Diagnosis Of Neuromyelitis Optica Research Articles

Biomarkers for neuromyelitis optica: a visual analysis of emerging research trends.

Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis. Over the past 20 years, the search for biomarkers for neuromyelitis optica has been ongoing. Here, we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis optica. Research in this area is consistently increasing, with China and the United States leading the way on the number of studies conducted. The Mayo Clinic is a highly reputable institution in the United States, and was identified as the most authoritative institution in this field. Furthermore, Professor Wingerchuk from the Mayo Clinic was the most authoritative expert in this field. Keyword analysis revealed that the terms "neuromyelitis optica" (261 times), "multiple sclerosis" (220 times), "neuromyelitis optica spectrum disorder" (132 times), "aquaporin 4" (99 times), and "optical neuritis" (87 times) were the most frequently used keywords in literature related to this field. Comprehensive analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple sclerosis. Furthermore, aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum disorder. Myelin oligodendrocyte glycoprotein-IgG is a diagnostic biomarker for myelin oligodendrocyte glycoprotein antibody-associated disease. Recent biomarkers for neuromyelitis optica include cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein, serum astrocyte damage biomarkers like FAM19A5, serum albumin, and gamma-aminobutyric acid. The latest prospective clinical trials are exploring the potential of these biomarkers. Preliminary results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelitis optica spectrum disorder. The ultimate goal of future research is to identify non-invasive biomarkers with high sensitivity, specificity, and safety for the accurate diagnosis of neuromyelitis optica.

Рецидивирующий оптический неврит при оптиконейромиелите

This report presents a clinical case of complex differential diagnosis of optical neuritis in demyelinating disease (multiple sclerosis and neuromyelitis optica). We observed 5 relapses of optic neuritis within 4 years from the onset of the disease, in the absence of both clinical and neuroimaging signs of myelitis. The diagnosis of neuromyelitis optica became valid only after the neurologist identified motor symptoms and the corresponding criteria on the MRI picture. Recurrent optic neuritis, especially bilateral with incomplete recovery of visual functions (despite the absence of acute myelitis and postrema area syndrome and a negative blood test for AQP4-IgG) requires special caution of the doctor and can be considered as a potential case of Devic’s neuromyelitis optica. Key words: devic’s neuromyelitis optica, neuromyelitis optica, optic neuritis, multiple sclerosis, neuromyelitis optica spectrum disorders, AQPR4

Mortality of the Danish Nationwide AQP4 Antibody-Seropositive Neuromyelitis Optica Spectrum Disorder Patient Cohort.

We aimed to evaluate the mortality of patients with AQP4 antibody-seropositive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) in Denmark compared with that in the general population. We identified patients with AQP4-Ab+ NMOSD fulfilling the 2015 International Panel for Neuromyelitis Optica Diagnosis (IPND) criteria from multiple sources (laboratories and the Danish Multiple Sclerosis Registry). We obtained detailed information about patients from hospital records and about the general population matched on age, sex, and calendar year from Statistics Denmark. We calculated standardized mortality ratio (SMR), excess number of deaths per 1,000 person-years (EDR), and life expectancies compared with those of the matched general population. We examined predictive factors of mortality and the cause of death. Of 66 patients with AQP4-Ab+ NMOSD between 2008 and 2020, 15 died. Overall, the SMR was 2.54 (95% CI 1.47-4.09), and the EDR was 16.8 (95% CI 4.6-34.3). The median life expectancy for patients with AQP4-Ab+ NMOSD was 64.08 years (95% CI 53.02-83.9), compared with 83.07 years for the general population. Risk of death over time was increased in the patient population with a hazard ratio (HR) of 2.22 (1.34-3.68; p = 0.002). The cause of death was directly related to NMOSD in 93% of the cases. The age at disease onset was an independent predictor of death (HR 1.042; 95% CI 1.006-1.079; p = 0.02). AQP4-Ab+ NMOSD is associated with increased mortality and shorter life expectancy compared with that in the general population, underlining the need for highly effective treatment approaches.

