Immunoadsorption as maintenance therapy for refractory neuromyelitis optica spectrum disorder.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system, affecting mainly optic nerves and spinal cord. NMOSD pathophysiology is associated with anti-aquaporin-4 (AQP4) immunoglobulin G (IgG) autoantibodies. Rapid extracorporeal elimination of autoantibodies with apheresis techniques, such as immunoadsorption (IA), was proven to be an effective treatment of NMOSD attacks. Data on the long-term use of IA to prevent attacks or progression of NMOSD are lacking. Objectives: The aim of this study was to evaluate efficacy and safety of maintenance IA for preventing recurrence of NMOSD attacks in patients refractory to other immunotherapies. Design: Case study. Methods: Retrospective analysis of two female patients with severe NMOSD refractory to conventional immunotherapies was performed. Both patients had responded to tryptophan IA (Tr-IA) as attack therapy and subsequently were treated with biweekly maintenance Tr-IA. Results: Patient 1 (AQP4-IgG seropositive, age 42 years) had 1.38 attacks of optic neuritis per year within 10.1 years before commencing regular Tr-IA. With maintenance Tr-IA for 3.1 years, one mild attack occurred, which was responsive to steroid pulse therapy. Expanded Disability Status Scale (EDSS) was stable at 5.0. Visual function score of the last eye improved from 3 to 1. Patient 2 (AQP4-IgG seronegative, age 43 years) experienced 1.7 attacks per year, mainly acute myelitis and optic neuritis, during the period of 10.0 years before the start of Tr-IA. During regular Tr-IA treatment, no further NMOSD attack occurred. The patient was clinically stable without any additional immunosuppressive treatment for 5.3 years. EDSS improved from 6.0 to 5.0, and the ambulation score from 7 to 1. Tolerability of Tr-IA was good in both patients. No serious adverse events occurred during long-term clinical trajectories. Conclusion: Tr-IA was well tolerated as maintenance treatment and resulted in clinical stabilization of two patients with highly active NMOSD, who were refractory to standard drug therapy.

Bilateral longitudinally extensive optic perineuritis post-COVID-19 presenting as "idiopathic" intracranial hypertension: A case report

Background: Severe acute respiratory syndrome coronavirus 2 (SARSCoV2) has been associated with several neuro-ophthalmic manifestations. We report a case of bilateral longitudinally extensive optic perineuritis suspected due to SARSCoV2. Case Presentation: A 32-year-old woman developed headaches, photophobia, pulsatile tinnitus, and blurred vision 8 d after having a positive SARS-CoV-2 qualitative polymerase chain reaction (PCR) testing for coronavirus disease 2019 (COVID-19). She was diagnosed with and treated for idiopathic intracranial hypertension (IIH) elsewhere. Repeat evaluation at our institution showed a poor visual acuity in both eyes with Frisen grade II papilledema and cotton wool spots on fundoscopic examination. Orbital magnetic resonance imaging (MRI) showed bilateral longitudinally extensive optic nerve sheath enhancement. Repeat lumbar puncture revealed an elevated cerebrospinal fluid (CSF) opening pressure and protein, a finding that is incompatible with the diagnosis of IIH. Myelin oligodendrocyte glycoprotein, aquaporin-4 (AQP4)-IgG antibodies, and other serological tests for optic neuritis were unremarkable. Her visual acuity partially improved after corticosteroids. With the growing association of demyelinating disorders and COVID-19, unremarkable serological workup, and temporal relation of the patient's symptoms to the infection, we believe that her diagnosis is SARS-CoV-2 associated bilateral optic neuritis. Conclusion(s): There is a growing association between demyelinating disorders and COVID-19 and COVID-19 vaccination, and it is essential to recognize CSF abnormalities that are incompatible with a diagnosis of IIH, such as increased protein in our case, and may lead to an incorrect diagnosis.Copyright © 2023 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society for Neuroimmunology.

