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Background@#and Purpose Unlike other immune-mediated neuropathies, anti-myelin-associated glycoprotein (MAG) neuropathy is often refractory to immunotherapy. It is necessary to compare the relative efficacies of various immunotherapies and develop objective biomarkers in order to optimize its clinical management. @*Methods@#This study recruited 91 patients with high anti-MAG antibody titers from 7 tertiary hospitals in South Korea. We analyzed the baseline characteristics, therapeutic outcomes, and nerve conduction study (NCS) findings of 68 patients and excluded 23 false positive cases. @*Results@#The rate of positive responses to treatment was highest using zanubrutinib (50%) and rituximab (36.4%), followed by corticosteroids (16.7%), immunosuppressants (9.5%), intravenous immunoglobulin (5%), and plasma exchange (0%). Disability and weakness were significantly associated with multiple NCS parameters at the time of diagnosis, especially distal compound muscle action potential (CMAP) amplitudes. Moreover, the longitudinal trajectory of the average CMAP amplitudes paralleled the clinical courses, with a 16.2 percentile decrease as an optimal cutoff for predicting a clinical exacerbation (area under the receiver operating characteristic curve=0.792). @*Conclusions@#Our study supports the use of NCS as an objective marker for estimating disease burden and tracking clinical changes in patients with anti-MAG neuropathy. We have described the beneficial effects of rituximab and a new drug, zanubrutinib, compared with conventional immunotherapies.

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Background@#and Purpose Despite the growing demands and challenges faced by patients with amyotrophic lateral sclerosis (ALS) in accessing healthcare services, our understanding of this access remains poor. This study aimed to investigate the healthcare utilization patterns and timing of nutritional and respiration support in patients with ALS in South Korea. @*Methods@#A retrospective cohort study was conducted on patients diagnosed with ALS at a single tertiary hospital between 2016 and 2019 and followed up for 2 years. We evaluated patient characteristics, healthcare utilization (hospital admissions, outpatient visits, and emergency department [ED] visits), and the timing of nutritional and respiration support (noninvasive positive pressure ventilation [NIPPV], tracheostomy, gastrostomy, and nasogastric tube) at 6-month intervals from the first outpatient visit. @*Results@#Among the 143 included patients, 73.4% were admitted at least once, 18.9% experienced unplanned admissions, and 30.1% visited the ED at least once during the study period.The most-common reason for ED visits was neurological symptoms during the first 6 months (59.1%), followed by respiratory symptoms. One fifth of patients who visited the ED underwent tracheostomy (20.9%) or NIPPV (20.9%). Two years after the first visit, 32.2% used a ventilator, and 13.3%, 26.6%, and 6.3% had undergone tracheostomy, gastrostomy, and nasogastric tube insertion, respectively. @*Conclusions@#During the 2 years following their first outpatient visit, 20% of patients with ALS experienced unplanned admissions and 30% visited the ED. An active and prompt supportivecare program should be implemented to ensure timely functional support in order to reduce these risks of unplanned admissions.

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Valosin-containing protein (VCP)-related multisystem proteinopathy (MSP1) is a rare genetic disorder marked by abnormal protein accumulation. This study presents the case of a 52-year-old woman with MSP1, showing progressive weakness, gait disturbances, and respiratory muscle weakness over five years. The clinical examination revealed diverse presentations, including neurogenic changes in electrophysiologic study, multifocal fatty changes of muscle, and cognitive impairment with a confirmed VCP gene mutation through genetic testing. Notably, we identified lobulated myofibers in the muscle biopsy, an unusual finding in MSP1. This is the first report of lobulated myofibers in MSP1 with multisystem involvement. Identifying unique muscle biopsy results in suspected MSP1 patients through careful neurological examinations and timely genetic testing may help in early diagnosis and appropriate management.

