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Lamotrigine is an antiepileptic drug which is believed to suppress seizures by inhibiting the release of excitatory neurotransmitters. Efficacy has been demonstrated for lamotrigine as add-on therapy to existing regimens in patients with resistant partial seizures. Total seizure frequency was reduced by 17 to 59% compared with placebo, and 13 to 67% of patients experienced reductions of > or = 50% in seizure frequency. Secondarily generalised tonic-clonic seizures respond well to lamotrigine, and there is preliminary evidence of improvement in patients with primary generalised seizures, Lennox-Gastaut syndrome and in children with multiple seizure types. Seizure control has been maintained in patients who have continued to receive lamotrigine as monotherapy after discontinuation of other medications. Results of one trial suggest similar efficacy for lamotrigine monotherapy as for carbamazepine, but confirmation of its use in this setting awaits more extensive controlled comparisons with established agents. Adverse events associated with lamotrigine as add-on therapy are typical of antiepileptic drugs, namely dizziness, ataxia and other CNS-related symptoms. Rash, which has occurred in 10% of patients in placebo-controlled trials, may be severe and its appearance has led to discontinuation of therapy in 1% of patients. Lamotrigine appears well tolerated in the longer term, but this facet of its profile requires further monitoring. Influences of valproic acid and enzyme-inducing anti-epileptics on lamotrigine eliminate necessitate dosage modification of lamotrigine. Conversely, lamotrigine has little apparent influence on the pharmacokinetics of other agents, although it may increase plasma concentrations of the active metabolite of carbamazepine during concomitant administration. Thus, lamotrigine permits improved seizure control in some patients with refractory partial seizures, and may prove to be especially effective in secondarily generalised tonic-clonic seizures. As is usual at this stage in a drug's development, several aspects of the profile of lamotrigine are incompletely defined, notably its efficacy in other seizure types, in children, as monotherapy, and its longer term tolerability. Nonetheless, lamotrigine presently offers a worthwhile alternative for the physician confronted with the challenge of treating patients with intractable partial seizures with or without secondarily generalised seizures, and shows potential for broader applications in other areas of epilepsy management.
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PMID:Lamotrigine. A review of its pharmacological properties and clinical efficacy in epilepsy. 769 4

Gabapentin is an antiepileptic drug with an unknown mechanism of action apparently dissimilar to that of other antiepileptic agents, and possessing some desirable pharmacokinetic traits. The drug is not protein bound, is not metabolised and does not induce liver enzymes, diminishing the likelihood of drug interactions with other antiepileptic agents and drugs such as oral contraceptives. Although gabapentin is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA), which does not cross the blood-brain barrier, gabapentin penetrates into the CNS and its activity is seemingly distinct from GABA-related effects. Present clinical evaluation is largely restricted to proof of efficacy trials of gabapentin as add-on therapy in patients with partial epilepsy resistant to conventional treatment. Gabapentin (usually 600 to 1800 mg/day) provides notable benefit, reducing seizure frequency by > or = 50% in 18 to 28% of patients with refractory partial seizures, as shown in 3 double-blind, placebo-controlled trials. Overall, seizure frequency decreased by 18 to 32% during 3-month treatment periods. Patients with complex partial seizures, and partial seizures secondarily generalised, are particularly likely to respond to gabapentin. Current experience with the drug in other seizure types, and as monotherapy, is limited. Mild adverse events, commonly somnolence, fatigue, ataxia and dizziness, have been reported in about 75% of gabapentin recipients. While the drug has been well tolerated when administered to a few patients for periods of up to 5 years, its long term tolerability profile has yet to be fully expounded. Thus, with its favourable pharmacokinetic profile, and efficacy in some refractory patients, gabapentin is poised to fill a niche as an adjunct to the treatment of partial epilepsy. Promising results obtained thus far warrant further work to clarify its long term tolerability, its possible efficacy in other seizure types, its position relative to other agents and its use as monotherapy. In the meantime, gabapentin is likely to provide a much-needed option in a therapeutic area requiring complex management.
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PMID:Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy. 769 32

Data of patients suffering from Alzheimer's disease and checked out in the special unit named Memory Clinic functioning from 1992 in the National Institute of Psychiatry and Neurology are summarized. Age average of the 60 patients was 63 years, the first symptoms of the disease had appeared in 57 p.c. before the age of 65, so the classical presenile form of the ailment is represented too in the material. Predominance of multifocal cortical function disturbances in the symptomatology is characteristic, association of the depression is outstandingly frequent. The atypical features, or those characteristic in diseases of cerebrovascular origin are not infrequently seen (headache, dizziness, slight symptoms of pyramidal lesions). The absence of epileptic seizures It was interesting even in considering the data of the literature too. The main points of clinical diagnostics and differential diagnostics are demonstrated with the aid of case reports. The author's material is the first Hungarian publication in the topics of clinical symptoms of patients suffering from Alzheimer's disease that had been investigated with up-to-date methods. Occurrence of the disease of very great frequency could be supposed to occur at general practitioners, the importance of differential diagnostics and planning of the complex longlasting therapy is extremely great.
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PMID:[Clinical symptoms of Alzheimer disease]. 774 55