The Longitudinal Study of Neuromyelitis Optica Spectrum Patients Epidemiological Characteristics, a Six Years Follow Up Survey from Isfahan, Iran

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, rare demyelinating disease of the central nervous system characterized by recurrent attacks which usually involve optic nerves and spinal cord. Although the most common symotoms are myelitis and optic neuritis, it can be presented as cerebral syndromes mainly those related to the brain stem and diencephalon. Since NMOSD is a rare disease and the epidemiological data on this disorder is still insufficient, the establishment of registry and long-term follow up studies are needed to assess the disease course and behavior over a period of time. Material(s) and Method(s): We stablished an electronic registry system for NMOSD patients in the MS center of Kashani hospital, Isfahan, Iran, since spring 2016. Every patient suspected for NMOSD and documented in our database was included in a follow up study to monitor their disease course and progression. Anti AQP4 antibody and Anti MOG antibody were checked for all patients in a unique lab by cell based assay method. Demographic data and clinical characteristics such as family history, comorbidities,education, number of relapses, presentation signs and radiological findings were recorded. Moreove, relapses, treatment change, triggers, and COVID-19 infection were documented. We investigated the effect of the COVID19 pandemic and vaccination on NMOSD patients. Result(s): This study included 173 cases with definite diagnosis of NMOSD, and 56 ones were seropositive for AQP4 Ab. 142 were females of which 46 were in the seropositive group. Their mean age was 40.02+/-11.11 years (45.78+/-12.88 in AQP4Ab positive group). The mean of age at disease onset was about 30.16+/-11.90 years. The mean time of follow up was 55.84+/-18.94 months until today. In 76 patients, there were LETM in the first cervical MRI. 123 patients revealedbabnormality in the first brain MRI. 27 patients had hypothyroidism as the most common comorbidity. 36 cases reported positive family history of multiple sclerosis and also 4 had a family history of NMOSD. Conclusion(s): The mean age of onset did not differ between seropositive and seronegative group but it was higher than MS patients. Brain MRI showed abnormality in NMOSD patients. Female/male was 4.4/1 which is lower than other studies.Copyright © 2022

A new short synthesis route for favipiravir and its analogue: Their tautomerization behaviour

The study of tautomerism in biologically relevant heterocycles is essential, as it directly affects their chemical properties and biological function. Lactam-lactim tautomerization in pyridine/pyrazine derivatives is such a phenomenon. Favipiravir, a pyrazine derivative, is an essential antiviral drug molecule having notable performance against SARS-CoV-2. Along with a better yielding synthetic method for favipiravir, we have also investigated the lactam-lactim tautomerization of favipiravir and its analogous molecules. Most of these molecules were crystalized and studied for various interactions in their lattice. Many interesting supramolecular interactions such as hydrogen bonding, pi-pi stacking and halogen bonding were revealed during the analysis. Some of these structures show interesting F-F halogen bonding and water channels in their solid state.Copyright © 2022 The Royal Society of Chemistry.

Familial neuromyelitis optica spectrum disorders: Case series and systematic review.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is considered a complex multifactorial disorder. Most cases are sporadic, and familial NMOSD is assumed as a rare occurrence. However, few studies reported familial aggregation of the disorder. OBJECTIVES: To report familial NMOSD cases in Thailand and conduct a systematic review of familial NMOSD. METHODS: A retrospective chart review of familial NMOSD patients at the university hospital was performed. Articles related to "genetic" and "NMOSD" were systematically searched and reviewed. We included NMOSD patients whose one or more relatives were diagnosed with the same disease or multiple sclerosis (MS). Data regarding demographics, clinical features, disease outcomes, and genetic testing were collected and analyzed using descriptive statistics. RESULTS: We identified 6 familial cases from 165 NMOSD cases (3.6%) at our hospital and gathered 77 cases from a systematic review, totaling 83 cases from 40 families. The mean (SD) age at onset was 37.2 (18.0) years. Familial NMOSD involved 1-2 generations with mainly 2 affected individuals. The most common kinship pattern was siblingship in 21 families (52.5%). Initial syndromes were mostly optic neuritis and transverse myelitis. Serum aquaporin-4 IgG was positive in 79.7% of cases. Median number of relapses was 3 (range 1-26). Median expanded disability status scale in the last visit was 2 (range 0-8). Reported human leukocyte antigens (HLA) alleles shared between familial cases were HLA-A*01 and HLA-DRB1*03. CONCLUSION: Familial clustering of NMOSD is more common than would be expected in the general population. The demographic, clinical, and outcome profiles of familial cases were not different from sporadic cases. Certain specific HLA haplotypes were shared among familial cases. Our systematic review highlighted complex genetic predisposition to NMOSD.

New developments and concepts in the diagnosis and management of diabetes insipidus (AVP-deficiency and resistance).

