Ulrich Specht

Valproic Acid–induced Hepatopathy: Nine New Fatalities in Germany from 1994 to 2003

Summary:  Purpose: Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for generalized and focal epilepsies. We provide an update on hepatotoxic side effects in Germany between 1994 and 2003.

Pharmacokinetic Interactions of the New Antiepileptic Drugs

SummaryTherapy with traditional antiepileptic drugs is associated with a wide range of pharmacokinetic drug-drug interactions. In particular, enzyme induction, enzyme inhibition and displacement from protein binding may result in important changes in serum concentrations of antiepileptics. Relevant interactions have also been described for some new antiepileptics.Felbamate increases serum concentrations of phenytoin, phenobarbital and valproic acid (sodium valproate). On the other hand, it reduces concentrations of carbamazepine and increases concentrations of its metabolite carbamazepine-10,11-epoxide. Concentrations of felbamate itself are reduced by phenytoin and carbamazepine. Concentrations of lamotrigine are considerably increased by valproic acid and decreased by phenytoin, carbamazepine and phenobarbital (phenobarbitone). Vigabatrin reduces serum concentrations of phenytoin by approximately 20%.On the other hand, some new antiepileptics have the important advantage of not interfering with the metabolism of other antiepileptics; this is the case for gabapentin, lamotrigine and oxcarbazepine. Furthermore, the pharmacokinetics of gabapentin, oxcarbazepine and vigabatrin are independent of concomitant drugs. These aspects are especially important as, until now, new antiepileptics have been most often utilised as add-on therapy.

MOSES: An Educational Program for Patients with Epilepsy and Their Relatives

Summary: The knowledge of patients with epilepsy about their own condition is poor, and thus the need for educational programs for people with epilepsy has long been recognized. However, no such programs have been established in their routine care. The Modular Service Package Epilepsy (MOSES) now tries to fill this gap for patients in German‐speaking countries. The program was developed by a multidisciplinary group (neurologists, nonmedical professional helpers, and representatives of national epilepsy associations) for people with epilepsy older than 16 years, independent of the kind and severity of their epilepsy. MOSES is designed for group education and can be used in inpatient and outpatient settings in epilepsy centers, in clinics, and by neurologists in private practice. The program aims to help patients achieve a better understanding of their disease, to gain more self‐confidence, and to take over responsibility, thus supporting patients to become experts in managing their own illness. Being modular in structure, MOSES includes nine units: living with epilepsy, epidemiology, basic knowledge, diagnostics, therapy, self‐control, prognosis, psychosocial aspects, and network epilepsy. MOSES consists of a workout manual for patients and a trainer manual. For potential trainers, special “train‐the‐trainer seminars” are offered and considered mandatory. About 400 patients have participated in a MOSES training program in Germany, Switzerland, and Austria. The efficacy of the program is currently been evaluated.

Effects of an inpatient rehabilitation program after temporal lobe epilepsy surgery and other factors on employment 2 years after epilepsy surgery

To evaluate the effects of a postsurgical rehabilitation program on employment status 2 years after temporal lobe epilepsy surgery in relation to other predictors.

Discontinuation of Clonazepam After Long-Term Treatment

Summary: Frequent unwanted side effects and development of tolerance are the main disadvantages of clonazepam (CZP) in long‐term treatment of epileptic patients. A review of the literature shows that CZP tolerance more often appears in severe forms of childhood epilepsy (West and Lennox‐Gastaut syndromes) than in other epileptic syndromes. We prospectively studied the consequences of CZP discontinuation in 40 consecutive children with difficult‐to‐treat epilepsies and multiple‐drug therapy. The CZP was reduced stepwise in a variable daily reduction rate (0.003‐0.16 mg/kg), while serum levels of the comedication were kept unchanged. In only three children (7.5%), CZP was believed to have had some antiepileptic effect; in 30 (75%) it had been ineffective, whereas in six (15%), a decrease in seizure frequency after CZP discontinuation even suggested a negative therapeutic effect. Discontinuation symptoms, mostly in the form of a transitory exacerbation of seizure frequency, occurred in 19 children (47.5%). These children had a significantly higher CZP dose and longer duration of treatment than did children without discontinuation symptoms, but there was no difference between the two groups related to the rate of CZP discontinuance.

