Clinical and Radiological Features of Korean Patients With Anti-HMGCR Myopathy

Background@#and Purpose To understand the characteristics of Korean patients with anti-3-hydroxy-3-methylglutaryl-coenxyme A reductase (HMGCR) myopathy, we measured antiHMGCR antibodies and analyzed the clinical, radiological, and pathological features of patients with anti-HMGCR myopathy. @*Methods@#We measured titers of anti-HMGCR antibodies in the sera of 99 patients with inflammatory myopathy, 36 patients with genetic myopathy, and 63 healthy subjects using an enzyme-linked immunosorbent assay. We tested 16 myositis-specific autoantibodies (MSAs) in all patients with anti-HMGCR myopathy. @*Results@#Positivity for the anti-HMGCR antibody was observed in 17 (4 males and 13 females) of 99 patients with inflammatory myopathy. The median age at symptom onset was 60 years.Ten (59%) of the patients with anti-HMGCR positivity had taken statins. The titer of antiHMGCR antibodies was significantly higher in the statin-naïve group (median=230 U/mL, interquartile range=170–443 U/mL) than in the statin-exposed group (median=178 U/mL, interquartile range=105–210 U/mL, p=0.045). The most common symptom was proximal muscle weakness in 15 patients (88%), followed by myalgia in 9 (53%), neck weakness in 4 (24%), dysphagia in 3 (18%), and skin lesions in 2 (12%). The median titer of anti-HMGCR antibody was 202 U/mL. We found eight different MSAs in nine (53%) patients. The median disease duration from symptom onset to diagnosis was significantly shorter in the MSA-positive group than in the MSA-negative group (p=0.027). @*Conclusions@#Our study was the first to measure anti-HMGCR antibodies in inflammatory myopathy. It has provided new findings, including the suggestion of the coexistence of other MSAs in Korean patients.

Characteristics of Diverse Verbal Pain Descriptors in South Korean Patients With Peripheral Neuropathic Pain:‘Jeorim’ (Tingling) and ‘Sirim’ (Cold) as Key Neuropathic Pain Descriptors

Background@#and Purpose The description of pain is the most-important indicator leading to the adequate treatment of patients with neuropathic pain (NeP). The purpose of this study was to identify and characterize the unique features of Korean verbal descriptions in patients with peripheral NeP. @*Methods@#This study included 400 patients (167 males and 233 females) and their 1,387 paindescription responses. Patients with peripheral NeP freely described their symptoms in Korean. Collected verbal descriptions were grouped according to terminologies with similar meanings. Participants completed validated patient-reported outcome scales including the neuropathic pain symptom inventory (NPSI) and painDETECT questionnaire (PD-Q). The frequencies of each verbal pain descriptor were compared between the NPSI and PD-Q scores. @*Results@#‘Jeorim’ (tingling) was the most common among 17 types of organized verbal pain descriptors, and the ‘Sirim’ (cold) symptom had a significantly higher rate of use in the 2 highseverity groups when participants were classified by their total scores on the NPSI and PD-Q. @*Conclusions@#Korean verbal NeP descriptors were significantly diverse. The Jeorim (tingling) and Sirim (cold) descriptors can be utilized in evaluations of Korean patients with NeP.

Subgrouping of Peripheral Neuropathic Pain Patients According to Sensory Symptom Profile Using the Korean Version of the PainDETECT Questionnaire

Background@#A culturally validated Korean version of the PainDETECT Questionnaire (PD-Q) was used to identify neuropathic pain components (NeP) in patients suffering from chronic pain. The purpose of this study was to determine if the Korean PD-Q can be used to subgroup patients with peripheral NeP according to sensory symptom profiles. @*Methods@#This study included 400 Korean patients with peripheral neuropathic pain diagnosed as probable or definite NeP. The total scores and subscores for each item in PD-Q were transformed into a Z-score for standardization. Hierarchical cluster analysis was performed to identify clusters of subjects by PD-Q scores. @*Results@#The mean total PD-Q score of the study participants was 14.57 ± 6.46. A hierarchical cluster analysis identified 5 clusters with distinct pain characteristic profiles. Cluster 1 had relatively severe burning and tingling sensations. The mean total PD-Q score for cluster 2 was the lowest of the 5 clusters. Cluster 3 tended to be vulnerable to pain in response to cold/heat stimulation. Cluster 4 showed relatively severe pain induced by physical stimuli, such as light touch or slight pressure. Cluster 5 had high scores for all NeP symptoms. @*Conclusion@#This study demonstrates the ability of patients to cluster by symptoms using the Korean PD-Q. Subgrouping of peripheral neuropathic pain by sensory symptom profile may be useful in making effective drug treatment decisions.