Diabetes insipidus (DI) is a disorder characterised by the excretion of large amounts of hypotonic urine, with a prevalence of 1 per 25,000 population. Central DI (CDI), better now referred to as arginine vasopressin (AVP)-deficiency, is the most common form of DI resulting from deficiency of the hormone AVP from the pituitary. The less common nephrogenic DI (NDI) or AVP-resistance develops secondary to AVP resistance in the kidneys. The majority of causes of DI are acquired, with CDI developing when more than 80% of AVP-secreting neurons are damaged. Inherited/familial CDI causes account for approximately 1% of cases. Although the pathogenesis of NDI is unclear, more than 280 disease-causing mutations affecting the AVP2 protein or AVP V2 receptor, as well as in aquaporin 2 (AQP2), have been described. Although the cAMP/protein kinase A pathway remains the major regulatory pathway of AVP/AQP2 action, in vitro data have also revealed additional cAMP independent pathways of NDI pathogenesis. Diagnosing partial forms of DI, and distinguishing them from primary polydipsia, can be challenging, previously necessitating the use of the water deprivation test. However, measurements of circulating copeptin levels, especially after stimulation, are increasingly replacing the classical tests in clinical practice because of their ease of use and high sensitivity and specificity. The treatment of CDI relies on desmopressin administration, whereas NDI requires the management of any underlying diseases, removal of offending drugs and, in some cases, administration of diuretics. A better understanding of the pathophysiology of DI has led to novel evolving therapeutic agents that are under clinical trial.

Immunotherapy-responsive recurrent extensive white matter disease without neuronal or glial surface antibodies: A case report

Background: Acute disseminated encephalomyelitis (ADEM) is classically considered as a monophasic immune-mediated demyelinating disorder. A relapse can occur in children but extremely rare in adults. Case-report: A 57-year-old man presented with fulminant ADEM-like episode without proceeding viral illness. Neurological deficits rapidly developed associated with extensive demyelinating brain lesions with vasogenic edema. After the initiation of aggressive immunotherapy, his symptoms resolved, but he relapsed twice during 26-month observation period;one was a mild episode characterized by rapidly evolving MRI lesions without development of symptoms, and the other was a fulminant ADEM-like episode similar to the first one. The second fulminant episode occurred only 2 days after getting a flu shot despite no clinical or radiological relapse when he received COVID-19 vaccinations. The patient's symptoms and extensive brain MRI lesions improved after the initiation of aggressive immunotherapy at the early stage. No autoantibodies against neuronal surface (such as GABA A receptor) or glial surface antigens (aquaporin 4, or myelin oligodendrocyte glycoprotein) were identified in either serum or CSF. Conclusion(s): Extensive white matter lesions can occur without neuronal or glial surface antibodies, recurrent fulminant ADEM-like episode can develop even in an adult patient, and flu shot may provoke fulminant ADEM-like episode.Copyright © 2022

Acute flaccid myelitis diagnosed after IVIG: a diagnostic dilemma

Case Report: A 4-year-old African American male presented to an outside emergency department (ED) following sudden inability to move left upper extremity. Past medical history was unremarkable and routine vaccinations were up to date. Radiograph of affected extremity ruled out fractures and patient was discharged to follow up with primary care physician. Two days later mother brought him to our ED due to persistent left upper extremity paralysis, poor appetite, and subjective fever. On exam his left arm was warm and tender to dull and sharp touch;he had definite loss of active movement, hypotonia and absence of deep tendon reflexes. The patient had winging of left scapula and could not shrug left shoulder. MRI of cervical and thoracic spine showed enlargement of spinal cord from C2-C6 level with gray matter hyperintensity, slightly asymmetric to the left. Laboratory studies showed leukocytosis (14 000/mcL) and CSF studies showed pleocytosis of 89 WBC/mcL (93.3% mononuclear cells and 6.7% polymorphonuclear cells), 0 RBCs, normal glucose and protein, and a negative CSF meningoencephalitis multiplex PCR panel. Due to high suspicion of demyelinating or autoimmune condition he was treated with high dose steroids and IVIG. Subsequently neuromyelitis optica was ruled out as aquaporin-4 receptor antibodies (AB) and myelin oligodendrocyte glycoprotein AB were normal. CSF myelin basic protein and oligoclonal bands were absent ruling out demyelinating disorders. CSF arboviruses IgM and West Nile IgM were negative. He showed minimal improvement in left upper extremity movement but repeat spinal cord MRI one week later showed improved cord thickness with less hyperintensity. Respiratory multiplex PCR was negative including enteroviruses. Repeat CSF studies after IVIG showed increased IgG index and IgG synthesis suggestive of recent spinal cord infection, consistent with acute flaccid myelitis (AFM). Pre-IVIG blood PCR was invalid for enteroviruses due to PCR inhibitors found in the sample. Blood post-IVIG was negative for mycoplasma IgM, West Nile IgM, and arboviruses IgM. Enterovirus panel titers (post-IVIG) were positive for coxsackie A (1:32), coxsackie B type 4 (1:80) and 5 (1:320), echovirus type 11 (1:160) and 30 (1:80) as well as positive for poliovirus type 1 and 3. These titers could not distinguish acute infection from patient's immunity or false-positives as a result of IVIG. He was discharged with outpatient follow-up visits with neurology, infectious disease, occupational and physical therapy, showing only mild improvement after discharge. Discussion(s):With the anticipated resurgence of AFM after the peak of COVID-19 pandemic, our case illustrates the need to consider this diagnostic possibility in patients with flaccid paralysis. It is important to remember CSF IgG synthesis is not affected by IVIG. In addition when treatment plans include IVIG, appropriate samples should be collected before IVIG to facilitate accurate work-up for infectious diseases. Copyright © 2023 Southern Society for Clinical Investigation.

