Mortality in epilepsy in the first 11 to 14 years after diagnosis: Multivariate analysis of a long‐term, prospective, population‐based cohort

Abstract

The United Kingdom National General Practice Study of Epilepsy is a prospective, population-based study of newly diagnosed epilepsy. A cohort of 792 patients has now been followed for up to 14 years (median follow-up [25th, 75th percentiles] 11.8 years, range 10.6-11.7 years), a total of 11,400 person-years. These data are sufficient for a detailed analysis of mortality in this early phase of epilepsy. Over 70% of patients in this cohort have developed lasting remission from seizures, although the mortality rate in the long term was still twice that of the general population. The standardized mortality ratio (SMR), the number of observed deaths per number of expected deaths, was 2.1 (95% confidence interval [CI] = 1.8, 2.4). Patients with acute symptomatic epilepsy (SMR 3.0; 95% CI = 2.0, 4.3), remote symptomatic epilepsy (SMR 3.7; 95% CI = 2.9, 4.6), and epilepsy due to congenital neurological deficits (SMR 25; 95% CI = 5.1, 73.1) had significantly increased long-term mortality rates, whereas patients with idiopathic epilepsy did not (SMR 1.3; 95% CI = 0.9, 1.9). This increase in mortality rate was noted particularly in the first few years after diagnosis. Multivariate Cox regression and time-dependent co-variate analyses were utilized for the first time in a prospective study of mortality in epilepsy. The former showed that patients with generalized tonic-clonic seizures had an increased risk of mortality. The hazard ratio (HR), or risk of mortality in a particular group with a particular risk factor compared to another group without that particular risk factor, was 6.2 (95% CI = 1.4, 27.7; p = 0.049). Cerebrovascular disease (HR 2.4; 95% CI = 1.7, 3.4; p < 0.0001), central nervous system tumor (HR 12.0; 95% CI = 7.9, 18.2; p < 0.0001), alcohol (HR 2.9; 95% CI = 1.5, 5.7; p = 0.004), and congenital neurological deficits (HR 10.9; 95% CI = 3.2, 36.1; p = 0.003) as causes for epilepsy and older age at index seizure (HR 1.9; 95% CI = 1.7,2.0; p < 0.0001) were also associated with significantly increased mortality rates. These hazard ratios suggest that epilepsy due to congenital neurological deficits may carry almost the same risk of mortality as epilepsy due to central nervous system tumors and that epileptic seizures subsequent to alcohol abuse may carry almost the same risk of mortality as epilepsy due to cerebrovascular disease. The occurrence of one or more seizures before the index seizure (the seizure that led to the diagnosis of epilepsy and enrolment in the study) was associated with a significantly reduced mortality rate (HR 0.57; 95% CI = 0.42, 0.76; p = 0.00001). Time-dependent co-variate analysis was used to examine the influence of ongoing factors, such as seizure recurrence, remission, and antiepileptic drug use, on mortality rates in the cohort. Seizure recurrence (HR 1.30; 95% CI = 0.84, 2.01) and antiepileptic drug treatment (HR 0.97; 95% CI = 0.67, 1.38) did not influence mortality rate. There were only 5 epilepsy-related deaths (1 each of sudden unexpected death in epilepsy, status epilepticus,...

Survival of Patients with Epilepsy: An Estimate of the Mortality Risk

“…Methods: We used MEDLINE database and Cumulative Index Medicus for 1960-2001, Excerpta Medica for 1948-1965, and relevant journals and bibliographies. We selected comparative studies investigating mortality in epilepsy patients conducted in the last 100 years.…”

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Summary:Purpose: To investigate the extent and causes of the differences in mortality found in studies on mortality in epilepsy based on a quantitative review of the literature.Methods: We used MEDLINE database and Cumulative Index Medicus for 1960-2001, Excerpta Medica for 1948-1965, and relevant journals and bibliographies. We selected comparative studies investigating mortality in epilepsy patients conducted in the last 100 years.

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Epilepsy: A Spectrum Disorder

“…The proportional mortality ratio is the proportion of death owing to a particular cause in a cohort of patients in a given period and can be used to compare the relative contribution of various causes to the overall mortality in a population. In large cohort studies of patients .15 years of age, the standardized mortality ratio ranged from 2.1 to 5.1 (Nashef et al 1995;Nilsson et al 1997;Shackleton et al 1999;Lindsten et al 2000;Lhatoo et al 2001). The majority of deaths in people whose seizures started in childhood occur in adulthood.…”

“…The proportional mortality ratio (PMR) for epilepsy-related conditions, range from 1% to 45% (Zielinski 1974;Hauser et al 1980;Annegers et al 1984;Cockerell et al 1994;Loiseau et al 1999;Lhatoo et al 2001;Ding et al 2006).…”

Sudden Unexpected Death in Epilepsy (SUDEP): an overview

“…The lowest incidence rates, 0.09 to 0.35/1,000 person-years, have been reported from unselected cohorts of incident cases of epilepsy. [1,10] Rates in chronic refractory epilepsy are between 1.1 to 5.9/1,000 person-years [9,[11][12][13][14] and in epilepsy surgery candidates or patients who continue to have seizures after surgery, 6.3-9.3/1,000 person-years. [15,16] In patients with chronic refractory epilepsy attending epilepsy referral centers, SUDEP has been the leading cause of premature death accounting for 10-50% of all deaths.…”