Neuromyelitis Optica with Negative AQP-4 Antibody

Abstract
 Introduction : Neuromyelitis Optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system that causes demyelination of the optic nerve and spinal cord. Approximately 75% of cases have antibodies against aquaporin 4 (AQP-4 Antibody).
 Case Illustration : A 42 years old male presented with progressing blurred vision in his right eye for 3 weeks. He described there was a black spot in his central vision which gradually enlarged to his peripheral vision, headache for 4 months, and transient tingling sensation and weakness on the left arm for 1 week. Positive RAPD in the right eye and signs of optic neuritis on funduscopy in Opthalmology examination. Campimetry examination revealed generalized depression in the right eye. The visual evoked potential (VEP) was consistent with right optic nerve demyelination. Spine MRI showed extensive transverse myelitis lesions >3 spinal cord hyperintensity on the level of C2-C6. However, the serum AQP-4 antibody was negative. The patient was treated with corticosteroid, and neuroprotector and was also being treated alongside the neurology department.
 Discussion : NMO is a rare autoimmune disease. NMO is characterized by segmented demyelination and inflammation of the spinal cord and the optic nerves which gives many ocular signs and symptoms like optic neuritis. A negative test result does not rule out the diagnosis of NMO. Brain and spine MRI plays an important role in diagnosing NMO. Treatment of NMO consists of corticosteroid and plasmapheresis or intravenous immunoglobulin.
 Conclusion : This case describes a diagnosis of NMO with a Negative AQP-4 antibody.

Efficacy and Safety of the Natural Killer T Cell-Stimulatory Glycolipid OCH-NCNP1 for Patients With Relapsing Multiple Sclerosis: Protocol for a Randomized Placebo-Controlled Clinical Trial.

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system that causes myelin sheath damage and axonal degeneration. The glycolipid (2S, 3S, 4R)-1-O-(α-d-galactosyl)-2-tetracosanoylamino-1,3,4-nonaetriol (OCH-NCNP1 or OCH) exerts an immunoregulatory action that suppresses T helper (Th)1 cell-mediated immune responses through natural killer T cell activation, selective interleukin-4 production, and Th2 bias induction in human CD4-positive natural killer T cells. This trial aims to investigate the efficacy and safety of the immunomodulator OCH in patients with relapsing MS through 24-week repeated administration. This protocol describes a double-blind, multicenter, placebo-controlled, randomized phase II clinical trial that was initiated in September 2019. The participants were randomly assigned to either a placebo control group or an OCH-NCNP1 group and the investigational drug (3.0 mg) was orally administered once weekly for the 24-week duration. Major inclusion criteria are as follows: patients had been diagnosed with relapsing MS (relapsing-remitting and/or secondary progressive MS) based on the revised McDonald criteria or were diagnosed with MS by an attending physician as noted in their medical records; patients with at least two medically confirmed clinical exacerbations within 24 months prior to consent or one exacerbation within 12 months prior to consent; patients with at least one lesion suspected to be MS on screening magnetic resonance imaging (MRI); and patients with 7 points or less in the Expanded Disability Status Scale during screening. Major exclusion criteria are as follows: diagnosis of neuromyelitis optica and one of optic neuritis, acute myelitis, and satisfying at least two of the following three items: (1) spinal cord MRI lesion extending across at least three vertebral bodies, (2) no brain MRI lesions during onset (at least four cerebral white matter lesions or three lesions, one of which is around the lateral ventricle), and (3) neuromyelitis optica-immunoglobulin G or antiaquaporin-4 antibody-positive. Outcome measures include the primary outcome of MRI changes (the percentage of subjects with new or newly expanded lesions at 24 weeks on T2-weighted MRI) and the secondary outcomes annual relapse rate (number of recurrences per year), relapse-free period (time to recurrence), sustained reduction in disability (SRD) occurrence rate, period until SRD (time to SRD occurrence), no evidence of disease activity, and exploratory biomarkers from phase I trials (such as gene expression, cell frequency, and intestinal and oral microbiome). We plan to enroll 30 patients in the full analysis set. Enrollment was closed in June 2021 and the study analysis was completed in March 2023. This randomized controlled trial will determine whether OCH-NCNP1 is effective and safe in patients with MS as well as provide evidence for the potential of OCH-NCNP1 as a therapeutic agent for MS. ClinicalTrials.gov NCT04211740; https://clinicaltrials.gov/study/NCT04211740. DERR1-10.2196/46709.

Rhino orbital mucormycosis: The new mimicker of neuro-ophthalmic lesions

It was always challenging to start steroids in a suspected optic neuritis case with rhino-orbital mucormycosis being the differentials in the COVID era. A 27-year-old female presented with headache and fever for 1 week, along with sinusitis and both eyes (BE) blurred vision for 2 days. There was history of tingling sensation in both lower limbs with urinary retention previously. History of COVID infection 1 month back. Vision in Right Eye (RE): 20/20 and Left Eye (LE): counting fingers (CF) CF with presence of relative afferent pupillary defect (RAPD) Grade 3. Humphrey Visual field gave a picture of Junctional scotoma with ganglion cell loss noted in BE. Magnetic resonance imaging (MRI) brain with orbit gave a picture of LE optic neuritis with right ethmoidal, sphenoidal sinusitis involving orbital apex making mucor a suspect. MRI spine showed focal myelitis. Patient underwent nasal endoscopy to rule out rhino-orbital mucormycosis following which she was started on intravenous methylprednisolone (IVMP) and vision improved drastically. Hence, a diagnosis of neuromyelitis optica was made. Three doses of IVMP along with a tapering dose of oral prednisolone were given and the patient is still in follow-up with no recurrence reported till now.

