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The new antiepileptic drug zonisamide was evaluated in a European multicenter parallel-group double-blind trial as add-on treatment for 139 patients with refractory partial epilepsy. During treatment with zonisamide complex partial seizures decreased by 27.7% compared to placebo (P < 0.05) and the median rate dropped from 12/month to 7.1/month with no changes in the placebo group (P < 0.007). During the 12-week double-blind phase a 50% reduction of all seizures was recorded in 29.9% of the patients treated with zonisamide vs. 9.4% during placebo. Complete remission was observed during treatment with zonisamide in 6.2%. The plasma concentrations of the concomitant antiepileptic drugs did not change markedly when zonisamide was added. Adverse events, mostly fatigue, somnolence, dizziness and ataxia, occurred in 59.2% of the patients compared to 27.9% during placebo. Zonisamide was withdrawn in two patients due to adverse events. Kidney stones were not observed nor any relevant clinical chemistry or hematological changes. Zonisamide is an effective antiepileptic drug for add-on treatment of refractory partial epilepsy.
Epilepsy Res 1993 May
PMID:Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial. 832 80

Sixty-five patients with Candida albicans fungaemia, admitted to intensive care units, were treated intravenously with fluconazole. All patients had at least one blood culture which was positive for C. albicans. The first group of 34 consecutive patients received fluconazole at a dose of 5 mg/kg bodyweight/day and the subsequent 31 patients received 10 mg/kg/day. Thirty patients in each group were evaluated. The clinical response rate was 60% in the 5 mg/kg once daily group and 83% in the group which received 10 mg/kg/day. Eradication of C. albicans from the blood was achieved in all but two patients in the 5 mg/kg group and in all patients in the 10 mg/kg group. As regards other sites of infection, eradication was achieved in only nine of 25 cases from the 5 mg/kg group and in 11 of 23 cases from the 10 mg/kg group. Death related to fungal infection occurred in eight patients receiving 5 mg/kg/day and in one patient receiving 10 mg/kg/day. Fluconazole was reasonably well tolerated. Raised concentrations of liver enzymes were observed in 14 patients. Other adverse effects were fatigue, nausea, gastric pain, sleepiness and epileptic seizure. In conclusion, fluconazole at a dose of 10 mg/kg/day would seem to be an effective and safe drug for the management of C. albicans fungaemia.
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PMID:Treatment of Candida albicans fungaemia with fluconazole. 847 60

Efficacy and tolerability of the new antiepileptic drug oxcarbazepine, was evaluated in a retrospective multicentre study. The records of all 947 epilepsy patients treated with oxcarbazepine in the eight participating centres from 1981 through 1990 were examined. The median daily dose of oxcarbazepine was 30 mg/kg in children, 18 mg/kg in adults, and 15 mg/kg in elderly patients, given b.i.d. or t.i.d. The mean plasma levels of the main active metabolite of oxcarbazepine was 88, 79, and 68 mumol/l in children, adults, and elderly, respectively. In patients shifted to oxcarbazepine treatment, seizure frequency was unchanged in 51-66%, 32-48% had a decrease, and 1-10% an increase in seizure frequency, considering the individual seizure types separately. Adverse events were reported in one third of patients, most frequently affecting the CNS (dizziness: 6%; sedation: 6%; fatigue: 6%). Rash was reported in 6% of patients, half of these patients had previously had an allergic reaction to carbamazepine. Hyponatremia was found in about a quarter of the patients from whom data were available. No congenital malformations were seen in nine live-born, first trimester oxcarbazepine-exposed children.
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PMID:Therapeutic experiences with 947 epileptic out-patients in oxcarbazepine treatment. 847 94

Drowsiness is a common complaint among patients with epilepsy taking antiepileptic drugs (AEDs) and may be of particular importance because of the potential effects on cognitive abilities. We used a novel EEG-based measure (the Awake Maintenance Task, AMT) to determine objectively whether patients on chronic, stable AED therapy had impaired ability to maintain wakefulness. Thirty patients receiving AEDs [carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), valproate (VPA)] were compared to 35 healthy controls, 12 seizure patients not taking AEDs, and 16 patients with multiple sclerosis. A structured EEG recording was conducted under controlled conditions, and subjects were tested to determine their ability to maintain wakefulness during a 6-min unstimulated trial. Testing also included Digit Symbol, auditory reaction time, and subjective measures of fatigue or sleepiness [Profile of Mood States (POMS), Stanford Sleepiness Scale (SSS)]. Patients receiving AEDs had a mean total drowsiness score of 101 s compared with < or = 12 s for each of the three control groups (P < 0.001). One third of the AED-treated patients had > 120 s of drowsiness, in contrast to only 1 of 63 controls (p < 0.001). Among patients receiving AEDs, objective EEG drowsiness did not correlate with AED levels or performance measures. Untreated seizure patients had significantly greater complaints of lack of vigor despite a near absence of objective drowsiness on the AMT. These results suggest that epilepsy patients receiving chronic AED therapy have impaired ability to maintain wakefulness. Patient self-reports of AED-related sleepiness may not accurately represent this problem.
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PMID:Assessment of drowsiness in epilepsy patients receiving chronic antiepileptic drug therapy. 863 29

