Practical Drug Treatment Recommendations on the Drug Refractory Epilepsy Patients: 2021 Clinical Guideline Subcommittee for Epilepsy in the Korean Neurological Association

One third of the overall epilepsy population are estimated to be a drug refractory epilepsy (DRE), defined as the patients who failed to control seizure reduction, even tried two or more appropriate antiepileptic drugs (AEDs) trials. Those people need additional AEDs trials or other treatment options (resective surgery, neuromoulation, etc.). Here, we, clinical guideline committee of the Korean Neurological Association (KNA) introduce the recommendations of AEDs treatments including not only old and new AEDs currently available in Korea but also AEDs planned to be launched in the new future for DRE patients with literature review to help efficient decision of the clinician. The authors reviewed literatures and assessed efficacy and tolerability on 12 currently available and four newly introduced/or planned AEDs applied to DRE patients, published from November 2015 to July 2021. Brivaracetam, eslicarbazepine, canabidiol and cenobamate are the four AEDs that are newly introduced or planned to be launched soon. The reviewed articles are publications after November 2015, 2018 American Association of Neurology guideline, new AEDs which were introduced or planned to be launched as of 2021. All AEDs are classified based on the therapeutic rating scheme, generating recommendations. Overall 173 papers have been reviewed and analyzed for recommendation rationales. KNA introduce additional add-on treatment or conversional monotherapy guidelines on the drug refractory focal and generalized epilepsy. We hope these guidelines or recommendations to help clinical decision for the treatment of drug refractory epilepsy patients

Patterns of Cerebrospinal Fluid Biomarkers and Amyloid Positron Emission Tomography in a Patient with Cerebral Amyloid Angiopathy-Related Inflammation

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a distinct subset of cerebral amyloid angiopathy characterized by the auto-inflammatory response to amyloid-laden small arteries of cerebral cortex and leptomeninges. Clinical features include cognitive-behavioral change, headache, focal neurologic deficits and seizure. Because anti-inflammatory treatments can rapidly relieve neurologic symptoms, early diagnosis is critical. Herein, we report a CAA-RI case with distinct laboratory findings of a decreased cerebrospinal fluid amyloid beta 1-42 level and relatively reduced florbetaben uptake in the focal inflammatory lesion during the acute phase of CAA-RI.

Patterns of Cerebrospinal Fluid Biomarkers and Amyloid Positron Emission Tomography in a Patient with Cerebral Amyloid Angiopathy-Related Inflammation

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a distinct subset of cerebral amyloid angiopathy characterized by the auto-inflammatory response to amyloid-laden small arteries of cerebral cortex and leptomeninges. Clinical features include cognitive-behavioral change, headache, focal neurologic deficits and seizure. Because anti-inflammatory treatments can rapidly relieve neurologic symptoms, early diagnosis is critical. Herein, we report a CAA-RI case with distinct laboratory findings of a decreased cerebrospinal fluid amyloid beta 1-42 level and relatively reduced florbetaben uptake in the focal inflammatory lesion during the acute phase of CAA-RI.

Epilepsy and Mortality

Epilepsy is associated with an increased risk of premature death. Epilepsy-related premature mortality imposes a significant burden on public health. This review aims to update the previous assessments of mortality among people with epilepsy and to identify associated factors, causes of death, and preventable causes of death in epilepsy patients. We also reviewed the mortality of epilepsy patients who had undergone epilepsy surgery. Finally, we suggest a further direction of studies about the mortality of people with epilepsy.

