Extensive Longitudinal Transverse Myelitis in Systemic Lupus Erythematosus: Case Report and Review of Current Literature

Extensive Longitudinal Transverse Myelitis in Systemic Lupus Erythematosus: Case Report and Review of Current Literature | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Extensive Longitudinal Transverse Myelitis in Systemic Lupus Erythematosus: Case Report and Review of Current Literature Abderrazzak AJERTIL, Abdeljalil EL QUESSAR This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5471728/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Acute transverse myelitis (TM) is an inflammatory condition that presents with quickly advancing motor, sensory, and autonomic symptoms, which can have severe consequences. The three leading causes of acute TM are demyelinating diseases, infections, and autoimmune inflammatory conditions like systemic lupus erythematosus (SLE). The American College of Rheumatology (ACR) includes TM as one of the 19 neuropsychiatric conditions linked with SLE, with an incidence rate of about 1–2% among SLE cases. Misdiagnosis is common, often resulting in high morbidity and mortality. This report examines the case of a 23-year-old woman with progressive muscle weakness in her lower limbs, dysesthesias from the abdomen to the feet, and loss of sphincter control. On examination, severe paraparesis with sensory level at T8 was identified. MRI of the thoracolumbar spine showed hyperintensity on T2 and STIR sequences from T7 to L1, consistent with TM. Due to resistance to initial treatment, cyclophosphamide was administered. After a week in the hospital, the patient showed partial neurological improvement. Recognizing TM in SLE patients requires high clinical suspicion, and early intervention is crucial to minimize severe complications and reduce the rates of morbidity and mortality. transverse myelitis neuropsychiatric lupus cyclophosphamide autoimmune Figures Figure 1 Introduction Acute Transverse Myelitis (TM) is a rapidly progressing inflammatory disease affecting motor, sensory, and autonomic functions, often leading to serious outcomes. The primary causes of acute TM include demyelinating diseases, infections, and autoimmune inflammatory disorders, such as systemic lupus erythematosus (SLE). Neurological and psychiatric symptoms associated with SLE (NPSLE) are diverse and are often linked with poor prognosis. Studies based on the American College of Rheumatology’s (ACR) classification report a prevalence rate of 37–95% for NPSLE [ 1 ]. This wide range may be due to factors such as the inclusion of minor symptoms, lack of a standard for diagnosis, and the challenges of attributing events to either primary NPSLE or secondary causes (like infections, medications, metabolic changes, and multiorgan damage). TM, one of the 19 NPSLE syndromes classified by ACR in 1999, appears in 1–2% of SLE cases [ 2 ]. TM in SLE cases is often severe; one-third of patients experience symptoms as an early indicator, though it can occur up to three years after diagnosis. Recurrence of TM ranges from 18–50%. In Colombia, the prevalence of SLE is about 9.19 per 10,000 people, comparable to other Latin American countries [ 3 ]. Myelitis affects between 1% and 2% of SLE patients and is about 1,000 times more common than idiopathic myelitis in the general population [ 2 ]. SLE-associated TM can involve grey matter, leading to hypotonia and hyporeflexia, or white matter, resulting in irreversible myelitis with spasticity and hyperreflexia. SLE-related TM has high morbidity, and rapid treatment with corticosteroids and cyclophosphamide can improve outcomes. However, due to limited awareness of its clinical presentations, SLE-related TM is often underdiagnosed [ 4 ]. This case report details a severe, longitudinal episode of TM in SLE, where early clinical suspicion, timely imaging, and prompt therapeutic intervention enabled a full recovery. Case Presentation A 23-year-old woman with no significant medical history, aside from autoimmune hemolytic anemia requiring transfusion and treatment with prednisolone, arrived at our hospital’s emergency department. She reported experiencing lower back pain, polyarthralgia, and progressive muscle weakness in her lower limbs. Over the past two weeks, she had also noticed a loss of bladder and bowel control and dysesthesias extending from her abdomen down to her feet. On examination, her temperature was normal at 37°C, and her blood pressure was 135/80 mmHg. Respiratory, cardiac, abdominal, and joint exams were unremarkable. Neurological assessment revealed a muscle strength of 1/5 in the lower limbs and 5/5 in the upper limbs, with reduced sensitivity to pain, touch, and temperature at the T8 dermatome level. Cranial nerve examination showed no abnormalities, but she had red, raised, scaly plaques on her skin. A lumbar puncture revealed clear fluid without