Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuromuscular junction is the target of a variety of autoimmune, neurotoxic and genetic disorders, most of which result in muscle weakness. Most of the diseases, and many neurotoxins, target the ion channels that are essential for neuromuscular transmission. Myasthenia gravis is an acquired autoimmune disease caused in the majority of patients by antibodies to the acetylcholine receptor, a ligand-gated ion channel. The antibodies lead to loss of acetylcholine receptor, reduced efficiency of neuromuscular transmission and muscle weakness and fatigue. Placental transfer of these antibodies in women with myasthenia can cause fetal or neonatal weakness and occasionally severe deformities. Lambert Eaton myasthenic syndrome and acquired neuromyotonia are caused by antibodies to voltage-gated calcium or potassium channels, respectively. In the rare acquired neuromyotonia, reduced repolarization of the nerve terminal leads to spontaneous and repetitive muscle activity. In each of these disorders, the antibodies are detected by immunoprecipitation of the relevant ion channel labelled with radioactive neurotoxins. Genetic disorders of neuromuscular transmission are due mainly to mutations in the genes for the acetylcholine receptor. These conditions show recessive or dominant inheritance and result in either loss of receptors or altered kinetics of acetylcholine receptor channel properties. Study of these conditions has greatly increased our understanding of synaptic function and of disease aetiology.
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PMID:Molecular targets for autoimmune and genetic disorders of neuromuscular transmission. 1108 82

Myasthenia gravis is an acquired disorder of the neuromuscular junction characterised by fatiguable weakness of the limbs, bulbar and facial muscles and may be complicated by respiratory muscle weakness and failure. One often confirms the diagnosis by a simple serological test looking for the presence of the nicotinic acetylcholine receptor antibody. However, seronegative myasthenia constitutes about 20% of cases and in the case of ocular myasthenia, only 50% will have the antibody. Therefore, the diagnosis can be less than straightforward especially if the patient presents with vague symptoms such as fatigue or presents to specialities other than neurology or ophthalmology. The fact that the diagnosis may prove to be challenging, compounded by the fact that the condition is relatively rare and that the antibody to the acetylcholine receptor is not always present, epidemiological data is often less than precise and indeed difficult to acquire. We felt it was necessary to try to establish the epidemiological data on seropositive myasthenia gravis in Tayside, (this has never been carried out) bearing in mind the above pitfalls, and see how the incidence compares with similar and previous studies.
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PMID:A limited epidemiological study of seropositive myasthenia gravis in Tayside. 1261 69

Difficulty clearing upper airway secretions (death rattle) is a frequent problem at the end of life. Treatment often includes the use of anticholinergic drugs. Myasthenia gravis is a disease characterized by muscle weakness and fatigue caused by an immune-mediated deficiency of acetylcholine receptors at the neuromuscular junction, and it is treated with anticholinesterase agents. We report the case of a patient dying of myasthenia gravis who had problems with the "death rattle" and who presented a dilemma as to whether the use of anticholinergics would be helpful or would cause deterioration of her myasthenia. This is accompanied by a review of the relevant literature.
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PMID:Anticholinergic agents for the treatment of "death rattle" in patients with myasthenia gravis. 1285 Jun 51

