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 clinical, pathophysiological and genetic features of some of the paroxysmal movement disorders are reviewed. Paroxysmal kinesigenic choreoathetosis/dyskinesias (PKC/PKD) is a condition in which brief and frequent dyskinetic attacks are provoked by sudden movement. PKC is more common in men and can be idiopathic (commonly familial) or due to a variety of causes. The pathophysiology of PKC is uncertain but it could be an ion-channel disorder. Antiepileptic drugs particularly carbamazepine are very helpful in a large proportion of cases. Paroxysmal exercise induced dystonia (PED) is a rare disorder manifesting as episodes of dystonia mostly affecting the feet induced by continuous exercise like walking or running. Although the initial cases were familial, there is a higher proportion of sporadic cases. The pathophysiology of PED is unknown and antiepileptic drugs are generally unhelpful. In paroxysmal dystonic choreoathetosis/non-kinesigenic dyskinesias (PDC/PNKD) the attacks are of long duration and induced by variety of factors including coffee, tea, alcohol and fatigue but not by sudden movement. PDC can be idiopathic (familial or sporadic) or symptomatic due to a variety of causes. The gene for familial PDC has been linked in 2 families to chromosome 2 q close to a cluster of ion channel genes again suggesting that this disorder may also be a channelopathy. Other paroxysmal disorders include paroxysmal nocturnal dyskinesia, a form of frontal lobe epilepsy in some cases which may be familial with autosomal dominant inheritance (ADNFLE). The gene for ADNFLE in one family has been found to be a mutation in the neuronal acetylcholine receptor gene (CHRNA4) on chromosome 20q. Tonic spasms in multiple sclerosis and Sandiffers syndrome producing intermittent torticollis in infants and children are other paroxysmal movement disorders.
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PMID:The paroxysmal dyskinesias. 1032 9

Camptocormia is characterized by severe forward flexion of the thoracolumbar spine which increases while walking and disappears in the recumbent position. We describe for the first time eight patients with presumed idiopathic Parkinson's disease (mean age 66+/-5 yrs; mean symptom duration 13.1+/-5.1 yrs) who developed camptocormia. This impressive abnormal posture emerged 4-14 years from disease onset, and in some patients stooped posture was the prominent symptom at diagnosis. There was no clear correlation between camptocormia and levodopa treatment. In some patients the camptocormic posture improved, and in others it was unchanged or even aggravated following levodopa administration. Three patients reported worsening of this symptom during "off" periods and also with fatigue. The pathogenesis of this phenomenon is unknown but might represent either a rare type of dystonia or an extreme form of rigidity.
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PMID:Camptocormia (bent spine) in patients with Parkinson's disease--characterization and possible pathogenesis of an unusual phenomenon. 1174 65

This study evaluated the influence of dystonia musculorum (dt) mutation, characterized by spinocerebellar fibers degeneration, on cardiac and skeletal muscles: one respiratory (diaphragm, Dia), three masticatory (anterior temporalis, AT; masseter superficialis, MS; and anterior digastric, AD), one hindlimb (soleus, S), tongue (T), and one cardiac (ventricle, V). Body and muscle weight, muscle protein content, and myosin heavy chain (MHC) isoforms relative expression were then compared in dt mutant mice and in normal mice, according to sex. Male body and muscle weight was always greater than that of females, but there was no specific muscle difference in females. dt mutant mice showed a reduced whole body growth but no specific muscle atrophy, as well as a global decrease in muscle protein content that made muscles more fragile. dt mutation induced a global reduction of muscle protein concentration, whereas a general influence of sex could not be disclosed. Concerning MHC relative composition, all the muscles were fast-twitch: Dia, AT, MS, AD, S, and T expressed predominantly the fast type 2 MHC isoforms, whereas V contained only MHC alpha, also a fast MHC. Female muscles were slower than male muscles, except for S, which was faster. However, classification of muscles in terms of shortening velocity was very different in normal males and females. In other respects, dt mutant muscles were slower and consequently more fatigue resistant than normal, except for S, which became faster and less fatigue resistant. dt mutation exhibits then a specific effect on this continually active postural muscle. In the other muscles, global increased fatigue resistance could constitute an adaptive response to work requirements modifications linked to the muscle damage. It should be noted that a developmental MHC (neonatal) was present in female dt AD. Innervation, which influences muscle structure, is altered in dt mutant and could be another causal factor of the fast-to-slow MHC switches. It appears that dystonin, the dt gene product, is very important in maintaining the structural integrity of both cardiac and skeletal muscle and in its absence, the muscle becomes more fragile and is damaged by modified activity.
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PMID:Dystonia musculorum mutation and myosin heavy chain expression in skeletal and cardiac muscles. 1038 Dec 65

