SCN1A variations and response to multiple antiepileptic drugs.

In the current study, we have used the haplotype-tagging single-nucleotide polymorphisms (SNPs) to determine associations between genetic variants in SCN1A and treatment response in 519 Caucasian patients with known response status for epilepsy treated with antiepileptic drugs (AEDs) with sodium channel blocking effects. Nine SNPs within SCN1A were genotyped in this cohort. The only association observed was for rs10188577. A greater proportion of drug-resistant patients were heterozygous compared with drug responsive patients (48.3% vs 35.4%, P=0.014). After correction for potential confounding factors, the association for rs10188577 was only marginally significant (P=0.049). In light of our findings, it seems unlikely that rs10188577 could be a major determinant of response to AEDs. However, looking at the influence of rs10188577 on the expressed quantitative trait association patterns within the immediate vicinity of SCN1A, we found significant associations with neighbouring sodium channel genes, SCN7A and SCN9A (P<0.025), which warrants further studies.

Validating a script concordance test for assessing neurological localization and emergencies.

BACKGROUND AND PURPOSE: Clinical judgment is the ability to weigh clinical information and make decisions under conditions of uncertainty. Although neurological localization (NL) and neurological emergencies (NE) present such uncertainties, no validated method is reported to assess these decision-making skills. A script concordance test (SCT) was designed and validated to assess clinical judgment in NL and NE. METHODS: Our SCT comprised 14 clinical scenarios (53 questions). Candidates picked the response they considered the best for the questions in each scenario. Undergraduates and internal medicine residents completed the SCT; their responses were scored against the scoring key derived from an expert panel of accredited neurologists. Scores were expressed as a percentage of the maximum score. RESULTS: Mean total scores for undergraduates (n = 52), residents (n = 37) and experts (n = 15) were 61.0 ± 0.9, 68.3 ± 1.1 and 76.6 ± 1.1 (mean ± standard error of the mean, P < 0.001). Mean scores for undergraduates, residents and experts were 59.3 ± 1.1, 66.4 ± 1.4 and 76.1 ± 1.8 (P < 0.001) for NL, and 62.9 ± 1.3, 70.4 ± 1.3 and 77.2 ± 1.6 (P < 0.001) for NE. Senior residents scored higher than junior residents (postgraduate years 2-5 versus postgraduate year 1, 69.7 ± 1.4 vs. 65.3 ± 1.1, P = 0.035). The higher scores with increasing clinical experience supports the construct validity of the SCT. The SCT showed acceptable reliability (G coefficient 0.74 ± 0.05). CONCLUSIONS: Our SCT is validated to reliably assess NL and NE in undergraduate and postgraduate learners; it is generalizable and feasible. It has potential as a valuable adjunct assessment tool for clinical judgment. Future plans to design SCTs to evaluate other topics in clinical neurology, as a multi-center study, are under way.

Spinocerebellar ataxia type 2 with focal epilepsy--an unusual association.

INTRODUCTION: The spinocerebellar ataxias are a rare group of inherited neurodegenerative disorders. Epilepsy has not previously been associated with spinocerebellar ataxia type 2 (SCA2). CLINICAL PICTURE: We describe a family with 3 affected members who had typical phenotypic and MRI features of SCA2. Two had focal epilepsy with complex partial seizures and epileptiform discharges on electroencephalography. Trinucleotide expansions in the pathological range were found in the SCA2 gene, confirming SCA2. Sequencing of the expanded SCA2 gene did not reveal any new mutations that could account for epilepsy. TREATMENT AND OUTCOME: The focal epilepsy was well-controlled with carbamazepine. CONCLUSION: We hypothesise that the new feature of focal epilepsy is due to co-existence of a separate unlinked epilepsy susceptibility gene with the expanded SCA2 gene. Under this oligogenic model, both genes must be present, and co-inheritance of this susceptibility gene with the expanded SCA2 gene causes a complex interaction which triggers epilepsy.

Clinical risk factors for non-convulsive status epilepticus during emergent electroencephalogram.

PURPOSE: Emergent electroencephalograms (EmEEG) are performed to exclude non-convulsive status epilepticus (NCSE) but are resource-intensive. Prior studies have identified a seizure or seizures in the acute setting preceding the EmEEG request as a risk factor of NCSE but few other consistent clinical risk factors have been identified. We aimed to identify clinical risk factors for NCSE in EmEEGs METHODS: We conducted a retrospective analysis of consecutive patients who underwent EmEEG to exclude NCSE over a 20-month period. One blinded investigator extracted clinical information from patient case records using a standardized form. Patients were grouped using EmEEG results into those with and without NCSE. We analyzed differences between these two groups. RESULTS: A total of 2333 EEGs were performed over the study period, 215 (9.3%) were EmEEGs ordered to exclude NCSE. 21 patients (9.8%) of the 215 patients were found to have NCSE. Three independent clinical risk factors for NCSE were identified--seizure(s) in the acute setting, ocular movements (nystagmus and/or gaze deviation) and ongoing CNS infection. The presence of seizure(s) in the acute setting showed the highest adjusted odds ratio (OR=8.8, 95% CI 2.0-39.4, p=0.005). In addition, prevalence of NCSE increased as more clinical risk factors were present. CONCLUSION: Seizures in the acute setting, ocular movements and ongoing CNS infection are associated with NCSE. By using these risk factors at the bedside, clinicians can prioritize patients for EmEEG, recognizing that risk of NCSE increases as more clinical risk factors are present.

Failure to confirm association of a polymorphism in ABCB1 with multidrug-resistant epilepsy.

Alteration of ATP-binding cassette subfamily B member 1 transporter (ABCB1) can plausibly cause drug-resistant epilepsy as it influences brain penetration of drugs. The CC genotype at the ABCB1 C3435T polymorphism was reported to be associated with multidrug resistance. A replication study in 401 drug-resistant and 208 drug-responsive subjects with epilepsy showed no significant association between the CC genotype and drug-resistant epilepsy. The authors suggest the initial association may have arisen by chance.