Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149958 (complex partial seizures)
 2,563 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ganaxolone is a member of a novel class of neuroactive steroids which modulates the GABA(A) receptor complex (GRC) via an unique recognition site, distinct from those of benzodiazepines and barbiturates. Preclinical data from an array of chemically- and electrically-induced seizure models demonstrate that ganaxolone possesses broad spectrum anticonvulsant activity with potential clinical utility in both generalised and partial seizures, as well as cocaine-induced seizures. Clinical data to date support a favourable safety profile with somnolence, an extension of GABAergic activity, being the most frequently reported adverse event at higher doses. Target indications include infantile spasms and complex partial seizures. Open-label data in paediatric patients with intractable epilepsy suggest that ganaxolone may be effective in treating infantile spasms. A controlled trial utilising an in-patient, monotherapy design demonstrated that ganaxolone effectively decreases complex partial seizure activity compared to placebo. An important area of further evaluation is ganaxolone's potential role in the treatment of women with catamenial epilepsy.
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PMID:Ganaxolone: a novel positive allosteric modulator of the GABA(A) receptor complex for the treatment of epilepsy. 1113 18

The study was designed to evaluate optimal use of add-on lamotrigine in the treatment of children and adults with refractory epilepsy of any type. Because of the available evidence from controlled studies, indicating the large spectrum of action of lamotrigine, we designed this prospective study to investigate the efficacy and safety of lamotrigine in everyday clinical practice, to collect useful information on its action in specific epilepsy syndromes and on the clinical results of specific co-medications. We studied 566 patients with a diagnosis of refractory epilepsy of any type currently receiving stable conventional regimens of antiepileptic therapy. Efficacy analysis was limited to 510 patients (388 patients aged 12 years or more, 122 patients aged 2 to 12 years) for which the exact number of seizures could be evaluated. Seizure characteristics were: simple and/or complex partial seizures in 298 (58p. cent) patients, partial seizures with secondary generalisation in 85 (17p. cent), generalised seizures of any type in 226 (44 percent). Syndromic diagnosis was partial symptomatic or cryptogenic epilepsy in 302 patients (59 percent), generalised symptomatic or cryptogenic epilepsy in 116 (23 percent) and idiopathic generalised epilepsy in 50 (10 percent). The percentage of patients who achieved at least 50 percent reduction in the frequency of seizures was evaluated around 40p. cent for all epilepsy categories, and up to 61 percent in idiopathic generalised epilepsies. Response to treatment with lamotrigine was usually obtained by the end of titration (4 weeks) and remained stable at 48 weeks. Thirty-three patients (7 percent) remained seizure-free at 48 weeks. In the group of patients with partial epilepsy, 19p. cent presented a more than 75 percent reduction in seizure frequency. A more than 50 percent reduction in secondary generalisation of partial seizures was observed in 45 percent of the patients. Efficacy results were similar in both the adult and paediatric age groups. They were better for patients receiving valproate co-medication (45 percent of the responders) as compared to other co-medications (37 percent of the responders), suggesting a synergistic action. Safety has been evaluated for all the patients having received lamotrigine (n=566). The incidence of adverse events attributed to lamotrigine was similar to the results of controlled studies, with somnolence reported in 10p. cent, a cutaneous reaction in 8 percent and episodes of transitory diplopia in 8 percent. A cutaneous reaction was more frequent in patients receiving carbamazepine (10 percent) as compared to valproate comedication (5 percent). However, the adverse event was sufficiently serious to necessitate hospitalisation in 3 patients receiving valproate. Dose escalation was not respected in two. Rash was reversible in all of the patients following discontinuation of the drug. The results of this study contribute to the overall understanding of the spectrum of lamotrigine effectiveness across seizure types and epileptic syndromes. Lamotrigine was well tolerated in children and adults.
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PMID:[Optimal use of lamotrigine in clinical practice: results of an open multicenter trial in refractory epilepsy]. 1143 72