An aura is generally understood to be the beginning of a seizure. Yet, following successful surgery for intractable epilepsy, patients may have persistent auras even though they are otherwise seizure free. Ninety patients with intractable seizures and auras underwent resective surgery. Forty-three patients had hippocampal sclerosis and 47 had temporal or extratemporal lesions such as glial tumors or vascular malformations. The semiology of the auras was found to have value in localization but not lateralization of the pathology. Epigastric auras as well as gustatory and olfactory auras were significantly more frequent in patients with hippocampal sclerosis than in those with temporal or extratemporal lesions. Auras of vertigo or dizziness were most frequent in patients with extratemporal pathology. There was a significant difference between the pathology groups in the efficacy of resection in eliminating the auras. Of the patients with hippocampal sclerosis who were rendered seizure free, 18.9% had persistent auras, whereas only one (2.6%) of the patients with temporal or extratemporal lesions who were rendered seizure free had persistent auras. These findings suggest that for patients with hippocampal sclerosis an anatomical dissociation between seizure and aura may occur, whereas this dissociation is not present in patients with lesions. Patients suspected of having hippocampal sclerosis should be counseled preoperatively as to the significant likelihood of persistent auras even if seizures are successfully abolished.
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PMID:The anatomy of epileptic auras: focal pathology and surgical outcome. 778 51

We report open-label clinical observations of additional lamotrigine (LTG) in 16 adult patients with refractory epilepsy, aimed to assess the long-term efficacy and safety of LTG in clinical use. LTG was added to the current antiepileptic drug (AED) regimen at a daily dosage of 200-400 mg depending on the concomitant treatment. Ten patients completed one year's treatment and were followed up to an overall exposure ranging 15-38 months. Six patients (38% of the initial group) had a reduction of seizure frequency greater than 50% of pre-treatment baseline after one year; the further follow-up indicated some efficacy decline, since the percentage of improved patients dropped to 19% after 2 years and 13% after 3 years. The dropouts during the first year were due to seizure breakthrough (two patients), Steven-Johnson-like syndrome (one patient) and reasons unrelated to treatment (three patients); in one patient LTG treatment was stopped due to macrocytic anemia after 23 months. Other reported adverse events were dizziness, mild ataxia, diplopia and localized purpura. No other hematological or biochemical changes were noted. LTG was not associated with any significant changes in plasma concentrations of concomitant AEDs. These findings confirm the moderate efficacy and low toxicity of long-term LTG in severe epilepsy.
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PMID:Long-term observations on the clinical use of lamotrigine as add-on drug in patients with epilepsy. 784 67

The aims of treating epilepsy are to stop seizures, and to neutralize any associated cognitive or psychosocial penalty associated with epilepsy or its treatment. Inappropriate medication and/or continuance of seizures have deleterious effects on quality of life. The Epilepsy Task Force devised a 30-item questionnaire which was sent to children with epilepsy whose families are members of the British Epilepsy Association. The 896 replies which were received within the first two weeks have been analysed. Forty-two per cent of respondents had tonic-clonic seizures. Thirty-five per cent had had no seizures within the previous six months, but 29% reported seizures which occurred at least once a week. Although 42% didn't mind their seizures, the remaining respondents described their seizures as making them feel helpless, scared, panicky, frustrated and different from others. The most common medications were carbamazepine and sodium valproate. Side effects attributed to the medication included tiredness, difficulty in concentrating, dizziness, headache, irritability and weight gain. Thirty-six per cent said that their doctor had never explained about their epilepsy. The questionnaire included space for free-text comments and these were made by more than 400 respondents.
Seizure 1994 Dec
PMID:Quality of life--a view from the playground. 789 45

Data from five almost identical protocols have been pooled to give the results of treatment with lamotrigine in 285 children with refractory epilepsy. All the children received lamotrigine as open, add-on therapy and efficacy was assessed after the first 12 weeks of maintenance dosage. More than 50% reduction in seizures was achieved for over 30% of patients with complex partial, secondary generalized tonic-clonic, myoclonic, primary generalized tonic-clonic and atonic seizures; and, more than 50% of those with typical or atypical absences. In children treated for more than a year, there was no evidence of development of tolerance. Evaluations by investigators and parents found lamotrigine to improve the child globally in 74% of cases. Lamotrigine was well tolerated. Dizziness, unsteadiness and other non-specific side-effects that have been noted in a small minority of adults were rarely complained of by children. Rash was the most frequently reported side effect, leading to withdrawal of the drug in 7.4% of patients. However, the rate was lower when lamotrigine dosage was increased slowly as recommended. Data from other, smaller trials have also been reviewed and it is concluded that lamotrigine is a very well tolerated drug with a broad spectrum of efficacy.
Seizure 1994 Dec
PMID:Lamotrigine--a clinical overview. 789 52

