Impact of COVID-19 Infection and Its Association With Previous Vaccination in Patients With Myasthenia Gravis in Korea: A Multicenter Retrospective Study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Serial Nerve Conduction Studies in Guillain-Barré Syndrome: Its Usefulness and Precise Timing.

PURPOSE: Nerve conduction study (NCS) is essential for subclassifying Guillain-Barré syndrome (GBS). It is well known that the GBS subclassification can change through serial NCSs. However, the usefulness of serial NCSs is debatable, especially in patients with early stage GBS. METHODS: Follow-up NCS data within 3 weeks (early followed NCS, EFN) and within 3 to 10 weeks (late-followed NCS, LFN) were collected from 60 patients with GBS who underwent their first NCS (FN) within 10 days after symptom onset. Each NCS was classified into five subtypes (normal, demyelinating, axonal, inexcitable, and equivocal), according to Hadden's and Rajabally's criteria. We analyzed the frequency of significant changes in classification (SCCs) comprising electrodiagnostic aggravation and subtype shifts between demyelinating and axonal types according to follow-up timing. RESULTS: Between FN and EFN, 33.3% of patients with Hadden's criteria and 18.3% with Rajabally's criteria showed SCCs. Between FN and LFN, 23.3% of patients with Hadden's criteria and 21.7% with Rajabally's criteria showed SCCs, of which 71.4% (Hadden's criteria) and 46.2% (Rajabally's criteria) already showed SCCs from the EFN. The conditions of delayed SCCs between EFN and LFN were very early FN, mild symptoms at the FN, or persistent electrophysiological deterioration 3 weeks after symptom onset. CONCLUSIONS: A substantial proportion of patients with GBS showed significant changes in neurophysiological classification at the early stage. Serial NCS may be helpful for precise neurophysiological classification. This study suggests that follow-up NCSs should be performed within 3 weeks of symptom onset in patients with GBS in whom FN was performed within 10 days of symptom onset.

More than autophony: a case of Kennedy's disease presenting with autophony as an early clinical manifestation.

BACKGROUND: As autophony can be accompanied by several conditions, it is important to find co-morbidities. This paper reports a patient with Kennedy's disease (spinobulbar muscular atrophy, an X-linked, hereditary, lower motor neuron disease) having autophony as the first symptom. CASE REPORT: A 62-year-old male presented to the otorhinolaryngology department with autophony that began 2 years previously and worsened after losing weight 3 months prior to presentation. Otoscopic examination demonstrated inward and outward movement of the tympanic membrane, synchronised with respiration. Although he had no other symptoms, facial twitching was found on physical examination. In the neurology department, lower motor neuron disease, with subtle weakness of the tongue, face and upper limbs, and gynaecomastia, were confirmed. He was diagnosed with Kennedy's disease based on genetic analysis. CONCLUSION: Autophonia was presumed to be attributed to bulbofacial muscle weakness due to Kennedy's disease, and worsened by recent weight loss. Patients with autophony require a thorough history-taking and complete physical examination to assess the nasopharynx and the integrity of lower cranial function.

Appendicular Skeletal Muscle Mass Associated with Sarcopenia as a Predictor of Poor Functional Outcomes in Ischemic Stroke.

Purpose: Several studies have examined the clinical impact of poststroke and stroke-related sarcopenia on stroke recovery. However, few studies have investigated the effect of sarcopenia detected shortly after stroke on functional prognosis. We predicted functional outcomes using early screening for sarcopenia in patients with acute ischemic stroke. We also examined the effect of sarcopenia detected shortly after stroke on functional prognosis. Patients and Methods: Patients diagnosed with acute ischemic stroke within 2 days of symptom onset were consecutively enrolled at a tertiary university hospital. Appendicular skeletal muscle mass (ASM) was measured using dual-energy X-ray absorptiometry during early hospitalization. Sarcopenia was diagnosed based on low ASM and strength criteria of the Asian Working Group for Sarcopenia (AWGS) and European Working Group on Sarcopenia in Older People (EWGSOP2). The primary outcome was poor functional outcome, defined as a modified Rankin score of 4-6 and all-cause mortality at 3 months. Results: Of the 653 patients, 214 (32.8%) and 174 (26.6%) had sarcopenia according to the AWGS and EWGSOP2 criteria, respectively. Irrespective of the definition, the sarcopenia group had a significantly higher proportion of patients with poor functional outcomes and all-cause mortality. Multivariate logistic regression analysis revealed that height-adjusted ASM was independently associated with poor functional outcomes (odds ratio: 0.61; 95% confidence interval: 0.40-0.91; P <0.005), and they were negatively correlated. However, the association between 3-month mortality, skeletal muscle mass, and sarcopenia was not sustained in multivariate analyses. Conclusion: Height-adjusted ASM associated with sarcopenia is a potential predictor of poor functional outcomes at 3 months in patients with acute stroke. However, owing to the limitations of this study, further research is required to confirm these findings.

