Elsevier

The Lancet

Volume 357, Issue 9251, 20 January 2001, Pages 216-222
The Lancet

Review
Neuropsychological effects of epilepsy and antiepileptic drugs

https://doi.org/10.1016/S0140-6736(00)03600-XGet rights and content

Summary

Epilepsy and its treatment can have deleterious cognitive and behavioural consequences. Affected individuals have a higher prevalence of neuropsychological dysfunction than the general population because of complex interactions among several multifaceted and overlapping influences–for example, underlying neuropathologies, ictal and interictal neuronal discharges, a plethora of antiepileptic drugs, and numerous psychosocial issues. Research into the clinical relevance of these factors has been dogged by a range of methodological pitfalls including lack of standardisation of neuropsychological tests, small numbers and multiple testing, and statistical failure to appreciate differential effects of interactive elements in individual patients. Although antiepileptic drugs can impair neuropsychological functioning, their positive effect on seizure control might improve cognition and behaviour. Each person should be assessed individually with respect to factors unique to his or her seizure disorder and its treatment.

Section snippets

Pitfalls in research methods

Although most of the following criticisms refer to studies that investigate cognitive and behavioural side-effects of antiepileptic drugs, they are equally applicable to those that explore the influence of the other factors mentioned above. Vermeulen and Aldenkamp, in reviewing 89 studies done over 25-years, concluded that no satisfactory answer could be given to the question of adverse cognitive effects of antiepileptics because most of these studies did not “pass fairly basic standards of

Cause and neuropathology

Most generally agree that there is no universal epileptic personality trait. There is, however, a diverse range of clinical changes indicating anatomical foci, patterns of seizure spread, and biological and psychological differences among patients. In localisation-related epilepsy, a range of cognitive defects have been suggested, which mainly relate to the presumed physiological function of the anatomical site of seizure focus–for example, greater memory deficit has been found in patients with

Neuronal discharges

Ictal cognitive and behavioural features are well recognised. John Hughlings Jackson first developed the concept of temporal-lobe epilepsy, correlating clinical behaviour with pathological lesions in a series of elegant case reports, toward the end of the 19th century. The introduction of electroencephalography (EEG) provided a powerful tool to delineate the characteristic ictal, as well as interictal, patterns observed in this type of epilepsy, correlating them with observable behavioural

Antiepileptic drugs

Huette first described the cognitive and behavioural sideeffects of bromide in 1850 before its suggested use as an anticonvulsant in 1857 by Sir Charles Locock. Data have since been obtained from normal volunteers, comparisons between treated and untreated patients, measurement of concentration-effect relations, and substitution and withdrawal studies. Early observations did not detect any mental effects of phenobarbital, but the investigators failed to control for the confounding factor of

Psychosocial factors

Epilepsy has long been a misunderstood and stigmatising disorder. Although in western societies it is no longer thought of as the product of demonic possession, misconception and prejudice remain. In a survey carried out in the USA in 1979, 92% of those interviewed thought epilepsy was not a form of insanity, but only 79% believed epilepsy patients should be employed, and only 89% would not object to their children playing with others who had epilepsy.66 Although there has been much improvement

Conclusion

A better appreciation of the complex cognitive and behavioural dimensions of epilepsy would allow clinicians to provide a more holistic and patient-centred approach to management. Underlying neuropathology, and ictal and subclinical neuronal discharges, can have adverse cognitive and behavioural consequences. Some of these psychosocial disabilities can be cumulative or even irreversible. Studies of surgical outcomes indicate that even when surgery is successful in eliminating seizures, patients

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