Amantadine and rimantadine are recommended for the treatment and prophylaxis of influenza A infections, and constitute an integral component of influenza control measures in the nursing home setting. However, optimal use necessitates a thorough understanding of the toxicity profiles of these agents, as well as strategies to reduce the risk of adverse reactions. Adverse reactions of these compounds predominantly involve the gastrointestinal tract and the central nervous system (CNS), including hyperexcitability, slurred speech, tremors, insomnia, dizziness, mood disturbance, ataxia, psychosis and fatigue. Based on data from comparative trials, rimantadine appears to exhibit a lesser propensity to cause adverse CNS reactions than amantadine, but a similar propensity to cause adverse gastrointestinal reactions. Factors enhancing the risk of adverse reactions to these agents include reduced renal function (especially for amantadine), drug-drug interactions with cationic drugs, which inhibit amantadine renal tubular secretion (e.g. trimethoprim, triamterene, and possibly cimetidine and procainamide), elevated peak and trough plasma concentrations, and a history of seizures. Careful attention to published dosage adjustment guidelines for these compounds, avoidance of interacting drugs and avoiding these agents in patients with a history of seizures may be the best means to reduce the risk of toxicity in elderly patients. Rimantadine may have an advantage over amantadine in the elderly population in light of its lesser propensity to cause adverse reactions, less complex dosage adjustment in the case of renal impairment and probable lack of drug-drug interaction potential with cationic drugs.
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PMID:Amantadine and rimantadine prophylaxis of influenza A in nursing homes. A tolerability perspective. 791 41

The antidepressant venlafaxine has a unique chemical structure and neuropharmacologic profile. It significantly inhibits reuptake of both serotonin and norepinephrine and lacks notable muscarinic-cholinergic or alpha-adrenergic effects. Premarketing studies involving more than 2000 patients showed the efficacy of venlafaxine to be significantly greater than placebo at dosages between 75 and 375 mg/day in both outpatients and inpatients. The medication may be administered twice or three times daily. Venlafaxine was found equally effective for patients older and younger than 60 years and in those with psychomotor retardation or agitation; it proved slightly more efficacious than fluoxetine in a comparison study with melancholic inpatients. A promising finding of these studies is the suggestion of a rapid onset of clinical effect for venlafaxine. In some studies, venlafaxine showed a consistent and robust clinical superiority over placebo by Week 1, and in the inpatient study involving melancholic patients, the superiority of venlafaxine was demonstrated as early as Day 4. In general, early responses are seen at the higher dosages. Venlafaxine has also shown promise in treating rigorously defined treatment-refractory depression. The adverse effects of venlafaxine that most often led to discontinuation from a clinical study were nausea (6%), somnolence (3%), insomnia (3%), and dizziness (3%). Although nausea was the most common adverse effect overall, it resolved rapidly--within the first 1 to 3 weeks of therapy. Other adverse events with incidences significantly higher than with placebo were dizziness, constipation, sweating, nervousness, and abnormal ejaculation. The seizure rate and potential for cardiac conduction changes or orthostatic hypotension with venlafaxine were comparable with rates seen with the serotonin selective reuptake inhibitors. A small number of patients experienced dose-dependent blood pressure elevation with venlafaxine in premarketing studies (3% to 5% of those receiving < or = 200 mg/day; 7% of those receiving 201-300 mg/day; 13% of those receiving > 300 mg/day vs. 2% receiving placebo). In general, venlafaxine is well tolerated, and its treatment discontinuation rate is similar to those of the newer antidepressants and superior to discontinuation rates with the first-generation agents.
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PMID:The role of venlafaxine in rational antidepressant therapy. 796 45

A 45-year-old man developed generalized convulsion and consciousness disturbance at age 43. An X-ray CT revealed hemorrhagic infarction in the left fronto-parieto-temporal area. A conventional angiography disclosed complete occlusion of the left cortical vein. In the chronic stage of the stroke, he had incomplete right quadrantopsia, a mild right hemiparesis and sensory aphasia. The patient has had partial somatosensory seizures since February 1990. Ictal EEG recordings showed epileptogenic discharges in the left parietal region. The seizures were adequately controlled with clonazepam. Since July 27, 1993, he has become aware of blurred vision in both eyes accompanied with headache and dizziness. On August 6, he was admitted to the hospital with right homonymons hemianopsia, sensory aphsia and tonic seizures in the right hand. Ictal EEG recordings demonstrated theta waves of the left parieto-occipital region and epileptogenic discharges in the left occipital region which consisted of spikes, sharp waves and spike-wave complexes. Single photon emission computed tomography (SEPCT) images obtained during seizures showed considerable hyperperfusion in the left occipital temporal lobes, while there was hypoperfusion in the left temporo-parietal area corresponding to the lesion of the old cerebral infarction. A T2-weighted MRI scan showed an abnormal high-intensity area in the left occipital lobe that suggested brain edema. After the admission, the patient was treated with additional anticonvulsant drugs. The tonic seizures in the right hand disappeared and right homonymous hemianopsia and sensory aphasia showed gradual improvement in the next four weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An unusual case of status epilepticus of simple partial seizure with an occipital lobe focus]. 799 93


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