The prognosis of newly diagnosed and treated epilepsies in adults

Mohanraj, Rajiv (2004) The prognosis of newly diagnosed and treated epilepsies in adults. PhD thesis, University of Glasgow.

Abstract

The prognosis for seizure control is an important consideration for patients diagnosed with epilepsy. Reversing the social restrictions imposed by seizures and returning to a productive life requires complete and sustained seizure control. The epilepsies are a heterogeneous group of disorders and clinicians discussing the prognosis of epilepsy need to be aware of the natural history of each epilepsy syndrome. Longitudinal follow up studies in newly diagnosed patient populations are required to delineate the natural history of the various syndromes. Previous studies have suggested that the early course of epilepsy is predictive of its longer-term behaviour in the majority of cases. If response to individual antiepileptic drugs (AEDs) in specific epilepsy syndromes can be predicted, prognosis can be assessed more accurately. Genetic influences on response to treatment are probably important in this regard. The completion of the Human Genome Project has opened up the possibility of correlating variations in the human genome with the variability of response to drugs. The discipline of pharmacogenomics, which seeks to study the genetic influence on response to drugs, has the potential to allow drug therapy to be optimised for each patient, maximising the chances of success. Identification of single nucleotide polymorphisms (SNPs) in candidate genes correlating with response to AED treatment can help identify patients at risk of developing drug resistant epilepsy. Epilepsy is associated with an increased mortality risk. The excess risk varies depending on the population studied, and is influenced by patients' clinical and demographic characteristics. Clinicians discussing mortality issues with patients need to be aware of the potential risk in each individual. This is best deduced from studies in representative patient groups. Risks need to be studied separately in patients with newly diagnosed and chronic epilepsy, as the prognoses in these two groups are likely to be different, in terms of both seizure control and survival. Treatment outcomes were analysed in patients newly diagnosed with epilepsy at the Epilepsy Unit, Western Infirmary, Glasgow over a 20-year period by retrospective review of research case notes. Response to treatment was defined as a 12-month seizure free period and those who remained seizure free till the end of follow up were considered to be in remission. A total of 890 patients had been diagnosed with epilepsy. Treatment outcomes were known for 780 who were included in the analysis of treatment outcomes. Four major categories of response to treatment were observed: those who responded rapidly and completely to treatment with the first AED (immediate responders), those who responded with further changes to therapy including combination treatment (delayed responders), those who had an initial period of good control before experiencing seizure recurrence and being subsequently uncontrolled (relapse), and those who never achieved 12 month seizure free period (uncontrolled). Over 90% of those responding to treatment achieved remission. Of those responding to treatment 83% had completed 12 seizure free months by 3 years from starting AEDs. Those failing the first AED had significantly lower likelihood of responding to further pharmacotherapy if the reason for failure was lack of efficacy rather than adverse effects. For patients failing 2 well tolerated antiepileptic drug regimes, the chances of seizure freedom with pharmacotherapy was less than 10% and for those failing 3 such regimes, this figure was only 3%. Alcohol abuse, history of head injury and febrile seizures, psychiatric co-morbidity and family history of epilepsy showed significant univariate association with uncontrolled epilepsy. Voltage gated sodium channels are important in the generation action potentials in the brain and also serve as molecular targets for a range of AEDs. SNPs resulting in altered amino acid sequence in the sodium channel a subunit have the potential to influence the response to AED treatment.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Martin J Brodie
• Keywords: Medicine
• Date of Award: 2004
• Depositing User: Enlighten Team
• Unique ID: glathesis:2004-74069
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 23 Sep 2019 15:33
• Last Modified: 23 Sep 2019 15:33
• URI: https://theses.gla.ac.uk/id/eprint/74069