Faculty Bibliography

The October 2002 Case of the Month (COM). The patient was a 27-year-old woman with a history of partial complex seizures at age 7. At age 20 her seizures changed in character and became progressively worse. Neuroimaging studies showed atrophy of the right hemisphere and contralateral cerebellar atrophy. Following a biopsy, she was scheduled for a surgical procedure, but unfortunately she expired at home during her sleep a week later. Examination of the brain confirmed the hemi-atrophy of the right cerebral hemisphere and left cerebellum. Microscopic examination showed severe gliosis and perivascular lymphocytic infiltrates in many areas. A diagnosis of Rasmussen's encephalitis was made. Rasmussen's encephalitis is a chronic neurological disorder, first described in 1958. The active neurological decline lasts from 1 to 20 years and the patients then remain stable with a fixed neurological deficit and residual seizures. Pathological examination shows a chronic encephalitis confined to one hemisphere. In the active phase, neuronophagia, activated microglial cells (rod cells), microglial nodules, and perivascular lymphocytic infiltrates, are present. In the more chronic phase neuronal loss and gliosis predominate. The etiology of Rasmussen's encephalitis is unknown but viral infection and autoimmunity have been implicated. The treatment of choice is functionally complete hemispherectomy with complete disconnection of the frontal and occipital lobes

OBJECTIVES/METHODS: To examine evidence for effectiveness of anteromesial temporal lobe and localized neocortical resections for disabling complex partial seizures by systematic review and analysis of the literature since 1990. RESULTS: One intention-to-treat Class I randomized, controlled trial of surgery for mesial temporal lobe epilepsy found that 58% of patients randomized to be evaluated for surgical therapy (64% of those who received surgery) were free of disabling seizures and 10 to 15% were unimproved at the end of 1 year, compared with 8% free of disabling seizures in the group randomized to continued medical therapy. There was a significant improvement in quantitative quality-of-life scores and a trend toward better social function at the end of 1 year for patients in the surgical group, no surgical mortality, and infrequent morbidity. Twenty-four Class IV series of temporal lobe resections yielded essentially identical results. There are similar Class IV results for localized neocortical resections; no Class I or II studies are available. CONCLUSIONS: A single Class I study and 24 Class IV studies indicate that the benefits of anteromesial temporal lobe resection for disabling complex partial seizures is greater than continued treatment with antiepileptic drugs, and the risks are at least comparable. For patients who are compromised by such seizures, referral to an epilepsy surgery center should be strongly considered. Further studies are needed to determine if neocortical seizures benefit from surgery, and whether early surgical intervention should be the treatment of choice for certain surgically remediable epileptic syndromes

About 20-40% of patients with epilepsy will be refractory to medical treatment with antiepileptic drugs. It is unclear whether patients are already drug-resistant at the time of their initial presentation, or whether they become so over the course of their illness. Identifying predictors for drug-refractory epilepsy may be important for directing epilepsy patients to an effective nonpharmacological treatment, such as surgery or the vagus nerve stimulator, in a timely manner. In addition, understanding the factors that lead to the drug-refractory state may facilitate the development of new therapies that are effective in the resistant subgroup. This paper identifies various predictors that have been associated with drug-refractory epilepsy, discusses the evidence behind each factor and recommends strategies for clarifying predictors of refractoriness

Pharmacokinetic interactions involving the antiepileptic drugs have long been considered to be an unavoidable component of epilepsy treatment. Many of the 'older' generation of antiepileptic drugs, including carbamazepine, phenytoin and phenobarbital, are recognized to cause hepatic induction of drug-metabolizing enzyme systems, such as the cytochrome P450 and UDP-gluculronyltransferase. Such interactions are not uncommonly implicated in resulting in clinically significant treatment complications. During the latter half of 1990s, a number of new antiepileptic drugs have become available to clinicians. Generally speaking, a common feature of these 'newer' generation medications are improved pharmacokinetic characteristics, including an improved drug interaction profile. The aim of this review is to summarize the data, both experimental and clinical, regarding pharmacokinetic interactions with the newer antiepileptic drugs

Whereas randomized controlled trials remain a standard for evaluating and comparing efficacy and safety of the new antiepileptic drugs (AEDs), postmarketing drug research offers a useful means of comparing efficacy and safety of new AEDs. However, differences in baseline characteristics of patients in different drug groups create the potential for bias in drug comparison studies. In this study, baseline demographic characteristics of 1,386 patients initiating lamotrigine (LTG), tiagabine (TGB), or topiramate (TPM) were compared to identify patient characteristics that may influence AED use in epilepsy patients. Data were collected at 14 epilepsy centers and included medications, seizure types and syndromes, and prior adverse events. There were 402 patients in the LTG group, 725 TPM, and 259 TGB. The groups differed both in their number of concurrent AEDs (p<0.001) and in their number of prior AEDs (p<0.01). There was no difference in proportion with partial versus generalized epilepsy syndromes. The groups differed in the proportions of patients with complex partial seizures (p=0.049), primary generalized tonic-clonic seizures (p=0.01), and myoclonic seizures (p=0.03). Baseline behavioral adverse event rate was lowest in patients initiating TPM (p<0.01); LTG patients had the lowest rate of prior AED-related rash (p=0.02). There was no relationship between AED assignment and patient age, age of epilepsy onset, epilepsy duration, institutionalization status, gender, or psychiatric history. Numerous epidemiological differences were identified among patients placed on the new AEDs, including current and prior AED profiles, seizure types, and prior adverse event history. Accounting for these differences is of crucial importance because they may bias conclusions of nonrandomized post-marketing trials comparing the drugs