Hyunmi Choi

ELECTROGRAPHIC SEIZURES AND PERIODIC DISCHARGES AFTER INTRACEREBRAL HEMORRHAGE

Objective: To determine the frequency and significance of electrographic seizures and other EEG findings in patients with intracerebral hemorrhage (ICH). Methods: We reviewed 102 consecutive patients with ICH who underwent continuous electroencephalographic monitoring (cEEG). Demographic, clinical, radiographic, and cEEG findings were recorded. Using multivariate logistic regression analysis, we determined factors associated with 1) electrographic seizures, 2) periodic epileptiform discharges (PEDs), and 3) poor outcome (death, vegetative or minimally conscious state) at hospital discharge. Results: Seizures occurred in 31% (n = 32) of patients with ICH, prior to cEEG in 19 patients. Eighteen percent (n = 18) of patients had electrographic seizures; only one of these patients also had clinical seizures while on cEEG. After controlling for demographic and clinical predictors, only an increase in ICH volume of 30% or more between admission and 24-hour follow-up CT scan was associated with electrographic seizures (33% vs 15%; OR 9.5, 95% CI 1.7 to 53.8). PEDs were less frequently seen in those with hemorrhages located at least 1 mm from the cortex (8% vs 29%; OR 0.2, 95% CI 0.1 to 0.7). PEDs were independently associated with poor outcome (65% vs 17%; OR 7.6, 95% CI 2.1 to 27.3). In patients with electrographic seizures, the first seizure was detected within the first hour of cEEG monitoring in 56% and within 48 hours in 94%. Conclusions: Seizures occurred in one third of patients with intracerebral hemorrhage (ICH) and over half were purely electrographic. Electrographic seizures were associated with expanding hemorrhages, and periodic discharges with cortical ICH and poor outcome. Further research is needed to determine if treating or preventing seizures or PEDs might lead to improved outcome after ICH. GLOSSARY: BIPLEDs = bilateral independent PLEDs; cEEG = continuous EEG monitoring; CLUES = clinically unrecognized electrographic seizures; EVD = external ventricular drain; IRDA = frontal intermittent rhythmic delta activity; GCS = Glasgow Coma Score; GOS = Glasgow Outcome Scale; GPDs = generalized periodic discharges; ICH = intracerebral hemorrhage; ICP = intracranial pressure; ICU = intensive care unit; IVH = intraventricular hemorrhage; NICU = neuroICU; PEDs = periodic epileptiform discharges; PLEDs = periodic lateralized epileptiform discharges; SAH = subarachnoid hemorrhage; SDH = subdural hematomas; SE = status epilepticus; SIRPIDS = stimulus-induced rhythmic, periodic, or ictal discharges.

Epilepsy surgery for pharmacoresistant temporal lobe epilepsy: a decision analysis.

CONTEXT Patients with pharmacoresistant epilepsy have increased mortality compared with the general population, but patients with pharmacoresistant temporal lobe epilepsy who meet criteria for surgery and who become seizure-free after anterior temporal lobe resection have reduced excess mortality vs those with persistent seizures. OBJECTIVE To quantify the potential survival benefit of anterior temporal lobe resection for patients with pharmacoresistant temporal lobe epilepsy vs continued medical management. DESIGN Monte Carlo simulation model that incorporates possible surgical complications and seizure status, with 10,000 runs. The model was populated with health-related quality-of-life data obtained directly from patients and data from the medical literature. Insufficient data were available to assess gamma-knife radiosurgery or vagal nerve stimulation. MAIN OUTCOME MEASURES Life expectancy and quality-adjusted life expectancy. RESULTS Compared with medical management, anterior temporal lobe resection for a 35-year-old patient with an epileptogenic zone identified in the anterior temporal lobe would increase survival by 5.0 years (95% CI, 2.1-9.2) with surgery preferred in 100% of the simulations. Anterior temporal lobe resection would increase quality-adjusted life expectancy by 7.5 quality-adjusted life-years (95%, CI, -0.8 to 17.4) with surgery preferred in 96.5% of the simulations, primarily due to increased years spent without disabling seizures, thereby reducing seizure-related excess mortality and improving quality of life. The results were robust to sensitivity analyses. CONCLUSION The decision analysis model suggests that on average anterior temporal lobe resection should provide substantial gains in life expectancy and quality-adjusted life expectancy for surgically eligible patients with pharmacoresistant temporal lobe epilepsy compared with medical management.

