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Objectives Hearing loss disrupts the balance of auditory-somatosensory inputs in the cochlear nucleus (CN) of the brainstem, which has been suggested to be a mechanism of tinnitus. This disruption results from maladaptive auditory-somatosensory plasticity, which is a form of axonal sprouting. Axonal sprouting is promoted by transforming growth factor (TGF)-β signaling, which can be inhibited by losartan. We investigated whether losartan prevents maladaptive auditory-somatosensory plasticity after hearing loss. Methods The study consisted of two stages: determining the time course of auditory-somatosensory plasticity following hearing loss and preventing auditory-somatosensory plasticity using losartan. In the first stage, rats were randomly divided into two groups: a control group that underwent a sham operation and a deaf group that underwent cochlea ablation on the left side. CNs were harvested 1 and 2 weeks after surgery. In the second stage, rats were randomly divided into either a saline group that underwent cochlear ablation on the left side and received normal saline or a losartan group that underwent cochlear ablation on the left side and received losartan. CNs were harvested 2 weeks after surgery. Hearing was estimated with auditory brainstem responses (ABRs). Western blotting was performed for vesicular glutamate transporter 1 (VGLUT1), reflecting auditory input; vesicular glutamate transporter 2 (VGLUT2), reflecting somatosensory input; growth-associated protein 43 (GAP-43), reflecting axonal sprouting; and p-Smad2/3. Results Baseline ABR thresholds before surgery ranged from 20 to 35 dB sound pressure level. After cochlear ablation, ABR thresholds were higher than 80 dB. In the first experiment, VGLUT2/VGLUT1 ratios did not differ significantly between the control and deaf groups 1 week after surgery. At 2 weeks after surgery, the deaf group had a significantly higher VGLUT2/VGLUT1 ratio compared to the control group. In the second experiment, the losartan group had a significantly lower VGLUT2/VGLUT1 ratio along with significantly lower p-Smad3 and GAP-43 levels compared to the saline group. Conclusion Losartan might prevent axonal sprouting after hearing loss by blocking TGF-β signaling thereby preventing maladaptive auditory-somatosensory plasticity.

Background The Clock Drawing Test (CDT) and Rey–Osterrieth Complex Figure Test (RCFT) are widely used as a part of neuropsychological test batteries to assess cognitive function. Our objective was to confirm the prediction accuracies of the RCFT-copy and CDT for cognitive impairment (CI) using convolutional neural network algorithms as a screening tool. Methods The CDT and RCFT-copy data were obtained from patients aged 60–80 years who had more than 6 years of education. In total, 747 CDT and 980 RCFT-copy figures were utilized. Convolutional neural network algorithms using TensorFlow (ver. 2.3.0) on the Colab cloud platform (www.colab.research.google.com) were used for preprocessing and modeling. We measured the prediction accuracy of each drawing test 10 times using this dataset with the following classes: normal cognition (NC) vs. mildly impaired cognition (MI), NC vs. severely impaired cognition (SI), and NC vs. CI (MI + SI). Results The accuracy of the CDT was better for differentiating MI (CDT, 78.04 ± 2.75; RCFT-copy, not being trained) and SI from NC (CDT, 91.45 ± 0.83; RCFT-copy, 90.27 ± 1.52); however, the RCFT-copy was better at predicting CI (CDT, 77.37 ± 1.77; RCFT, 83.52 ± 1.41). The accuracy for a 3-way classification (NC vs. MI vs. SI) was approximately 71% for both tests; no significant difference was found between them. Conclusions The two drawing tests showed good performance for predicting severe impairment of cognition; however, a drawing test alone is not enough to predict overall CI. There are some limitations to our study: the sample size was small, all the participants did not perform both the CDT and RCFT-copy, and only the copy condition of the RCFT was used. Algorithms involving memory performance and longitudinal changes are worth future exploration. These results may contribute to improved home-based healthcare delivery.

Although the evidence for attentional bias to pain-related information among individuals with chronic pain has been well established, there are a number of inconsistencies in the research that have been observed due to sample characteristics. Therefore, the present study expanded upon previous studies by including patients with a variety of chronic pain conditions and compared a chronic pain patient sample with healthy community sample. We also investigated how pain catastrophizing and other psychological factors in chronic pain patients affected attentional patterns to pain-related information. Forty chronic pain patients from the departments of neurology and rheumatology of an academic medical center hospital and 40 participants without chronic pain from a university that is located in Seoul, South Korea were recruited for the present study. Patients observed pictures of faces displaying pain that were presented simultaneously with faces with neutral expressions, while their eye movements were measured using an eye-tracking system. Independent t-tests were conducted to investigate attentional preferences to pain stimuli between the chronic pain and control groups. No significant attentional differences in pain-neutral pairs were found for both chronic pain and control group. A one-way MANOVA was conducted to examine the role of pain catastrophizing on psychological factors and attentional engagement to pain stimuli. No significant results for the attentional bias to pain stimuli among chronic pain patients may indicate that chronic pain patients who have suffered from chronic pain for a long time and have been treated for their chronic pain in the hospital may interpret pain-related information not as threatening. Clinical implications related to use in pain treatment and future research suggestions are discussed.

