RARE DISEASE
Acute transverse myelitis
Acute transverse myelitis
Acute transverse myelitis
Drug discovery
2
drugs
With orphan designations
Overview
Acute Transverse Myelitis (ATM) is an acute inflammatory disorder affecting spinal cord gray and white matter, typically presenting with bilateral motor, sensory, and autonomic deficits below the lesion. Common etiologies include multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), infections, autoimmune conditions, or idiopathic causes. Diagnosis relies on MRI, cerebrospinal fluid analysis, and exclusion of compressive lesions. Initial treatment involves high-dose IV corticosteroids and plasma exchange for refractory cases. Prognosis varies, with one-third recovering fully, one-third retaining residual deficits, and one-third experiencing severe disability [1][2][3][5][7].
Burden
Disability: ~33% require ambulatory aids or lifelong care; severe bladder/bowel dysfunction in 80–94% [1][3][5].
Mortality: Up to 10% in longitudinal studies, often due to comorbidities or complications [4][7].
Economic impact: High costs from prolonged rehabilitation, missed work, and chronic care needs [4][7].
Therapies
Categories: rare neurological diseases
Research Papers
405 drug discovery papers about Acute transverse myelitis, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
405 drug discovery papers about Acute transverse myelitis, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-14 | Seronegative Longitudinally Extensive Transverse Myelitis in a Filipino Adult: Diagnostic Challenges and Characteristic Longitudinal MRI Findings.
Longitudinally extensive transverse myelitis (LETM) is a radiologic pattern of longitudinal spinal cord involvement most commonly associated with antibody-mediated autoimmune diseases such as neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease. Seronegative inflammatory cases remain diagnostically challenging because they require careful exclusion of infectious, autoimmune, vascular, neoplastic, metabolic, and structural etiologies. A 45-year-old Filipino female presented with a three-day history of severe upper back pain, followed by rapidly progressive bilateral upper and lower extremity weakness, sensory disturbances, and urinary retention. Neurologic examination revealed asymmetric quadriparesis, a sensory level at the fourth thoracic dermatome, preserved vibration and proprioception, and mixed hyperreflexia and hyporeflexia with bilateral Babinski signs. Spinal magnetic resonance imaging (MRI) demonstrated a poorly defined, non-expansile intramedullary T2-hyperintense lesion extending contiguously from C3 to T2 without discrete enhancement. Diffusion-weighted imaging demonstrated no restricted diffusion. Cerebrospinal fluid analysis showed mild lymphocytic pleocytosis with normal IgG index and absence of oligoclonal bands. Extensive infectious, inflammatory, autoimmune, and metabolic investigations were unrevealing, including negative serum aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies. Follow-up spinal MRI performed 3.5 months later demonstrated persistent longitudinal non-enhancing intramedullary T2 hyperintensity with evolution toward chronic myelomalacic change, providing important longitudinal imaging evidence supporting an inflammatory antibody-negative myelopathy over competing diagnostic considerations. The patient was treated with high-dose intravenous methylprednisolone, followed by an oral prednisone taper and subsequent initiation of azathioprine because of persistent severe deficits. Despite immunotherapy and rehabilitation, she remained wheelchair-dependent with persistent dysesthesias and neurogenic bladder at follow-up. Following comprehensive multidisciplinary evaluation and longitudinal follow-up, an inflammatory antibody-negative LETM was considered the most likely diagnosis after exclusion of competing etiologies. This case highlights the diagnostic complexity, therapeutic challenges, and potentially severe neurologic outcomes associated with seronegative LETM. It also underscores the importance of systematic exclusion of alternative etiologies, longitudinal follow-up, repeat serologic evaluation, and individualized consideration of escalation immunotherapy in patients with incomplete response to corticosteroid treatment.
2026-08-08 | Complement C3 inhibitory peptide AMY-101 ameliorates brain injury in a mouse model of NMOSD.
