Neuropsychiatric profile in tuberous sclerosis complex patients with epilepsy
Authors: Osman Mahmoud Fawzi , Hadid Faisal , ben Omran Tawfeg , Aden Munira , Al-Maadid Fatima , Altaraqji Sondos , Mohamed Khalid , Benini Ruba 
Published: January 2025

Background

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by mutations in the TSC1 or TSC2 genes, leading to dysregulation of the mTOR pathway and multisystemic manifestations. Epilepsy is a common neurologic feature of TSC, frequently accompanied by neuropsychiatric comorbidities. Understanding the relationship between epilepsy severity, TSC-associated neuropsychiatric disorders (TAND), and cognitive outcomes is crucial for optimizing patient care.

Methods

A retrospective study was conducted at a pediatric tertiary care hospital in Qatar, involving 38 TSC patients (20 female, 18 male) aged 1–18 years, diagnosed between October 2018 and March 2020. Epilepsy severity was assessed using the Early Childhood Epilepsy Severity Scale (E-Chess), and TAND was evaluated using the TAND checklist. Genetic analysis was performed for all patients, and statistical analyses were used to explore correlations between epilepsy severity, TAND, and cognitive outcomes.

Results

The majority (82%) of TSC patients had epilepsy, with a mean onset age of 9.2 months. Uncontrolled seizures were associated with higher rates of intellectual disability and more pronounced TAND manifestations compared to controlled seizures. Autism spectrum disorder (ASD) was reported in 42% of the cohort, with significant correlations found between epilepsy severity and ASD-related domains on the TAND checklist. Intellectual disability was prevalent (67.6%), with variability attributed to genetic background and early severe neurological presentations.

Discussion

This study reinforces the link between epilepsy severity and neuropsychiatric comorbidities in TSC, confirming earlier findings. Significant correlations were observed between epilepsy severity and ASD-related domains, and the high prevalence of intellectual disability in TSC patients was highlighted. However, the relationship between ASD, TSC, and epilepsy remains complex and requires further investigation. Despite advances in treatment options, including mTOR inhibitors and newer antiepileptic drugs, unmet needs remain in the comprehensive care of TSC patients. Optimizing seizure control is a clear priority, but equally important is the need for addressing the cognitive and behavioral components of TAND. Early intervention with tailored, multidisciplinary approaches including neurology, psychiatry, psychology, and educational specialists could mitigate the long-term impact of these comorbidities, particularly in children. These approaches must be individualized to each patient's unique set of challenges, emphasizing not only seizure control but also psychosocial support and educational adaptation to improve their overall quality of life.

Conclusion

This study sheds light on the intricate interactions between epilepsy severity, neuropsychiatric manifestations, and cognitive outcomes in TSC patients. The findings emphasize the need for tailored management approaches, focusing on early seizure control and comprehensive multidisciplinary care. Further research is required to clarify the mechanisms underlying these associations and to develop targeted interventions for improving the quality of life for individuals with TSC and epilepsy.