Subacute Combined Degeneration Associated with Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism

Subacute combined degeneration (SCD) is a metabolic disease caused by deficiency of vitamin B12. Rarely, it could be associated with genetic problem. An old male presented with progressive both hands weakness. Laboratory study showed deficiency of vitamin B12, but the cause was not clear. We performed a genetic study and methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism with 30% of normal enzyme activity was confirmed. This case suggests SCD may occur in association with a genetic problem with MTHFR C677T polymorphism.

The Role of Neurologists in Pain Management – Based on the Survey Conducted by the Korean Neurological Association in 2020

Background@#Pain is one of the most common chief complaints in neurological field. Authors try to inform the current situation of pain medicine in neurological practice and present an effective method for pain-related education during neurology residency and for practicing neurologists. @*Methods@#A survey was conducted from November 16 to November 27, 2020 for members of the Korean Neurological Association, and the results were analyzed. @*Results@#About two-thirds of neurologists replied that more than 25% of their patients were suffered from diverse pain including headache, spine pain or neuropathic pain. Despite many patients are visiting to neurologist for pain treatment, most neurologists are aware that they have not received sufficient practical pain education in the past and present. Therefore, they want more educational opportunities in pain medicine including interventional pain management and physical and pharmacologic therapies for more effective treatment. @*Conclusions@#More follow-up studies on pain treatment and education should be conducted. It is also essential that the members of the society continue to interest and participate in the change of the pain education program.

Etiology and epidemiology of neuropathic pain

Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system either at the peripheral or central level. In most cases, neuropathic pain is associated with poor general health and has a problem of suboptimal response to medical treatment. This review will discuss the neurologic and non-neurologic conditions that cause neuropathic pain and the results of epidemiologic studies on neuropathic pain.Current Concepts: Epidemiology would be a useful clinical tool for designing management and prevention strategies for various neuropathic pain syndromes. Validated neuropathic pain screening questionnaires are widely used as useful tools for the epidemiologic study of neuropathic pain. There are also validated Korean versions of these questionnaires. The overall prevalence of neuropathic pain was estimated at 6.9-10%. Common neuropathic pain syndromes include diabetic neuropathy, herpes zoster, and trigeminal neuralgia. In addition, neuropathic pain can also occur in central nervous system disorders such as spinal cord injury or stroke, and other conditions like cancerous diseases, intervertebral disc disease, and joint diseases.Discussion and Conclusion: Neuropathic pain does not respond well to medical treatment, which leaves both patients and physicians are less satisfied with such treatments. Therefore, physicians must identify the causes of the pain, explain them to the patient, and proceed with the treatment together with patients.

The Role of Neurologists in Pain Management – Based on the Survey Conducted by the Korean Neurological Association in 2020

Background@#Pain is one of the most common chief complaints in neurological field. Authors try to inform the current situation of pain medicine in neurological practice and present an effective method for pain-related education during neurology residency and for practicing neurologists. @*Methods@#A survey was conducted from November 16 to November 27, 2020 for members of the Korean Neurological Association, and the results were analyzed. @*Results@#About two-thirds of neurologists replied that more than 25% of their patients were suffered from diverse pain including headache, spine pain or neuropathic pain. Despite many patients are visiting to neurologist for pain treatment, most neurologists are aware that they have not received sufficient practical pain education in the past and present. Therefore, they want more educational opportunities in pain medicine including interventional pain management and physical and pharmacologic therapies for more effective treatment. @*Conclusions@#More follow-up studies on pain treatment and education should be conducted. It is also essential that the members of the society continue to interest and participate in the change of the pain education program.