Paroxysmal tonic upgaze of childhood is a rare, distinctive, childhood syndrome that may be associated with ataxia and sometimes strabismus or amblyopia. Neurological examination as well as metabolic studies, electroencephalogram and neuroradiological investigations are normal in these patients. Although it has been considered as an age-related, dopa-sensitive dystonia, the exact pathogenetic mechanism is still unknown. Aggravation of attacks by fatigue, intercurrent infection or vaccination, and possible corticomesencephalic dysmaturation may underlie this abnormality. We report on a sporadic case of paroxysmal tonic upgaze with ataxia in which there was prompt aggravation of symptoms with sleep without response to levodopa treatment. This case suggests a different underlying pathogenetic mechanism from dopaminergic pathways for this syndrome.
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PMID:A case of paroxysmal tonic upgaze of childhood with ataxia. 1046 69

There is nothing more discouraging than for a patient to be given a specific diagnosis, then to be told that there is nothing that can be done. Physicians are equally disheartened to see exponential progress being made in the understanding of the pathophysiology of a complex disorder but few direct benefits resulting for their patients. Over the past 5 years, molecular genetic research has completely revolutionized the way in which the progressive cerebellar ataxias are classified and diagnosed, but it has yet to produce effective gene-based, neuroprotective, or neurorestorative therapies. The treatment of cerebellar ataxia remains primarily a neurorehabilitation challenge, employing physical, occupational, speech, and swallowing therapy; adaptive equipment; driver safety training; and nutritional counseling. Modest additional gains are seen with the use of medications that can improve imbalance, incoordination, or dysarthria (amantadine, buspirone, acetazolamide); cerebellar tremor (clonazepam, propranolol); and cerebellar or central vestibular nystagmus (gabapentin, baclofen, clonazepam). Many of the progressive cerebellar syndromes have associated features involving other neurologic systems (eg, spasticity, dystonia or rigidity, resting or rubral tremor, chorea, motor unit weakness or fatigue, autonomic dysfunction, peripheral or posterior column sensory loss, neuropathic pain or cramping, double vision, vision and hearing loss, dementia, and bowel, bladder, and sexual dysfunction), which can impede the treatment of the ataxic symptoms or can worsen with the use of certain drugs. Treatment of the associated features themselves may in turn worsen the ataxia either directly (as side effects of medication) or indirectly (eg, relaxation of lower limb spasticity that was acting as a stabilizer for an ataxic gait). Secondary complications of progressive ataxia can include deconditioning or immobility, weight loss or gain, skin breakdown, recurrent pulmonary and urinary tract infections, aspiration, occult respiratory failure, and obstructive sleep apnea, all of which can be life threatening. Depression in the patient and family members is common. Although no cures exist for most of the causes of cerebellar ataxia and there are as yet no proven ways to protect neurons from premature cell death or to restore neuronal populations that have been lost, symptomatic treatment can greatly improve the quality of life of these patients and prevent complications that could hasten death. Supportive interventions should always be offered-- education about the disease itself, genetic counseling, individual and family counseling, referral to support groups and advocacy groups, and guidance to online resources. Misinformation, fear, depression, hopelessness, isolation, and financial and interpersonal stress can often cause more harm to the patient and caregiver than the ataxia itself.
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PMID:Cerebellar Ataxia. 1109 49

For nearly a century, physicians have been aware of a syndrome consisting of a relatively stereotyped presentation, usually in young patients, who complain of fatigue, malaise and effort intolerance, sometimes of trembling and weakness of the lower limbs. This is associated with an excessive tachycardia in the orthostatic position. This syndrome has recently been called idiopathic orthostatic tachycardia. The tilt test has enabled "quantification" of normal responses. Patients complaining of the symptoms described above and which, during the first minutes of orthostatism, increase their heart rates by more than 30 beats per minute or attain a rate of at least 110/min, are considered to be suffering from this syndrome. The physiopathology is not clear but, globally, there seems to be two sub-groups, the first considered to be a partial dysautonomic disorder and the second, the result of hypersensitivity of the beta-receptors. Besides the tilt test, the diagnosis can also be presumed after an excessive tachycardia response to an intravenous infusion of 1 microgram/min of isoprenaline. The treatment of these patients is uncertain as there is no single approach which is always effective. In addition to "simple" but essential advice, a number of drugs may be used although there is no means of predicting the efficacy of the result in a given patient. A major principle should be emphasised: ablation of the sinus node for inappropriate tachycardia may eliminate the only compensatory mechanism of autonomic dystonia and make the patients even more symptomatic than they were.
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PMID:[Idiopathic orthostatic tachycardia. Etiology, diagnosis and treatment]. 1122 22

A 4-year-old boy presented with a history of paroxysmal dystonic posturing since birth. Episodes were triggered by stress, fatigue, and cold. Sleep, for as short as 1 minute, resulted in complete resolution of dystonia. He was developmentally normal, with no focal neurologic deficits. Cerebrospinal fluid, homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were borderline low. On ictal spectroscopy, there was reduced blood flow to the right temporal region, caudate nuclei, and thalami. The typical infantile form of dystonia is benign, resolving by 2 years of age in an otherwise normal child. Our patient remains symptomatic at 4 years of age.
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PMID:Infantile-onset paroxysmal dystonia: a diagnostic dilemma. 1130 92