Nationwide analysis of neuromyelitis optica in systemic lupus erythematosus and Sjogren's syndrome.

Neuromyelitis optica (NMO), also known as Devic's disease, is a rare inflammatory demyelinating disorder causing myelitis and optic neuritis. While there have been reports of systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (SS) occurring with NMO, a formal association is not established. We aimed to investigate the occurrence of NMO in SLE and SS patients and study the clinical characteristics and outcomes of NMO and SLE/SS hospitalizations utilizing the national inpatient sample (NIS) database. The NIS database from 2016 to 2019 was used to extract data. Adult hospitalizations with the principal or secondary diagnosis of NMO were included. We classified NMO patients with and without concomitant diagnosis of SLE or Sjogren's syndrome. We evaluated and compared the clinical characteristics and outcomes of NMO hospitalizations with and without SLE or Sjogren's syndrome. STATA17 was used for data analysis. We also calculated the odds ratio of NMO in SLE and Sjogren's syndrome. There were a total of 16,360 adult hospitalizations with the principal or secondary discharge diagnosis of NMO. Among all NMO hospitalizations, 1425 (8.71%) had the primary or secondary diagnosis of SLE or SS. The odds of NMO in SLE and Sjogren's syndrome were noted to be 12.29 and 5.56, respectively. NMO with SLE/SS group had higher proportion of females (89.82% vs 79%, P value < 0.001), African Americans (56.63% vs 38.28, P value < 0.001), and Asians (5.73% vs 3.25, P value 0.04). The Charlson comorbidity index was higher for NMO-SLE/SS overlap (2.44 vs 1.28, P value < 0.001). There was no significant difference in overall mortality rates of both groups (2.11% vs 1.2%, P value 0.197). There were significantly higher reported seizures (14.73% vs 6.05, P value < 0.001) and paraplegia (21.75% vs 13.93%, P value < 0.001) in NMO-SLE/SS patients. These patients also had a longer length of stay in comparison to the reference group (7 vs 5 days, P value < 0.001) as well as higher total charges. NMO patients had a 12-fold higher risk of SLE and 5-fold higher risk of Sjogren's disease when compared to general population. Patients with overlap of NMO and SLE or Sjogren's were predominantly women and were more likely to be African-American. Co-existence of these autoimmune disorders was associated with poor prognosis in terms of higher morbidity for patients and increased health care burden. Key Points • NMO is a rare autoimmune disease seen predominantly in women in the middle age group with low overall mortality. • SLE and Sjogren's have increased odds of NMO in comparison to general population. • NMO patients have high rates of several complications such as paraplegia, quadriplegia, seizures, blindness, sepsis, and respiratory failure with even higher rates of seizures and paraplegia in those with concomitant SLE or Sjogren's.

Neuromyelitis Optica Spectrum Disorder (Device’s Disease): - A Case Report Of Full Recovery With Corticosteroids, Therapeutic Plasmapheresis And Immunotherapy

Neuromyelitis optica is a severely disabling inflammatory disorder of autoimmune etiology of the central nervous system, mainly affecting the optic nerves and spinal cord. Here, we present a case report of neuromyelitis optica in a 28-year-old Indian woman who presented with sudden painless loss of vision with tingling followed by weakness of all four limbs with bowel involvement that developed over a period of one week, with a significant history of recent vaccination with COVISHIELD (ChAdOx1 nCoV- 19) vaccine . Clinical evaluation showed diminished vision in both eyes, which progressed to loss of power across all major muscle groups in all limbs and bowel involvement. Magnetic resonance imaging of brain with contrast was done which showed T2W/FLAIR hyperintense non enhancing signal in bilateral thalami extending caudally in mid brain on left side and in midline anterior medulla with subtle T2 hyperintense signal in body of corpus callosum, similar foci are seen in bilateral frontoparietal white matter suggestive of ADEM or demyelination. Also T2 hyperintense signal in both optic nerves [left&gt; right] in posterior part of orbit suggestive of optic neuritis. MRI whole spine showed multiple patchy hyperintense signals on T2 and hypointensity on T1 all over cervical and dorsal vertebrae through whole segment in contiguous manner. The patient was immediately started on intravenous methylprednisolone pulse therapy followed by plasmapheresis and immunomodulator therapy. The diagnosis of neuromyelitis optica was later confirmed with strongly positive neuromyelitis optica immunoglobulin G. Since, treatment was started early patient responded very well and made full recovery. Hence, early initiation of aggressive immunosuppressive treatment is essential in such cases.