Evaluation of the Relationship Between Aquaporin-1, Hepcidin, Zinc, Copper, and Iron Levels and Oxidative Stress in the Serum of Critically Ill Patients with COVID-19.

Our study aims to determine the relationship between hepcidin, aquaporin (AQP-1), copper (Cu), zinc (Zn), iron (Fe) levels, and oxidative stress in the sera of seriously ill COVID-19 patients with invasive mechanical ventilation. Ninety persons with and without COVID-19 were taken up and separated into two groups. The first group included seriously COVID-19 inpatients having endotracheal intubation in the intensive care unit (n = 45). The second group included individuals who had negative PCR tests and had no chronic disease (the healthy control group n = 45). AQP-1, hepcidin, Zn, Cu, Fe, total antioxidant status (TAS), and total oxidant status (TOS) were studied in the sera of both groups, and the relations of these levels with oxidative stress were determined. When the COVID-19 patient and the control groups were compared, all studied parameters were found to be statistically significant (p < 0.01). Total oxidant status (TOS), oxidative stress index (OSI), and AQP-1, hepcidin, and Cu levels were increased in patients with COVID-19 compared to healthy people. Serum TAC, Zn, and Fe levels were found to be lower in the patient group than in the control group. Significant correlations were detected between the studied parameters in COVID-19 patients. Results indicated that oxidative stress may play an important role in viral infection due to SARS-CoV-2. We think that oxidative stress parameters as well as some trace elements at the onset of COVID-19 disease will provide a better triage in terms of disease severity.

Aquaporin-4 IgG neuromyelitis optica spectrum disorder onset after Covid-19 vaccination: Systematic review.

Neuromyelitis optica spectrum disorder (NMOSD) is rarely reported following Coronavirus disease 2019 (COVID-19) vaccination. We identified 16 cases of new onset NMOSD with positive aquaporin-4 IgG (AQP4-IgG) following COVID-19 vaccination. Transverse myelitis was the most common clinical presentation (75%). Most patients received high dose steroids for acute treatment and maintenance therapy was started in 12 patients (75%). Twelve patients (75%) had improvement of their symptoms at the time of discharge or follow-up. The included cases share similar epidemiology and natural course to non-vaccine related cases. Clinicians should be aware of possible post-vaccination NMOSD to help with earlier diagnosis and treatment.

