Long-term outcomes of epilepsy surgery in tuberous sclerosis complex

Liang, Shuli; Zhang, Juncheng; Yang, Zhixian; Zhang, Shaohui; Cui, Zhiqiang; Cui, Jianfei; Zhang, Jiwu; Liu, Na; Ding, Ping

doi:10.1007/s00415-017-8507-y

Cited by 46 publications

(71 citation statements)

References 30 publications

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“…25 The number of patients not controlled on treatment at baseline was much lower in our study (infantile spasms, 15.5%; focal seizures; 38%) than the 62.5% reported in a previous study by Chu-Shore et al 1 This lower number of treatmentresistant patients could be explained by the earlier diagnosis age shown by the high number of young patients enrolled in our study and by the fact that patients were diagnosed and managed in specialized reference centers that follow established recommended guidelines. 32 The correlation between intellectual ability and seizure control in TSC has been reported. The recommendations of serial EEG studies before clinical seizures have allowed the detection of some patients with subtle or infraclinical seizures.…”

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confidence: 99%

“…30,31 This might be the main limiting factor for epilepsy surgery but should be a reminder to refer patients with pharmacoresistant epilepsy early on to expert epilepsy surgery centers to define the possibility of such therapy that is showing fair results, even in patients with multiple foci. 32 The correlation between intellectual ability and seizure control in TSC has been reported. [33][34][35][36][37] Patients with uncontrolled seizures had a higher rate of intellectual disability compared to those with controlled seizures.…”

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confidence: 99%

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Epilepsy in tuberous sclerosis complex: Findings from the TOSCA Study

Nabbout

Belousova

Benedik³

et al. 2018

Epilepsia Open

133

135

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Summary Objective To present the baseline data of the international TuberOus SClerosis registry to increase disease Awareness (TOSCA) with emphasis on the characteristics of epilepsies associated with tuberous sclerosis complex (TSC). Methods Retrospective and prospective patients’ data on all aspects of TSC were collected from multiple countries worldwide. Epilepsy variables included seizure type, age at onset, type of treatment, and treatment outcomes and association with genotype, seizures control, and intellectual disability. As for noninterventional registries, the study protocol did not specify any particular clinical instruments, laboratory investigations, or intervention. Evaluations included those required for diagnosis and management following local best practice. Results Epilepsy was reported in 83.6% of patients (1852/2216) at baseline; 38.9% presented with infantile spasms and 67.5% with focal seizures. The mean age at diagnosis of infantile spasms was 0.4 year (median <1 year; range <1‐30 years) and at diagnosis of focal seizures was 2.7 years (median 1 year; range <1‐66 years). A total of 1469 patients (79.3%) were diagnosed with epilepsy <2 years. The rate of infantile spasms was higher in patients with a TSC2 mutation than in patients with a TSC1 mutation (47.3% vs 23%). ɣ‐aminobutyric acid (GABA)ergic drugs were the most common treatment modality for both infantile spasms (78.7%) and focal seizures (65.5%). Infantile spasms and focal seizures were controlled in 76.3% and 58.2% of patients, respectively. Control of seizures was associated with lower rates of intellectual disability in both groups. Significance This registry reports the largest international cohort of patients with TSC. Findings confirmed the typical onset pattern of infantile spasms and other focal seizures in the first 2 years of life, and the high rates of infantile spasms in patients with TSC2 mutation. Our results underscored the occurrence of focal seizures at all ages, including an onset that preceded emergence of infantile spasms. Seizure control was shown to be associated with lower rates of intellectual disability but did not preclude the presence of intellectual disability.

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confidence: 99%

mentioning

confidence: 99%

Epilepsy in tuberous sclerosis complex: Findings from the TOSCA Study

Nabbout

Belousova

Benedik³

et al. 2018

Epilepsia Open

133

135

View full text Add to dashboard Cite

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“…After epilepsy surgery, authors have reported rates of seizure freedom (Engel Class I outcome) between 48 and 84% depending on the follow-up interval (Arya et al, 2015;Fallah et al, 2015;Liang et al, 2017;Weiner, 2006;Zhang et al, 2013). An extensive presurgical evaluation is carried out and each patient is discussed at a multidisciplinary conference to determine surgical candidacy.…”