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease of the central nervous system, clinically characterized primarily by optic neuritis and transverse myelitis. This study aimed to investigate the therapeutic potential of the complement C3 inhibitory peptide AMY-101 in experimental models of NMOSD. In vitro experiments were performed using AQP4-transfected cells exposed to AQP4-IgG and human complement to assess complement-dependent cytotoxicity and membrane attack complex (MAC) deposition. In vivo efficacy was evaluated in an intracerebral injection mouse model of NMOSD, in which histopathological changes after AMY-101 treatment were compared with those in untreated controls. AMY-101 significantly attenuated AQP4-IgG- and complement-mediated cytotoxicity and inhibited MAC formation in vitro. In the NMOSD mouse model, AMY-101 treatment markedly reduced astrocyte loss, AQP4 depletion, and demyelination compared with controls. These findings demonstrate that complement C3 inhibition with AMY-101 effectively ameliorates key pathological features of NMOSD in experimental models, supporting its potential as a therapeutic strategy and providing a rationale for further preclinical and clinical investigation.
2026-07-30 | Area postrema syndrome and longitudinally extensive transverse myelitis masquerading as leptomeningeal carcinomatosis.
Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune demyelinating disease of the central nervous system commonly associated with aquaporin-4 (AQP4) antibodies. Area postrema syndrome (APS), characterized by intractable nausea, vomiting, and hiccups, is a core clinical feature but is frequently misdiagnosed as a gastrointestinal disorder, leading to delays in diagnosis and treatment. A 63-year-old woman with a history of treated breast cancer presented with one week of intractable nausea, vomiting, progressive left lower extremity weakness, and sensory changes. Initial evaluation was unrevealing. MRI demonstrated longitudinally extensive transverse myelitis and an enhancing dorsal medullary lesion consistent with APS, along with diffuse leptomeningeal enhancement raising concern for neoplastic or inflammatory etiologies. Cerebrospinal fluid analysis showed lymphocytic pleocytosis and elevated protein. The patient developed respiratory failure requiring intensive care support. Empiric treatment with high-dose intravenous methylprednisolone and plasma exchange was initiated. AQP4-IgG serology returned positive, confirming NMOSD. Following treatment, nausea and mental status improved, with partial neurological recovery, although significant residual left leg weakness and neurogenic bladder persisted. The patient was discharged to rehabilitation with plans for long-term immunosuppressive therapy. This case highlights APS as an important early manifestation of NMOSD that may mimic gastrointestinal or neoplastic conditions, particularly in patients with complex medical histories. Early recognition of APS and prompt immunotherapy are critical to prevent severe neurological disability and improve outcomes.
2026-07-03 | Longitudinally extensive transverse myelitis with encephalopathy following acute dengue infection
Dengue is a common arboviral infection in tropical/subtropical regions; neurologic complications occur in ~5% of cases, usually as encephalopathy from systemic illness (1). Viral neurotropism and immune-mediated injury are rare and mimic infectious/inflammatory etiologies (2,3). Although corticosteroids are not routinely recommended, case reports describe high-dose steroids usage with favorable outcomes (4,5). A previously healthy 25-year-old man in Brazil developed fever and retro-orbital headache followed by disorientation, hallucinations, abdominal pain, urinary retention, and rapidly progressive areflexic paraparesis. CSF showed lymphocytic pleocytosis (140 cells/µL); infectious and autoimmune/demyelinating tests were negative. MRI revealed longitudinally extensive intramedullary hyperintensity from upper cervical cord to conus with leptomeningeal enhancement. Dengue IgM with IgM/IgG seroconversion confirmed acute infection. IV methylprednisolone (1 g/day) improved symptoms within 72h; he walked by day 5 and fully recovered within 1 year. In endemic settings, neurodengue is a possibility when alternatives are excluded. Once infection is ruled out, immunotherapy should be considered.
2026-06-22 | Spinal Cord Involvement in Neurosarcoidosis: A Case of Longitudinally Extensive Transverse Myelitis at Disease Onset.