pleocytosis, a glucose level of 53 mg/dL (normal range: 40–80 mg/dL), with a concurrent blood glucose level of 112 mg/dL, and total protein at 83 mg/dL (normal range: 40–60 mg/dL). Cerebrospinal fluid (CSF) tests for infections were negative. Her ANA antibodies were positive, anti-DNA antibodies were measured at 1664 IU/mL, with C3 at 36 mg/dL and C4 at 6.6 mg/dL. With a suspicion of complete spinal cord syndrome, an MRI was performed, which ruled out extramedullary compression and showed a mild increase in spinal cord diameter, along with T2 and STIR hyperintensity from T7 to L1. These findings were consistent with a longitudinally extensive TM (Fig. 1 ). Treatment was initiated with high-dose methylprednisolone at 1 gram per day for two days. Discussion Systemic lupus erythematosus (SLE) is a complex multisystem disorder with the potential to impact any organ. Its most common manifestations involve the skin and joints, though renal involvement and neuropsychiatric manifestations (NPSLE) are also significant. The presence of NPSLE often correlates with more severe disease and affects the overall prognosis [ 5 ]. NPSLE encompasses a range of neurological and psychiatric complications attributed to SLE, posing diagnostic challenges due to its broad spectrum and variability in clinical presentation [ 6 ]. In 1999, the American College of Rheumatology (ACR) categorized NPSLE into 19 distinct syndromes, dividing them into central nervous system (CNS) manifestations—further classified into focal and diffuse—and peripheral nervous system (PNS) manifestations. Among the focal CNS manifestations is transverse myelitis (TM), which represents more than just a pathological or radiological spinal lesion. TM reflects acute or subacute spinal cord dysfunction on a sensory level and, if complete, results in motor and autonomic impairments (affecting bladder, bowel, and sexual function) below the lesion level. Partial TM, on the other hand, involves either motor or sensory deficits but not both[ 7 ]. The pathogenesis of NPSLE remains incompletely understood, but small-vessel vasculitis and thrombosis, as suggested by pathological and serological findings, likely contribute to axonal injury through ischemia and necrosis. In cases of TM, the spinal level and extent of involvement may indicate which pathophysiological mechanisms are at play. Thoracic involvement is common, given that this segment contains smaller caliber vessels in the spinal vasculature and is thus more vulnerable to thrombosis. If antiphospholipid antibodies (aPL) are present, this might suggest a thrombotic mechanism at work [ 8 ]. Studies show that among NPSLE patients with TM, between 50% and 100% have associated aPL antibodies. For example, Katsiari CG et al. (2011) reported no benefit from anticoagulant therapy in such cases[ 9 ]. This association underscores the importance of testing for these antibodies, as they may heighten the risk of neurological complications in SLE patients. Additionally, some SLE patients are seropositive for anti-aquaporin 4 (AQP4) antibodies, which are specific markers for neuromyelitis optica (NMO). These antibodies induce direct CNS injury through astrocytic damage via complement- and antibody-dependent cytotoxicity. The presence of AQP4 during an initial TM episode suggests a higher likelihood of recurrence and possible optic neuritis development within the year. While AQP4 positivity in SLE is relatively low (2–3%), it is significantly higher (27%) in NPSLE cases[ 10 ]. The International Consensus on NMO Spectrum Disorders suggests that, in cases where AQP4 testing is unavailable, diagnosis can rely on clinical evaluation, two core clinical criteria, and ruling out alternative diagnoses [ 11 ]. In the case described, there was no evidence of NMO-associated regional CNS spread or symptomatic cerebral or area postrema involvement at the onset of myelitis. There was also no further CNS involvement in the six clinical regions of interest for NMO diagnosis prior to the patient's passing. Regarding diagnosis, the ACR defined lupus-associated TM diagnostic criteria in 1999. Based on the clinical picture, affected patients present with acute or subacute paraplegia or quadriplegia, typically bilateral but not always symmetrical, along with a sensory level identified at the spinal level, and/or bowel or bladder dysfunction. Rapid neuroimaging is essential to rule out spinal cord compression. Contrast-enhanced MRI is the diagnostic tool of choice for confirming TM and ruling out other causes, such as spinal cord hemorrhages or tumors. Longitudinal spinal involvement (71%) is more common than transverse involvement (28%) in imaging studies[ 4 ]. CSF findings may include lymphocytic pleocytosis and slightly reduced glucose levels (usually > 30 mg/dL). However, normal CSF results do not exclude TM. Two TM subtypes are reported based on clinical