Sarcopenia, which refers to the muscle loss that accompanies aging, is a complex neuromuscular disorder with a clinically high prevalence and mortality. Despite many efforts to protect against muscle weakness and muscle atrophy, the incidence of sarcopenia and its related permanent disabilities continue to increase. In this study, we found that treatment with human placental hydrolysate (hPH) significantly increased the viability (approximately 15%) of H2 O2 -stimulated C2C12 cells. Additionally, while H2 O2 -stimulated cells showed irregular morphology, hPH treatment restored their morphology to that of cells cultured under normal conditions. We further showed that hPH treatment effectively inhibited H2 O2 -induced cell death. Reactive oxygen species (ROS) generation and Mstn expression induced by oxidative stress are closely associated with muscular dysfunction followed by atrophy. Exposure of C2C12 cells to H2 O2 induced abundant production of intracellular ROS, mitochondrial superoxide, and mitochondrial dysfunction as well as myostatin expression via nuclear factor-κB (NF-κB) signaling; these effects were attenuated by hPH. Additionally, hPH decreased mitochondria fission-related gene expression (Drp1 and BNIP3) and increased mitochondria biogenesis via the Sirt1/AMPK/PGC-1α pathway and autophagy regulation. In vivo studies revealed that hPH-mediated prevention of atrophy was achieved predominantly through regulation of myostatin and PGC-1α expression and autophagy. Taken together, our findings indicate that hPH is potentially protective against muscle atrophy and oxidative cell death.

Background and purpose Upper respiratory infection (URI), including influenza, may exacerbate the symptoms of myasthenia gravis (MG), which is an autoimmune disease that causes muscle weakness. There is also concern that the influenza vaccine may trigger or worsen autoimmune diseases. The objective of this study was to determine the impacts of influenza infection and vaccination on symptom severity in MG patients. Methods Patients diagnosed with MG were enrolled from 10 university-affiliated hospitals between March and August 2015. Subjects completed a questionnaire at the first routine follow-up visit after enrolling in the study. The patient history was obtained to determine whether a URI had been experienced during the previous winter, if an influenza vaccination had been administered before the previous winter, and whether their MG symptoms were exacerbated during or following either a URI or vaccination. Influenza-like illness (ILI) was defined and differentiated from the common cold as a fever of ≥38°C accompanied by a cough and/or a sore throat. Results Of the 258 enrolled patients [aged 54.1±15.2 years (mean±SD), 112 men, and 185 with generalized MG], 133 (51.6%) had received an influenza vaccination and 121 (46.9%) had experienced a common cold (96 patients) or ILI (25 patients) during the analysis period. MG symptoms were aggravated in 10 (40%) patients after ILI, whereas only 2 (1.5%) experienced aggravation following influenza vaccination. The rate of symptom aggravation was significantly higher in patients experiencing an ILI (10/25, 40%) than in those with the common cold (15/96, 15.6%, p=0.006). Conclusions The results of this study suggest that the potential risk of aggravating autoimmune disease is higher for ILI than for influenza vaccination, which further suggests that influenza vaccination can be offered to patients with MG.

Introduction Several clinical studies using tacrolimus revealed reasonable therapeutic mechanisms and efficacy in patients with myasthenia gravis (MG). However, long-period studies in a large number of patients with MG are limited; therefore, the aim of this study was to investigate the therapeutic efficacies and safety of tacrolimus in patients with MG during a 12-month follow-up period. Methods Tacrolimus was administered to 150 patients with MG who were recruited based on the inclusion criteria. Fifteen medical centers in Korea participated in this study. The efficacy of tacrolimus was assessed using MG composite scales (MGCS) and the prednisolone-sparing effect. And the adverse drug reactions (ADRs) of tacrolimus were monitored in each patient from the beginning of tacrolimus treatment to the end of the follow-up period. Results After starting tacrolimus, the 32 patients were affected by ADRs, and consequentially 134 patients of the enrolled patients were followed up for 12 months. They showed that the mean prednisolone dosage significantly decreased (6.1 ± 7.6 mg/day), compared to that in the baseline (11.3 ± 9.5 mg/day), and MGCS significantly improved after 12 months of tacrolimus treatment, compared to that at the baseline. Conclusions Our study showed that tacrolimus would be an effective immunosuppressant as an initial therapeutic agent in patients with MG; in addition, it showed tolerable safety profiles during the 12-month follow-up evaluation.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an immune related systemic disease that is caused by vasculitis affecting multiple organ systems. It is characterized by asthma, fever, eosinophilia, cardiac problems, renal injury, and peripheral neuropathy. In this report, we describe a patient with EGPA with concurrent cerebral infarction and acute polyneuropathy mimicking a Guillain-Barre syndrome (GBS). A 46-year-old man presented with rapidly progressing gait disturbance, muscular weakness, and tingling sensation in all four limbs. A nerve conduction study revealed sensorimotor polyneuropathy in all four limbs, and a test of the cerebrospinal fluid showed an albumin-cytologic dissociation. In addition, brain magnetic resonance imaging (MRI) using fluid-attenuated inversion recovery and diffusion weighted MRI revealed high signal intensity lesions with gadolinium enhancement on T1-weighted MRI in the right caudate nucleus. After performing laboratory tests, paranasal sinus computed tomography, and a nasal smear, the patient was diagnosed with EGPA and treated with high dose glucocorticoid and oral cyclophosphamide. In conclusion, our findings indicate that a diagnosis of EGPA should be considered when a patient presents with rapidly progressing polyneuropathy mimicking a GBS along with unusual systemic symptoms or brain lesions.

Objectives: We compared validity of 2010 McDonald and newly proposed 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria for dissemination in space (DIS) in predicting the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS). Methods: Between 2006 and 2016, we enrolled 170 patients who had a first clinical event suggestive of multiple sclerosis (MS) from seven referral hospitals in Korea. Patients were classified into two groups based on the main outcome at the last follow-up: CDMS converters, who experienced a second attack, and non-converters. Results: Of 170 patients with mean follow-up duration of 54 months, 51% converted to CDMS. The sensitivity, specificity, accuracy, and positive and negative predictive values of 2010 McDonald criteria were 70.9%, 63.1%, 67.1%, 66.3%, and 67.9%, and those for 2016 MAGNIMS criteria were 88.4%, 46.4%, 67.7%, 62.8%, and 79.6%, respectively. When we excluded 80 patients who underwent disease-modifying therapy before the second clinical event, the specificity increased to 92.3% and 84.6%, but the sensitivity decreased to 58.8% and 82.4% for 2010 McDonald and 2016 MAGNIMS criteria, respectively. Conclusion: 2016 MAGNIMS magnetic resonance imaging (MRI) criteria for DIS showed higher sensitivity but lower specificity than 2010 McDonald criteria in predicting conversion to CDMS in CIS patients.