A Genome-Wide Association Study Identifies UTRN Gene Polymorphism for Restless Legs Syndrome in a Korean Population

OBJECTIVE: Restless legs syndrome (RLS) is a highly heritable and common neurological sensorimotor disease disturbing sleep. The objective of study was to investigate significant gene for RLS by performing GWA and replication study in a Korean population. METHODS: We performed a GWA study for RLS symptom group (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We subsequently performed a replication study in RLS and normal controls (227 RLS and 229 controls) to confirm the present GWA study findings as well as previous GWA study results. RESULTS: In the initial GWA study of RLS, we observed an association of rs11645604 (OR=1.531, p=1.18×10−6) in MPHOSPH6 on chromosome 16q23.3, rs1918752 (OR=0.6582, p=1.93×10−6) and rs9390170 (OR=0.6778, p=7.67×10−6) in UTRN on chromosome 6q24. From the replication samples, we found rs9390170 in UTRN (p=0.036) and rs3923809 and rs9296249 in BTBD9 (p=0.045, p=0.046, respectively) were significantly associated with RLS. Moreover, we found the haplotype polymorphisms of rs9357271, rs3923809, and rs9296249 (overall p=5.69×10−18) in BTBD9 was associated with RLS. CONCLUSION: From our sequential GWA and replication study, we could hypothesize rs9390170 polymorphism in UTRN is a novel genetic marker for susceptibility to RLS. Regarding with utrophin, which is encoded by UTRN, is preferentially expressed in the neuromuscular synapse and myotendinous junctions, we speculate that utrophin is involved in RLS, particularly related to the neuromuscular aspects.

Early Electrodiagnostic Features of Upper Extremity Sensory Nerves Can Differentiate Axonal Guillain-Barré Syndrome from Acute Inflammatory Demyelinating Polyneuropathy

BACKGROUND AND PURPOSE: Serial nerve conduction studies (NCSs) are recommended for differentiating axonal and demyelinating Guillain-Barré syndrome (GBS), but this approach is not suitable for early diagnoses. This study was designed to identify possible NCS parameters for differentiating GBS subtypes. METHODS: We retrospectively reviewed the medical records of 70 patients with GBS who underwent NCS within 10 days of symptom onset. Patients with axonal GBS and acute inflammatory demyelinating polyneuropathy (AIDP) were selected based on clinical characteristics and serial NCSs. An antiganglioside antibody study was used to increase the diagnostic certainty. RESULTS: The amplitudes of median and ulnar nerve sensory nerve action potentials (SNAPs) were significantly smaller in the AIDP group than in the axonal-GBS group. Classification and regression-tree analysis revealed that the distal ulnar sensory nerve SNAP amplitude was the best predictor of axonal GBS. CONCLUSIONS: Early upper extremity sensory NCS findings are helpful in differentiating axonal-GBS patients with antiganglioside antibodies from AIDP patients.

Modeling of Recovery Profiles in Mentally Disabled and Intact Patients after Sevoflurane Anesthesia; A Pharmacodynamic Analysis

PURPOSE: Mentally disabled patients show different recovery profiles compared to normal patients after general anesthesia. However, the relationship of dose-recovery profiles of mentally disabled patients has never been compared to that of normal patients. MATERIALS AND METHODS: Twenty patients (10 mentally disabled patients and 10 mentally intact patients) scheduled to dental surgery under general anesthesia was recruited. Sevoflurane was administered to maintain anesthesia during dental treatment. At the end of the surgery, sevoflurane was discontinued. End-tidal sevoflurane and recovery of consciousness (ROC) were recorded after sevoflurane discontinuation. The pharmacodynamic relation between the probability of ROC and end-tidal sevoflurane concentration was analyzed using NONMEM software (version VII). RESULTS: End-tidal sevoflurane concentration associated with 50% probability of ROC (C50) and gamma value were lower in the mentally disabled patients (C50=0.37 vol %, gamma=16.5 in mentally intact patients, C50=0.19 vol %, gamma=4.58 in mentally disabled patients). Mentality was a significant covariate of C50 for ROC and gamma value to pharmacodynamic model. CONCLUSION: A sigmoid Emanx model explains the pharmacodynamic relationship between end-tidal sevoflurane concentration and ROC. Mentally disabled patients may recover slower from anesthesia at lower sevoflurane concentration at ROC an compared to normal patients.

Erratum: Reduced Frontal P3a Amplitude in Migraine Patients during the Pain-Free Period

The author wishes to apologize for incorrectly displaying the references.