PESOS-Fragebogen für Menschen mit Epilepsie—

The PESOS questionnaire was developed at the Epilepsy Center Bethel in order to assess individual problems of patients with epilepsy in social and occupational surroundings (diagnostic function) and to investigate effects of treatment and counselling on quality of life (evaluative function). Clinical and demographic data, objective and subjective indicators of quality of life and modules (subscales) for specific patient groups (e. g. for students, employees) are included. The psychometric properties of the PESOS scales ‘Restrictions in daily life due to epilepsy’ ‘Epilepsy-related fear’, ‘Stigma’, and ‘Emotional adaptation’ were investigated in a multi-center study. The results indicate that the investigated subscales of the PESOS are reliable, valid and sensitive regarding effects of seizure frequency and tolerability of antiepileptic drugs.ZusammenfassungDer PESOS-Fragebogen wurde im Epilepsiezentrum Bethel entwickelt, um die individuellen Auswirkungen von Epilepsien auf soziale und berufliche Bereiche zu erfassen (diagnostische Funktion) und Effekte der Behandlung und Beratung auf die Lebensqualität der Betroffenen zu untersuchen (evaluierende Funktion). Erfasste Bereiche: medizinische und demographische Daten, objektive und subjektive Indikatoren der Lebensqualität sowie Module für spezielle Patientengruppen (z. B. Schüler/Studenten, Beschäftigte/Arbeitslose). Die psychometrischen Eigenschaften der PESOS-Skalen ‚Beeinträchtigungen im täglichen Leben durch die Epilepsie‘, ‚Epilepsiespezifische Angst‘, ‚Stigma‘ und ‚Emotionale Adaption an Epilepsie‘) wurden in einer multizentrischen Studie überprüft. Die Ergebnisse zeigen, dass die untersuchten Skalen des PESOS reliabel, valide und sensitiv hinsichtlich der Anfallsfrequenz sowie der Verträglichkeit der Antiepileptika-Therapie sind.

Should patients with psychogenic nonepileptic seizures be allowed to drive? Recommendations of German experts

In the absence of evidence-based regulations on the driving ability of patients with psychogenic nonepileptic seizures (PNES), we asked 41 German epileptologists via e-mail for their recommendations on driving with PNES. This survey was modeled on an earlier study by Benbadis et al. in the United States and was compared with it. Thirty-four (82.9%) epileptologists responded. Three responses were possible: (A) same restrictions as stipulated for patients with epilepsy, answered by 11 epileptologists (32.4%); (B) no restrictions at all, which no German expert gave as an answer (0%); (C) decision on an individual basis, answered by 23 experts (67.6%). The divergent approaches reflect the poor data on motor vehicle accidents of patients with PNES and the great variability of PNES with respect to semiology, psychiatric morbidity, and prognosis. In the study by Benbadis et al., 49% chose A, 32% B, and 19% C. The considerable national differences may be explained by differences between the two countries with respect to driving regulations and cultural aspects.

Risk factors for early disability pension in patients with epilepsy and vocational difficulties — Data from a specialized rehabilitation unit

PURPOSE The purpose of this study was to assess the risk factors for early disability pension (EDP) in adult patients with epilepsy in a specialized epilepsy rehabilitation setting. METHODS In a retrospective study, 246 patients with epilepsy and employment difficulties leading to referral to an inpatient rehabilitation unit were evaluated with a questionnaire on admission and after a mean of 2.5years after discharge. Patients already receiving EDP at baseline were excluded. Epilepsy-related, demographic, and employment-related data as well as cognitive functioning and psychiatric comorbidity were assessed as risk factors for EDP at follow-up and analyzed using logistic regression models. RESULTS Seventy-six percent of the patients had uncontrolled epilepsy, and 66.7% had psychiatric comorbidity. At follow-up, 33.7% received an EDP. According to multivariate logistic regression analysis, age>50years (odds ratio (OR) 5.44, compared to age<30years), application for an EDP prior to admission (OR 3.7), sickness absence>3months in the previous year (OR 3.30, compared to sickness absence<3months), and psychiatric comorbidity (OR 2.79) were significant risk factors for an EDP at follow-up, while epilepsy-related factors and cognitive impairment showed an effect only in the univariate analyses. CONCLUSIONS Potential risk factors for EDP in patients with epilepsy were evaluated using multivariate analysis. Knowledge of such factors may help to develop appropriate criteria for rehabilitation candidacy and interventions to reduce the risk for EDP. This might lead to an amelioration of both psychosocial burden of patients and economic burden on society.

