional implications remain unknown. Therefore, the purpose of this study was to measure the functional implications of BTX-A on force production and possible weakness of a target muscle and a non-injected neighbouring muscle. The cat soleus was chosen as the target muscle and was injected with 3.2-3.5U of BTX-A/kg in one hind limb, while the soleus of the other hind limb served as a non-injected control. Force-length properties within and exceeding the functional range of motion were determined at frequencies of stimulation of 10, 30 and 50Hz. Force-length properties of the adjacent non-injected plantaris were also determined in the experimental and contralateral hind limb. Four weeks following BTX-A injections, peak soleus forces were decreased by 30% (50Hz), 29% (30Hz) and 29% (10Hz) and peak plantaris forces were decreased by 11% (50Hz), 16% (30Hz) and 16% (10Hz), in the experimental compared to the contralateral hind limb. Absolute BTX-associated force loss was significantly different at all frequencies of stimulation and all lengths for the soleus, while in the plantaris there was a significant force loss across long (> or = -4mm) but not short muscle lengths. Decreases in peak force were independent of the stimulation frequency. We concluded from the results of this study that BTX-A injection in the target muscle caused a measurable effect on force production and that force production was decreased in non-target neighbouring muscles at and near lengths of peak force production. These results are of particular importance in therapeutic procedures where isolated muscles are targeted for treatment. They should also be considered in neurophysiological studies in which BTX-A injections are used to selectively diminish muscle function.     

Myasthenia Gravis: Brief Guide to Diagnosis and Management

Physicians should consider the possibility of myasthenia gravis in patients complaining of fluctuating muscle weakness and easy fatigability. The disorder may occur in either sex at any age. Repeated measurements of multiple muscle groups and functions to include baseline strength and response to a control as well as anticholinesterase drugs are desirable in reaching a diagnosis. Appropriate doses of anticholinesterase medication reduce weakness and fatigability in most patients. Selected patients may benefit from thymectomy. Patients in crisis failing to respond to anticholinesterase drugs, having difficulty maintaining a patent airway or adequate respiratory exchange are best managed by prompt tracheostomy using a cuffed tube, with adequate tracheobronchial toilet and mechanical respiratory assistance.     

The role of muscles in joint degeneration and osteoarthritis

The purpose of this work was to establish a controlled and reversible muscle weakness model for studying the effects of weakness on joint degeneration leading to osteoarthritis (OA). The knee extensor muscles of rabbits were injected with single or repeat doses of Botulinum type-A toxin (BTX-A) to partially inhibit acetylcholine (ACh) release at the neuromuscular junction. BTX-A-injected muscles atrophied, they became weaker and push-off forces during hopping were reduced compared to control. BTX-A injections had the greatest effect at short-muscle length and low-stimulation frequencies. Superimposing BTX-A injections on anterior cruciate ligament transection did not cause greater muscle atrophy or weakness than BTX-A injections alone. Monthly repeat injections could be used to keep muscles weak for half a year without any obvious adverse effects to the animals. Gross morphology of the knees and histology of articular cartilage suggested that, in some animals, 4 weeks of muscle weakness resulted in initial signs of joint degeneration, indicating that weakness may be an independent risk factor for joint degeneration leading to OA.     

Influence of weak hip abductor muscles on joint contact forces during normal walking: probabilistic modeling analysis

The weakness of hip abductor muscles is related to lower-limb joint osteoarthritis, and joint overloading may increase the risk for disease progression. The relationship between muscle strength, structural joint deterioration and joint loading makes the latter an important parameter in the study of onset and follow-up of the disease. Since the relationship between hip abductor weakness and joint loading still remains an open question, the purpose of this study was to adopt a probabilistic modeling approach to give insights into how the weakness of hip abductor muscles, in the extent to which normal gait could be unaltered, affects ipsilateral joint contact forces. A generic musculoskeletal model was scaled to each healthy subject included in the study, and the maximum force-generating capacity of each hip abductor muscle in the model was perturbed to evaluate how all physiologically possible configurations of hip abductor weakness affected the joint contact forces during walking. In general, the muscular system was able to compensate for abductor weakness. The reduced force-generating capacity of the abductor muscles affected joint contact forces to a mild extent, with 50th percentile mean differences up to 0.5 BW (maximum 1.7 BW). There were greater increases in the peak knee joint loads than in loads at the hip or ankle. Gluteus medius, particularly the anterior compartment, was the abductor muscle with the most influence on hip and knee loads. Further studies should assess if these increases in joint loading may affect initiation and progression of osteoarthritis.     

Hoffman's syndrome: muscle stiffness,pseudohypertrophy and hypothyroidism

Primary hypothyroidism is a chronic and insidious disease caused by failure of thyroid hormone production. We observed a 38-year-old woman admitted to our hospital due to progressive proximal weakness, muscle pain and fatigue during mild exercise. Laboratory tests showed features of rhabdomyolysis and hypothyroidism. After examination of the thyroid, we reached a diagnosis of Hashimoto's thyroiditis and hypothyroid myopathy. Hypothyroidism should be considered as a differential diagnosis of creatine kinase elevation; actually, neuromuscular symptoms and signs occur in most newly diagnosed patients with thyroid diseases. Hypothyroidism presenting as muscle stiffness and pseudohypertrophy is called 'Hoffman's syndrome'.     