In a double-blind, randomized, parallel-group trial, we compared topiramate (TPM) with placebo as add-on therapy in patients with refractory partial epilepsy. TPM was titrated either to the target dosage of 800 mg/ day [400 mg twice daily (b.i.d)] or to the maximal tolerated dose if lower. Twenty-eight (28) patients were randomized to each treatment group. In the intent-to-treat analysis, the net median percent reduction relative to placebo in average monthly seizure rate was 54% for patients in the TPM group (p < 0.001). None of the placebo-treated patients and 43% of the patients treated with TPM experienced > or = 50% reduction in seizures (p = 0.001), and 36% of patients assigned to TPM had a 75-100% reduction in seizures (p < 0.01). Secondarily generalized seizures were also significantly reduced in the TPM group (p = 0.044). The most common adverse events (AE) reported in the TPM group were fatigue, impaired concentration, weight loss, dizziness, and paresthesias. AE occurring either during the rapid titration of TPM or at high dosages led 21% of TPM-treated patients to withdraw from the study. Half of these occurred during the titration study period. No serious AE or clinically important changes in clinical laboratory measures were observed. The present study further establishes the favorable profile and good benefit/risk ratio of TPM in resistant partial epilepsy.
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PMID:Double-blind, placebo-controlled trial of topiramate as add-on therapy in patients with refractory partial seizures. 864 Dec 30

We report a mentally retarded 30-year-old woman with partial trisomy of chromosome 9 (46, XX-6, +der(6)t(6,9)pat) who has had epilepsy since age 11 months. She had been treated with various combinations of drugs. After 1 year of treatment with valproate (VPA) and ethosuximide (ESM), the patient developed arthralgias, muscle weakness, fatigue, and fever. Laboratory examination showed increased sedimentation rate, hypergammaglobulinemia, and high titers of antinuclear antibodies (ANA). The possibility of VPA-induced systemic lupus erythematosus (SLE) was considered. This diagnosis was supported by detection of antihistone antibodies and the HLA-DR4 antigen. VPA dosage was tapered and discontinued, with accompanying resolution of clinical, immunological and hematological signs of SLE 6 weeks after VPA discontinuation. This is the fourth reported case of VPA-induced SLE.
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PMID:Valproate-induced systemic lupus erythematosus in a patient with partial trisomy of chromosome 9 and epilepsy. 864 Dec 38

Primary Generalized Epilepsy (PGE) has been more hotly debated over the past decades than other forms of epileptic seizure disorder. The sudden synchronous appearance of bilateral spikes and spike-waves (mainly with myoclonus resp. absence) used to perplex the earliest generation of electroencephalographers, and the enigmatic genesis of these discharges (and seizures) has not ceased to fascinate the investigators of this phenomenon. A "centrencephalic" concept with paroxysmal discharges arising from thalamic structures and "projecting" to the cortex was championed for many years and eventually laid aside. More recently, the role of the thalamic level has been re-emphasized, mainly on the basis of experimental work. In this article, the bulk of experimental work is critically reviewed: the simian model (Papio papio), the feline, and the rodent models (Wistar rat, tottering mouse). Stress is being laid on fundamental differences between all of these models and human PGE. EEG evidence indicates a superior frontal origin of bilateral-synchronous spikes and spike-waves; depth EEG recordings in patients have failed to demonstrate primary thalamic spike generation. The heart of the matter in PGE appears to be the mechanism underlying paroxysmal discharges; above all the role of arousal. It is not awakening from sleep but the ensuing period that is critical in its epileptogenic thrust caused by alternating periods of return to drowsiness and arousing stimuli. This biphasic process gradually escalates EEG bursts to myoclonus (or absences) and possibly to a generalized tonic-clonic convulsion. Most conducive to this crescendo is the state of tiredness following a night of poor sleep. Bilateral synchrony is not precise and small time differences exist. The line between primary and secondary bilateral synchrony (with a primary cortical focus) can become blurred. Genetic predisposition to generalized paroxysms must always be considered, even in the face of a primary focus with secondary bilateral synchrony. Photosensitivity is a second paroxysm-inducing mechanism in PGE; it is much less common than the abnormal arousal ("dyshormia"); both mechanisms can be present in the same patient. Therapy and prevention of seizures in PGE are finally discussed. The concept of abnormal arousal mechanisms can be put into practice in order to prevent seizures: avoidance of sleepless nights, not always an easy task in adolescents and young adults.
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PMID:Primary (idiopathic) generalized epilepsy and underlying mechanisms. 871 97

