Disease relevance of Muscle Weakness

• Emery-Dreifuss muscular dystrophy (EMD) is an X-linked disorder characterized by contractures, progressive muscle weakness and cardiomyopathy [1].
• In three patients with very-long-chain acyl-CoA dehydrogenase deficiency, this treatment led rapidly to clinical improvement that included the permanent disappearance of chronic cardiomyopathy, rhabdomyolysis, and muscle weakness (for more than 2 years in one child), and of rhabdomyolysis and weakness in the others [2].
• In Crohn's disease, severe skeletal demineralization, secondary hyperparathyroidism, and muscle weakness can occur [3].
• Central core disease (CCD) is a human congenital myopathy characterized by fetal hypotonia and proximal muscle weakness that is linked to mutations in the gene encoding the type-1 ryanodine receptor (RyR1) [4].
• A variable combination of developmental delay, retinitis pigmentosa, dementia, seizures, ataxia, proximal neurogenic muscle weakness, and sensory neuropathy occurred in four members of a family and was maternally transmitted [5].

Psychiatry related information on Muscle Weakness

• Ndrg1-deficient mice showed muscle weakness, especially in the hind limbs, but complicated motor skills were retained [6].
• Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder primarily affecting young boys, often causing mental retardation in addition to the well-known progressive muscular weakness [7].
• Lethargy, marked muscle weakness and rigidity, a maximal temperature of 40 degrees C, and a maximal creatine kinase value of 17,240 IU/liter developed in a 36-year-old woman following treatment with several neuroleptics [8].
• 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 [9].
• This inhibitory effect of ethanol may be implicated in the development of muscle weakness with alcohol consumption [10].

High impact information on Muscle Weakness

• The KIF1B heterozygotes have a defect in transporting synaptic vesicle precursors and suffer from progressive muscle weakness similar to human neuropathies [11].
• An apparently identical deletion in one family gave classical BMD in two brothers (presenting in their teens) and only very mild muscle weakness in their 86-year-old great-great-uncle [12].
• Five cases of a new disease presented with muscular weakness or cramping after exercise; three of the cases also had an elevated serum creatine phosphokinase [13].
• In the mouse, a deficiency in both lamin A and lamin C leads to slow growth, muscle weakness, and death by 6 weeks of age [14].
• In the present study, rabbits immunized with MuSK ectodomain protein manifested MG-like muscle weakness with a reduction of AChR clustering at the NMJs [15].

Chemical compound and disease context of Muscle Weakness

• Thus muscle weakness in MFS may be caused by a serum factor, likely to be GQ1b antibody, that leads to failure of acetylcholine release from motor nerve terminals [16].
• Muscle weakness and tenderness together with a rise in serum creatine kinase (C.K.) were noted in five uraemic patients treated with 1-2 g of clofibrate ('Atromid-S') daily [17].
• These findings indicate that muscle weakness suffered by individuals possessing the I4898T mutation involves a functional uncoupling of sarcolemmal excitation from SR Ca(2+) release, rather than the expression of overactive or leaky SR Ca(2+) release channels [4].
• Long-chain acyl CoA dehydrogenase deficiency is differentiated from medium-chain acyl CoA dehydrogenase deficiency by younger age at presentation, more profound cardiorespiratory depression, evidence of cardiomyopathy, and sequelae of muscle weakness, hypotonia and developmental delay [18].
• MRS findings were normal in 2 additional patients who had improved with prednisone treatment and in 1 patient who had no muscle weakness (amyopathic variant of JDM) [19].

