Multi-organ involvement caused by Scedosporium apiospermum infection after near drowning: a case report and literature review.

BACKGROUND: Scedosporium apiospermum (S. apiospermum) is a rare fungal pathogen that causes disseminated infections. It rarely affects immunocompetent individuals and has a poor prognosis. CASE PRESENTATION: A 37-year-old woman presented with multiple lesions in the lungs, brain, and eyes, shortly after near drowning in a car accident. The primary symptoms were chest tightness, limb weakness, headache, and poor vision in the left eye. S. apiospermum infection was confirmed by metagenomic next-generation sequencing (mNGS) of intracranial abscess drainage fluid, although intracranial metastases were initially considered. After systemic treatment with voriconazole, her symptoms improved significantly; however, she lost vision in her left eye due to delayed diagnosis. CONCLUSION: While S. apiospermum infection is rare, it should be considered even in immunocompetent patients. Prompt diagnosis and treatment are essential. Voriconazole may be an effective treatment option.

The diagnostic value of serum YKL-40 for myocardial involvement in immune-mediated necrotising myopathy.

OBJECTIVES: This study aimed to determine the diagnostic value of YKL-40 for myocardial involvement in immune-mediated necrotising myopathy (IMNM). METHODS: We retrospectively analysed the data of patients with IMNM admitted to the Neurology Department at Tongji Hospital between April 2013 and August 2022. Clinical data including patients' demographics, clinical characteristics (disease duration, muscle strength, atrophy, rash, dysphagia, dyspnoea, and myalgia) and laboratory test results were collected from the electronic medical record system. Serum YKL-40 levels were measured using an enzyme-linked immunosorbent assay. A receiver operating characteristic (ROC) curve was drawn, and the area under the ROC curve was calculated to evaluate the diagnostic value of YKL-40 for cardiac involvement in IMNM. RESULTS: 29 patients with IMNM and15 sex and age-matched volunteers without history of heart diseases were recruited for the study. Compared with the healthy controls, serum YKL-40 levels were notably up-regulated [96.3 (55.5 120.6) pg/ml versus 19.6 (13.8 20.9) pg/ml; p=0.000] in patients with IMNM. We compared 14 patients with IMNM with cardiac abnormalities and 15 patients with IMNM without cardiac abnormalities. The most important finding was that serum YKL-40 levels were higher in the patients with IMNM with cardiac involvement based on cardiac magnetic resonance (CMR) examination [119.2 (88.4 185.69) pm/ml versus 72.5 (35.7 98) pm/ml; p=0.002]. YKL-40 had a specificity and sensitivity of 86.7% and 71.4% respectively, at a cut-off value of 105.46 pg/ml for predicting myocardial injury in patients with IMNM. CONCLUSIONS: YKL-40 could be a promising non-invasive biomarker for diagnosing myocardial involvement in IMNM. However, larger prospective study is warranted.

Primary intramedullary spinal cord lymphoma misdiagnosed as longitudinally extensive transverse myelitis: a case report and literature review.

BACKGROUND: Primary intramedullary spinal cord lymphoma (PISCL) is rare and easily misdiagnosed with the lack of typical clinical features and non-specific imaging manifestations. CASE PRESENTATION: A 49-year-old man was admitted to our hospital because of persistent limbs numbness, pinprick-like pain in the posterior neck and unsteady gaits. He has brisk tendon reflexes and positive Babinski's sign. Magnetic resonance imaging (MRI) of the cervical spine showed an abnormal signal with aberrant reinforcement at medulla oblongata and the level of C1-C7. He was clinically diagnosed as longitudinally extensive transverse myelitis (antibody-negative). Steroid pulse therapy was administered and resulted in reduced symptoms. One month later, his situation was exacerbated compared to the onset. We launched a new cascade of steroid pulse therapy. But it did not improve his symptoms. Finally, the biopsy pathology confirmed PISCL. Chemotherapy, radiotherapy and zanubrutinib were administered and until now about 3 years into treatment the patient is still survival. CONCLUSIONS: Based on our case and literature review, we recommend that spinal onset patients react ineffectively to standard immunoglobulins or hormonal treatments or experience a relapse after a short time relief should take PISCL into consideration.

