Preventive Antiepileptic Treatment in Tuberous Sclerosis Complex: A Long-Term, Prospective Trial

Sergiusz Jozwiak,Monika Słowińska,Julita Borkowska,Krzysztof Sadowski,Barbara Łojszczyk,Dorota Domańska-Pakieła,Dariusz Chmielewski,Magdalena Kaczorowska-Frontczak,Jagoda Głowacka,Kamil Sijko,Katarzyna Kotulska

doi:10.1016/j.pediatrneurol.2019.07.008

Sergiusz Jozwiak, Monika Słowińska + Show 9 more

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https://doi.org/10.1016/j.pediatrneurol.2019.07.008

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Abstract

BackgroudDrug-resistant epilepsy is the main risk factor for future intellectual disability in patients with tuberous sclerosis complex. Clinical epileptic seizures are often preceded by electroencephalographic changes, which provide an opportunity for preventive treatment. We evaluated the neuropsychologic and epilepsy outcomes at school age in children with tuberous sclerosis complex who received preventive antiepileptic treatment in infancy. MethodsWe performed a prospective, nonrandomized clinical trial with 14 infants diagnosed with tuberous sclerosis complex in whom serial electroencephalographic recordings were performed and preventive treatment with vigabatrin initiated when active epileptic discharges were detected. An age-matched control group consisted of 31 infants with tuberous sclerosis complex in whom treatment with vigabatrin was given only after onset of clinical seizures. Results of clinical assessment of epilepsy and cognitive outcomes were analyzed. ResultsAll patients in the preventive group (n = 14) and 25 of 31 patients in the standard treatment group were followed through minimum age five years, median 8.8 and 8.0 years in the preventive and standard groups, respectively. The median intelligence quotient was 94 for the preventive group when compared with 46 for the standard group (P < 0.03). Seven of 14 patients (50%) in the preventive group never had a clinical seizure when compared with one of 25 patients (5%) in the standard treatment group (P = 0.001). ConclusionsThis study provides evidence that preventive antiepileptic treatment in infants with tuberous sclerosis complex improves long-term epilepsy control and cognitive outcome at school age.

Highlights

Tuberous sclerosis complex (TSC) is a multisystem disorder characterized by hamartomatous growths that may affect the brain, skin, retina, heart, kidneys, and lungs, which is due to mutation in either TSC1 or TSC2.1 Some TSC lesions, such as cardiac rhabdomyomas and cortical tubers, are often detected prenatally, whereas other lesions develop much later in life.[1,2] Neurological manifestations of TSC, including seizures and intellectual disability, are major issues in the care of infants and children with TSC and have significant impact on the quality of life of the patients and their families.[3]
We evaluated the neuropsychologic and epilepsy outcomes at school age in children with tuberous sclerosis complex who received preventive antiepileptic treatment in infancy
Refractory epilepsy is diagnosed in half of individuals with TSC and is predictive of development of intellectual disability, which occurs in 40% to 70% patients with TSC.[5,6,7]

Summary

Introduction

Tuberous sclerosis complex (TSC) is a multisystem disorder characterized by hamartomatous growths that may affect the brain, skin, retina, heart, kidneys, and lungs, which is due to mutation in either TSC1 or TSC2.1 Some TSC lesions, such as cardiac rhabdomyomas and cortical tubers, are often detected prenatally, whereas other lesions develop much later in life.[1,2] Neurological manifestations of TSC, including seizures and intellectual disability, are major issues in the care of infants and children with TSC and have significant impact on the quality of life of the patients and their families.[3]. Epileptogenesis is a cascade of molecular and cellular events, which begins with a brain insult (injury, genetic predisposition, metabolic disease) It has been shown in both clinical and preclinical models that between the triggering factor and clinical seizure onset there is a latent period of epileptogenesis which may last for weeks or months.[9,10] Experimental and a few clinical studies have shown that the introduction of an antiepileptic treatment during epileptogenesis and before the start of clinical seizures may prevent epilepsy onset and lead to a reduction in drug-resistant epilepsy.[10,11,12]

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