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.

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Summary 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.

BackgroundTuberous sclerosis complex (TSC) is a genetic disorder with an incidence of 1:6000 live births and associated with the development of benign tumors in several organs. It is also characterized by high rates of neurological and neuropsychiatric abnormalities, including epilepsy affecting 70–90% of patients and being one of the major risk factors of intellectual disability. The first seizures in TSC patients appear usually between the 4th and the 6th months of life. Recent studies have shown the beneficial role of preventative antiepileptic treatment in TSC patients, with the possibility for improvement of cognitive outcome. Moreover, European recommendations suggest early introduction of Vigabatrin if ictal discharges occur on EEG recordings, with or without clinical manifestation.The aim of this study was to define the most useful approach to make the diagnosis of TSC before seizure onset (before age 4th months), in order to start early EEG monitoring with possible preventative treatment intervention.MethodsWe performed a retrospective review of children who were suspected of having TSC due to single or multiple cardiac tumors as the first sign of the disease. We analyzed the medical records in terms of conducted clinical tests and TSC signs, which were observed until the end of the 4th month of age. Subsequently, we described the different clinical scenarios and recommendations for early diagnosis.Results82/100 children were diagnosed with TSC within the first 4 months of life. Apart from cardiac tumors, the most frequently observed early TSC signs were subependymal nodules (71/100, 71%), cortical dysplasia (66/100, 66%), and hypomelanotic macules (35/100, 35%). The most useful clinical studies for early TSC diagnosis were brain magnetic resonance imaging (MRI), skin examination and echocardiography. Genetic testing was performed in 49/100 of the patients, but the results were obtained within the first 4 months of life in only 3 children.ConclusionsEarly diagnosis of TSC, before seizure onset, is feasible and it is becoming pivotal for epilepsy management and improvement of cognitive outcome. Early TSC diagnosis is mostly based on clinical signs. Brain MRI, echocardiography, skin examination and genetic testing should be performed early in every patient suspected of having TSC.

a b s t r a c tBackgroud: 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 agematched 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 ¼ 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 ¼ 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.

The 2017 Polish Consensus Statement (PCS 2017)

Aim of the study. This study aimed to evaluate the effects of nusinersen therapy in Polish children with SMA type 1.Clinical rationale of study. Spinal muscular atrophy (SMA) is a neuromuscular disorder that is characterised by the loss of motor neurons, progressive muscle weakness and atrophy, leading to increased disability and mortality. Nusinersen, an antisense oligonucleotide that promotes production of the functional survival motor neuron protein is approved for the treatment of SMA 5q in the European Union. In 2017, an early access programme (EAP) for nusinersen was launched in Poland. In this study, we present the results of nusinersen treatment in Polish patients participating in the EAP. Materials and methods.We collected prospectively clinical data including mutational analysis of SMN1 and SMN2 genes, motor function outcomes as measured on a standardized scales, ventilatory and nutritional status, on SMA type 1 patients receiving nusinersen in three EAP centres in Poland. Scores on the CHOP-INTEND scale after 18-26 months of treatment were compared to baseline. Results. We analysed data from 26 patients with SMA type 1, mean age 4.79 (2-15) years. The mutational analysis revealed two SMN2 gene copies in the majority of patients (61.54%). Three and four copies were found in 34.62% and 3.84%, respectively. Median disease duration was 21 months. Half (n = 13) of the patients required mechanical ventilation at baseline and 57.69% (n = 15) were fed by nasogastric tube or percutaneous endoscopic gastrostomy. No patient worsened during the follow-up. Mean improvement in CHOP-INTEND from baseline to the last follow-up was 7.38 points (p < 0.001). CHOP-INTEND scores did not decline for any patient. Patients with three or more SMN2 gene copies had higher scores than did the patients with two copies (p = 0.013), and they tended to show greater improvement over time, but the difference was not significant (p = 0.324). Shorter disease duration and higher CHOP-INTEND baseline score were associated with a better response (p = 0.015). Patients with a CHOP-INTEND score above the median had higher scores overall than the rest (p < 0.0013), and they improved significantly more than the rest (p = 0.037). Nusinersen was well tolerated, no new safety findings were identified.Conclusions and clinical implications. Our data indicates that nusinersen treatment might be effective in SMA type 1 patients, regardless of their age and functional status.