A single-center observational study on long-term neurodevelopmental outcomes in children with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare multisystem disorder caused by mutations in the TSC1 or TSC2 gene. More than 90% of patients with TSC develop neurological and/or neuropsychiatric manifestations. The aim of the present study was to determine the developmental and cognitive long-term outcomes of pediatric TSC patients. METHODS: This cross-sectional, monocenter study included pediatric TSC patients who received multidisciplinary long-term care with a last visit between 2005 and 2019. Neurological manifestations and cognitive development (BSID, K-ABC) were analyzed in relation to age and type of mutation. RESULTS: Thirty-five patients aged 13.5 ± 7.8 years were included in the study. Diagnosis was confirmed genetically in 65.7% of patients (TSC1, 26.1%; TSC2, 65.2%; NMI, 8.7%). Mean age at diagnosis was 1.3 ± 3.5 years; 74.3% of the patients had been diagnosed within the first year of life due to seizures (62.9%) or/and cardiac rhabdomyomas (28.6%). The most common TSC manifestations included structural brain lesions (cortical tubers, 91.4%; subependymal nodules, 82.9%), epilepsy (85.7%), and cardiac rhabdomyomas (62.9%). Mean age at seizure onset was 1.5 ± 2.3 years, with onset in 80.0% of patients within the first two years of life. Infantile spasms, which were the first seizure type in 23.3% of the patients, developed earlier (0.6 ± 0.4 years) than focal seizures (1.8 ± 2.5 years). Refractory epilepsy was present in 21 (70.0%) patients, mild or severe intellectual impairment in 66.6%, and autism spectrum disorders in 11.4%. Severe cognitive impairment (33.3%) was significantly associated with epilepsy type and age at seizure onset (p < 0.05). CONCLUSIONS: The results emphasized the phenotypic variability of pediatric-onset TSC and the high rate of neurological and neuropsychiatric morbidity. Early-onset refractory epilepsy was associated with impaired cognitive development. Children of all ages with TSC require multidisciplinary long-term care and individual early-intervention programs.

Long-term outcomes of very-low-birth-weight and low-birth-weight preterm newborns with neonatal seizures: A single-center perspective.

OBJECTIVE: Newborn seizures are frequent in preterm newborns and indicate brain lesions in many cases. The objective of this observational study was to investigate the long-term outcome of very-low-birth-weight (VLBW) and low-birth-weight (LBW) preterm infants with neonatal seizures. METHODS: We examined 54 preterm infants (40 VLBW and 14 LBW cases) born between 2008 and 2011 with clinical seizures during the neonatal period confirmed by interictal or ictal electroencephalography recordings in a retrospective single-center study. Neurodevelopmental follow-up included an expert neurological examination and cognitive testing (Kaufman Assessment Battery for Children) at a mean age of six years. RESULTS: The (mean ± standard deviation) gestational ages of the VLBW and LBW infants were 27.2 ± 1.9 weeks and 33.4 ± 1.7 weeks, respectively, and the postnatal age at seizure onset was 13 ± 11 days in VLBW infants and 9 ± 8 days in LBW infants, with a wide range of one to 62 days. LBW infants more frequently developed non-motor seizures (50.0%) than VLBW infants did (25.0%), and higher-grade intracranial hemorrhage was the predominant etiology in the VLBW group (18.0%), while the etiology in the LBW group was more heterogeneous and included central nervous system malformations and genetic syndromes. At the mean age of 6.2 ± 2.0, years, 25/54 patients were assessed and 44.4% of the VLBW group and 71.4% of the LBW group showed intellectual impairment. Infantile cerebral palsy was present in 22% of VLBW and 42.9% of LBW infants, respectively. SIGNIFICANCE: The present analysis of long-term neurodevelopmental outcomes of preterm neonates who experienced seizures shows that the risk for intellectual impairment is not limited only to VLBW infants but may significantly affect LBW infants as well. The etiological spectrum differs in relation to gestational age.