Tapani Keränen

Comparison of oxcarbazepine and carbamazepine: a double-blind study

The antiepileptic efficacy and side-effects of oxcarbazepine (OXC), a new carbamazepine derivate, were evaluated in a double-blind study. Forty ambulatory epileptics with unsatisfactory seizure control or unwanted effects due to phenytoin monotherapy were changed to OXC or carbamazepine (CBZ) and were then followed for 48-50 weeks. Thirty-four of the patients completed the study. The seizure frequencies on the trial drugs were not significantly different and the antiepileptic efficacy of OXC was comparable to CBZ. The incidence of side-effects during the initiation phase was lower with OXC suggesting better tolerability of OXC compared to CBZ.

Incidence and prevalence of epilepsy in adults in Eastern Finland

Summary: In Finland, only limited data exist on the epidemiology of epilepsy in adults. This prompted us to study the incidence and prevalence of epilepsy in a population over IS years of age, residing in Eastern Finland. In a retrospective study, various medical data sources were used to identify and reexamine all patients with established or suspected epileptic seizures during 1960–1979. A total of 1,233 patients with active epilepsy were identified. Mean annual incidence of epilepsy was 24/ 100,000. Age‐specific incidence ratios tended to increase with advancing age. Prevalence of active epilepsy was 629/100,000. Both prevalence and incidence were higher in males than in females. Age‐specific prevalence of active epilepsy increased until 40–50 years of age, and declined in the oldest age groups. Of the various seizure types, highest prevalence ratios were observed for partial secondarily generalized seizures, complex partial seizures, and tonic‐clonic seizures. Prevalence of partial seizures and generalized seizures had a different age‐related pattern.

Increased plasma levels of cytokines after seizures in localization-related epilepsy

Objectives –  Experimental studies suggest increased cerebral production of inflammatory cytokines after prolonged seizures. Whether a single non‐prolonged seizure in human patients is associated with activation of cytokine network is still unknown.

The balance of inhibitory and excitatory cytokines is differently regulated in vivo and in vitro among therapy resistant epilepsy patients

PURPOSE Excessive neuronal activity and seizures directly stimulate cytokine expression. In this study we investigated cytokine production in circulating blood and peripheral blood mononuclear cells (PBMC) in order to assess the cellular origin of these cytokines in patients with therapy resistant epilepsy. METHODS We compared the levels of plasma IL-1beta, IL-1Ra and IL-6 in 10 patients with therapy resistant localization-related epilepsy and in healthy volunteers. The spontaneous and exogenously stimulated production of these cytokines was studied in PBMC cultures using EIA. Moreover, cell-specific cytokine production was studied using flow cytometry. RESULTS Highly pro-inflammatory cytokine profile (high IL-6, low IL-1Ra and low IL-1Ra/IL-1beta ratio) was observed in plasma from patients with epilepsy. Spontaneous and LPS stimulated cytokine release was similar in PBMC cultures of patients and control subjects. When cells were stimulated with OKT3 the cytokine response profiles in patients with epilepsy were almost opposite (anti-inflammatory) to the profile which was observed in circulating blood. Low IL-6 was observed in cell cultures of patients when stimulated with PDBu + A23187. Flow cytometric analysis revealed that the percentages of IL-1beta, IL-1Ra and IL-6 positive monocytes were similar in patients and control subjects. CONCLUSIONS Patients with therapy resistant epilepsy display a pro-inflammatory profile of plasma cytokines without any evidence of increased production from PBMC. These results suggest that the most likely origin for these cytokines is the brain, where cytokines can exert neuromodulatory functions.

Distribution of Seizure Types in an Epileptic Population

Summary: The distribution of seizure types was investigated in an epidemiological survey of 1,220 patients over 15 years of age. Classification of clinically dominant seizure type according to the International Classification of Epileptic Seizures (ICES) was possible in 1,005 cases (82.5%). Fifty‐six percent of patients had partial seizures and 26.5% had generalized seizures. Subclassification of partial seizures revealed simple partial seizures (SPS) in 7.5% of the cases, complex partial seizures (CPS) in 23%, and partial secondarily generalized seizures (PSGS) in 25.5% of the cases. Simple partial onset was seen in 56% of the patients with CPS, and impairment of consciousness at the onset occurred in the remaining 44%). PSGS started with simple partial onset in 92% of the cases and the remaining 8% started with a complex partial phase. Tonic‐clonic seizures were the most common type of generalized seizures, accounting for 23% of all and 88% of generalized seizures. Absence seizures were seen in 1% of the cases. A single seizure type was observed in 737 patients (60%) and the remaining 40% had multiple seizure types. SPS, CPS, and absence seizures were most commonly combined with other seizure types. The study revealed that distribution of seizure type varies as a function of age. Although the present study finds ICES relevant, difficulties in its utilization in epidemiological context are demonstrated.