Tiagabine (TGB) is indicated as adjunctive therapy for partial seizures in adults and children aged 12 years and older. Double-blind, placebo-controlled studies of TGB treatment are under way in younger children with various forms of epilepsy. The results of pediatric pharmacokinetic trials indicate patterns similar to those seen in adults. An open-label study was conducted in the United States in 31 children with refractory complex partial seizures, with doses escalated every 2 weeks by 0.25 mg/kg up to a maximal daily dose of 1 mg/kg. Twenty-nine patients were treated with TGB for >1 year; 26 completed the study, of whom 18 were receiving monotherapy at study completion. A European dose-escalation study evaluated TGB (0.25-1.5 mg/kg/day) as add-on therapy in 52 children aged 2-15 years. TGB appeared to be more effective in localization-related epilepsy syndromes, with 17 of 23 patients with localization-related epilepsy having a 33% median reduction of seizure rate compared with baseline in the fourth month of treatment, and six patients having > or =50% seizure rate reduction. In this study, myoclonic seizures and spasms showed a poor response as opposed to encouraging findings reported by other groups with these seizure types. The adverse effect profile of TGB in children with epilepsy is similar to that in adults. In the U.S. study, most common adverse events were related to the central nervous system (CNS) and decreased over time. In the European study, mostly mild to moderate adverse events, including asthenia (19%), nervousness (19%), dizziness (17%), and somnolence (17%), were reported by 83% of TGB-treated children (39% of children reported adverse events during the single-blind placebo period). In summary, preliminary pediatric data with TGB suggest particular efficacy against epilepsy characterized by partial seizures or other syndromes, and further investigation is warranted.
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PMID:Tiagabine (gabitril) experience in children. 1152 Mar 24

Second generation antiepileptics lamotrigine (LTG) and tiagabine (TGB) were primarily licensed for adjunctive treatment of simple and complex partial seizures with/without secondary generalisation as similarly effective drugs. Reduction of seizures frequency is the most important index of drug efficacy, but overall therapeutic benefit estimated as a quality of life is nowadays the target goal of management. In this study efficacy and tolerability of LTG or TGB as short-term add-on treatment in patients with refractory complex partial seizures were assessed by the use of both physician-rated measures (mean monthly seizure frequency, responders rate, adverse events, clinical biochemistry) and patients perceived change in their own quality of life estimation (descriptive scale and visual analogue scale-VAS). Comparable efficacy of LTG (n-22, 378 mg/day) and TGB (n-26, 43 mg/g) was assessed as 41 and 35% of responders and above half of patients with noticeable improvement. 25% of patients in both groups reported reduction of seizures severity in 4-points descriptive scale. Biochemistry values did not show clinically significant changes after treatment. 13% of patients on LTG reported adverse events (headache, asthenia, irritability, insomnia). This coefficient was greater for TGB-35% (asthenia, headache, sleepiness, vertigo). However, no case of discontinuation as a result of adverse events was reported for either of the tested drugs. Even if efficacy of LTG and TGB was comparable in objective measurements, only patients on LTG reported a significant quality of life improvement in VAS. This might be the consequence of more frequent adverse events and treatment schedule of TGB (triple dosing/day). This trial confirmed that VAS might be used as an easy additional test in evaluation of antiepileptic drug for individual patient in everyday clinical practice.
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PMID:Clinical evaluation of Gabitril and Lamictal for drug-resistant epilepsy in adults. 1197 39

BECTS is characterized by the presence of simple partial motor seizures in the face and/or oropharynx, with or without sensory symptoms and often with secondary generalization. These seizures tend to occur more often during sleep or drowsiness. According to some authors, generalized seizures prevail over other types particularly among children aged five or less. The purpose of this study is to determine the characteristics of the first epileptic episode among children with BECTS, grouped by age as of their first epileptic seizure, as well as to analyze how such seizures change over the course of clinical evolution. A total of 61 children were examined, 16 of whom below the age of 5 and 45 above. With regard to the first and recurrent epileptic episodes, our final assessment showed that partial seizures occurred more frequently than generalized tonic-clonic seizures in both groups. Although no conclusive relation could be established between the type of partial seizure (i.e. simple versus complex) and the children's age as of their first epileptic episode, it was possible to correlate the type of epileptic seizure with their clinical evolution, in which case simple partial seizures proved to be more frequent than complex partial seizures. It should be noted that the number of children under the age of five was relatively small, which evidences the need for further studies. It should also be borne in mind that the reported frequency of generalized seizures in these children's first epileptic episode may be due to their parents' lack of attention and familiarity with this pathology and their attendant difficulty in characterizing its clinical symptoms.
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PMID:Benign focal epilepsy of childhood with centrotemporal spikes (BECTS): clinical characteristics of seizures according to age at first seizure. 1213 38