Reduced Frontal P3a Amplitude in Migraine Patients during the Pain-Free Period

BACKGROUND AND PURPOSE: Neuropsychological and neuroimaging studies both suggest that frontal lobe dysfunction is present in migraineurs. Since P3a abnormalities manifest in other diseases associated with attention problems, such as attention deficit hyperactivity disorder, we hypothesized that migraine patients have P3a abnormalities, particularly in the frontal region. METHODS: Event-related potentials were measured using a passive auditory oddball paradigm in 16 female migraineurs (aged 22.9+/-2.0 years, mean+/-SD) during the interictal period and in 16 age-matched healthy females (22.6+/-2.0 years). The amplitudes and latencies were analyzed independently using repeated-measures analysis of variance. Nonparametric statistical testing using a cluster-level randomization method was performed to localize the abnormalities. RESULTS: The mean P3a amplitude at frontal areas during the third trials was significantly lower in migraineurs (1.06 microV) than in controls (1.69 microV, p=0.026). P3a amplitudes were negatively correlated with the duration of the migraine history (r=-0.618, p=0.014). Cluster-based nonparametric statistical analysis showed that the amplitudes over left frontal areas were significantly lower in migraine patients than in controls. CONCLUSIONS: A reduced P3a amplitude of migraineurs reflects attentional deficits and frontal dysfunction. The negative correlation between P3a amplitude and the duration of the migraine history suggests that attentional deficits and frontal dysfunction are either the cause or the result of headache.

Pitfalls in Using Electrophysiological Studies to Diagnose Neuromuscular Disorders

Electrodiagnostic testing is used widely for the full characterization of neuromuscular disorders and for providing unique information on the processes underlying the pathology of peripheral nerves and muscles. However, such testing should be considered as an extension of anamnesis and physical examination, not as pathognomonic of a specific disease entity. There are many pitfalls that could lead to erroneous interpretation of electrophysiological study results when the studies are not performed properly or if they are performed in the presence of anatomical aberrations. The diagnostic reliability of electrodiagnostic studies can be improved and the associated pitfalls overcome if the physician is familiar with all of those possible pitfalls. In this article we discuss the most common and important pitfalls associated with electrodiagnostic medicine.

Unilateral Restless Legs Syndrome

No abstract available.

The effect of weather and air pollution on the prevalence of headaches

Background: Some epidemiological studies have indicated that weather and air pollution can cause adverse health conditions and that these effects can exhibit regional variation. The prevalence of headache is so high and it is a common cause of morbidity. Therefore, this study evaluated whether weather and air pollution were associated with the prevalence of headaches. Methods: A symmetric bidirectional case-crossover design was applied, using conditional logistic regression models to determine the association between headaches and weather and air pollution. From January 2006 to August 2007, a total of 245 patients with headaches were recruited. Headache subtypes were classifi ed as migraine, tension-type headaches, and others. Meteorological data (average temperature and relative humidity) and values related to air pollutants (CO, NO2 , O3 , SO2 , and particulate matter with an aerodynamic diameter of less than 10 μm) were obtained. Results: Higher average temperatures were associated with the total number of headaches (hazard ratio 1.124-1.130; P<0.001). With regard to headache subtype, O3 seems to provoke headaches, especially those related to tension and those listed as other headache varieties. Conversely, other pollutants, especially CO and SO2 , showed the opposite association. Conclusions: These fi ndings indicated that temperature and some air pollutants are able to affect headaches, suggesting that weather and air pollution levels seem to have an effect on the risk of headache.

Dentatorubropallidoluysian Atrophy (DRPLA) With Comitant Esotropia

The possibility of a central origin should be considered for late-onset concomitant esotropia. Concomitant esotropia has been reported to occur with spinocerebellar ataxia types 1, 2, and 3, but not with other degenerative cerebellar ataxia disorders. We report on a 28-year-old woman with ataxia in whom a detailed ophthalmologic examination revealed concomitant esotropia. She was subsequently diagnosed with dentatorubropallidoluysian atrophy (DRPLA). We suggest that the presence of concomitant esotropia could be used to differentiate DRPLA from other hereditary ataxias.

Neuromyelitis Optica With Positive Anti-Ro and Anti-La Antibodies

No abstract available.