and imaging findings: gray matter TM, which presents with fever, flaccid weakness, hyporeflexia, and urinary retention, with rapid onset. This subtype is linked to anti-DNA antibodies. White matter TM is associated with positive aPL antibodies, recurrent thrombosis, and anti-Ro/SSA antibodies. In Birnbaum J et al.'s 2009 cohort, overlap between TM-SLE and NMO showed predominant white matter involvement, with a history of optic neuritis, longitudinal TM (> 3 vertebral segments), recurrent relapses, and MRI findings not characteristic of multiple sclerosis. White matter TM is often recurrent, while gray matter involvement tends to show a monophasic recurrence pattern. In a subset of antiphospholipid syndrome (APS) patients, white matter lesions with positive lupus anticoagulant are found in over half, whereas gray matter involvement is under 20%. Anti-DNA and anti-Ro/SSA antibodies did not significantly differ between these groups[ 12 ]. The case described did not meet NMO or APS criteria, and, although mixed features were present, gray matter involvement was predominant. As for treatment, the European League Against Rheumatism (EULAR) recommends initiating IV methylprednisolone and cyclophosphamide early for NPSLE, ideally within hours of symptom onset, even if CSF findings suggest possible meningitis while awaiting microbiological results. This combination is considered the standard treatment for this neuropsychiatric complication. Typical doses include IV methylprednisolone pulses of 1 gram daily for three days, combined with IV cyclophosphamide at 0.75–1 g/m² monthly for six months, followed by every three months for a year, alongside oral prednisone at 1 mg/kg/day starting on day four, tapering over 1–3 months. Plasmapheresis may be added for refractory cases, although it does not appear to improve prognosis[ 13 ]. IV immunoglobulin has also been employed in initial or refractory cases, either alone or with standard therapy. Anticoagulation, while used in aPL-positive TM cases, has not shown additional therapeutic benefit beyond immunosuppression. Emerging data on biologics like rituximab, alone or combined with cyclophosphamide, show promise but require larger studies[ 14 ]. Maintenance therapy options include azathioprine, methotrexate, or mycophenolate combined with low-dose steroids, generally recommended for three years or longer; however, the optimal duration is not yet defined. Conclusions Le LED peut parfois causer une conséquence neurologique grave appelée myélite transverse extensive longitudinale (LETM). La littérature manque considérablement d’informations sur l’évolution clinique, les résultats et l’efficacité thérapeutique. Les infections, les affections démyélinisantes et les tumeurs compressives sont toutes incluses dans le diagnostic différentiel large de la LETM. En raison de l’importance clinique et pronostique du MT-LED, une reconnaissance et une intervention immédiates sont nécessaires pour prévenir les résultats catastrophiques qui se produisent chez jusqu’à un tiers des patients. Si l’amélioration clinique n’est pas obtenue avec la corticothérapie initiale, l’ajout d’une prise en charge immunomodulatrice incluant le cyclophosphamide ou la plasmaphérèse ne doit pas être retardé en raison de son impact favorable sur l’invalidité et la survie, en particulier dans les cas réfractaires. Notre patient avait une LETM et présentait une détérioration neurologique substantielle. Une intervention opportune a permis une récupération progressive remarquable de la fonction, et notre patient atteint de LED a pu marcher et récupérer la fonction et la sensation du sphincter sans présenter de séquelles à long terme. Abbreviations MRI : Magnetic Resonance Imaging TM : Transverse myelitis SLE : Systemic lupus erythematosus ACR : American College of Rheumatology CSF : Cerebrospinal fluid NPSLE : Neurological and psychiatric symptoms associated with SLE EULAR : European League Against Rheumatism CNS : Central nervous system PNS : Peripheral nervous system NMO : Neuromyelitis optica AQP4 : Anti-aquaporin 4 aPL : Antiphospholipid antibodies Declarations Ethics Approval and Consent to Participate This study was approved by the Clinical Ethics Committee of the International University Hospital Cheikh Zaid. The patient provided informed consent to participate in the study, including consent to share the MRI images used in this work. All participants involved in this study have also given their consent to contribute to the research. Consent for Publication The patient has given explicit consent for the use and publication of their MRI images in this study. Competing Interests The authors declare that they have no conflicts of interest. Funding There were no financial means or external funding sources for this study. Acknowledgements The authors wish to thank Professor El quessar for his invaluable assistance in