Results of a Survey on Diagnostic Procedures and Treatment Choices for Neuromyelitis Optica Spectrum Disorder in Korea: Beyond the Context of Current Clinical Guidelines

Background@#and Purpose Neuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease of the central nervous system (CNS). We investigated the medical behaviors of experts in Korea when they are diagnosing and treating NMOSD. @*Methods@#An anonymous questionnaire on the diagnosis and treatment of NMOSD was distributed to experts in CNS demyelinating diseases. @*Results@#Most respondents used the 2015 diagnostic criteria for NMOSD and applied a cerebrospinal fluid examination, magnetic resonance imaging (MRI) of the brain and spine, and anti-aquaporin-4 antibody testing to all suspected cases of NMOSD. All respondents prescribed steroid pulse therapy as an first-line therapy in the acute phase of NMOSD, and 67% prescribed azathioprine for maintenance therapy in NMOSD. However, details regarding monitoring, the tapering period of oral steroids, second-line therapy use in refractory cases, management during pregnancy, and schedule of follow-up MRI differed according to the circumstances of individual patients. We analyzed the differences in response rates between two groups of respondents according to the annual number of NMOSD patients that they treated.The group that had been treating ≥10 NMOSD patients annually preferred rituximab more often as the second-line therapy (p=0.011) and had more experience with rituximab treatment (p=0.015) compared with the group that had been treating <10 NMOSD patients. @*Conclusions@#This study has revealed that NMOSD experts in Korea principally follow the available treatment guidelines. However, the differences in specific clinical practices applied to uncertain cases that have been revealed will need to be investigated further in order to formulate suitable recommendations.

Shape Analysis of the Subcortical Nuclei in Amyotrophic Lateral Sclerosis without Cognitive Impairment

Background@#and Purpose: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that mainly affects the pyramidal motor system. However, recent studies have suggested that degeneration of the extramotor system plays a role in the disability experienced by patients with ALS. We investigated the local shape changes and mean volumes of the subcortical nuclei in sporadic ALS patients with preserved cognition. @*Methods@#The participants comprised 32 patients with ALS and 43 age- and sex-matched healthy controls. Three-dimensional T1-weighted structural images were acquired. Surfacebased vertex analysis was performed with fully automated segmentation of both amygdalae, hippocampi, caudate nuclei, nuclei accumbens, putamina, pallida, and thalami, and the brainstem. The scalar distances from the mean surfaces of the individual subcortical nuclei were compared between groups, and correlations of the local shape distances with initial Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALS-FRS-R) scores and the delta FRS-R and with the disease duration were analyzed. @*Results@#ALS patients showed regional shape contractions on the lateral surfaces of both pallida, the lateroposterior surface of the right putamen, and the anterior basal surface of the right accumbens. Delta FRS-R scores were negatively correlated with local shape distances in the right hippocampus and the putamina. However, the initial ALS-FRS-R score and disease duration were not correlated with local shape distances. @*Conclusions@#Subcortical gray-matter structures are involved in the neurodegenerative process of ALS before cognitive impairment becomes evident.

Heart-Rate-Based Machine-Learning Algorithms for Screening Orthostatic Hypotension

Background@#and Purpose: Many elderly patients are unable to actively stand up by themselves and have contraindications to performing the head-up tilt test (HUTT). We aimed to develop screening algorithms for diagnosing orthostatic hypotension (OH) before performing the HUTT. @*Methods@#This study recruited 663 patients with orthostatic intolerance (78 with and 585 without OH, as confirmed by the HUTT) and compared their clinical characteristics. Univariate and multivariate analyses were performed to investigate potential predictors of an OH diagnosis. Machine-learning algorithms were applied to determine whether the accuracy of OH prediction could be used for screening OH without performing the HUTT. @*Results@#Differences between expiration and inspiration (E-I differences), expiration:inspiration ratios (E:I ratios), and Valsalva ratios were smaller in patients with OH than in those without OH. The univariate analysis showed that increased age and baseline systolic blood pressure (BP) as well as decreased E-I difference, E:I ratio, and Valsalva ratio were correlated with OH. In the multivariate analysis, increased baseline systolic BP and decreased Valsalva ratio were found to be independent predictors of OH. Using those variables as input features, the classification accuracies of the support vector machine, k-nearest neighbors, and random forest methods were 84.4%, 84.4%, and 90.6%, respectively. @*Conclusions@#We have identified clinical parameters that are strongly associated with OH. Machine-learning analysis using those parameters was highly accurate in differentiating OH from non-OH patients. These parameters could be useful screening factors for OH in patients who are unable to perform the HUTT.