Etiology and epidemiology of neuropathic pain

Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system either at the peripheral or central level. In most cases, neuropathic pain is associated with poor general health and has a problem of suboptimal response to medical treatment. This review will discuss the neurologic and non-neurologic conditions that cause neuropathic pain and the results of epidemiologic studies on neuropathic pain.Current Concepts: Epidemiology would be a useful clinical tool for designing management and prevention strategies for various neuropathic pain syndromes. Validated neuropathic pain screening questionnaires are widely used as useful tools for the epidemiologic study of neuropathic pain. There are also validated Korean versions of these questionnaires. The overall prevalence of neuropathic pain was estimated at 6.9-10%. Common neuropathic pain syndromes include diabetic neuropathy, herpes zoster, and trigeminal neuralgia. In addition, neuropathic pain can also occur in central nervous system disorders such as spinal cord injury or stroke, and other conditions like cancerous diseases, intervertebral disc disease, and joint diseases.Discussion and Conclusion: Neuropathic pain does not respond well to medical treatment, which leaves both patients and physicians are less satisfied with such treatments. Therefore, physicians must identify the causes of the pain, explain them to the patient, and proceed with the treatment together with patients.

Ulnar Neuropathy at the Upper Arm after Parallel-Bars Swinging Exercise

No abstract available.

‘Sirim’ (Cold) Pain as a Common Symptom in Korean Patients with Clinically Suspected Small-Fiber Neuropathy

BACKGROUND AND PURPOSE: Diagnosing small-fiber neuropathy (SFN) is challenging because there is no gold-standard test and few diagnostic tests. This study investigated the clinical symptom profile and its associations with the results of quantitative sensory testing (QST) and the quantitative sudomotor axon reflex test (QSART) as well as the quality of life (QOL) in patients with clinically suspected SFN. METHODS: This study involved 63 patients with clinically suspected length-dependent SFN. Assessments were performed using QST, QSART, SFN Symptoms Inventory Questionnaire, Neuropathic Pain Symptom Inventory, ‘Sirim’ frequency and ‘Sirim’ (cold) pain severity, and 36-item Short-Form Health Survey. Multiple logistic and linear regression analyses were performed to predict risk factors for QST or QSART abnormalities and QOL, respectively. RESULTS: ‘Sirim’ and ‘Sirim’ pain was the most-common (84%) and the most-severe complaint (mean score of 6.3 on a numerical rating scale ranging from 0 to 10) in patients with clinically suspected SFN. The findings of QST [cold detection threshold (CDT)] and QSART were abnormal in 71% (n=45/57) and 62% (n=39/56) of the patients, respectively. An abnormal CDT was correlated with more-severe stabbing pain (odds ratio=2.23, 95% CI=1.02–4.87, p=0.045). Restless-leg symptoms (β=−7.077) and pressure-evoked pain (β=−5.034) were independent predictors of the physical aspects of QOL. CONCLUSIONS: ‘Sirim’ pain, similar to cold pain, should be considered a major neuropathic pain in SFN. Among pain characteristics, stabbing pain of a spontaneous paroxysmal nature may be more pronounced in the setting of dysfunctional Aδ fibers with functional autonomic C fibers.

Anti-N-methyl-D-aspartate Receptor Encephalitis after Herpes Simplex Virus Infection

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis has clinical features of psychiatric symptoms, loss of memory, seizure, dyskinesia and autonomic dysfunction. While Anti-NMDA receptor encephalitis was initially reported in young women with ovarian teratoma, viral infections can trigger anti-NMDA receptor encephalitis as well. Among them, herpes virus is the most common. We report a patient who developed the anti-NMDA receptor encephalitis 47 days after herpes virus encephalitis, which is, to our knowledge, the first case in Korea.

