Faculty Bibliography

With many new medications on the market and new data about the various side-effects of antiepilepsy drugs (AEDs), the medical management of epilepsy can seem unnecessarily complicated for the non-specialist. The process can be thought of taking place in 7 steps: 1) assessing the need for medications; 2) defining the seizures and classifying the epilepsy syndrome; 3) knowing which medications are best used in which syndromes; 4) taking into account patient priorities when choosing a medication, such as cotreatment or avoidance of neurobehavioral issues and weight loss or gain; 5) considering other life issues, such as planning a pregnancy and breastfeeding; 6) choosing a maintenance dose and deciding when to consider a change to another medication or to use dual therapy; and 7) if seizure-free, which patients to consider AED reduction or withdrawal. The goal is simply, no seizures and no side-effects. Seizure freedom is an important goal to reduce injury, mortality and improve quality of life. Improving tolerability is equally as important, as both acute and chronic side-effects of AEDs can be as disabling as seizures themselves.

BACKGROUND: Epileptic seizures may be misdiagnosed if they manifest as psychiatric symptoms or seizures occur in patients with known psychiatric illness. METHODS: We present clinical profiles of six patients with epilepsy (three male, mean age 39 +/- 12 years) that presented with prominent psychiatric symptoms. RESULTS: Two patients had pre-existing psychiatric illnesses. Three patients were initially diagnosed with panic attacks, two with psychosis, and one with schizophrenia. Five patients had temporal lobe epilepsy (TLE) while the sixth patient was subsequently found to have absence status epilepticus (SE). Cranial computed tomogram (CT) including contrast study was unremarkable in five patients and showed post-traumatic changes in one patient. Cranial magnetic resonance imaging (MRI) revealed dysembryoplastic neuroepithelial tumour (DNET) in one patient, cavernous hemangioma in one, and post-traumatic changes plus bilateral mesial temporal sclerosis in another patient but it was normal in two TLE patients. Routine electroencephalography (EEG) revealed absence SE in one patient but it was non-diagnostic in the TLE patients. Video-EEG telemetry in the epilepsy monitoring unit (EMU) was necessary to establish the diagnosis in four TLE patients. None of the patients responded to medications aimed at treating psychiatric symptoms alone. Two patients required surgery while the other four required treatment with anti-epileptic drugs. All the patients had favorable response to the treatment of their epilepsy. CONCLUSIONS: This case series illustrates that epileptic patients may experience non-convulsive seizures that might be mistaken as primary psychiatric illnesses. In this subset of patients, evaluation by an epileptologist, MRI of the brain, and/or video-EEG telemetry in an EMU was necessary to confirm the diagnosis of epilepsy if routine EEGs and cranial CT are normal.

In 2009, the US Food and Drug Administration approved three medications for the treatment of epilepsy: rufinamide, lacosamide, and vigabatrin. In addition, extended-release formulations of lamotrigine and levetiracetam were approved recently. When added to the dozen medications for treating epilepsy, the choice is a luxury in terms of additional options, but also a challenge for practitioners to use them all with expertise. Recently, there has been much interest surrounding medications for epilepsy and their possible association with osteoporosis, safety during pregnancy, biological equivalence to generic versions, and possible association with higher rates of suicidality. This review discusses these issues and provides a current overview for the medical management of epilepsy.

Continuous electroencephalographic monitoring in critically ill patients has improved detection of nonconvulsive seizures and periodic discharges, but when and how aggressively to treat these electrographic patterns is unclear. A review of the literature was conducted to understand the nature of periodic discharges and the strength of the data on which management recommendations have been based. Periodic discharges are seen from a wide variety of etiologies, and the discharges themselves are electrographically heterogeneous. This spectrum suggests a need to consider these phenomena along a continuum between interictal and ictal, but more important clinically is the need to consider the likelihood of neuronal injury from each type of discharge in a given clinical setting. Recommendations for treatment are given, and a modification to current criteria for the diagnosis of nonconvulsive seizures is suggested.

Patients with Parkinson's Disease (PD) have a variable response to tolcapone, a catechol-O-methyltransferase (COMT) inhibitor. In addition, a subset of patients develop severe diarrhea as a side effect. Two codominant alleles for the COMT gene exist, coding for low and high activity, resulting in low-, medium-, and high-activity genotypes. This study investigates the relationship between this variation in genotype and clinical effects in patients with PD taking tolcapone. To investigate the relationship between COMT polymorphism and clinical response, 24 patients who completed tolcapone clinical trials provided blood samples for COMT genotype analysis. Change in levodopa dose and United Parkinson Disease Rating Scale (UPDRS) Part III (motor subscale) were analyzed at baseline, at 1-2 weeks, and 6 months after initiation of tolcapone. Genotype analysis was performed on seven patients who had diarrhea as a side effect. There was no significant correlation between genotype and improvement in UPDRS score (p = 0.29) according to a linear models approach that adjusted for the subject's severity of PD, tolcapone dose (either 100 or 200 mg three times daily) and initial differences in baseline scores. No significant difference was seen in change in daily levodopa intake and genotype. There was also no relation between diarrhea and COMT genotype. These results indicate that, in the treatment of Parkinson's disease, COMT genotype is not a major contributor to the clinical response to tolcapone.