reviewing and correcting the manuscript. Authors' Information Dr Abderrazzak Ajertil is a specialist in medical imaging and currently a resident in interventional neuroradiology at the International University of Abulcasis, Rabat, at the International University Hospital Cheikh Zaid. Dr Abdeljalil El Quessar is a professor and the head of the Department of Neuroimaging and Interventional Neuroradiology at the International University Hospital Cheikh Zaid, Rabat. Author Contribution Dr. AJERTIL is the primary author, and Professor EL QUESSAR contributed to the development of this work by providing her expertise in writing. References Clinical features of transverse myelitis associated with systemic lupus erythematosus, Zhang S, Wang Z, Zhao J et al (2020) Lupus 29:389–397 The American College (1999) of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 42:599–608 Prevalence of systemic lupus erythematosus in Colombia (2019) Fernández-Ávila DG, Bernal-Macías S, Rincón-Riaño DN, Gutiérrez Dávila JM, Rosselli D. Lupus 28:1273–1278: data from the national health registry 2012–2016 Distinct subtypes of myelitis in systemic lupus erythematosus, Birnbaum J, Petri M, Thompson R, Izbudak I, Kerr D (2009) Arthritis Rheum 60:3378–3387 Diversity of neuropsychiatric manifestations in systemic lupus erythematosus (2020) Fujieda Y Immunol Med 43:135–141 Systemic lupus erythematosus, Yamazaki-Nakashimada MA (2016) Is it one disease? Rivas-Larrauri F. Reumatol Clin 12:274–281 Transverse myelitis, Beh SC, Greenberg BM, Frohman T, Frohman EM (2013) Neurol Clin 31:79–138 Myelitis in systemic, Hryb JP, Chiganer E, Contentti EC, Di Pace JL, Lessa C, Perassolo MB (2016) lupus erythematosus: clinical features, immunological profile and magnetic resonance imaging of five cases. Spinal Cord Ser Cases 2:16005 Acute transverse myelitis and antiphospholipid antibodies in lupus. No evidence for anticoagulation. Katsiari CG, Giavri I, Mitsikostas DD, Yiannopoulou KG, Sfikakis PP (2011) Eur J Neurol. ;18:556–563 Understanding the antibody, Mader S, Jeganathan V, Arinuma Y et al (2018) repertoire in neuropsychiatric systemic lupus erythematosus and neuromyelitis optica spectrum disorder: do they share common targets? Arthritis Rheumatol 70:277–286 International consensus diagnostic criteria for neuromyelitis optica spectrum disorders, Tan CT, Mao Z, Qiu W, Hu X, Wingerchuk DM, Weinshenker BG (2016) Neurology 86:491–492 Myelitis and lupus: clinical manifestations, diagnosis and treatment., Chiganer EH, Hryb JP (2017) Carnero Contentti E. Reumatol Clin. ;13:344–348 Guidelines on the use, Padmanabhan A, Connelly-Smith L, Aqui N et al (2019) of therapeutic apheresis in clinical practice - Evidence-based approach from the writing committee of the American Society for Apheresis: the eighth special issue. J Clin Apher 34:171–354 O17 Effectiveness of rituximab in the treatment of neuro-psychiatric SLE: results from the British Isles Lupus Assessment Group Biologics Register, David T, Hum RM, Sutton E et al (2021) Rheumatology 60:0 Additional Declarations No competing interests reported. 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The primary causes of acute TM include demyelinating diseases, infections, and autoimmune inflammatory disorders, such as systemic lupus erythematosus (SLE). Neurological and psychiatric symptoms associated with SLE (NPSLE) are diverse and are often linked with poor prognosis. Studies based on the American College of Rheumatology\u0026rsquo;s (ACR) classification report a prevalence rate of 37\u0026ndash;95% for NPSLE [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This wide range may be due to factors such as the inclusion of minor symptoms, lack of a standard for diagnosis, and the challenges of attributing events to either primary NPSLE or secondary causes (like infections, medications, metabolic changes, and multiorgan damage). TM, one of the 19 NPSLE syndromes classified by ACR in 1999, appears in 1\u0026ndash;2% of SLE cases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. TM in SLE cases is often severe; one-third of patients experience symptoms as an early indicator, though it can occur up to three years after diagnosis. Recurrence of TM ranges from 18\u0026ndash;50%. In Colombia, the prevalence of SLE is about 9.19 per 10,000 people, comparable to other Latin American countries [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Myelitis affects between 1% and 2% of SLE patients and is about 1,000 times more common than idiopathic myelitis in the general population [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. SLE-associated TM can involve grey matter, leading to hypotonia and hyporeflexia, or white matter, resulting in irreversible myelitis with spasticity and hyperreflexia. SLE-related TM has high morbidity, and rapid treatment with corticosteroids and cyclophosphamide can improve outcomes. However, due to limited awareness of its clinical presentations, SLE-related TM is often underdiagnosed [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. This case report details a severe, longitudinal episode of TM in SLE, where early clinical suspicion, timely imaging, and prompt therapeutic intervention enabled a full recovery.