L-Carnitine (L-beta-hydroxy-gamma-N,N,N-trimethylaminobutyric acid) plays an essential role in fatty acid transport in the mitochondrion. Conditions that appear to benefit from exogenous supplementation of L-carnitine include anorexia, chronic fatigue, cardiovascular disease, hypoglycemia, male infertility, muscular myopathies, renal failure and dialysis. D-Carnitine is not biologically active and might interfere with the proper utilization of the L isomer, and so there are claims that the racemic mixture (DL-carnitine) should be avoided. Despite the fact that it is known about the systemic manifestations of oral intake of this compound, oral supplementation with DL-carnitine for treatment of primary and secondary carnitine deficiency syndromes has been used in Russia for 25 years. The purpose of the present review was to contrast the differences in pharmacokinetics, phannacodynamics, biochemistry, and toxicity between treatments of L- and DL-carnitine. There is some evidence that L-carnitine and D-carnitine compete for uptake in small intestine and tubular re-absorption in kidneys. After intestinal absorption, L- and D-carnitine is transferred to organs whose metabolism is dependent on fatty acid oxidation, such as heart and skeletal muscle, and D-carnitine competitively depletes muscle level of L-carnitine. Whereas L-carnitine is found to be essential for the oxidation of fatty acids, D-carnitine causes a depletion of L-carnitine, and hindered fatty acid oxidation and energy formation. Pharmacological effects of carnitine are stereospecific, since L-carnitine was effective in various animals and clinical studies, while D- and DL-carnitine was found to be ineffective or toxic, for example, to muscle cells and to the myocardium. DL-Carnitine causes symptoms of myasthenia and cardiac arrhythmias, which disappeared after L-carnitine administration. Clinically toxic effect of D-carnitine was described in patients with renal failure on long-term haemodialysis, in adriamycin (doxorubicin) cardiotoxicity and in stable angina pectoris.
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PMID:[Stereopharmacology of carnitine]. 1649 28

Myasthenia gravis is uncommon in patients with scleroderma, and when diagnosed is usually associated with previous use of d-penicillamine. Clinically, both myasthenia and scleroderma may present with fatigue, weakness and bulbar symptoms, so one of diagnoses may be delayed. We report two new cases and review clinical features of 12 other reported cases of co-existing scleroderma and myasthenia gravis, unrelated to previous d-penicillamine therapy. Co-occurrence of myasthenia and scleroderma was reported almost exclusively (13/14) in women with a mean latency of 7.03 years. Most patients (10/11) had seropositive generalized myasthenia, and there were no cases with exclusively ocular symptoms. Three patients with pre-existing myasthenia were safely treated with d-penicillamine. Myasthenia and scleroderma occur in the context of an underlying autoimmune diathesis, but their co-occurrence could be underreported as the recognition of either disorder may be delayed by overlapping clinical symptoms. Our findings also suggest that d-penicillamine may be cautiously used in selected patients with pre-existing scleroderma and myasthenia, when potential benefits outweigh the risk of possible myasthenia exacerbation.
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PMID:Myasthenia gravis and scleroderma: two cases and a review of the literature. 1728 Jul 77

Ocular myasthenia can mimic central disorders of eye movements. We compared horizontal saccades in two patients with myasthenia gravis who presented as pseudo-internuclear ophthalmoplegia (pseudo-INO), two patients with true INO due to multiple sclerosis (MS), and five healthy subjects. In myasthenics, peak velocity of horizontal saccades was similar to, or greater than, controls; in MS patients, adducting saccades were slower than controls. Differences between the peak velocity of abducting and adducting eyes for each saccade were similar to controls for myasthenic pseudo-INO, but greater than controls for true INO. Using the technique of phase-plane analysis, in which eye velocity is plotted against eye position, we found that initial components of abducting and adducting saccades in the myasthenics were as conjugate as controls, even though later components of myasthenic saccades were highly and variably disjunctive. Conversely, phase planes of saccades in true INO showed disjunctive early components of abducting and adducting saccades. Two hypotheses have been offered to account for preservation of fast saccades despite reduced range of eye movements in ocular myasthenia. The first is intrasaccadic neuromuscular fatigue, which is variable over time. Our finding that initial components of saccades were consistently conjugate in the myasthenics gives support to a second hypothesis: selective sparing of pale global fibers, which are important for generating highspeed eye movements, and which are unique amongst extraocular fibers in possessing well developed synaptic folding.
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PMID:Ocular myasthenia revisited: insights from pseudo-internuclear ophthalmoplegia. 1771 27