Amyotrophic lateral sclerosis (ALS), the most common adult onset motor neuron disease, is pathologically characterized by progressive loss of the upper and lower motor neurons. Mutations in the Cu/Zn superoxide dismutase gene (SOD1) account for about 20% of familial ALS cases and a small percentage of sporadic ALS (SALS) cases, and have revealed a validated genotype-phenotype correlation. Herein, we report a p.Gly13Arg mutation in SOD1 exon 1 in a patient with SALS who presented with a rapidly progressive course, predominantly affecting the lower motor neurons. A 48-year-old man presented with progressive weakness and muscle atrophy of the left upper and lower limbs, followed by muscle fasciculation and cramping. The clinical features of the patient were clearly suggestive of ALS, and implied a sporadic form with rapid progression, predominantly affecting the lower motor neurons. Sequencing of the SOD1 gene by PCR revealed a missense mutation of G to C (c.37G>C) in exon 1, and amino acid substitution of glycine by arginine (p.Gly13Arg). This is the first case identifying the p.Gly13Arg mutation of SOD1 in the Korean population, and clinical assessments of this patient revealed a different phenotype compared with other cases.

We investigated the prevalence and mechanisms of neurological deterioration after endovascular thrombectomy. Between January 2011 and October 2017, acute ischemic stroke patients treated by endovascular thrombectomy in a tertiary university hospital were included. Early neurological deterioration (END) was defined as an increase of 2 or more National Institute of Health Stroke Scale (NIHSS) compared to the best neurological status after stroke within 7 days. The END mechanism was categorized into ischemia progression, symptomatic hemorrhage, and brain edema. A total of 125 acute ischemic stroke patients received endovascular thrombectomy. Neurological deterioration was detected in 44 patients, and 38 cases (86.4% of END) occurred within 72 h. The END mechanism included 20 ischemia progression, 16 brain edema and 8 hemorrhagic transformation cases. Multivariable logistic regression analysis revealed that the patients who experienced END were more likely to have poor functional outcome defined as modified Rankin scale 3–6 at 90 days than neurologically stable patients (odds ratio (OR) = 4.06, confidence interval (CI) = 1.39–11.9). The risk factor of END due to ischemia progression was stroke subtype of large artery atherosclerosis (OR = 6.28, CI = 1.79–22.0). Successful recanalization (OR = 0.11, CI = 0.03–0.39) and NIHSS after endovascular thrombectomy (OR = 1.15 per one-point increase, CI = 1.06–1.24) were significantly associated with END due to hemorrhage or brain edema. Neurological deterioration frequently occurs after endovascular thrombectomy, and the risk factors of END differ according to the mechanism of END.

Background The motor and sensory symptoms caused by compressive radial neuropathy are well-known, but the involvement of the autonomic nervous system or the dermatologic symptoms are less well known. We report an unusual case of compressive radial neuropathy with reversible reddish skin color change. Case presentation A 42-year-old man was referred for left wrist drop, finger drop and a tingling sensation over the lateral dorsum of the left hand. Based on clinical information, neurologic examinations and electrophysiologic studies, he was diagnosed with compressive radial neuropathy. In addition, a reddish skin color change was observed at the area of radial sensory distribution. After two weeks of observation without specific treatment, the skin color had recovered along with a marked improvement in weakness and aberrant sensation. Conclusions Compressive radial neuropathy with a reversible reddish skin color change is unusual and is considered to be due to vasomotor dysfunction of the radial autonomic nerve. Compressive radial neuropathy is presented with not only motor and sensory symptoms but also autonomic symptoms; therefore, careful examination and inspection are needed at diagnosis.

Objectives: To evaluate the validity of the revised 2017 McDonald criteria for multiple sclerosis (MS) compared with the 2010 McDonald criteria to predict conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS). Methods: A total of 163 patients from seven referral hospitals in Korea, who experienced a first clinical event suggestive of MS between 2006 and 2017, were enrolled. Patients were stratified into two groups according to outcome at the last visit: CDMS converters who experienced a second clinical event and non-converters. Results: Of the 163 patients with a mean follow-up of 63 months, 60% converted to CDMS. The sensitivity, specificity, positive and negative predictive values and accuracy were, respectively, 88.8%, 43.1%, 70.2%, 71.8% and 70.6% for the 2017 McDonald criteria and 53.1%, 69.2%, 72.2%, 49.5% and 59.5% for the 2010 McDonald criteria. After exclusion of 82 patients who received disease-modifying agents before the second attack, the specificity of the 2017 and 2010 McDonald criteria increased to 85.0% and 95.0%, but sensitivity decreased to 83.6% and 47.5%, respectively. Conclusion: The 2017 McDonald criteria afforded higher sensitivity and accuracy but lower specificity compared with the 2010 McDonald criteria for prediction of conversion to CDMS in Korean CIS patients.