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Background@#and Purpose Cognitive and behavioral changes are common in amyotrophic lateral sclerosis (ALS), with about 15% of patients presenting with overt frontotemporal dementia and 30%–50% with varying degrees of impairments. We aimed to develop and validate the Korean version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS-K), a brief multidomain assessment tool developed for ALS patients with physical disability. @*Methods@#We developed the ECAS-K according to the translation guidelines, and administered it to 38 patients with ALS and 26 age- and education-level-matched controls. We also administered the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB) to investigate convergent validity, and the Center for Neurologic Study-Liability Scale to assess the association between pseudobulbar affect and cognitive/behavioral changes. @*Results@#Internal consistency among the ECAS-K test items was found to be high, with a Cronbach’s alpha of 0.87. Significant differences were found between patients with ALS and the controls in language, fluency, and memory functions (p<0.05). Abnormal performance based on the ECAS total score was noted in 39.4% of patients, and 66.6% presented behavioral changes in at least one domain. Significant correlations were observed between the scores of the ECAS-K and those of other cognitive screening tools (MoCA and FAB, with correlation coefficients of 0.69 and 0.55, respectively; p<0.01). @*Conclusions@#We developed and validated the ECAS-K which could be used as an effective tool to screen the cognitive and behavioral impairments in Korean patients with ALS.

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The phosphorylated 43-kDa transactive response DNA-binding protein (TDP-43) was identified as a major disease protein in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. We present a case with progressive muscle weakness who was diagnosed with sporadic ALS. On postmortem examination, TDP-43 immunoreactive neuronal cytoplasmic inclusions were noted in motor cortex, hippocampus and anterior horns of spinal cord, which was compatible with ALS-TDP, stage 4. This is the first documented autopsy-confirmed ALS case with ALS-TDP pathology in Korea.

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Objective@#Tacrolimus, a macrolide immunosuppressant, is approved in Korea for the treatment of rheumatoid arthritis (RA), lupus nephritis (LN) and myasthenia gravis (MG). We report three prospective post-marketing surveillance studies of tacrolimus conducted in South Korea in these indications. @*Methods@#Studies were conducted according to South Korean Ministry of Food and Drug Safety requirements. Patients were followed up for the duration of the study (up to 4 years) or until treatment discontinuation. Occurrence and likely relationship with tacrolimus of adverse events (AEs), adverse drug reactions (ADRs; defined as AEs where causal relationship to tacrolimus could not be excluded) and serious AEs were recorded. Association of AEs with demographic and medical factors was evaluated by multivariable analysis. @*Results@#The studies included 740 (RA), 307 (LN) and 104 (MG) patients. The incidence of AEs was 12.7% in RA (64.2% of AEs potentially related to tacrolimus), 20.9% (37.8% potentially related) in LN and 29.8% (56.8% potentially related) in MG. The incidence of ADRs was 8.4%, 9.8% and 20.2%, respectively. Serious AEs were reported in 0.7%, 7.2% and 8.7%, respectively. The most common AEs were abdominal pain (RA), pharyngitis (LN) and diarrhea (MG). Unexpected AEs occurred in 3.5% of patients with RA, 2.9% in LN and 8.7% in MG; no pattern of unexpected AEs was apparent. Multivariable analysis demonstrated that patients with comorbidity had higher probability of experiencing an AE in RA and MG studies. @*Conclusion@#The incidence of AEs and the safety profile of tacrolimus in each indication was consistent with previous reports.

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Motor neuron diseases (MND) are heterogeneous spectra of disorders that that primarily affect the motor neurons (MN) resulting in motor nerve and muscle degeneration. The pathophysiological mechanisms of MN cell death are known to be combined with disturbance of proteostasis, ribonucleostasis and exaggerated neuro-inflammation. Amyotrophic lateral sclerosis is the prototypic disease of MND followed by spinal and bulbar muscular atrophy, spinal muscular atrophy, benign focal amyotrophy and other various diseases. Although diverse spectra of these diseases share common symptoms, significant differences are known in their clinical manifestations and their clinical progression. With increasing number of new clinical trials, the importance of selecting appropriate clinical scales for the monitoring of clinical progression in different types of MNDs should be emphasized. The purpose of this review is to illustrate different types of clinical scales and demonstrate how to utilize these in the clinical research field with consensus. With these efforts, we hope to be ready to understand different kinds of clinical scales in MND in participating global standard clinical trials.