Acute-onset neurological deficits in otherwise healthy individuals warrant a broad differential diagnosis. Neurosarcoidosis presenting as longitudinally extensive transverse myelitis is rare, mimicking demyelinating, infectious, or neoplastic disorders. Early recognition, histopathological confirmation, and timely immunosuppressive therapy are crucial. Further research is mandatory in optimizing treatment regimens, especially for refractory neurosarcoidosis cases.
proteins
2025-08-27 | Telitacicept Inhibits the Maturation and Differentiation of B Lymphocytes in NMOSD.
Telitacicept, a novel recombinant fusion protein comprising the ligand-binding domain of the TACI receptor and the Fc component of human IgG, has rarely been studied for the treatment of neuromyelitis optica spectrum disorders (NMOSD). This study aimed to explore the effects of telitacicept in NMOSD mice. An NMOSD mouse model was constructed. Fifty microliters of 0.8 mg/mL telitacicept was injected intravenously on Days 4, 8, 12 and 16 postimmunization (p.i.). Behavioral scoring, magnetic resonance imaging and histopathological evaluation were conducted on Day 19. B lymphocytes and their subgroups were analyzed by flow cytometry. Concentration of serum IgM was measured using an ELISA kit. Concentrations of B lymphocyte stimulator (BLyS) and IL-6 were measured via LEGENDplex. Differentially expressed genes of B lymphocytes were screened via mRNA sequencing and verified by qPCR. Behavioral score of telitacicept-treated NMOSD mice significantly decreased (p < 0.0001). Inflammation, demyelination, loss of AQP4 and GFAP in the spinal cord were markedly alleviated (p < 0.05). B lymphocytes and their subsets were reduced to varying degrees (p < 0.05). Telitacicept treatment significantly reduced serum IgM levels (p < 0.01), as well as BLyS and IL-6 concentrations (p < 0.05). Telitacicept induced differential gene expression in B lymphocytes, inhibiting the expression of transcription factors related to B lymphocyte maturation, such as IRF8, BLIMP1, and Pou2af1, as well as cell surface receptors such as CD19 and CD21. Telitacicept has a therapeutic effect on NMOSD mice by regulating the differentiation of B lymphocyte subsets and inhibiting the production of pathogenic antibodies.
2024-10-28 | Overview of emerging therapies for demyelinating diseases.
This paper provides an overview of autoimmune disorders of the central nervous system, specifically those caused by demyelination. We explore new research regarding potential therapeutic interventions, particularly those aimed at inducing remyelination. Remyelination is a detailed process, involving many cell types-oligodendrocyte precursor cells (OPCs), astrocytes, and microglia-and both the innate and adaptive immune systems. Our discussion of this process includes the differentiation potential of neural stem cells, the function of adult OPCs, and the impact of molecular mediators on myelin repair. Emerging therapies are also explored, with mechanisms of action including the induction of OPC differentiation, the transplantation of mesenchymal stem cells, and the use of molecular mediators. Further, we discuss current medical advancements in relation to many myelin-related disorders, including multiple sclerosis, optic neuritis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, transverse myelitis, and acute disseminated encephalomyelitis. Beyond these emerging systemic therapies, we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries. Despite these aforementioned scientific advancements, this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients' quality of life.
2024-09-02 | Effects of intravenous pulse methylprednisolone in neuromyelitis optica during the acute phase.
