Yong-Won Cho

A case of isolated nodulus infarction presenting as a vestibular neuritis

We reported a patient with cerebellar infarction who presented with purely isolated vertigo, ipsilesional spontaneous nystagmus, and contralesional axial lateropulsion without usual symptoms or signs of cerebellar dysfunction. An MRI of the brain showed a small left cerebellar infarct selectively involving the nodulus. A pure vestibular syndrome in our patient may be explained by ipsilateral involvement of nodulo-vestibular inhibitory projection to vestibular nucleus. Clinicians should be aware of the possibility of a nodulus infarction in patient with acute vestibular syndrome, even if the pattern of nystagmus and lateropulsion is typical of a vestibular neuritis.

Marital status of people with epilepsy in Korea

A multicentre face-to-face interview was conducted to identify factors contributing to the marital status of people with epilepsy (PWE) in Korea. The marriage rate of PWEs was only 80% and the divorce rate was more than double that in the general population. Among the single subjects, 34% replied that they were unmarried because of epilepsy, and 76% of divorced PWEs replied that epilepsy was the cause of the divorce. The factors affecting the single and divorced status in PWEs included gender, an earlier onset of seizure and seizure onset before marriage. Not informing the spouse of the disease before marriage for fear of discrimination was not related to disadvantage in marriage negotiation or to divorce. Social stigmatization of epilepsy continues and impacts on the marital status of PWEs in Korea. However, there is no correlation between the perceived and the enacted stigmas of epilepsy.

Bilateral infarcts in the territory of the superior cerebellar artery: Clinical presentation, presumed cause, and outcome

BACKGROUNDS AND PURPOSEnThe aim of this study was to document the clinical presentation, vascular topographic patterns, stroke mechanism, and outcome of bilateral infarcts in the territory of the superior cerebellar artery (SCA) based on data collected from a prospective acute stroke registry.nnnMETHODSnWe studied the clinical and radiological features of 11 patients with bilateral infarctions in the territory of the SCA diagnosed by brain MRI.nnnRESULTSnBilateral SCA infarcts represented 23.4% (11/47) of all SCA territory infarction. Bilateral SCA infarcts mostly associated with brainstem (n = 5), cerebral (n = 5), or non-SCA cerebellar lesions (n = 4). The most common clinical presentation at onset was sudden fall with axial lateropulsion and dysarthria (n = 6). In five patients with a coexisting infarct(s) in the brainstem, limb weakness and/or mental change were prominent and often masked the signs of cerebellar dysfunction. Six patients showed no stenosis or occlusion in the vertebrobasilar system on brain MRA. Five had an obvious cardiac source of emboli. Eight patients showed favorable outcomes with complete recovery or minimal disability, but three patients with additional extensive brainstem infarcts died within 1 week.nnnCONCLUSIONSnBilateral SCA territory infarcts show variable clinical, vascular topographic, and prognostic features. They usually result from cardiac emboli.

Evidence for epistatic interactions in antiepileptic drug resistance

To investigate the epistatic interactions involved in antiepileptic drug (AED) resistance, 26 coding single-nucleotide polymorphisms (SNPs) were selected from 16 candidate genes. A total of 200 patients with drug-resistant localization-related epilepsy and 200 patients with drug-responsive localization-related epilepsy were genotyped individually for the SNPs. Rather than using the traditional parametric statistical method, a new statistical method, multifactor dimensionality reduction (MDR), was used to determine whether gene–gene interactions increase the risk of AED resistance. The MDR method indicated that a combination of four SNPs (rs12658835 and rs35166395 from GABRA1, rs2228622 from EAAT3 and rs2304725 from GAT3) was the best model for predicting susceptibility to AED resistance with a statistically significant testing accuracy of 0.625 (P<0.001) and cross-validation consistency of 10/10. This best model had an odds ratio of 3.68 with a significant 95% confidence interval of 2.32–5.85 (P<0.0001). Our results may provide meaningful information on the mechanism underlying AED resistance and, to the best of our knowledge, this is the first report of evidence for gene–gene interactions underlying AED resistance.

Autosomal dominant nocturnal frontal lobe epilepsy and mild memory impairment associated with CHRNB2 mutation I312M in the neuronal nicotinic acetylcholine receptor

Certain paroxysmal nocturnal behaviors have been established as features of nocturnal frontal lobe epilepsy (NFLE). Despite insight into its genetics, the majority of patients with NFLE are not linked to a known mutation and clinical diagnosis remains a challenge. We describe a family presenting with stereotyped nocturnal arousals from non-rapid eye movement sleep, bilateral hand posturing, and pelvic thrusting in the mother, but subtle motor activity in the daughter, and minimal or no epileptiform EEG discharges. Despite normal IQ, there were moderate and severe verbal memory deficits in the mother and daughter, respectively. Genetic testing revealed the CHRNB2 mutation I312M in transmembrane region 3 (M3) of the neuronal nicotinic acetylcholine receptor. Phenotypic similarities in unrelated families suggest the determining role of this mutation in NFLE, whereas different inter- and intrafamilial cognitive profiles point to other factors. The absence of clear motor features of NFLE in the daughter emphasizes the shortcomings of current clinical criteria and the potential for genetic testing to further guide clinical diagnostic criteria.