The clinical, pathophysiological and genetic features of some of the familial (idiopathic) paroxysmal movement disorders are reviewed. The paroxysmal dyskinesias share features and therefore may have the same pathophysiological mechanisms as other episodic neurological disorders which are known to be channelopathies. Paroxysmal kinesigenic choreoathetosis/dyskinesias (PKC/PKD) is a condition in which brief and frequent dyskinetic attacks are provoked by sudden movement. Antiepileptics particularly carbamazepine are very helpful for this condition. PKC has similarities to episodic ataxia type 1 which is caused by mutations of the KCNA1 gene. PKC and a related disorder in which infantile convulsions are associated (ICCA syndrome) have recently been linked to the pericentromic region of chromososme 16 in the vicinity of some ion channel genes. Paroxysmal exercise-induced dystonia (PED) is a rare disorder manifesting as episodes of dystonia mostly affecting the feet induced by continuous exercise like walking or running. The pathophysiology of PED is unknown and antiepileptic drugs are generally unhelpful. In paroxysmal dystonic choreoathetosis/nonkinesigenic dyskinesias (PDC/PNKD) the attacks are of long duration and induced by a variety of factors including coffee, tea, alcohol and fatigue but not by sudden movement. The gene for familial PDC has been linked to chromosome 2q close to a cluster of ion channel genes. Paroxysmal nocturnal dyskinesia is now known to be a form of frontal lobe epilepsy in some cases which may be familial with an autosomal dominant inheritance and has been given the eponym ADNFLE. ADNFLE is a genetically heterogenous condition. Mutations of the neuronal nicotinic acetylcholine receptor gene that have chromosome 20q have been reported in some families with ADNFLE. However, another family with ADNFLE has been linked to chromosome 15 in the area of another nicotinic acetylcholine receptor gene. Thus the familial paroxysmal dyskinesias appear to be clinically and genetically heterogeneous.
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PMID:Familial (idiopathic) paroxysmal dyskinesias: an update. 1134 27

Doxorubicin chemomyectomy is a potent method for the permanent removal of a muscle or group of muscles after direct local injection, and has been used successfully to treat blepharospasm and hemifacial spasm patients. The efficacy of doxorubicin chemomyectomy on reducing muscle strength after direct injection of doxorubicin into rabbit sternocleidomastoid muscle was tested. One- and 6-month postinjection force assessment was performed in vitro to measure alterations in peak twitch and tetanic force generation, as well as fatigue responses for the treated muscles compared to control. There were significant reductions of both twitch and tetanic peak amplitudes in the doxorubicin-treated muscles. One month after treatment, the decreases in force were greater after 2 mg doxorubicin injections than after 1 mg doxorubicin. While there was a significant reduction in force generation after doxorubicin treatment, fatigue resistances for the doxorubicin-treated muscles were increased compared to the controls. There were significant reductions in muscle mass after doxorubicin treatment, and by 6 months, the myosin heavy chain isoform distribution was similar to normal sternocleidomastoid, except for an increase in slow myosin-positive fibers. Doxorubicin chemomyectomy resulted in a significant reduction in functional force generation in the treated sternocleidomastoid muscles. These findings suggest a potential clinical use of doxorubicin chemomyectomy to treat cervical dystonia patients.
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PMID:Physiological assessment of muscle strength in vitro after direct injection of doxorubicin into rabbit sternocleidomastoid muscle. 1148 92

To study possibilities of a therapeutic correction of asthenic syndrome in individuals with chronic arterial hypotension with malate citrulline, the study was made of 12 women and 3 men with psychoautonomic syndrome (autonomic dystonia), combined with chronic constitutional arterial hypotension. Their age was from 27 to 45 years (mean age--37.6). A control group comprised 14 healthy individuals. Both a state of autonomic nervous system and manifestations of arterial hyportension were analyzed by means of complex scored questionnaires. Mental condition was assessed by the tests of Spilberger (evaluation of reactive and personal anxiety) and of Beck (estimation of depressive manifestations). In all the examined individuals with chronic arterial hypotension, there was psychoautonomic syndrome combined with complaints to asthenic manifestations, namely, to low performance and fatigue. Stimol was prescribed in the form of 50% solution in daily dose of 6 g (3 administrations). The therapy resulted in regression of clinical manifestations of both psychoautonomic syndrome and asthenic symptoms. A mechanism of the drug's action works through favourable changes in cerebral and muscular cells, that, in turn, had an influence on other manifestations of psychoautonomic syndrome.
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PMID:[Use of citrulline malate (stimol) in patients with autonomic dystonia associated with arterial hypotension]. 1153 Apr 55


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