Section: Treatment Strategiesmentioning

confidence: 99%

“…An extensive presurgical evaluation is carried out and each patient is discussed at a multidisciplinary conference to determine surgical candidacy. After epilepsy surgery, authors have reported rates of seizure freedom (Engel Class I outcome) between 48 and 84% depending on the follow-up interval (Arya et al, 2015;Fallah et al, 2015;Liang et al, 2017;Weiner, 2006;Zhang et al, 2013). Positive predictors of seizure freedom after surgery include younger age at seizure onset, greater extent of resection, focal EEG abnormalities, EEG and MRI concordance, and the absence of generalized seizures or significant developmental delay (Fallah et al, 2013;Fallah et al, 2015;Zhang et al, 2013).…”

Section: Treatment Strategiesmentioning

confidence: 99%

Central nervous system manifestations of tuberous sclerosis complex

Karas

Krueger

et al. 2018

American J of Med Genetics Pt C

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Tuberous sclerosis complex (TSC) is a neurocutaneous autosomal-dominant genetic syndrome marked by development of hamartomatous lesions arising from dysfunction of the mammalian target of rapamycin (mTOR) pathway. Although TSC remains a heterogeneous clinical entity, the recent inclusion of genetic diagnostic criteria reflects advancement in our understanding of its underlying etiopathogenesis. Abnormal cellular growth, differentiation, and migration result in multisystem sequelae, with neurologic manifestations of TSC representing the primary cause of morbidity and mortality for the majority of individuals. Modern imaging techniques aid in the diagnosis of TSC and guide treatment strategies by revealing central nervous system findings. Cortical tubers are the namesake lesion of the disorder and occur in up to 90% of cases, often exerting significant epileptogenic potential. Subependymal nodules are found in 80% of patients as calcified tumors lining the ependyma of the lateral ventricles. In some cases, these nodules are thought to progress to subependymal giant cell astrocytomas and may present with obstructive hydrocephalus. Retinal astrocytic hamartomas are also common, present in 50% of patients. Surgery remains the treatment of choice for large or symptomatic lesions, though clinical trials have highlighted a potential role for mTOR pathway antagonism. A multidisciplinary approach is necessary for achieving optimal patient outcomes.

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“…Cortical tubers and the perituberal cortex in TSC have long been implicated in the generation of seizures [21][22][23][24][25]. Cortical tubers are characterized by laminar dysorganization, dysmorphic neurons, eosinophilic giant cells, and severe gliosis [26].…”

Section: Introductionmentioning

confidence: 99%

High glucose concentrations mask cellular phenotypes in a stem cell model of tuberous sclerosis complex

Rocktäschel

Sen

Cader

2019

Epilepsy & Behavior

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Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder caused by deletions in the TSC1 or TSC2 genes that is associated with epilepsy in up to 90% of patients. Seizures are suggested to start in benign brain tumors, cortical tubers, or in the perituberal tissue making these tubers an interesting target for further research into mechanisms underlying epileptogenesis in TSC. Animal models of TSC insufficiently capture the neurodevelopmental biology of cortical tubers, and hence, human stem cell-based in vitro models of TSC are being increasingly explored in attempts to recapitulate tuber development and epileptogenesis in TSC. However, in vitro culture conditions for stem cell-derived neurons do not necessarily mimic physiological conditions. For example, very high glucose concentrations of up to 25 mM are common in culture media formulations. As TSC is potentially caused by a disruption of the mechanistic target of rapamycin (mTOR) pathway, a main integrator of metabolic information and intracellular signaling, we aimed to examine the impact of different glucose concentrations in the culture media on cellular phenotypes implicated in tuber characteristics. Here, we present preliminary data from a pilot study exploring cortical neuronal differentiation on human embryonic stem cells (hES) harboring a TSC2 knockout mutation (TSC2−/−) and an isogenic control line (TSC2+/+). We show that the commonly used high glucose media profoundly mask cellular phenotypes in TSC2−/− cultures during neuronal differentiation. These phenotypes only become apparent when differentiating TSC2+/+ and TSC2−/− cultures in more physiologically relevant conditions of 5 mM glucose suggesting that the careful consideration of culture conditions is vital to ensuring biological relevance and translatability of stem cell models for neurological disorders such as TSC. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

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Long-term outcomes of epilepsy surgery in tuberous sclerosis complex

Cited by 46 publications

References 30 publications

Epilepsy in tuberous sclerosis complex: Findings from the TOSCA Study

Epilepsy in tuberous sclerosis complex: Findings from the TOSCA Study

Central nervous system manifestations of tuberous sclerosis complex

High glucose concentrations mask cellular phenotypes in a stem cell model of tuberous sclerosis complex

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