Introduction: Split hand is considered to be a spe- cific feature of amyotrophic lateral sclerosis (ALS). Methods: We evaluated the pattern difference of intrinsic hand muscles of upper limb-onset ALS (UL-ALS), upper limb-onset progressive muscular atrophy (UL-PMA), brachial amyotrophic diplegia (BAD), and Hirayama disease (HD) by measuring objective electrophysiological markers. Results: The abductor digiti minimi (ADM)/abductor pollicis brevis (APB) compound muscle action potential (CMAP) amplitude ratio was significantly higher in UL- ALS than other variants, but a considerable proportion of UL- ALS cases had an amplitude ratio in the range of other var- iants. Absent APB CMAP and abnormally high ADM/APB CMAP amplitude ratio (4) occurred only with UL-ALS. Con- versely, an absent ADM CMAP was identified only in UL-PMA and BAD. Conclusions: The absolute ADM/APB CMAP ampli- tude ratio was not specific for ALS; however, several findings from simple electrophysiological measurements may help pre- dict prognosis in patients with motor neuron diseases and may be early diagnostic markers for ALS. Muscle Nerve 51: 333-337, 2015

Background and Purpose— The aim of this study was to determine the association between 25-hydroxyvitamin D (25(OH)D) and neuroimaging correlates of cerebral small vessel disease. Methods— We identified 759 consecutive patients with acute ischemic stroke or transient ischemic attack. Lacunes, white matter hyperintensity, and cerebral microbleed (CMB) were assessed using MR images. Deep CMB was defined as the presence of CMB in basal ganglia, thalamus, or brain stem. The association between 25(OH)D and small vessel disease was tested using linear and logistic regression analyses. Results— Mean age was 68 (±13) years. Mean level of 25(OH)D was 34.1±17.8 nmol/L. On bivariate analysis, a 25-nmol/L decrease in 25(OH)D was associated with lacunes (regression coefficient, 0.23; 95% confidence interval [CI], 0.02–0.45), severe white matter hyperintensity (odds ratio, 2.05; 95% CI, 1.41–3.08), and deep CMB (odds ratio, 1.28; 95% CI, 1.01–1.63). Also, 25(OH)D deficiency (≤25 nmol/L) was associated with lacunes (regression coefficient, 0.5; 95% CI, 0.04–0.95), severe white matter hyperintensity (odds ratio, 2.74; 95% CI, 1.31–6.45), and deep CMB (odds ratio, 1.68; 95% CI, 1.03–2.78). The association remained significant even after multivariable adjustment and in the subgroup of previously healthy patients. Conclusions— 25(OH)D is inversely associated with lacunes, white matter hyperintensity, and deep CMB. Our findings suggest that 25(OH)D is linked to small vessel disease, and in future trials it should be tested whether 25(OH)D supplementation can prevent small vessel disease.

Background: There are currently few studies regarding late-onset neuromyelitis optica spectrum disorder (LO-NMOSD). Objective: We aimed to describe the characteristic features of patients with LO-NMOSD in Korea. Methods: Anti-aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder (NMOSD) from nine tertiary hospitals were reviewed retrospectively. The patients were divided into two groups based on age of onset: LO-NMOSD (⩾50 years of age at onset) versus early-onset neuromyelitis optica spectrum disorder (EO-NMOSD) (Results: Among a total of 147 patients (125 female; age of onset, 39.4 ± 15.2 years), 45 patients (30.6%) had an age of onset of more than 50 years. Compared to patients with EO-NMOSD, patients with LO-NMOSD had more frequent isolated spinal cord involvement at onset (64.4% vs 37.2%, p = 0.002), less frequent involvement of the optic nerve (40.0% vs 67.7%, p = 0.002), and less frequent brain MRI lesions (31.1% vs 50.0%, p = 0.034). Furthermore, there was a significant positive correlation between age of onset and Expanded Disability Status Scale (EDSS) score at last follow-up ( r = 0.246, p = 0.003). Conclusion: Age of onset could be an important predictor of lesion location and clinical course of patients with NMOSD.

Background: The Expanded Disability Status Scale (EDSS) is the most widely employed ordinal disability scale in multiple sclerosis (MS). However, how far apart the individual EDSS levels are along the disability spectrum has not been formally quantified. Objectives: The objective of this paper is to generate refined disability weights (DWs) for each of the ordinal EDSS levels. Methods: We performed the person trade-off (PTO) procedure to derive DWs of five representative EDSS categories (2, 4, 6, 7 and 9), and DWs of the remaining EDSS categories were assigned by linear interpolation. The modified Delphi process was used to achieve consensus among raters. Results: DWs were 0.021 for EDSS 2, 0.199 for EDSS 4, 0.313 for EDSS 6, 0.617 for EDSS 7, and 0.926 for EDSS 9. Panel members achieved a high degree of consensus for each DW, as indicated by low coefficients of variation. Conclusions: Our DWs confirmed that EDSS is an ordinal scale with highly variable intervals. The availability of DW for each EDSS level allows direct comparison of each MS outcome state with other health states and provides a foundation for the estimation of the disability-adjusted life-years lost of individual patients.

Highlights • The robotic surgery is a creative and effective technique; however, the risk of this technique has not been fully documented. • We describe neurological complication of hypoglossal nerve palsy after robotic thyroidectomy. • Hypoglossal nerve palsy is usually presented with tongue deviation, atrophy and dysarthria. • Nerve conduction study (NCS) can be used to confirm the hypoglossal nerve injury., Background Endoscopic surgical techniques with robotic system in the thyroid cancer have been reported to show good results and advantages; however the risk of these techniques has not been fully documented. Presentation of the case We experienced an uncommon complicated case of a 20-year-old woman with a papillary thyroid carcinoma. After the robotic thyroidectomy, she complained of the tongue deviation, speech and swallowing difficulties of hypoglossal nerve palsy. Discussion In this case, a few etiologies could be suggested for the development of hypoglossal nerve palsy. It might be associated with direct stretching or entrapment of hypoglossal nerve during tumor resection; lateral placement of the laryngoscope on the tongue base; the hyperinflation of the laryngeal mask airway; and histological disruption of the intraneural connective tissue and blood circulation. Conclusion Although the robotic surgery is a creative technique and has been known to be safe and effective, the risk of this surgery including traumatic nerve injury should be taken into account before surgery.