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Background@#Pompe disease is a rare autosomal recessive disorder caused by the deficiency of a lysosomal enzyme, acid alpha-glucosidase (GAA). Early diagnosis and initiation of treatment with enzyme replacement therapy have remarkable effects on the prognosis of Pompe disease. We performed the expanded screening for late onset Pompe disease (LOPD) at eight centers in Korea. @*Methods@#From September 1, 2015, GAA activity were measured from both dried blood spot (DBS) and mixed leukocyte for 188 available patients. For 12 patients with low GAA activity, we performed Sanger sequencing of GAA gene. @*Results@#Among 188 patients, 115 were males. The mean of age of symptom onset and diagnosis were 34.3 years and 41.6 years. Among 12 patients with decreased GAA activity, two patients were confirmed to have LOPD with genetic test (c.1316T>A [p.M439K] + c.2015G>A [p.R672Q], c.1857C>G [p.S619R] + c.546G>C [leaky splicing]). Other two patients had homozygous G576S and E689K mutation, known as pseudodeficiency allele. @*Conclusions@#This study is expanded study of LOPD screening for targeted Korean population. We found two patients with LOPD, and the detection rate of LOPD is 1.06%. With application of modified GAA cutoff value (0.4), which was previously reported, there were no false positive results of GAA activity test using DBS. Therefore, it could be an appropriate screening test for LOPD in especially East-Asian population, in which pseudodeficiency allele is frequent.

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Hereditary spastic paraplegia (HSP) is a heterogeneous group of monogenic neurodegenerative disorders characterized by progressive spasticity of the lower limbs. The clinical features and imaging abnormalities vary greatly according to the affected genes. HSP is classified clinically as pure and complex forms, depending upon the presence or absence of additional neurological defects other than spastic lower limbs. Despite the recent advances in next-generation sequencing technology and its wide availability, a genetic diagnosis of HSP is still not made in more than half of all suspected cases of HSP. In this review, we summarized the various phenotypes of relatively common HSP in clinical practice according to the inheritance pattern, highlighting their clinical, radiological, and neurophysiological features. We further discussed the practical approach to patients with suspected HSP in the current era of next-generation sequencing.

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Objective@#Tacrolimus, a macrolide immunosuppressant, is approved in Korea for the treatment of rheumatoid arthritis (RA), lupus nephritis (LN) and myasthenia gravis (MG). We report three prospective post-marketing surveillance studies of tacrolimus conducted in South Korea in these indications. @*Methods@#Studies were conducted according to South Korean Ministry of Food and Drug Safety requirements. Patients were followed up for the duration of the study (up to 4 years) or until treatment discontinuation. Occurrence and likely relationship with tacrolimus of adverse events (AEs), adverse drug reactions (ADRs; defined as AEs where causal relationship to tacrolimus could not be excluded) and serious AEs were recorded. Association of AEs with demographic and medical factors was evaluated by multivariable analysis. @*Results@#The studies included 740 (RA), 307 (LN) and 104 (MG) patients. The incidence of AEs was 12.7% in RA (64.2% of AEs potentially related to tacrolimus), 20.9% (37.8% potentially related) in LN and 29.8% (56.8% potentially related) in MG. The incidence of ADRs was 8.4%, 9.8% and 20.2%, respectively. Serious AEs were reported in 0.7%, 7.2% and 8.7%, respectively. The most common AEs were abdominal pain (RA), pharyngitis (LN) and diarrhea (MG). Unexpected AEs occurred in 3.5% of patients with RA, 2.9% in LN and 8.7% in MG; no pattern of unexpected AEs was apparent. Multivariable analysis demonstrated that patients with comorbidity had higher probability of experiencing an AE in RA and MG studies. @*Conclusion@#The incidence of AEs and the safety profile of tacrolimus in each indication was consistent with previous reports.

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Motor neuron diseases (MND) are heterogeneous spectra of disorders that that primarily affect the motor neurons (MN) resulting in motor nerve and muscle degeneration. The pathophysiological mechanisms of MN cell death are known to be combined with disturbance of proteostasis, ribonucleostasis and exaggerated neuro-inflammation. Amyotrophic lateral sclerosis is the prototypic disease of MND followed by spinal and bulbar muscular atrophy, spinal muscular atrophy, benign focal amyotrophy and other various diseases. Although diverse spectra of these diseases share common symptoms, significant differences are known in their clinical manifestations and their clinical progression. With increasing number of new clinical trials, the importance of selecting appropriate clinical scales for the monitoring of clinical progression in different types of MNDs should be emphasized. The purpose of this review is to illustrate different types of clinical scales and demonstrate how to utilize these in the clinical research field with consensus. With these efforts, we hope to be ready to understand different kinds of clinical scales in MND in participating global standard clinical trials.