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 23-year-old woman with no significant medical history, aside from autoimmune hemolytic anemia requiring transfusion and treatment with prednisolone, arrived at our hospital\u0026rsquo;s emergency department. She reported experiencing lower back pain, polyarthralgia, and progressive muscle weakness in her lower limbs. Over the past two weeks, she had also noticed a loss of bladder and bowel control and dysesthesias extending from her abdomen down to her feet. On examination, her temperature was normal at 37\u0026deg;C, and her blood pressure was 135/80 mmHg. Respiratory, cardiac, abdominal, and joint exams were unremarkable. Neurological assessment revealed a muscle strength of 1/5 in the lower limbs and 5/5 in the upper limbs, with reduced sensitivity to pain, touch, and temperature at the T8 dermatome level. Cranial nerve examination showed no abnormalities, but she had red, raised, scaly plaques on her skin. A lumbar puncture revealed clear fluid without pleocytosis, a glucose level of 53 mg/dL (normal range: 40\u0026ndash;80 mg/dL), with a concurrent blood glucose level of 112 mg/dL, and total protein at 83 mg/dL (normal range: 40\u0026ndash;60 mg/dL). Cerebrospinal fluid (CSF) tests for infections were negative. Her ANA antibodies were positive, anti-DNA antibodies were measured at 1664 IU/mL, with C3 at 36 mg/dL and C4 at 6.6 mg/dL.\u003c/p\u003e \u003cp\u003eWith a suspicion of complete spinal cord syndrome, an MRI was performed, which ruled out extramedullary compression and showed a mild increase in spinal cord diameter, along with T2 and STIR hyperintensity from T7 to L1. These findings were consistent with a longitudinally extensive TM (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Treatment was initiated with high-dose methylprednisolone at 1 gram per day for two days.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eSystemic lupus erythematosus (SLE) is a complex multisystem disorder with the potential to impact any organ. Its most common manifestations involve the skin and joints, though renal involvement and neuropsychiatric manifestations (NPSLE) are also significant. The presence of NPSLE often correlates with more severe disease and affects the overall prognosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. NPSLE encompasses a range of neurological and psychiatric complications attributed to SLE, posing diagnostic challenges due to its broad spectrum and variability in clinical presentation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In 1999, the American College of Rheumatology (ACR) categorized NPSLE into 19 distinct syndromes, dividing them into central nervous system (CNS) manifestations\u0026mdash;further classified into focal and diffuse\u0026mdash;and peripheral nervous system (PNS) manifestations. Among the focal CNS manifestations is transverse myelitis (TM), which represents more than just a pathological or radiological spinal lesion. TM reflects acute or subacute spinal cord dysfunction on a sensory level and, if complete, results in motor and autonomic impairments (affecting bladder, bowel, and sexual function) below the lesion level. Partial TM, on the other hand, involves either motor or sensory deficits but not both[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe pathogenesis of NPSLE remains incompletely understood, but small-vessel vasculitis and thrombosis, as suggested by pathological and serological findings, likely contribute to axonal injury through ischemia and necrosis. In cases of TM, the spinal level and extent of involvement may indicate which pathophysiological mechanisms are at play. Thoracic involvement is common, given that this segment contains smaller caliber vessels in the spinal vasculature and is thus more vulnerable to thrombosis. If antiphospholipid antibodies (aPL) are present, this might suggest a thrombotic mechanism at work [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Studies show that among NPSLE patients with TM, between 50% and 100% have associated aPL antibodies. For example, Katsiari CG et al. (2011) reported no benefit from anticoagulant therapy in such cases[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This association underscores the importance of testing for these antibodies, as they may heighten the risk of neurological complications in SLE patients. Additionally, some SLE patients are seropositive for anti-aquaporin 4 (AQP4) antibodies, which are specific markers for neuromyelitis optica (NMO). These antibodies