Cognitive impairment and behavioral problems were recognized in patients with epilepsy in ancient times1 and documented in nineteenth century neurologic literature.2,3 Gowers4 found that although most patients demonstrated a normal intellect and pattern of behavior, some had interictal abnormalities. He recognized that the etiology of this change was multifactorial but hypothesized that epilepsy was the most important cause.

Lennox5 expanded on Gowers’ work, identifying five potential factors in the cognitive and behavioral decline associated with epilepsy:

• heredity
• brain injury prior to seizure onset
• medication
• psychological handicaps
• epilepsy itself

The insights of Gowers and Lennox remain valid. The study of mental deterioration in epilepsy focuses on their observations and their suggested mechanisms. Nevertheless, progressive cognitive and behavioral decline in epilepsy remains a debated issue for several reasons.

The first problem is one of methodology: No set of standards exists by which to measure behavioral, intellectual, and neuropsychological functioning in patients with epilepsy. Studies with longitudinal designs and those that use time as a variable strongly suggest cognitive and behavioral decline, but agreement is not universal.

Measurement of cognitive function
Longitudinal studies of cognitive change

Other variables studied include etiology, type, severity, and laterality of seizures. Symptomatic epilepsy is more often associated with a severe decline than is idiopathic epilepsy. The cognitive changes caused by SE, generalized tonic-clonic seizures, and complex partial seizures must be separated from those caused by underlying structural damage. Absence seizures were traditionally considered benign, but recent studies have shown long-term cognitive and behavioral problems. The cause of these problems in patients with absence epilepsy remains unknown.

Age of onset, frequency, and duration
Etiology of epilepsy
Type and severity of epilepsy

Although postictal and interictal psychoses are well-documented phenomena, the issue of progression from postictal to interictal psychosis requires further exploration.

Psychosis and epilepsy

Pathologic and radiologic findings demonstrate progressive cell loss and atrophy in selected cases, and further work is needed to correlate changes in neuropsychological and intellectual performance with anatomic changes. In addition, the identification of seizure, epilepsy, and individual patient characteristics that predispose individuals to progressive cell loss will be critical.

Pathologic and radiologic findings

AEDs are an important variable in the study of cognitive and behavioral decline: Successful control of seizures may prevent cognitive decline, but many drugs have recognized cognitive side effects.

Cognitive effects of antiepileptic drugs

Poor psychosocial adjustment and subclinical epileptiform discharges have subtle effects on performance, and further study of these two variables is needed.

Psychosocial factors
Subclinical epileptiform discharges

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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