Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-four adult outpatients with poorly controlled complex partial seizures were treated with valproic acid. Previous therapy with antiepileptic agents was continued to maintain stable plasma drug levels. Initially 12 patients experienced greater than 50% seizure reduction. Only five patients maintained longterm benefit. In the other seven patients a tolerance developed to valproic acid's efficacy. Duration of seizure control seemed to be a function of initial seizure frequency. Toxic effects were generally mild. No hepatotoxic effect was noted and no hematological abnormalities developed. Weight changes occurred in 17 patients (14 gained weight) and five patients experienced a postural tremor. Eighteen patients experienced nausea.
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PMID:Valproic acid therapy for complex partial seizures. Its efficacy and toxic effects. 640 1

We describe the development of temporal lobe epilepsy in an 84-year-old man who had suffered domoic acid intoxication. Following intoxication he had nausea, vomiting, confusion, and coma. Generalized convulsions and complex partial status epilepticus progressively developed. After 3 weeks he improved and was seizure free with severe residual memory deficit. Electroencephalograms initially showed periodic epileptiform discharges, later evolving to epileptic abnormalities over frontotemporal regions with diffuse slow waves. Eight months after the intoxication the electroencephalogram was normal. One year after the acute episode, complex partial seizures developed. Electroencephalograms showed epileptic discharges independently over both temporal lobes, with left-sided predominance. Magnetic resonance imaging revealed a hyperintense T2-weighted signal and atrophy of both hippocampi; a positron emission tomographic scan showed bitemporal decreased glucose metabolism. Pneumonia developed and the patient died 3 1/4 years after the intoxication. Autopsy disclosed severe bilateral hippocampal sclerosis. The seizures following acute domoic acid intoxication, the postmortem pathology, and the fact that temporal lobe epilepsy developed 1 year after intoxication indicate that the human hippocampus is also vulnerable to kainate receptor excitotoxicity, and provide strong evidence supporting the role of excitotoxic injury in epileptogenesis. This report provides a unique human parallel to, and validates the animal model of, kainate-induced epilepsy as an important tool for studying temporal lobe epilepsy.
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PMID:Temporal lobe epilepsy caused by domoic acid intoxication: evidence for glutamate receptor-mediated excitotoxicity in humans. 781 46

Thirteen children with refractory epilepsy received a ketogenic diet (medium chain triglyceride oil diet) as an alternative therapy since September 1997. Their seizure patterns included (1) generalized tonic-clonic seizures, (2) myoclonic seizures, (3) generalized tonic + atonic seizures, (4) complex partial seizures, (5) generalized clonic + atonic + myoclonic seizures, (6) head nodding + myoclonic + gelastic seizures, and (7) generalized tonic-clonic + myoclonic + atonic seizures. Major concerns emphasized on the efficacy and side effects of the diet. Clinical observation one month after the diet revealed that 53.8% of the patients had a > 75% reduction in seizure frequency and 76.9% of the patients had a > 50% reduction in seizure frequency. Six patients had some degrees of improvement in cognitive function and/ or school performances. The most common side effects were body weight loss (n = 6) and diarrhea (n = 5). Others included bad temper (n = 1), abdominal cramps (n = 2), nausea (n = 2), bad body smell (n = 1), and renal stones (n = 1). Even after discontinuation of the diet, 61.5% of patients still had a > 50% reduction in seizure frequency. We concluded that the ketogenic diet deserves a trial in children with refractory epilepsy.
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PMID:Clinical experience of ketogenic diet on children with refractory epilepsy. 1091 May 95

We report a 20-year-old man with temporal lobe epilepsy (TLE) accompanied by hereditary motor and sensory neuropathy (HMSN). He had experienced complex partial seizures (CPS), which started with a nausea-like feeling, followed by loss of consciousness and automatism, since he was 6 years old. The frequency of attacks was at first decreased by phenytoin. However, attacks increased again when he was 18 years old. On admission, neurological examination showed mild weakness of the toes, pes cavus, hammer toe and mildly impaired vibratory sensation in his legs. Ten people in four generations of his family showed a history of epilepsy in the autosomal dominant inheritance form. His younger sister and mother had a history of epilepsy accompanied with pes cavus, hammer toe, weakness of toe and finger extension and mildly impaired vibratory sensation as well. Direct sequencing of the glioma-inactivated leucine-rich gene (LGI1), in which several mutations were reported in patients with familial lateral temporal lobe epilepsy, showed no specific mutation in this family. On consecutive video-EEG monitoring, paroxysmal rhythmic activity was confirmed in his left fronto-temporal region when he showed automatism, and then a generalized slow burst activity was detected when he lost consciousness. For his seizures, TLE with secondary generalization was diagnosed. In the nerve conduction study, delayed nerve conduction, distal motor latency and decreased amplitudes of the compound muscle action potentials (CMAP) of bilateral peroneal nerves were observed, indicating the existence of mild axonal degeneration. Based on these data, we consider that this family to be a new phenotype of autosomal dominant TLE accompanied by motor and sensory neuropathy.
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PMID:[A family with autosomal dominant temporal lobe epilepsy accompanied by motor and sensory neuropathy]. 1519 38

