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Thyrotoxic periodic paralysis is a rare endocrine disorder most prevalent among individuals of Asian descent that presents as proximal muscle weakness, hypokalemia, and signs of hyperthyroidism. We present the case report of a patient with previously undiagnosed hyperthyroidism, protracted muscle weakness with transient exacerbations, and nocturnal onset of periodic paralysis affecting the upper and lower limbs.
A Caucasian girl developed slowly progressive sensory neural deafness and bulbar and spinal muscle weakness typical of the Vialetto-Van Laere syndrome. As the condition progressed the major disabilities became dysphagia, respiratory muscle weakness and postural hypotension. Treatment with gastrostomy feedings, oxygen and fludrocortisone acetate produced worthwhile functional improvement.
BACKGROUND: Rehabilitation services after hip arthroplasty (HA) usually occur in the first 6 months following surgery. Reports in the literature suggest that 9 months to several years after HA surgery, patients are generally satisfied with pain relief. However, many express dissatisfaction with their ability to perform domestic and social activities. Reduced walking ability and long-term lower extremity (LE) muscle weakness may contribute to decreased mobility. The purpose of this study was to compare the within-group LE muscle strength, gait, and self-assessed functional mobility in adults 9 months to 6 years after HA surgery to age- and gender-matched controls. METHODS: Thirty subjects (15 HA and 15 control) were studied. LE muscle strength was assessed using the Spark handheld dynamometer. Gait parameters were measured using the GAITMAT II, and self-assessed mobility was evaluated using the hip-rating questionnaire. RESULTS: The HA group walked significantly more slowly than the control group at maximum walking speed. The operative LE of the HA group had less muscle strength than the nonoperative LE, and the hip abductors were the most affected muscle group in that LE. The HA group scored lower in the domains of impact, pain, and function on the hip-rating questionnaire. CONCLUSION: Because of long-term residual impairments and disabilities noted after HA surgery, intervention beyond the initial post-surgical rehabilitation is needed.
Myotonic dystrophy (DM) is an autosomal dominant multisystem disorder involving muscle, brain, heart, eyes and endocrine organs, among others. The molecular basis is an unstable trinucleotide repeat at the 3'-untranslated end of the myotonin protein kinase gene on chromosome 19 q 13.3, and the number of repeats correlates with the severity of muscle weakness. We performed a clinical, psychometric and MRI study on 43 patients with DM and correlated findings with the molecular analysis. Nineteen patients had mild distal muscle weakness, 17 moderate und 7 severe weakness. Thirteen had marked cognitive deficits with reduced speed of cognition, low IQ, and apathy. MRI showed pathological muscle signal in 35 cases with a characteristic mosaic involving distal muscle groups, often sparing the posterior tibial muscle. Cerebral MRI showed significant subcortical white matter lesions in 20 cases and brain atrophy in 15 cases. Clinical and MRI findings of CNS and muscle both correlated with CTG repeat length, but did not parallel each other. DM is a significant disease of the brain as well as muscle, and several aspects of the disease correlate with molecular findings, with a threshold effect for repeats exceeding 1000 trinucleotides. The individual predominance of specific organ involvement probably depends on variable somatic mosaicism of the molecular defect.
The functional and histologic picture of steroid-induced myopathy was systematically examined in eight patients with chronic obstructive pulmonary disease (COPD) and compared with control patients with COPD matched for age, sex, and degree of airflow obstruction. Steroid-induced myopathy was associated with severe peripheral muscle weakness, quadriceps force being 23 +/- 14 versus 71 +/- 23% in control patients with COPD (p < 0.001). In addition, clear ventilatory muscle weakness was present. PImax was 37 +/- 15 versus 67 +/- 24% in control patients (p < 0.001 ), and PEmax averaged 34 +/- 10 versus 74 +/- 23% (p < 0.001). Vital capacity tended to be slightly reduced compared with that in control patients (69 +/- 21 versus 80 +/- 16%, p = 0.11). The only biochemical abnormalities associated to steroid-induced myopathy were a moderately increased lactic dehydrogenase level (697 +/- 301 versus 421 +/- 128 IU/L, p < 0.001) and an increased creatine excretion in 24-h urine (990 +/- 609 versus 159 +/- 219 mg/24 h, p< 0.001). On quadriceps biopsy steroid-induced myopathy was characterized by increased variation in diameter of fibers, with several angular atrophic fibers and diffuse necrotic and basophilic fibers. In addition, increased amount of connective tissue in between fibers and increased number of subsarcolemmal and central nuclei were present. On ATPase stain diffuse fiber atrophy predominantly affecting fast fibers was present, but there was no indication that atrophy was confined to type IIb fibers in contrast to conventional thinking. On follow-up, survival of patients with steroid-induced myopathy was reduced in comparison with control patients with COPD with similar degree of airflow obstruction (p < 0.025).