NEUROMYELITIS OPTICA. CASE REPORT

Introduction. Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease that causes severe demyelination, especially in the optic nerve and spinal cord with typical clinical manifestations of acute optic neuritis and transverse myelitis. The frequency of occurrence worldwide is estimated at 1-2 people out of every 100,000 people. Case report. Our patient was a 37-year-old woman. She felt a sudden vision loss since May 2022. She related this condition to another case of unknown etiology that she encountered in January of that year - numerous vesicular-type rashes appeared on the abdomen and back and lasted for 3 days, but the traces of those rashes remained for some time in the form of hypopigmentation. In November 2022, she has a sudden vision loss again. "Vitiligo-type" white spots were visible around the eyes and on the hands. In neurological examination: eyeball movements are complete in all directions, photoreaction is preserved (D=S), nose-lip folds are symmetrical (D=S), tongue is on the midline, swallowing is not disturbed. Muscle tone and muscle strength in upper and lower limbs are normal, reflexes have increased (D=S). No changes in gait and sensory disturbances have been observed. The functions of the pelvic organs have not been disturbed. Intellect appears appropriate for age, speech has not changed. Ophthalmologist's examination, both eyes have high degree of myopia, myopic astigmatism. Contrasted Cranial MRI- Angiography revealed increased signal in the intracranial segments of the bilateral optic nerve, chiasm, and bilateral optic tract level. The MRI image was initially evaluated in favor of bilateral optic neuritis. USG of the thyroid gland showed sonographic changes in favor of Hashimoto's thyroiditis, and autoimmune thyroiditis was detected. In chest MRI, a demyelinating lesion of 3 mm at C4 level, a 2 mm broad-based protrusion at C4-5 disc that minimally compresses the spinal cord, an annular swelling at C5-6 disc that compresses the anterior subarachnoid area, Th1 – 6 mm, Th5 – 12 mm, Th9 – 10-38 mm long demyelinating lesions were seen. Discussion. According to the available literature, the detection of AQP-4 protein antibodies in serum, which has a role in the pathogenesis of the disease, can play a decisive role in differential diagnosis. In clinical practice, despite the phenotypic and serological characteristics of this disease, the diagnosis is often difficult. Because there are various autoimmune, infectious and neoplastic etiologies phenotypic, manifestations of diseases can mimic neuromyelitis optica. However, based on the clinical symptoms and the results of instrumental examinations, our patient was diagnosed with neuromyelitis optica. She was treated with hormonal therapy and plasmapheresis, and a significant positive change in neurological symptoms was observed. Conclusion. Despite the difficulties in the differential diagnosis of neuromyelitis optica with other demyelinating diseases, especially with multiple sclerosis, it is possible to correctly assess the diagnostic criteria by understanding the detailed clinical, radiological and prognostic differences.

Rectifying global inequities in neuromyelitis optica diagnosis and treatment

The standard of care for patients with neuromyelitis optica (NMO) has become highly unequal globally. Sufficient data have been published to demonstrate that NMO is a disabling—and at times, fatal—disease needing preventive immunosuppressive treatment. Since 2019, there are multiple regulatory authority-approved disease-modifying therapies (DMTs) for aquaporin-4 antibody seropositive NMO for patients. Reframing the picture of NMO globally is now needed. When considered as a disease of high mortality when left untreated, parallel programs to those for cancer, HIV/AIDS, or tuberculosis can be considered. Nine collective goals for rectifying global inequities in NMO diagnosis and treatment are proposed.

Перспективы диагностики оптического неврита при оптиконейромиелите Девика

The review presents data on the prospects for the diagnosis of optic neuritis in neuromyelitis optica (NMO). The differential diagnosis of NMO with multiple sclerosis and other autoimmune diseases is complicated by the similarity of the clinical manifestations of optic neuritis. The diagnostic approach, tactics of using and interpreting the results of modern laboratory, instrumental and hardware research methods are described. Additional diagnostic criteria are described for AQPR4-IgGseronegative patients with clinical symptoms of acute urinary tract infections. NMO is characterized by severe unilateral damage to the optic nerve with poor recovery of visual functions after conservative therapy, frequent recurrences of optic neuritis in one or both eyes, bilateral simultaneous damage to the optic nerves or chiasm. Timely diagnosis makes it possible to prescribe pathogenetic therapy for NMO and reduce the number of relapses of optic neuritis and prevent patients’ blindness. Key words: neuromyelitis optica, optic neuritis, OCT, multiple sclerosis, neuromyelitis optica spectrum disorders, AQPR4