Clinical Features, Treatment, and Prognostic Factors of Childhood-Onset Myasthenia Gravis in a Large Chinese Cohort.

BACKGROUND: To describe the clinical features of patients with childhood-onset myasthenia gravis (MG) (CMG) and explore predictors affecting the treatment outcomes. METHODS: A retrospective observational cohort analysis of 859 patients with CMG with disease onset before age 14 years was performed at Tongji Hospital. RESULTS: Patients in the pubertal-onset group (n = 148) had a worse disease course than those in the prepubertal group (n = 711), including a higher incidence of generalized MG (GMG) at presentation, generalization of ocular MG (OMG), and more severe Myasthenia Gravis Foundation of America (MGFA) classification. All patients were initially treated with pyridostigmine, 657 with prednisone, and 196 with immunosuppressants (ISs). However, 226 patients were resistant to prednisone treatment. Multivariate analysis revealed that thymic hyperplasia, higher MGFA class, disease duration before prednisone administration, and thymectomy before prednisone administration were independent predictors of prednisone resistance. At the last visit, 121 of the 840 patients with OMG had developed GMG after a median of 10.0 years from symptom onset and 186 patients (21.7%) achieved complete stable remission (CSR). In multivariable analysis, age at onset, thymic hyperplasia, prednisone, and IS treatment were associated with generalization, whereas age at onset, disease duration, anti-acetylcholine receptor antibodies (AChR-ab), MGFA class II, short-term prednisone treatment, and IS treatment were associated with CSR. CONCLUSIONS: The majority of patients with CMG have mild clinical symptoms and favorable outcomes, especially those with earlier onset age, shorter disease duration, and negative AChR-ab. In addition, early prednisone and ISs are shown to be effective and safe for most patients with CMG.

Increased expression of cell adhesion molecules in myofasciitis.

Background: Myofasciitis is a heterogeneous group of diseases pathologically characterized by inflammatory cell infiltration into the fascia. Endothelial activation plays a critical role in the pathogenesis of the inflammatory response. However, the expression of cellular adhesion molecules (CAMs) in myofasciitis has not been investigated. Methods: Data on clinical features, thigh magnetic resonance imaging, and muscle pathology were collected from five patients with myofasciitis. Immunohistochemical (IHC) staining and Western blot (WB) of the muscle biopsies from patients and healthy controls were performed. Results: Increased levels of serum pro-inflammatory cytokines, including IL-6, TNF-α, and IL-2R, were detected in four patients. IHC staining and WB indicated significantly increased expression of cell adhesion molecules in blood vessels or inflammatory cells within the perimysium in muscle and fascia tissues of patients with myofasciitis compared to controls. Conclusion: The up-regulation of CAMs in myofasciitis indicates endothelial activation, which may be potential therapy targets for the treatment of myofasciitis.

TWEAK and Fn14 are overexpressed in immune-mediated necrotizing myopathy: implications for muscle damage and repair.

OBJECTIVES: TNF-like weak inducer of apoptosis (TWEAK) and its sole receptor fibroblast growth factor-inducible 14 (Fn14) are involved in various inflammatory conditions. This study was performed to investigate the potential role of TWEAK/Fn14 in immune-mediated necrotizing myopathy (IMNM). METHODS: Muscle biopsies from patients with IMNM (n = 37) and controls (n = 11) were collected. Human muscle cells were treated with TWEAK in vitro. Muscle biopsies and cultured muscle cells were analysed by immunostaining and quantitative PCR. Serum levels of TWEAK and Fn14 were detected by ELISA. RESULTS: TWEAK and Fn14 were overexpressed in IMNM muscle biopsies. The percentage of Fn14-positive myofibers correlated with disease severity, myonecrosis, regeneration and inflammation infiltrates. Fn14-positive myofibers tended to be surrounded or invaded by CD68+ macrophages. TWEAK treatment had a harmful effect on cultured muscle cells by inducing the production of multiple chemokines and pro-inflammatory cytokines. Serum Fn14 levels were increased in patients with IMNM and correlated with muscle weakness. CONCLUSIONS: TWEAK/Fn14 signalling was activated in IMNM, most likely aggravating muscle damage via amplifying inflammatory response and macrophages chemotaxis. Fn14 seems to be a biomarker for assessing disease severity in IMNM. In addition, Fn14 may also contribute to muscle injury repair.