Masticatory muscle electromyograms (EMGs) were recorded while patients with bulbar myasthenia gravis chewed artificial food and compared with those of patients with ocular myasthenia gravis, patients in clinical remission who had previously suffered from bulbar myasthenia gravis and healthy individuals. Masticatory performance and EMGs were significantly smaller in the bulbar group. There were no indications of subclinical masticatory muscle weakness in patients with bulbar myasthenia gravis in remission and in patients with ocular myasthenia gravis. Patients with bulbar myasthenia gravis barely compensated for muscular weakness by chewing at a higher percentage of their maximal EMG. These quantitative findings, when combined with subjective reports of masticatory muscle weakness, show that a need to support the jaw is characteristic of patients with bulbar myasthenia gravis who produce low EMG activity.
The purpose of this study was to determine whether or not losses of strength or endurance following eccentric and concentric exercise are associated with reduced excitation. The effects of eccentric and concentric work on maximal voluntary isometric contraction (MVC) and surface electromyogram (EMG) of the quadriceps were studied in 10 healthy male subjects following bench-stepping for 20 min with a constant leading leg. Prior to stepping and at 0, 0.25, 0.50, 0.75, 1, 3, 24 and 48 h afterwards the subjects performed a 30 s leg extension MVC with each leg during which the isometric force and the root mean square voltage of the EMG were recorded. In the eccentrically exercised muscles (ECC), MVC0-3 (force during the first 3 s of contraction) fell immediately after the bench-stepping exercise to 88+/-2% (mean+/-SE) of the pre-exercise value and remained significantly lower than the concentrically exercised muscles (p<0.05). The muscle weakness in the ECC could not be attributed to central fatigue as surface EMG amplitude at MVC0-3 increased during the recovery period. Muscle weakness after eccentric exercise appears to be due to contractile failure, which is not associated with a reduction in excitation as assessed by surface EMG. Muscular fatigue over 30 s did not change in the two muscle groups after exercise (p = 0.79), indicating that the ECC were weaker but not more fatiguable after exercise.
We attempted to correlate the marked neurological asymmetry observed in two amyotrophic lateral sclerosis patients with their histopathological lesions. Patient 1, a 52-year-old man, developed dysarthria and dysphagia, followed by muscle weakness in the left arm and then of the left leg. Patient 2, a 44-year-old man, developed muscle weakness in the left hand, left leg, tongue with left-sided predominance, right hand and right leg in that order of progression. Both patients exhibited moderate to marked left-sided predominant involvement of the lower motor neuron system, accompanied by retained or hyperactive deep tendon reflexes on the left side in the early stage of their illness. Most of the asymmetry in the lower motor neuron system involvement persisted until the death of the patients. Histopathological examinations, including semiquantitative analysis, revealed that both patients exhibited left-sided predominant degeneration of the lower motor neuron system at those spinal cord levels where the neurological asymmetry was of a moderate to marked degree. In addition left-sided predominant degeneration of the lateral corticospinal tracts was seen in both patients and right-sided predominant involvement of Betz cells in the leg area of the motor cortex of patient 1. This pattern of both the neurological and histopathological asymmetry suggested the probable existence of an intimate somatotopically related linkage between the upper motor neuron system degeneration and lower motor neuron system degeneration in both patients.