Absence of interaction between oxcarbazepine and erythromycin.

When erythromycin (ERY) is co‐administrated with the antiepileptic carbamazepine (CBZ), a drug interaction may cause an increase in CBZ plasma concentrations, which can result in CBZ related toxic symptoms. This cross‐over study was designated to investigate whether ERY influences the pharmacokinetics of the new antiepileptic oxcarbazepine (OXC) and its metabolites. In 8 healthy volunteers there were no significant differences in AUC, peak plasma concentrations or time to peak concentration when OXC was administered either with or without ERY. The results of this study suggest that OXC may offer an important advantage over CBZ especially when concomitant therapy with ERY is required.

Interleukin-6, interleukin-1 receptor antagonist and interleukin-1beta production in patients with focal epilepsy: A video–EEG study

UNLABELLED Experimental and clinical studies have shown that prolonged seizures result in increased cytokine production in the central nervous system. The purpose of this study was to examine plasma concentrations of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and interleukin-1 beta (IL-1beta) in 20 patients with epilepsy undergoing a video-EEG study. Plasma samples were obtained at the onset of the recordings and 3, 6, 12 and 24 h after the index seizure. Localization of the seizure focus and classification of epilepsy was based on concordant electroclinical findings in the video-EEG study, and on MRI examination. Patients were divided into two groups: temporal lobe epilepsy (TLE) (n=11), and extratemporal lobe epilepsy (XLE) (n=9). RESULTS Only the TLE group showed significant increase in plasma levels of IL-6 peaking at 6 h postictally. Postictal plasma levels of IL-1RA and IL-1beta did not significantly differ from baseline levels in either of the patient groups. IL-1RA showed a decreasing trend (p>0.059) in TLE patients during 12 to 24 postictal hours. CONCLUSIONS This study further supports the role of focal seizures in regulation of cytokine responses.

The effects of carbamazepine and sodium valproate on SEPs and BAEPs

SEPs and BAEPs were studied in 36 previously untreated epileptics receiving either carbamazepine (CBZ) or sodium valproate (VPA) monotherapy. CBZ prolonged central conduction times in SEPs and BAEPs. SEP latency prolongation correlated with serum CBZ levels. VPA had minimal effects on evoked potentials. The present study gives evidence of similar effects of carbamazepine and phenytoin on central neural conduction.

Visual Evoked Potentials, Brainstem Auditory Evoked Potentials, and Quantitative EEG in Baltic Progressive Myoclonus Epilepsy

Summary: Visual and brainstem auditory evoked potentials (VEP and BAEP, respectively) and quantitative EEG were studied in 16 patients with Baltic progressive myoclonus epilepsy (PME). The study demonstrated significantly delayed VEP latencies but normal amplitudes in Baltic PME. BAEPs showed slight but significant prolongation in central conduction time. Quantitative EEG revealed diminution of beta and alpha activity and accentuation of theta and delta activity. The slowing in VEP latencies is suggested to be due to impaired synaptic transmission and to reflect dopaminergic dysfunction in Baltic PME. We conclude that there is a multimodal disturbance in sensory projections to cortical areas in Baltic PME. The results give further evidence that nondemyelinating disorders—but with synaptic transmission defects—can produce changes in evoked potentials. The changes in epileptic brain are not confined to hyperexcitable epileptic neurons, but more widespread electrophysiological phenomena are produced.

Side effects of carbamazepine, valproate and clonazepam during long-term treatment of epilepsy

ABSTRACT Side effects of carbamazepine (CBZ), valproate (VPA) and clonazepam (CZP) are rare during long‐term use but rather common and usually transient during the early phases of treatment. The usual side effects of CBZ are drowsiness, dizziness, and diplopia, which are dose dependent in long‐term use, but CBZ does not seem to cause cognitive disturbances, as do phenobarbital and phenytoin. Other reactions to CBZ may include leukopenia, hyponatremia, disturbances of vitamin D metabolism and fortunately rarely, agranulocytosis and hepatitis. Use of VPA can lead to gastrointestinal discomfort, weight gain, hair loss, tremor and sedation, but these side effects are rather uncommon, mild, and transient during VPA monotherapy. Potentially hazardous reactions such as hepatitis and pancreatitis have occurred in a few patients on VPA, generally with multidrug therapy. Some of the side effects are dose related. They infrequently lead to withdrawal of VPA. Side effects limited to initiation of CZP therapy include drowsiness, ataxia, and behavioral changes; they are usually transient but can lead to dose reduction or even withdrawal of the drug. Except for development of tolerance, CZP seems to be practically free of long‐term side effects.