Biological context of Muscle Weakness

• To discern whether this axis could participate in an autoimmune response, we immunized NOS2-deficient mice with the autoantigen acetylcholine receptor, inducing muscle weakness characteristic of myasthenia gravis, a T cell-dependent Ab-mediated autoimmune disease [20].
• C57BL/6 (B6) mice respond to immunization with acetylcholine receptor (AChR) from Torpedo californica as measured by T cell proliferation, antibody production, and the development of muscle weakness resembling human myasthenia gravis [21].
• Baseline characteristics that did not predict SRC included age, sex, race, Health Assessment Questionnaire score, fist closure, handspread, lung involvement, muscle weakness, erythrocyte sedimentation rate, and platelet count [22].
• Following immunization with Torpedo (t) AChR, the IL-4(-/-) mice readily developed signs of muscle weakness and succumbed to clinical EAMG with kinetics similar to the susceptibility of IL-4(+/+) mice [23].
• These mutations accompanied a clinical phenotype that is distinguishable from recessive myotonia congenita by progressive generalized muscle weakness, severe distal muscle atrophy, joint contractures, high serum creatine kinase levels, and conspicuous myopathic changes on muscle histopathology [24].

Anatomical context of Muscle Weakness

• Individuals in the two unlinked families met the clinical criteria for the diagnosis of FSHD, including facial weakness, clavicular flattening, scapula winging, proximal muscle weakness, and myopathic changes on muscle biopsies without inflammatory or mitochondrial pathology [25].
• We hypothesize that dystrophin deficiency leads to the constant release of basic fibroblast growth factor, which in turn contributes to fibrosis and muscle weakness by stimulating connective tissue and suppressing skeletal muscle differentiation [26].
• RESULTS: The MMF patients (4 men and 8 women, mean +/- SD age 47.8 +/- 8.7 years) had chronic myalgia (n = 11; predominantly in the lower limbs), asthenia (n = 10), arthralgia (n = 7), mild muscle weakness (n = 5), and high serum creatine kinase levels (n = 6) [27].
• The delayed onset and reduced muscle weakness were associated with decreased AChR-specific lymphocyte proliferation and decreased levels of anti-AChR Abs of the IgG2a and IgG2b isotypes in serum [28].
• Dystonin-deficient mice exhibit an intrinsic muscle weakness and an instability of skeletal muscle cytoarchitecture [29].

Gene context of Muscle Weakness

• In contrast, inactivation of the CNTF gene leads only to a slight muscle weakness, mainly during adulthood, suggesting that CNTFR binds to a second ligand that is important for development [30].
• Recessive mutations in two of the three collagen VI genes, COL6A2 and COL6A3, have recently been shown to cause Ullrich congenital muscular dystrophy (UCMD), a frequently severe disorder characterized by congenital muscle weakness with joint contractures and coexisting distal joint hyperlaxity [31].
• Recent studies have shown that heterozygous mutations in KCNJ11, which encodes Kir6.2, the pore-forming subunit of the ATP-sensitive potassium (K(ATP)) channel, cause permanent neonatal diabetes either alone (R201C, R201H) or in association with developmental delay, muscle weakness and epilepsy (V59G,V59M) [32].
• Hexa -/- mice suffer no obvious behavioral or neurological deficit, while Hexb -/- mice develop a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor and ataxia [33].
• Most patients with CAV3 alterations present with rippling muscle disease (RMD) characterized by signs of increased muscle irritability without muscle weakness [34].

Analytical, diagnostic and therapeutic context of Muscle Weakness

• Two siblings and two other unrelated patients had congenital muscular weakness and dystrophic changes but normal immunocytochemical stainings for merosin, dystrophin, and dystrophin-related proteins on muscle biopsy [35].
• BACKGROUND: The role of plasma exchange is well established in the management of myasthenia gravis, an autoimmune disorder characterized by muscle weakness and caused by circulating IgG antibodies with specificity against the acetylcholine receptor [36].
• A retrospective study of ten patients with infant botulism who received gentamicin or kanamycin suggests that aminoglycoside antibiotics potentiate muscular weakness and precipitate respiratory failure as late as 27 days after onset of the disease [37].
• PURPOSE:: Organ transplant patients treated with cyclosporine-A (CsA) often exhibit weight loss and muscle weakness [38].
• After treatment with clindamycin and corticosteroids both cases had only partial improvement, case 1 with a residual muscle weakness and case 2 with residual cardiac insufficiency (requiring digoxin) [39].

References