Introduction: The Ketogenic Diet (KD) is a high fat – low carbohydrate diet used for the treatment of drug resistant epilepsy and as first line therapy in GLUT-1 deficiency and pyruvat-dehydrogenase deficiency. The aim of this study was to assess the efficacy and tolerability of the KD in different seizure types and epileptic syndromes, as well as the effect on seizure frequency, and interictal EEG.

STUDY OBJECTIVE:To assess the effect of topiramate (TPM) on body mass index (BMI) in paediatric epilepsy patients and to examine predictors of weight loss.DESIGN:Retrospective, observational study.SETTING:University clinic epilepsy outpatient department.SUBJECTS:Patients below age 18 years who received TPM for at least 12 months.MEASUREMENTS AND MAIN RESULTS:Changes in BMI (kg/m2) standard deviation scores (S.D.S.) from baseline to the follow-up periods of 12, 24 and 36 months were evaluated. The repeated measures t-test for paired samples, revealed significant decreases for BMI S.D.S. at 12 months (P = 0.004; n = 53) and 24 months (P = 0.044; n = 35), but no significant decrease at 36 months (n = 21). Analysis of variance revealed a predictor value of sex for BMI S.D.S. at 12 months (females more likely to lose weight; P = 0.037) and a predictor value of baseline BMI for BMI S.D.S. at 24 months (patients with a higher baseline BMI were more likely to lose weight; P = 0.047).CONCLUSION:Weight loss is common in paediatric epilepsy patients who receive TPM and is sustained for at least one year. The pattern of weight loss differs according to sex and baseline BMI.

In comparison to most other groups with intellectual disability individuals with Down syndrome are at lower risk for significant psychopathology, although relative to their typically developing peers they have higher rates of behavioural and emotional problems. A total of 43 Down syndrome patients (21 females and 22 males), who ranged in age from 5.33 to 30.58 years, were examined for the presence of age-related changes in the spectrum of externalizing and internalizing problems. Intelligence tests included Hamburg-Wechsler-Intelligenz Test für Kinder III (HAWIK-III), Hamburg-Wechsler-Intelligenz Test für Erwachsene (HAWIE-R) and Kaufman-Assessment-Battery for Children, German Version (K-ABC). Behavioural and emotional problems were assessed by the the Strengths and Difficulties Questionnaire for Parents, German Version (SDQ) and the Clinical Assessment Scale for Child and Adolescent Psychopathology (CASCAP). IQ was significantly inversly related to the age of patients. Externalizing behaviours (dominant, opposing/refusing, impulsiveness, inattention and increased motor activity) were significantly higher in the 5-10 years old group, whereas internalizing behaviours (shy/insecure, low self confidence, decreased motor activity) where more prevalent in adolescents and adults (10-30 years). Possible relationships between this age-related changes and increased risks of later-onset psychopathology (depression and dementia) are discussed.

Two families, each with occurrence of West syndrome in two siblings, are presented. Monozygotic twins in family 1 developed infantile spasms at the age of 4 months. Two female siblings in family 2 started to have seizures at the age of 6 months, but 2 years apart. The family history; development prior to West syndrome; clinical, electroencephalographic, and neuroradiologic findings; diagnostic work-up; and treatment are described. The outcome in family 1 (follow-up after 2 years) showed no conspicuous findings on physical and neurologic examination, and psychomotor development appropriate to cognitive, motor, and language developmental age in both twins. In family 2 (follow-up after 3 and 5 years), the older sister only was one standard deviation below mean in intellectual developmental age. Simultaneous occurrence of infantile spasms in both siblings from these two families but with variable clinical expression suggests there is a genetic susceptibility and variable phenotypic expression. Long-term follow-up will demonstrate whether these cases may be classified as "familial idiopathic West syndrome."

Caffeine- and taurine-containing drinks have been on the European market for about a decade, and research on the individual constituents of these drinks indicates an improvement in cognitive performance resulting from consumption of such drinks.

Down's syndrome involves age-dependent neuropathological and neurochemical changes similar to Alzheimer's disease, with cholinergic deficits being the most consistent. There is currently no proven treatment for Down's syndrome. We investigated the effect of nicotine-agonistic stimulation with 5 mg transdermal patches, compared with placebo, on cognitive performance in five adults with the disorder. Improvements possibly related to attention and information processing were seen for Down's syndrome patients compared with healthy controls. Our preliminary findings are encouraging, although not generalisable because of small numbers.