induce direct CNS injury through astrocytic damage via complement- and antibody-dependent cytotoxicity. The presence of AQP4 during an initial TM episode suggests a higher likelihood of recurrence and possible optic neuritis development within the year. While AQP4 positivity in SLE is relatively low (2\u0026ndash;3%), it is significantly higher (27%) in NPSLE cases[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The International Consensus on NMO Spectrum Disorders suggests that, in cases where AQP4 testing is unavailable, diagnosis can rely on clinical evaluation, two core clinical criteria, and ruling out alternative diagnoses [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In the case described, there was no evidence of NMO-associated regional CNS spread or symptomatic cerebral or area postrema involvement at the onset of myelitis. There was also no further CNS involvement in the six clinical regions of interest for NMO diagnosis prior to the patient's passing.\u003c/p\u003e \u003cp\u003eRegarding diagnosis, the ACR defined lupus-associated TM diagnostic criteria in 1999. Based on the clinical picture, affected patients present with acute or subacute paraplegia or quadriplegia, typically bilateral but not always symmetrical, along with a sensory level identified at the spinal level, and/or bowel or bladder dysfunction. Rapid neuroimaging is essential to rule out spinal cord compression. Contrast-enhanced MRI is the diagnostic tool of choice for confirming TM and ruling out other causes, such as spinal cord hemorrhages or tumors. Longitudinal spinal involvement (71%) is more common than transverse involvement (28%) in imaging studies[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. CSF findings may include lymphocytic pleocytosis and slightly reduced glucose levels (usually\u0026thinsp;\u0026gt;\u0026thinsp;30 mg/dL). However, normal CSF results do not exclude TM.\u003c/p\u003e \u003cp\u003eTwo TM subtypes are reported based on clinical and imaging findings: gray matter TM, which presents with fever, flaccid weakness, hyporeflexia, and urinary retention, with rapid onset. This subtype is linked to anti-DNA antibodies. White matter TM is associated with positive aPL antibodies, recurrent thrombosis, and anti-Ro/SSA antibodies. In Birnbaum J et al.'s 2009 cohort, overlap between TM-SLE and NMO showed predominant white matter involvement, with a history of optic neuritis, longitudinal TM (\u0026gt;\u0026thinsp;3 vertebral segments), recurrent relapses, and MRI findings not characteristic of multiple sclerosis. White matter TM is often recurrent, while gray matter involvement tends to show a monophasic recurrence pattern. In a subset of antiphospholipid syndrome (APS) patients, white matter lesions with positive lupus anticoagulant are found in over half, whereas gray matter involvement is under 20%. Anti-DNA and anti-Ro/SSA antibodies did not significantly differ between these groups[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The case described did not meet NMO or APS criteria, and, although mixed features were present, gray matter involvement was predominant.\u003c/p\u003e \u003cp\u003eAs for treatment, the European League Against Rheumatism (EULAR) recommends initiating IV methylprednisolone and cyclophosphamide early for NPSLE, ideally within hours of symptom onset, even if CSF findings suggest possible meningitis while awaiting microbiological results. This combination is considered the standard treatment for this neuropsychiatric complication. Typical doses include IV methylprednisolone pulses of 1 gram daily for three days, combined with IV cyclophosphamide at 0.75\u0026ndash;1 g/m\u0026sup2; monthly for six months, followed by every three months for a year, alongside oral prednisone at 1 mg/kg/day starting on day four, tapering over 1\u0026ndash;3 months. Plasmapheresis may be added for refractory cases, although it does not appear to improve prognosis[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. IV immunoglobulin has also been employed in initial or refractory cases, either alone or with standard therapy. Anticoagulation, while used in aPL-positive TM cases, has not shown additional therapeutic benefit beyond immunosuppression. Emerging data on biologics like rituximab, alone or combined with cyclophosphamide, show promise but require larger studies[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMaintenance therapy options include azathioprine, methotrexate, or mycophenolate combined with low-dose steroids, generally recommended for three years or longer; however, the optimal duration is not yet defined.