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

PURPOSE: To examine evidence for effectiveness of anteromesial temporal lobe and localized neocortical resections for disabling complex partial seizures. METHODS: Systemic 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

Physicians treating patients with epilepsy have a host of thera-peutic options. Drug choice is dictated first by the seizure(s) and/or epilepsy syndrome. Age is also a factor. Special considerations apply to women, particu-larly during their childbearing years, and to patients who are learning-disabled. Drug selection is further influenced by such characteristics as spectrum of activity, rapid response, low potential for drug-drug interactions, and ease of use. In addition to clinical trial data, postmarketing assessments of the new antiepileptic drugs provide useful clinical information on efficacy and safety. Levetiracetam has specific characteristics that make it an optimal choice for many patient populations

OBJECTIVES: Topiramate (TPM) is a new antiepileptic drug (AED) that has been found to be associated with a high prevalence of cognitive adverse events (CAEs). The prevalence of psychiatric adverse events (PAEs) has yet to be established. The purpose of this study was to determine the prevalence of PAEs related to TPM when used in polytherapy regimens in a large cohort of adult patients with epilepsy, to identify any association between the occurrences of CAEs and PAEs and to identify predictors of PAEs and CAEs. METHODS: Investigators from 16 epilepsy centers (PADS group) prospectively obtained postmarketing safety and efficacy data on 596 patients aged 16 years and older. All data were recorded on standardized data retrieval forms, completed at the initial visit, while follow-up data were obtained every 6 months or at the time of discontinuation. RESULTS: PAEs were identified in 75 (12.6%) patients: 30 (5%) experienced symptoms of depression and 34 (5.7%) of aggressive behavior and irritability, while 9 patients experienced symptoms of psychosis (1.5%). CAEs were reported by 247 (41.5%) patients. There was a significant association between the occurrences of CAEs and PAEs. A past psychiatric history was a predictor of CAEs, while older age and past psychiatric history were predictors of PAEs. CONCLUSIONS: The use of TPM in polytherapy regimens can cause PAEs and CAEs and their occurrence is significantly correlated. Patients with a past psychiatric history may be at a higher risk for experiencing PAEs and CAEs

Levetiracetam (Keppra) was evaluated in a subset of patients aged >/=65 years (n=78) enrolled in a large (n=1030) open-label, phase IV trial (the KEEPER trial). A 4-week dose adjustment was followed by a 12-week evaluation period. An overall median reduction in partial seizures of 80.1% (n=65) was observed. Overall, 76.9% of patients were >/=50% responders, 56.9% were >/=75% responders, and 40.0% were 100% responders. Levetiracetam was well tolerated, with 42.3% of patients reporting one or more adverse events. A total of 15 patients (19.2%) experienced an adverse event that led to discontinuation. Somnolence (n=13,16.7%) and dizziness (n=7,9.0%) were the most commonly reported adverse events. Despite the limitations of the open-label study design, these data provide information regarding the use of levetiracetam as add-on therapy for the treatment of partial-onset seizures in patients >/=65 years of age, including those requiring concomitant medications

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