Despite continuously improving diagnostic facilities, respiratory chain disorders (RCDs) are easily overlooked or misdiagnosed. We thus studied phenotype variability and the diagnostic potential of clinical and laboratory investigations in patients with RCD. We retrospectively evaluated clinical and laboratory investigations in 130 patients with RCD: 63 women and 67 men, aged 17-87 years, diagnosed between January 1992 and December 1999. mtDNA mutations were found in 20 patients; a respiratory chain defect but no mutation in 4; an abnormal lactate stress test but no mutation or biochemical defect in 66; and ragged-red fibres or reduced oxidative enzyme staining but no mutation, biochemical defect or abnormal lactate stress test in 40 patients. The most frequent initial manifestation of RCD were limb weakness, muscle pain and sensory disturbances. The most frequent clinical findings at diagnosis were muscle pain, fatiguability, limb weakness, reduced tendon reflexes and muscle wasting, irrespective of the diagnostic evidence. Mean age at onset, disease duration and time until diagnosis were 39, 14 and 13 years, respectively, without sex differences. The family history was positive in 29% of the patients. Hyperlipidaemia was found in 45%, hyper-CK-aemia in 42%, short stature in 33%, thyroid dysfunction in 17%, diabetes in 12%, and epilepsy in 8% of the patients. Laboratory investigations that prove useful to support the diagnosis of RCD are muscle biopsy, electromyography, lactate stress testing, echocardiography and mtDNA analysis. Systems most often involved in RCDs were the PNS, CNS, endocrine system and heart. The diagnosis of RCD requires awareness of the great phenotypic heterogeneity and an individualized, integral, multidisciplinary approach.
BACKGROUND: Mutations of the LMNA gene, encoding the nuclear envelope proteins lamins A and C, have been associated with 7 distinct pathologic conditions. OBJECTIVE: To report 5 cases with the same missense mutation in exon 6 of the LMNA gene, resulting in an E358K substitution in the central rod domain. DESIGN: Case report. SETTING: Three muscle centers in England. PATIENTS: Five patients with missense mutations of the LMNA gene. RESULTS: All 5 individuals had muscle involvement, but the onset, severity, distribution of muscle weakness, and presence of associated features were highly variable. Three patients had humeroperoneal distribution of weakness and typical features of Emery-Dreifuss muscular dystrophy. Two other patients showed additional novel features. One had congenital onset and predominant axial weakness, with poor neck control and inability to sit independently at the age of 21 months. Another patient presented in childhood with an unusual pattern of muscle weakness, short stature, and midface hypoplasia with striking fat accumulation around the face and neck, in contrast to wasting of adipose tissue and muscle in the limbs. She developed both respiratory failure and cardiac arrhythmias in her late 20s. CONCLUSION: Our cases expand the clinical spectrum associated with mutations in the LMNA gene and further illustrate the overlapping phenotypes of the laminopathies.
Involvement of respiratory muscles is a nearly constant feature of neuromuscular disorders, leading to respiratory failure. A careful respiratory follow up adapted to the variable time course of each disease is therefore mandatory. As the first step, a systematic clinical evaluation is essential to detect the subtle respiratory symptoms and signs related to respiratory muscle failure. Dyspnea and orthopnea are often late findings in patients with a usually severe functional impairment due to peripheral muscle weakness. Nocturnal respiratory events (obstructive sleep apnea syndrome and hypoventilation) are strongly suggested by daytime hypersomnolence and frequent morning headaches. Physical evaluation is essential to detect accessory muscle recruitment, supine abdominal paradox, and encumbrance of upper or lower airways. Vital capacity (VC) is the most classical lung function test. The major limitation of spirometry is its poor sensitivity to detect a moderate inspiratory muscle weakness. Supine VC may improve the detection of diaphragmatic involvement. Peak expiratory flow during cough (cough PEF) gives an overall evaluation of cough efficiency, values below 160 to 270 L/min suggesting poor airway clearance. Arterial blood gases are performed in case of clinical signs, significant deterioration of lung function tests, or sleep desaturations. Hypercapnia is weakly related to lung function results in patients with Steinert dystrophy and those with bulbar involvement. A specific evaluation of respiratory muscle strength is mandatory, as these tests are both sensitive and highly prognostic. Possible discrepancies (particularly in bulbar patients) between maximal inspiratory pressure (PImax) and sniff nasal inspiratory pressure (SNIP) justify to perform both measurements and to select the highest pressure. A maximal expiratory pressure (PEmax) below 45 cm H2O may indicate a compromised cough efficiency but the correlation with cough PEF may be poor. A screening nocturnal oxymetry is useful to detect sleep apneas and hypoventilation. Criteria defining significant desaturations remain however controversial. Suspicion of obstructive sleep apnea syndrome on clinical grounds or oxymetry findings should be confirmed by a conventional polysomnography.
