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Muscle Weakness (muscle + weakness)
Kinds of Muscle Weakness Selected AbstractsMuscle Weakness and Falls in Older Adults: A Systematic Review and Meta-AnalysisJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2004Julie D. Moreland MSc Objectives: To evaluate and summarize the evidence of muscle weakness as a risk factor for falls in older adults. Design: Random-effects meta-analysis. Setting: English-language studies indexed in MEDLINE and CINAHL (1985,2002) under the key words aged and accidental falls and risk factors; bibliographies of retrieved papers. Participants: Fifty percent or more subjects in a study were aged 65 and older. Studies of institutionalized and community-dwelling subjects were included. Measurements: Prospective cohort studies that included measurement of muscle strength at inception (in isolation or with other factors) with follow-up for occurrence of falls. Methods: Sample size, population, setting, measure of muscle strength, and length of follow-up, raw data if no risk estimate, odds ratios (ORs), rate ratios, or incidence density ratios. Each study was assessed using the validity criteria: adjustment for confounders, objective definition of fall outcome, reliable method of measuring muscle strength, and blinded outcome measurement. Results: Thirty studies met the selection criteria; data were available from 13. For lower extremity weakness, the combined OR was 1.76 (95% confidence interval (CI)=1.31,2.37) for any fall and 3.06 (95% CI=1.86,5.04) for recurrent falls. For upper extremity weakness the combined OR was 1.53 (95% CI=1.01,2.32) for any fall and 1.41 (95% CI=1.25,1.59) for recurrent falls. Conclusion: Muscle strength (especially lower extremity) should be one of the factors that is assessed and treated in older adults at risk for falls. More clinical trials are needed to isolate whether muscle-strengthening exercises are effective in preventing falls. [source] Acute botulinum toxin-induced muscle weakness in the anterior cruciate ligament-deficient rabbitJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2005David Longino Abstract We established botulinum type-A toxin (BTX-A) injections as a powerful tool to cause knee extensor weakness in New Zealand White (NZW) rabbits. The purpose of this study was to determine if BTX-A induced quadriceps weakness causes muscle dysfunction beyond that caused by anterior cruciate ligament (ACL) transection in the knee of NZW rabbits. Twenty animals were randomly divided into four study groups (n = 5 each); uninjected controls, BTX-A injection alone, ACL transection alone, BTX-A injection and ACL transection combined. Isometric knee extensor torque, quadriceps muscle mass, and vertical and anterior,posterior ground reaction forces were measured four weeks post single (BTX-A and ACL), unilateral intervention. Muscle weakness, muscle atrophy and decrease in ground reaction forces were all significantly greater for the experimental compared to the untreated contralateral legs. BTX-A injection produced a greater deficit in quadriceps mass and knee extensor torque than ACL transection alone, but produced smaller deficits in the ground reaction forces. ACL transection superimposed on BTX-A injection did not change either knee extensor torque production or muscle mass. Together these results suggest that BTX-A injection causes great force and muscle mass deficits, and affects functional gait in a significant manner, but it has no measurable functional effect when superimposed on ACL transection, at least not in the acute protocol tested here. Hopefully, BTX-A injection for acutely enhancing the degree of muscle weakness in otherwise untreated animals, or in experimental models of osteoarthritis, will help in investigating the role of muscle weakness in joint degeneration. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutationANNALS OF NEUROLOGY, Issue 1 2010Hans Knoblauch MD We investigated a large German family (n = 37) with male members who had contractures, rigid spine syndrome, and hypertrophic cardiomyopathy. Muscle weakness or atrophy was not prominent in affected individuals. Muscle biopsy disclosed a myopathic pattern with cytoplasmic bodies. We used microsatellite markers and found linkage to a locus at Xq26-28, a region harboring the FHL1 gene. We sequenced FHL1 and identified a new missense mutation within the third LIM domain that replaces a highly conserved cysteine by an arginine (c.625T>C; p.C209R). Our finding expands the phenotypic spectrum of the recently identified FHL1-associated myopathies and widens the differential diagnosis of Emery,Dreifuss,like syndromes. ANN NEUROL 2010;67:136,140 [source] Neuromuscular involvement in various types of Ehlers,Danlos syndrome,ANNALS OF NEUROLOGY, Issue 6 2009Nicol C. Voermans MD Objective Ehlers,Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Muscle involvement is plausible based on recently discovered interactions between muscle cells and extracellular matrix molecules; however, muscle symptoms are only sporadically reported. We designed a cross-sectional study to find out whether neuromuscular features are part of EDS. Methods Standardized questionnaires, physical examination, nerve conduction studies, electromyography, muscle ultrasound, and muscle biopsy were performed in 40 EDS patients with the vascular, classic, tenascin-X (TNX),deficient type EDS, and hypermobility type of EDS caused by TNXB haploinsufficiency. Results Muscle weakness, myalgia, and easy fatigability were reported by the majority of patients. Mild-to-moderate muscle weakness (85%) and reduction of vibration sense (60%) were common. Nerve conduction studies demonstrated axonal polyneuropathy in five patients (13%). Needle electromyography myopathic features in nine patients (26%) and a mixed neurogenic-myopathic pattern in most (60%). Muscle ultrasound showed increased echo-intensity (48%) and atrophy (50%). Mild myopathic features were seen on muscle biopsy of five patients (28%). Overall, patients with the hypermobility type EDS caused by TNXB haploinsufficiency were least affected. Interpretation Mild-to-moderate neuromuscular involvement is common in various types of EDS, with a remarkable relation between residual TNX level and degree of neuromuscular involvement, compatible with a dose,effect relation. The findings of this study should increase awareness of neuromuscular symptoms in EDS patients and improve clinical care. They also point to a role of the extracellular matrix in muscle and peripheral nerve function. This is an updated version of this article that originally published online on June 29, 2009. Ann Neurol 2009;65:687,697 [source] Double-Blind, Randomized, Placebo-Controlled Pilot Study of the Safety and Efficacy of Myobloc (Botulinum Toxin Type B) for the Treatment of Palmar