Seizure remission and relapse in adults with intractable epilepsy: A cohort study

Purpose: To investigate the cumulative probabilities of ≥12 month seizure remission and seizure relapse following remission, and to test the associations of clinical characteristics with these two study end points in a prevalence cohort of intractable adult epilepsy patients during medical management.

Review of lamotrigine and its clinical applications in epilepsy

Lamotrigine is an anti-epileptic agent with broad efficacy. Lamotrigine works at voltage-sensitive sodium channels, thereby stabilising the neuronal membrane and inhibiting the release of excitatory neurotransmitters such as glutamate and aspartate. Early preclinical animal studies indicate its broad-spectrum efficacy, which was later confirmed in clinical trials. Multiple randomised, placebo-controlled and comparative trials demonstrate its efficacy against partial and secondarily generalised seizures. Open-label trials show its efficacy against generalised seizures, especially absence seizures of childhood absence epilepsy and generalised seizures of juvenile myoclonic epilepsy. Lamotrigine has a wide clinical dose range and possesses favourable pharmacokinetic properties. It has a good tolerability and safety profile, which enhance compliance. Its small risk of serious skin rash should be weighed against its potential benefits when choosing lamotrigine on an individual basis. Lamotrigine is an excellent therapeutic option in epilepsy.

Seizure remission in adults with long-standing intractable epilepsy: An extended follow-up

Recent studies have provided much needed data on the probability of seizure remission among adults with chronic intractable epilepsy treated medically. Here we provide an extended follow-up to our earlier study in order to provide a more comprehensive picture of long-term prognosis in this patient population during medical treatment. The prevalence cohort was followed for two outcomes-complete seizure remission for ≥ 12 months and subsequent seizure relapse among those attaining a seizure remission. The study outcomes were estimated using Kaplan-Meier analysis. We found that the probability of attaining a ≥ 12 months of complete seizure freedom to be approximately 3-4% per year through 8 years of follow-up. By year 5 since the start of seizure remission, the cumulative probability of seizure relapse was 81%, although only half of the patients with seizure relapse went on to experience their previous seizure frequency.

Evaluation of duration of epilepsy prior to temporal lobe epilepsy surgery during the past two decades

We examined whether duration of epilepsy prior to temporal lobe resection has decreased over the years as a result of increasing body of evidence in the literature showing the benefits of anterior temporal resection. We stratified the 213 patients, who had their first temporal lobe resection at our center between 1996 and 2007 into three groups in order to detect any trends in duration of epilepsy: group A (surgery between 1996 and 1999); group B (surgery between 2000 and 2003); group C (surgery between 2004 and 2007). No difference in mean duration of epilepsy was detected between the three groups (p=0.54). The mean duration in epilepsy prior to temporal lobe resection has persisted at greater than 20 years during the past two decades.

A Randomized, Double-Blind, Placebo-Controlled Trial of Donepezil to Improve Memory in Epilepsy

Summary:  Purpose: To determine whether an acetylcholinesterase inhibitor, such as donepezil, would improve memory or other cognitive/psychological functions in epilepsy patients with subjective memory complaints.

Classification of partial seizure symptoms in genetic studies of the epilepsies

Objectives: To develop standardized definitions for classification of partial seizure symptoms for use in genetic research on the epilepsies, and evaluate inter-rater reliability of classifications based on these definitions. Methods: The authors developed the Partial Seizure Symptom Definitions (PSSD), which include standardized definitions of 41 partial seizure symptoms within the sensory, autonomic, aphasic, psychic, and motor categories. Based on these definitions, two epileptologists independently classified partial seizures in 75 individuals from 34 families selected because one person had ictal auditory symptoms or aphasia. The data used for classification consisted of standardized diagnostic interviews with subjects and family informants, and medical records obtained from treating neurologists. Agreement was assessed by kappa. Results: Agreement between the two neurologists using the PSSD was “substantial” or “almost perfect” for most symptom categories. Conclusions: Use of standardized definitions for classification of partial seizure symptoms such as those in the Partial Seizure Symptom Definitions should improve reliability and accuracy in future genetic studies of the epilepsies.