We investigated the validity of the 2005 and 2010 McDonald magnetic resonance imaging (MRI) criteria for dissemination in space (DIS) to predict the conversion of clinically definite multiple sclerosis (CDMS) in 94 Korean patients with clinically isolated syndromes (CIS). The sensitivity, specificity, accuracy, positive and negative predictive values of the 2005, 2010 McDonald DIS criteria were comparable to those observed in the Caucasian population. This finding suggests that after careful exclusion of alternative explanations, particularly neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD), both the 2005 and 2010 McDonald DIS criteria are also useful to predict conversion to CDMS in Korean patients with CIS.

This study was performed to investigate the asymmetry of motor unit number estimate (MUNE) and its longitudinal course in patients with amyotrophic lateral sclerosis. A modified statistical MUNE was performed at the hypothenar muscles bilaterally in a total of 135 patients, and 18 of these patients underwent a follow-up study. The degree of asymmetry varied considerably among those patients whose average MUNE of both sides was moderately reduced, whereas it tended to be low in those whose average MUNE was either severely reduced or close to normal. The rate of motor unit loss was also asymmetric, and two distinct patterns were identified. In patients whose MUNE was greater than 30 in both sides (n = 7), the rate of motor unit loss tended to be greater in the initially more affected side compared with the contralateral one, yielding the so-called lead phenomenon. In contrast, the other patients (n = 11) tended to show the opposite pattern of "catch-up," that is, MUNE declined faster in the initially less affected side compared with the contralateral one. This study shows that not only the MUNE but also the rate of motor unit loss are frequently asymmetric in amyotrophic lateral sclerosis patients.

Introduction Lateral spread response is observed in patients with hemifacial spasm (HFS) by eletrically stimulating one branch of the facial nerve activates facial muscles innervated by other branches of the facial nerve by electromyography. Nowadays, LSR has been used to confirm adequacy of microvascular decompression (MVD). The aim of this study was to evaluate the prognostic value of intra- and extra-operative lateral spread response (LSR) in microvascular decompression (MVD) surgeries of hemifacial spasm (HFS). Methods A retrospective review was made of consecutive 25 patients who underwent continuous intraoperative monitoring during MVD. LSR and continuous electromyography were monitored in the frontalis, orbicularis oculi, and mentalis muscles. Extra-operative LSRs were done pre- and postoperatively. The neurological status of each patient was evaluated before and immediately after surgery, on discharge, and at 3 months after surgery. Results Intraoperative neurophysiologic monitorings were successful in all patients. On admission and discharge, extra-operative LSR recordings were done in 23 patients. Twenty-one patients completed a follow- up evaluation. In 17, the intraoperative LSRs disappeared during surgery. In 5, the intraoperative LSRs were absent before incision and remained the same until the end of surgery. In one, the intraoperative LSR were present before incision and persisted despite MVD. For extra-operative LSRs, they disappeared after surgery in 10. LSRs were absent before and after surgery in 7. In 6, LSRs were present before surgery and persisted after MVD. For 5, intraoperative LSRs disappeared during surgery but extra-operative LSRs were persisted despite adequate MVD. In one, intraoperative LSRs were absent before incision and remained during the surgery. But extra-operative LSRs were present before surgery and disappeared after adequate MVD. Statistically, the extra-operative disappearance of LSR was correlated with the HFS relief in 4 days after surgery and the 3-month follow up period. (P = 0.049 and 0.044). However, the intaroperative disapearance of LSR was not. Conclusion In our study, extra-operative LSR monitoring may be more predictive of the surgical outcome compared with intraoperative LSR during the 3-month follow up.

Limb-girdle muscular dystrophies (LGMD) are heterogeneous disorders with autosomal inheritance. Autosomal dominant LGMD mapped to 7q36.3 has been classified as LGMD type 1D (LGMD1D) in the Human Gene Nomenclature Committee Database. LGMD1D is characterized predominantly by limb-girdle weakness and may also show a bulbar symptom in some cases. In the past, the frequency of this disease was uncommon, and this disorder was mainly found in Europe and the United States. However, recently, this disorder has been reported in Asia, including Japan, Korea, and Taiwan. Here, we report on three LGMD1D patients, including one with a novel mutation in DNAJB6, c.298T>A. While two patients complained of limb-girdle weakness, as would be expected, one patient had distal weakness. They had various serum creatine kinase levels. Radiologic findings in one patient showed fatty degeneration and atrophy in the posterior part of distal muscles. Pathologic findings in one of the patients showed rimmed vacuoles. Although LGMD1D is still uncommon in Korea, we discovered three Korean patients with LGMD1D, including one novel mutation in DNAJB6, p.Phe100Ile (c.298T>A).

Background and Purpose Patients treated with interferon-beta (IFN-β) can develop neutralizing antibodies (NAbs) against IFN-β that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeutic response to IFN-β in Korean patients with multiple sclerosis (MS). Methods This was a multicenter study involving 150 MS patients from 9 Korean medical centers who were treated with IFN-β for at least 6 months. Sera that had not been influenced by acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluate the association between persistent positivity for NAbs and disease activity, NAbs were tested at 2 different time points in 75 of the 150 patients. Disease activity was defined as the presence of clinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivity was confirmed. Results NAbs were found in 39 of the 150 (26%) MS patients: 30 of the 85 (35%) who were treated with subcutaneous IFN-β-1b, 9 of the 60 (15%) who were treated with subcutaneous IFN-β-1a, and 0 of the 5 (0%) who were treated with intramuscular IFN-β-1a. Thirty of the 39 patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibited persistent NAb positivity. Disease activity was observed more frequently in patients with persistent NAb positivity than in those with transient positivity or persistent negativity [16/20 (80%) vs. 4/55 (7%), respectively; p

