Tuberous sclerosis : clinical factors in long term outcome

• Main Author: Hancock, Eleanor
• Published: University of Bath 2003
• Subjects: 616; Medicine
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269678

Tuberous sclerosis (TSC) is a dominantly inherited disorder with a high spontaneous mutation rate and a birth incidence of 1 in 10,000. It is a systemic disorder characterised by the growth of hamartomas, which in turn give rise to the clinical manifestations, for example, epilepsy and learning difficulties. Although some patients with TSC are only mildly affected and lead a normal life with typical life expectancy, there is an immense amount of morbidity associated with this disease. In addition, for the majority of patients there is reduced life expectancy. The purpose of this thesis is to look at the clinical factors that contribute to the morbidity and mortality seen in TSC and examine means of reducing the impact of these factors on long-term outcome. It reports a longitudinal population study of a small but defined group of patients looking at the epidemiology and natural history (the morbidity and mortality) suffered by in this population. It investigates the current treatment regimes for the types of epilepsy (infantile spasms and nonconvulsive status epilepticus) known to be associated with the highest risk of learning difficulties in order to determine the most efficacious treatment for the seizures potentially reducing long-term psychomotor delay. A cochrane review of the treatment of infantile spasms was performed. This thesis also examines the effect of exogenous melatonin on sleep disorders (one of the major causes of morbidity) in tuberous sclerosis and the natural circadian rhythms in patients with sleep disorder in TSC and compares them with the normal population. Two important causes of premature mortality in TSC patients are respiratory and renal failure. This thesis examines the prevalence and underlying causes of end stage renal failure in adults with TSC and reviews the literature of LAM (in patients both with and without TSC) investigating further the natural history and treatment of LAM in TSC.