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Background@#Pompe disease is a rare autosomal recessive disorder caused by the deficiency of a lysosomal enzyme, acid alpha-glucosidase (GAA). Early diagnosis and initiation of treatment with enzyme replacement therapy have remarkable effects on the prognosis of Pompe disease. We performed the expanded screening for late onset Pompe disease (LOPD) at eight centers in Korea. @*Methods@#From September 1, 2015, GAA activity were measured from both dried blood spot (DBS) and mixed leukocyte for 188 available patients. For 12 patients with low GAA activity, we performed Sanger sequencing of GAA gene. @*Results@#Among 188 patients, 115 were males. The mean of age of symptom onset and diagnosis were 34.3 years and 41.6 years. Among 12 patients with decreased GAA activity, two patients were confirmed to have LOPD with genetic test (c.1316T>A [p.M439K] + c.2015G>A [p.R672Q], c.1857C>G [p.S619R] + c.546G>C [leaky splicing]). Other two patients had homozygous G576S and E689K mutation, known as pseudodeficiency allele. @*Conclusions@#This study is expanded study of LOPD screening for targeted Korean population. We found two patients with LOPD, and the detection rate of LOPD is 1.06%. With application of modified GAA cutoff value (0.4), which was previously reported, there were no false positive results of GAA activity test using DBS. Therefore, it could be an appropriate screening test for LOPD in especially East-Asian population, in which pseudodeficiency allele is frequent.

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Hereditary spastic paraplegia (HSP) is a heterogeneous group of monogenic neurodegenerative disorders characterized by progressive spasticity of the lower limbs. The clinical features and imaging abnormalities vary greatly according to the affected genes. HSP is classified clinically as pure and complex forms, depending upon the presence or absence of additional neurological defects other than spastic lower limbs. Despite the recent advances in next-generation sequencing technology and its wide availability, a genetic diagnosis of HSP is still not made in more than half of all suspected cases of HSP. In this review, we summarized the various phenotypes of relatively common HSP in clinical practice according to the inheritance pattern, highlighting their clinical, radiological, and neurophysiological features. We further discussed the practical approach to patients with suspected HSP in the current era of next-generation sequencing.

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Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorders mediated by various autoantibodies. Although most patients with MG require chronic immunosuppressive treatment to control disease activity, appropriate surveillance biomarkers that monitor disease activity or potential toxicity of immunosuppressants are yet to be developed. Herein, we investigated quantitative distribution of peripheral blood B cell subsets and transcriptional profiles of memory B cells (CD19+ CD27+) in several subgroups of MG patients classified according to the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification. This study suggests potential immunologic B-cell markers that may guide treatment decision in future clinical settings.

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BACKGROUND: Multiple sclerosis (MS) is an immune-associated inflammatory disorder of the central nervous system and results in serious disability. Although many disease-modifying therapy drugs have been developed, these drugs have shown limited clinical efficacy and some adverse effects in previous studies, therefore, there has been reasonable need for less harmful and cost-effective therapeutics. Herein, we tested the anti-inflammatory effect of sulforaphane (SFN) in a mouse model of experimental autoimmune encephalomyelitis (EAE). METHODS: The EAE mice were randomly assigned into two experimental groups: the phosphate-buffered saline (PBS)-treated EAE group and SFN-treated EAE group. After EAE mice induction by auto-immunization against the myelin oligodendrocyte glycoprotein peptide, we evaluated EAE symptom scores and biochemical analyses such as infiltration of inflammatory cells and demyelination of the spinal cord. Furthermore, western blotting was performed using the spinal cords of EAE mice. RESULTS: In the behavioral study, the SFN-treated EAE mice showed favorable clinical scores compared with PBS-treated EAE mice at the 13th day (1.30 ± 0.15 vs. 1.90 ± 0.18; P = 0.043) and 14th day (1.80 ± 0.13 vs. 2.75 ± 0.17; P = 0.003). Additionally, the biochemical studies revealed that SFN treatment inhibited the inflammatory infiltration, demyelinating injury of the spinal cords, and the up-regulation of inducible nitric oxide synthase in the EAE mice. CONCLUSION: The SFN treatment showed anti-inflammatory and anti-oxidative effects in the EAE mice. Conclusively, this study suggests that SFN has neuroprotective effects via anti-inflammatory processing, so it could be a new therapeutic or nutritional supplement for MS.

