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 aim of this study was to compare the effect of treatment with lamotrigine (LTG) or carbamazepine (CBZ) on health-related quality of life (HRQOL) and to demonstrate the use of the SEALS Inventory as a comparative tool in clinical trials. Two hundred and sixty patients with newly diagnosed epilepsy were randomized to 48 weeks of treatment with LTG (n = 131) or CBZ (n = 129). HRQOL was measured at baseline and weeks 4, 12, 24, and 48 using the modified Side Effect and Life Satisfaction (SEALS) Inventory-a 38-item questionnaire divided into five subscales: Worry, Temper, Cognition, Dysphoria, and Tiredness. Overall, SEALS scores in the LTG group decreased (improved) significantly from baseline (P = 0.001). The LTG group had improvement in all five subscales over the 48 weeks of the study. CBZ patients had significantly worse SEALS scores than LTG patients at week 4 (P < 0.038). There was no significant change (positive or negative) in subsequent SEALS assessments. Analysis of SEALS data by subscale showed that the the CBZ group experienced more cognitive side-effects in general and more general changes in energy levels and affect during the first 4 weeks of treatment. These changes may help explain the difference in study completion rate: LTG 65%, CBZ 51% (P = 0.018). LTG offers the patient with newly diagnosed epilepsy significant benefits of greater tolerability and better health-related quality of life compared with CBZ. The SEALS Inventory is an effective tool for use in clinical trials of AEDs; it was a better predictor of trial completion than seizure counts, and used as a covariate enabled better detection of treatment effects. In general practice, the use of the SEALS Inventory to assess HRQOL has the potential to improve quality of care for people with epilepsy.
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PMID:A double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy with health-related quality of life as an outcome measure. 1098 91

The aim of this study was to evaluate the safety of long-term treatment with tiagabine. We reviewed the case report forms of patients with refractory partial epilepsy who took tiagabine for longer than 6 months in two long-term studies. We classified all adverse events based on severity and persistence, and recorded the dose at onset of each adverse event. We then divided patients into those treated for 6-12 months, 12-24 months and > 24 months. We compared the adverse event profile and change in seizure frequency among the three groups. Forty-two patients took tiagabine for longer than 6 months. The mean duration of treatment was 22.6 months. The mean monthly seizure frequency was 12.7 at baseline and 8.1 at study termination (36% decrease). The most common adverse events were: tiredness (56%), headache (46%), dizziness (44%), visual symptoms (blurring, difficulty focusing, diplopia) (39%), altered mentation (32%), and tremor (31%). The adverse event profile was comparable among the three groups. Seizure frequency was significantly more improved in the > 24 months group. Long-term treatment with tiagabine is well tolerated. The most important predictor of long-term therapy with tiagabine was the degree of seizure improvement.
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PMID:Safety of long-term treatment with tiagabine. 1098 2

Parasomnias emerging from NREM sleep such as sleep walking, sleep terrors and confusional arousals are considered arousal disorders. Nocturnal video-polysomnography is the gold standard to diagnosing and differentiating parasomnias from other arousals with atypical motor behaviors such as nocturnal frontal lobe epilepsy (NFLE). This form of nocturnal seizures with prominent dystonic-dyskinetic components, in some cases genetic, has been recently identified by means of detailed video-analysis of movements during sleep. The clinical picture of parasomnias (with onset in early childhood, rare episodes of long duration, absence of stereotypy, general disappearance after puberty) is different from that of NFLE (which first occurs between the age of 10 and 20, manifests frequent complex and repetitive behaviors of short duration excluding rare prolonged seizures, nocturnal agitation, some daytime complaints such as fatigue or sleepiness, persistence into adulthood). Patients show no difference from classical sleep parameters whilst microstructure analysis shows sleep instability and arousal fluctuations in parasomnias and NFLE. In children as well, at least in our experience, the differential diagnosis between the two disorders is difficult and requires one or more complete nocturnal video-polygraphic recording. In any case the diagnosis of NFLE should be considered in children with nocturnal motor episodes or nocturnal motor agitation, when the attacks persist; this diagnosis is probably more frequent than expected.
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PMID:NREM parasomnias: arousal disorders and differentiation from nocturnal frontal lobe epilepsy. 1099 66

Randomized, controlled studies of new antiepileptic drugs are carried out following strict rules and do not always predict the drug's tolerability in clinical practice. The authors gathered 361 cases of focal epilepsies treated with topiramate (TPM) as an add-on to other antiepileptic drugs prior to marketing, in order to retrospectively analyze the incidence of adverse effects (AE). These patients had been treated by neurologists in a clinical setting, with free choice of associated drugs, titration and final daily dose. Compared with controlled studies, TPM was titrated slowly (mean rate: 43 mg/week, vs 100-200), and was given at a lower final dose (296 mg/d, vs 200 to 1000). This analysis shows that AE were less frequent and that TPM had an original tolerability profile, with CNS-related AE, often combined in the same patient (somnolence: 16. 1p.100, fatigue: 11.9p.100, mental slowing: 9.1p.100, slurred speech: 2,2p.100), and weight loss (14.7p.100 of patients, mean 4.5 kg or 6.6p.100 of body weight). Severe AE were uncommon (psychosis, 1; skin rash, 2; urinary lithiasis, 2). Withdrawal of TPM was caused by AE (13.6p.100), lack of efficacy (8.3p.100), aggravation of epilepsy (6.1p.100) or by a combination of these (5p.100). It is useful to use slow titration, in order to allow the greatest possible number of patients to benefit from its efficacy as an add-on drug in the treatment of resistant focal epilepsies.
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PMID:[Use of topiramate in clinical practice (part 2). Multicentric retrospective evaluation of its safety]. 1113 28

