These results confirm previous reports of the efficacy and safety of vigabatrin in patients with infantile spasms, particularly among those with spasms secondary to tuberous sclerosis.

Approximately 40 - 50% of individuals affected by tuberous sclerosis (TSC) develop autism spectrum disorders (ASD). One possible explanation for this partial penetrance is an interaction between TSC gene mutations and other risk factors such as gestational immune activation. Here, we report interactive effects of these two ASD risk factors in a mouse model of TSC. Combined, but not single exposure had adverse effects on intrauterine survival. Additionally, provisional results suggest that these factors synergize to disrupt social approach behavior in adult mice. Moreover, studies in human populations are consistent with an interaction between high seasonal flu activity in late gestation and TSC mutations in ASD. Taken together, our studies raise the possibility of a gene × environment interaction between heterozygous TSC gene mutations and gestational immune activation in the pathogenesis of tuberous sclerosis-related ASD.

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Summary:We examined the hypothesis that the introduction of an inflammatory agent would augment status epilepticus (SE)-induced neuronal injury in the developing rat brain in the absence of an increase in body temperature. Postnatal day 7 (P7) and P14 rat pups were injected with an exogenous provocative agent of inflammation, lipopolysaccharide (LPS), 2 h prior to limbic SE induced by either lithium-pilocarpine (LiPC) or kainic acid. Core temperature was recorded during the SE and neuronal injury was assessed 24 h later using profile cell counts in defined areas of the hippocampus. While LPS by itself did not produce any discernible cell injury at either age, it exacerbated hippocampal damage induced by seizures. In the LiPC model, this effect was highly selective for the CA1 subfield, and there was no concomitant rise in body temperature. Our findings show that inflammation increases the vulnerability of immature hippocampus to seizure-induced neuronal injury and suggest that inflammation might be an important factor aggravating the long-term outcomes of seizures occurring early in life.

Utilizing the multicenter Tuberous Sclerosis Complex (TSC) Natural History Database including 2034 subjects, this study aimed to identify predictors of drug-resistant epilepsy in TSC. Basic epilepsy data were available for 1965 individuals in the database. Supplemental data were further collected from 1546 of these subjects through directed site queries, addressing additional epilepsy characteristics including the presence of drug-resistant epilepsy, therapies trialed, and outcomes of specific therapies. Epilepsy was reported in 86.4% of individuals with TSC. Infantile spasms were reported in 45.2% of individuals and focal seizures were reported in 84.4% of individuals. In those with focal epilepsy, drug-resistance was reported in 59.6%, with focal seizure onset prior to age 1 year (OR 1.9, CI 1.4–2.5, p<0.001), infantile spasms (OR 2.0, CI 1.5–2.5, p<0.001), and infantile spasms incompletely responsive to therapy (OR 47.6, CI 6.7–333.3, p<0.001) being associated with an increased likelihood of drug-resistance.

Disease burden associated with tuberous sclerosis complex, a genetic disorder characterized by benign tumor growth including lesions in multiple organs, puts tremendous demands on families. This analysis examines the physical and mental health burden of tuberous sclerosis complex caregivers in the United States. An institutional review board-approved web-based survey of tuberous sclerosis complex caregivers collected information; descriptive analyses were conducted on age-based subgroups. A total of 275 caregivers of tuberous sclerosis complex patients responded. Mean patient age ≤ 18 years was 6.9 (±4.4) and 42.3 (±18.2) for patients >18 years of age. Caregivers reported multiple tuberous sclerosis complex manifestations and high health care utilization for patients. Caregivers spending more time on doctor visits or researching tuberous sclerosis complex had lower physical and mental health-related quality of life scores and more depressive symptoms. Tuberous sclerosis complex caregivers had significantly lower physical and mental health-related quality of life scores and more depressive symptomatology compared to US healthy adult population norms.

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Tuberous sclerosis complex is a genetic disorder characterized by benign tumor growth including lesions in the ventricular system of the brain known as subependymal giant cell astrocytomas. This analysis focuses on the clinical presentation, management, and associated burden of subependymal giant cell astrocytomas in patients with tuberous sclerosis complex in the United States. An institutional review board-approved web-based survey of tuberous sclerosis complex patients and caregivers collected information, and descriptive analyses were conducted on age-based subgroups. A total of 116 tuberous sclerosis complex-subependymal giant cell astrocytoma patients or caregivers responded (17% of the total tuberous sclerosis complex sample). Mean and median patient ages were 25.5 and 23.5 years. Besides subependymal giant cell astrocytomas, patients also experienced skin lesions (72%), seizures (65%), and cognitive concerns (60%). Forty-five percent reported having brain surgery (22% for subependymal giant cell astrocytoma). In the past year, 42% of patients were admitted at least once to the hospital whereas 39% went to the emergency department. Results demonstrate that tuberous sclerosis complex-subependymal giant cell astrocytoma is associated with significant clinical burden, resource utilization, and decreased well-being.