What Is Our Current Understanding of Epilepsy Prognosis?
Abstract & Commentary
By Padmaja Kandula, MD
Assistant Professor of Neurology and Neuroscience, Comprehensive
Epilepsy Center, Weill Cornell Medical College
Dr. Kandula reports no financial relationships relevant to this field of study. This article
originally appeared in the December 2013 issue of Neurology Alert.
Synopsis: This paper summarizes and focuses on the National General Practice Study of Epilepsy with emphasis on epilepsy prognosis after initial diagnosis.
Source: Shorvon SD, Goodridge DM. Longitudinal cohort studies of the prognosis of epilepsy: Contribution of the National General Practice Study of Epilepsy and other studies. Brain 2013;136(Pt 11):3497-3510.
Our current understanding of epilepsy prognosis stems from the cumulative data of large cohort studies published over the last few decades. In this paper, Shorvon and colleagues review the details of the National General Practice Study of Epilepsy (NGPSE), the first and largest prospective, population-based study of adults and children with epilepsy. The principal endpoint of the study was to describe the prognosis of newly diagnosed seizures with regard to seizure recurrence and remission and mortality. Secondary endpoints included treatment patterns and psychosocial aspects of epilepsy.
Patients for the NGPSE were prospectively recruited through 275 general practitioners (GP) within Great Britain from 1984-1987. At 6-month follow-up, patients were classified into febrile convulsions (220 patients), definite epileptic seizures (564 patients), and possible epileptic seizures (228 patients). Stratification was based on combined clinical information from the referring GP and selected adult and pediatric neurologists with epilepsy training. Of the 564 definite epilepsy cases, 346 were idiopathic/cryptogenic, 119 remote symptomatic, 83 acute symptomatic, and 16 with neurologic deficit. Cerebrovascular disease and stroke were the two most common symptomatic etiologies. Patients were followed at 6 months and subsequently had annual evaluations over a median of 22 years.
Of the 564 patients with definite seizures, 67% and 78% had recurrence at 12 months and 36 months, respectively. Seizures associated with a fixed neurologic deficit from birth had 100% recurrence at 12 months in contrast to 40% recurrence from acute brain insults. In addition, those < 16 years or > 59 years of age also had a high risk of seizure recurrence (83%). Other factors associated with risk of recurrence included partial seizures (94%) vs 72% for generalized seizures. The rate of relapse was inversely related to duration of seizure freedom. The hazard rate for seizure recurrence or percentage risk of having a recurrence was 0.033 per week in the first 6 months after the first seizure, then fell to 0.007 per week at 6-12 months, and finally 0.004 per week in the next 24 months. The overall relapse rate at 3 years after the first seizures was roughly 75%, but 44% if no relapse in the first 6 months, 32% if no relapse after 12 months, and 17% if no relapse at 18 months.
In terms of remission, the number of seizures in the first 6 months after study notification (seizure density) predicted chance of remission. Hence, for an individual with two seizures during the 6-month period, the chance of making the 1-year remission rate was 95% and 47% for 5-year remission vs 75% and 24%, respectively, for individuals with high seizure density (≥ 10 seizures during the 6-month period).
For individuals with febrile convulsions, 6% of the children ultimately developed epilepsy (mean follow-up of 21.6 years). The standardized mortality rate (SMR; ratio quantifying the increase or decrease in mortality of a study cohort with respect to the general population) for patients with possible epilepsy was 2.5 vs 3 for those with definite epilepsy. The SMR was the highest at 5.1 during the initial year of diagnosis, then declined to 2.5 and 1.3 at 3 and 5 years, respectively. The SMR for those with idiopathic epilepsy was 1.6, remote symptomatic epilepsy 4.3, and acute symptomatic epilepsy 2.9. The authors concluded that the mortality rate was higher in those with newly diagnosed epilepsy largely due to underlying cause. Seizure recurrence and antiepileptic drug treatment did not influence mortality rate. At median follow-up of 22.8 years, SMR for those with definite epilepsy was 2.55, with pneumonia and cerebrovascular disease as most common causes of death.
In terms of treatment patterns, nearly 50% of those on treatment were in 5-year remission. Twenty-nine percent of patients with one or more seizures a week had never tried a second agent and only 23% had tried four or more antiepileptic drugs.
Using the Washington psychosocial inventory, a questionnaire was sent to 216 patients with an 89% response rate. The four major problem areas identified by patients were fear of seizures, fear of stigma in employment, adverse effects on leisure, and lack of energy. The conclusion of the questionnaire was that psychosocial impact was related to severity of the illness rather than the diagnosis itself.
Based on this longitudinal, prospective study, a few generalizations regarding epilepsy prognosis can be made. Overall, epilepsy has a good prognosis, with 65-85% remission rate. In particular, the long-term prognosis for febrile seizures developing into epilepsy in children was 6%. The likelihood of long-term remission is better in newly diagnosed cases rather than chronic cases. Early treatment response to seizures is an indicator of overall long-term prognosis. The longer the overall remission period, the less likelihood of subsequent seizure recurrence. In contrast, the longer the epilepsy is active, the prognosis is poorer. Remission periods followed by relapse were less common than initial active seizures with remission and no remission at all (refractory state). Epilepsy has the highest mortality rate in the initial years after diagnosis and appears to be dependent largely on underlying cause. Lastly, clinical factors predicting worse prognosis are presence of fixed neurologic deficit early in life, high seizure density before treatment, poor initial response to antiepileptic drug treatment, and certain epilepsy syndromes.
Perhaps the most puzzling question is why epilepsy prognosis continues to improve. Although it seems intuitive that the ever-increasing clinical armamentarium of second- and now third-generation antiepileptic agents may have a large role in the matter, to date there have been no epidemiologic data to firmly support this hypothesis. In the future, an analysis comparing epilepsy prognosis in patients treated with first- and second-generation medications is warranted to thoroughly answer this clinical question.