Current concepts on epilepsy management in tuberous sclerosis complex

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease affecting approximately 1 in 6,000 people, and represents one of the most common genetic causes of epilepsy. Epilepsy affects 90% of the patients and appears in the first 2 years of life in the majority of them. Early onset of epilepsy in the first 12 months of life is associated with high risk of cognitive decline and neuropsychiatric problems including autism. Prenatal or early infantile diagnosis of TSC, before the onset of epilepsy, provides a unique opportunity to monitor EEG before the onset of clinical seizures, thus enabling early intervention in the process of epileptogenesis. In this review, we discuss the current status of knowledge on epileptogenesis in TSC, and present recommendations of American and European experts in the field of epilepsy.

The Important Role of Perituberal Tissue in Epileptic Patients with Tuberous Sclerosis Complex by the Transcriptome Analysis

“…More than 90% of TSC patients have structural lesions in the central nervous system, which have not only seriously affected their quality of life but also imposed a heavy economic burden on family and society [ 11 , 12 ]. Even though antiepileptic drugs, mTOR inhibitors, and surgical treatment can be chosen if necessary, the management of refractory epilepsy is still very intractable, attributing to the unclear etiopathogenesis [ 3 , 13 , 14 ]. In addition to CT, which has been confirmed to be able to cause epilepsy, recent literatures have thrown new light on PT, which may also be responsible for epileptogenesis [ 15 ].…”

“…However, it is not easy to locate epileptogenic tubers accurately in clinic, and it is even more difficult to divide the borders of PT exactly. Therefore, the extent of surgical resection of PT is still controversial and needs further study [ 3 ]. Here, we analyzed the different transcriptomic characteristics of PT comparing with CT and NC in detail, aiming to further deepen the understanding of PT and to restate the necessity of surgical resection.…”

“…Of which, epilepsy is most common, accounting for 70-90% [ 2 ]. Even though great progresses have been made in recent years, management of epilepsy remains most challenging and controversial [ 3 ]. Therefore, it is very urgent to further clarify the pathogenesis of epilepsy.…”

Everolimus as adjunctive therapy for tuberous sclerosis complex-associated partial-onset seizures

“…Regarding surgery, presurgical evaluation should be promptly considered in those with drug-resistant epilepsy (those who have treatment failure with the first two AEDs), particularly in very young patients, as early surgical intervention can increase the probability of seizure-freedom [11,13]. Presurgical evaluation should occur even in complex cases, such as those with multiple tubers, multiple interictal foci, bilateral seizures, or epileptic spasms since a single epileptogenic tuber can be found responsible for the most impairing seizures [14].…”

High-frequency oscillations for the non-invasive localisation of the seizure onset zone

“…In cases with unilateral basal-temporal discharges, the resection of the irritative zone was a predictor of good surgical outcome (Dodrill et al, 1986) (Tonini et al, 2004). Similarly, in patients with unilateral epileptogenic lesions, IEDs can often mislead the localisation of the epileptogenic tissue due to the presence of generalised or contralateral spikes (Wyllie et al, 2007) such as in cases of tuberous sclerosis (Canevini et al, 2018) and…”