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 anti-HMGCR 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 anti-HMGCR 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.

Predicting Stenosis Aggravation in Follow-Up High-Resolution Magnetic Resonance Images of Patients with Intracranial Atherosclerosis.

BACKGROUND: High-resolution magnetic resonance imaging (HRMRI) can provide information on the histopathological characteristics of intracranial atherosclerotic lesions causing arterial stenosis; however, its clinical application in intracranial atherosclerosis lacks standardization for predicting stenosis. Therefore, this study investigated the characteristics of HRMRI that can predict progression based on comparisons of follow-up HRMRI. METHODS: We retrospectively enrolled patients who underwent HRMRI within 7 days of symptom onset to evaluate the characteristics associated with intracranial stenotic lesions. Among them, patients diagnosed with severe stenosis due to atherosclerosis and who underwent follow-up HRMRI 12-24 months after initial HRMRI were included in the final study. We analyzed distinct features, such as stenosis aggravation, the presence of initial plaque enhancement, increment of plaque enhancement, the existence of both eccentric and concentric plaques, and the presence of initial intraplaque hematoma on initial and follow-up HRMRI. RESULTS: Among 442 patients who underwent HRMRI for severe stenosis due to atherosclerosis, 35 underwent follow-up HRMRI 12-24 months later. Patients with stenosis aggravation showed a higher incidence of plaque enhancement (87.5% vs. 3.7%, p < 0.001) and the presence of both concentric and eccentric plaques (75.0% vs. 11.1%; p = 0.001). The area under the curve for the increment of plaque enhancement was 0.92 (95% confidence interval [CI] 0.78-1.00, p ≤ 0.001), while that for the presence of both concentric and eccentric plaques was 0.82 (95% CI 0.63-1.00, p < 0.007). CONCLUSIONS: The presence of both concentric and eccentric plaques and an increase in plaque enhancement were the strongest predictors of aggravation of intracranial artery stenosis.

Impaired spleen structure and chemokine expression in ME7 scrapie-infected mice.

We have previously demonstrated that prion protein-deficient (Prnp(0/0)) Zürich I mice display impaired T zone structure resulting from decreased splenic expression of the T cell homing chemokines, CCL19 and CCL21. Prions are transported to, and colonise in, the secondary lymphoid tissues. Therefore, in order to investigate how scrapie infection affects the splenic white pulp structure, we infected C57BL/6 mice with the mouse-adapted scrapie strain ME7 and analysed end-stage prion disease. We found that the white pulp regions of ME7-infected spleens were smaller, and contained markedly diminished T zones, as compared to control spleens. Although lymphoid tissue inducer cells were not affected, the expression of both CCL19 and CCL21 was decreased. In addition, the networks of follicular dendritic cells, which are known to express high levels of the cellular prion protein (PrP(C)) and to accumulate PrP(Sc) following scrapie infection, were larger in ME7-infected spleens. Further, they were associated with increased numbers of B cells expressing high levels of IgM. These data indicate that ME7-infected spleens display phenotype characteristics different from those reported for Prnp(0/0) spleens mainly due to the gain of PrP(Sc) function and suggest that the PrP(C) is required, not only to form the splenic white pulp structure, but also to maintain the intact T zone structure.

Prion protein-deficient mice exhibit decreased CD4 T and LTi cell numbers and impaired spleen structure.

The cellular prion protein is expressed in almost all tissues, including the central nervous system and lymphoid tissues. To investigate the effects of the prion protein in lymphoid cells and spleen structure formation, we used prion protein-deficient (Prnp(0/0)) Zürich I mice generated by inactivation of the Prnp gene. Prnp(0/0) mice had decreased lymphocytes, in particular, CD4 T cells and lymphoid tissue inducer (LTi) cells. Decreased CD4 T cells resulted from impaired expression of CCL19 and CCL21 in the spleen rather than altered chemokine receptor CCR7 expression. Importantly, some of the white pulp regions in spleens from Prnp(0/0) mice displayed impaired T zone structure as a result of decreased LTi cell numbers and altered expression of the lymphoid tissue-organizing genes lymphotoxin-α and CXCR5, although expression of the lymphatic marker podoplanin and CXCL13 by stromal cells was not affected. In addition, CD3(-)CD4(+)IL-7Rα(+) LTi cells were rarely detected in impaired white pulp in spleens of these mice. These data suggest that the prion protein is required to form the splenic white pulp structure and for development of normal levels of CD4 T and LTi cells.

