The motor unit number index (MUNIX) refers to an electrophysiologic technique that measures the approximate number of motor units using the surface electromyographic interference pattern (SIP) recorded during voluntary contraction. This study was done to assess the reproducibility of MUNIX performed on hypothenar muscles in 62 normal controls and 22 amyotrophic lateral sclerosis (ALS) patients. Inter- and intraoperator correlation coefficients for MUNIX were 0.74 and 0.86, respectively, in normal controls, and 0.95 and 0.93, respectively, in ALS patients (P < 0.01 in all). Inter- and intraoperator coefficients of variation for MUNIX measurements were 17.5% and 15.3%, respectively, in normal controls, and 23.7% and 24.0%, respectively, in ALS patients. This study shows a good correlation for MUNIX between intra- and interoperator results in both normal controls and ALS patients. The test-retest variability seems to be greater in ALS patients compared with normal controls, but this will need to be confirmed in future studies. Sources of variability should be identified and corrected for clinical use.

Objectives: The aims of this study were to obtain data on the frequency with which Korean patients with autoimmune myasthenia gravis (MG) present solely with ocular disturbances and progress to develop generalized disease and to identify the prognostic factors associated with secondary generalization. Methods: We conducted a retrospective multicenter survey in which a total of 376 adult patients who were newly diagnosed with MG from 2000 through 2005 were reviewed for analysis. Patients with ocular MG at the time of symptom presentation (n = 202, 53.7%) were divided into two subgroups according to their prognosis: the patients whose disease remained ocular throughout the follow-ups were placed in the OMG-R group, and the patients who progressed to develop generalized disease were placed in the OMG-G group. Clinical characteristics and laboratory findings were compared between the two subgroups. Results: Secondary generalization developed in 47 (23.3%) of the 202 study subjects, mostly within the first 6 months after symptom presentation, while the disease remained ocular throughout the follow-up duration (median 11.8 months) in the remaining 155 patients (76.7%). AChR antibody, abnormal repetitive nerve stimulation tests (RNST) and thymoma were more frequently observed in the patients in the OMG-G group than in those in the OMG-R group (p b 0.01 in all). In seropositive cases, the titers of AChR antibody were also significantly higher in the OMG-G group than in the OMG-R group (median, 3.8 nM vs. 6.4 nM; p b 0.05). Cox proportional hazards regression analyses showed that early oral prednisolone treatment significantly reduced the risk of secondary generalization (HR, 0.24; 95% CI, 0.11-0.56), whereas abnormal AChR antibody (HR, 5.34; 95% CI,) and thymoma (HR, 2.32; 95% CI, 1.21-4.45) were predictive of the development of secondary generalization. Conclusions: Our findings suggest that several factors, including the AChR antibody, thymoma, early corticosteroid treatment, and possibly latent neuromuscular abnormality revealed by RNST, may have an impact on the risk of developing generalized disease in Korean patients presenting with ocular myasthenia.

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Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset, progressive neurodegenerative disorder with no known cure. Cu/Zn-superoxide dismutase (SOD1) was the first identified protein associated with familial ALS (fALS). Recently, TAR DNA-binding protein 43 (TDP-43) has been found to be a principal component of ubiquitinated cytoplasmic inclusions in neurons and glia in ALS. However, it remains unclear whether these ALS-linked proteins partly have a shared pathogenesis. Here, we determine the association between mutant SOD1 and the modification of TDP-43 and the relationship of pathologic TDP-43 to neuronal cytotoxicity in SOD1 ALS. In this work, using animal model, human tissue, and cell models, we provide the evidence that the association between the TDP-43 modification and the pathogenesis of SOD1 fALS. We demonstrated an age-dependent increase in TDP-43 C-terminal fragments and phosphorylation in motor neurons and glia of SOD1 mice and SOD1G85S ALS patient. Cytoplasmic TDP-43 was also observed in iPSC-derived motor neurons from SOD1G17S ALS patient. Moreover, we observed that mutant SOD1 interacts with TDP-43 in co-immunoprecipitation assays with G93A hSOD1-transfected cell lines. Mutant SOD1 overexpression led to an increase in TDP-43 modification in the detergent-insoluble fraction in the spinal cord of SOD1 mice and fALS patient. Additionally, we showed cellular apoptosis in response to the interaction of mutant SOD1 and fragment forms of TDP-43. These findings suggest that mutant SOD1 could affect the solubility/insolubility of TDP-43 through physical interactions and the resulting pathological modifications of TDP-43 may be involved in motor neuron death in SOD1 fALS.

the present study aimed to investigate the prognostic importance of the neutrophil-to-lymphocyte ratio (NLR) in patients with amyotrophic lateral sclerosis (ALS). Among 322 patients diagnosed as having definite, probable, or possible ALS at a single tertiary hospital, 194 patients were included in the final analysis. Patients were divided into three groups (T1, T2, and T3) according to the tertile of their NLR. Survival rate was significantly lower in T3 compared to the other groups (log-rank test; T1 vs. T3, p = 0.009; T2 vs. T3, p = 0.008). Median survival duration was 37. 0 (24.0-56.0), 32.5 (19.5-51.2), and 22.0 (17.0-38.0) months in T1, T2, and T3, respectively. In a multivariable Cox proportional hazards regression analysis, the hazard ratio of age at onset, bulbar-onset, and NLR (T3/T1) was 1. 04 (1.02-1.06, p < 0.001), 1.68 (1.10-2.57, p = 0.015), and 1.60 (1.01-2.51, p = 0.041), respectively. A high baseline NLR may serve as a useful indicator for short survival duration in patients with ALS.

Background: The objective of this study was to evaluate the efficacy and safety of repeated low-dose rituximab treatment guided by monitoring circulating CD19+ B cells in patients with refractory myasthenia gravis (MG). Methods: Patients with refractory MG who had received rituximab treatment at two teaching hospitals between September 2013 and January 2017 were reviewed retrospectively. The treatment protocol consisted of an induction treatment with low-dose rituximab (375 mg/m2 twice with a 2-week interval), followed by retreatment (375 mg/m2 once). Retreatment was based on either circulating CD19+ B-cell repopulation or clinical relapse. Outcome measures included the MG Foundation of America (MGFA) clinical classification and postintervention status, prednisolone dose, CD19+ B-cell counts, clinical relapse, and adverse effects. Results: Of 17 patients, 11 (65%) achieved the primary endpoint, defined as the minimal manifestation or better status with prednisolone ⩽5 mg/day, after median 7.6 months (range, 2–17 months) following rituximab treatment. Over a median follow up of 24 months (range, 7–49 months), a total of 30 retreatments were undertaken due to clinical relapse without B-cell repopulation ( n = 6), on the basis of B-cell repopulation alone ( n = 16) and both ( n = 8). B-cell recovery appeared to be in parallel with clinical relapse on the group level, although the individual-level association appeared to be modest, with B-cell repopulation observed only at 57% (8/14) of clinical relapses. Conclusions: The repeated low-dose rituximab treatment based on the assessment of circulating B-cell depletion could be a cost-effective therapeutic option for refractory MG. Further studies are needed to verify the potentially better cost-effectiveness of low-dose rituximab, and to identify biomarkers that help optimize treatment in MG patients.

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.