R. Bombardieri

Topical Review: Intractable Seizures in Tuberous Sclerosis Complex: From Molecular Pathogenesis to the Rationale for Treatment

Tuberous sclerosis complex is a multisystem autosomal dominant genetic disorder resulting from mutations in one of two genes, TSC1 and TSC2. Pathologically, tuberous sclerosis complex is characterized by abnormal cellular differentiation and proliferation, as well as abnormal neuronal migration. Epilepsy occurs in about 90% of patients, with onset frequently in the first year of life. In a sizable proportion of individuals, seizures tend to be refractory to antiepileptic drug treatment. This article reviews the progress in understanding drug-resistant seizures in tuberous sclerosis complex, from molecular pathogenesis to the pathophysiologic mechanisms of epileptogenesis, and the rationale for appropriate medical and surgical treatment. (J Child Neurol 2005;20:318—325).

The management of subependymal giant cell tumors in tuberous sclerosis: a clinician's perspective

BackgroundTuberous sclerosis (TSC) is a genetic multisystem disorder associated with hamartomas in several organs including subependymal giant cell tumors (SGCT). SGCT have the potential to grow and therefore to become symptomatic and are one of the main causes of death in TSC individuals. Surgical resection is the procedure of choice for SGCT. However, the discovery of mTOR pathway upregulation in TSC-associated tumors and recent evidence that mTOR inhibitors may induce regression of SGCT open up new treatment strategies. Based on a review of the currently available literature and on personal experience, current options for the management of TSC patients and appropriate indications, taking into account benefits and risks of surgery and pharmacotherapy, are discussed.DiscussionAn earlier diagnosis of SGCT in neurologically asymptomatic children may allow a precocious surgical removal of the tumor, thus minimizing surgery-related morbidity and mortality. Biologically targeted pharmacotherapy with mTOR inhibitors such as sirolimus and everolimus provides a safe and efficacious treatment option for patients with SGCT and has the potential to change the clinical management of these tumors. However, whether pharmacotherapy is sufficient to control growth or if it only delays the need for surgical removal of symptomatic SGCT remains unclear. Further studies are needed to determine the optimal levels of mTOR inhibitors that preserve maximal anti-tumor efficacy while minimizing side effects.

Neuroimaging findings of Sturge–Weber Syndrome in a child with Tuberous Sclerosis

MRI appearance of Sturge-Weber Syndrome (SWS) in patients with Tuberous Sclerosis (TSC) has been rarely reported. We describe a new patient with confirmed diagnosis of TSC and MRI appearance of SWS and review the pertinent literature. We discuss these findings on the basis of the new classifications of brain malformations, which take into account the role of neural-crest. The coexistence of signs of both diseases in the same individuals could be explained by common altered pathways that could lead to an anomalous angiogenesis.

Medical treatment in children with central nervous system malformations

Publisher Summary The management of children affected by the malformations of the central nervous system (CNS) is particularly complex and needs diagnosis, assessment, treatment, care, counseling, and periodic diagnostic review and reassessment. The assessment of epilepsy in children with developmental abnormalities presents particular problems. It is necessary to admit the child to hospital for serial observations to determine the type of seizure and epileptic syndrome. The use of video electroencephalography (EEG) recording is often helpful for the classification of the epileptic phenomenon and it is crucial for an early definition of intractability and proper decision for treatment. Drug resistance, defined as the persistence of seizures despite maximum tolerated doses of antiepileptic drugs (AEDs) in mono- or polytherapy, is frequent in children with developmental disorders of the CNS. A thorough assessment of a childs cognitive abilities and social-communication skills and a functional analysis of aberrant behaviors allows for the formulation of a comprehensive and effective therapy plan. It is critical that clinicians utilize therapeutic interventions that are individualized and tailored to the needs of the child, rather than more global, nonspecific practices.