Postinfectious Aquaporin-4-positive Neuromyelitis Optica Syndrome Disorder and Nephrotic Syndrome

Neuromyelitis optica (NMO), or Devic's disease, is one of the demyelinating disorders of the central nervous system, with autoimmune inflammatory etiology. The optic nerves and spinal cord are the major organs involved in the disease; however, the involvement of the brain can also be seen in rare instances. Here, we report a case of a 34-year-old female, diagnosed with NMO and concurrent nephrotic syndrome (NS). NMO was diagnosed by positive Aquaporin-4 antibodies in the serum, radio imaging such as magnetic resonance imaging of the brain and spinal cord showing the demyelinating lesions, as well as the presence of optic neuritis on visually evoked potential. Biochemical investigations revealed heavy proteinuria, hypoalbuminemia, and hypertriglyceridemia, meeting the diagnostic criteria of NS. Therefore, considering the diagnosis of NMO with NS, the patient was treated with plasmapheresis and methylprednisolone pulse therapy. This concurrence is very uncommon in clinical practice, as previously only two such cases are reported to date.

The pathogenesis and treatment of posterior reversible encephalopathy syndrome after neuromyelitis optica spectrum disorder: a case report and literature review

BackgroundPosterior reversible encephalopathy syndrome (PRES) is a rare disease characterized by reversible subcortical vasogenic brain edema. Neuromyelitis optica spectrum disorder (NMOSD) is a frequent neurological autoimmune disease that is rarely reported to complicate PRES.Case presentationHere, we report a case of neuromyelitis optica (NMO) concurrent with PRES. A 50-year-old woman presented with severe impairment of her health visual acuity, with significantly worsening of the motor weakness in both lower limbs during methylprednisolone therapy after her diagnosis of NMO. MRI showed new-onset brain edematous lesions of the bilateral frontal, occipital, and parietal lobes. PRES was considered. Her vision impairment and weakness of the extremities were alleviated after antihypertensive treatment and dehydration. The edema lesions detected by MRI also completely disappeared.ConclusionsWe reviewed 14 cases of NMO with PRES and concluded that the etiology of NMOSD concurrent PRES may be multifactorial, involving pathogenic IgGs against aquaporin-4 (AQP-4) and immunotherapy treatment. Different underlying pathogeneses require different treatment approaches.

Sensitivity and specificity of visual evoked potentials for early diagnosis of demyelinating diseases

IntroductionInternational criteria are used for the diagnosis of multiple sclerosis (MS) and Isolated Clinical Syndrome (ACS), and Neuromyelitis Optica (NMO). PEVs are not included in any of them. We intend to analyse the sensitivity and specificity of visual evoked potentials in the initial diagnosis of MS, ACS, and NMO. Patients and methodsDescriptive, observational, retrospective study of patients treated for a first episode of RR-EM, NMO, or ACS. VEPs are performed during the study of the first episode, with and without ocular symptoms, between October 2012 and March 2019. Results142 patients with suspected demyelinating disease, 100 with disease. Of them, 61 women (61%), mean age: 38.82 years ± SD 4.6. Of the total, 83 with RREM, 6 NMO, 11 ACS. Of the 6 patients with NMO, 1 (16.66%) had altered VEPs; of 11 with ACS, 2 (18.18%) with altered VEP; Of the 83 patients with RR-MS, 45 patients (54.21%) had altered VEP. The sensitivity and specificity of visual evoked potentials in MS was 92.86% and 84.74%, respectively. In NMO, the sensitivity was 16.66%, and the specificity was 93.34%. In ACS, the sensitivity was 18.18%, and the specificity was 96.94%. ConclusionThe sensitivity of VEP in our series is slightly higher than other series published in optic neuritis in RR-MS, being very low in patients with NMO and ACS. However, the very high specificity of the test in these variants can help its diagnosis. These data should be corroborated in larger series.

