Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The existence of chronic "limb-girdle" form of myasthenia gravis (MG) has been questioned. We report here 12 such patients (10 women and two men) who constituted 3.8% of 314 MG patients in our study. The duration of disease ranged from 4 months to 7 years before the diagnosis. In almost all cases, the initial diagnosis was other than MG. None of the patients had any oculobulbar weakness. Acetylcholine receptor antibody was positive in five cases, although not all in the first assay. Repetitive nerve stimulation test was positive in all cases, although not necessarily the first time. Single-fiber EMG was positive in 11 cases. All patients responded to acetylcholinesterase inhibitors, and two thirds underwent immunotherapy. Diagnosis of limb-girdle MG requires a strong index of suspicion.
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PMID:Chronic limb-girdle myasthenia gravis. 160 41

We encountered two children with fluorescent antinuclear antibody-positive pauciarticular juvenile arthritis who later developed myasthenia gravis. Acetylcholine receptor binding, blocking, and modulating antibodies, retrospectively tested on frozen serum, yielded negative results before the onset of myasthenic symptoms but all yielded strongly positive results coincident with the onset of weakness. In both children, myasthenia gravis responded to thymectomy, and one child had a beneficial response to plasmapheresis. Although, to our knowledge, only two patients with juvenile arthritis and myasthenia gravis have been described in the past, the presence of two additional children with both diseases in a single clinic population suggests that the association may be more prevalent than previously suspected.
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PMID:The association of pauciarticular juvenile arthritis and myasthenia gravis. 192 13

An unusual case of neonatal myasthenia gravis is reported in an infant who had respiratory failure due to diaphragmatic weakness. Although power and tone in the limbs were normal, fatiguability of both diaphragm and peripheral muscles was demonstrated. Acetylcholine receptor antibodies were absent in the mother, which suggests that an alternative humoral mechanism may have been responsible for the transient (6-week) neonatal weakness.
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PMID:An unusual case of neonatal myasthenia. 330 89

Acetylcholine receptor (AChR) binding and AChR modulating antibodies were found with approximately the same frequency (86%) in 349 patients with myasthenia gravis (MG). However, the total yield of positive serological results was significantly improved (90%) by assaying AChR modulating antibodies when AChR binding antibodies were not detected, because in 27 patients (8%) only one of the two tests was positive. The immunoprecipitation test for AChR blocking antibodies yielded fewer positive results (52%), but there was a significant correlation between the degree of AChR blockade and generalization of muscle weakness. In no patient was this the only positive test, because the test for AChR modulating antibodies in this study detected both AChR blocking and modulating antibodies. Human muscle AChR was used as antigen in all tests. False positive results were rare and were attributed to unexplained antibodies to 125I-alpha-Bgt (AChR binding antibody assay) and recent general anesthesia using muscle relaxants (AChR blocking and AChR modulating antibody assays). Unexplained positive results, documented previously in 5% of patients with the Lambert-Eaton myasthenic syndrome and amyotrophic lateral sclerosis (ALS), were found in this study in two of 22 patients with ALS, but in none of 427 patients with miscellaneous neurological diseases. Patients with severe generalized MG and/or thymoma tended to have higher titers of AChR binding antibodies and greater AChR modulating antibody activity. However, some patients with severe muscle weakness had low titers of antibodies, and some patients in remission or with only ocular manifestations had high titers. These seemingly paradoxical results reflect heterogeneity in the specificities, affinities, and isotypes of anti-AChR antibodies. To effect pathogenicity, antibodies must have access in vivo to extracellular antigenic sites on the AChR. One would anticipate that antibodies with greatest pathophysiological potential would be of an IgG with greatest pathophysiological potential would be of an IgG subclass that activates complement, or of a specificity that competes for acetylcholine's binding site on the receptor or readily cross-links two AChR molecules to trigger receptor modulation (e.g., by binding to sites on the duplicated alpha-subunit). In patients with suspected MG who lack serological evidence of anti-AChR antibodies, motor endplate biopsy is required for microelectrophysiological, immunochemical, and ultrastructural studies to establish with certainty whether or not the condition is acquired MG.
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PMID:Clinical correlations of antibodies that bind, block, or modulate human acetylcholine receptors in myasthenia gravis. 347 35

Fifteen patients with ocular myasthenia gravis were examined in detail for 21 different signs, and tested for acetylcholine receptor antibodies. The major signs of ocular myasthenia gravis included ptosis, disorders of ocular rotations, weakness of eyelid closure, "pseudosupranuclear" signs and the lid twitch sign. Acetylcholine receptor antibodies were found in eight of the 15 patients. One hundred and four normal, non-myasthenic patients were also examined for the lid twitch response, and the relationship between the lid twitch of ocular myasthenia gravis and that found in normal subjects is discussed.
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PMID:An evaluation of signs in ocular myasthenia gravis and correlation with acetylcholine receptor antibodies. 383 99

Two children, now 5 1/2 and 6 years of age, presented as neonates with hypotonia, multiple joint contractures, ptosis, extraocular weakness, bulbar symptoms, and respiratory distress. Fluctuations and episodic exacerbations of weakness necessitated respiratory support. Both children are developmentally delayed and cannot walk independently, although one child underwent bilateral tenotomies. Biochemical investigations and electromyography, including slow-rate, repetitive nerve stimulation, were normal. Acetylcholine receptor antibodies in serum were absent. Single-fiber electromyography with axonal stimulation revealed prolonged mean jitter in the tibialis anterior and extensor digitorum muscles, with more than 2 abnormal individual jitter values in each muscle. Muscle biopsy demonstrated normal pattern and morphology of muscle fibers; immunohistochemical staining for cholinesterase was positive. Electron microscopy revealed abnormalities in motor endplates: atrophy, flattening of primary synaptic clefts, and paucity of side branches. These findings represent one of the postsynaptic abnormalities (i.e., acetylcholine receptor deficiency or paucity of synaptic folds). Both children improved clinically on pyridostigmine therapy. Arthrogryposis congenital multiplex due to congenital myasthenic syndrome, as diagnosed in our patients, has been reported once before. The diagnosis can be established by clinical history, neurologic examination, and electrophysiologic and pathologic findings. Clinical improvement can be achieved with high-dose anticholinesterase therapy.
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PMID:Arthrogryposis multiplex congenita due to congenital myasthenic syndrome. 761 91