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BACKGROUND AND PURPOSE: This retrospective cross-sectional study included 18 patients from unrelated families harboring mutations of the transthyretin gene (TTR), and analyzed their characteristics and geographical distribution in South Korea. METHODS: The included patients had a diagnosis of systemic amyloidosis, clinical symptoms, such as amyloid neuropathy or cardiomyopathy, and confirmation of a TTR gene mutation using genetic analysis recorded between April 1995 and November 2014. RESULTS: The mean age at disease onset was 49.6 years, and the mean disease duration from symptom onset to diagnosis was 3.67 years. Fifteen of the 18 patients were classified as mixed phenotype, 2 as the neurological phenotype, and only 1 patient as the cardiac phenotype. The most-common mutation pattern in South Korea was Asp38Ala, which was detected in eight patients. Thirteen patients reported their family hometowns, and five of the eight harboring the Asp38Ala mutation were from the Gyeongsang province in southeast Korea. The other eight patients exhibited a widespread geographical distribution. A particularly noteworthy finding was that the valine at position 30 (Val30Met) mutation, which was previously reported as the most-common TTR mutation worldwide and also the most common in the Japanese population, was not detected in the present South Korean patients. CONCLUSIONS: South Korean patients with hereditary TTR amyloidosis exhibited heterogeneous TTR genotypes and clinical phenotypes. The findings of this study suggest that the distribution of TTR amyloidosis in South Korea is due to de novo mutations and/or related to the other countries in East Asia.

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Multiple sclerosis (MS) is a T-lymphocyte-mediated autoimmune disease that is characterized by inflammation in the central nervous system (CNS). Although many disease-modifying therapies (DMTs) are presumed effective in patients with MS, studies on the efficacy and safety of DMTs for preventing MS relapse are limited. Therefore, we tested the immunosuppressive anti-inflammatory effects of oral-formulated tacrolimus (FK506) on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE). The mice were randomly divided into 3 experimental groups: an untreated EAE group, a low-dose tacrolimus-treated EAE group, and a high-dose tacrolimus-treated EAE group. After autoimmunization of the EAE mice with myelin oligodendrocyte glycoprotein, symptom severity scores, immunohistochemistry of the myelination of the spinal cord, and western blotting were used to evaluate the EAE mice. After the autoimmunization, the symptom scores of each EAE group significantly differed at times. The group treated with the larger tacrolimus dose had the lowest symptom scores. The tacrolimus-treated EAE groups exhibited less demyelination and inflammation and weak immunoreactivity for all of the immunization biomarkers. Our results revealed that oral-formulated tacrolimus inhibited the autoimmunization in MS pathogenesis by inactivating inflammatory cells.

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Zika is a re-emerging, mosquito-borne viral infection, which has been recently shown to cause microcephaly and Guillain-Barré syndrome. Since 2015 the number of infected patients has increased significantly in South America. The purpose of this study was to identify the epidemiologic and clinical characteristics of patients with Zika virus (ZIKV) infections in Korea. Patients who had visited areas of risk and tested positive in the ZIKV reverse transcriptase polymerase chain reaction (RT-PCR) in blood, urine, or saliva specimens were included. The first Korean case of ZIKV infection was reported in March 2016, and 14 cases had been reported by October 2016. The median age of the patients was 34 years (19–64 years). Ten patients had been exposed in Southeast Asia and 4 in Latin America. Rash was the most common symptom (92.9%; 13/14), followed by myalgia (50.0%; 7/14), and arthralgia (28.6%, 4/14). There were no neurologic abnormalities and none of the patients was pregnant. Results of biochemical tests were normal. Positivity rates of RT-PCR for ZIKV in serum, urine, and saliva were 53.8%, 100.0%, and 83.3%, respectively in the first week of symptoms. In conclusion, 14 patients with ZIKV infections were reported in Korea by October 2016 and all of them had mild clinical symptoms.

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No abstract available.

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