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.

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*

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

To explore the clinical features and influencing factors of first-onset neuromyelitis optica spectrum disease (NMOSD) within 1 year after delivery. A single center, observational cohort study was used to retrospectively analyze 12 patients with first-onset NMOSD within 1 year after delivery hospitalized in the Department of Neurology of Beijing Tong Ren Hospital from June 2015 to June 2018(short as the postpartum onset group). 12 patients with first-onset NMOSD without 1 year after delivery hospitalized in our department during the same period were selected (short as the control group). The results showed the next recurrence interval in the postpartum onset group was longer than the control group [the postpartum onset group: (6.1±3.5) years, the control group: (1.6±1.5) years, t=3.622,P=0.005], the times of relapses were less than the control group [the postpartum onset group: (1.8±1.4) times, the control group:4.0 (3.0, 7.3) times, Z=-3.122,P=0.002], and expanded disability status scale (EDSS) of the last follow-up was lower than the control group [the postpartum onset group: 3.0(2.3, 3.9), the control group: 4.5(4.0, 6.0), Z=-3.358,P=0.001] with statistically significant differences. The recurrence rates of 1 year, 3 years and 5 years in the postpartum onset group (0%, 16.7%, 33.3%) were lower than control group (58.3%, 83.3%, 91.7%) with statistically significant differences (χ²=8.000,P=0.014;χ²=10.667,P=0.003; χ²=8.711,P=0.009). After the second delivery, the recurrence rate in postpartum onset group was 100% (n=3) and in control group was 50%(n=2), but the difference was not statistically significant (χ²=2.100,P=0.429). In the postpartum onset group, combination of autoimmune disease was consistent with positive in serum AQP-4 antibody moderately (Kappa=0.5, P=0.046). Positive in other autoimmune antibodies were consistent with positive in serum AQP-4 antibody moderately (Kappa=0.5, P=0.046). Combination of autoimmune disease were consistent with positive in serum other autoimmune antibodies well (Kappa=0.667, P=0.021). In conclusion, the first-onset NMOSD within 1 year after delivery have longer next recurrence interval, less times of relapses, lower relapse rate, better long-term prognosis of central nervous system, and they have trend to suffering from recurrent after the second delivery. For the females, combined with autoimmune disease or autoimmune antibody, who are ready for pregnancy, could detect serum AQP-4; if serum AQP-4 positive, they are recommended to prevent the occurrence of NMOSD after delivery.
Pregnancy ; Female ; Humans ; Neuromyelitis Optica/diagnosis* ; Retrospective Studies ; Cohort Studies ; Postpartum Period ; Recurrence

Central nervous system involvement in primary Sjögren's syndrome (pSS) is less common and usually presents as white matter lesions, neuromyelitis optica spectrum disorder (NMOSD), or transverse myelitis. NMOSD is an immune-mediated inflammatory demyelinating disease of the central nervous system with a high rate of relapse and significant disability. Studies have shown that patients with pSS combined with NMOSD have more severe symptoms and poorer prognosis. Here, we present a case of critical illness in pregnancy-associated NMOSD combined with Sjögren's syndrome. The patient was a 30-year-old pregnant woman with a history of Sjögren's syndrome who was diagnosed with NMOSD. She received combination therapy with steroids, intravenous immunoglobulin (IVIG), and hydroxychloroquine during pregnancy, resulting in partial resolution of numbness below the waist. However, due to irregular medication adherence outside the hospital setting, she developed weakness in her right lower limb accompanied by inability to move it, while her left lower limb still had some mobility but occasional numbness along with urinary and fecal incontinence. Ten days later, she was admitted to the emergency department where an emergency cesarean section was performed to deliver a healthy baby boy. However, her condition worsened postpartum as she developed high fever accompanied by bilateral lower limb paralysis and weakness along with loss of voluntary control over urination and defecation. The patient underwent ano-ther course of treatment consisting of steroids and IVIG; however there was limited improvement in symptoms observed after this intervention. Following administration of rituximab for the first time, the patient developed urinary tract infection which was successfully managed before continuing regular infusions. In later stages the patient could walk slightly with a limp and regained control over urination and defecation, allowing her to resume normal activities. This case suggests that combination therapy with steroids, IVIG, and hydroxychloroquine should be considered for the patients with pregnancy-associated NMOSD combined with Sjögren's syndrome. Rituximab can significantly improve symptoms such as postpartum paralysis in patients with NMOSD, however, there may be a risk of infection associated with its use.
Adult ; Female ; Humans ; Pregnancy ; Cesarean Section/adverse effects* ; Critical Illness ; Hydroxychloroquine/therapeutic use* ; Hypesthesia/complications* ; Immunoglobulins, Intravenous/therapeutic use* ; Inflammation/complications* ; Neuromyelitis Optica/diagnosis* ; Paralysis/complications* ; Pregnancy Complications/therapy* ; Rituximab/therapeutic use* ; Sjogren's Syndrome/complications* ; Steroids/therapeutic use* ; Vision Disorders

To explore the clinical features and influencing factors of first-onset neuromyelitis optica spectrum disease (NMOSD) within 1 year after delivery. A single center, observational cohort study was used to retrospectively analyze 12 patients with first-onset NMOSD within 1 year after delivery hospitalized in the Department of Neurology of Beijing Tong Ren Hospital from June 2015 to June 2018(short as the postpartum onset group). 12 patients with first-onset NMOSD without 1 year after delivery hospitalized in our department during the same period were selected (short as the control group). The results showed the next recurrence interval in the postpartum onset group was longer than the control group [the postpartum onset group: (6.1±3.5) years, the control group: (1.6±1.5) years, t=3.622,P=0.005], the times of relapses were less than the control group [the postpartum onset group: (1.8±1.4) times, the control group:4.0 (3.0, 7.3) times, Z=-3.122,P=0.002], and expanded disability status scale (EDSS) of the last follow-up was lower than the control group [the postpartum onset group: 3.0(2.3, 3.9), the control group: 4.5(4.0, 6.0), Z=-3.358,P=0.001] with statistically significant differences. The recurrence rates of 1 year, 3 years and 5 years in the postpartum onset group (0%, 16.7%, 33.3%) were lower than control group (58.3%, 83.3%, 91.7%) with statistically significant differences (χ²=8.000,P=0.014;χ²=10.667,P=0.003; χ²=8.711,P=0.009). After the second delivery, the recurrence rate in postpartum onset group was 100% (n=3) and in control group was 50%(n=2), but the difference was not statistically significant (χ²=2.100,P=0.429). In the postpartum onset group, combination of autoimmune disease was consistent with positive in serum AQP-4 antibody moderately (Kappa=0.5, P=0.046). Positive in other autoimmune antibodies were consistent with positive in serum AQP-4 antibody moderately (Kappa=0.5, P=0.046). Combination of autoimmune disease were consistent with positive in serum other autoimmune antibodies well (Kappa=0.667, P=0.021). In conclusion, the first-onset NMOSD within 1 year after delivery have longer next recurrence interval, less times of relapses, lower relapse rate, better long-term prognosis of central nervous system, and they have trend to suffering from recurrent after the second delivery. For the females, combined with autoimmune disease or autoimmune antibody, who are ready for pregnancy, could detect serum AQP-4; if serum AQP-4 positive, they are recommended to prevent the occurrence of NMOSD after delivery.
Pregnancy ; Female ; Humans ; Neuromyelitis Optica/diagnosis* ; Retrospective Studies ; Cohort Studies ; Postpartum Period ; Recurrence

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