The technique of repetitive nerve stimulation was developed as a means of confirming a diagnosis of MG. The application of this test in the clinical evaluation of patients with muscle weakness has identified other disorders of neuromuscular transmission such as LEMS, infantile botulism, and several forms of congenital myasthenia. Repetitive nerve stimulation to several different nerves, before and after exercising the muscles, usually permits identification of disorders of neuromuscular transmission more readily than very detailed study of one muscle. There are other useful electrodiagnostic tests, but in most cases, repetitive nerve stimulation of weak muscles will permit the identification of a disorder of neuromuscular transmission.
The discovery of the genetic basis of hereditary lower motor neuron disease (LMND) and the recognition of multifocal motor neuropathy as a distinct clinical entity necessitate a new classification of LMND. To this end, we studied the clinical and electrophysiological features of 49 patients with sporadic adult-onset LMND in a cross-sectional study. Disease duration was more than 4 years to exclude the majority of patients with amyotrophic lateral sclerosis. Based on the pattern of weakness, we identified three groups: 13 patients with generalized weakness (group 1); eight patients with symmetrical, distal muscle weakness (group 2); and 28 patients with non-generalized asymmetrical weakness of the arms in most patients (group 3). Group 3 could be subdivided into patients with weakness in predominantly the distal (group 3a) or the proximal (group 3b) muscle groups, both with disease progression to adjacent spinal cord segments. Distinctive features of group 1 were an older age at onset, more severe weakness and muscle atrophy, lower reflexes, greater functional impairment, more widespread abnormalities on concentric needle EMG, respiratory insufficiency and serum M-protein. In groups 2 and 3, concentric needle EMG findings also suggested a more widespread disease process. Retrospectively, the prognosis of sporadic adult-onset LMND appears to be favourable, because clinical abnormalities were still confined to one limb in most patients after a median disease duration of 12 years. We propose to classify the patients in the different subgroups as slowly progressive spinal muscular atrophy (group 1), distal spinal muscular atrophy (group 2), segmental distal spinal muscular atrophy (group 3a) and segmental proximal spinal muscular atrophy (group 3b). The described clinical phenotypes may help to distinguish between different LMND forms.
Muscle weakness in the elderly is prevalent and morbid, closely linked to the frailty, functional decline, immobility, falls, and injuries in this population. The marked decrease in skeletal muscle strength and size with aging is a multifactorial syndrome which may be attributable in part to: (a) biological changes of aging itself; (b) the accumulation of acute and chronic diseases; (c) the assumption of a sedentary life style, and (d) selective or generalized nutritional inadequacies. Inactivity and undernutrition are potentially at least partially reversible with appropriate interventions, and therefore the delineation of the attributable risk of these two factors to the muscle weakness of aging is a critical research goal. Similarly, identification of appropriate modalities of physical activity and nutrition which have positive effects on muscle physiology in the aged is the focus of major investigations currently.
The pathogenic events leading to the progressive muscle weakness in patients with a E706K mutation in the head of the myosin heavy chain (MyHC) IIa were analyzed at the muscle cell and motor protein levels. Contractile properties were measured in single muscle fiber segments using the skinned fiber preparation and a single muscle fiber in vitro motility assay. A dramatic impairment in the function of the IIa MyHC isoform was observed at the motor protein level. At the single muscle fiber level, on the other hand, a general decrease was observed in the number of preparations where the specific criteria for acceptance were fulfilled irrespective of MyHC isoform expression. Our results provide evidence that the pathogenesis of the MyHC IIa E706K myopathy involves defective function of the mutated myosin as well as alterations in the structural integrity of all muscle cells irrespective of MyHC isoform expression.
