Preventive Antiepileptic Treatment in Tuberous Sclerosis Complex: A Long-Term, Prospective Trial.

BACKGROUD: Drug-resistant epilepsy is the main risk factor for future intellectual disability in patients with tuberous sclerosis complex. Clinical epileptic seizures are often preceded by electroencephalographic changes, which provide an opportunity for preventive treatment. We evaluated the neuropsychologic and epilepsy outcomes at school age in children with tuberous sclerosis complex who received preventive antiepileptic treatment in infancy. METHODS: We performed a prospective, nonrandomized clinical trial with 14 infants diagnosed with tuberous sclerosis complex in whom serial electroencephalographic recordings were performed and preventive treatment with vigabatrin initiated when active epileptic discharges were detected. An age-matched control group consisted of 31 infants with tuberous sclerosis complex in whom treatment with vigabatrin was given only after onset of clinical seizures. Results of clinical assessment of epilepsy and cognitive outcomes were analyzed. RESULTS: All patients in the preventive group (n = 14) and 25 of 31 patients in the standard treatment group were followed through minimum age five years, median 8.8 and 8.0 years in the preventive and standard groups, respectively. The median intelligence quotient was 94 for the preventive group when compared with 46 for the standard group (P < 0.03). Seven of 14 patients (50%) in the preventive group never had a clinical seizure when compared with one of 25 patients (5%) in the standard treatment group (P = 0.001). CONCLUSIONS: This study provides evidence that preventive antiepileptic treatment in infants with tuberous sclerosis complex improves long-term epilepsy control and cognitive outcome at school age.

Long-term effect of everolimus on epilepsy and growth in children under 3 years of age treated for subependymal giant cell astrocytoma associated with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by increased mammalian target of rapamycin (mTOR) activation and growth of benign tumors in several organs throughout the body. In young children with TSC, drug-resistant epilepsy and subependymal giant cell astrocytomas (SEGAs) present the most common causes of mortality and morbidity. There are also some reports on the antiepileptic and antiepileptogenic potential of mTOR inhibitors in TSC. However, the data on everolimus efficacy and safety in young children are very limited. AIMS: To show the long-term safety data and the effect of everolimus treatment on epilepsy in children under the age of 3 who received everolimus for SEGAs associated with TSC. METHODS: We present the results of everolimus treatment in 8 children under the age of 3 who participated in EXIST-1 study. Five patients presented with active, drug-resistant epilepsy at baseline. The mean follow-up is 35 months (33-38 months) and all children are still on treatment. RESULTS: In 6 out of 8 children, at least a 50% reduction in SEGA volume was observed. In 1 child with drug-resistant epilepsy, everolimus treatment resulted in cessation of seizures and in 2 other children, at least a 50% reduction in the number of seizures was noted. The incidence of adverse events (AE) was similar to that observed in older children and adults. CONCLUSIONS: This study suggests that everolimus is effective and safe in infants and young children with epilepsy and SEGA associated with TSC and offers a valuable treatment option.

Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex.

BACKGROUND: Epilepsy appears in 70-80% of patients with tuberous sclerosis complex, most commonly in the first year of age. Early manifestation of epilepsy is associated with drug-resistant epilepsy and mental retardation in more than 80% of patients. Clinical epileptic seizures are preceded by deterioration of EEG recording thus infants with high risk of epilepsy can be identified. AIMS: We hypothesized that preventative antiepileptic treatment of infants with multifocal activity on EEG might lower the incidence of drug-resistant epilepsy and mental retardation. METHODS: Forty-five infants with early diagnosis of tuberous sclerosis complex were included in the open-label study. They were divided in two groups: standard (n=31) and preventative one (n=14). In standard group the antiepileptic treatment was launched early, but after the onset of seizures. In preventative group medication was commenced when active epileptic discharges were seen on EEG, but before the onset of clinical seizures. Children were followed till the end of 2 years of age. RESULTS: At 24 months of age mental retardation was significantly more frequent and severe in "standard" vs "preventative" group (48% vs 14%; p=0.031; mean IQ score 68.7 vs 92.3; p<0.05). The "preventative" group was characterized by higher ratio of seizure-free patients (93% vs 35%; p=0.004), lower incidence of drug-resistant epilepsy (7% vs 42%; p=0.021) and lower number of patients requiring polytherapy (21% vs 55%; 0.039) than the "standard group. CONCLUSIONS: Preventative antiepileptic treatment of infants with tuberous sclerosis complex and high risk of epilepsy markedly improves their neurodevelopmental outcome and reduces the incidence of drug-resistant seizures.

Cerebral tuber count and its impact on mental outcome of patients with tuberous sclerosis complex.

PURPOSE: The aim of the study was to reveal the relationships between the tuber count of the brain found in patients with tuberous sclerosis complex (TSC) and their cognitive outcome. METHODS: A single-center, retrospective analysis was performed of patients with documented TSC seen from 1988 to 2010 at the Children's Memorial Health Institute, Warsaw, Poland. KEY FINDINGS: Sixty-two patients were analyzed, and there was a significant correlation between younger age at the first seizure and developmental delay. The patients who did not develop seizures had normal development, despite some presenting with higher tuber load than those with seizures. There was a statistically significant negative correlation between the number of tubers within the right temporal lobe and cognition. SIGNIFICANCE: Our findings confirm our hypothesis that the cognitive outcome in TSC is more dependent on the age of the seizure onset rather than on the tuber count.

[Psychomotor development rate of children with infantile neuronal ceroid lipofuscinosis]. / Ocena dynamiki rozwoju psychoruchowego dzieci z wczesnodziecieca neuronalna ceroidolipofuscynoza.

BACKGROUND: Late infantile neuronal ceroid lipofuscinosis (LINCL) is the most common childhood progressive encephalopathy. Severe psychodegradation with diminish of cognitive functions together with ataxia, myoclonus, resistant epilepsy, paresis and blindness in aged 3-6 yrs are observed. THE AIM OF STUDY: Cognition of psychomotor development in children with LINCL. MATERIAL AND METHODS: In group of 65 children with LINCL diagnosed by ultrastructural conjunctive examinations and/or low activity of TPP1 enzyme in leukocytes, the psychological assessment during 3 years of disease was performed. 25 children had done psychological test with use Psyche Cattell Scale for Small Children twice in 1-3 years intervals. In next 40 children clinical, neurological observations during some years was made. RESULTS: In 25 children Psyche Cattell tests revealed severe mental retardation (IQ 20-35) in 16% and profound mental retardation in 84%. In the first year of disease 56% of children was degraded to the profound mental retardation (44% in moderate and 12% in severe mental retardation). In all 65 affected children already in the first neurological visit the delay and regress in global of mental development was observed (any of children hadn't have IQ rates on average level). Analysis of psychodegradation rate revealed in 60% of children after 1-3 years from onset of disease very rapid mental retardation and decreased IQ above 2 SD and in 24% above 3SD. CONCLUSIONS: Common progressive encephalopathy LINCL caused very rapid severe mental degradation, already at the first stage of the development of disease and that is very important diagnostic sign.