COVID-19 Associated Optic Neuritis

Purpose : While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well known for its respiratory complications, ocular manifestations are emerging. This case report describes a patient with bilateral optic neuritis associated with coronavirus disease 2019 (COVID-19). Methods : A 46-year-old male presented with two weeks of pain with eye movement immediately after testing positive for COVID-19 and four days of bilateral blurry vision. Data including history, ocular examination, Humphrey visual field testing (HVF), magnetic resonance imaging (MRI), and serological testing was collected. Results : Visual acuity (VA) was 20/100 in the right eye (OD) and 20/70 in the left eye (OS) with pinhole VA of 20/40 in each eye. Pupil exam, intraocular pressures, and confrontational visual fields were normal. Ocular motility was full, however the patient endorsed pain with eye movement in all directions. The right optic nerve had blurred disc margins while the left optic nerve was unremarkable on exam. Color vision was decreased to 13/15 by Ishihara testing in each eye. MRI of the brain and orbits revealed bilateral thickening and T2 hyperintensity and hyperenhancement of the intercanalicular and intraorbital optic nerves with sparing of the nerve sheath and no demyelinating lesions (Figure 1). Bilateral central scotomas were seen on HVF (Figure 2). At this point, the patient's clinical picture was concerning for optic neuritis associated with COVID-19. A complete blood count, comprehensive metabolic panel, myelin-oligodendrocyte glycoprotein antibody, and aquaporin 4 antibody were unremarkable. Testing for tuberculosis, sarcoidosis, syphilis, thyroid disease, and rheumatologic and autoimmune disorders was normal. The patient was treated with corticosteroids. Within three to six weeks, the patient's symptoms and abnormal exam findings resolved. Conclusions : Infectious pathogens and their subsequent inflammation can cause optic neuritis. It is postulated that T cells release inflammatory mediators and cytokines that cross the blood brain barrier and lead to destruction of myelin, neuronal cell death, axonal degeneration, and vision loss. SARS-CoV-2 could cause a similar inflammatory response leading to optic neuritis and is important to consider in cases without a clear etiology.

Use of Rituximab versus Azathioprine Therapy in Neuromyelitis Optica Spectrum Disorder Patients

Background: A severe antibody-mediated inflammatory demyelinating disease of the central nervous system is neuromyelitis optica spectrum disorder (NMOSD). Azathioprine (AZA) and Rituximab (RTX) were used to treat NMO-SD patients though not FDA approved yet. Aim of the study: To compare the effectiveness and safety of rituximab treatment versus azathioprine in treating individuals with NMOSDs. Methods: Seventy four Egyptian individuals with NMOSDs in this retrospective observational study and collecting their medical records from multiple sclerosis (MS) clinics, Neurology Departments, El-Maadi Military Hospital, and Cairo University hospitals. Fourty four patients received either treatment over two year duration, Group 1 (rituximab group) consisted of 19 patients, while group 2 (azathioprine group) consisted of 25 patients. Their full medical history, general and neurological examination, MRI brain and spinal cord results, and laboratory investigation were collected including immune assays and AQP-4 antibody. Results: There was no statistically significant difference between the groups in terms of brain MRI data at the baseline and outcomes. Between the two groups, there were statistically significant differences in last observer spinal MRI (p=0.025), annual relapse rate before treatment with RTX group (P=0.021), EDSS pretreatment (p=0.005), annual relapse rate post-treatment. When it came to the number of relapses after treatment, there was a high statistically significant difference between the two groups (p=0.016), with group 1 (RTX group) having zero relapses. There was a statistically significant decrease comparing EDDS scores pre-and post-treatment regarding the RTX group (p=0.003). Adverse events were Infusion rate reaction (5.3%) and pneumonic COVID (9.5%) of patients. Conclusion: RTX is more helpful and less harmful for NMO-SD patients than AZA.

Infectious issues of therapeutic monoclonal antibodies in multiple sclerosis and neuromyelitis optica spectrum disorders

Various effective monoclonal antibodies (mAbs) have been approved for both multiple sclerosis (MS) and anti-aquaporin-4-seropositive neuromyelitis optica spectrum disorders worldwide, including in Japan. As these newer mAbs have distinct modes of action that effectively suppress the recurrence of inflammation and slow disability progression, they can modulate and interfere with the protective immune response against pathogens, resulting in various infectious complications. Among various mAbs, natalizumab (NTZ) has the highest risk of causing progressive multifocal leukoencephalopathy (PML), a rare but fatal opportunistic brain infection caused by John Cunningham polyomavirus. Switching from NTZ to B-cell-depleting mAbs, such as ocrelizumab, is also a possible risk factor for PML development. Alemtuzumab carries the risk of reactivation of varicella-zoster virus (VZV);therefore, prophylactic acyclovir treatment is required. NTZ has also been associated with VZV reactivation. Eculizumab can cause severe meningococcal infection due to Neisseria meningitis, and vaccination prior to treatment induction is required. Attention to the reactivation of hepatitis B or Mycobacterium tuberculosis is also needed during mAb therapy. Additionally, in the era of severe acute respiratory syndrome coronavirus 2 infection (COVID-19), the risk for of developing severe COVID-19 may be associated with some mAbs, such as B-cell-depleting agents. Thorough understanding and mitigation strategies for infectious risks are essential.