HyperhidrosisDERMATOLOGIC SURGERY, Issue 3 2005Leslie Baumann MD Background Palmar hyperhidrosis is a problem of unknown etiology that affects patients both socially and professionally. Botulinum toxin type B (Myobloc), approved by the Food and Drug Administration for use in the treatment of cervical dystonia in the United States in December 2000, has subsequently been used effectively in an off-label indication to treat hyperhidrosis. There are sparse data, however, in the literature evaluating the safety and efficacy of BTX-B for the treatment of palmar hyperhidrosis. Objective We evaluated the safety and efficacy of Myobloc in the treatment of bilateral palmar hyperhidrosis. This was a double-blind, randomized, placebo-controlled study to report on the safety and efficacy of Myobloc. Methods Twenty participants (10 men, 10 women) diagnosed with palmar hyperhidrosis were injected with either Myobloc (5,000 U per palm) or a 1.0 mL vehicle (100 mM NaCl, 10 mM succinate, and 0.5 mg/mL human albumin) into bilateral palms (15 Myobloc, 5 placebo). The participants were followed until sweating returned to baseline levels. The main outcome measures were safety, efficacy versus placebo, and duration of effect. Results A significant difference was found in treatment response at day 30, as determined by participant assessments, between 15 participants injected with Myobloc and 3 participants injected with placebo. The duration of action, calculated in the 17 participants who received Myobloc injections and completed the study, ranged from 2.3 to 4.9 months, with a mean duration of 3.8 months. The single most reported adverse event was dry mouth or throat, which was reported by 18 of 20 participants. The adverse event profile also included indigestion or heartburn (60%), excessively dry hands (60%), muscle weakness (60%), and decreased grip strength (50%). Conclusion Myobloc proved to be efficacious for the treatment of palmar hyperhidrosis. Myobloc had a rapid onset, with most participants responding within 1 week. The duration of action ranged from 2.3 to 4.9 months, with a mean of 3.8 months. The adverse event profile included dry mouth, indigestion or heartburn, excessively dry hands, muscle weakness, and decreased grip strength. MYOBLOC WAS PROVIDED FOR THIS STUDY BY ELAN PHARMACEUTICALS. [source] Decreased Tear Expression with an Abnormal Schirmer's Test Following Botulinum Toxin Type A for the Treatment of Lateral Canthal RhytidesDERMATOLOGIC SURGERY, Issue 2 2002Seth L. Matarasso MD background. Inactivation of muscles of facial expression by chemodenervation with botulinum toxin remains an off-label indication. Nevertheless, it continues to be a safe and effective technique to improve dynamic rhytides and is the treatment of choice for the hypertrophic lateral fibers of the orbicularis oculi muscle that can cause the superimposed crow's feet. objective. Although infrequent and self-limiting, the complication of unexpected muscle weakness from toxin diffusion or erroneous placement is documented. methods. However, injection into the pretarsal portion of the orbicularis oculi muscle resulting in unilateral ocular irritation and diminished tear expression as evidenced by a dry eye and an abnormal Schirmer's test has rarely been reported. Direct injection into the pretarsal fibers of the muscle as opposed to diffusion of the toxin into the muscle fibers or the lacrimal gland was consistent with the onset of action of the toxin and the prolonged duration of the ocular symptoms. results. Treatment consisted of ocular lubrication until the effects of the toxin dissipated and muscle tone returned. Subsequent treatment did not result in a result in a recurrence of adverse sequelae. conclusions. Facial muscles are small, not isolated, and often have fibers that interdigitate. An important factor in the administration of botulinum toxin is the identification of the muscles responsible for the corresponding rhytide. Precise knowledge of muscular anatomy and function will aid in minimizing this and other potential complications. [source] Decreased activities of mitochondrial respiratory chain complexes in non-mitochondrial respiratory chain diseasesDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2006Joannie Hui MBBS The aim of this study was to illustrate the difficulties in establishing a diagnosis of mitochondrial respiratory chain (MRC) disorders based on clinical grounds in combination with intermediate activities of the MRC enzyme complexes. We reviewed retrospectively all medical and laboratory records of patients initially considered likely to have MRC disorders on clinical grounds, and subsequently diagnosed with other disorders (n=20; 11 males, 9 females). Data were retrieved from hospital records, referral letters, and results of enzymatic analysis at a reference laboratory. Clinical symptoms included developmental delay, epilepsy, hypotonia, movement disorder, spastic quadriplegia, tetany, microcephaly, visual problems, carpopedal spasms, dysmorphism, hearing loss, muscle weakness and rhabdomyolysis, and fulminant hepatitis. Blood and cerebrospinal fluid lactate levels were elevated in 13/20 and 9/20 respectively. One or more MRC complex activities (expressed as ratios relative to citrate synthase and/or complex II activity) were less than 50% of control mean activity in 11/20 patients (including patients with deficiencies of pyruvate dehydrogenase complex, pantothenate kinase, holocarboxylase synthetase, long-chain hydroxy acyl-CoA dehydrogenase, molybdenum co-factor, and neonatal haemochromatosis). One patient had a pattern suggestive of mitochondrial proliferation. We conclude that intermediate results of MRC enzymes should be interpreted with caution and clinicians should be actively looking for other underlying diagnoses. [source] Serious psychiatric and neurological adverse effects of herbal medicines , a systematic reviewACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2003E. Ernst Objective: Psychiatric and neurological patients frequently try herbal medicines often under the assumption that they are safe. The aim of this systematic review was to provide a summary of recent data on severe psychiatric and neurological adverse effects of herbal remedies. Method: Computerized literature searches were carried out to identify all reports of psychiatric and neurological adverse effects associated with herbal medicines. These data were subsequently extracted, validated and summarized in narrative and tabular form. Results: Numerous case reports comprise a diverse array of adverse events including cerebral arteritis, cerebral oedema, delirium, coma, confusion, encephalopathy, hallucinations, intracerebral haemorrhage, and other types of cerebrovascular accidents, movement disorders, mood disturbances, muscle weakness, paresthesiae and seizures. Several fatalities are on