Anti-signal recognition particle positive necrotizing myopathy-sjogren's syndrome overlap syndrome: a descriptive study on clinical and myopathology features.

BACKGROUND AND OBJECTIVE: The aim of this study was to elucidate the clinical and myopathological characteristics of patients with anti-signal recognition particle (SRP) positive immune-mediated necrotizing myopathy (IMNM) overlap Sjogren's syndrome (SS). MATERIALS AND METHODS: We retrospectively analyzed the data of anti-SRP positive IMNM patients admitted in the Neurology Department of Tongji Hospital between January 2011 to December 2020. Patients were divided into two groups: anti-SRP IMNM overlap SS group and anti-SRP IMNM control group. The clinical features, laboratory results, histological features, treatment, and prognosis were compared between the two groups. RESULTS: A total of 30 patients with anti-SRP IMNM were included, including six anti-SRP IMNM overlap SS patients (two males, four females), with a median age of 39 years, and 24 anti-SRP IMNM patients (ten males, fourteen females), with a median age of 46 years. The anti-SRP IMNM overlap SS group had a lower prevalence of muscle atrophy (0 vs 50%, p = 0.019), and a higher prevalence of extramuscular manifestations, including cardiac abnormalities and ILD (Interstitial lung disease). CD4 + and CD68 + inflammatory infiltrations were significantly increased in anti-SRP IMNM overlap SS patients, with an increased presence of CD4 + cells in both necrotic(p = 0.023) and endomysial areas (p = 0.013), and more CD68 + cells (p = 0.016) infiltrated the endomysial area. Deposition of membrane attack complex (MAC) on sarcolemma (p = 0.013) was more commonly seen in the anti-SRP IMNM overlap SS group. CONCLUSION: Our data revealed that anti-SRP IMNM-SS overlap patients may present with milder muscular manifestation, but worse extramuscular manifestations compared to anti-SRP IMNM patients without SS. CD4 + and CD68 + inflammatory infiltrations and MAC deposition were remarkably increased in anti-SRP IMNM-SS overlap patients.

Dynamic nomogram for predicting generalized conversion in adult-onset ocular myasthenia gravis.

PURPOSE: To explore the factors and risk mapping model of progression from ocular myasthenia gravis (OMG) to generalized myasthenia gravis (GMG) in adult-onset patients. METHODS: A retrospective, observational cohort study was performed for 435 OMG patients with onset age older than 14 years old. Multivariate Cox regression was used to identify the independent factors affecting generalized conversions that then were incorporated into the construction of the nomogram. RESULTS: Two hundred thirty-seven patients (54.5%) had transformed into GMG after a median of 1.1 years (range 0.1--9.1 years). The 6-, 12-, and 24-month generalized conversion rates were 31.7%, 49.8%, and 65.4%, respectively. Multivariable analysis showed that the early-onset age, male sex, concomitant autoimmune diseases (AID), positive results of anti-acetylcholine receptor antibodies, repetitive nerve stimulation abnormalities, the presence of thymoma, and prednisone treatment were significantly associated with the generalized conversions (hazard ratio [HR] = 0.598, 0.686, 1.554, 1.541, 2.020, 2.510, and 0.556, respectively). A nomogram was established to predict the possibility of generalization-free survival (GFS) in adult-onset OMG patients, and the model demonstrated good predictive performance with a C-index of 0.736 (95% confidence interval 0.703 ~ 0.769). Moreover, subgroup analyses were performed based on the presence or absence of prednisone therapy, and the results indicated that prednisone therapy has better prevention of generalized conversions in male, non-thymoma patients, and patients without other AID. CONCLUSION: A new predictive nomograph and web-based survival calculator we developed show favorable applicability and accuracy in predicting long-term GFS in adult-onset OMG patients.