Fatal neuromyelitis optica after COVID-19 vaccination

We read with interest the report by Motahharynia and coworkers (Motahharynia et al., 2022Motahharynia A. Naghavi S. Shaygannejad V. Adibi I. Fulminant neuromyelitis optica spectrum disorder (NMOSD) following COVID-19 vaccination: a need for reconsideration?.Mult. Scler. Relat. Disord. 2022; 104035https://doi.org/10.1016/j.msard.2022.104035Abstract Full Text Full Text PDF Scopus (2) Google Scholar) that showed a new-onset Neuromyelitis Optica diagnosis with a fatal outcome after COVID-19 vaccination. The authors report a 70-year-old woman who exhibited neurological symptoms (numbness and weakness in her left limbs) seven days after receiving the third dose of a SARS-CoV-2 inactivated vaccine (Sinovac: CoronaVac). She rapidly progressed to paraplegia, while spinal cord magnetic resonance imaging showed an extensive hemorrhagic lesion in the cervical cord (C1-C7). Cerebrospinal fluid analysis was unremarkable (including the absence of oligoclonal bands), but the patient tested positive for anti-Aquaporin-4. Unfortunately, the patient was refractory to all therapeutic interventions (methylprednisolone pulse therapy, plasma exchange and cyclophosphamide) and died two months after hospitalization (Motahharynia et al., 2022Motahharynia A. Naghavi S. Shaygannejad V. Adibi I. Fulminant neuromyelitis optica spectrum disorder (NMOSD) following COVID-19 vaccination: a need for reconsideration?.Mult. Scler. Relat. Disord. 2022; 104035https://doi.org/10.1016/j.msard.2022.104035Abstract Full Text Full Text PDF Scopus (2) Google Scholar). Neuromyelitis Optica Spectrum Disorder (NMOSD) is rare autoimmune neuro-inflammatory disease that affects the central nervous system (CNS) with predilection for causing lesions in the optic nerves/spinal cord. Usually, the median age for onset is 40-years, although the disease can occur at any age as proposed in this report. CNS-damage during NMOSD is mainly attributed to the presence of autoantibodies such as specific NMO-IgG against astrocyte-end-feet Aquaporin-4 (anti-AQP4) in association with complement system, innate cells (e.g., eosinophils/neutrophils) and pro-inflammatory cytokines (Jarius et al., 2020Jarius S. Paul F. Weinshenker B.G. Levy M. Kim H.J. Wildemann B. Neuromyelitis optica, Nature Reviews Disease Primers. Springer US, 2020https://doi.org/10.1038/s41572-020-0214-9Crossref Scopus (120) Google Scholar). Considering the accumulated reports during the pandemic, we speculate that antiviral immune responses against SARS-CoV-2 natural infection/immunization may trigger CNS-damage in some individuals. Here, we hypothesize that repetition of vaccination with the same vaccine type (inactivated SARS-CoV-2) evoked a robust antiviral immune response including, among others: (I) effector or even senescent/exhausted CD8+ T lymphocytes with massive cytotoxic capacity (e.g., granzymes); (II) pro-inflammatory cytokines derived from CD4+ Th1 (IFN-γ, TNF-α) and Th17 (IL-17, IL-22); (III) neutrophil extracellular traps (NETs) and pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF-α) derived from innate immune cells. All of these components are known to promote blood-brain barrier disruption. In parallel to neutralizing antibodies against SARS-CoV-2, autoreactive clones of B cells may differentiate in plasma cells and release anti-AQP4 due to loss of peripheral autotolerance. Furthermore, it is not possible so far to exclude that neutralizing antibodies against SARS-CoV-2 may also exhibit cross-reactivity with self-antigens in the CNS. More broadly, post-COVID syndrome as well as manifestations after COVID-19 vaccination may share common immunological features (summarized in Fig. 1). The increasing number of reports suggest the occurrence of new-onset/exacerbating NMOSD and related disorders, such as Multiple Sclerosis, in the context of SARS-CoV-2 natural infection/immunization (Finsterer, 2022Finsterer J. Neuromyelitis optica complicating COVID vaccinations.Mult. Scler. Relat. Disord. 2022; 62103809https://doi.org/10.1016/j.msard.2022.103809Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar; Fragoso et al., 2022Fragoso Y.D. Gomes S. Gonçalves M.V.M. Mendes Junior E. Oliveira B.E.S. Rocha d. Santos C.F. dos G.A.C. Tauil C.B. Araujo R.V. Peron J.P.S. New relapse of multiple sclerosis and neuromyelitis optica as a potential adverse event of AstraZeneca AZD1222 vaccination for COVID-19.Mult. Scler. Relat. Disord. 2022; 57: 1-5https://doi.org/10.1016/j.msard.2021.103321Abstract Full Text Full Text PDF Scopus (8) Google Scholar; Khayat-Khoei et al., 2022Khayat-Khoei M. Bhattacharyya S. Katz J. Harrison D. Tauhid S. Bruso P. Houtchens M.K. Edwards K.R. Bakshi R. COVID-19 mRNA vaccination leading to CNS inflammation: a case series.J. Neurol. 2022; 269: 1093-1106https://doi.org/10.1007/s00415-021-10780-7Crossref PubMed Scopus (32) Google Scholar). Despite the need for continuous massive vaccination against SARS-CoV-2, which proved to be effective and safe, we should be aware of rare, aggressive and even fatal CNS-manifestations such as NMOSD in a small proportion of individuals. V.O.B. and C.L.Y. wrote the manuscript. Was in accordance with ethical guidelines. Not applicable. Not applicable. Not applicable. The author declares no conflicts of interest.