Clinical Heterogeneity of Anti-GM2-Ganglioside-Antibody Syndrome

BACKGROUND AND PURPOSE: Antiganglioside antibodies are known to play a pathogenic role in Guillain-Barré syndrome (GBS). Either an immunoglobulin (Ig)G- or IgM-type anti-GM2 antibody is detected in rare cases in GBS patients. However, the specific pathogenic role of these antibodies in GBS has not been reported previously. This study aimed to define and characterize the clinical spectrum of GBS with anti-GM2 positivity. METHODS: We reviewed the database of the Dong-A University Neuroimmunology Team, which has collected sera of GBS and its variants from more than 40 general and university-based hospitals in Korea. Detailed information about the involved patients was often obtained and then corrected by the charge doctor applying additional questionnaires. RESULTS: Four patients with acute monophasic peripheral neuropathy or cranial neuropathy with isolated IgM-type anti-GM2-antibody positivity were recruited. In addition, IgG-type anti-GM2 antibody was solely detected in the sera of another four patients. The IgM-positive group comprised heterogeneous syndromes: two cases of acute motor axonal neuropathy, one of acute inflammatory demyelinating polyneuropathy, and one of isolated facial diplegia. In contrast, all of the cases enrolled in the IgG-positive group manifested with dizziness with or without oculomotor palsy due to cranial neuropathy syndrome. CONCLUSIONS: This study has identified that anti-GM2 antibody can be found in various subtypes of GBS and its variants in rare cases. Compared to the clinical heterogeneity of the IgM-positive group, the IgG-positive group can be characterized by cranial-dominant GBS variants presenting mainly with oculomotor and vestibular dysfunctions.

Severe Right Internal Carotid Artery Stenosis Mimicking Behavioral Variant Frontotemporal Dementia

Many kinds of degenerative, psychiatric, and cerebrovascular diseases can mimic behavioral variant frontotemporal dementia. We present a 73-year-old woman who presented with apathy, inappropriate social behavior, and persecutory delusion. A neuropsychological examination revealed frontal/executive dysfunction with relative sparing of episodic memory. Magnetic resonance imaging and F-18 fluorodeoxyglucose positron-emission tomography produced normal findings. However, magnetic resonance angiography revealed severe right internal carotid stenosis. After carotid stenting, her behavioral symptoms disappeared and did not recur during an 18-month follow-up.

Spontaneous Thrombosis of Posterior Inferior Cerebellar Artery Aneurysm Presenting as Cerebellar Infarction

Ischemic stroke caused by spontaneous thrombosis of posterior inferior cerebellar artery (PICA) aneurysm has been rarely reported. A 52-year-old man presented with sudden headache, dizziness, and gait disturbance. Diffusion-weighted MRI showed acute infarction in left PICA territory. A saccular aneurysm with internal thrombus at the distal PICA was detected by CT angiography and conventional angiography. The thrombus resolved spontaneously at 2 months after stroke onset with aspirin medication. At that time, endovascular coiling was underwent successfully to prevent aneurysmal rupture.

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.

Clinical Features of Post-Vaccination Guillain-Barré Syndrome (GBS) in Korea

Guillain-Barré syndrome (GBS) is the most common immune-mediated polyradiculoneuropathy and it is also the most commonly reported severe adverse event following immunization in adults. To evaluate the results of clinical and laboratory features of GBS after vaccination in Korea, we analyzed the claims-based data from 2002 to 2014 using materials collected for the Advisory Committee Vaccination Injury Compensation (ACVIC) meeting including, clinical features, nerve conduction studies (NCSs), cerebrospinal fluid (CSF) profiles, treatment, and outcomes. Forty-eight compensated GBS cases (median age, 15 years; interquartile range [IQR], 13–51; male:female ratio, 1:1) of 68 suspected GBS were found following immunization and all of them with influenza immunizations with either monovalent (n = 35) or trivalent (n = 13). Among them, 30 cases fulfilled the Brighton criteria level 1–3 (62.5%). The median duration between the onset of symptoms to nadir, duration of the nadir, and total admission period were 3 (IQR, 2–7 days), 2 (IQR, 1–5 days), and 14 (IQR, 6–33 days) days, respectively. The most frequently reported symptom was quadriparesis which was present in 36 cases (75%) at nadir. CSF examination revealed albuminocytologic dissociation in 25.0% and NCS was abnormal in 61.8%. After treatment, most of them showed improvement. Clinical features were similar to typical post-infectious GBS and there were both demyelinating and axonal forms suggesting heterogeneous pathogenic mechanism. In order to improve the diagnostic certainty of post-vaccination GBS, careful documentation of clinical features and timely diagnostic work-up with follow-up studies are needed.