The accumulation of muscle RING finger-1 in regenerating myofibers: Implications for muscle repair in immune-mediated necrotizing myopathy.

Background: Muscle RING finger-1 (MuRF-1) plays a key role in the degradation of skeletal muscle proteins. We hypothesize the involvement of MuRF-1 in immune-mediated necrotizing myopathy (IMNM). Methods: Muscle biopsies from patients with IMNM (n = 37) were analyzed and compared to biopsies from patients with dermatomyositis (DM, n = 13), dysferlinopathy (n = 9) and controls (n = 7) using immunostaining. Results: MuRF-1 staining could be observed in IMNM, DM and dysferlinopathy biopsies, whereas the percentage of MuRF-1 positive myofibers was significantly higher in IMNM than in dysferlinopathy (p = 0.0448), and positively correlated with muscle weakness and disease activity in IMNM and DM. Surprisingly, MuRF-1 staining predominantly presented in regenerating fibers but not in atrophic fibers. Moreover, MuRF-1-positive fibers tended to be distributed around necrotic myofibers and myofibers with sarcolemma membrane attack complex deposition. Abundant MuRF-1 expression in IMNM and DM was associated with rapid activation of myogenesis after muscle injury, whereas relatively low expression of MuRF-1 in dysferlinopathy may be attributed to damaged muscle regeneration. Conclusions: MuRF-1 accumulated in regenerating myofibers, which may contribute to muscle injury repair in IMNM and DM. MuRF-1 staining may help clinicians differentiate IMNM and dysferlinopathy.

The Clinicopathological Distinction between Immune-Mediated Necrotizing Myopathy and Limb-Girdle Muscular Dystrophy R2: Key Points to Prevent Misdiagnosis.

Background: Limb−girdle muscular dystrophy R2 (LGMD R2) is most frequently misdiagnosed as immune-mediated necrotizing myopathy (IMNM). This study aimed to compare the clinicopathological data of IMNM and LGMD R2 to find distinguishing features. Methods: We retrospectively reassessed the medical data of patients with IMNM (n = 41) and LGMD R2 (n = 8) treated at Tongji Hospital from January 2017 to December 2021. Results: In our cohort, patients with LGMD R2 had a longer interval of onset to first visit, mild muscle weakness with late upper limb involvement, less myalgia, no cervical muscle weakness or dysphagia, no extramuscular organs affected except cardiac involvement, and lack of various autoantibodies, such as antinuclear antibodies. These features were completely reversed in IMNM. Moreover, thigh MRIs showed that muscle edema prominently affecting the adductor magnus was a characteristic of IMNM, while extensive fatty replacement was more common in LGMD R2 (p = 0.0086). Necrotic myofibers presented in both entities (p = 0.1693), while features such as ring/whorled and splitting myofibers were more often found in LGMD R2 (p = 0.0112 and p < 0.0001, respectively). Conversely, sarcoplasmic p62 expression was more pronounced in IMNM (p < 0.05). There were 4 of 8 (50%) patients with LGMD R2 initially considered as seronegative IMNM, and therefore unnecessarily treated with immunosuppressive drugs. Insufficient recognition of the early clinical, imaging, and histopathological features of LGMD R2 is the main reason for misdiagnosis. Conclusions: These findings may help clinicians differentiate seronegative IMNM and LGMD R2, reducing early misdiagnosis and mismanagement. Particularly, prominent adductor magnus edema on MRI and abundant p62 staining seem to be good markers for IMNM, while the presence of splitting myofibers is a crucial clue to early hereditary myopathy, including LGMD R2.