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eLe LED peut parfois causer une cons\u0026eacute;quence neurologique grave appel\u0026eacute;e my\u0026eacute;lite transverse extensive longitudinale (LETM). La litt\u0026eacute;rature manque consid\u0026eacute;rablement d\u0026rsquo;informations sur l\u0026rsquo;\u0026eacute;volution clinique, les r\u0026eacute;sultats et l\u0026rsquo;efficacit\u0026eacute; th\u0026eacute;rapeutique. Les infections, les affections d\u0026eacute;my\u0026eacute;linisantes et les tumeurs compressives sont toutes incluses dans le diagnostic diff\u0026eacute;rentiel large de la LETM. En raison de l\u0026rsquo;importance clinique et pronostique du MT-LED, une reconnaissance et une intervention imm\u0026eacute;diates sont n\u0026eacute;cessaires pour pr\u0026eacute;venir les r\u0026eacute;sultats catastrophiques qui se produisent chez jusqu\u0026rsquo;\u0026agrave; un tiers des patients. Si l\u0026rsquo;am\u0026eacute;lioration clinique n\u0026rsquo;est pas obtenue avec la corticoth\u0026eacute;rapie initiale, l\u0026rsquo;ajout d\u0026rsquo;une prise en charge immunomodulatrice incluant le cyclophosphamide ou la plasmaph\u0026eacute;r\u0026egrave;se ne doit pas \u0026ecirc;tre retard\u0026eacute; en raison de son impact favorable sur l\u0026rsquo;invalidit\u0026eacute; et la survie, en particulier dans les cas r\u0026eacute;fractaires. Notre patient avait une LETM et pr\u0026eacute;sentait une d\u0026eacute;t\u0026eacute;rioration neurologique substantielle. Une intervention opportune a permis une r\u0026eacute;cup\u0026eacute;ration progressive remarquable de la fonction, et notre patient atteint de LED a pu marcher et r\u0026eacute;cup\u0026eacute;rer la fonction et la sensation du sphincter sans pr\u0026eacute;senter de s\u0026eacute;quelles \u0026agrave; long terme.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMRI : Magnetic Resonance Imaging\u003c/p\u003e\n\u003cp\u003eTM : Transverse myelitis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSLE : Systemic lupus erythematosus\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eACR : American College of Rheumatology\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCSF : Cerebrospinal fluid\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNPSLE : Neurological and psychiatric symptoms associated with SLE\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEULAR : European League Against Rheumatism\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCNS : Central nervous system\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePNS : Peripheral nervous system\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNMO : Neuromyelitis optica\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAQP4 : Anti-aquaporin 4\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eaPL : Antiphospholipid antibodies \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Clinical Ethics Committee of the International University Hospital Cheikh Zaid. The patient provided informed consent to participate in the study, including consent to share the MRI images used in this work. All participants involved in this study have also given their consent to contribute to the research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient has given explicit consent for the use and publication of their MRI images in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere were no financial means or external funding sources for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors wish to thank Professor El quessar for his invaluable assistance in reviewing and correcting the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; Information\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr Abderrazzak Ajertil is a specialist in medical imaging and currently a resident in interventional neuroradiology at the International University of Abulcasis, Rabat, at the International University Hospital Cheikh Zaid.\u003c/p\u003e\n\u003cp\u003eDr Abdeljalil El Quessar is a professor and the head of the Department of Neuroimaging and Interventional Neuroradiology at the International University Hospital Cheikh Zaid, Rabat.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. AJERTIL is the primary author, and Professor EL QUESSAR contributed to the development of this work by providing her expertise in writing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eClinical features of transverse myelitis associated with systemic lupus erythematosus, Zhang S, Wang Z, Zhao J et al (2020) Lupus 29:389\u0026ndash;397\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThe American College (1999) of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 42:599\u0026ndash;608\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrevalence of systemic lupus erythematosus in Colombia (2019) Fern\u0026aacute;ndez-\u0026Aacute;vila DG, Bernal-Mac\u0026iacute;as S, Rinc\u0026oacute;n-Ria\u0026ntilde;o DN, Guti\u0026eacute;rrez D\u0026aacute;vila JM, Rosselli D. Lupus 28:1273\u0026ndash;1278: data from the national health registry 2012\u0026ndash;2016\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDistinct subtypes