Afterdischarges during cortical stimulation at different frequencies and intensities

PURPOSEnThe occurrence of unwanted afterdischarges (ADs) impedes cortical stimulation for mapping purposes. We investigated the safety of several stimulation paradigms.nnnMETHODSnWe compared the incidence of ADs and behavioral responses of two stimulation frequencies (50 and 100 Hz), at two intensities (1 and 0.2 ms pulse widths).nnnRESULTSnStimulation with 100 Hz was more likely to cause ADs than 50 Hz, and stimulation using 1 ms pulse width was more likely to cause ADs than 0.2 ms.nnnCONCLUSIONSnStimulation using 50 Hz frequency with a pulse width of 0.2 ms might be safer during cortical mapping.

Autosomal dominant nocturnal frontal lobe epilepsy: a genotypic comparative study of Japanese and Korean families carrying the CHRNA4 Ser284Leu mutation

Autosomal dominant nocturnal frontal lobe epilepsy is a familial partial epilepsy syndrome and the first human idiopathic epilepsy known to be related to specific gene defects. Clinically available molecular genetic testing reveals mutations in three genes, CHRNA4, CHRNB2 and CHRNA2. Mutations in CHRNA4 have been found in families from different countries; the Ser280Phe in an Australian, Spanish, Norwegian and Scottish families, and the Ser284Leu in a Japanese, Korean, Polish and Lebanese families. Clear evidence for founder effect was not reported among them, including a haplotype study carried out on the Australian and Norwegian families. Japanese and Koreans, because of their geographical closeness and historical interactions, show greater genetic similarities than do the populations of other countries where the mutation is found. Haplotype analysis in the two previously reported families showed, however, independent occurrence of the Ser284Leu mutation. The affected nucleotide was highly conserved and associated with a CpG hypermutable site, while other CHRNA4 mutations were not in mutation hot spots. Association with a CpG site accounts for independent occurrence of the Ser284Leu mutation.

The Severity and Pattern of Autonomic Dysfunction in Idiopathic Rapid Eye Movement Sleep Behavior Disorder

Autonomic dysfunction in idiopathic rapid eye movement sleep behavior disorder patients has not yet been quantified. The aim of this study was to characterize dysautonomia in patients with idiopathic rapid eye movement sleep behavior disorder using the Composite Autonomic Severity Score, which is a validated instrument for the quantitation of autonomic failure.

Association of a synonymous GAT3 polymorphism with antiepileptic drug pharmacoresistance

It would be likely that the genetic variants of the GTA3 gene encoding GAT-3, an astrocytic GABA transporter, may alter gamma-aminobutyric acid (GABA) neurotransmission in the synaptic cleft in the epileptic brain and cause antiepileptic drugs (AEDs) pharmacoresistance. A candidate gene association analysis with fine mapping was performed to dissect the genetic contributions of GAT3 to AEDs pharmacoresistance. Two independent case sample sets were recruited (Samples 1 and 2), and each set was divided into two groups (drug-resistant and drug-responsive) according to the treatment outcomes with AEDs. Sample1 (n=400) was used for the initial exploratory stage of the study and sample 2 (n=435) was used for confirmation of the genetic association in the replication stage of the study. A GAT3 polymorphism (GAT3 c.1572 C>T, rs2272400) was nominally associated with AEDs pharmacoresistance (PCC vs PCT/TT=0.012, Pallelic=0.01). The odds ratio (OR) for AED pharmacoresistance was 1.6 (95% confidence interval (CI), 1.11–2.24; P=0.01) in the additive models of inheritance. The statistical significance remained after we adjusted for a confounding factor, the etiology of epilepsy, at 0.012 (adjusted OR: 1.73, 95% CI: 1.13–2.67) and used Bonferronis correction for multiple comparisons at 0.048. Importantly, the positive association of c.1572 T was reproduced in the replication stage (Pallelic=0.037, joint P-value of the replication=0.001). The results suggest that GAT3 c.1572T may be one of the contributing factors with a modest effect on AEDs pharmacoresistance in the epileptic brain, shed light on a better understanding of the underlying mechanisms and serve as an impetus for new avenues of treatment for AEDs pharmacoresistance.

Clinical characterization of unknown/cryptogenic status epilepticus suspected as encephalitis: A multicenter cohort study

Autoimmune and unknown/cryptogenic encephalitis have been increasingly noted in the inflammatory etiology of new-onset status epilepticus (SE). We aimed to investigate clinical characteristics and the potential role of immunotherapy in encephalitis-related adult SE through our multicenter prospective SE registry. Among the 274 patients with SE, 35 (12.8%) patients demonstrated an inflammatory etiology and 19 out of 35 (54.3%) patients demonstrated unknown/cryptogenic cause. Patients with autoimmune and unknown/cryptogenic encephalitis shared similar clinical features. In unknown/cryptogenic encephalitis, the proportion of favorable outcomes (mRS 0-3) showed a different propensity at 3-6months after discharge between patients receiving active immunotherapy and not receiving any immunotherapy, although it was not statistically significant (at admission 28.6% vs 20%, p=0.603; at discharge 57.1% vs 60%, p=0.570; at 3-6months after discharge 90% vs 60%, p=0.214 in patients treated with active immunotherapy or without immunotherapy, respectively). Extensive autoantibody screening should be carried out and empirical immunotherapy may be potentially helpful even in patients without antibodies, although longer term and multi-national studies may be necessary to make a stronger recommendation.