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

We assessed the quality of life (QOL) of patients with epilepsy using the Quality of Life in Epilepsy Inventory (QOLIE-31). As the first step we compared our results with the data from an American survey in order to validate the test in Hungary. The results show that the Hungarian values were lower but that they followed the same trends as the American data. There was only one controversial result in the question-group of the 'the effects of treatment', which could be explained by the differences in habits and conventions, opportunities and expectations between Hungarian and American epileptic patients. We found significant differences in many aspects of quality of life with respect to (a) gender (general quality of life, seizure worry), (b) pharmacological treatment form (cognitive functions, medication effects, total score and social and role functioning) and (c) economic activity of patients (cognitive functions, emotional well-being, energy/fatigue, medication effects, overall quality of life, overall scores, seizure worry, social and role functioning). We have tried to explain the differences found by taking either the characteristics of epilepsy or the social background of the epileptic patient into consideration. Based on previous knowledge we have tried to define the situations where the assessment of quality of life for people with epilepsy, may be beneficial to their core.
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PMID:Quality of life of patients with epilepsy (Hungarian survey). 1140 52

(1) Gabapentin is now licensed for first-line or replacement monotherapy of partial epilepsy, in patients over 12 years of age. (2) The assessment file concurs with current recommendations of medicines agencies. (3) One comparative trial of first-line monotherapy showed a similar efficacy/adverse effects ratio of gabapentin and carbamazepine. Gabapentin has not been compared with valproate sodium. (4) In one trial, involving patients with refractory epilepsy, various doses of gabapentin were added to an ongoing inadequately effective treatment, which was then gradually stopped. Gabapentin monotherapy was considered satisfactory in a minority of patients. (5) The adverse effects of gabapentin are limited to neuropsychological disorders, namely dizzy spells, drowsiness, fatigue and headache. The risk of interactions is also limited. (6) The optimal dose regimen of gabapentin is not yet established.
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PMID:Gabapentin monotherapy: new indication. Sometimes helpful. 1150 84

This review summarizes the current knowledge of the biosynthesis of neurosteroids in the human brain, the enzymes mediating these reactions, their localization and the putative effects of neurosteroids. Molecular biological and biochemical studies have now firmly established the presence of the steroidogenic enzymes cytochrome P450 cholesterol side-chain cleavage (P450SCC), aromatase, 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase in human brain. The functions attributed to specific neurosteroids include modulation of gamma-aminobutyric acid A (GABAA), N-methyl-d-aspartate (NMDA), nicotinic, muscarinic, serotonin (5-HT3), kainate, glycine and sigma receptors, neuroprotection and induction of neurite outgrowth, dendritic spines and synaptogenesis. The first clinical investigations in humans produced evidence for an involvement of neuroactive steroids in conditions such as fatigue during pregnancy, premenstrual syndrome, post partum depression, catamenial epilepsy, depressive disorders and dementia disorders. Better knowledge of the biochemical pathways of neurosteroidogenesis and their actions on the brain seems to open new perspectives in the understanding of the physiology of the human brain as well as in the pharmacological treatment of its disturbances.
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PMID:Neurosteroid metabolism in the human brain. 1172 Aug 89

Topiramate (TPM) is a new anti-epileptic drug with proven efficacy against partial seizures in adults. Its use in children is less well documented. In a retrospective study, 41 patients with intractable childhood epilepsy were treated with TPM as add-on therapy for an average period of 15 months. They were classified according to seizure type and etiology. The dose was titrated for effect and ranged between 2 and 24 mg/kg/d. Of the 41 patients being treated, six became seizure free, ten had a seizure reduction of more than 75% and eight a seizure reduction of between 50 and 75%. The most remarkable effect was seen in seven patients with West syndrome. Of these, four patients became seizure free and one had more than 75% seizure reduction. Adverse effects including sedation, fatigue, difficulties with verbal expression and anorexia were noted in 15 patients. None of these effects were important enough to interrupt treatment. We conclude that TPM as adjunctive therapy is a promising drug in children with intractable epilepsy, especially in the patients with West syndrome.
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PMID:Retrospective study of topiramate in a paediatric population with intractable epilepsy showing promising effects in the West syndrome patients. 1181 66

Paroxysmal tonic upgaze deviation (PTU) is a rare neuro-ophthalmological disorder with onset in infancy or early childhood. It consists of episodes of sustained, conjugate, upward deviation of the eyes, down beating saccades in attempted downgaze, apparently preserved horizontal eye movements, frequent association with mild ataxia or clumsiness at time of illness, normal metabolic, electroencephalographic and neuroradiological findings. Symptoms are frequently relieved by sleep and can be exacerbated by fatigue or illness. Although PTU generally tends to disappear spontaneously within a few months or years, subsequent case reports have demonstrated the heterogeneous nature of the syndrome with respect to outcome. To date, the pathogenesis of the condition is still unknown. We present a new case of PTU with ataxia occurring in an otherwise healthy child, as documented by video recording of the phenomenon.
Epileptic Disord 2001 Dec
PMID:Benign paroxysmal tonic upgaze of childhood with ataxia. 1184 15


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