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Longitudinally Extensive Transverse Myelitis: a Retrospective Study Differentiating Neuromyelitis Optica Spectrum Disorder from Other Etiologies

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Longitudinally Extensive Transverse Myelitis: a Retrospective Study Differentiating Neuromyelitis Optica Spectrum Disorder from Other Etiologies Open Access Original Article DOI: 10.7759/cureus.13968 Longitudinally Extensive Transverse Myelitis: A Retrospective Study Differentiating Neuromyelitis Optica Spectrum Disorder From Other Etiologies Sunanda Paudel 1 , Gaurav Nepal 2 , Sandesh Guragain 3 , Sangam Shah 4 , Basanta S. Paudel 4 , Rajeev Ojha 1 , Reema Rajbhandari 5 , Ragesh Karn 5 , Bikram P. Gajurel 6 , Sunanda Paudel 7 1. Neurology, Tribhuvan University Teaching Hospital, Kathmandu, NPL 2. Internal Medicine, Tribhuvan University Institute of Medicine, Kathmandu, NPL 3. Neurology, Nepal Medical College Teaching Hospital, Kathmandu, NPL 4. Neurology, Maharajgunj Medical Campus, Kathmandu, NPL 5. Neurology, Tribhuvan University Institute of Medicine, Kathmandu, NPL 6. Vascular Neurology, Tribhuvan University Teaching Hospital, Kathmandu, NPL 7. Neurology, Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, NPL Corresponding author: Sunanda Paudel, [email protected] Abstract Background Longitudinally extensive transverse myelitis (LETM) is characterized by contiguous immune-mediated inflammatory lesion of the spinal cord extending more than three vertebral segments. Neuromyelitis optica spectrum disorder (NMOSD) is the most common and important cause of LETM. This study aims to evaluate the demographic profile, clinical presentations, neuroimaging features, laboratory parameters, and etiologies of LETM and differentiates NMOSD from other etiologies of LETM. Methodology This retrospective cross-sectional study was conducted at the Department of Neurology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal. After receiving clearance from the ethical committee, a retrospective chart review was conducted and records of all the inpatient LETM cases admitted from March 2018 to June 2020 were obtained. From the patient records, the following information was extracted: the demographic profile, clinical presentations, neuroimaging features, cerebrospinal fluid analysis, serum anti- aquaporin-4 (AQP4) immunoglobulin G status, hemogram, infectious disease profile, inflammatory markers, and auto-immune panels. Descriptive analysis of data was performed with SPSS statistics 23.0 version (IBM Corp, Armonk, NY, USA). Results In our study, the mean age of LETM patients was 36.58 years, and 12 out of 19 (63.15%) patients were young, with an age less than 40 years. A total of 13 (68.40%) patients were male, with a male-to-female ratio of 2.16. Seven (36.80%) patients had a clinical diagnosis of NMOSD with anti-AQP4 antibody-positive status, Review began 03/08/2021 four (21.10%) had unknown etiology, three (15.8%) had post-infectious transverse myelitis, and three Review ended 03/15/2021 (15.80%) had a diagnosis of idiopathic transverse myelitis. There was a single case (5.30%) of cervical Published 03/18/2021 spondylotic myelopathy and leukemic transverse myelitis each. The common presenting symptoms of LETM © Copyright 2021 were bladder dysfunction, paraparesis, quadriparesis, and visual impairment. Visual involvement, either Paudel et al. This is an open access unilateral or bilateral, was common in NMOSD and LETM of unknown etiology category. Similarly, brain article distributed under the terms of the lesion was common in patients with NMOSD and LETM of unknown etiology category. Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any Conclusion medium, provided the original author and source are credited. LETM is a heterogeneous disorder with diverse etiologies and clinical presentations. NMOSD is an important cause of LETM that predominantly affects females. Optic neuritis can be seen in LETM of various etiologies, but it is more common in anti-AQP4-positive NMOSD patients. Brain lesions in LETM are common in anti-AQP4-positive NMOSD. Categories: Neurology Keywords: longitudinally extensive transverse myelitis, letm, nmosd, aquaporin-4, neuromyelitis optica spectrum disorder Introduction Longitudinally extensive transverse myelitis (LETM) is an entity with a substantial spinal cord lesion that spans three or more vertebral segments on spinal magnetic resonance imaging (MRI) [1]. Neuromyelitis optica spectrum disorder (NMOSD) invariably is the most common cause of LETM [2]. However, multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody disorders (MOGAD), acute disseminated encephalomyelitis (ADEM), glial fibrillary acidic protein (GFAP) astrocytopathy, spinal cord infarction, How to cite this article Paudel S, Nepal G, Guragain S, et al. (March 18, 2021) Longitudinally Extensive Transverse Myelitis: A Retrospective Study