Human DNAse I (EC 3.1.21.1) is an enzyme most probably involved in apoptotic processes. Splicing of the DNAse I primary transcript in normal and apoptotic cells into up to 20 splicing forms and the recent description of a different family of caspase-activated DNAses, hampered studies on the role of DNAse I in apoptosis research.Performing gene hunting in fetal brain of patients with DS we found a sequence with 100% homology to DNAse I and this formed the Rationale for studies in adult DS brain. It was therefore the aim of the study to evaluate DNAse I - mRNA steady state levels in DS brain using adult brain without brain pathologies and Alzheimer's Disease (AD) brain as control, in order to rule out that DNAse I - overexpression may not be specific for DS but rather reflecting apoptosis per se, a hallmark of both disorders.Determination of DNAse I - mRNA steady state levels was carried out by a blotting method in frontal, parietal, temporal occipital lobe and cerebellum.We found significantly increased DNAse I transcripts in brain of DS and AD both, when normalized versus the house-keeping gene beta actin or total RNA.We demonstrate the significant increase of DNAse I - transcript in the pathogenesis of DS and AD suggesting a role for this enzyme in the apoptotic process known to occur in both disorders. We are now going to carry out protein and enzyme activity levels in our laboratory to confirm our findings at the transcriptional level.

Subjects with Down syndrome exhibit various types of cognitive impairment. Besides abnormalities in a number of neurotransmitter systems (e.g. cholinergic), histaminergic deficits have recently been identified. Brainstem auditory evoked potentials (BAEPs) and auditory event-related potentials (ERPs), were recorded from 10 children (aged 11-20 years) with Down syndrome and from 10 age- and sex-matched healthy control subjects. In Down subjects, BAEPs revealed shortened latencies for peaks III and V with shortened interpeak latencies I-III and I-V. ERPs showed a delay of components N1, P2, N2 and P3. In addition, subjects with Down syndrome failed to show P3 amplitude reduction during repeated stimulation. To evaluate the cognitive effects of histaminergic dysfunction, ERPs were recorded from 12 healthy adults (aged 20-28 years) before and after antihistaminergic intervention (pheniramine) compared to placebo. Whereas components N1, P2, N2 remained unchanged after H1-receptor antagonism, P3 latency increased and P3 amplitude showed no habituation in response to repeated stimulation. The results suggest that the characteristic neurofunctional abnormalities present in children with Down syndrome must be the consequence of a combination of structural and neurochemical aberrations. The second finding was that antihistaminergic treatment affects information processing tested by ERPs similar to that seen with anticholinergic treatment.

OBJECTIVE To investigate whether young IDDM patients develop central nervous dysfunction and to establish a possible relationship with various disease parameters. RESEARCH DESIGN AND METHODS Thirty-two patients, aged 13.5 ± 2 years, with disease duration of 6 ± 2.6 years and age of onset of 7.7 ± 3.2 years (group 1), and 21 patients with short-term disease, age 9.7 ± 3.5 years, duration of disease < 2 years and age of onset of 9.4 ± 3.3 years (group 2) were compared with age- and sex-matched control subjects. Exclusion criteria were clinical signs of neuropathy, retinopathy, nephropathy, or hearing impairment. Neurophysiological studies included auditory and visually evoked potentials (EPs). RESULTS Patients in group 1 revealed increased P100 latencies of visually EPs (103.4 ± 4.5 vs. 96.8 ± 3.7 ms) and interpeak latencies I-V of auditory EPs (4.16 ± 0.10 vs. 3.99 ± 0.09 ms) and had abnormal latencies (values outside 2.5 SD) in 37%. However, short-term patients (group 2) had results within normal limits compared with control subjects. In group 1, longer disease duration and younger age at onset correlated with an increase of P100 latency (P < 0.001) and IPL I-V (P < 0.001). Patients with a history of severe hypoglycemic episodes had increased latencies compared with patients without hypoglycemia (P < 0.05). Furthermore, metabolic control during the last 2 years was related to P100 latencies (P < 0.05). CONCLUSIONS EPs noninvasively detect subclinical central nervous system involvement in children and adolescents with IDDM. Most important risk factors are duration of disease and frequency of severe hypoglycemia.

The aim of this study was to investigate the prognosis of childhood epilepsy and to analyze prognostic factors in addition to remission rate in a follow-up of newly referred patients. Two hundred eighty-one patients were followed for a mean period of 5.3 years. Overall, 253 patients (90%) achieved 1-year remission. The beginning of a 1-year seizure-free period was achieved in 77.9% by 1 year, in 84% by 2 years and in 88.6% by 3 years after onset of treatment. Early onset of seizures, symptomatic etiology, and neurologic handicap predicted a worse prognosis. In 44 of 253 children with complete suppression of seizures for 1 year, relapses occurred within the follow-up period. In one child with a relapse, remission could not be achieved in the 2nd year thereafter. In conclusion, our study shows a good prognosis for most children with epilepsy, especially in patients with idiopathic epilepsy and late onset of seizures and without neurologic dysfunction. Moreover, our data strongly suggest that the long-term pattern of seizure control is largely established during the first 2 years of treatment.