Background We investigated the incidence and risk factors of early neurological worsening according to ischemia progression among acute cerebral infarction patients after intravenous thrombolysis. Methods The medical records of consecutive cerebral infarction patients treated with intravenous thrombolysis from 2 university hospitals were reviewed. Early neurological deterioration (END) was defined as 2 or more National Institutes of Health Stroke Scale aggravations within 24 hours after thrombolysis, and its etiologies were categorized by follow-up imaging into 3 groups: ischemia progression, symptomatic hemorrhage, and brain edema. We compared clinical variables between the group of patients with ischemia progression and the patients without neurological deterioration to derive etiology-specific risk factors. Results A total of 210 patients were included in this study, with 57 (26.2%) patients experiencing neurological deterioration. The prevalence of patients with END due to ischemia progression (27 patients, 12.9%) outnumbered the prevalence of patients with neurological deterioration due to symptomatic hemorrhage (n = 13) or brain edema (n = 15). Compared to the group of patients without END, the patients with ischemia progression were more likely to have a stroke subtype of large-artery atherosclerosis, to be current smokers, and to have less severe initial neurological deficits. Multivariate logistic regression analysis revealed that large-artery atherosclerosis was an independent predictor of END due to ischemia progression (odds ratio = 3.8, confidence interval = 1.6-9.3). Conclusions A major contributor to END within 24 hours after intravenous thrombolysis was ischemia progression, and the stroke subtype of large-artery atherosclerosis predicted ischemia progression.

Background and purpose The prognostic value of contrast accumulation from non-contrast brain computed tomography taken immediately after endovascular reperfusion treatment in acute ischaemic stroke patients to predict symptomatic hemorrhage was studied. Methods Between July 2007 and August 2014, acute anterior circulation ischaemic stroke patients who were treated by intra-arterial thrombolysis or thrombectomy were included. Contrast accumulation was defined as a high attenuation area from non-contrast brain computed tomography immediately taken after endovascular reperfusion treatment, and patients were categorized into three groups according to the presence and location of contrast: (i) negative, (ii) cortical involvement and (iii) non-cortical involvement. The rates of symptomatic hemorrhage after 24 h and functional outcome at discharge were compared between patients with and without cortical involvement. Results Of 64 patients who were treated by endovascular intervention, contrast accumulation was detected in 56, including 33 patients with cortical involvement and 23 patients without cortical involvement. The cortical involvement pattern was more frequently associated with symptomatic hemorrhage (13 vs. 1 patient, P = 0.003) and with grave outcome at discharge with modified Rankin Scale 5 or 6 (14 vs. 4, P = 0.048) than the non-cortical involvement group. Multivariate logistic regression analysis including initial collateral status and occlusion site disclosed that cortical involvement pattern independently predicted symptomatic hemorrhage after endovascular treatment (odds ratio 19.0, confidence interval 1.6–227.6, P = 0.020). Conclusion Our study provides evidence that the cortical involvement of contrast accumulation is associated with symptomatic hemorrhage after endovascular reperfusion treatment.

Objectives Early identification of suboptimal responders to multiple sclerosis (MS) treatment is critical for optimizing therapeutic decisions. The Rio score (RS) and modified Rio score (MRS) were developed to discriminate the responses to interferon-beta (IFNB) treatment in MS patients. This study was performed to evaluate the utility of RS and MRS in daily clinical practice in Korea. Methods This was a real-world setting, multicenter, retrospective study of MS patients treated with IFNB from 10 hospitals in Korea. We investigated whether the RS and MRS at the early stage of IFNB therapy could predict treatment responses over 3 years. Suboptimal treatment responses at 3 years were defined as the presence of clinical relapse and/or EDSS progression and/or patients who had been treated with INFB for at least for 1 year and therapy was switched due to perceived treatment failure during the 2 years of follow-up. Results Seventy patients (50 females and 20 males) were enrolled; 92% (12/13) of patients with high RS and 86% (12/14) of patients with high MRS (score 2 or 3) were suboptimal responders, whereas 93% (53/57) of patients with low RS and 93% (52/56) patients with low MRS (score 0 or 1) showed optimal responses. New active lesions on MRI with clinical relapse in high RS and MRS were the most common combination in suboptimal responders. Conclusions We confirmed that RS and MRS at 6–15 months of IFNB therapy were useful for predicting poor responders over 3 years.

We validated the use of medial temporal volume measurements via the automated volumetric method of Individual Brain Atlases using Statistical Parametric Mapping (IBASPM) in screening for Alzheimer's disease (AD). We also determined the optimal cut-off values for hippocampal volumes. This study included T1-weighted MRI of 89 patients with AD and 33 normal controls. To determine age-specific cut-off values we grouped subjects according to age. The regional structural volumes of each group were measured using individual atlas-based volumetry with IBASPM. The normalized value of left hippocampal volume in patients with AD was significantly lower than that of normal controls in all age groups. The area under the curve values of the left hippocampus in receiver operating characteristic curves were also the largest in the medial temporal lobe, indicating that left hippocampal volume is the most useful factor in AD screening. The optimal cut-off values of the left hippocampus for diagnosing AD were 4.06 in the 60-64 year age group, 4.05 in the 65-69 group, 4.07 in the 70-74 group and 3.63 in patients older than 75. Measurements of left hippocampal volume using the IBASPM may be useful for AD screening in clinical practice, and could provide a useful biomarker for AD.