Prevalence and Incidence of Neuromyelitis Optica Spectrum Disorderin Korea: Population Based Study

Background@#Although neuromyelitis optica spectrum disorder (NMOSD) is known to be a rare disease, its prevalence and incidence have not yet been studied in Korea. We performed a population-based study to examine the prevalence and incidence of NMOSD in Korea using data from the Korean National Health Insurance (NHI) claims database. @*Methods@#Data from 2013 to 2017 were obtained, with a washout period set as 2013 and 2014. The prevalence and incidence of NMOSD in 2016 and 2017 were calculated using population census data. Subjects were divided into 5 groups at 15-year intervals, depending on the age at which the diagnostic code was entered. The relative risk (RR) for each age group was compared with the oldest (≥ 60 years) age group. @*Results@#The overall prevalence was estimated to be 3.36 and 3.56 per 100,000 individuals, with an incidence of 0.41 and 0.65 per 100,000 individuals-year in 2016 and 2017, respectively. The mean age was 43.08 (standard deviation, 14.56) years, and the ratio of male to females was 1:4.7. The incidence was higher in female individuals aged between 30 and 59 years (RR, 2.8–3.05; P < 0.05). @*Conclusion@#Nationwide prevalence of NMOSD in Korea was 3.36 and 3.56/100,000 and its incidence was 0.41 and 0.65/100,000-year in 2016 and 2017 respectively.

Tissue-Clearing Technique and Cutaneous Nerve Biopsies: Quantification of the Intraepidermal Nerve-Fiber Density Using Active Clarity Technique-Pressure Related Efficient and Stable Transfer of Macromolecules Into Organs

BACKGROUND AND PURPOSE: Cutaneous nerve biopsies based on two-dimensional analysis have been regarded as a creditable assessment tool for diagnosing peripheral neuropathies. However, advancements in methodological imaging are required for the analysis of intact structures of peripheral nerve fibers. A tissue-clearing and labeling technique facilitates three-dimensional imaging of internal structures in unsectioned, whole biological tissues without excessive time or labor costs. We sought to establish whether a tissue-clearing and labeling technique could be used for the diagnostic evaluation of peripheral neuropathies. METHODS: Five healthy individuals and four patients with small-fiber neuropathy (SFN) and postherpetic neuralgia (PHN) were prospectively enrolled. The conventional methods of indirect immunofluorescence (IF) and bright-field immunohistochemistry (IHC) were adopted in addition to the tissue-clearing and labeling method called active clarity technique-pressure related efficient and stable transfer of macromolecules into organs (ACT-PRESTO) to quantify the intraepidermal nerve-fiber density (IENFD). RESULTS: The mean IENFD values obtained by IF, bright-field IHC, and ACT-PRESTO in the healthy control group were 6.54, 6.44, and 90.19 fibers/mm², respectively; the corresponding values in the patients with SFN were 1.99, 2.32, and 48.12 fibers/mm², respectively, and 3.06, 2.87, and 47.21 fibers/mm², respectively, in the patients with PHN. CONCLUSIONS: This study has shown that a tissue-clearing method provided not only rapid and highly reproducible three-dimensional images of cutaneous nerve fibers but also yielded reliable quantitative IENFD data. Quantification of the IENFD using a tissue-clearing and labeling technique is a promising way to improve conventional cutaneous nerve biopsies.