record. They are caused by improper use, toxicity of herbal ingredients, contamination and adulteration of preparations and herb/drug interactions. Conclusion: Herbal medicines can cause serious psychiatric and neurological adverse effects. [source] Different pathophysiological mechanisms of intramitochondrial iron accumulation in acquired and congenital sideroblastic anemia caused by mitochondrial DNA deletionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2006Thomas Matthes Abstract:, Sideroblastic anemias (SA) are characterized by iron accumulation in the mitochondria of erythroblasts. Although we have evidence of mitochondrial gene alterations in sporadic congenital cases, the origin of acquired forms [refractory anemia with ring sideroblasts (RARS)], is still largely unknown. Here, we report the analysis of respiratory chain function in a patient with a large mitochondrial deletion and in patients with RARS. A young boy with SA showed symptoms typical of a mitochondrial disease with metabolic acidosis, muscle weakness and cerebral involvement. His bone marrow DNA was analyzed for the presence of mitochondrial deletions. We found a new mitochondrial (mt)DNA deletion spanning 3614 bp and including all the mt genes encoding complex IV, plus ATPase 6 and 8, and several transfer (t)RNAs. All tissues analyzed (liver, skeletal muscle, brain, pancreas) showed a heteroplasmic distribution of this mutant DNA. Bone marrow homogenates were obtained from five patients with RARS and from three patients with normal bone marrow and respiratory chain function assayed by spectrophotometric analysis. Cytochrome c oxidase (CCO) activity was greatly reduced in the patient's bone marrow. In contrast, CCO activity and global respiratory chain function were conserved in patients with RARS. We conclude that deficient CCO activity secondary to mtDNA deletions is related to intramitochondrial iron accumulation, as in our patient or in those with Pearson's syndrome, whereas other mechanisms, e.g. nuclear DNA mutations, have to be proposed to be involved in the acquired forms of SA. [source] EFNS guideline on diagnosis and management of limb girdle muscular dystrophiesEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2007F. Norwood The limb girdle muscular dystrophies (LGMD) are termed as such as they share the characteristic feature of muscle weakness predominantly affecting the shoulder and pelvic girdles; their classification has been completely revised in recent years because of elucidation of many of the underlying genetic and protein alterations in the various subtypes. An array of diagnostic measures is possible but with varying ease of use and availability. Several aspects of muscle cell function appear to be involved in the causation of muscle pathology. These cellular variations may confer some specific clinical features thus permitting recognition of the LGMD subtype and hence directing appropriate levels of monitoring and intervention. Despite an extensive literature on the individual limb girdle dystrophies, these publications may be impenetrable for the general neurologist in this increasingly complex field. The proposed guidelines suggest an approach to the diagnosis and monitoring of the limb girdle dystrophies in a manner accessible to general neurologists. [source] The structure and mode of action of different botulinum toxinsEUROPEAN JOURNAL OF NEUROLOGY, Issue 2006J. O. Dolly The seven serotypes (A,G) of botulinum neurotoxin (BoNT) are proteins produced by Clostridium botulinum and have multifunctional abilities: (i) they target cholinergic nerve endings via binding to ecto-acceptors (ii) they undergo endocytosis/translocation and (iii) their light chains act intraneuronally to block acetylcholine release. The fundamental process of quantal transmitter release occurs by Ca2+ -regulated exocytosis involving sensitive factor attachment protein-25 (SNAP-25), syntaxin and synaptobrevin. Proteolytic cleavage by BoNT-A of nine amino acids from the C-terminal of SNAP-25 disables its function, causing prolonged muscle weakness. This unique combination of activities underlies the effectiveness of BoNT-A haemagglutinin complex in treating human conditions resulting from hyperactivity at peripheral cholinergic nerve endings. In vivo imaging and immunomicroscopy of murine muscles injected with type A toxin revealed that the extended duration of action results from the longevity of its protease, persistence of the cleaved SNAP-25 and a protracted time course for the remodelling of treated nerve,muscle synapses. In addition, an application in pain management has been indicated by the ability of BoNT to inhibit neuropeptide release from nociceptors, thereby blocking central and peripheral pain sensitization processes. The widespread cellular distribution of SNAP-25 and the diversity of the toxin's neuronal acceptors are being exploited for other therapeutic applications. [source] Signs and symptoms at diagnosis of amyotrophic lateral sclerosis: a population-based study in southern ItalyEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2006S. Zoccolella Amyotrophic lateral sclerosis (ALS) diagnostic criteria are used to select patients for clinical trials based on different levels of diagnostic certainty, according to the spread of upper (UMN) and lower motoneuron (LMN) signs in different anatomic regions. However, the clinical presentation of ALS patients is extremely variable and this can delay the time to diagnosis and decrease the likelihood for trial entry. The aims of the study were to describe the signs and symptoms of diagnosis in a population-based incident cohort of ALS cases, using the El Escorial (EEC) and the Revised Airlie Diagnostic Criteria (AHC). The source of the study was a prospective population-based registry established in Puglia, southern Italy, in 1997. The diagnosis and the classification of the cases were based on EEC and AHC. All incident ALS cases during the period 1998,1999 were enrolled and followed up. During the surveillance period, we identified 130 ALS incident cases, and bulbar-ALS represented 20% of our cohort. The highest risk for bulbar onset was among subjects aged >75 years [RR: 20.1, 95% confidence interval (CI) 3.4,118.0] compared with subjects aged <55 years and among females compared with males (Relative risk (RR): 2.75, 95% CI: 1,7.3). The vast majority of patients (72%) referred progressive muscle weakness in the limbs as the presenting symptom. Eighty percent of cases presented contemporary bulbar or spinal involvement; UMN signs in the bulbar region were present in 24% of cases and any motoneuronal sign in thoracic region in only 15% of the cases. In this population-based series, progressive muscle weakness was the most common presenting sign; bulbar onset was associated with advanced age and female sex. UMN signs in the bulbar