Valproate-associated reversible encephalopathy in a 3-year-old girl with Pallister-Killian syndrome.

Valproic acid (VPA) is considered to be a drug of first choice for the therapy of generalized and focal epilepsies, including special epileptic syndromes. The drug is usually well tolerated, rare serious complications may occur in some patients, including hemorrhagic pancreatitis, coagulapathies, bone marrow suppression, VPA-induced hepatotoxicity and encephalopathy. We report a case of VPA-associated encephalopathy without hyperammonemia in a 3-year-old girl with Pallister-Killian-Syndrom, combined with a mild hepatopathy and thrombopathy. After withdrawal of VPA, the clinical symptoms and the electroencephalography-alterations vanished rapidly.

Vagus nerve stimulation improves severely impaired heart rate variability in a patient with Lennox-Gastaut-Syndrome.

Vagus nerve stimulation (VNS) is a new therapeutic option for refractory epilepsy. We report a patient with Lennox-Gastaut-Syndrome (LGS) and a severe impairment of heart rate variability (HRV), we could demonstrate in our patient that HRV was improved by VNS.

Internet-based knowledge management database for children and adults with epilepsy: a possible model project for evidence-based medicine in the future.

With an incidence of nearly 1%, epilepsy represents one of the most frequent diseases in the population. Nevertheless substantial information gaps exist as to the exact incidence, prevalence, therapy and particularly to associated therapeutic success. Adequate studies are not performed on many of these issues which are primarily beyond the current interests of the pharmaceutical industry. An Internet-based knowledge management database is presented to illustrate initial results of the online system with a focus on medication and side effects (http://www.ligaepilepsie.org/KnowledgeDB/index.htm). Further, it is worth noting that this database was designed as a potential model for similar projects in other medical fields.

Reversible hepatotoxicity, pancreatitis, coagulation disorder and simultaneous bone marrow suppression with valproate in a 2-year-old girl.

Valproic acid (VPA) is considered to be a drug of first choice for the therapy of generalized and focal epilepsies, including special epileptic syndromes like the WEST-syndrome. The drug is usually well tolerated; rare serious complications may occur in some patients, including haemorrhagic pancreatitis, coagulapathies, bone marrow suppression, VPA-induced hepatotoxicity and encephalopathy. We report a case of combined appearance of several severe VPA-associated side effects in a two- and a half-year-old girl with lissencephaly.

Effects of valproate on acylcarnitines in children with epilepsy using ESI-MS/MS.

PURPOSE: To determine the influence of valproate (VPA) treatment on acylcarnitines in children with epilepsy. METHODS: Determination of acylcarnitines (including free carnitine and acylcarnitines from C2 to C18) in dried blood spot specimens using tandem-mass spectrometry. Longitudinal study of changes in acylcarnitines in children under VPA treatment without pretreatment (group 1) or with pretreatment with other antiepileptic drugs (group 2) before the start of VPA treatment at an early and a late treatment interval (12-66, 90-260 days after the beginning of treatment, respectively). Cross-sectional comparison of these two VPA groups and of a group receiving carbamazepine monotherapy (group 3) with controls. RESULTS: Acylcarnitines in epileptic patients before VPA therapy did not differ from control values. In group 1, decreases of C0 (-26%), C2 (-12%), C16 (-31%), C18 (-41%), C(total) (-10%), increases of C5OH (+31%), C8 (+33%) in the early treatment interval, and decreases of C16 (-21%), C18 (-42%), and increases of C2 (+26%), C5OH (+44%) in the late treatment interval were significant. In group 2, both in the longitudinal and the cross-sectional study, only a decrease of C18 (-41%, -43%, respectively) in the late treatment interval was found. In group 3, no significant changes have been observed. CONCLUSIONS: We could prove changes in acylcarnitine subspecies, which were associated with VPA treatment in children with epilepsy. The treatment interval with the most marked changes coincides with the interval of highest risk for VPA-induced hepatotoxicity. The observed specific acylcarnitine pattern might point to the impaired intermediary metabolism that is responsible for VPA-induced hepatotoxicity.

Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.

Valproic acid-induced hepatopathy: nine new fatalities in Germany from 1994 to 2003.

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. METHODS: We mailed a questionnaire to all members of the German Section of the International League Against Epilepsy, asking for VPA-induced side effects, especially severe side effects such as hepatopathy. RESULTS: As a result of our questionnaire, we found 31 cases of reversible hepatotoxicity and nine cases of lethal hepatopathies in Germany from 1994 to 2003. CONCLUSIONS: The outcome of patients with severe hepatotoxicity is better than that in the past. The risk of a VPA-induced hepatopathy is not limited to patients younger than 2 years, receiving polytherapy, or patients with congenital or acquired metabolic diseases.