of myelitis in systemic lupus erythematosus, Birnbaum J, Petri M, Thompson R, Izbudak I, Kerr D (2009) Arthritis Rheum 60:3378\u0026ndash;3387\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiversity of neuropsychiatric manifestations in systemic lupus erythematosus (2020) Fujieda Y Immunol Med 43:135\u0026ndash;141\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSystemic lupus erythematosus, Yamazaki-Nakashimada MA (2016) Is it one disease? Rivas-Larrauri F. Reumatol Clin 12:274\u0026ndash;281\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTransverse myelitis, Beh SC, Greenberg BM, Frohman T, Frohman EM (2013) Neurol Clin 31:79\u0026ndash;138\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMyelitis in systemic, Hryb JP, Chiganer E, Contentti EC, Di Pace JL, Lessa C, Perassolo MB (2016) lupus erythematosus: clinical features, immunological profile and magnetic resonance imaging of five cases. Spinal Cord Ser Cases 2:16005\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAcute transverse myelitis and antiphospholipid antibodies in lupus. No evidence for anticoagulation. Katsiari CG, Giavri I, Mitsikostas DD, Yiannopoulou KG, Sfikakis PP (2011) \u003cem\u003eEur J Neurol.\u003c/em\u003e ;18:556\u0026ndash;563\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUnderstanding the antibody, Mader S, Jeganathan V, Arinuma Y et al (2018) repertoire in neuropsychiatric systemic lupus erythematosus and neuromyelitis optica spectrum disorder: do they share common targets? Arthritis Rheumatol 70:277\u0026ndash;286\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInternational consensus diagnostic criteria for neuromyelitis optica spectrum disorders, Tan CT, Mao Z, Qiu W, Hu X, Wingerchuk DM, Weinshenker BG (2016) Neurology 86:491\u0026ndash;492\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMyelitis and lupus: clinical manifestations, diagnosis and treatment., Chiganer EH, Hryb JP (2017) Carnero Contentti E. \u003cem\u003eReumatol Clin.\u003c/em\u003e ;13:344\u0026ndash;348\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuidelines on the use, Padmanabhan A, Connelly-Smith L, Aqui N et al (2019) of therapeutic apheresis in clinical practice - Evidence-based approach from the writing committee of the American Society for Apheresis: the eighth special issue. J Clin Apher 34:171\u0026ndash;354\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO17 Effectiveness of rituximab in the treatment of neuro-psychiatric SLE: results from the British Isles Lupus Assessment Group Biologics Register, David T, Hum RM, Sutton E et al (2021) Rheumatology 60:0\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"transverse myelitis, neuropsychiatric lupus, cyclophosphamide, autoimmune","lastPublishedDoi":"10.21203/rs.3.rs-5471728/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5471728/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAcute transverse myelitis (TM) is an inflammatory condition that presents with quickly advancing motor, sensory, and autonomic symptoms, which can have severe consequences. The three leading causes of acute TM are demyelinating diseases, infections, and autoimmune inflammatory conditions like systemic lupus erythematosus (SLE). The American College of Rheumatology (ACR) includes TM as one of the 19 neuropsychiatric conditions linked with SLE, with an incidence rate of about 1\u0026ndash;2% among SLE cases. Misdiagnosis is common, often resulting in high morbidity and mortality. This report examines the case of a 23-year-old woman with progressive muscle weakness in her lower limbs, dysesthesias from the abdomen to the feet, and loss of sphincter control. On examination, severe paraparesis with sensory level at T8 was identified. MRI of the thoracolumbar spine showed hyperintensity on T2 and STIR sequences from T7 to L1, consistent with TM. Due to resistance to initial treatment, cyclophosphamide was administered. After a week in the hospital, the patient showed partial neurological improvement. Recognizing TM in SLE patients requires high clinical suspicion, and early intervention is crucial to minimize severe complications and reduce the rates of morbidity and mortality.\u003c/p\u003e","manuscriptTitle":"Extensive Longitudinal Transverse Myelitis in Systemic Lupus Erythematosus: Case Report and Review of Current Literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-03 15:04:37","doi":"10.21203/rs.3.rs-5471728/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d10da51f-6217-4d5d-8904-ddb7a4ee880d","owner":[],"postedDate":"December 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-03T15:04:37+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-03 15:04:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5471728","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5471728","identity":"rs-5471728","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}