Temporal lobe epilepsy is a partial epileptic disorder in which mesial structures are responsible for the principal ictal symptoms. Its characteristic feature is the recurrence of simple and complex partial seizures, associated with postictal confusion and amnesia of the event. The facilitating effect of NREM sleep on the propagation of the seizure, as well as the sleep abnormalities provoked by epilepsy were evident in our two patients. Yawning is a physiological reflex induced by arousal and drowsiness and may appear in different neurological conditions. Its relation with epilepsy of limbic origin has been rarely reported. We describe in a 95 year old male patient, the occurrence of yawning followed by complex partial seizure during a state of drowsiness. His EEG showed independent bilateral interictal foci of temporal sharp waves and after being medicated with carbamazepine 400 mg/day, the episode did not recur. Another patient, a 17 year old female, displayed complex partial seizures and secondarily generalized seizures with yawning during the posictal period, after naps. The EEG was normal and her polysomnography showed bilateral synchronous temporal spikes and slow waves with secondarily generalization during stage 2 of NREM sleep that produce paroxysmal microarousals and increased stages 1 and 2 of NREM sleep and REM sleep diminished. After being medicated with divalproex sodium 750 mg/day, she suffered no further seizures. Temporal lobe epilepsy, sleep-wake cycles and yawning seem not only to share the same anatomic structures but also the same neurochemical mechanisms. The fact that endogenous opiods are considered as part of a protective system that stop and prevent seizures may allow us to postulate that yawning would be the expression of the endogenous opiods induced mechanisms that stop and prevent the recurrence of the temporal lobe epilepsy. Another hypothesis may be that this is only a particular form of temporal lobe epilepsy.
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PMID:[Yawning and temporal lobe epilepsy]. 1279 82

Knowledge on the effects of gabapentin (GBP) in learning disabled patients is limited. The objective of this study was to assess antiepileptic efficacy and tolerability of GBP in routine therapy. A retrospective open observational study design was applied. Twenty-nine consecutive residential patients with simple and/or complex partial seizures with or without secondary generalization and with different degrees of learning disability were included. All patients had severe therapy-resistant epilepsy. GBP was administered as add-on therapy. Dosages were progressively increased up to 1600-2400 mg/day (in a number of cases up to 4800 mg/day), in accordance with clinical requirements. The seizure frequency was recorded and compared between a baseline and a treatment period (after 3 months of titration) of 3 months duration each. Only three patients (10.3%) had a reduction of their seizure frequency by 50% or more. No patient became seizure-free. Unwanted side effects, mostly mild and dose-dependent, occurred in 37.9% of all patients. Somnolence and ataxia were the most frequently observed unwanted effects. In two cases hyperphagia/weight increase, and in two other cases edema occurred.We conclude the efficacy of GBP in learning disabled patients with highly therapy-resistant partial seizures is limited.
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PMID:Limited efficacy of gabapentin in severe therapy-resistant epilepsies of learning-disabled patients. 1463 May 2

We report a case of new-onset seizures and narcolepsy in a previously healthy 40-year-old man. He developed severe daytime somnolence and cataplexy over the course of a few months. Brain MRI was normal, and polysomnography with multiple sleep latency testing confirmed a diagnosis of narcolepsy. His HLA haplotype is DQB1*0602 and cerebrospinal fluid analysis showed no detectable hypocretin. Approximately 18 months later, he developed complex partial seizures. Further MRI showed a progressively enlarging lesion involving the left frontotemporal and insular areas. Pathology from a partial resection was consistent with Rasmussen's syndrome. Evaluation for tumor, infectious, and paraneoplastic etiologies was negative. There was no further progression of the residual lesion on serial MRI. Although the pathophysiologic bases of narcolepsy and Rasmussen's syndrome are unknown, they may have an autoimmune basis. This unique case of both disorders in a single patient suggests the possibility of a common underlying disease process.
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PMID:Rasmussen's syndrome and new-onset narcolepsy, cataplexy, and epilepsy in an adult. 1469 22

We examined the antiepileptic effect and side effects of sulthiame in 28 patients with intractable epilepsy. The patients' ages ranged from 6 months to 34 years (mean: 8 years 7 months), and 26 of them were under 18-years-old. Nineteen patients had severe physical and mental disabilities. Sixteen patients had generalized seizures, and 12 had partial seizures. Sulthiame was administered at the dose of 50-300 mg/day (4-14 mg/kg body weight) as add-on therapy in all except one patient. Among the 28 patients, two with complex partial seizures (7%) became seizure-free. Eight patients (29%) (6 patients with generalized seizures and 2 patients with partial seizures) showed seizure reduction by > 50%. Among these 10 patients who showed positive responses, six developed tolerance within 2-5 months. Side-effects were observed in 5 patients, including enuresis, drowsiness, and drooling, none of which caused discontinuation of treatment. Therefore, we conclude that sulthiame is an effective and safe antiepileptic drug for the treatment of intractable epilepsy.
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PMID:[Sulthiame treatment for patients with intractable epilepsy]. 1917 11

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


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