Behavioral Symptoms May Correlate With the Load and Spatial Location of Tubers and With Radial Migration Lines in Tuberous Sclerosis Complex

Abstract

Objective: Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous genetic disorder. The clinical manifestations are extensive and include neurological, dermatological, cardiac, ophthalmic, nephrological, and neuropsychiatric manifestations. The prediction and pathophysiology of neuropsychiatric disorders such as emotional symptoms, conduct problems, hyperactivity, and poor social behavior are poorly understood. The aim of the study was to diagnose neuropsychiatric symptoms in individuals with TSC, and to examine their possible correlations with quantity, magnitude, and spatial location of tubers and radial migration (RM) lines.Methods: The cohort comprised 16 individuals with TSC, aged 5–29 years, with normal or low normal intelligence. The participants or their parents were requested to fill Strengths and Difficulties Questionnaire (SDQ) and the TAND (TSC-associated neuropsychiatric disorders) Checklist for assessment of their neuropsychiatric symptoms. Correlations were examined between these symptoms and the magnitude, quantities, and locations of tubers and white matter RM lines, as identified in T2/FLAIR brain MRI scans.Results: The SDQ score for peer relationship problems showed correlation with the tuber load (r = 0.52, p < 0.05). Tuber load and learning difficulties correlated significantly in the temporal and parietal area. Mood swings correlated with tubers in the parietal area (r = 0.529, p < 0.05). RM lines in the temporal area correlated with abnormal total SDQ (r = 0.51, p < 0.05). Anxiety and extreme shyness were correlated with RM lines in the parietal area, r = 0.513, p < 0.05 and r = 0.593, p < 0.05, respectively. Hyperactive/inattention correlated negatively with RM lines in the parietal area (r = −707, p < 0.01).Conclusions: These observations may lead to future studies for precise localization of neuropsychiatric symptoms, thereby facilitating directed therapy.

Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease

“…These patients have been shown with several neurological disorders such as autism, intellectual disability, epilepsy, anxiety, sleep disturbances, and brain tumors. 188 , 189 TSC has been characterized as an autosomal disorder caused by the loss of either TSC1 or TSC2. Moreover, the hyperactivation of mTORC1 because of the Tsc1 or Tsc2 loss in the neural cells in the murine models displayed severe epileptic seizures.…”

Ketogenic Diet Therapy for Drug-Resistant Epilepsy and Cognitive Impairment in Children With Tuberous Sclerosis Complex

“…The common neurodevelopmental disorders associated with TSC are autism spectrum disorders (ASDs) (40–50%) and attention deficit hyperactivity disorder (30–50%) ( 11 – 13 ). Tubers have traditionally been considered as the critical pathological substrate: the tubers can directly cause seizures and the tuber load correlates with intellectual disability and autism ( 14 ). Recently, studies in knockout mice with TSC gene inactivation specifically in glial cells have shown cell-autonomous effects within glia.…”