Whole-Body Muscle MRI in Patients with Hyperkalemic Periodic Paralysis Carrying the SCN4A Mutation T704M: Evidence for Chronic Progressive Myopathy with Selective Muscle Involvement.

BACKGROUND AND PURPOSE: Hyperkalemic periodic paralysis (hyperKPP) is a muscle sodium-ion channelopathy characterized by recurrent paralytic attacks. A proportion of affected individuals develop fixed or chronic progressive weakness that results in significant disability. However, little is known about the pathology of hyperKPP-induced fixed weakness, including the pattern of muscle involvement. The aim of this study was to characterize the patterns of muscle involvement in hyperKPP by whole-body magnetic resonance imaging (MRI). METHODS: We performed whole-body muscle MRI in seven hyperKPP patients carrying the T704M mutation in the SCN4A skeletal sodium-channel gene. Muscle fat infiltration, suggestive of chronic progressive myopathy, was analyzed qualitatively using a grading system and was quantified by the two-point Dixon technique. RESULTS: Whole-body muscle MRI analysis revealed muscle atrophy and fatty infiltration in hyperKPP patients, especially in older individuals. Muscle involvement followed a selective pattern, primarily affecting the posterior compartment of the lower leg and anterior thigh muscles. The muscle fat fraction increased with patient age in the anterior thigh (r=0.669, p=0.009), in the deep posterior compartment of the lower leg (r=0.617, p=0.019), and in the superficial posterior compartment of the lower leg (r=0.777, p=0.001). CONCLUSIONS: Our whole-body muscle MRI findings provide evidence for chronic progressive myopathy in hyperKPP patients. The reported data suggest that a selective pattern of muscle involvement-affecting the posterior compartment of the lower leg and the anterior thigh-is characteristic of chronic progressive myopathy in hyperKPP.

Immunomodulatory Effects of ZYM-201 on LPS-stimulated B Cells.

ZYM-201 is a methyl ester of triterpenoid glycoside from Sanguisorba officinalis which has been used for treatment of inflammatory and metabolic diseases. In this study, immunomodulatory effects of ZYM-201 on B cells were examined in vitro and in vivo. When splenocytes were activated with lipopolysaccharide (LPS), the major population which had shown an increase in cell numbers was B cells. However, when the B cells were treated with ZYM-201 after LPS activation, their cell numbers and the expression of major costimulatory molecules, CD80 and CD86, were decreased. Furthermore, the effect of LPS, which induces activation of NF-κB, was abolished by ZYM-201: LPS-stimulated B cells showed decrease of phosphorylation after treatment of ZYM-201. The same results were shown in vivo experiments. These results suggest that ZYM-201 may play a role in the modulation of inflammatory responses through inhibiting NF-κB activation and downregulating the expression of costimulatory molecules on B cells.

PSSK modulation scheme for high-data rate implantable medical devices.

In this paper, we propose a new modulation scheme for high-data rate wireless body area network inbody communication systems. Simulation results are presented in terms of performance, modulation options, spectrum regrowth by nonlinearity and roll-off values of a pulse shaping filter. In addition, the planning for link budget explains that the proposed modulation approach is appropriate for high-data rate applications in the body channel environment.

Tensor-based AAM with continuous variation estimation: application to variation-robust face recognition.

The Active appearance model (AAM) is a well-known model that can represent a non-rigid object effectively. However, the fitting result is often unsatisfactory when an input image deviates from the training images due to its fixed shape and appearance model. To obtain more robust AAM fitting, we propose a tensor-based AAM that can handle a variety of subjects, poses, expressions, and illuminations in the tensor algebra framework, which consists of an image tensor and a model tensor. The image tensor estimates image variations such as pose, expression, and illumination of the input image using two different variation estimation techniques: discrete and continuous variation estimation. The model tensor generates variation-specific AAM basis vectors from the estimated image variations, which leads to more accurate fitting results. To validate the usefulness of the tensor-based AAM, we performed variation-robust face recognition using the tensor-based AAM fitting results. To do, we propose indirect AAM feature transformation. Experimental results show that tensor-based AAM with continuous variation estimation outperforms that with discrete variation estimation and conventional AAM in terms of the average fitting error and the face recognition rate.

Linear frequency modulation reverberation suppression using difference of singular values.

This letter proposes a reverberation suppression method to improve the target detection probability in reverberation environment induced by a linear frequency modulation signal. Using the singular value decomposition and an assumption of local spatial stationarity, the proposed algorithm suppresses reverberation utilizing the difference of singular values between the reference beam and the current beam of interest. Several experiments using real oceanic reverberation data justify the validity of the proposed algorithm.