Differentiating Neuromyelitis Optica Spectrum Disorder From Other Etiologies. Cureus 13(3): e13968. DOI 10.7759/cureus.13968 parainfectious myelopathy, neurosarcoidosis, Sjögren syndrome, systemic lupus erythematosus, neuro- Behçet disease, paraneoplastic myelitis, and dural arteriovenous fistula are also known to cause LETM [2]. The NMOSD characteristically involves the optic nerve, spinal cord, area postrema, brainstem, diencephalon, or cerebrum, which bestow the core clinical characteristics of NMOSD. Nevertheless, the aforementioned conditions can easily mimic NMOSD as they might also involve optic nerves and/or spinal cord, presenting with bilateral optic neuritis and LETM. The above-mentioned conditions may even have brain lesions resembling those of NMOSD [3]. Therefore, it is imperative to exclude all causes of LETM before diagnosing NMOSD. As NMOSD is one of the disabling diseases of the central nervous system, early diagnosis and management are essential for optimal outcome and better quality of life [3,4]. As mentioned above, LETM has an important and characteristic association with NMOSD, and almost half of the adult LETM cases are due to NMOSD [5]. NMOSD is found in all races around the world, and recent population-based studies have shown that NMOSD is more common in non-white races. Studies published in Asia show that the prevalence of NMOSD has increased recently, and the ratio of NMOSD to MS is higher compared with Western countries [6,7]. Nevertheless, in the medical literature, there are no clinical studies on LETM from Nepal, an Asian country. Therefore, we conducted a retrospective study in our tertiary care center to evaluate the demographic characteristics, clinical manifestations, neuroimaging characteristics, laboratory parameters, and etiology of LETM patients. Materials And Methods This study was approved by the Institutional Review Board (IRB) of Tribhuvan University Institute of Medicine (approval number, 34/ (6-11) E2/ 077/ 078). We conducted this retrospective cross-sectional study at the Department of Neurology, Tribhuvan University Teaching Hospital (TUTH). TUTH, located in the capital city of Kathmandu with 700 beds and 32 departments, is the largest hospital in the country and a tertiary referral center for all kinds of diseases and conditions including neurological disorders. After receiving clearance from the ethical committee of the IRB, a retrospective chart review was done. Records of all inpatient LETM cases admitted from March 2018 to June 2020 were obtained. The inclusion criteria were extensive longitudinal involvement of three or more segments of the spinal cord on MRI in patients aged ≥16 years. From the patient records, the following information was extracted: demographic profile, clinical presentations, neuroimaging features (MRI brain and spine with T1-weighted, T2-weighted, fluid- attenuated inversion recovery, diffusion-weighted imaging, and gadolinium contrast images), cerebrospinal fluid (CSF) analysis for cytology, biochemistry and oligoclonal bands, and serum anti-aquaporin-4 (AQP4)- immunoglobulin G (IgG) status. Other non-specific investigations done were complete blood count, serum vitamin B12 level, thyroid function tests, infectious disease profile, inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), and auto-immune panel including antinuclear antibodies, anti- double-stranded DNA antibodies, anti-nucleosome, anti-histones, anti-Sm, anti SS-A, anti-SS-B, anti-RO, anti-Scl-70, anti RibP-protein, and anti-JO. Patient records with incomplete routine evaluation, neuroimaging features, CSF reports, infectious, inflammatory, and auto-immune profiles were excluded. NMOSD was diagnosed using the 2015 American Academy of Neurology international consensus diagnostic criteria [8]. The 2017 revisions of the McDonald criteria were used to diagnose MS [9]. With proper evaluation of clinical, neuroimaging, and laboratory findings, patients were divided into three diagnostic categories: NMOSD, LETM of unknown etiology, and other causes of LETM. Descriptive analysis was performed and various study variables were compared among these three groups. Descriptive analysis of data was performed using SPSS statistics 23.0 version (IBM Corp, Armonk, NY, USA). Results A total of 19 patients were included in this study. The mean age of the patients was 36.58 years with a standard deviation of 19.33. Twelve out of 19 patients (63.15%) were young, with an age of less than 40 years. Of the total number of patients, 13 (68.40%) were male, with a male-to-female ratio of 2.16. A total of four (21.10%) patients had a history of antecedent respiratory infection. Nine (47.40%) patients had symptoms that progressed over hours, and the remaining 10 (52.60%) patients had progression over days (Table 1). 2021 Paudel et al. Cureus 13(3): e13968. DOI 10.7759/cureus.13968 2 of 6 Variables Frequency
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