Temporal lobectomy appears to be an effective treatment for medically intractable epilepsy. However, the influences of pre-operative health status and post-operative reductions in seizure activity on post-surgical health-related quality of life (HRQOL) are not well understood. We used the Epilepsy Surgery Inventory 55 (ESI-55) to evaluate changes between pre- and post-operative HRQOL in 47 temporal lobectomy patients. Patients exhibited significantly improved scores in five HRQOL domains: health perceptions; energy fatigue; social function; cognitive function and role limitations due to physical problems. Although significant improvements in HRQOL were observed, this was not the case for all patients. Specifically, patients with low or medium pre-operative HRQOL scores were found to have the greatest degree of improvement post-operatively. Patients with high pre-operative scores did not exhibit these same improvements, although they continued to report high scores. The results indicate that the ESI-55 is a satisfactory instrument to measure change in HRQOL but also emphasizes that the magnitude of change in post-operative HRQOL scores tends to vary according to baseline scores. The outcome of temporal lobectomy is not entirely based upon the procedure's ability to reduce the frequency of seizures, but is also influenced by level of HRQOL prior to surgery.
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PMID:Determinants of health-related quality of life after temporal lobe epilepsy surgery. 876 8

Topiramate is a recently licensed and marketed antiepileptic drug in the UK for use as add-on therapy for refractory partial epilepsy. It has multiple modes of action involving voltage-dependent sodium channels, GABA receptors and glutamate receptors. Topiramate has very favourable pharmacokinetics as it is primarily excreted unchanged. Its metabolism is, however, increased by enzyme inducers, and it can inhibit the metabolism of phenytoin in some patients. Its efficacy as adjunctive treatment in refractory partial epilepsy in adults appears good, over 40% of patients have a 50% or greater reduction in seizure frequency when topiramate is added to their regime with up to 7% becoming seizure free. The main adverse events are ataxia, impaired concentration, confusion, dizziness, fatigue, parasthesia, somnolence and "thinking abnormal'. Most of these occurred during rapid titration. During long-term treatment, weight loss also occurred and nephrolithiasis occurred in 1.5% of patients receiving topiramate. Topiramate is a useful and well-tolerated addition to our treatment of refractory epilepsy, but it should be titrated slowly in order to avoid adverse events.
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PMID:Topiramate: a new antiepileptic drug for refractory epilepsy. 890 21

The efficacy of gabapentin (Neurontin), in generalized seizures was evaluated in this 14 week, double-blind, placebo-controlled, parallel-group, add-on, multicenter study. A total of 129 patients with refractory generalized seizures were randomized to receive either placebo or 1200 mg/day gabapentin as add-on therapy. Patients received their standard regimens of antiepileptic drugs (AEDs) during a 12 week baseline period, and gabapentin or placebo was added-on in the subsequent 14 week evaluation period. Results of both an intent-to-treat (ITT) and evaluable-patient analyses showed that gabapentin provided greater reduction in the frequency of generalized tonic-clonic seizures than did placebo; however, the differences between treatments were not statistically significant. Gabapentin did not affect the frequency of absence or myoclonic seizures. Adverse events were reported by 67% of gabapentin-treated patients and by 56% of placebo-treated patients. The most frequently occurring adverse events among patients receiving gabapentin were somnolence, fatigue, and dizziness. Gabapentin is well tolerated by patients with generalized seizures. The results of this study show a trend toward an effect of gabapentin in reducing the frequency of generalized tonic-clonic seizures and suggest that further exploration of high dose gabapentin in generalized epilepsy is warranted.
Epilepsy Res 1996 Nov
PMID:Gabapentin in generalized seizures. 895 16


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