Remission and relapses of myasthenia gravis on long-term tacrolimus: a retrospective cross-sectional study of a Chinese cohort.

Objective: To identify the factors that predict the remission and relapses in myasthenia gravis (MG) patients improved by prednisone and tacrolimus treatment. Methods: A retrospective, observational cohort analysis of MG patients who achieved remission after receiving prednisone and tacrolimus were performed at Tongji Hospital. The main outcome measures were the time to remission, prednisone discontinuation, tacrolimus reduction-associated relapse, and treatment outcome. Results: After adding tacrolimus, 256 patients were able to achieve remission with a mean time to remission of 2.1 ± 1.4 months. After a median follow-up of 2.9 years, 167 patients (65.2%) discontinued prednisone, and 20 patients (7.8%) achieved complete stable remission. Moreover, 53 of the 109 patients who were tapering tacrolimus experienced relapses. In multivariable analysis, female sex, low tacrolimus concentrations, and quantitative myasthenia gravis (QMG) scores have a positive correlation with the time to remission; concomitant additional autoimmune disease (AID) and high anti-acetylcholine receptor antibody (AChR-ab) levels were significantly associated with low probabilities of prednisone discontinuation [odds ratio (OR) = 0.312-0.912, respectively]; rapid tacrolimus decrement speed (⩾0.76 mg/year) was an independent predictor for the development of relapse during tapering tacrolimus (OR = 5.662). Conclusion: Sex, tacrolimus concentrations, and QMG scores can be used as potential predictors of the time to remission in MG patients treated with tacrolimus and prednisone. Prednisone should be tapered slowly, especially in patients with additional AID or high serum titers of AChR-ab. To avoid symptoms recurrence, the dose of tacrolimus should reduce slowly, not exceeding 0.76 mg/year.

Tacrolimus Combined with Corticosteroids Improved the Outcome of CIDP Patients with Autoantibodies Against Paranodal Proteins.

Purpose: To investigate the response of tacrolimus to chronic inflammatory demyelinating polyneuropathy (CIDP) with autoantibodies against paranodal proteins, including neurofascin-155 (NF155), contactin-1 (CNTN1) and contactin-associated protein 1 (Caspr1). Methods: We retrospectively reviewed all CIDP patients who carried anti-NF155, CNTN1 and Caspr1 antibodies and were treated with tacrolimus at Tongji hospital from Jan 2018 to Apr 2021. Results: There were 58 patients with CIDP and only 9 patients had autoantibodies against paranodal proteins (17.2%). Five of the 9 patients received tacrolimus treatment with an initial dose of 2-3 mg once daily. One patient with anti-CNTN1 antibody started tacrolimus and corticosteroid treatment, at the first episode and eventually achieved full clinical remission without relapse. Four patients with anti-NF155 or -Caspr1 antibodies experienced relapse during corticosteroids tapering. Then, they were given oral tacrolimus and presented with clinical improvement. During follow-up, only one patient developed worsening weakness due to unreasonable tacrolimus discontinuation. Moreover, 3 patients were successfully withdrawn from corticosteroids and 2 patients took corticosteroids at low maintenance dose (10mg/d) after tacrolimus treatment. No severe adverse events were observed in all the patients. Conclusion: Patients with autoantibodies against paranodal proteins had a better long-term outcome after adding tacrolimus. Combination therapy with corticosteroids and tacrolimus may be an effective therapeutic regimen.

Using multi-parametric quantitative MRI to screen for cardiac involvement in patients with idiopathic inflammatory myopathy.