Serum levels of interleukin-6 and Vitamin D at the onset of multiple sclerosis and neuromyelitis optica: A pilot study.

Interleukin-6 (IL-6) is an important mediator in the acute phase of inflammatory diseases such as neuromyelitis optica (NMO) and multiple sclerosis (MS). The level of IL-6 is higher in cerebrospinal fluid and serum of NMO patients compare to MS. Vitamin D has a regulatory effect on IL-6, so it may have a negative correlation with IL-6 in the acute phase of these diseases. This study was performed to evaluate the serum levels of IL-6 and Vitamin D in NMO and MS patients at the onset of disease to find differences that may help in early diagnosis. This case-control study was done on patients with the first episode of optic neuritis, transverse myelitis, and area postrema syndrome who were referred to Kashani MS Center in Isfahan, Iran, between January 2018 and January 2020. The serum levels of Vitamin D and IL-6 were assessed using enzyme-linked immunosorbent assay in blood sample taken at the time of first presentation in patients who had a definitive diagnosis of NMO and MS during subsequent workup. During a 2-year follow-up, definitive diagnosis of NMO was given in 25 cases, and they were compared with 25 cases that were randomly selected from patients with definite MS. Nineteen patients in the NMO group and 21 patients in the MS group were female. The mean age of patients in the NMO and MS groups was 29.64 ± 1.47 and 30.20 ± 1.42, respectively (P = 0.46). The mean of serum level of Vitamin D was 24.88 ± 15.2 in NMO patients and 21.56 ± 18.7 in MS patients without significant difference (P = 0.48). The mean of IL-6 was 30.1 ± 22.62 in the NMO group and 23.35 ± 18.8 in the MS group without significant difference (P = 0.28). The serum levels of Vitamin D were insufficient in both groups. No correlation between Vitamin D and IL-6 levels was found in our study (P > 0.05). Our results showed that serum IL-6 levels were higher at the onset of NMO disease compared with MS. The serum levels of Vitamin D were low in both groups and there was no association between serum levels of Vitamin D and IL-6 in either group. Future studies with large sample size are needed to confirm these findings.

SYRINGOMYELIA IN NEUROMYELITIS OPTICA SEROPOSITIVE FOR AQUAPORIN-4 ANTIBODY: A CASE REPORT

Neuromyelitis Optica (previously called Devics disease) is an autoimmune-induced demyelinating disorder of the central nervous system that primarily affects the optic nerves and spinal cord. This manuscript presents a case of a 28-yearold female patient who clinically presented with acute lower extremity weakness and numbness associated with unilateral impairment of vision. Later in the course of the disease, magnetic resonance imaging of the cervico-thoracic spine showed multi-level abnormal non-enhancing and enhancing lesions from levels C3 to T8 levels which were identified to be combined transverse myelitis and cord syrinx. An anti-aquaporin-4 receptor antibody was obtained and yielded to be seropositive. Given the patients clinical manifestations, combined with imaging and laboratory examinations, led to a diagnosis of Neuromyelitis Optica (NMO). The patient was managed with high-dose steroids. The significant discovery of anti-aquaporin-4 antibodies served as a key factor in the NMO immunopathogenesis. It is currently regarded as a specific biomarker of the diagnostic process, making it distinguishable from multiple sclerosis. This case highlights the mechanism of formation of a fluid-filled syrinx-like cavity in the cord in the setting of Neuromyelitis Optica.

