Humans ; Lupus Vasculitis, Central Nervous System/pathology* ; Magnetic Resonance Imaging/methods* ; Diffusion Tensor Imaging/methods* ; Patients ; Lupus Erythematosus, Systemic/pathology* ; Brain/pathology*

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

INTRODUCTION

Demyelinating central nervous system (CNS) disorders such as transverse myelitis (TM) and multiple sclerosis (MS) have been reported with mRNA Covid-19 vaccine. Some cases were relapses of a pre-existing condition but de novo and initial presentation of MS after BNT162b2 COVID-19 mRNA vaccine has very rarely been documented.

We report a 72-year-old female, right-handed, Filipina, with a one-month history of bilateral lower extremity weakness which occurred 7 days after she received her first booster dose of BNT162b2 mRNA vaccine. This was later accompanied by fecal and urinary incontinence. On examination, she had motor deficit below L1 myotome manifesting with loss of hip flexion, knee extension, dorsiflexion, and plantar flexion. There was also sensory deficit below T10 level with relative 80% sensation of vibratio, proprioception, light touch and complete loss of pain and temperature sensation. The initial impression was Transverse Myelitis which may be related to a post-vaccination state. Spinal magnetic resonance imaging (MRI) revealed long segment enhancing T2W hyperintense lesion at T2 to T7. Cranial MRI revealed ovoid areas of heterogeneous, predominantly T2/FLAIR hyperintense signals exhibiting restricted diffusion in the periventricular white matter of the fronto-parietal lobes. Cerebrospinal fluid (CSF) analysis was negative for infectious causes such as tuberculosis but with high levels of CSF immunoglobulin G. She was then diagnosed to have Multiple Sclerosis (MS) and was treated with high dose oral prednisone. However, there was no improvement in neurological deficits on follow-up.

This case adds to the reported rare cases of initial presentation of MS occurring after vaccination for COVID-19 and the first reported case in the Philippines. Early recognition and prompt treatment is important to improve outcomes.

Miller Fisher syndrome（MFS）is a clinical variant of Guillain-Barre syndrome（GBS）and has the main clinical features of ataxia，ophthalmoplegia，and tendon areflexia，with pupil changes and abnormal pupillary light reflex in rare cases. There are generally no symptom fluctuations，and positive anti-GQ1b IgG antibodies can be detected in some patients. This article reports a case of MFS with positive anti-GQ1b，anti-GT1a，and anti-sulfatide antibodies and fluctuating extraocular muscle paralysis as the initial presentation，accompanied by bilateral pupil dilation，delayed light reflex，and numbness and weakness in the limbs. The symptoms are rare and atypical，which may easily lead to misdiagnosis in clinical practice.
Miller Fisher Syndrome ; Ophthalmoplegia

Humans ; Herpesvirus 3, Human ; Myelitis, Transverse/complications* ; Guillain-Barre Syndrome/complications* ; Herpes Zoster/complications* ; Varicella Zoster Virus Infection/complications*

OBJECTIVE: To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action. METHODS: This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively. RESULTS: GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45⁺CD11b⁺ and CD45⁺CD4⁺ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05). CONCLUSION GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.
Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental/pathology* ; Grape Seed Extract/therapeutic use* ; Interleukin-17 ; Interleukin-1beta ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Th1 Cells ; Mice, Inbred C57BL ; Interferon-gamma/therapeutic use* ; Th17 Cells/metabolism* ; Interleukin-12/therapeutic use* ; Cytokines/metabolism*

Different autoantibodies can be detected in patients with coronavirus disease 2019 (COVID-19). It is reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could induce autoimmune diseases (AID), including children's multisystem inflammatory syndrome (MIS-C), Guillain Barre syndrome (GBS), Autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP) and thyroid autoimmune diseases. This article mainly reviews the similarities between COVID-19 and AID, the possibility of COVID-19 inducing AID, the risk of AID patients infected or vaccinated against COVID-19. The purpose is to provide strategies for the prevention, management and treatment of AID during the epidemic.
Child ; Humans ; COVID-19 ; SARS-CoV-2 ; Guillain-Barre Syndrome/therapy* ; Epidemics