Systemic Lupus Erythematous Flare Up Presenting as Myelitis

Objective: Present a case of lupus myelitis occurring in a patient already receiving immunosuppression. Background: Neurologic complications of systemic lupus erythematosus span the central and peripheral nervous systems. We present a case of lupus myelitis in a patient previously well controlled with immunosuppression. Design/Methods: N/A Results: A 24-year-old woman with history of systemic lupus erythematosus presented with acute onset inability to walk due to bilateral leg weakness and numbness, associated with constipation and urinary retention. A week before, she experienced runny nose, sore throat, headache and neck pain radiating down her shoulders. Her medication regimen prior to admission included mycophenolate mofetil 1500 mg BID, hydroxychloroquine 200 mg daily, and prednisone 2.5 mg daily. Examination revealed bilateral lower limb weakness, more pronounced on right, hyperesthesia in the right leg, decreased proprioception bilaterally. She had intact pinprick, light touch, and vibration sense. Ankle reflexes were absent bilaterally. Laboratory testing showed pancytopenia, elevated anti-DsDNA (107 IU/mL), ESR of 69 mm/h, low serum C3/C4 and proteinuria. COVID-19 testing was negative. CSF analysis showed WBC of 890/mm3 , neutrophil predominance (93%), decreased glucose (32 mg/dL) and elevated protein (129 g/L). CSF cultures were negative. Aquaporin-4 receptor antibodies testing is pending. MRI of thoracic spine revealed patchy FLAIR hyperintensities at the level of T2, T4 and T10- T11 with mild enhancement at the level of the lesion T10-11, following intravenous gadolinium. The patient was treated IV methylprednisolone followed by cyclophosphamide and maintenance daily oral steroids with significant improvement of motor symptoms. She had mild residual right dorsiflexion weakness. Urinary and bowel function normalized. Conclusions: Lupus myelitis is a rare and potentially devastating complication of systemic lupus erythematosus. The timely recognition is crucial for proper management. CSF picture resembles an infection and may be misleading. While aquaporin-4 receptor antibodies report is pending, her very good recovery with methylprednisolone and cyclophosphamide strongly suggests lupus myelitis.

Severe Presentation of Neuromyelitis Optica with Positive Antibody Following COVID-19 Vaccination

Objective: To report a case of antibody-positive neuromyelitis optica (NMO) after COVID-19 vaccination. Background: Neuromyelitis optica spectrum disorder is a rare demyelinating disorder of the central nervous system characterized by longitudinally extensive transverse myelitis (LETM) and severe, sometimes bilateral optic neuritis. The majority of cases have serologic or CSF antibody for aquaporin-4 (AQP4). Design/Methods: Case report Results: A 19 year old woman with no prior medical history presented with two days of progressive, severe weakness and sensory changes first in the arms, then legs. On the morning of presentation, she woke with urinary incontinence. She had received COVID-19 vaccination (Moderna) fifteen days preceding her onset of symptoms. Examination revealed sinus tachycardia, MRC grade 3-4/5 power in the arms, 0/5 in the legs with approximately T4 sensory level. Cervical spine MRI revealed T2 prolongation in the spinal cord extending from the cervicomedullary junction to the conus medullaris. CSF revealed neutrophilic pleocytosis with increased IgG synthesis rate and positive CSF AQP4 antibody;serum AQP4 and MOG antibodies were negative. Bilateral, saddle pulmonary emboli were discovered shortly after admission. Her NMO was treated with high-dose intravenous methylprednisolone, plasmapheresis, and rituximab. Conclusions: This case describes a severe, new presentation of antibody-positive neuromyelitis optica following vaccination against COVID-19.

A Pediatric Case of Severe, Treatment-Resistant, COVID-19 Associated Acute Longitudinally Extensive Transverse Myelitis with Masquerading Confounding Variables