Myasthenia gravis (MG) is a chronic neuromuscular disease which leads to varying degrees of weakness in the skeletal muscles. Some of the symptoms of the disorder include weakness of the eye muscles, difficulty in swallowing and slurred speech. When only the muscles of the eyes are affected, the illness is termed ocular myasthenia, which is often characterized by abrupt onset of diplopia and ptosis of the eyelid. In most patients with ocular-onset MG, there is a progression to involvement of other muscle groups within the first two years (generalized myasthenia). In the case reported here, a 39-year-old male of Ecuadorian descent complained of difficulty seeing, double vision, dizziness, unsteady gait, difficulty maintaining balance and fatigue for the previous two days. Neurological examination was remarkable for total external ophthalmoplegia. There was no external bulbar muscle paralysis, motor weakness, muscle wasting, sensory deficits or sphincter dysfunction. His laboratory workup was significant for elevated acetylcholine receptor antibody. He was diagnosed with ocular MG after differential diagnoses were ruled out based on the onset and presentation of symptoms, the patient's age and a normal magnetic resonance imaging exam. No signs of generalized myasthenia were detected. His symptoms improved dramatically after treatment with Acetyl cholinesterase (AchE) inhibitors and steroids, regaining much of his ocular mobility and ability to walk without gait imbalance. At follow-up visits, the patient remained healthy with no evidence development of other myasthenic signs. This case is atypical since ocular MG does not normally occur in the absence of other myasthenic forms.
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PMID:An atypical course of myasthenia gravis. 1860 52

A female in her late 60s with chronic kidney disease was admitted to the emergency department with complaints of dizziness four days prior to hospitalization. Cibenzoline (300 mg/day) was administered for atrial fibrillation, which was detected in an electrocardiogram. After three days, she experienced blepharoptosis and was admitted for suspected myasthenia gravis. However, the anti-acetylcholine receptor antibody and edrophonium tests were negative. On day four after hospitalization, she suffered from pneumonia with pleural effusion and she was put on a respirator for four days. From day 16 after hospitalization, she had diarrhea and her renal function worsened. At the same time, a gradual aggravation of right blepharoptosis, dull headache, weakness and difficulty in chewing were noted. She experienced dyspnea on day 31 after hospitalization. Chest X-ray film did not show a pneumonia shadow or pleural effusion, and arterial blood gases revealed hypercapnia; she was diagnosed as having CO2 narcosis due to respiratory muscle fatigue and was put on a respirator again. Myasthenia-like syndrome was suspected because of a probable overdose of cibenzoline and administration of cibenzoline was withdrawn. Her condition improved and she was taken off the respirator on day 35 after hospitalization. Repetitive stimulation of 5 Hz was applied to her right facial nerve along with evoked electromyogram(EMG) on days 2 and 11 after discontinuing cibenzoline. On day 2, the EMG showed a waning phenomenon, whereas no such phenomenon was seen on day 11. The blood concentration of cibenzoline immediately after withdrawal was extremely high (2448 ng/mL). When this drug is administered to a patient with chronic kidney disease, attention must be paid to the indication, dose, and manifestation of the possible side effects.
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PMID:[Myasthenia-like syndrome induced by cibenzoline overdose in a patient with chronic kidney disease]. 1906 53

Myasthenia gravis (MG) is an acquired autoimmune disorder causing skeletal muscle fatigue and weakness. This is a report of one woman and her daughter presenting with myasthenia and gravis and Grave's disease. It highlights possible hereditary component of this condition which has not been commonly reported in our setting.
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PMID:Myasthenia gravis associated with autoimmune thyroid disease: a report of two patients. 1914 67

The dynamics and kinematics of saccades in a patient with severe ocular myasthenia were studied before and after treatment with intravenous immunoglobulin (IVIG). Before therapy, horizontal saccades were hypometric, but faster than similar-sized saccades made by normal subjects. During a 5-minute test period, saccades decreased in size (fatigue effect), but remained faster than those of controls. Listing's plane of the eye with greater ophthalmoplegia was increased in thickness. After IVIG treatment, the range of eye movements improved, but saccades remained faster than those of controls. Also, no fatigue was observed and the thickness of Listing's plane was reduced toward the normal range. Increased peak velocity, despite progressive hypometria due to fatigue, supports the hypothesis that the pale global extraocular muscle fibers are relatively spared in myasthenia. Involvement of other extraocular muscle-fiber types leads to limited range of eye movements and an increase in the thickness of Listing's plane.
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PMID:Changes in dynamic and kinematic properties of saccades in ocular myasthenia following intravenous immunoglobulin treatment. 1964 50


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