Anatomical Courses of Lateral Antebrachial and Medial Antebrachial Cutaneous Nerves: A Cadaveric Study

No abstract available.

Patterns of Orthostatic Blood Pressure Changes in Patients with Orthostatic Hypotension

BACKGROUND AND PURPOSE: The objective of this study was to determine the patterns of blood pressure (BP) changes during the head-up tilt (HUT) test, particularly in terms of its clinical significance for patients with orthostatic hypotension (OH). METHODS: OH was divided into four categories based on systolic BP changes occurring within the first 10 minutes of the HUT test: sustained orthostatic hypotension (SOH), progressive orthostatic hypotension (POH), orthostatic hypotension with partial recovery (OHPR), and transient orthostatic hypotension (TOH). RESULTS: In total, 151 patients were analyzed: 65 with SOH, 38 with POH, 21 with OHPR, and 27 with TOH. POH patients exhibited the greatest reduction in systolic BP after HUT and were also the most likely to develop symptoms requiring early termination of the HUT test (42.1%, p < 0.001). Additionally, SOH patients exhibited smaller heart-rate variation with deep breathing values (p=0.003) and Valsalva ratios (p=0.022) compared to POH patients. The sweat volume was greatest in OHPR patients. CONCLUSIONS: Clinical characteristics, including the findings of autonomic function tests, differed between the OH patient groups. This might reflect differences in the underlying pathophysiologic mechanisms. Determining the patterns of BP changes during the HUT test may facilitate the development of effective management strategies in patients with OH.

Current Clinical Applications of Diffusion-Tensor Imaging in Neurological Disorders

Diffusion-tensor imaging (DTI) is a noninvasive medical imaging tool used to investigate the structure of white matter. The signal contrast in DTI is generated by differences in the Brownian motion of the water molecules in brain tissue. Postprocessed DTI scalars can be used to evaluate changes in the brain tissue caused by disease, disease progression, and treatment responses, which has led to an enormous amount of interest in DTI in clinical research. This review article provides insights into DTI scalars and the biological background of DTI as a relatively new neuroimaging modality. Further, it summarizes the clinical role of DTI in various disease processes such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's dementia, epilepsy, ischemic stroke, stroke with motor or language impairment, traumatic brain injury, spinal cord injury, and depression. Valuable DTI postprocessing tools for clinical research are also introduced.

Neutralizing Antibodies Against Interferon-Beta in Korean Patients with Multiple Sclerosis

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 < 0.001]. When disease activity was compared between patients with persistent and transient NAb positivity, the difference was unchanged and remained statistically significant [16/20 (80%) vs. 2/10 (20%), p=0.004]. CONCLUSIONS: These results further support that persistent NAb positivity is associated with disease activity in MS patients treated with IFN-β.

The Impacts of Influenza Infection and Vaccination on Exacerbation of Myasthenia Gravis

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℃ 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.

Does Diabetes Mellitus Influence Carpal Tunnel Syndrome?

BACKGROUND AND PURPOSE: Diabetes mellitus (DM) has been proposed as a risk factor for carpal tunnel syndrome (CTS), but this remains controversial. We investigated the association between DM and CTS using both ultrasonography (US) and nerve conduction study (NCS) data. METHODS: We analyzed a prospectively recruited database of neuromuscular US and medical records of subjects who had undergone NCSs and electromyography for symptoms suggestive of CTS. Subjects were assigned to the follow groups: Group I, CTS with DM; Group II, CTS without DM; Group III, no CTS with DM; and Group IV, no CTS without DM. US cross-sectional area (CSA) and NCS measurements at the median nerve (MN) were compared among groups. We used a general linear mixed model to adjust for statistically significant covariates. RESULTS: The 230 participants comprised 22, 83, 19, and 106 in Groups I–IV, respectively. In multivariate analyses, the MN action potential amplitude in females was the only variable that was significantly associated with DM (p<0.001). Groups with DM tended to have a longer latency, smaller amplitude, and lower conduction velocity in the NCSs compared to groups without DM. The measured US CSA values did not differ significantly among the groups. CONCLUSIONS: NCS measurements of the MN tended to differ between DM and non-DM patients regardless of the presence or absence of CTS. However, US did not reveal any statistically significant relationship between CTS and DM.