ASTA Medica is developing retigabine, a carbamic acid ethyl ester and a selective potassium channel opener, for the treatment of complex partial seizures. Phase II trials have commenced [249117], and a multicenter placebo-controlled dosage-finding study has begun in Europe and Australia [392702]. Retigabine is also undergoing phase II testing in Germany, Switzerland, Russia and the US for the potential treatment of epilepsy [323383]. Phase II trials have shown >50% reduction in seizure frequency in 12 of 35 patients with refractory epilepsy [373379]. Phase I clinical trials for epilepsy were successfully completed in Germany in 1995 [180371]. Single and multiple dose trials demonstrated the tolerability and favorable pharmacokinetic behavior of the compound [264306]. The compound showed good compatibility and exhibits an antisense anticonvulsive effect in various preclinical epilepsy models [250565,299344]. Side effects of mild to moderate tiredness, fatigue and nausea were observed [276123]. The spectrum of activity of retigabine resembles that of valproate, but its potency is greater and toxicity is reduced [373379]. The mechanism of action of retigabine is probably multifactorial. Research has shown that retigabine acts as a selective K+ channel opener in neuronal cells and this can be expected to contribute to its anticonvulsant effect [273670]. In addition it demonstrates potentiation of GABA transmission and possibly also weak modulation of sodium and calcium channels [299344]. Retigabine also has neuroprotective activity with potential for the treatment of stroke and neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease and multiple sclerosis [249381]. In February 2000, Lehman Brothers predicted product launch could be as early as 2002 for epilepsy in the US [357788]. In February 1999, Lehman Brothers predicted that the first major launch date of the drug would be 2003, and the year of peak sales to be 2011 [319225].
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PMID:Retigabine (ASTA Medica). 1603 7

Clinical lateralizing signs are the phenomena which can unequivocally refer to the hemispheric onset of epileptic seizures. They can improve the localization of epileptogenic zone during presurgical evaluation, moreover, their presence can predict a success of surgical treatment. Primary sensory phenomena such as visual aura in one half of the field of vision or unilateral ictal somatosensory sensation always appear on the contralateral to the focus. Periictal unilateral headache, although it is an infrequent symptom, is usually an ipsilateral sign. Primary motor phenomena like epileptic clonic, tonic movements, the version of head ubiquitously appear contralateral to the epileptogenic zone. Very useful lateralization sign is the ictal hand-dystonia which lateralizes to the contralateral hemisphere in nearly 100%. The last clonus of the secondarily generalized tonic-clonic seizure lateralizes to the ipsilateral hemisphere in 85%. The fast component of ictal nystagmus appears in nearly 100% on the contralateral side of the epileptic focus. Vegetative symptoms during seizures arising from temporal lobe such as spitting, nausea, vomiting, urinary urge are typical for seizures originating from non-dominant (right) hemisphere. Ictal pallor and cold shivers are dominant hemispheric lateralization signs. Postictal unilateral nose wiping refers to the ipsilateral hemispheric focus compared to the wiping hand. Ictal or postictal aphasia refers to seizure arising from dominant hemisphere. Intelligable speech during complex partial seizures appears in non-dominant seizures. Automatism with preserved consciousness refers to the seizures of non-dominant temporal lobe.
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PMID:[Brain lateralization and seizure semiology: ictal clinical lateralizing signs]. 1876 78

Partial epilepsy comprises simple partial seizures, complex partial seizures, and secondarily generalized seizures, and covers more than 60% of patients with epilepsy. Antiepileptic drugs are generally considered to be the major therapeutic intervention for epilepsy but, despite a broad range of commonly used antiepileptic drugs, approximately 30% of adult patients and approximately 25% of children with epilepsy have inadequate seizure control. Eslicarbazepine acetate (ESL) is a novel voltage-gated sodium channel-blocking agent with presumed good safety and efficacy for adjunctive treatment of patients with drug-resistant partial epilepsy. ESL is a prodrug of eslicarbazepine (the active entity responsible for pharmacologic effects), and is rapidly and extensively hydrolyzed during first pass by liver esterases after oral administration. The half-life of eslicarbazepine at steady-state plasma concentrations is 20-24 hours, compatible with once-daily administration. ESL 800 mg and 1200 mg significantly reduces seizure frequency and shows a favorable safety profile in adult patients with drug-resistant partial-onset seizures, as demonstrated in previous Phase II and III trials. In children, ESL showed a clear dose-dependent decrease in seizure frequency with good tolerability. The most commonly reported adverse events associated with ESL are dizziness, somnolence, nausea, diplopia, headache, vomiting, blurred vision, vertigo, and fatigue. In conclusion, these characteristics suggest that ESL might be a valid and well tolerated treatment option for patients with drug-resistant partial-onset epilepsy. The convenience of once-daily dosing and a short, simple titration regimen would be of special interest for children, although conclusive published data are lacking to date. Hence, there is an urgent need to establish the therapeutic value of ESL in this special population in the near future.
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PMID:Update on treatment of partial onset epilepsy: role of eslicarbazepine. 2112 91