15th May 2008 (Thursday), Oral presentations 14.45−16.15 S9

2 males and 7 females). We identified 46 late-onset cases. 24of them have A208T mutation (in 3 separate families). Despitebenign character of this mutation there was 10 males deadin five generations of 2 families. For all of them the firsthyperammonemic crisis developed after adolescence and hadfatal course.Conclusions: 1) Majority of the Polish patients with OTCD aredetected beyond neonatal period. 2) Simply diagnostic tests(ammonia, orotic acid) should be more widely available.

14.45−16.15Epilepsy of early childhood

INV21 Synaptogenesis in the fetal and neonatal brain

H.B. Sarnat1,2, L. Flores-Sarnat2. 1University of Calgary Facultyof Medicine, Calgary, Canada, 2Alberta Children’s Hospital,Calgary, Alberta, Canada

Introduction: Synapse formation is a fundamental processin brain development. No presently available clinical orneuroimaging methods can determine synaptogenesis in thehuman brain of fetuses, premature infants, neonates or inpostnatal life. EEG patterns reflect large fields of thousandsof cortical synapses, but do not identify individual synapses.Magnetoencephalography is unable to demonstrate synapseformation. Synaptophysin, an immunoreactive structuralprotein of the synaptic vesicle wall, is capable of demon-strating synapses in surgical or postmortem sections of braintissue, hence the temporal and spatial pattern of synaptogen-esis in the fetal brain was studied by this method as a markerof synaptic maturation in relation to gestational age.Materials and Methods: Synaptophysin was prospectivelystudied postmortem in sections of brain of 162 normalhuman fetal and neonatal brains of both genders, rangingin age from 6−41 weeks gestation. Anti-synaptophysinantibodies (Novacastra Laboratories, U.K.) were used at adilution of 1:25 with thermal intensification and avidin-biotindemonstration of reactivity by light microscopy. Appropriatecontrols and an array of other immunoreactive neuronaland glial markers of cellular maturation were also applied.The hippocampus, cerebral neocortex and basal gangliawere studied and here reported. The brainstem, cerebellumand spinal cord also were examined at various gestationalages, but are not described in this report. Twelve additionalbrains of various fetal ages, with postmortem autolysis,were examined to determine the reliability of synaptophysinreactivity after death.Results: A consistent temporal and spatial pattern ofnormal synaptophysin reactivity was demonstrated in thehippocampus and cerebral neocortex of infants at similargestational ages, the initial appearance and increasingintensity of reactivity reflecting synaptogenesis. In thehippocampus, the first region to become reactive was themolecular zone of the dentate gyrus at 12 weeks, followedby the CA2 sector of Ammon’s horn at 14 weeks and thenCA3, CA4 at 15−16 weeks and finally CA1 at 28 weeks. Inneocortex, reactivity is seen just above and below the corticalplate, but not within it, as early as 12 weeks, and then aroundCajal-Retzius neurons of the molecular zone and pyramidalneurons of layers 5 and 6, and finally neurons of layers 2 and4. At 33 weeks, layers 2 and 4 were still less reactive thanother layers, and uniformity between all cortical layers wasachieved at 36 weeks. Ascending thalamocortical axons werereactive as early as 12 weeks gestation and well demonstratedby 26 weeks. In the corpus striatum, both the caudatenucleus and putamen exhibit a patchy, striated pattern ofreactivity from 15 to 34 weeks gestation that correspondsto the “striosomes of Graybiel” and may explain the normalathetoid movments seen in preterm infants of 26−32 weeks

gestation, as described by A. Peiper in 1961. The globuspallidus and substantia nigra, by contrast, show uniformreactivities throughout development. Immunoreactivity ofsynaptophysin was well preserved for 96+ hours postmortem,hence findings are not artifactual.Conclusions: Synaptophysin is a reliable marker of synapto-genesis in normal human fetal brain and provides an objec-tive assessment of this aspect of brain maturation. Normaldata are primordial for understanding abnormal synapticpatterns in many pathological conditions, such as cerebralmalformations, genetic and chromosomal diseases, fetalmetabolic and toxic encephalopathies including maternalabuse of alcohol and other drugs during pregnancy, epilepsiesand to demonstrate maturational delay. Correlations can beextrapolated to clinical neurological and EEG findings in livingpreterm neonates.

INV22 Infantile spasms can we manage better?

S. Jozwiak. Department of Child Neurology and Epileptology, TheChildren’s Memorial Health Institute, Warsaw, Poland

Infantile spasms are one of the most frequent typeof childhood epilepsy and one of the most frequenttype of epileptogenic encephalopathy. The incidence ofinfantile spasms ranges from 2.9 to 4.5/100,000 live births.Neurological abnormalities affect 33−89 percent of cases.Motor impairment, including diplegia, tetraplegia, ataxiaor athetosis result from the brain lesions that cause theepilepsy.The onset of infantile spasms is relatively insidious, and fol-lowed either by recovery or by the development of a chronicdisorder with cognitive, motor, and epileptic sequelae. Theheterogeneity of the condition in term of etiology and ofneuropathological background determines variable responsesto treatment schedules. Another important predictor oftreatment efficacy is the duration of treatment lag.There are only few large surveys to determine the drugof choice for the treatment of infantile spasms. The majordrugs that have been shown to be effective in infantilespasms are steroids and vigabatrin. Ketogenic diet could bealso effective in some patients with drug resistant infantilespasms. Effectiveness and possible side effects of suchtreatment will be discussed.

INV23 Favourable prognostic factors in infantile spasms

R. Riikonen. University of Kuopio, Kuopio, Finland

Outcome measures include complete cessation of spasms,resolution of hypsarrhythmia, relapse rate, developmentaloutcome, and presence or absence of epilepsy or anepileptiform EEG.Does the etiology influence the outcome of infantile spasms? Notonly patients with a cryptogenic etiology have a favourableoutcome.Does the treatment influence the outcome? Steroids andvigabatrin (VGB) are the first-line drugs for infantile spasms inEurope. In a new prospective study from the UK (107 patients),response rate for synthetic ACTH was 76%, for prednisolone70%, and for VGB 54% at day 14. Tuberous sclerosis wasexcluded from that study. However, the numbers of patientswho are seizure-free at 3−4 months in different studiesare very similar 42−44%, even at 14 months (UK study).Therapeutic risks should be avoided. The side effects ofsteroids are all treatable and reversible. In Finland ACTHtherapy is given at the minimum effective dose and for theminimum effective time (with minimal side effects). The risksof VGB include visual field defects, which are irreversible. Asof yet there is no method to examine the visual fields becauseof the young age of the patients. Recent studies in animalshave shown that drugs which increase brain GABA (VGB) cancause apoptotic degeneration of the brain.