Rates and predictors of patient-reported cognitive side effects of antiepileptic drugs: An extended follow-up

PURPOSE Impact of adverse effects of antiepileptic medications (AEDs) such as cognitive side effects (CSEs) on quality of life can be significant. Here we provide an extended follow-up to our earlier study to investigate the predictors of cognitive side effects (CSEs) and relative frequency of CSEs among all commonly used AEDs. METHODS In this retrospective study, medical records of 2860 adult outpatients with epilepsy seen at our center over a 12-year period who had taken one or more AEDs were examined. RESULTS Of 2860 patients, 15% had intolerable CSEs attributed to at least one AED. On multiple logistic regression analysis, independent predictors of intolerable CSEs were lack of intellectual disability and polytherapy. In polytherapy, we found that intolerable CSEs were most commonly seen with topiramate (22.8% of 281 patients), significantly more than with almost all other AEDs. This was true in monotherapy as well, with significantly more intolerable CSEs occurring with topiramate (18.5% of 54 patients) than with gabapentin, carbamazepine, lamotrigine, and levetiracetam. AEDs with consistently low rates of ICSEs included gabapentin, pregabalin, lamotrigine, levetiracetam and carbamazepine. CONCLUSION These data can help facilitate selection of AEDs.

Cosmetic side effects of antiepileptic drugs in adults with epilepsy

OBJECTIVE Cosmetic side effects (CSEs) such as weight gain and alopecia are common, undesirable effects associated with several AEDs. The objective of the study was to compare the CSE profiles in a large specialty practice-based sample of patients taking both older and newer AEDs. METHODS As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 1903 adult patients (≥16years of age) newly started on an AED. Cosmetic side effects were determined by patient or physician report in the medical record and included acne, gingival hyperplasia, hair loss, hirsutism, and weight gain. We compared the overall rate of CSEs and intolerable CSEs (ICSEs-CSEs that led to dosage reduction or discontinuation) between different AEDs in both monotherapy and polytherapy. RESULTS Overall, CSEs occurred in 110/1903 (5.8%) patients and led to intolerability in 70/1903 (3.7%) patients. Weight gain was the most commonly reported CSE (68/1903, 3.6%) and led to intolerability in 63 (3.3%) patients. Alopecia was the second most common patient-reported CSE (36/1903, 1.9%) and was intolerable in 33/1903 (1.7%) patients. Risk factors for CSEs included female sex (7.0% vs. 4.3% in males; p<0.05) and any prior CSE (37% vs. 2.9% in patients without prior CSE; p<0.001). Significantly more CSEs were attributed to valproic acid (59/270; 21.9%; p<0.001) and pregabalin (14/143; 9.8%; p<0.001) than to all other AEDs. Significantly less CSEs were attributed to levetiracetam (7/524; 1.3%; p=0.002). Weight gain was most frequently associated with valproic acid (35/270; 13.0%; p<0.001) and pregabalin (12/143; 8.4%; p<0.001). Hair loss was most commonly reported among patients taking valproic acid (24/270; 8.9%; p<0.001). Finally, gingival hyperplasia was most commonly reported in patients taking phenytoin (10/404; 2.5%; p<0.001). Cosmetic side effects leading to dosage change or discontinuation occurred most frequently with pregabalin and valproic acid compared with all other AEDs (13.3 and 5.6% vs. 2.3%; p<0.001). For patients who had been on an AED in monotherapy (n=677), CSEs and ICSEs were still more likely to be attributed to valproic acid (30.2% and 17.1%, respectively) than to any other AED (both p<0.001). SIGNIFICANCE Weight gain and alopecia were the most common patient-reported CSEs in this study, and weight gain was the most likely cosmetic side effect to result in dosage adjustment or medication discontinuation. Particular attention should be paid to pregabalin, phenytoin, and valproic acid when considering cosmetic side effects. Female patients and patients who have had prior CSE(s) to AED(s) were more likely to report CSEs. Knowledge of specific CSE rates for each AED found in this study may be useful in clinical practice.