region and any motoneuronal sign in the thoracic region were observed in 20% of our case series. This may represent the main limitation to show the spread of signs during diagnostic assessment for inclusion in epidemiological studies and clinical trials. [source] Severely impaired neuromuscular synaptic transmission causes muscle weakness in the Cacna1a -mutant mouse rolling NagoyaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2007Simon Kaja Abstract The ataxic mouse rolling Nagoya (RN) carries a missense mutation in the Cacna1a gene, encoding the pore-forming subunit of neuronal Cav2.1 (P/Q-type) Ca2+ channels. Besides being the predominant type of Cav channel in the cerebellum, Cav2.1 channels mediate acetylcholine (ACh) release at the peripheral neuromuscular junction (NMJ). Therefore, Cav2.1 dysfunction induced by the RN mutation may disturb ACh release at the NMJ. The dysfunction may resemble the situation in Lambert,Eaton myasthenic syndrome (LEMS), in which autoantibodies target Cav2.1 channels at NMJs, inducing severely reduced ACh release and resulting in muscle weakness. We tested neuromuscular function of RN mice and characterized transmitter release properties at their NMJs in diaphragm, soleus and flexor digitorum brevis muscles. Clinical muscle weakness and fatigue were demonstrated using repetitive nerve-stimulation electromyography, grip strength testing and an inverted grid hanging test. Muscle contraction experiments showed a compromised safety factor of neuromuscular transmission. In ex vivo electrophysiological experiments we found severely impaired ACh release. Compared to wild-type, RN NMJs had 50,75% lower nerve stimulation-evoked transmitter release, explaining the observed muscle weakness. Surprisingly, the reduction in evoked release was accompanied by an ,,3-fold increase in spontaneous ACh release. This synaptic phenotype suggests a complex effect of the RN mutation on different functional Cav2.1 channel parameters, presumably with a positive shift in activation potential as a prevailing feature. Taken together, our studies indicate that the gait abnormality of RN mice is due to a combination of ataxia and muscle weakness and that RN models aspects of the NMJ dysfunction in LEMS. [source] Decrease of Hsp25 protein expression precedes degeneration of motoneurons in ALS-SOD1 miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2004Arjen Maatkamp Abstract We have investigated the expression of Hsp25, a heat shock protein constitutively expressed in motoneurons, in amyotrophic lateral sclerosis (ALS) mice that express G93A mutant SOD1 (G93A mice). Immunocytochemistry and Western blotting showed that a decrease of Hsp25 protein expression occurred in motoneurons of G93A mice prior to the onset of motoneuron death and muscle weakness. This decrease in Hsp25 expression also preceded the appearance of SOD1 aggregates as identified by cellulose acetate filtration and Western blot analysis. In contrast to Hsp25 protein levels, Hsp25 mRNA as determined by in situ hybridization and RT-PCR, remained unchanged. This suggests that the decrease in Hsp25 protein levels occurs post-transcriptionally. In view of the cytoprotective properties of Hsp25 and the temporal relationship between decreased Hsp25 expression and the onset of motoneuron death, it is feasible that reduced Hsp25 concentration contributes to the degeneration of motoneurons in G93A mice. These data are consistent with the idea that mutant SOD1 may reduce the availability of the protein quality control machinery in motoneurons. [source] Angiotensin-Converting Enzyme Genotype Affects the Response of Human Skeletal Muscle to Functional OverloadEXPERIMENTAL PHYSIOLOGY, Issue 5 2000Jonathan Folland The response to strength training varies widely between individuals and is considerably influenced by genetic variables, which until now, have remained unidentified. The deletion (D), rather than the insertion (I), variant of the human angiotensin-converting enzyme (ACE) genotype is an important factor in the hypertrophic response of cardiac muscle to exercise and could also be involved in skeletal muscle hypertrophy , an important factor in the response to functional overload. Subjects were 33 healthy male volunteers with no experience of strength training. We examined the effect of ACE genotype upon changes in strength of quadriceps muscles in response to 9 weeks of specific strength training (isometric or dynamic). There was a significant interaction between ACE genotype and isometric training with greater strength gains shown by subjects with the D allele (mean ± S.E.M.: II, 9.0 ± 1.7%; ID, 17.6 ± 2.2%; DD, 14.9 ± 1.3%, ANOVA, P 0.05). A consistent genotype and training interaction (ID DD II) was observed across all of the strength measures, and both types of training. ACE genotype is the first genetic factor to be identified in the response of skeletal muscle to strength training. The association of the ACE I/D polymorphism with the responses of cardiac and skeletal muscle to functional overload indicates that they may share a common mechanism. These findings suggest a novel mechanism, involving the renin-angiotensin system, in the response of skeletal muscle to functional overload and may have implications for the management of conditions such as muscle wasting disorders, prolonged bed rest, ageing and rehabilitation, where muscle weakness may limit function. [source] DMD exon 1 truncating point mutations: Amelioration of phenotype by alternative translation initiation in exon 6,HUMAN MUTATION, Issue 4 2009Olga L. Gurvich Abstract Mutations in the DMD gene result in two common phenotypes associated with progressive muscle weakness: the more severe Duchenne muscular dystrophy (DMD) and the milder Becker muscular dystrophy (BMD). We have previously identified a nonsense mutation (c.9G>A; p.Trp3X) within the first exon of the DMD gene, encoding the unique N-terminus of the 427-kDa muscle isoform of the dystrophin protein. Although this mutation would be expected to result in severe disease, the clinical phenotype is very mild BMD, with ambulation preserved into the seventh decade. We identify the molecular mechanism responsible for the amelioration of disease severity to be initiation of translation at two proximate AUG codons within exon 6. Analysis of large mutational data sets suggests that this may be a general mechanism of phenotypic rescue for point mutations within at least the first two exons of the DMD gene. Our results directly demonstrate, for the first time, the use of alternate translational initiation codons within the DMD gene, and suggest that dystrophin protein lacking amino acids encoded by the first five exons retains significant function. Hum Mutat 0:1,8, 2009. © 2009 Wiley-Liss, Inc. [source] Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating,HUMAN MUTATION, Issue 