Epilepsy in adult patients with tuberous sclerosis complex.

Aglaia Vignoli,Maria Paola Canevini,Elena Zambrelli,Ilaria Viganò,Katherine Turner,Chiara Vannicola,Fabio Bruschi,Valentina Chiesa,Francesca La Briola,Angela Peron

doi:10.1111/ane.13416

Aglaia Vignoli, Maria Paola Canevini + Show 8 more

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https://doi.org/10.1111/ane.13416

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Abstract

ObjectivesLittle is known about the evolution of epilepsy in individuals with tuberous sclerosis complex (TSC) in adulthood. This study aims at describing the characteristics of epilepsy in adult TSC patients attending a single multidisciplinary clinic.Materials and MethodsWe collected data about epilepsy (age at onset, seizure types, history of infantile spasms (IS), epilepsy diagnosis and outcome), genetic and neuroradiological findings, cognitive outcome and psychiatric comorbidities.ResultsOut of 257 adults with TSC, 183 (71.2%) had epilepsy: 121 (67.2%) were drug‐resistant; 59 (32.8%) seizure‐free, at a median age of 18 years. 22% of the seizure‐free patients (13/59) discontinued medication.Median age at seizure onset was 9 months. Seventy‐six patients (41.5%) had a history of IS. TSC2 pathogenic variants (p = 0.018), cortical tubers (p < 0.001) and subependymal nodules (SENs) (p < 0.001) were more frequent in those who developed epilepsy. Cognitive functioning was lower (p < 0.001) and psychiatric disorders more frequent (p = 0.001). We did not find significant differences regarding age, gender, mutation and tubers/SENs in seizure‐free vs drug‐resistant individuals. Intellectual disability (p < 0.001) and psychiatric disorders (p = 0.004) were more common among drug‐resistant patients.ConclusionsEpilepsy in TSC can be a lifelong disorder, but one‐third of individuals reach seizure freedom by early adulthood. In the long term, age at epilepsy onset has a crucial role in drug resistance and in developing intellectual disability, both in drug‐resistant and drug‐sensible patients. Patients with drug‐refractory seizures tend to develop psychiatric issues, which should be recognized and adequately treated.

Highlights

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder characterized by the development of benign hamartomas in multiple organ systems
We considered the potential role of the duration of epilepsy (< or >5 years) on the cognitive outcome: patients experiencing a shorter time of active seizures had a statistically significant better intellectual functioning (Figure 3, p < 0.024)
Epilepsy is a major burden in people with tuberous sclerosis complex (TSC), and seizure control is a critical issue in their clinical management.[13]

Summary

Introduction

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder characterized by the development of benign hamartomas in multiple organ systems. 1:6,000–10,000 live births, and the prevalence around 1:20,000 in the general population.[1] Inactivating mutations of TSC1 (chr 9p34) or TSC2 (chr 16p13) can be identified in up to 90% of the clinically affected people. . |2 development and cellular proliferation.[2] Only 30% of the cases are inherited, whereas the majority of affected individuals has a de novo pathogenic variant. TSC2 mutations are detected 4–5 times more than TSC1 mutations, whereas in inherited cases TSC1 and TSC2 mutations are identified.[3,4] The identification of a pathogenic variant is a stand-alone diagnostic criterion.[1] no mutations are identified (NMI) in 10–25% of affected people using conventional testing methods and in 5–10% when generation sequencing techniques are applied. It is important to keep in mind that negative genetic results do not exclude the diagnosis when clinical criteria are met.[5,6]

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