Idiopathic inflammatory myopathies (IIM) is a group of heterogeneous autoimmune systemic diseases, which not only involve skeletal muscle but also myocardium. Cardiac involvement in IIM, which eventually develops into heart failure, is difficult to identify by conventional examinations at early stage. The aim of this study was to investigate if multi-parametric cardiac magnetic resonance (CMR) imaging can screen for early cardiac involvement in IIM, compared with clinical score (Myositis Disease Activity Assessment Tool, MDAAT). Forty-nine patients of IIM, and 25 healthy control subjects with comparable age-range and sex-ratio were enrolled in this study. All subjects underwent CMR examination, and multi-slice short-axis and 4-chamber cine MRI were acquired to evaluate biventricular global circumferential strain (GCS) and global longitudinal strain (GLS). Native T1 and T2 mapping were performed, and post-contrast T1 mapping and LGE were acquired after administration of contrast. A CMR score was developed from native T1 mean and T2 mean for the identification of cardiac involvement in the IIM cohort. Using contingency tables MDAAT and CMR were compared and statistically analyzed using McNemar test. McNemar's test revealed no significant difference between CMR score and MDAAT (p = 0.454). CMR score had potential to screen for early cardiac involvement in IIM patients, compared to MDAAT.

Application of kNN and SVM to predict the prognosis of advanced schistosomiasis.

Predictive models for prognosis of small sample advanced schistosomiasis patients have not been well studied. We aimed to construct prognostic predictive models of small sample advanced schistosomiasis patients using two machine learning algorithms, k nearest neighbour (kNN) and support vector machine (SVM) utilising routinely available data under the government medical assistance programme. The predictive models were derived from 229 patients from Xiantao and externally validated by 77 patients of Jiayu, two county-level cities in Hubei province, China. Candidate predictors were selected according to expert opinions and literature reports, including clinical features, sociodemographic characteristics, and medical examinations results. An area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the models' predictive performances. The AUC values were 0.879 for the kNN model and 0.890 for the SVM model in the training set, 0.852 for the kNN model, and 0.785 for the SVM model in the external validation set. The kNN and SVM models can be used to improve the health services provided by healthcare planners, clinicians, and policymakers.

Endoplasmic Reticulum Stress Is Involved in Muscular Pathogenesis in Idiopathic Inflammatory Myopathies.

Objectives: Endoplasmic reticulum (ER) stress plays pivotal roles in the regulation of skeletal muscle damage and dysfunction in multiple disease conditions. We postulate the activation of ER stress in idiopathic inflammatory myopathies (IIM). Methods: Thirty-seven patients with immune-mediated necrotizing myopathy (IMNM), 21 patients with dermatomyositis (DM), 6 patients with anti-synthetase syndrome (ASS), and 10 controls were enrolled. The expression of ER stress-induced autophagy pathway was detected using histological sections, Western blot, and real-time quantitative Polymerase Chain Reaction. Results: ER stress-induced autophagy pathway was activated in biopsied muscle of patients with IMNM, DM, and ASS. The ER chaperone protein, glucose-regulated protein 78 (GRP78)/BiP expression in skeletal muscle correlated with autophagy, myofiber atrophy, myonecrosis, myoregeneration, and disease activity in IMNM. Conclusion: ER stress was involved in patients with IIM and correlates with disease activity in IMNM. ER stress response may be responsible for skeletal muscle damage and repair in IIM.

Contribution of relapse-associated worsening to overall disability accrual in patients with relapsing-onset multiple sclerosis: A mediation analysis.

OBJECTIVE: The neurological disability accumulation in patients with relapsing-onset multiple sclerosis (MS) is commonly attributed to relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). Using a mediation model, this research aimed to investigate and quantify the contributions of RAW and PIRA to the overall disability accrual. METHODS: Clinical data, containing Expanded Disability Status Scale (EDSS) scores, duration, attack number, and demographics, were collected from 121 patients with relapsing-onset MS in China and included in the mediation model. Two phases were defined: an early phase, from the clinical onset to EDSS 3, and a later phase, greater than EDSS 3. RESULTS: Clinical attack number partly mediated the relationship between duration and neurological disability (Duration â†’ Attack â†’ EDSS score) only in the early phase, with the ratio of indirect (RAW) to total effect of 0.414; while this mediator effect became negligible (<10%) in the later phase, with a predominating direct effect (PIRA). Onset age positively correlated with EDSS scores during the early stage, independent of the clinical attack number (the direct effect was significant, but the indirect effect was not), while this association was insignificant later. Besides, compared to females, male patients appeared to relapse less frequently before reaching EDSS 3 but were vulnerable to an accelerated progression after that. CONCLUSIONS: In relapsing-onset MS, PIRA is the major contributor to the irreversible disability accrual throughout the whole disease course, albeit RAW is also partly involved during the early stage. The correlations between the disabled outcome and the onset age or sex vary in different phases.