6 2008Marian Kroos Abstract Pompe disease was named after the Dutch pathologist Dr JC Pompe who reported about a deceased infant with idiopathic hypertrophy of the heart. The clinical findings were failure to thrive, generalized muscle weakness and cardio-respiratory failure. The key pathologic finding was massive storage of glycogen in heart, skeletal muscle and many other tissues. The disease was classified as glycogen storage disease type II and decades later shown to be a lysosomal disorder caused by acid ,-glucosidase deficiency. The clinical spectrum of Pompe disease appeared much broader than originally recognized. Adults with the same enzyme deficiency, alternatively named acid maltase deficiency, were reported to have slowly progressive skeletal muscle weakness and respiratory problems, but no cardiac involvement. The clinical heterogeneity is largely explained by the kind and severity of mutations in the acid ,-glucosidase gene (GAA), but secondary factors, as yet unknown, have a substantial impact. The Pompe disease mutation database aims to list all GAA sequence variations and describe their effect. This update with 107 sequence variations (95 being novel) brings the number of published variations to 289, the number of non-pathogenic mutations to 67 and the number of proven pathogenic mutations to 197. Further, this article introduces a tool to rate the various mutations by severity, which will improve understanding of the genotype-phenotype correlation and facilitate the diagnosis and prognosis in Pompe disease. © 2008 Wiley-Liss, Inc. [source] Nodular vasculitis in systemic lupus erythematosusINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2008Annet Westers-Attema MD A 42-year-old man presented with fever, photosensitivity, headaches, myalgia, hyperhidrosis, muscle weakness, alopecia, nasal crustae, weight loss, painful nails, arthritis, oral ulcers, erythema, discoid cutaneous lesions, and painful subcutaneous nodes. We made a diagnosis of systemic lupus erythematosus (SLE), type II cryoglobulinemia, and nodular vasculitis. In the skin, different types of vasculitis may be observed. Typically, histology shows leukocytoclastic vasculitis of superficial vessels both in SLE and mixed cryoglobulinemia, which clinically results in palpable purpura. In our patient, however, histopathological examination of the subcutaneous nodes not only revealed leukocytoclastic vasculitis of the superficial vasculature but also showed even more extensive involvement of dermal and subdermal small and medium sized vessels, giving rise to a nodular vasculitis. [source] Acute febrile neutrophilic dermatosis (Sweet's syndrome) with nodular episcleritis and polyneuropathyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2002Taizo Kato MD A 56-year-old Japanese housewife presented with multiple erythematous lesions in association with ocular hyperemia and pain in the right upper and lower extremities, including the hands and feet. These symptoms were preceded by a sore throat with persistent fever higher than 38.5 °C for about 1 week. Dermatologic examination showed tender, dull-red, erythematous lesions, measuring 1,2 cm in diameter, located predominantly on the forehead, cheeks, auricular region, neck, forearm, hands, and feet. A biopsy specimen obtained from an erythematous lesion on the right forearm revealed prominent edema in the papillary dermis and remarkable inflammatory cell infiltration throughout the entire dermis (Fig. 1). The infiltrate predominantly consisted of neutrophils and nuclear dust without signs of vasculitis. In routine examination, the leukocyte count was 15,000/mL (normal range, 4000,8000/mL) with severe neutrophilia (80%). The C-reactive protein (CRP) level was 17.65 mg/dL (normal range, < 0.5 mg/dL) and the anti-streptolysin (ASLO) level was 611 IU/mL (normal range, < 166 IU/mL). In human leukocyte antigen (HLA) testing, HLA-A2, -B39, -B35, -Cw2, and -Cw7 were positive, and HLA-B51, -B54, and -Cw1 were negative. Figure Figure 1 . Histologic picture showing a dermal infiltrate of neutrophils Ocular hyperemia was caused by episcleritis forming a nodule and surrounding congestion of the superficial episcleritic vessels at the central portion of the sclera (Fig. 2). The patient suffered from pain once an hour, continuing for about 3 min, at the lateral portion of the right upper and lower extremities, as well as the right small finger. Neurologic examination demonstrated moderate or slight muscle weakness in the extremities. Hand grasping powers were 9 and 7 kg on the right and left, respectively. The patient was right-handed. Dysesthesia and paresthesia were also observed on the hands and feet. The deep tendon reflexes were preserved, however, even in the distal portion of the upper and lower limbs. In addition, essential tremor localized to the neck was recognized. Magnetic resonance imaging did not show any episodes of transient abnormal signal intensity in the central nervous system. Figure 2. Nodular episcleritis (right eye). Telangiectasia of winding vessels with nodular elevation was observed at the upper portion of the sclera The patient was treated with prednisolone (initial dose of 30 mg/day) and intravenous injection of cefazolin sodium (2 g/day for 5 days). Almost complete regression of the ocular and neurologic manifestations, as well as the skin lesions, was achieved in 2 weeks. Prednisolone was reduced gradually and suspended after 4 weeks. Leukocyte and neutrophil counts, CRP, and ASO returned to normal on suspension of therapy. Slight paresthesia remained in the right small finger even after stopping steroid. There was no recurrence at follow-up 6 months later. [source] Dermatomyositis presenting as panniculitisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2000Yen-Yu Chao MD A 44-year-old obese woman was transferred to our clinic with a diagnosis of panniculitis. Examination showed multiple, indurated, erythematous, painful nodules and plaques distributed on the shoulders, back, forechest, abdomen, buttock, and bilateral thighs. These skin lesions appeared 2 months previously, measured 5,8 cm, and were tender on palpation. No obvious inducing factor was traced. The lesions seemed unresponsive to treatment with nonsteroidal anti-inflammatory drugs (ibuprofen, 400 mg three times a day) as similar lesions appeared in subsequent visits. Progressive proximal muscle weakness was found 1 month later. She was then admitted via the emergency room because of extensive painful skin plaques and abdominal pain. Diffuse erythematous to violaceous swelling of the face, neck, and shoulder was noted at about the same time ( Fig. 1). A skin biopsy specimen from the nodular lesion showed poikilomatous epidermal changes ( Fig. 2), and marked mononuclear cell infiltration in the dermis and subcutaneous fat ( Fig. 3). Dermatomyositis was