Acetylcholine receptor (AChR) deficiency is a recessively inherited congenital myasthenic syndrome in which fatigable muscle weakness results from impaired neuromuscular transmission caused by reduced AChR numbers. In mature muscle, AChRs consist of alpha2 betadelta together with the adult-specific epsilon subunit. We have identified a deletion of the first nucleotide in exon 12 of the AChR epsilon-subunit gene (epsilon1267delG) and demonstrate its recessive inheritance segregates with disease in 6 unrelated cases of AChR deficiency. In addition, we found that both healthy and AChR-deficient muscle contain a population of AChR epsilon-subunit mRNA transcripts that retain intron 11. We investigated the possible consequences of combining this mutation with the alternative mRNA species through AChR expression studies in human embryonic kidney cells and Xenopus oocytes. Epsilon1267delG generates a polypeptide that lacks M4 and is not detected in surface AChR, whereas retention of intron 11 in the RNA transcript restores the reading frame, conserves M4, and generates a polypeptide that is incorporated into functional surface AChR, although at a reduced level, consistent with the disease phenotype. Our results indicate that for some AChR deficiency mutations located between M3 and M4, the retention of intron 11 in the epsilon-subunit mRNA transcripts may rescue adult AChR function.
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PMID:Novel functional epsilon-subunit polypeptide generated by a single nucleotide deletion in acetylcholine receptor deficiency congenital myasthenic syndrome. 1051 2

Patients with myasthenia gravis (MG) who do not respond to conventional immunotherapeutic agents, or cannot tolerate their side effects, are considered "refractory." Ablation of the immune system followed by bone marrow transplant has been shown to cure experimental MG in rats. It is now known that immunoablative treatment with high-dose cyclophosphamide does not damage hematopoietic "stem cells," permitting repopulation of the immune system without bone marrow transplant. Recent evidence indicates that this treatment can induce durable remissions in autoimmune diseases. We treated three myasthenic patients, for whom treatment with thymectomy, plasmapheresis, and conventional immunotherapeutic agents failed, by using high-dose cyclophosphamide (50mg/kg/day intravenously for 4 days) followed by granulocyte colony stimulating factor. All three patients tolerated the treatment well and have had marked improvement in myasthenic weakness, permitting reduction of immunosuppressive medication to minimal levels. Acetylcholine receptor (AChR) antibody levels decreased in two AChR antibody-positive patients, and anti-MuSK antibody levels decreased in one "AChR antibody-negative" patient. The patients have been followed for up to 3.5 years, with no recurrence of symptoms. High-dose cyclophosphamide treatment appears to be an effective and safe treatment for selected patients with refractory MG. Further follow-up of these and additional patients will be needed to determine whether the benefit is durable.
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PMID:Treatment of refractory myasthenia: "rebooting" with high-dose cyclophosphamide. 1250 42

Here, we present a case of a 64-year-old female suffering from a severe form of antibody-positive myasthenia gravis. Under an immunosuppressive regimen with cyclosporine A, she experienced an episode of thoracic herpes zoster followed by intense post-herpetic neuralgia. In order to avoid drug interactions as well as adverse effects of carbamazepine in myasthenia gravis, gabapentin was chosen for the treatment of neuropathic pain. Within a few days she noticed increasing weakness, but continued medication for 8 weeks as gabapentin was not identified as the hazardous agent by her physician. Acetylcholine receptor antibody levels remained unchanged, but increased decrement was observed clinically and in repetitive nerve stimulation. After withdrawal of gabapentin, she recovered quickly to her previous condition.
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PMID:Treatment of post-herpetic pain in myasthenia gravis: exacerbation of weakness due to gabapentin. 1285 53

We report the clinical and electrophysiological findings in seven patients with Lambert-Eaton myasthenic syndrome (LEMS). All patients were males aged 40-73 years old. Six presented proximal muscle weakness and one both proximal and distal. The tendon reflexes were absent in four patients, depressed in two and normal in one patient. Three patients presented ophthalmic and four autonomic symptoms. The syndrome was diagnosed 3-12 months after the onset of symptoms in six patients and 4 years later in one. Acetylcholine receptor antibodies were negative in all patients. Voltage-gated calcium channel antibodies (VGCC) were measured in five patients and were positive in four. All patients had low compound muscle action potential (CMAP) at rest, a decrement in CMAP amplitude of 20-47% at 3 Hz repetitive nerve stimulation, and an increment of 200-700% at 40 Hz. In three patients the syndrome was associated with histologically verified small-cell lung cancer (SCLC). In the younger patient (40 years old), a lymph node biopsy performed nine years before the diagnosis of LEMS, had shown an atypical microcellular cancer of undetermined origin, which was treated with chemotherapy. LEMS 9 years after the diagnosis of cancer has not been described previously. The fifth patient had a two years history of bladder cancer (grade II). Three years after the diagnosis of LEMS he presented chronic lymphogenic leukemia. No malignancy was found in the remaining 2 patients.
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PMID:Lambert-Eaton myasthenic syndrome. Clinical and electrophysiological findings in seven cases. 1537 68


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