Faculty Bibliography

Behavioral changes are common in epilepsy patients, with the overall spectrum of behavior in this population skewed toward cognitive impairment and psychopathology. Unfortunately, in many cases, the diagnosis is overlooked and therapeutic opportunities are missed. The pathogenesis of these disorders may include central nervous system pathology, ictal and interictal epileptiform activity, antiepileptic drugs, psychologic and environmental factors, and genetic predisposition. Although therapy for behavioral disorders is often deferred for fear of exacerbating epilepsy, treatment with psychopharmacologic agents is unlikely to increase seizure severity or frequency. Indeed, treating depression, anxiety, psychosis, and other disorders can improve sleep, reduce stress, and may even reduce seizure activity. Antiepileptic drugs have psychotropic properties that can be positive or negative and their effects may differ in epilepsy and purely psychiatric populations

Cognition-induced epilepsy comprises a group of loosely tied syndromes characterized by seizures regularly precipitated by cognitive tasks. Linguistic operations (e.g., reading, writing) and decision making associated with visuospatial manipulation are the most frequent and best-characterized triggers. The syndromes reviewed have a high degree of overlap and clinical/EEG variability, suggesting that any of the neural networks subserving these complex tasks may promote seizures on either a topographic basis or a functional/connective basis. Treatment options include typical pharmacological and surgical interventions as well as stimulus alteration, threshold alteration, and avoidance conditioning. We postulate that more commonly encountered epilepsy syndromes also have complex triggers

Antiepileptic drugs (AEDs) possess potent negative or positive psychotropic effects. Clear evidence of benefit exists for valproate, carbamazepine, and lamotrigine in bipolar disorder. Reports of benefit from various AEDs in mood, anxiety, impulse control, and personality disorder are reviewed. Further research is needed to clarify which patients are likely to benefit. Clinicians must closely attend to the ongoing risk/benefit analysis and consider possible iatrogenic worsening of neuropsychiatric symptoms

Studies on nonepileptic seizures (NES) provide dichotomous data sets: extensive observational findings, but a paucity of controlled treatment data. Psychosocial stressors, whose full impact may lie outside a patient's awareness, often underlie NES. These stressors, along with patient's learned patterns of coping, may bring forth or potentiate comorbid psychiatric disorders. Patients with NES often have dysfunction in emotion regulation and family dynamics, as well as unemployment/disability. High percentages of comorbid disorders such as major depressive disorder, post-traumatic stress disorder, and cluster B personality with impulsivity (all disorders associated with serotonin system function) also exist in the NES population. The preliminary observational evidence suggests that specific psychotherapies and pharmacotherapy directed at comorbid conditions may be the most effective treatment for NES.

Responds to G. C. Fong et al's comments (see record 2002-06521-015) on K. Alper et al's article (see record 2001-09677-006) which reported interest in the relationship between seizure cluster characteristics, presence of mood disorder among first- and second-decree relatives, and postictal psychosis. The current authors agree that the approach would be useful. (PsycINFO Database Record (c) 2007 APA, all rights reserved)

Refractory seizures are common in patients with tuberous sclerosis and can contribute to developmental delay and behavioral problems. Surgical intervention can reduce the seizure burden in selected patients with tuberous sclerosis and refractory epilepsy, thereby improving cognitive function, behavior, and quality of life. However, the risks of surgery are usually considered unacceptable when the epileptogenic focus lies over dominant hemisphere eloquent cortex or is multilobar. Multistage invasive monitoring can provide detailed data regarding the location and number of ictal foci and functional extraoperative mapping can precisely delineate the boundaries of eloquent areas of the brain. If independent ictal onsets are demonstrated, a staged surgical approach can allow a more aggressive yet safe procedure in selected patients. A combination of staged resection and multiple subpial transections may provide an opportunity to treat epileptogenic foci located over eloquent cortex. Bilateral staged resections can be used when independent bihemispheric foci are present in patients with tuberous sclerosis. This article presents two cases, one of which (case 2) was previously reported, on successful multistage surgical treatment of epileptogenic foci located over an eloquent cortex or in both hemispheres in children with tuberous sclerosis. This case is represented since there is additional follow-up available and the prior report was to a neurosurgical audience. This multistage approach permitted resection of epileptogenic foci that would traditionally have been considered inoperable

This multicentre, randomised, double-blind, placebo-controlled, parallel-group study investigated the efficacy, safety and pharmacokinetics of remacemide hydrochloride in adult patients ( n= 59) with refractory epilepsy, undergoing reduced or discontinued antiepileptic drug (AED) usage, as part of an evaluation for epilepsy surgery. On discontinuation or reduction of maintenance AEDs, patients received remacemide hydrochloride, up to 600 mg daily, or placebo, for up to ten days or until they experienced a fourth complex partial (CPS) or a generalised tonic-clonic (GTC) seizure. Pre- and post-study blood and urine samples were taken for analysis. Remacemide hydrochloride showed a significantly ( P= 0.045) longer median time to fourth seizure compared with placebo (6.8 vs. 3.8 days). Median nine-day seizure counts were significantly ( P= 0.0327) lower with remacemide hydrochloride than placebo (6.2 vs. 12.8). Eleven remacemide hydrochloride patients and six placebo patients completed ten days' treatment. Remacemide and desglycinyl metabolite levels were lower in patients receiving concomitant carbamazepine or phenytoin than in those receiving non-inducing AEDs or remacemide hydrochloride alone. No serious adverse events occurred; all patients receiving remacemide hydrochloride completed the study. Remacemide hydrochloride was well tolerated and showed significant therapeutic activity in this patient population