Background: Multiple sclerosis (MS) in Asia is thought to have different clinical characteristics from MS in Western countries; however, previous studies in Asia were performed without properly differentiating neuromyelitis optica (NMO) from MS. Objectives: To evaluate the clinical characteristics of MS in Korea after careful exclusion of potential explanations other than MS, particularly NMO spectrum disorder (NMOSD). Methods: This study is a retrospective review of consecutive MS patients attending five referral hospitals in Korea. All patients’ MS diagnoses were re-evaluated. Results: Of the 105 patients, 70 were female and 35 were male. The mean age of onset was 30.4 years and the mean disease duration was 5.4 years. On initial magnetic resonance imaging (MRI), 58% and 64% fulfilled the criteria for dissemination in space for the 2005 and 2010 McDonald criteria, respectively. Spinal cord lesions were observed in 78% of patients, primarily present as multiple small lesions with a mean length of 0.9 vertebral segments. The median time from disease onset to an Expanded Disability Status Scale 6 was 20 years. Conclusions: After careful exclusion of NMOSD, we found that the clinical pattern of MS in Korea does not fundamentally differ from that seen in Western countries.

Objective: To investigate the influence of pregnancy on patients with neuromyelitis optica spectrum disorder (NMOSD). Methods: A total of 190 women with NMOSD were enrolled from 7 referral hospitals in 4 countries. We reviewed medical records and used a structured questionnaire to investigate gravidity, parity, and the number of relapses during the 2 years before pregnancy, during each trimester of pregnancy, during the first and second trimesters after delivery, and for 6 months thereafter. The annualized relapse rate (ARR) was calculated for each period. Results: Of the 190 women with NMOSD, 40 patients experienced 54 informative pregnancies, and all of them were seropositive for aquaporin-4 antibody. Fourteen patients developed the first symptoms of NMOSD either during the pregnancy (3 patients) or within a year after delivery or abortion (8 and 3 patients, respectively). Twenty-six patients experienced 40 pregnancies after the onset of NMOSD (26 deliveries and 14 abortions [1 spontaneous and 13 elective]). There was one preterm delivery with birth defects and no stillbirths. The ARR during pregnancy did not differ from that before pregnancy, but it increased significantly during the first and second trimesters after delivery (5.3 and 3.7 times, respectively). Moreover, 77% of the deliveries were associated with postpartum relapses. Conclusion: The significantly increased relapse rate and numerous cases of NMOSD onset after pregnancy suggest that delivery adversely affects the course of NMOSD. Prospective studies are needed to confirm our findings.

White matter hyperintensity (WMH) is commonly detected in patients with Alzheimer's disease (AD), but its role in cortical impairment is unclear. This study investigated the effects of WMH on gray matter (GM) volume in patients with AD. We consecutively enrolled 84 patients with AD and 35 normal controls, who underwent brain MRI and were then classified according to WMH grade, based on a combination of deep white matter hyperintensity (DWMH) and periventricular white matter hyperintensity (PVWMH). The volume changes in GM were observed using voxel-based morphometry. It was found that global GM volume decreased with increasing WMH. Regional atrophies were in the dorsolateral frontal lobes, orbitofrontal gyri and insula (false discovery rate [FDR], p0.01). After controlling for PVWMH, DWMH affected cortical atrophy in the frontal lobe, insula and precuneus (FDR, p0.05), but PVWMH did not. Thus, WMH in AD is associated with GM volume reduction, especially in the frontal lobe, and DWMH is independently related to cortical atrophy.

Purpose Transcranial Doppler sonography (TCD) is commonly used for the diagnosis of middle cerebral artery (MCA) stenosis. However, TCD indices to predict distal MCA (M2) stenosis have not yet been established. We compared TCD and magnetic resonance angiography (MRA) to validate a new index for the diagnosis of M2 stenosis. Methods Consecutive patients who underwent TCD and MRA were included. Based on MRA, M2 stenosis was defined as >50% narrowing beyond the bifurcation area. TCD index of the M2/M1 ratio was defined as the ratio between the mean flow velocity (MFV) obtained at a depth of 30–44 mm (M2) and a depth of 45–65 mm (M1). Sensitivity and specificity of the M2/M1 ratio were calculated from the receiver operating characteristic curve. The diagnostic yield of elevated MFV (>80 cm/s) and asymmetry index of >30% for M2 stenosis were also investigated. Results Among the consecutive patients, 105 with M2 stenosis were compared with 123 without MCA stenosis. The M2/M1 ratio was significantly higher in the M2 stenosis group (1.10 versus 0.86, p < 0.001). Sensitivity and specificity for M2 stenosis were most satisfying when the M2/M1 ratio of 0.97 was adopted as the cutoff value. Diagnostic yield of the M2/M1 ratio was better than MFV or asymmetry index. Conclusions The M2/M1 ratio may be a highly specific parameter for assessing M2 stenosis with TCD. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound 38:420–425, 2010

Longitudinally extensive transverse myelitis (LETM) is a syndrome with extensive spinal cord lesions spanning three or more vertebral segments on spinal cord MRI. Although many reports have indicated that LETM is a characteristic feature of neuoromyelitis optica (NMO) in Western countries, the clinical characteristics and risk for development of NMO in Korean patients with LETM is not clear. We retrospectively investigated the clinical, laboratory, radiological features, and prognosis of Korean patients with a first-ever episode of idiopathic LETM. Patients were classified into four subgroups, depending on their clinical course: monophasic LETM, recurrent LETM, NMO, and classic multiple sclerosis (MS). We compared various clinical, laboratory, and radiological features between groups. Of 20 patients with first-ever LETM, 15 (75%) were men, and 13 (65%) experienced clinical relapse over a mean follow-up period of 58 months. Three of 20 patients (two with NMO, one with recurrent myelitis) were seropositive for anti-AQP4 antibodies. The predominance of men in the monophasic and recurrent LETM groups compared to the NMO group was remarkable. In conclusion, Korean patients with LETM are predominantly male and have low seropositivity for anti-AQP4 antibody, which distinguishes them from LETM patients in Western countries. Patients with LETM and seropositivity for anti-AQP4 antibody have a high risk of relapse. The male predominance and the relatively low seropositive rate for anti-AQP4 suggests that rather than being a limited form of NMO, recurrent LETM is a new clinical entity in Koreans.

