Neurocutaneous Syndromes and Epilepsy—Issues in Diagnosis and Management

Abstract

Summary: Epilepsy may be seen as a feature of many of the neurocutaneous syndromes. The challenge lies within the diagnosis of the specific disorder and ultimately control of the epilepsy. Tuberous sclerosis is the most common of the disorders with a frequency of 4.9/100,000. An autosomal-dominant condition, diagnostic features may be unclear under 2 years of age. Population studies suggest a prevalence of epilepsy of 78%, the majority presenting under the age of 12 months, with a high association between the occurrence of seizures and the presence of learning disability. Although an apparent multifocal disease, surgery may have a role to play where seizures are demonstrated to probably arise from a single tuber. Other less common neurocutaneous syndromes also have a high prevalence of epilepsy in association with cerebral malformations; unilateral or lobar malformations should be referred early for surgical consideration. Neurofibromatosis is the second most common of the disorders but the prevalence of epilepsy in this population is relatively low; in addition, a greater proportion may be easier to treat with medication.Key Words: Epilepsy-Neurocutaneous Syndromes-Tuberous sclerosis-Sturge-Weber syndrome-Neurofibromatosis-Pigmentation disordersProteus syndrome.The neurocutaneous syndromes are a group of disorders where characteristic skin lesions are seen in association with abnormalities of the central nervous system, and by consequence are at risk of presenting with epilepsy. Although the features of some disorders have included abnormalities of the cerebrum within diagnostic criteria, advances in imaging and genetics have further delineated some of the rarer forms and outlined associations with malformations of cerebral development. This has major implications for management as it is apparent that many, if drug resistant epilepsy is a feature, may be suitable for resective surgery. Although in some diagnostic criteria and/or genetics are clear, in others they may be more subtle and may present issues for diagnosis within the epilepsy clinic. Such diagnoses are important to guide prognosis and counseling for the individual, as well as determine possible merits of surgical referral. TUBEROUS SCLEROSISTuberous sclerosis (TS) is the most common of the neurocutaneous syndromes occurring in a frequency of 4.9/100,000. First described by Bourneville in 1880 as "tuberous sclerosis of the cerebral convolutions," it was the triad of seizures, learning difficulty, and adenoma sebaceum (now facial angiomatosis) that became almost Table 1). It is an autosomal condition with variable expression and high sporadic mutation rate (estimated at 66%). Recurrence in siblings of individuals with unaffected parents is rare. Two loci have been documented where mutations lead to the clinical phenotype; TSC1 located at 9q34 that codes for the protein hamartin, and TSC2 located at 16p13.3 responsible for the protein tuberin. The two proteins appear to function in the same complex, sharing a common biochemical pathway involved in cel...

Tüberoskleroz kompleksi tanılı hastalarda epilepsinin özellikleri ve klinik seyri

“…Tüberoskleroz kompleksinde en sık nörolojik bulgu %80-90 oranında görüldüğü bildirilen epilepsidir (7,(15)(16)(17)(18)(19)(20) (15,21). Bu çalışmada, bir grup epileptik TSK tanılı hastada epileptik nöbet özelliklerini, nöbetlerin seyrini ve nöbet seyrini etkileyebilecek etmenleri araştırdık.…”

Mechanisms of Epileptogenesis in Pediatric Epileptic Syndromes: Rasmussen Encephalitis, Infantile Spasms, and Febrile Infection-related Epilepsy Syndrome (FIRES)

“…Mutations in various genes along the phosphatidylinositol 3-kinase-AKTmTOR pathway have been identified in hemimegalencephaly, patients with which often present with IS. These include mutations in the phosphatase and tensin homolog (PTEN) and AKT genes, or de novo somatic mutations of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha, AKT3, or mTOR genes detected in the affected brain tissue, but not in peripheral blood [70,[93][94][95][96]. Polyhydramnios, microcephaly and symptomatic epilepsy syndrome can manifest with IS, and has been linked to mutations in STE20-related kinase adaptor alpha (STRAD-alpha) [97][98][99].…”

New insights into the pathogenesis and prevention of tuberous sclerosis-associated neuropsychiatric disorders (TAND)

“…An identified genetic mutation in either TSC1 or TSC2 is also an independent criterion for diagnosis. Epilepsy (90%) 6– 13 , intellectual disability (45%) 14– 18 , and autism (61%) 19– 33 are prominent features of TSC but are relatively non-specific and are not diagnostic. Autism, intellectual disability, and related conditions are classified as TSC-associated neuropsychiatric disorders (TAND) 34 .…”