Neuromyelitis optica with brain stem involvement in a middle-aged Ethiopian woman: a case report and review of literature

IntroductionNeuromyelitis optica is a demyelinating disease of the central nervous system that predominantly affects the optic nerves and spinal cord. In neuromyelitis optica, white blood cells and antibodies primarily attack the optic nerves and the spinal cord, but may also attack the brain. Brainstem manifestation has been described recently. So far, neuromyelitis optica is very rare in Ethiopia and there were only two case reports, but this is the first case report of neuromyelitis optica with brainstem involvement.Case presentationA 47-year-old Addis Ababa woman presented to Saint Paul’s Hospital Millennium Medical College with a history of visual loss of 7 years and bilateral lower limb weakness of 4 days duration. She had bilateral oculomotor nerve palsy. Her past medical history showed systemic hypertension for 18 years and dyslipidemia for 1 year. The objective evaluation of the patient revealed right optic nerve atrophy suggesting optic neuritis and flaccid paraplegia with sensory level at the fourth thoracic vertebra. Diagnostic work-up using electromyography and spinal magnetic resonance imaging revealed demyelinating anterior visual pathway dysfunction and signs of extensive cervicothoracic transverse myelitis from the third cervical to lower thoracic vertebrae, respectively. Then a diagnosis of neuromyelitis optica was established. After treatment with high-dose systemic steroid followed by azathioprine, the patient was stable for several months with significant improvement of vision and lower-extremity weakness with no relapse of symptoms.ConclusionThe case described here is a rare inflammatory demyelinating disorder of the central nervous system occurring in East Africa. It reminds clinicians to suspect neuromyelitis optica in a patient who presented with unexplained recurrent optic neuritis to make a timely diagnosis and prevention of permanent neuronal damage. Neuromyelitis optica can also be associated with oculomotor nerve involvement.

Challenges in the diagnosis and treatment of neuromyelitis optica: A serial cases

The diagnosis of Neuromyelitis Optica spectrum disorder (NMOSD) can be challenging especially in patients with atypical presentations and unknown serostatus for aquaporin-4 antibodies (AQP4-Ab). We present three cases with different onset variations and relapsing episodes and aims to present and compare the clinical, radiological and evoked potential findings.

Status of the neuromyelitis optica spectrum disorder in Latin America

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) is an increasing diagnostic and therapeutic challenge in Latin America (LATAM). Despite the heterogeneity of this population, ethnic and socioeconomic commonalities exist, and epidemiologic studies from the region have had a limited geographic and population outreach. Identification of some aspects from the entire region are lacking. ObjectivesTo determine ethnic, clinical characteristics, and utilization of diagnostic tools and types of therapy for patients with NMOSD in the entire Latin American region. MethodsThe Latin American Committee for Treatment and Research in MS (LACTRIMS) created an exploratory investigational survey addressed by Invitation to NMOSD Latin American experts identified through diverse sources. Data input closed after 30 days from the initial invitation. The questionnaire allowed use of absolute numbers or percentages. Multiple option responses covering 25 themes included definition of type of practice; number of NMOSD cases; ethnicity; utilization of the 2015 International Panel criteria for the diagnosis of Neuromyelitis optica (IPDN); clinical phenotypes; methodology utilized for determination of anti-Aquaporin-4 (anti­ AQP4) antibodies serological testing, and if this was performed locally or processed abroad; treatment of relapses, and long-term management were surveyed. ResultsWe identified 62 investigators from 21 countries reporting information from 2154 patients (utilizing the IPDN criteria in 93.9% of cases), which were categorized in two geographical regions: North-Central, including the Caribbean (NCC), and South America (SA). Ethnic identification disclosed Mestizos 61.4% as the main group. The most common presenting symptoms were concomitant presence of optic neuritis and transverse myelitis in 31.8% (p=0.95); only optic neuritis in 31.4% (more common in SA), p<0.001); involvement of the area postrema occurred in 21.5% and brain stem in 8.3%, both were more frequent in the South American cases (p<0.001). Anti-AQP4 antibodies were positive in 63.9% and anti-Myelin Oligodendrocyte Glycoprotein (MOG) antibodies in 4.8% of total cases. The specific laboratorial method employed was not known by 23.8% of the investigators. Acute relapses were identified in 81.6% of cases, and were treated in 93.9% of them with intravenous steroids (IVS); 62.1% with plasma exchange (PE), and 40.9% with intravenous immunoglobulin-G (IVIG). Therapy was escalated in some cases due to suboptimal initial response. Respondents favored Rituximab as long-term therapy (86.3%), whereas azathioprine was also utilized on 81.8% of the cases, either agent used indistinctly by the investigators according to treatment accessibility or clinical judgement. There were no differences among the geographic regions. ConclusionsThis is the first study including all countries of LATAM and the largest cohort reported from a multinational specific world area. Ethnic distributions and phenotypic features of the disease in the region, challenges in access to diagnostic tools and therapy were identified. The Latin American neurological community should play a determinant role encouraging and advising local institutions and health officials in the availability of more sensitive and modern diagnostic methodology, in facilitating the the access to licensed medications for NMOSD, and addressing concerns on education, diagnosis and management of the disease in the community.