Elsevier

Neurologic Clinics

Volume 27, Issue 4, November 2009, Pages 1003-1013
Neurologic Clinics

Identification of Pharmacoresistant Epilepsy

https://doi.org/10.1016/j.ncl.2009.06.001Get rights and content

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Recognizing pharmacoresistance as it occurs

Although the prevalence of pharmacoresistance at a given point in time is important for public health and needs assessments, it is not necessarily the subject of greatest clinical relevance when considering treatment and management of individual patients. Identifying which patients are at high risk of pharmacoresistance and prospectively identifying drug resistance as soon as it becomes evident are arguably more important. This corresponds to the clinical situation in which a case is followed

Seizure frequency and duration of treatment

Patient characteristics, in particular seizure frequency, may play a role in how quickly drug efficacy or inefficacy can be determined. In patients who typically have multiple daily seizures, determination of a drug's efficacy or lack thereof may be made in a matter of a week in many cases, although for complete control of seizures (success) there is no specific criterion. In one study, a year of seizure freedom was required before considering a drug trial successful.10 Trials of drugs that

Predictors of pharmacoresistance

Prognostic information about who will develop pharmacoresistance is limited. In adult-onset epilepsy, there are no adequate studies based on well-defined and characterized cohorts and using a meaningful definition of pharmacoresistance. In childhood-onset epilepsy, three large prospective and representative cohort studies provide a mixed message on this matter. All three studies found that the epileptic encephalopathy or secondary generalized syndromes had higher risks than other forms of

Current referral recommendations

The pediatric epilepsy surgery subcommission of the International League against Epilepsy recommends that children whose seizures have failed fully to respond to trials of 2 or 3 AEDs be evaluated at a comprehensive epilepsy center.26 The National Association of Epilepsy Centers recommends that patients whose seizures are not fully controlled after 1 year be evaluated at a specialized center.27 This issue was also highlighted in a practice parameter that recognized that failure of 2 drugs was

Why is it necessary to identify pharmacoresistance as soon as possible?

Uncontrolled seizures can have a devastating effect on the individual and family. School, employment, driving, and all aspects of social functioning and activities can be adversely affected. Psychiatric complications, particularly depression and anxiety, may, in part, be consequences of uncontrolled seizures,44 although there is clearly a complex and bidirectional association between epilepsy and depression.45 Mortality is considerably increased in people with epilepsy.46 This is of particular

Cognition as a facet of intractable epilepsy

The concerns with the adverse effect on cognition, especially in the developing brain, raise another issue: is control of seizures the full measure of whether a patient's epilepsy is drug-responsive or pharmacoresistant? On the one hand, there is reason to suspect that mechanisms underlying the developmental syndromes known as the epileptic encephalopathies may differ from those of garden variety focal epilepsy. It would be reasonable to investigate the mechanisms of pharmacoresistance and

Future challenges

There remains much to do at this point. First and foremost, the field needs a valid and robust operational definition of pharmacoresistance, one that can be meaningfully used in most, if not all, clinical research settings and that is relevant to clinical patient care. This definition must include explicit guidelines for what constitutes a drug's failure, and how many different drugs should be failed for a patient's epilepsy to be deemed pharmacoresistant. At this point, consensus seems to be

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    This work was supported by Grant R37-31146 from the NIH-NINDS.

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