Age of onset and cognitive function

Most studies indicate that early age of onset of seizures is an important correlate of poor cognitive function in epilepsy.30–36 Several studies emphasize that age of onset is, in fact, the most important predictor of cognitive outcome in patients with epilepsy.37,38 In a series of 1,141 patients, Strauss et al.38 demonstrated a linear decline in IQ, from age of onset before 1 year (mean IQ, 84.4) to adult onset (mean IQ, 93.4).

A similar study measured scores of 410 patients with various seizure types:32

The question of whether younger patients are at greater risk for cognitive change as adults remains unanswered. Neyens' longitudinal study found that children who had an earlier age of onset had a smaller gain in FSIQ score during 1.5 years of follow-up than did children with later-onset seizures.28 Poor prognosis may result from disruption of intellectual development at an earlier age.28 Children with later-onset seizures may have a greater opportunity for intellectual growth before being affected by seizures. Support for this theory is provided by Gomez’s study of the prevalence of mental retardation in children with tuberous sclerosis.34 Mental retardation was observed in 72 of 79 children with seizure onset before age 1 year, whereas only 6 of 25 children with seizures after age 4 exhibited mental retardation.

Holmes53 explored the role of age at seizure onset in the cognitive outcome of rodents. He induced status epilepticus (SE) with kainic acid in prepubescent and mature rats and then compared their mental development. The mature group showed greater cognitive impairment, suggesting a role for neuronal plasticity in adapting to the adverse consequences of severe seizures. A similar protective effect during early human development may exist, but studies have not yet demonstrated this protection. It is possible that this effect is indeed found in humans but that underlying structural damage causes irreversible cognitive dysfunction that masks any independent effect of seizures.

Seizure frequency and cognitive function

Several studies have found that seizure frequency was negatively correlated with cognitive outcome.19,39–41 Other researchers found that this was not the case, however.23,42

In monozygotic twins with the same form of epilepsy but different seizure frequency, the twin with the more frequent seizures showed greater cognitive impairment.43 Another twin study involved two sets of twins with tuberous sclerosis. One twin from each set experienced frequent generalized seizures, whereas the second twin had infrequent or short-lived seizures. The more severely affected twins were more likely to be mentally retarded.34

Another group found that significant cognitive impairment was best correlated with the number and severity of seizures.44 The number of seizures around the time of testing was not correlated with IQ changes, however, consistent with a slowly progressive and sustained effect of seizures.

Duration of epilepsy and cognitive function

Long duration of epilepsy is another factor associated with cognitive decline.23,40,45 Jokeit and Ebner46 separated patients with epilepsy into groups on the basis of seizure duration. Their statistics showed that patients with epilepsy of more than 30 years’ duration had significantly lower Full-Scale IQ scores than patients with a duration of epilepsy of 15 to 30 years or fewer than 15 years.

A statistic derived from duration of seizures is “years with seizures.”40 This number is obtained by subtracting the number of 12-month periods in which no seizures occurred from the number of years since onset. Years with seizures showed a stronger negative correlation to intelligence than did simple number of years since onset.40 Other researchers have found that years with seizures may be the best way to relate time to neuropsychological functioning in epilepsy, because it combines measurement of frequency of attacks with the length of time over which they occurred.47

Education also may contribute to the effects of epilepsy duration and cognitive outcome. Jokeit and Ebner46 found that patients with higher educational levels had stable Full-Scale IQs for longer periods. This suggests that education level as an indicator of higher brain reserve may contribute to cognitive preservation, a theory that has been similarly advanced for other neurologic disorders.48–52

Adapted from: Devinsky O and Tarulli A. Progressive cognitive and behavioral changes in epilepsy. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;133–149.
With permission from Elsevier (www.elsevier.com).
Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

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