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 approximately 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 underlying genetic defect and pathophysiology in TSC is unclear, but is thought to involve an impairment of normal cell migration resulting in dysplastic and dysfunctional organ systems. Involvement of the CNS is responsible for much of the mortality and morbidity that is associated with TSC. Epilepsy and learning difficulties (mental retardation) are the most frequent CNS manifestations. This combination of symptoms are reflected 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 lesser extent, treatment of TSC has progressed significantly in the 100 years since the initial description of the condition. Unfortunately, TSC is largely nonpreventable and patients with the disorder cannot be cured. Attention has therefore focused on the attempted suppression or control of symptoms, usually by pharmacotherapy and educational/psychological support and rarely by surgical procedures. These approaches have had varying success. Epilepsy is the most common and, in many ways, the most frustrating neurological symptom. Seizure control is frequently difficult and occasionally impossible, but has benefited from the advent of the new antiepileptic drugs including vigabatrin and lamotrigine. Learning disabilities, autism and other neuropsychiatric manifestations of TSC are generally not amenable to drug therapy and are reliant more on specific educational and behavioural manipulation. Disturbed 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.