Neuropathy and fatal hepatitis in a patient receiving amiodarone.

Muscle weakness, neuropathy, and transient rises in hepatic enzyme activity have been reported with the use of the antiarrhythmic agent amiodarone. A 68 year old teetotaller with normal liver function was given amiodarone for resistant supraventricular arrhythmias. He presented 19 months later with vomiting, muscle weakness and wasting, sensory neuropathy, and hepatomegaly. Liver biopsy showed fibrosis and the presence of hyaline. The amiodarone was withdrawn. Three months later he developed ascites. Oesophageal varices were found and he later died. The liver showed micronodular cirrhosis. The large volume of distribution and long half life of amiodarone may explain the persistence of toxicity, which may have been aggravated by simultaneously administered doxepin in this case. Amiodarone should be withdrawn if abnormal liver function or neuropathy develops.     

Diaphragmatic weakness and myositis associated with systemic juvenile rheumatoid arthritis.

An unusual presentation of systemic juvenile rheumatoid arthritis in a young adult is reported. Among the major manifestations were severe muscle weakness and dyspnea, which were found to be due to myositis and diaphragmatic weakness. The evolution of the disease and its response to therapy are described.     

Frequency and length-dependent effects of Botulinum toxin-induced muscle weakness

While the pathogenesis of Botulinum toxin type A (BTX-A)-induced muscle weakness has been systematically researched, little is known about the effects of motor fibre paralysis on the mechanical properties of skeletal muscle. Here, the long-term effect of BTX-A injection on the force-length and force-frequency properties of rabbit knee extensors is investigated. BTX-A-induced muscle weakness was greater at short compared to long muscle lengths and at low compared to high stimulation frequencies four weeks following intervention. Therefore, we conclude that the paralysing effects of BTX-A are not uniform, and must be considered in biomechanical models of musculoskeletal rehabilitation in which BTX-A is used therapeutically, as for example in patients with cerebral palsy. Although the present results could be explained through a variety of mechanisms, this study does not allow for drawing firm conclusions about the length and frequency-dependent effects of BTX-A.     

Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation.

We report the clinical, biochemical, and molecular genetic findings in a family with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA glutamic acid mutation at position 14709. The proband and his sister presented with congenital myopathy and mental retardation and subsequently developed cerebellar ataxia. Other family members had either adult-onset diabetes mellitus with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies. Biochemical studies of muscle mitochondria showed reduced complex I and IV activities. The mtDNA mutation was heteroplasmic in blood and muscle in all matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures containing high proportions of mutant mtDNA exhibited impaired mitochondrial translation. These observations indicate that mtDNA tRNA point mutations should be considered in the differential diagnosis of congenital myopathy. In addition they illustrate the diversity of phenotypes associated with this mutation in the same family and further highlight the association between mtDNA mutations and diabetes mellitus.     

Surgical treatment of primary hyperparathyroidism in the elderly.

Twelve patients aged over 70 with primary hyperparathyroidism (persistent hypercalcaemia and raised serum parathyroid hormone concentrations) underwent parathyroidectomy, which was well tolerated by all. After operation serum calcium concentrations returned to normal and the commonest symptoms before operation (muscle weakness, malaise, and mild to severe dementia), although not related in severity to the degree of hypercalcaemia, improved. Mental function was greatly improved. The findings suggest that primary hyperparathyroidism should be sought in any elderly patient with hypercalcaemia and that more such patients with the diagnosis should be considered for parathyroidectomy irrespective of age.     

Factors involved in strain-induced injury in skeletal muscles and outcomes of prolonged exposures.

Repetitive motion disorders can involve lengthening of skeletal muscles to perform braking actions to decelerate limbs under load often resulting in muscle strains and injury. Injury is a loss of isometric force (weakness) requiring days to recover. The capacity of skeletal muscle to tolerate repeated strains is dependent on multiple factors including individual variation. The most important factors producing muscle strain injury are the magnitude of the resisting force (peak-stretch force) and the number of strains. Other factors such as muscle length and fiber type contribute to the susceptibility to injury as well, but to a lesser degree. Strain injury can also lead to inflammation and pain. Chronic exposure to repeated strains can result in fibrosis that is not completely reversed after months of rest. Long rest times appear to be the only factor reported to prevent inflammation in rats following repeated strain injury. Further understanding of the mechanism for prevention of histopathologic changes by long rest times should provide a rationale for prevention of negative outcomes.     

Non-uniform muscle adaptations to eccentric exercise and the implications for training and sport

Due to the variations in morphological and architectural characteristics of fibers within a skeletal muscle, regions of a muscle may be differently affected by eccentric exercise. Although eccentric exercise may be beneficial for increasing muscle mass and can be beneficial for the treatment of tendinopathies, the non-uniform effect of eccentric exercise results in regional muscle damage and as a consequence, non-uniform changes in muscle activation. This regional muscle weakness can contribute to muscle strength imbalances and may potentially alter the load distribution on joint structures, increasing the risk of injury. In this brief review, the non-uniform effects of eccentric exercise are reviewed and their implications for training and sport are considered.