considered as the diffuse violaceous facial erythema could be a form of heliotrope eruption, but Gottron's papule was not found. At admission, serum creatinine phosphokinase (CPK) was mildly elevated (436 IU/L; normal range, 20,170 IU/L), but serum asparagine transaminase (AST) and lactate dehydrogenase (LDH) levels were within normal limits (36 IU/L; normal, 11,47 IU/L; and 108 IU/L; normal, 90,280 IU/L, respectively). Antinuclear antibody was 1 : 80 positive with an atypical speckled pattern. Muscle strength was weakest during the first 2 days, about grade 3 by the Medical Research Council (MRC) of Great Britain scale. Gower's sign was positive. An electromyogram showed myopathic changes and a nerve conduction velocity study was normal. Serum enzymes were elevated further on the third day: AST, 55 IU/L; CPK, 783 IU/L with 100% MM form. The diagnosis of dermatomyositis was established. As for the work-up result, anti-dsDNA antibody, anti-ENA antibody, and anti-Jo1 antibody were negative. Tumor marker screen (,-HCG, AFP, CEA, and CA-125), was negative, and rhinolaryngopharyngoscope examination and gynecologic sonography were normal. Figure 1. Diffuse erythematous swelling with subtle violaceous hue extending from the temporal area to the cheeks, neck, and shoulders. The crusted lip ulcers of herpes simplex were also noted Figure 2. Basketweave hyperkeratosis, mild acanthosis, subtle vacuolar degeneration of the basal cells, and melanin incontinence (hematoxylin and eosin, ×400) Figure 3. Heavy mononuclear cells infiltrated in the subcutaneous fat tissue (hematoxylin and eosin, ×100) Pancreatitis was initially suspected because of epigastric pain and tenderness, elevated serum lipase (382 U/L; normal, 23,200 U/L), and amylase (145 U/L; normal, 35,118 U/L). No evidence of pancreatitis could be found in abdominal sonography and abdominal computed tomography (CT), however. The epigastric pain and tenderness subsided soon after admission and the serum pancreatic enzyme level declined on the second day (amylase 69 U/L; lipase, 276 U/L). The patient was then diagnosed with dermatomyositis and treated with prednisolone (120 mg/day). CPK dropped dramatically from 3286 IU/L the day before treatment to 1197 IU/L 3 days after. Panniculitis lessened and the muscle power improved after 1 week of treatment. The disease activity fluctuated even with treatment with prednisolone and the patient often felt listless and weak. The muscle weakness sometimes deteriorated to affect the patient's mobility. Facial erythema and panniculitis-like lesions were found during the worse times. Methotrexate and azathioprine were then added (7.5 mg and 250 mg per week, respectively), but CPK was still mildly elevated (189 IU/L), and the patient still felt ill. Human immune globulin (5%, 500 mL per day, 5 days per month) intravenous infusion was initiated thereafter. There was a dramatic response. Full muscle strength was retained and CPK was within the normal range in the following 6 months with only immune globulin therapy. [source] Tissue oedema is not associated with skeletal muscle weakness in septic patientsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2010H. F. Ginz No abstract is available for this article. [source] Inflammatory myositis in systemic sclerosis: a South Australian perspectiveINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2005T. Y.-T. Abstract Background:, Muscle atrophy and weakness occurs commonly in patients with systemic sclerosis, especially late in the course of the disease. However, profound proximal muscle weakness secondary to myositis is an infrequent finding. Aim:, To determine the frequency and disease characteristics of patients with myositis in our cohort of systemic sclerosis patients. Methods:, A retrospective case note review of the clinical course of all patients enrolled on the South Australian scleroderma register, a population-based register of 374 living and 234 deceased patients with systemic sclerosis, last updated to the end of December 2002. Results:, Twenty patients with myositis were identified, the majority with diffuse cutaneous systemic sclerosis and overlap syndromes. The calculated frequency of this complication was 3.3% in our population-based cohort. All patients suffered profound proximal muscle weakness complicated by functional impairment. Other clinical features included weakness of cervical musculature (15%), dyspnoea (10%) and dysphagia (10%). Creatine kinase level was elevated in 80% of the patients, with the mean peak creatine kinase level of 1129 U/L. When further investigations were undertaken, 80% of patients demonstrated myopathic changes on electromyography and 92% of patients were found to have histological findings characteristic of an inflammatory process. Positive antinuclear antibodies were identified in all patients, including two with anti-PM-Scl autoantibodies. Conclusion:, Myositis is an infrequent clinical feature in patients with systemic sclerosis. Profound proximal weakness in association with elevated creatine kinase levels and myopathic changes on electromyography should alert the clinician to this complication. The presence of anti-PM-Scl autoantibodies in association with overlap syndromes may have a more favourable prognostic significance. [source] The adenine nucleotide translocase type 1 (ANT1): A new factor in mitochondrial diseaseIUBMB LIFE, Issue 9 2005J. Daniel Sharer Abstract Mitochondrial disorders of oxidative phosphorylation (OXPHOS) comprise a growing list of potentially lethal diseases caused by mutations in either mitochondrial (mtDNA) or nuclear DNA (nDNA). Two such conditions, autosomal dominant progressive external ophthalmoplegia (adPEO) and Senger's Syndrome, are associated with dysfunction of the heart and muscle-specific isoform of the adenine nucleotide translocase (ANT1), a nDNA gene product that facilitates transport of ATP and ADP across the inner mitochondrial membrane. AdPEO is a mtDNA deletion disorder broadly characterized by pathology involving the eyes, skeletal muscle, and central nervous system. In addition to ANT1, mutations in at least two other nuclear genes, twinkle and POLG, have been shown to cause mtDNA destabilization associated with adPEO. Senger's syndrome is an autosomal recessive condition characterized by congenital heart defects, abnormalities of skeletal muscle mitochondria, cataracts, and elevated circulatory levels of lactic acid. This syndrome is associated with severe depletion of ANT1, which may be the result of an as yet unidentified ANT1-specific transcriptional or translational processing error. ANT1 has also been associated with a third condition, autosomal dominant facioscapulohumeral muscular dystrophy (FSHD), an adult onset disorder characterized by variable muscle weakness in the face, feet, shoulders, and hips. FSHD patients possess specific