Application of Near-Infrared Spectroscopy in Neurological Disorders: Especially in Orthostatic Intolerance

Near-infrared spectroscopy (NIRS), a noninvasive optical method, utilizes the characteristic absorption spectra of hemoglobin in the near-infrared range to provide information on cerebral hemodynamic changes in various clinical situations. NIRS monitoring have been used mainly to detect reduced perfusion of the brain during orthostatic stress for three common forms of orthostatic intolerance (OI); orthostatic hypotension, neurally mediated syncope, and postural orthostatic tachycardia syndrome. Autonomic function testing is an important diagnostic test to assess their autonomic nervous systems for patients with symptom of OI. However, these techniques cannot measure dynamic changes in cerebral blood flow. There are many experimentations about study of NIRS to reveal the pathophysiology of patients with OI. Research using NIRS in other neurologic diseases (stroke, epilepsy and migraine) are ongoing. NIRS have been experimentally used in all stages of stroke and may complement the established diagnostic and monitoring tools. NIRS also provide pathophysiological approach during rehabilitation and secondary prevention of stroke. The hemodynamic response to seizure has long been a topic for discussion in association with the neuronal damage resulting from convulsion. One critical issue when unpredictable events are to be detected is how continuous NIRS data are analyzed. Besides, NIRS studies targeting pathophysiological aspects of migraine may contribute to a deeper understanding of mechanisms relating to aura of migraine. NIRS monitoring may play an important role to trend regional hemodynamic distribution of flow in real time and also highlights the pathophysiology and management of not only patients with OI symptoms but also those with various neurologic diseases.

Surfer's Myelopathy Mimicking Infectious Myelitis

No abstract available.

Reversible Corpus Callosal Lesions Associated with the Use of Adalimumab for Ulcerative Colitis

No abstract available.

The Effects of Sleep Apnea and Variables on Cognitive Function and the Mediating Effect of Depression / 수면정신생리

OBJECTIVES: This study aimed to analyze causality among sleep apnea, depression and cognitive function in patients with obstructive sleep apnea. METHODS: We reviewed the medical records of 105 patients with sleep apnea and snoring who underwent overnight polysomnography (PSG). We analyzed various biological data, sleep variables (sleep duration and percentage) and respiratory variables [arousal index (AI), periodic leg movement index (PLM index), snoring Index (SI), mean SpO2, minimum SpO2, apnea-hypopnea index (AHI), and respiratory disturbance index (RDI)]. We also analyzed various data by sleep, cognition, and mood related scales: Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), snoring index by scale (SIS), Montreal Cognitive Assessment-Korean (Moca-K), Mini-mental State Examination-Korean (MMSE-K), clinical dementia rating (CDR), and Beck Depression Inventory (BDI). We analyzed causation among sleep, and respiratory, mood, and cognition related scales in obstructive sleep apnea patients. We analyzed the mediating effects of depression on sleep apnea patient cognition. RESULTS: As Duration N1 increased and Total sleep time (TST) decreased, MOCA-K showed negative causality (p < 0.01). As BDI and supine RDI increased, causality was negatively related to MOCA-K (p < 0.01). As PSQI (p < 0.001) and SIS (p < 0.01) increased and as MMSE-K (p < 0.01) decreased, causality was positively related to BDI. BDI was found to mediate the effect of age on MOCA-K in patients with obstructive sleep apnea. CONCLUSION: Duration N1, total sleep time, BDI, and supine RDI were associated with cognitive function in obstructive sleep apnea patients. Depression measured by BDI partially mediated cognitive decline in obstructive sleep apnea patients.

Suggestions for a standard clinical practice curriculum and learning objectives for physical therapy education in Korea / 보건의료교육평가

No abstract available.

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.