OBJECTIVE: West Nile virus has recently become a public health concern in the United States, after an outbreak in New York City in 1999. It is a mosquito-borne virus that causes a spectrum of disease from flu-like symptoms to encephalopathy, muscle weakness, and, in some cases, death. STUDY DESIGN: Case Report. METHODS: A patient infected with West Nile virus presented with progressive muscle weakness, and later developed bilateral vocal fold paresis. His clinical presentation, physical and laboratory examination findings, and course of illness will be discussed. RESULTS: After a prolonged hospital stay, and presumptive treatment for Guillain-Barré, repeat CSF analysis revealed infection with the West Nile virus. The patient developed bilateral vocal fold paralysis during his hospital course. At long-term follow-up, the patient's left vocal fold paralysis persisted, while the right vocal fold paralysis had resolved. CONCLUSIONS: Although several viruses have been associated with recurrent laryngeal nerve injury, this is the first report of West Nile virus induced vocal fold paralysis.
OBJECTIVE: The purpose of this study was to assess sleep and breathing in patients with amyotrophic lateral sclerosis (ALS) with bulbar muscle involvement. DESIGN: Prospective, controlled study of sleep and breathing measured during polysomnography. SETTING: University teaching hospital and referral center. PATIENTS: Patients with definite ALS and healthy age-matched control subjects. INTERVENTIONS: Eighteen ALS patients and 10 age-matched control subjects underwent one night of polysomnography. Thirteen patients with ALS were studied for a second night. RESULTS: The ALS patients had more arousals per hour (p = 0.008), more stage 1 sleep (p = 0.01), and a shorter total sleep time (TST) (279 +/- 69 vs 331.4 +/- 55.9 min, mean +/- SD, p = 0.04) than the control subjects. The ALS patients had mild sleep-disordered breathing with a greater apnea/hypopnea index (AHI) than the control subjects (p = 0.005). On the second night of polysomnography, there was an increase in TST (p = 0.003) and rapid eye movement (REM) sleep (p = 0.009), an improvement in sleep efficiency (p = 0.02), and less stage 1 sleep (p = 0.04). Eight ALS patients had sleep-disordered breathing consisting of periods of hypoventilation, predominantly during REM sleep. CONCLUSIONS: Sleep-disordered breathing occurs in patients with ALS and is similar to patients without ALS with respiratory muscle weakness. No obstructive sleep apnea was observed. One potential reason for its absence might be the inability of patients with respiratory muscle weakness to generate an inspiratory pressure greater than the upper airway closing pressure. This hypothesis should be addressed in future studies.
BACKGROUND: Loss of muscle strength and cross-sectional area is a well-recognized consequence of spaceflight. Existing countermeasures have not been fully effective in preventing muscle weakness and atrophy in microgravity. Resistance exercise programs that consist of both eccentric and concentric actions have resulted in strength and muscle mass gains in ground-based studies. HYPOTHESES: 1) A concentric/eccentric combination exercise regimen (with a bias of either concentric or eccentric exercise) will result in a greater strength gain than concentric exercise alone; and 2) an eccentrically biased regimen will result in the greatest strength gain of all. METHODS: The 31 subjects were randomly assigned to one of three isokinetic exercise groups (CON-ECC: 75% concentric and 25% eccentric; ECC-CON: 75% eccentric and 25% concentric; CON: 100% concentric); each subject trained the right leg 3 d per week for 5 wk. Pre- and post-training isokinetic concentric/ eccentric strength tests and DEXA scans assessed changes in muscle strength and/or mass. RESULTS: All three groups showed an increase in eccentric muscle strength with the CON group showing the smallest gain (10.1%). Significantly larger gains were noted in the two combination groups (19.5%, 18.1%; p < 0.042), with the largest gains in eccentric strength. No significant change was noted in muscle mass. CONCLUSIONS: A resistance exercise protocol which includes eccentric as well as concentric exercise, particularly when the eccentric exercise is emphasized, appears to result in greater strength gains than concentric exercise alone. Findings suggest eccentric exercise may be an important component of the in-flight resistance exercise protocol for long-duration spaceflight.