In a prospective study 50 children with new onset epilepsy were investigated. Routine screening for complete blood count, serum protein, albumin, y-glutamyltransferase (γ-GT), aspartate aminotransferase (AST), alkaine aminotransferase (ALT), alkaline phosphatase, and coagulation studies before, 3, 6 and 9 weeks after commencement of antiepileptic therapy with valproate were carried out. Serum B12 and folate levels were also determined in 29 patients. The aim of the study was to evaluate the effect of VPA on these laboratory findings. We found a significant reduction of red blood count and platelet count, whereas MCV showed a significant upward trend. Vitamin B12 levels were elevated after starting VPA therapy. We found no elevations of liver enzymes, but a significant transient reduction of ALT after 3 and 6 weeks and significantly reduced serum protein and albumin after 3, 6 and 9 weeks. Coagulation studies revealed a significant downward trend in serum fibrinogen and upward trend in thrombin time. The other parameters showed no significant changes after onset of VPA treatment. We think that reduced red blood cell and platelet counts, and elevated MCV indicate a direct toxic effect on a hematopoietic precursor or stem cell in patients treated with VPA. Furthermore, reduced protein, albumin and fibrinogen indicate an impaired liver synthetic function in asymptomatic children treated with VPA monotherapy.

The aim of this study was to investigate the influence of metabolic control on quantitative electroencephalographic (EEG) abnormalities in young diabetic patients. We compared quantitative EEGs of 44 insulin-dependent diabetic patients with age-matched controls. Furthermore, differences in EEG variables of diabetic patients and controls were correlated with the age of onset and duration of diabetes, hemoglobin A1c concentrations, and episodes with severe hypoglycemia. We found a correlation between high values of hemoglobin A1c and decreased relative power of the alpha band. Patients with previous ketoacidotic episodes had increased relative power of the delta/theta band and decreased relative power of the alpha band. Patients with hemoglobin A1c values less than 8.5% exhibited slowing of background activity compared with normal controls. We conclude that metabolic control influences the EEG and that improvement of glucose metabolism is an important factor in avoiding EEG abnormalities in young diabetic patients. (J Child Neurol 1995; 10:330-334).

A number of studies have already been undertaken to investigate involvement of oxyradicals in muscle diseases by means of measurements of oxyradical protective enzymes. We investigated o-tyrosine, which is a biomarker for OH radical damage in vivo, in 10 mdx and 10 control mice. We also measured mitochondrial enzymes in muscle homogenates of 10 mdx and 10 control mice. Mdx mice had significantly elevated values for o-tyrosine, succinat-phenacinmetosulfat oxidoreductase. NADH O-2 oxido-reductase and cytochrome C oxidoreductase. Our findings confirm the suggestion that elevated oxyradical production occurs in muscular dystrophies with lack of dystrophin. Furthermore, our results demonstrate that OH radical damage does not impair mitochondrial enzyme activities in the mdx mouse.

Quantitative EEGs of 30 patients undergoing open heart surgery were investigated before, 6 days, 11 days and 44 days after operation. The study was conducted in order to investigate whether quantitative EEGs can show postoperative changes in children after open heart surgery. In 28 children, no new neurological signs of cerebral involvement were seen postoperatively. The most striking feature in these children was a significant decrease in the beta and the alpha 2 bands 6 and 11 days postoperatively. The pattern in the delta band was dominated by an increase 6 days postoperatively. Except for a slight decrease in alpha 2 waves, all variables were restored to preoperative values at 44 days after the operation. We found a significant decrease in plasma sodium and chloride after surgery but children with no or slight declines (1-3 mmol/l) also showed increased slow activity postoperatively. Therefore we conclude that an organic brain syndrome, although usually mild and transient, is a general phenomenon after open heart surgery.

The incidence of Duchenne muscular dystrophy (DMD) in Eastern Austria was investigated. From 1968-1983 302,643 boys were born, 68 of whom were subsequently identified as having Duchenne muscular dystrophy. The overall incidence with respect to live male births is 1:4451 (22.5 x 10(-5)). The mean age of the children at the occurrence of the first symptoms was 3.1 (SD 1.1), at first presentation to a physician 4.8 (SD 2.0), and at diagnosis 5.5 (SD 1.7) years. DMD occurred in 56 families. These families had 73 boys with DMD, 5 of whom were born before or after the observation period. Thirteen families had two affected boys and two families even had three. In 4 families a second boy suffering from DMD was born although the diagnosis of DMD had already been established in another close male relative. If a newborn male screening system had been in function, 13 cases could possibly have been avoided. However, since in 3 cases the affected siblings were not both born within the observation period, they were excluded, leaving 10 cases. Hence, a prevention rate of 14.7% might have been achieved through creatine kinase (CK) screening and genetic counselling.

We report on two siblings, a boy and a girl, with agenesis of corpus callosum and neuronopathy. The children show diffuse hypotonia, delayed motor and mental development. Neurophysiological examinations revealed reduction of the motor nerve conduction velocity, absence of sensory nerve action potentials, abnormal somatosensory and visual evoked potentials. Nerve biopsies showed reduced density of myelinated and unmyelinated fibres in both children. We also found signs of hypomyelination and suggest this is secondary to degeneration of peripheral sensory and motor neurons. Our findings are consistent with the diagnosis of Andermann syndrome. This is the first report of the occurrence of Andermann syndrome out of French Canada.