Enteroviral CNS infection is common and its clinical course is usually benign. In immunocompromised patients, however, it can cause meningoencephalitis, presenting with altered mentality and seizure. We describe a previously healthy female patient with enteroviral meningoencephalitis who showed rapidly progressive aphasia. Examination of her cerebrospinal fluid (CSF) showed pleocytosis with lymphocyte dominance, elevated protein, and normal glucose, findings compatible with viral encephalitis. Fluid-attenuated inversion recovery (FLAIR) brain MRI showed hyperintensity in the left frontal and parietal cortices. Enterovirus in the CSF was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) of the CSF. Although her neurological deficits had progressed to global aphasia, conservative management resulted in complete improvement within 3 months. This case provides unusual clinical manifestations and imaging findings in enteroviral encephalitis.

Objective: Development of an electrophysiological biomarker of corticospinal tract (CST) degeneration for application as an electrodiagnostic test in Amyotrophic Lateral Sclerosis (ALS). ALS is a sporadic, progressive and fatal neurodegenerative disorder, which is characterised by loss of motoneurones within the brainstem and spinal cord, and degeneration of corticospinal tract (CST) neurons. While electrodiagnostic techniques for identifying motoneurone degeneration in ALS are well established, those for CST disease are not. We now have evidence from experiments in macaque monkeys that 15 30Hz intermuscular coherence (IMC), which is a measure of coupling between two EMG signals in the 15 30Hz frequency range, can be used to assess the integrity of the CST. We have therefore begun investigating the utility of IMC as an electrodiagnostic test in ALS patients. Methods: IMC was measured in 23 patients with ALS, including 10 patients with primary lateral sclerosis (PLS), the pure upper motor neurone variant of ALS in which there is only CST degeneration, and 6 patients with progressive muscular atrophy (PMA) the pure lower motor neurone variant of ALS. We also performed similar measures on healthy age-matched controls. Results: Significant 15 30Hz IMC was found in all patients with PMA, all age-matched controls (n = 15) and all non age-matched controls (n = 20) tested to date. However, none of the patients with PLS had significant 15 30Hz IMC. Conclusions: 15 30Hz IMC is dependent upon an intact CST and appears to be an inexpensive, simple and robust measure of CST degeneration in ALS. We are now investigating the diagnostic sensitivity and specificity of 15 30Hz IMC prospectively in a group of patients with clinically suspected/possible ALS, in which a significant proportion are likely to have an ALS mimic syndrome.

Hemorrhagic complications associated with aspirin use occur primarily at skin or gastrointestinal sites but can occasionally occur in the central nervous system. In particular, spontaneous spinal epidural hemorrhage (SSEH) associated with aspirin is very rare. We report a case of low-dose (100 mg daily) aspirin-related SSEH that was successfully treated with medical management. Our case indicates that low-dose aspirin could induce SSEH and that conservative treatment with close observation and repeated imaging studies should be considered in cases with neurological improvement or mild deficits.

Lumbar spinal stenosis (LSS) is a common spinal disease in the elderly. The cardinal symptom of LSS is neurogenic claudication, but not all patients present with such typical symptom. The clinical symptoms are often confused with symptoms of peripheral neuropathy, musculo-skeletal disease and other medical conditions in elderly patients. In particular, LSS presenting with rapid progression of leg weakness must be distinguished from other combined diseases. We report a case of rapid progressive leg weakness in a patient with LSS and iatrogenic adrenal insufficiency that was induced by obscure health supplement.

We report a case of 54-yr-old woman who presented with 4-extremities weakness and sensory changes, followed by cervical spinal cord lesion in magnetic resonance imaging. Based on the suspicion of spinal tumor, spinal cord biopsy was performed, and the histology revealed multinucleated giant cells, lymphocytes and aggregated histiocytes within granulomatous inflammation, consistent with non-caseating granuloma seen in sarcoidosis. The patient was treated with corticosteroid, immunosuppressant and thalidomide for years. Our case indicates that diagnosis of spinal cord sarcoidosis is challenging and may require histological examination, and high-dose corticosteroid and immunosuppressant will be a good choice in the treatment of spinal cord sarcoidosis, and the thalidomide has to be debated in the spinal cord sarcoidosis.

Background Multifocal motor neuropathy (MMN) is an immune-mediated disorder that is characterized by slowly progressive and asymmetrical weakness, but its pathophysiological mechanism is uncertain. The hypothesis that MMN is an immunological disease has been supported by the proven therapeutic effects of intravenous immunoglobulin and the detection of antiganglioside antibodies in MMN patients. The coexistence of MMN with other immune diseases has been rarely reported. Case Report A 37-year-old woman visited our hospital complaining of weakness in both hands. The clinical manifestations coincided well with MMN: predominantly distal upper-limb weakness, asymmetric involvement, a progressive course, absence of sensory symptoms, absence of pyramidal signs, and sparing of the cranial muscles. The electrophysiological findings also supported a diagnosis of MMN, with motor nerve conduction block in the median, ulnar, and radial nerves, without sensory nerve involvement. The patient was simultaneously diagnosed as having Hashimoto's thyroiditis, which is a well-known immune-mediated disease. Conclusions The concurrence of MMN and Hashimoto's thyroiditis in our patient is significant for understanding the immunological characteristics of the two diseases.