NEUROLOGICAL MANIFESTATIONS OF TUBEROUS SCLEROSIS COMPLEX - PATHOPHYSIOLOGY AND DRUG-TREATMENT OPTIONS

Tuberous sclerosis complex (TSC) is one of the most commonly occurring and recognised neurocutaneous syndromes, with a prevalence of approxi mately 1 in 30 000 and a birth incidence of 1 in 10 000. It is a multi -system disorder affecting predominantly the CNS and skin. The underly ing genetic defect and pathophysiology in TSC is unclear, but is thoug ht to involve an impairment of normal cell migration resulting in dysp lastic and dysfunctional organ systems. Involvement of the CNS is resp onsible for much of the mortality and morbidity that is associated wit h TSC. Epilepsy and learning difficulties (mental retardation) are the most frequent CNS manifestations. This combination of symptoms are re flected in the historical alternative, but inappropriately pejorative, name 'epiloia', a conjoint description of epilepsy and anoia (meaning 'mindlessness'). The state of knowledge, understanding and, to a less er extent, treatment of TSC has progressed significantly in the 100 ye ars since the initial description of the condition. Unfortunately, TSC is largely nonpreventable and patients with the disorder cannot be cu red. Attention has therefore focused on the attempted suppression or c ontrol of symptoms, usually by pharmacotherapy and educational/psychol ogical support and rarely by surgical procedures. These approaches hav e had varying success. Epilepsy is the most common and, in many ways, the most frustrating neurological symptom. Seizure control is frequent ly difficult and occasionally impossible, but has benefited from the a dvent of the new antiepileptic drugs including vigabatrin and lamotrig ine. Learning disabilities, autism and other neuropsychiatric manifest ations of TSC are generally not amenable to drug therapy and are relia nt more on specific educational and behavioural manipulation. Disturbe d sleep is common in children with TSC, and for their caregivers this is often the most distressing and medically neglected manifestation of the disease. The use of melatonin in treating dysfunctional sleep has offered some real hope for this specific neurological symptom of TSC.