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.

The Usefulness of Proximal Radial Motor Conduction in Acute Compressive Radial Neuropathy

BACKGROUND AND PURPOSE: The objective of this study was to determine diagnostic and prognostic values of proximal radial motor conduction in acute compressive radial neuropathy. METHODS: Thirty-nine consecutive cases of acute compressive radial neuropathy with radial conduction studies-including stimulation at Erb's point-performed within 14 days from clinical onset were reviewed. The radial conduction data of 39 control subjects were used as reference data. RESULTS: Thirty-one men and eight women (age, 45.2+/-12.7 years, mean+/-SD) were enrolled. All 33 patients in whom clinical follow-up data were available experienced complete recovery, with a recovery time of 46.8+/-34.3 days. Partial conduction block was found frequently (17 patients) on radial conduction studies. The decrease in the compound muscle action potential area between the arm and Erb's point was an independent predictor for recovery time. CONCLUSIONS: Proximal radial motor conduction appears to be a useful method for the early detection and prediction of prognosis of acute compressive radial neuropathy.

Identification of causative mutations in patients with Leigh syndrome and MERRF by mitochondrial DNA-targeted next-generation sequencing

PURPOSE: Mitochondrial diseases are clinically and genetically heterogeneous disorders, which make their exact diagnosis and classification difficult. The purpose of this study was to identify pathogenic mitochondrial DNA (mtDNA) mutations in 2 Korean families with myoclonic epilepsy with ragged-red fibers (MERRF) and Leigh syndrome, respectively. MATERIALS AND METHODS: Whole mtDNAs were sequenced by the method of mtDNA-targeted next-generation sequencing (NGS). RESULTS: Two causative mtDNA mutations were identified from the NGS data. An m.8344A>G mutation in the tRNA-Lys gene (MT-TK ) was detected in a MERRF patient (family ID: MT132), and an m.9176T>C (p.Leu217Pro) mutation in the mitochondrial ATP6 gene (MT-ATP6) was detected in a Leigh syndrome patient (family ID: MT130). Both mutations, which have been reported several times before in affected individuals, were not found in the control samples. CONCLUSION: This study suggests that mtDNA-targeted NGS will be helpful for the molecular diagnosis of genetically heterogeneous mitochondrial diseases with complex phenotypes.

Clinical and Genetic Aspects in Twelve Korean Patients with Adrenomyeloneuropathy

PURPOSE: This study was designed to investigate the characteristics of Korean adrenomyeloneuropathy (AMN) patients. MATERIALS AND METHODS: We retrospectively selected 12 Korean AMN patients diagnosed by clinical analysis and increased plasma content of very long chain fatty acids. RESULTS: All 12 patients were men. Patient ages at symptom onset ranged from 18 to 55 years. Family history was positive in two patients. The phenotype distributions consisted of AMN without cerebral involvement in seven patients, AMN with cerebral involvement in two patients, and the spinocerebellar phenotype in three patients. Nerve conduction studies revealed abnormalities in four patients and visual evoked tests revealed abnormalities in three patients. Somatosensory evoked potential tests revealed central conduction defects in all of the tested patients. Spinal MRI showed diffuse cord atrophy or subtle signal changes in all 12 patients. Brain MRI findings were abnormal in six of the nine tested patients. These brain abnormalities reflected the clinical phenotypes. Mutational analysis identified nine different ABCD1 mutations in 10 of 11 tested patients. Among them, nine have been previously reported and shown to be associated with various phenotypes; one was a novel mutation. CONCLUSION: In conclusion, the present study is the first to report on the clinical and mutational spectrum of Korean AMN patients, and confirms various clinical presentations and the usefulness of brain MRI scan.