Objective: To report a pediatric case of severe, treatment-resistant, COVID-19-associated acute longitudinally extensive transverse myelitis (LETM). Background: Since the COVID-19 global pandemic, there is evolving literature reporting the neurological manifestations of the novel coronavirus. COVID-19-associated acute LETM was first reported in an elderly Asian man with lower-extremity weakness <1-week after onset of fever and respiratory distress. In childhood, this is rarely reported with only few reports of COVID-19-associated acute LETM. Design/Methods: We reviewed clinical and radiographic reports of our patient. We searched PubMed for literature using terms “transverse myelitis & COVID-19” and “pediatric transverse myelitis&COVID-19.” Results: A 5-year-old previously healthy boy presented with altered mental status. Prior to admission, he was exposed to COVID-19 and had consumed an unknown quantity of sertraline and risperidone tablets. Thereafter, he stated that he could not feel his legs, fell, and hit his head. In the emergency department, he was intubated. EKG revealed QTc prolongation (486-ms). SARS-CoV-2-PCR positive. Thereafter, flaccid quadriparesis, bulbar dysfunction, left-sided numbness, and hyperreflexia were noted;he communicated by eye blinking. MRI-spine revealed C1-C4 hyperintensity (T2-weighted) consistent with LETM;DWI negative for acute stroke. CSF basic labs, viral and MS panels, and ACE unremarkable. Serum anti-aquaporin-4 and myelin-oligodendrocyte-glycoprotein antibodies negative. Serum West Nile-IgM-IgG negative. Mycoplasma pneumoniae IgM-reactive, IgG-positive;confirmatory IgM immunofluorescence assay-negative. He received IV-methylprednisolone ×5-days, plasmapheresis ×10-sessions, pulsed steroid ×3-days. Minimal neurological improvement was noted. Repeat MRI-spine 2-weeks later unchanged. Tracheostomy and gastric tube were placed. He was transferred to a neurology topic. Conclusions: COVID-19-associated acute LETM in childhood can have a rapid, devastating clinical course. Clinicians should maintain a high-index of suspicion for LETM in COVID-19 pediatric patients presenting with neurological manifestations and consider alternative strategies for severe, treatment-resistant cases.

Longitudinal Extensive Transverse Myelitis:rare immunotherapy related adverse effect vs COVID19-related immunization complication

Objective: To report an acute presentation of long extensive transverse myelitis (LETM) in the setting of Atezolizumab monotherapy and COVID-19 mRNA immunization Background: Patients being treated with immune checkpoint inhibitors (ICI) for advanced malignancy have an increased propensity of developing neuro-immune complications. With the advent of the COVID-19 pandemic there have been reported cases of TM following COVID-19 immunization. The reported infrequency of TM with both aforementioned causes makes delineating the etiology challenging. Design/Methods: A 58-year-old male with metastatic SCLC completed 4 cycles of Atezolizumab, Carboplatin and Etoposide and was transitioned to Atezolizumab maintenance. He previously underwent Atezolizumab infusion and was administered the second dose of COVID-19 mRNA vaccine one day prior to developing acute lower extremity paralysis, sensory loss from chest down and overflow incontinence. MRI spine illustrated centromedullary enhancing lesions from C7-T7. CSF analysis showed 25 WBC, 116/uL RBC, 94 mg/dL protein, normal glucose, negative oligoclonal bands and normal IgG index. CSF bacterial and virology studies were negative. Additionally, serum anti-myelin oligodendrocyte glycoprotein (MOG) and antiaquaporin receptor 4 (AQP4) antibodies were unremarkable. Results: 5-day course of pulsed methylprednisolone followed by three therapeutic plasma exchanges produced minimal improvement in lower extremities strength and sensory level. Conclusions: This case demonstrates the complication and symptomatology of TM in the setting of anti-PD-L1 monoclonal antibody with the co-incidental COVID-19 mRNA vaccine administration. The causal relationship between the vaccine and TM is difficult to establish due to limited data and the presence of a known inciting factor but hints at a possible exaggeration of the existing neuroinflammatory process. Currently, CDC recommends that individuals who are moderately to severely immunocompromised receive an additional dose of an mRNA COVID-19 Vaccine (Pfizer-BioNTech or Moderna) at least 28 days after the completion of the initial mRNA COVID-19 vaccine series. Caution should be given for those patients who are on ICI therapy.

Case Series of New-Onset CNS Immunological Disorders Temporally Associated with mRNAbased COVID-19 Vaccines