Objective: To investigate the misdiagnosis of area postrema syndrome (APS) manifesting as intractable nausea, vomiting and hiccups in neuromyelitis optic spectrum disease (NMOSD) and reduce the risk of misdiagnosis. Methods: We retrospectively analyzed data from NMOSD patients attending the Department of Neurology at the First Medical Center of PLA General Hospital between January 2019 and July 2021. SPSS25.0 was then used to analyze the manifestations, misdiagnosis, and mistreatment of APS. Results: A total of 207 patients with NMOSD were included, including 21 males and 186 females. The mean age of onset was 39±15 years (range: 5-72 years). The proportion of patients who were positive for serum aquaporin 4 antibody was 82.6% (171/207). In total, 35.7% (74/207) of the NMOSD patients experienced APS during the disease course; of these patients, 70.3% (52/74) had APS as the first symptom and 29.7% (22/74) had APS as a secondary symptom. The misdiagnosis rates for these conditions were 90.4% (47/52) and 50.0% (11/22), respectively. As the first symptom, 19.2% (10/52) of patients during APS presented only with intractable nausea, vomiting and hiccups; 80.8% (42/52) of patients experienced other neurological symptoms. The Departments of Gastroenterology and General Medicine were the departments that most frequently made the first diagnosis of APS, accounting for 54.1% and 17.6% of patients, respectively. The most common misdiagnoses related to diseases of the digestive system and the median duration of misdiagnosis was 37 days. Conclusions: APS is a common symptom of NMOSD and is associated with a high rate of misdiagnosis. Other concomitant symptoms often occur with APS. Gaining an increased awareness of this disease/syndrome, obtaining a detailed patient history, and performing physical examinations are essential if we are to reduce and avoid misdiagnosis.
Male ; Female ; Humans ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Neuromyelitis Optica/diagnosis* ; Area Postrema ; Retrospective Studies ; Hiccup/complications* ; Vomiting/etiology* ; Nausea/etiology* ; Inflammation ; Syndrome ; Autoantibodies ; Diagnostic Errors ; Aquaporin 4

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Aicardi-Goutières syndrome 3 (AGS3). METHODS: Trio whole exome sequencing was carried out for the child and his parents, and candidate variants were verified by Sanger sequencing. To further clarify their pathogenicity, the crystal structure of the variants was simulated and analyzed, and the plasmid of variants was expressed in vitro. A literature search was also carried out to summarize the phenotypic and genetic characteristics of AGS3. RESULTS: The child was found to harbor novel compound heterozygous variants of the RNASEH2C gene, namely c.434G>T (p.Arg145Leu) and c.494G>C (p.Ter165Ser), which were inherited from his mother and father, respectively. Analysis of protein crystal structure suggested that the c.434G>T (p.Arg145Leu) variant may affect the stability of local structure, and in vitro experiments showed that this variant can lead to protein degradation. The c.494G>C (p.Ter165Ser) variant has destroyed the stop codon, resulting in prolonged variant. CONCLUSION The novel compound heterozygous variants of the RNASEH2C gene probably underlay the AGS3 in this child, which has enriched the phenotypic and mutational spectrum of this disorder.
Humans ; Child ; Mutation ; Autoimmune Diseases of the Nervous System/genetics* ; Nervous System Malformations/genetics*

OBJECTIVE: To analyze and compare the characteristics and causes of F wave changes in patients with Charcot-Marie-Tooth1A (CMT1A) and chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Thirty patients with CMT1A and 30 patients with CIDP were enrolled in Peking University Third Hospital from January 2012 to December 2018. Their clinical data, electrophysiological data(nerve conduction velocity, F wave and H reflex) and neurological function scores were recorded. Some patients underwent magnetic resonance imaging of brachial plexus and lumbar plexus, and the results were analyzed and compared. RESULTS: The average motor conduction velocity (MCV) of median nerve was (21.10±10.60) m/s in CMT1A and (31.52±12.46) m/s in CIDP. There was a significant difference between the two groups (t=-6.75, P < 0.001). About 43.3% (13/30) of the patients with CMT1A did not elicit F wave in ulnar nerve, which was significantly higher than that of the patients with CIDP (4/30, 13.3%), χ²=6.65, P=0.010. Among the patients who could elicit F wave, the latency of F wave in CMT1A group was (52.40±17.56) ms and that in CIDP group was (42.20±12.73) ms. There was a significant difference between the two groups (t=2.96, P=0.006). The occurrence rate of F wave in CMT1A group was 34.6%±39%, and that in CIDP group was 70.7%±15.2%. There was a significant difference between the two groups (t=-5.13, P < 0.001). The MCV of median nerve in a patient with anti neurofascin 155 (NF155) was 23.22 m/s, the latency of F wave was 62.9-70.7 ms, and the occurrence rate was 85%-95%. The proportion of brachial plexus and lumbar plexus thickening in CMT1A was 83.3% (5/6) and 85.7% (6/7), respectively. The proportion of brachial plexus and lumbar plexus thickening in the CIDP patients was only 25.0% (1/4, 2/8). The nerve roots of brachial plexus and lumbar plexus were significantly thickened in a patient with anti NF155 antibody. CONCLUSION The prolonged latency of F wave in patients with CMT1A reflects the homogenous changes in both proximal and distal peripheral nerves, which can be used as a method to differentiate the CIDP patients characterized by focal demyelinating pathology. Moreover, attention should be paid to differentiate it from the peripheral neuropathy caused by anti NF155 CIDP. Although F wave is often used as an indicator of proximal nerve injury, motor neuron excitability, anterior horn cells, and motor nerve myelin sheath lesions can affect its latency and occurrence rate. F wave abnormalities need to be comprehensively analyzed in combination with the etiology, other electrophysiological results, and MRI imaging.
Humans ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/pathology* ; Median Nerve/pathology* ; Ulnar Nerve/pathology* ; Brachial Plexus/pathology* ; Magnetic Resonance Imaging/methods*