Fahreignung bei psychogenen nicht-epileptischen Anfällen

Due to their semiologcal similarities, psychogenic nonepileptic seizures (PNES) represent an important and frequent differential diagnosis for epileptic seizures. According to the German driving regulations, patients with PNES are, like patients with epilepsy, considered unable to drive as long as a “substantial” recurrence risk exists. There are few data about driving accidents in patients with PNES; however existing evidence does not show an increased accident risk. PNES vary considerably concerning type and semiology, frequency, etiology, risks of injuries and prognosis, suggesting an individual assessment of driving ability. In an expert panel this was the opinion of more than two-thirds of the experts surveyed. A defined seizure-free period (e.g. one year) is the core of driving regulations in epilepsy; however such fixed seizure-free intervals are not suitable for patients with PNES, since they do not allow sufficient conclusions on the recurrence risk in this population. A psychiatric/psychotherapeutic assessment of prognosis, usually in the context of a psychotherapeutic process, is essential. Within such a process, comparably short seizure-free periods (e.g. 3–6 months) may be sufficient to consider a patient with PNES able to drive. Moreover, selected patients, in whom seizures occur exclusively provoked by identifiable mechanisms or situations, or who have long warnings preceding their seizures enabling the patient to stop or avoid driving, may even be allowed to drive with persisting seizures.ZusammenfassungPsychogene nicht-epileptische Anfälle (PNEA) sind wegen phänomenologischer Ähnlichkeiten eine häufige Differenzialdiagnose zu epileptischen Anfällen. Nach den deutschen Begutachtungsleitlinien zur Kraftfahrereignung von 2000 sind Patienten mit PNEA analog zu den Regelungen bei Epilepsie nicht fahrgeeignet, solange ein wesentliches Rezidivrisiko besteht. Die – insgesamt spärlichen – empirischen Daten sprechen allerdings nicht für ein erhöhtes Unfallrisiko bei Patienten mit PNEA. PNEA variieren in Bezug auf Art und Semiologie, Häufigkeit, Ätiologie, Verletzungsrisiko und Prognose erheblich und legen daher eine individuelle Beurteilung der Fahreignung nahe. Dies entspricht auch der Meinung von zwei Dritteln der dazu in Deutschland befragten Experten. Eine feste anfallsfreie Frist (z. B. ein Jahr), die bei Epilepsie den Kern der Fahreignungskriterien ausmacht, ist bei PNEA als alleiniger Beurteilungsmaßstab ungeeignet, weil sie keinen ausreichend verlässlichen Rückschluss auf das Rezidivrisiko erlaubt. Entscheidend ist eine psychiatrisch-psychotherapeutische Beurteilung der Prognose, in der Regel im Rahmen eines psychotherapeutischen Behandlungsverlaufes. In einem solchen Kontext können dann auch vergleichsweise kurze anfallsfreie Zeiten (z. B. 3–6 Monate) ausreichend sein, um eine Fahreignung zu bejahen. In Einzelfällen mit z.B. protektiv verwertbarer situativer Bindung der Anfälle oder ausreichend langen Prodromi ist ggf. auch Fahreignung bei Persistenz von PNEA denkbar.

Patients' perspectives on management and barriers of regular antiepileptic drug intake

PURPOSE The aim of our study was to assess the management of drug intake and potential barriers to adherence reported by two different patient groups. METHODS The study was performed in cooperation with the Regional Chamber of Pharmacists of Rhineland-Palatinate and three neurologists in private practice specialized in epileptology. In total, 108 patients surveyed in 43 pharmacies (Group P) and 118 patients treated by the specialized neurologists (Group N) completed anonymously a questionnaire on intake of antiepileptic drugs (AEDs). The statistical evaluation was performed using nonparametric tests and logistic regression analyses. RESULTS Group N more often used adherence aids, compared with Group P (68.6% vs. 46.3%, p<0.01), and the number of doses per day was significantly lower in Group N (Mann-Whitney test, p=0.046), but the percentage of patients who reported problems with the regular intake of their medication did not differ significantly between groups (Group N vs. P: 47.0% vs. 40.0%). If patients noticed that they missed a dose, 45.3% completely skipped the missed dose (Group N vs. P: 43.0% vs. 48.1%, n.s.). In a multivariate analysis, significant risk factors of problems with regular drug intake were age<25yrs. (p<0.01) and patient-reported adverse effect of AED (p<0.01), followed by the number of AED doses per day (p<0.05), while gender, intake habits, usage of adherence aids, and patient-rated efficacy of AEDs were not significant. CONCLUSION Patients treated by neurologists specialized in epileptology did not report less problems with adherence than patients surveyed in pharmacies. Since barriers for a regular intake are diverse, the use of a short questionnaire on management of drug intake may lead to an individually tailored counseling of patients to improve adherence.