Objective: To present a single-health system retrospective analysis of post-mRNA-based COVID-19 vaccination CNS autoimmunity conducted in the greater New York City area. Background: There have been rare reports associating mRNA-based COVID-19 vaccines with central nervous system (CNS) inflammation. We report a case series of five patients with newonset neurological disorders of immunological origin temporally associated with these vaccines. Design/Methods: Case-series. Results: Five cases of post-vaccination CNS disorders of immune origin were observed within two weeks of inoculation with either the first or second dose of mRNA-based COVID-19 vaccines (Moderna = 3, Pfizer = 2). This includes: Fatal ADEM (n = 1), new-onset NMO (n = 2), new-onset fulminant MS (n = 1), and meningoencephalitis (n = 1). The age of our patients ranged from 27 to 81, and three were female. None of the patients had pre-existing neurological illnesses and one had a pre-existing autoimmune condition (immune thrombocytopenia purpura). New-onset focal neurological symptoms were present in all five patients, including quadriparesis, numbness, diplopia, and encephalopathy. CSF pleocytosis was present in all patients, and three had elevated protein. All but one patient (meningoencephalitis) had contrastenhancing lesions involving either the cerebrum or spinal cord. Both NMO patients had longitudinally extensive transverse lesions involving the central thoracic cord. Aquaporin-4 serum antibody was present in one NMO patients and aquaporin-4 CSF antibody present in the other. All but one patient (fatal ADEM) clinically improved with pulse steroids or plasmapheresis. Conclusions: These are among the emerging cases of CNS immunological events temporally associated with mRNA-based COVID-19 vaccines. These findings should be interpreted with great caution as they neither prove a link nor imply a potential long-term increased risk in postvaccination CNS autoimmunity. Larger prospective studies are needed. The mRNA-based SARS-CoV-2 vaccines should continue to be strongly encouraged given their high efficacy in overcoming this pandemic.

A Case Presenting with Neuromyelitis Optica Spectrum Disorder and Infectious Polyradiculitis Following BNT162b2 Vaccination and COVID-19.

A 37-year-old woman presented with paraparesis and paresthesia in both legs 19 and 3 days after BNT162b2 vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, respectively. Cerebrospinal fluid (CSF) analysis, nerve conduction study, electromyography, magnetic resonance imaging, and autoantibody tests were performed. Neurological examination showed hyperesthesia below the T7 level and markedly impaired bilateral leg weakness with absent deep tendon reflexes on the knees and ankles. CSF examination revealed polymorphonuclear dominant pleocytosis and elevated total protein levels. Enhancement of the pia mater in the lumbar spinal cord and positive sharp waves in the lumbar paraspinal muscles indicated infectious polyradiculitis. In contrast, a high signal intensity of intramedullary spinal cord on a T2-weighted image from C1 to conus medullaris and positive anti-aquaporin-4 antibody confirmed neuromyelitis optica spectrum disorder (NMOSD). The patient received intravenous methylprednisolone, antiviral agents, and antibiotics, followed by a tapering dose of oral prednisolone and azathioprine. Two months after treatment, she was ambulatory without assistance. The dual pathomechanism of NMOSD triggered by coronavirus disease 2019 (COVID-19) vaccination and polyradiculitis caused by SARS-CoV-2 infection may have caused atypical clinical findings in our patient. Therefore, physicians should remain alert and avoid overlooking the possibilities of diverse mechanisms associated with neurological manifestations after SARS-CoV-2 infection and COVID-19 vaccination.

Antibody-Positive Neuromyelitis Optica Spectrum Disorder After Second COVID-19 Vaccination: a Case Report.

In the era of the COVID-19 pandemic declared in March 2020, widespread vaccination protocols were initiated to mitigate the severity and spread of COVID-19. Although COVID-19 vaccines have been generally considered safe, adverse events post-vaccination have been reported, including the development of demyelinating disease. We report a rare case of de novo aquaporin-4-positive neuromyelitis optica spectrum disorder (NMOSD) in an 80-year-old man following BNT162b SARS-CoV-2 vaccination to raise the awareness of this possible severe adverse event in an older adult. An 80-year-old South Asian man presented 2 days following his second dose of the Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine with progressive left-sided leg weakness and numbness resulting in falls. MRI of the spine revealed a longitudinally extensive transverse myelitis from T3-T4 to T9-T10. Serum antibody testing revealed positive aquaporin-4 (AQP4) antibodies. He was diagnosed with AQP4-positive NMOSD and was treated with high-dose intravenous methylprednisolone and plasma exchange with some improvement. He was subsequently treated with mycophenolate mofetil and a slow steroid wean. This case report adds to the existing literature and suggests that COVID-19 vaccinations may trigger de novo NMOSD or NMOSD relapses in some individuals. Although rare, our patient presented with new-onset NMOSD in his 80 s following COVID-19 vaccination. As such, it is relevant to consider AQP4 testing in those presenting with a post-vaccination myelitis, regardless of age. Ongoing vaccine surveillance and research are needed to understand the risk of NMOSD post-COVID-19 vaccinations further.