Efficacy of tacrolimus as long-term immunotherapy for neuronal surface antibody-mediated autoimmune encephalitis.

AIMS: We aimed to verify the efficacy and safety of tacrolimus as long-term immunotherapy for the treatment of neuronal surface antibody-mediated autoimmune encephalitis (AE) during the first attack. METHODS: In this retrospective observational cohort study, patients with neuronal surface antibody-mediated AE who experienced the first attack were enrolled. We compared the outcomes of 17 patients who received tacrolimus with those of 47 patients treated without tacrolimus. Patients were assessed at onset and 3, 6, and 12 months, as well as at the last follow-up, by using the modified Rankin scale (mRS) and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The efficacy of tacrolimus was also compared in a subgroup of patients with anti-NMDA receptor encephalitis. RESULTS: Among all patients with neuronal surface antibody-mediated AE, those receiving tacrolimus had lower median mRS scores [1 (IQR = 0-1) versus 2 (IQR = 1-3) in controls, p = 0.001)], CASE scores [2 (IQR = 1-3) versus 3 (IQR = 2-7), p = 0.006], and more favorable mRS scores (94.1% versus 68.1%, p = 0.03) at the 3-month follow-up. No difference was found at the last follow-up. There was no significant difference in the occurrence of relapse and adverse events between the two groups (11.8% versus 14.9%, p = 0.75). In the subgroup of patients with anti-NMDA receptor encephalitis, patients treated with tacrolimus had a lower median mRS score at the 3-month follow-up [1 (IQR = 0-2) versus 2 (IQR = 1-3), p = 0.03]; however, no difference in the outcome was detected at the last follow-up. CONCLUSION: Tacrolimus can be used as long-term immunotherapy in patients with neuronal surface antibody-mediated AE during the first attack. Treatment with tacrolimus appears to accelerate the clinical improvement of neuronal surface antibody-mediated AE.

Distinct Immunological Features of Inflammatory Demyelinating Diseases of the Central Nervous System.

OBJECTIVE: The immunological features between neuromyelitis optica spectrum disorder (NMOSD), multiple sclerosis (MS), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), lacked systemic comparisons. Accordingly, we aimed to investigate immunological differences between NMOSD, MS, and MOGAD. METHODS: Patients with MOGAD, MS, and NMOSD who received immunological tests including cytokine profiles and cytometry analysis of the lymphocyte subgroups were retrospectively reviewed and divided into training and validation sets. Discriminatory models based on immunological data were established to identify optimal classifiers using orthogonal partial least square discriminant analysis (OPLS-DA). Constructed models were tested in another independent cohort. RESULTS: OPLS-DA of the immunological data from 50 patients (26 NMOSD, 14 MS, and 10 MOGAD) demonstrated the discriminatory values of a relatively low level of T-lymphocyte subsets, especially the CD4+ T cells, in MOGAD; a decreased NK cell, eosinophil, and lymphocyte level; an elevated neutrophil-to-lymphocyte ratio in NMOSD; and a declined IFN-γ-producing CD4+ T cells/Th with an increased IL-8 concentration in MS. All the models (NMOSD vs. MS, NMOSD vs. MOGAD, and MS vs. MOGAD) exhibited a significant predictive value and accuracy (>85%). CONCLUSIONS: NMOSD, MS, and MOGAD may be different in pathogenesis, and several immunological biomarkers can serve as potential classifiers clinically.