Neuromyelitis optica spectrum disorder (NMOSD) is an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. While intravenous pulse methylprednisolone (IVMP) is the recommended initial treatment option for acute onset NMOSD, its therapeutic mechanism remains unclear. We hypothesized that IVMP would reduce the expression of pro-inflammatory factors and increase the resolution of inflammation in patients with NMOSD. Mendelian randomization (MR) analysis was used to screen meaningful inflammatory and resolution factors for inclusion. Three MR methods with inverse variance weighting (IVW) were primarily used to identify positive results. Interleukin (IL)-10, IL-1β, IL-6, C-X-C motif chemokine ligand 12 (CXCL12), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were screened from 41 inflammatory factors, and resolvin D1 (RvD1), maresin 1 (MaR1), and lipoxin A4 (LXA4) were screened from 6 resolution markers for inclusion. Subsequently, 12 patients with NMOSD were enrolled and treated with IVMP. Serum levels of the aforementioned inflammatory and resolution markers were measured by enzyme-linked immunosorbent assay before and after IVMP treatment. High levels of TRAIL, CXCL12, and IL-1β were associated with an increased risk of NMOSD (TRAIL: odds ratio [OR], 1.582; 95% confidence interval [CI], 1.003-2.495; CXCL12: OR, 3.610; 95% CI, 1.011-12.889; IL-1β: OR, 4.500; 95% CI, 1.129-17.927). High levels of RvD1, MaR1, and LXA4 were associated with a reduced risk of NMOSD (RvD1: OR, 0.725; 95% CI, 0.538-0.976; MaR1: OR, 0.985; 95% CI, 0.970-0.999; LXA4: OR, 0.849; 95% CI, 0.727-0.993). Among patients with NMOSD, serum levels of IL-6, CXCL12, and TRAIL significantly decreased following IVMP treatment, compared with pretreatment levels, while levels of IL-1β, LXA4, and MaR1 significantly increased after IVMP treatment (p < 0.05). A significant positive correlation was observed between CXCL12 levels and Expanded Disability Status Scale (EDSS) scores (r = 0.451, p < 0.05). Several systemic inflammatory regulators associated with the pathogenesis of NMOSD were identified. The protective roles of LXA4 and MaR1 may be indispensable components of glucocorticoid treatment. Therefore, the use of resolution markers may be a potential strategy for improving central nervous system injury in individuals with NMOSD.
2012-10-02 | Botulinum toxin A in the treatment of spasticity - An open label study.
To assess the efficacy of botulinum toxin type A in spasticity in upper-motor neuron syndromes. Twenty-three patients with spasticity resulted from stroke-related hemiplegia, transverse myelitis and multiple sclerosis took part in the study. Following the history and physical examinations of the patients, injections of botulinum toxin-A were applied. The dose ranged from 80 to 400 mouse unit (MU) depending on the size of the muscle injected. In all patients, spasticity, spasms and pain were measured using the Ashworth Scale, Spasm Frequency Score, and Visual Analogue Scale prior to the therapy, at the 1st week, 1st month and 3rd month of the therapy. In all patients, botulinum toxin type A led to a significant decrease in spasticity, spasms and pain after the 1st week, 1st and 3 rd months of the treatment when compared to the baseline values (p<0.001). No significant side effects or complications were observed. Our results have demonstrated that botulinum toxin type A is effective in the management of patients with spasticity due to stroke-related hemiplegia, transverse myelitis and multiple sclerosis, without major adverse effects.
2007-07-03 | Successful treatment with botulinum toxin A after failed augmentation ileocystoplasty.
A 49-year old man initially underwent clam ileocystoplasty 14 years ago. A revision of this original procedure was required 11 years ago for intractable detrusor overactivity secondary to transverse myelitis; he experienced only temporary symptomatic improvement that lasted 6 months after each procedure. Despite the use of oral anticholinergic drugs, the patient subsequently needed to perform clean intermittent self-catheterization approximately 10 times every 24 h, and when he presented to our department, he still suffered from occasional episodes of urgency incontinence that required the regular use of a penile sheath. Symptom severity was assessed using a 4-day bladder diary. Cystometry confirmed the presence of terminal detrusor overactivity. After the patient provided his informed consent, he was treated as an outpatient with intradetrusor injections of botulinum toxin A, delivered under local anesthesia by a minimally invasive technique that used a flexible cystoscope. A significant improvement was noted in the patient's lower urinary tract symptoms, urodynamic parameters and quality of life, measured at 4 and 16 weeks after treatment. The patient was completely dry at both follow-up visits and was able to discontinue the use of anticholinergic drugs and the penile sheath for a total of 11 months.
antibodies
2026-08-13 | AQP4-IgG-positive myelitis occurring in a patient with small cell lung cancer: a case report.
