Since our last report on valproate (VPA)-related hepatotoxicity in 1988, 8 other children have died of VPA-associated liver failure in Germany and Switzerland. We compared the clinical course of these children with that of 6 children with a reversible outcome of severe hepatotoxicity related to VPA. Thirty-five percent of patients with fatal liver failure were normally developed, 23.5% were receiving VPA monotherapy, and 35.3% were aged < or = 2 years. The initial clinical symptoms of VPA-related hepatotoxicity were nausea, vomiting, apathy or coma, and increasing seizures in more than 50% of patients, in combination with febrile infections at onset of symptoms. As compared with the series of German patients reported in 1988, one third of the fatalities occurred after the first 6 months of therapy as compared with 6% in the 1988 series. Clinical symptoms and laboratory findings were the same in patients with reversible and with fatal outcome. Early or immediate withdrawal of VPA after the first signs of VPA-associated hepatotoxicity may be responsible for the increased number of children who recovered after VPA-related severe liver failure. The pathogenesis of liver failure during VPA treatment remains unknown; metabolic defects and cofactors such as polypharmacy or infections have become increasingly likely to contribute by depleting intracellular CoA. Worldwide, 132 patients have died of VPA-associated liver failure and/or pancreatitis. Because a group at risk for fatalities with VPA cannot be defined precisely, patients treated with VPA and their families must be made well aware of the clinical symptoms of hepatotoxicity such as apathy, vomiting, or increased seizure frequency, especially in the presence of febrile infections. Laboratory tests and clinical controls during the first 6 months of therapy should not be neglected.

Summary:Purpose: We present three children with severe therapy-refractory epilepsy who tolerated valproate (VPA) well in various combinations with other antiepileptic drugs (AEDs) but developed typical VPA side effects in combination with topiramate (TPM).Methods: The clinical symptoms began with apathy in all three children; two of them also had hypothermia. Furthermore all children had elevated blood ammonia levels, one child in combination with increased liver transaminases and one with thrombocytopenia.Results: All children recovered completely after discontinuation of VPA or TPM.Conclusions: TPM seems likely to enhance the risk of side effects usually attributed to VPA and not described in TPM monotherapy. Our case reports suggest that possible adverse effects of VPA should be given particular attention when VPA is combined with TPM.

SUMMARY Six children with neonatal cerebral infarction of the middle cerebral artery are reported. Seizures or respiratory distress were the initial symptoms. In some cases abnormal findings appeared earlier on EEG than on ultrasound. The EEG changes were concordant with the localization of the lesion. Ultrasound examinations revealed an echodense structure within the vascular territory, after a phase of appearing to be normal, highly suggestive of cerebral infarction. The diagnosis was confirmed by CT scan. Findings on EEG, cranial ultrasound and CT suggested that the stroke represented a late intra‐uterine event. At long‐term follow‐up, six children had failed to develop normally for age and had become obviously hemiplegic as gross motor development proceeded. Four of the patients had developed epilepsy. These data indicate that the outcome of neonatal stroke may not be as positive as previously reported. RÉSUMÉ Attaque sylvienne chez le nourrisson à terme: description clinique. EEG. imagerie et devenir L'article décrit six nourrissons après un infarctus sylvien à la naissance. Une crise comitiale ou une détresse respiratoire ont constitué le symptôme initial. Dans quelques cas, les données anormales sont apparues plus tôt à l'EEG qu'a l'échographie. Les modifications EEG étaient en accord avec la localisation de la lésion, l'échographie révélait un signal dense dans le territoire vasculaire, après une période de normalité, ce qui est hautement suggestif d'un infarctus cérébral. Le diagnostic fut confirmé par le scanner. Les données de l'EEG, de l'échographie transcranienne et du scanner suggéraient une attaque survenant à la période intra‐utérine tardive. Au suivi à long terme, les six enfants ne se développerent pas normalement pour l'âge, devinrent de plus en plus manifestemcnt hémiplégiques au cours de développement moteur global. Une épilepsie apparut chez quatre enfants au suivi. Ces données indiquent que le devenir d'une attaque sylvienne á la naissance peut ne pas être aussi favorable que cela avait été rapporte. ZUSAMMENFASSUNG Apoplex der A. cerebri media beim reifen Neugeborenen: klinisches Bild, EEC‐ und bildgebende Unsuchungsbefunde und Outcome Es werden sechs Kinder mit neonatalem Apoplex der A. cerebri media vorgestellt. Die lnitialsymptome waren Anfälle oder Atemnot. Bei einigen Fällen erschienen die Befunde im EEG früher als Ultraschall. Die EEG‐Veränderungen stimmten mit der Lokalisation der Läsion überein. Die Ultraschalluntersuchungen ergaben–nach anfänglich normal erscheinendem Befund–einen echodichten Bereich im Gefäßgebiet, was sehr für einen cerebralen Infarct sprach. Die Diagnose wurde durch CT‐Befunde bestätigt. EEG‐, Ultraschalund CT‐Befunde lassen vermuten, daß sich der Apoplex in der späten intra‐uterinen Phase ereignet hat. Im Verlauf der Langzeitbeobachtung entwickelten sich sechs Kinder nicht altersentsprechend und wurden mit fortschreitender grobmotorischer Entwicklung hemiplegisch. Vier der Patienten entwickelten im Beobachtungszeiiraum cine Epilepsie. Diese Daten zeigen, daß d...

Two children with GM-2 gangliosidosis type 0 (Sandhoff's disease) followed up by MRI at 1.5 Tesla for 1.8 years are reported. One was presymptomatic at the first MRI examination. As her neurological status deteriorated, MRI showed low signal in bilaterally, on T2-weighted images the white matter with involvement of the optic radiations. In the second, MRI correlated well with the clinical progression of the disease, showing in the different stages involvement of thalamus and basal ganglia. There was no contrast enhancement and the grey matter remained normal.

We describe the long-term follow up of infants after neonatal stroke of the middle cerebral artery (MCA). Stroke was diagnosed by CT scan in eight full-term neonates. Three dimensional (volume) magnetic resonance angiography (MRA) is a noninvasive technique that images the arterial vessels without contrast agents. All patients, aged from 1.5 to 8.4 years, were investigated by MRI and MRA and by neuropsychological tests. Cognitive development was investigated by intelligence tests, tests of visual perception, motor and language development. Out of the eight patients, seven had a retarded mental and motor development, and 50% of the children were treated for epilepsy. Seven patients had a spastic hemiparesis. Seven out of eight children showed major cognitive deficits. In all patients, MRI revealed clear parenchymal defects with variable distribution patterns. MRA studies showed abnormalities corresponding to the expected vascular distribution. Children with complications at delivery, with seizures, and an interruption of the main stem of MCA as demonstrated on MRA had the least favourable long-term follow up prognosis with severe cognitive delays.