Overlapping syndrome mimicking infectious meningoencephalitis in a patient with MOG and GFAP IgG.

BACKGROUND: Central nervous system overlapping autoimmune syndromes are uncommon, especially with the coexistence of MOG-IgG and GFAP-IgG. CASE PRESENTATION: A 23-year-old woman presented with transient convulsions, a loss of consciousness, persistent fever, headache, and vomiting. Cerebrospinal fluid (CSF) analysis revealed elevated cellularity, and magnetic resonance imaging (MRI) showed diffuse leptomeningeal enhancement. She had fever and headache with antiviral and antibiotic treatment for 2 weeks, and she had empirical anti-tuberculosis treatment and oral prednisolone therapy. She was followed for 3 months after presentation with improved symptoms and normal CSF analysis. A 3-month follow-up MRI showed asymmetric lesions in the cerebellum, corona radiata, and white matter with enhancement. The anti-tuberculosis treatment was continued, and steroid therapy was discontinued. After she stopped taking prednisolone, an interrupted headache gradually appeared. MRI at 4 months after presentation revealed a partial reduction in lesions but enlarged areas in the left cerebellum and right parietal white matter and a new lesion in the region of the right ependyma with linear enhancement. Her CSF was positive for anti-myelin oligodendrocyte glycoprotein (MOG) and anti-glial fibrillary acidic protein (GFAP) antibodies using a transfected cell-based assay. She was diagnosed with overlapping syndrome of MOG­IgG­associated disease and GFAP astrocytopathy. She received steroid pulse therapy (methylprednisolone, 1 g for 5 days), followed by a gradual tapering of oral prednisolone and the addition of an immunosuppressant (tacrolimus, 3 mg per day). Six months after the initial presentation, she had no symptoms. An MRI showed that the lesions had diminished, and no enhancement was found. CONCLUSIONS: We report a case that was positive for double antibodies, which was initially misdiagnosed as infectious meningoencephalitis. This case broadens the clinical and phenotypic presentation of the overlapping syndrome spectrum.

Characteristics of immune and inflammatory responses among different age groups of pediatric patients with COVID-19 in China.

BACKGROUND: Severe cases of coronavirus disease 2019 (COVID-19) among pediatric patients are more common in children less than 1 year of age. Our aim is to address the underlying role of immunity and inflammation conditions among different age groups of pediatric patients. METHODS: We recruited pediatric patients confirmed of moderate COVID-19 symptoms, admitted to Wuhan Children's Hospital from January 28th to April 1st in 2020. Patients were divided into four age groups (≤ 1, 1-6, 7-10, and 11-15 years). Demographic information, clinical characteristics, laboratory results of lymphocyte subsets test, immune and inflammation related markers were all evaluated. RESULTS: Analysis included 217/241 (90.0%) of patients with moderate clinical stage disease. Average recovery time of children more than 6 years old was significantly shorter than of children younger than 6 years (P = 0.001). Reduced neutrophils and increased lymphocytes were significantly most observed among patients under 1 year old (P < 0.01). CD19+ B cells were the only significantly elevated immune cells, especially among patients under 1 year old (cell proportion: n = 12, 30.0%, P < 0.001; cell count: n = 13, 32.5%, P < 0.001). While, low levels of immune related makers, such as immunoglobulin (Ig) G (P < 0.001), IgA (P < 0.001), IgM (P < 0.001) and serum complement C3c (P < 0.001), were also mostly found among patients under 1 year old, together with elevated levels of inflammation related markers, such as tumor necrosis factor γ (P = 0.007), interleukin (IL)-10 (P = 0.011), IL-6 (P = 0.008), lactate dehydrogenase (P < 0.001), and procalcitonin (P = 0.007). CONCLUSION: The higher rate of severe cases and long course of COVID-19 among children under 1 year old may be due to the lower production of antibodies and serum complements of in this age group.