Tuberous Sclerosis Complex: Early Screening and Infant Outcome in NICU

Abstract

Objective We describe the clinical and genetic features, drug use and neuropsychiatric disorders of infants diagnosed with tuberous sclerosis complex (TSC) within 3 months of age at a neonatal intensive care unit (NICU) to better understand the different outcomes from early screening. Methods In this retrospective study, we consisted of 42 infants with a definitive TSC diagnosis by genetic criteria (TSC1 = 8, TSC2 = 34). The different phenotypes and outcomes between patients with TSC1 and TSC2 mutations were analyzed. Results The most common initial presenting features of TSC were cortical tubers on magnetic resonance imaging (50%), hypomelanotic macules on skin (47.61%) and spasm (42.85%), when they were diagnosed. Following disease progression to time of follow-up 1 year later, we found that the rate of epilepsy increased from 42.85% to 75.61% and that of cardiac rhabdomyoma increased from 28.57% to 43.9%. The median age at first presentation was 7.84 ± 1.88 months. We also found that 54.83% of patients on medication were seizure free for over 1 year, and that 43.9% of patients have intellectual disability. In total, 42 variants of TSC were detected, including 12 novel variants. We found no evidence of an association between different clinical features and their outcomes among patients with different gene mutations. Conclusion Early diagnosis of TSC in NICU opens a window of opportunity for early, more effective treatment of epilepsy as well as reduces the risk of neurological conditions.

Progress of clinical research studies on tuberous sclerosis complex‐related epilepsy in China

“…The main structural abnormalities in brain include subependymal nodules (181/214, 84.6%), cortical tubers (157/214, 73.4%) and subependymal giant cell astrocytoma (18/214, 8.4%) 4,5 . The common neurological presentations are epilepsy, intelligence disability (203/359, 56.5%) and TSC‐associated neuropsychiatric disorders (95/111, 83.2%) 4–7 . In a study including infants with TSC in neonatal intensive care units, seizure occurred in 75.6% patients with TSC, and the first seizure was observed at the median age 7.84 ± 1.88 months 6 .…”

“…The common neurological presentations are epilepsy, intelligence disability (203/359, 56.5%) and TSC‐associated neuropsychiatric disorders (95/111, 83.2%) 4–7 . In a study including infants with TSC in neonatal intensive care units, seizure occurred in 75.6% patients with TSC, and the first seizure was observed at the median age 7.84 ± 1.88 months 6 . In another population‐based study, epilepsy occurred in 83.5% (248/297) of the individuals, and 46.2% (188/407) and 52.7% (147/279) patients presented epileptic spasm and focal seizure, respectively 4,6,7 .…”

“…In a study including infants with TSC in neonatal intensive care units, seizure occurred in 75.6% patients with TSC, and the first seizure was observed at the median age 7.84 ± 1.88 months 6 . In another population‐based study, epilepsy occurred in 83.5% (248/297) of the individuals, and 46.2% (188/407) and 52.7% (147/279) patients presented epileptic spasm and focal seizure, respectively 4,6,7 . In addition, 54.1% (151/279) patients with TSC suffered drugs resistant epilepsy (DRE) 6,7 .…”

“…In another population‐based study, epilepsy occurred in 83.5% (248/297) of the individuals, and 46.2% (188/407) and 52.7% (147/279) patients presented epileptic spasm and focal seizure, respectively 4,6,7 . In addition, 54.1% (151/279) patients with TSC suffered drugs resistant epilepsy (DRE) 6,7 . Another study included 223 patients with tuberous sclerosis who underwent intelligence and epilepsy severity assessments.…”

“…However, sirolimus was first used for epilepsy in children with TSC by professor Liping Zou in October 2011 in China and is still the most common off‐label use of mTOR inhibitors in patients with TSC‐related epilepsy 13 . Treatment with mTOR inhibitors, everolimus or sirolimus, for over 1 year resulted in 54.83% of infants being seizure‐free 6 . A total of 91 children were treated with sirolimus (1 mg/m 2 ·d with a blood concentration of 5–10 ng/ml).…”