DNA deletions on chromosome 4, which appear to cause derepression of several nearby genes, including ANT1. Early development of FSHD may involve mitochondrial dysfunction and increased oxidative stress, possibly associated with overexpression of ANT1. IUBMB Life, 57: 607-614, 2005 [source] Effectiveness of exercise programmes on shoulder mobility and lymphoedema after axillary lymph node dissection for breast cancer: systematic reviewJOURNAL OF ADVANCED NURSING, Issue 9 2010Dorothy N.S. Chan chan d.n.s., lui l.y.y. & so w.k.w. (2010) Effectiveness of exercise programmes on shoulder mobility and lymphoedema after axillary lymph node dissection for breast cancer: systematic review. Journal of Advanced Nursing,66(9), 1902,1914. Abstract Aim., This article is a report of a review of the effectiveness of exercise programmes on shoulder mobility and lymphoedema in postoperative patients with breast cancer having axillary lymph node dissection, as revealed by randomized controlled trials. Background., Breast cancer is the most common malignancy in women. After surgery, the most common postoperative complications are reduced range of motion in the shoulder, muscle weakness in the upper extremities, lymphoedema, pain and numbness. To reduce these impairments, shoulder exercises are usually prescribed. However, conflicting results regarding the effect and timing of such exercises have been reported. Data sources., Studies were retrieved from a systematic search of published works over the period 2000,2009 indexed in the Cumulative Index to Nursing and Allied Health Literature, Ovid Medline, the British Nursing Index, Proquest, Science Direct, Pubmed, Scopus and the Cochrane Library, using the combined search terms ,breast cancer', ,breast cancer surgery', ,exercise', ,lymphoedema', ,shoulder mobility' and ,randomized controlled trials'. Methods., A quantitative review of effectiveness was carried out. Studies were critically appraised by three independent reviewers, and categorized according to levels of evidence defined by the Joanna Briggs Institute. Results., Six studies were included in the review. Early rather than delayed onset of training did not affect the incidence of postoperative lymphoedema, but early introduction of exercises was valuable in avoiding deterioration in range of shoulder motion. Conclusion., Further studies are required to investigate the optimal time for starting arm exercises after this surgery. Nurses have an important role in educating and encouraging patients to practise these exercises to speed up recovery. [source] Muscle Weakness and Falls in Older Adults: A Systematic Review and Meta-AnalysisJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2004Julie D. Moreland MSc Objectives: To evaluate and summarize the evidence of muscle weakness as a risk factor for falls in older adults. Design: Random-effects meta-analysis. Setting: English-language studies indexed in MEDLINE and CINAHL (1985,2002) under the key words aged and accidental falls and risk factors; bibliographies of retrieved papers. Participants: Fifty percent or more subjects in a study were aged 65 and older. Studies of institutionalized and community-dwelling subjects were included. Measurements: Prospective cohort studies that included measurement of muscle strength at inception (in isolation or with other factors) with follow-up for occurrence of falls. Methods: Sample size, population, setting, measure of muscle strength, and length of follow-up, raw data if no risk estimate, odds ratios (ORs), rate ratios, or incidence density ratios. Each study was assessed using the validity criteria: adjustment for confounders, objective definition of fall outcome, reliable method of measuring muscle strength, and blinded outcome measurement. Results: Thirty studies met the selection criteria; data were available from 13. For lower extremity weakness, the combined OR was 1.76 (95% confidence interval (CI)=1.31,2.37) for any fall and 3.06 (95% CI=1.86,5.04) for recurrent falls. For upper extremity weakness the combined OR was 1.53 (95% CI=1.01,2.32) for any fall and 1.41 (95% CI=1.25,1.59) for recurrent falls. Conclusion: Muscle strength (especially lower extremity) should be one of the factors that is assessed and treated in older adults at risk for falls. More clinical trials are needed to isolate whether muscle-strengthening exercises are effective in preventing falls. [source] Increased CaV,1a expression with aging contributes to skeletal muscle weaknessAGING CELL, Issue 5 2009Jackson R. Taylor Summary Ca2+ release from the sarcoplasmic reticulum (SR) into the cytosol is a crucial part of excitation,contraction (E-C) coupling. Excitation,contraction uncoupling, a deficit in Ca2+ release from the SR, is thought to be responsible for at least some of the loss in specific force observed in aging skeletal muscle. Excitation,contraction uncoupling may be caused by alterations in expression of the voltage-dependent calcium channel ,1s (CaV1.1) and ,1a (CaV,1a) subunits, both of which are necessary for E-C coupling to occur. While previous studies have found CaV1.1 expression declines in old rodents, CaV,1a expression has not been previously examined in aging models. Western blot analysis shows a substantial increase of CaV,1a expression over the full lifespan of Friend Virus B (FVB) mice. To examine the specific effects of CaV,1a overexpression, a CaV,1a -YFP plasmid was electroporated in vivo into young animals. The resulting increase in expression of CaV,1a corresponded to decline of CaV1.1 over the same time period. YFP fluorescence, used as a measure of CaV,1a -YFP expression in individual fibers, also showed an inverse relationship with charge movement, measured using the whole-cell patch-clamp technique. Specific force was significantly reduced in young CaV,1a -YFP electroporated muscle fibers compared with sham-electroporated, age-matched controls. siRNA interference of CaV,1a in young muscles reduced charge movement, while charge movement in old was restored to young control levels. These studies imply CaV,1a serves as both a positive and negative regulator CaV1.1 expression, and that endogenous overexpression of CaV,1a during old age may play a role in the loss of specific force. [source] A review of nutrition in Duchenne muscular dystrophyJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 5 2009Z. E. Davidson Abstract Duchenne muscular dystrophy (DMD) is a recessive X linked genetic disorder characterised by progressive muscle weakness and reduced muscle tone. Affecting only boys, it limits life expectancy to approximately 20 years. A literature review was conducted using MEDLINE and the Cochrane Library, employing the term ,Duchenne muscular dystrophy'. A total of 1491 articles in English were recovered. These papers were searched thematically under the headings: body composition (n = 10), energy expenditure (n = 10), nutrition (n = 6), corticosteroid therapy (n = 55) and gene therapy (n = 199). Key dietetic practice points were identified relevant to nutritional management. Papers supporting these key themes were assigned a level of evidence and grade of recommendation. There is limited high-quality evidence to guide the nutritional management of boys with DMD. Currently, the majority of evidence is based on expert opinion and clinical expertise. Delayed growth, short stature, muscle wasting and increased fat mass are characteristics of DMD and impact on nutritional status and energy requirements. The early introduction of steroids has altered the natural history of the disease, but can exacerbate weight gain in a population already susceptible to obesity. Prior to commencing steroids, anticipatory guidance for weight management should be provided. Malnutrition is a feature of end stage disease requiring a multidisciplinary approach, such as texture modification and supplemental feeding. Micronutrient requirements are yet to be determined but, as a result of corticosteroid treatment, vitamin D and calcium should be supplemented. Some evidence exists supporting supplementation with creatine monohydrate to improve muscle strength. More research is needed to provide a higher quality of evidence for dietitians working within this area. [source] Disease progression of human SOD1 (G93A) transgenic ALS model ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2006Arifumi Matsumoto Abstract The recent development of a rat model of amyotrophic lateral sclerosis (ALS) in which the rats harbor a mutated human SOD1 (G93A) gene has greatly expanded the range of potential experiments, because the rats' large size permits biochemical analyses and therapeutic trials, such as the intrathecal injection of new drugs and stem cell transplantation. The precise nature of this disease model remains unclear. We described three disease phenotypes: the forelimb-, hindlimb-, and general-types. We also established a simple, non-invasive, and objective evaluation system using the body weight, inclined plane test, cage activity, automated motion analysis system (SCANET), and righting reflex. Moreover, we created a novel scale, the Motor score, which can be used with any phenotype and does not require special apparatuses. With these methods, we uniformly and quantitatively assessed the onset, progression, and disease duration, and clearly presented the variable clinical course of this model; disease progression after the onset was more aggressive in the forelimb-type than in the hindlimb-type. More importantly, the disease stages defined by our evaluation system correlated well with the loss of spinal motor neurons. In particular, the onset of muscle weakness coincided with the loss of approximately 50% of spinal motor neurons. This study should provide a valuable tool for future experiments to test potential ALS therapies. © 2005 Wiley-Liss, Inc. [source] Acute botulinum toxin-induced muscle weakness in the anterior cruciate ligament-deficient rabbitJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2005David Longino Abstract We established botulinum type-A toxin (BTX-A) injections as a powerful tool to cause knee extensor weakness in New Zealand White (NZW) rabbits. The purpose of this study was to determine if BTX-A induced quadriceps weakness causes muscle dysfunction beyond that caused by anterior cruciate ligament (ACL) transection in the knee of NZW rabbits. Twenty animals were randomly divided into four study groups (n = 5 each); uninjected controls, BTX-A injection alone, ACL transection alone, BTX-A injection and ACL transection combined. Isometric knee extensor torque, quadriceps muscle mass, and vertical and anterior,posterior ground reaction forces were measured four weeks post single (BTX-A and ACL), unilateral intervention. Muscle weakness, muscle atrophy and decrease in ground reaction forces were all significantly greater for the experimental compared to the untreated contralateral legs. BTX-A injection produced a greater deficit in quadriceps mass and knee extensor torque than ACL transection alone, but produced smaller deficits in the ground reaction forces. ACL transection superimposed on BTX-A injection did not change either knee extensor torque production or muscle mass. Together these results suggest that BTX-A injection causes great force and muscle mass deficits, and affects functional gait in a significant manner, but it has no measurable functional effect when superimposed on ACL transection, at least not in the acute protocol tested here. Hopefully, BTX-A injection for acutely enhancing the degree of muscle weakness in otherwise untreated animals, or in experimental models of osteoarthritis, will help in investigating the role of muscle weakness in joint degeneration. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Proposed model of botulinum toxin-induced muscle weakness in the rabbitJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2005D. Longino Abstract Osteoarthritic patients show only a weak association between radiographic signs of joint disease and joint pain and disability. Conversely, muscle weakness is one of the earliest and most common symptoms of patients with osteoarthritis (OA). However, while many experimental models of osteoarthritis include a component of muscular weakness, no model has isolated this factor satisfactorily. Therefore, the purpose of this study was to develop and validate an experimental animal model of muscle weakness for future use in the study of OA. Botulinum Type-A toxin (BTX-A) was uni-laterally injected into the quadriceps musculature of New Zealand white rabbits (3.5 unit/kg). Isometric knee extensor torque at a range of knee angles and stimulation frequencies, and quadriceps muscle mass, were quantified for control animals, and at one- and six-months post-repeated injections, in both, the experimental and the contralateral hindlimb. Ground reaction forces were measured in all animals while hopping across two force platforms. Isometric knee extension torque and quadriceps muscle mass was systematically decreased in the experimental hindlimb. Vertical ground reaction forces in the push off phase of hopping were also decreased in the experimental compared to control hindlimbs. We conclude that BTX-A injection into the rabbit musculature creates functional and absolute muscle weakness in a reproducible manner. Therefore, this model may be used to systematically study the possible effects of muscle weakness on joint degeneration, either as an isolated intervention, or in combination with other interventions (anterior cruciate ligament transection, meniscectomy) known to create knee joint degeneration. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] | |||||||||||||||||||||||||||||||||||||