Faculty Bibliography

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

PURPOSE: To study the history of epilepsy from 1880 to 1920. METHODS: We reviewed all 40 volumes of The Alienist and Neurologist and identified articles concerning primarily epilepsy. We analyzed three of these articles in greater detail. RESULTS: The Alienist and Neurologist published 'Original Contributions,''Selections,' (abstracts from other journals written by the editorial board), 'Editorials,' and (book) 'Reviews.' Of 258 epilepsy articles, there were 40 Original Contributions, 164 Selections, 39 Editorials, and 15 Reviews. These articles included 71 on therapy (41 medication, 13 surgery, and 17 other therapies); 66 general discussions; 46 on etiology or symptoms; 34 case studies; 28 social/legal articles; and 13 autopsy or pathology articles. CONCLUSIONS: Analysis of The Alienist and Neurologist provides a unique and valuable perspective on the clinical practice and academic world of epileptology during the decades around the turn of the twentieth century

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

Epilepsy and developmental disabilities (DD) often occur together but affect individuals differently and have a complex causal relationship. Most epilepsy in the population with DD is partial or symptomatic generalized. Seizures and antiepileptic drugs (AEDs) can further delay development, and the DD can complicate treatment and adjustment to epilepsy. Medical care and decision making require careful coordination of health care providers and the family, especially because of the trend for the patients to live in group homes. Behavioral and psychiatric disorders are difficult to diagnose but common in those with DD and epilepsy; psychiatric disorders are perhaps up to sevenfold higher in this group than in the general population. Psychotropic medications-antidepressants, anxiolytics (but use caution with benzodiazepines), antipsychotics, and stimulants-are appropriate for those with psychiatric disorders. Diagnostic difficulties may lead to undertreatment, and the motivation to lessen certain behaviors may lead to overtreatment. Because those with DD may be unusually sensitive to adverse effects of both seizures and AEDs, cognitive and behavioral side effects must be carefully monitored. Few relevant studies exist. For some patients, comorbid psychiatric disorders may be treated with one AED, such as carbamazepine, lamotrigine, or valproate. Phenobarbital and phenytoin may be inappropriate for those with epilepsy and DD. Studies have shown some success with oxcarbazepine (for partial and generalized epilepsy) and with adjunctive lamotrigine. For those on medication regimens, perhaps taking combinations of drugs for numerous years, queries about earlier attempts to reduce AEDs and gradual efforts to substitute less toxic mediations are worthwhile. Vagus nerve stimulation and epilepsy surgery for those with medically refractory epilepsy may be options after careful evaluation

PURPOSE: Because the number and variety of patients at any single facility is not sufficient for clinical or statistical analysis, data from six major epilepsy centers that performed multiple subpial transections (MSTs) for medically intractable epilepsy were collected. METHODS: A meta-analysis was performed to elucidate the indications and outcome, and to assess the results of the procedure. Overall, 211 patients were represented with data regarding preoperative evaluation, procedures, seizure types and frequencies before and after surgery, postoperative deficits, and demographic information. Fifty-three patients underwent MST without resection. RESULTS: In patients with MST plus resection, excellent outcome (>95% reduction in seizure frequency) was obtained in 87% of patients for generalized seizures, 68% for complex partial seizures, and 68% for simple partial seizures. For the patients who underwent MST without resection, the rate of excellent outcome was only slightly lower, at 71% for generalized, 62% for complex partial, and 63% for simple partial seizures. EEG localization, age at epilepsy onset, duration of epilepsy, and location of MST were not significant predictors of outcome for any kinds of seizures after MST, with or without resection. New neurologic deficits were found in 47 patients overall, comparable in MST with resection (23%) or without (19%). CONCLUSIONS: These preliminary results suggest that MST has efficacy by itself, with minimal neurologic compromise, in cases in which resective surgery cannot be used to treat uncontrolled epilepsy. MST should be investigated as a stand-alone procedure to allow further development of criteria and predictive factors for outcome

The first step in evaluation of a presumed seizure is to determine whether the event was indeed a seizure and which diagnostic studies are needed. The second step is to correctly diagnose the seizure on the basis of the medical history and findings from the physical, neurologic, and laboratory evaluation. The third step is to decide whether drug treatment is necessary. Every paroxsymal event is unique, and not every seizure needs to be treated. When treatment is deemed appropriate, an antiepileptic drug should be chosen after discussion with the patient and consideration of the risk-benefit profile of the available agents