A Rare Manifestation of Hypothyroid Myopathy: Hoffmann's Syndrome

Hypothyroid myopathy is observed frequently and the resolution of the clinical manifestations of myopathy following thyroid hormone replacement is well known. However, a specific subtype of hypothyroid myopathy, Hoffmann's syndrome, characterized by increased muscular mass (pseudohypertrophy), proximal muscle weakness, muscle stiffness and cramps, is rarely reported. Herein, we describe a 34-year-old male who presented with proximal muscle weakness and non-pitting edema of the lower extremities. He initially visited the neurology department where he was suspected of having polymyositis. Additional laboratory evaluation revealed profound autoimmune hypothyroidism and elevated muscle enzymes including creatine kinase. The patient was started on levothyroxine treatment and, subsequently, clinical symptoms and biochemical parameters resolved with the treatment. The present case highlights that hypothyroidism should be considered in the differential diagnosis of musculoskeletal symptoms even in the absence of overt manifestations of hypothyroidism. To our knowledge, this is the first case reported in Korea.

Electromyographicanalysis of prevalence and characteristics of radiculopathy in Parkinson’s disease

Background & Objectives: To determine the prevalence and characteristics of radiculopathy in Parkinson’s disease (PD) patients through electrodiagnostic tests, to assess associated radicular pain characteristics,and to investigate the relationship between pain and other clinical manifestations of PD. Methods: Electrodiagnostic testing including nerve conduction studies and needle electromyographywas performed to investigate comorbid peripheral neuropathy or radiculopathy. All patients were asked to complete aquality of life (QOL) measurement related to pain. Results: Thirty-two (39%) of 82 PD patients had radiculopathy based on electrodiagnostic testing. 46.9% with radiculopathy patients had involvement of multiple roots level. The most commonly involved root was L5 (83.3%). Patients with radiculopathy had longer PD durations (p=0.011) and higher posture-related axial scores on the UPDRS scale (p=0.017).There was a trend for pain in the leg and low back to occur more frequently in PD patients with radiculopathy. QOL is not significantly different according to the presence of radiculopathy in PD. Conclusions: This study demonstrates a high prevalence of radiculopathy, particularly multiple root involvement, and is correlated with pain complaints and with axial motor scores on UPDRS. These findings might be related to increased shear force at the intervertebral disc by axial rigidity and flexed posture in PD along with the duration and severity of PD disease course.

Effects of Total Thyroidectomy and Radioactive Iodine Therapy for Thyroid Cancer Patients on Sleep Apnea and Snoring / 신경정신의학

OBJECTIVES: Some paper claim thyroidectomy decreases snoring and sleep apnea symptoms and the opposite. The aim of this study is to evaluate and compare the effects of sleep apnea and snoring by total thyroidectomy and radioactive iodine (RI) therapy. METHODS: A total of 88 patients who underwent total thyroidectomy and RI therapy for thyroid cancer in the outpatient clinic of the department of surgery of a general hospital were recruited. Interviewers completed their demographic data, past medical history, and data on total thyroidectomy and sleep apnea with snoring, and also preoperative and postoperative Pittsburgh Sleep Quality Index (PSQI), preoperative and postoperative Epworth Sleepiness Scale (ESS), preoperative and postoperative Snoring Index (SI), preoperative and postoperative global life satisfaction (index of well-being) scale, and postoperative Beck Depression Inventory. RESULTS: The Wilcoxon Signed Ranks Test showed PSQI preoperative-postoperative p=0.750, ESS preoperative-postoperative p=0.000, SI preoperative-postoperative p=0.034, life satisfaction preoperative-postoperative p=0.216 (based on negative ranks). CONCLUSION: The above results indicate that snoring and daytime sleepiness increased after total thyroidectomy and RI therapy, suggesting that the patency of upper airway (UA) was reduced or the collapsibility of the UA increased after total thyroidectomy and RI therapy. That is, the above results indicate that sleep apnea and snoring were aggravated after total thyroidectomy and RI therapy.