Acute myelopathy in patients with small cell lung cancer (SCLC) is often attributed to metastatic spinal cord involvement. However, non-compressive inflammatory conditions, particularly aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD), can produce similar clinical and radiologic features, creating substantial diagnostic uncertainty. A male aged 65 years with extensive-stage SCLC presented with acute urinary retention followed by rapidly progressive paraplegia. Spinal magnetic resonance imaging (MRI) revealed longitudinally extensive intramedullary T2-hyperintense lesions affecting the cervical and thoracic spinal cord, with patchy contrast enhancement and no evidence of vertebral destruction, epidural mass, or spinal cord compression. Cerebrospinal fluid (CSF) examination demonstrated inflammatory abnormalities without malignant cells, and infectious causes were excluded. Serum and CSF testing were strongly positive for AQP4-IgG, establishing a diagnosis of AQP4-IgG-positive NMOSD. The patient received high-dose intravenous methylprednisolone followed by adjunctive intravenous immunoglobulin (IVIG). Plasma exchange was not performed because of advanced malignancy and concerns regarding procedural risks. Satralizumab was initiated during corticosteroid tapering for maintenance immunotherapy. Neurological function subsequently stabilized, and partial recovery of independence in activities of daily living was achieved. This case highlights that AQP4-IgG-positive myelitis can occur in patients with SCLC. In patients presenting with non-compressive longitudinally extensive transverse myelitis (LETM), particularly when imaging shows no evidence of compression and CSF cytology is negative for malignant cells, prompt AQP4-IgG testing is critical to prevent misdiagnosis and enable early initiation of appropriate immunotherapy.
2026-08-06 | Case Report: Anti-GQ1b antibody–positive overlap syndrome: a pediatric case involving the brainstem, spinal cord, and peripheral nerves
Disorders associated with anti-GQ1b antibodies predominantly encompass Bickerstaff brainstem encephalitis (BBE), Guillain–Barré syndrome (GBS), and Miller Fisher syndrome. Concurrent presentation of BBE, GBS, and acute transverse myelitis is exceptionally rare and presents significant diagnostic and therapeutic challenges. This report describes an 8-year-old boy who exhibited clinical features consistent with all three conditions, including impaired consciousness, ophthalmoplegia, ataxia, and limb weakness. Laboratory investigations revealed positive serum anti-GQ1b IgG antibodies, elevated cerebrospinal fluid protein levels with mild lymphocytic pleocytosis, and neurophysiological findings indicative of peripheral nerve demyelination. Magnetic resonance imaging of the brain and spinal cord demonstrated evidence of brainstem encephalitis and extensive spinal cord involvement. Following treatment with intravenous immunoglobulin and corticosteroid pulse therapy, marked neurological improvement was observed, and follow-up evaluations demonstrated favorable resolution of radiological abnormalities. This case highlights that anti-GQ1b antibody–associated syndrome may simultaneously affect the brainstem, spinal cord, and peripheral nerves. Early recognition and prompt initiation of combined immunotherapy may be critical for optimizing clinical outcomes.
2026-06-26 | Hantavirus infection: Neurologic manifestations should not be overlooked.
Hantavirus infection is primarily associated with hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), with predominant renal and pulmonary involvement. However, neurological manifestations affecting both the central nervous system (CNS) and peripheral nervous system (PNS) are increasingly recognized. We conducted a narrative review of the literature to summarize the current evidence regarding hantavirus-associated neurological involvement. Reported CNS manifestations included encephalitis, encephalopathy, seizures, meningitis, neurocognitive alterations, posterior reversible encephalopathy syndrome, transverse myelitis, and cerebral hemorrhage. PNS involvement appeared less frequent and included Guillain-Barré syndrome, cranial nerve palsies, neuropathic pain, and sensory disturbances. Neuroimaging findings were heterogeneous, while cerebrospinal fluid analysis often demonstrated nonspecific inflammatory changes. Advanced molecular techniques such as metagenomic next-generation sequencing may improve diagnostic sensitivity, particularly in immunocompromised patients. Current evidence suggests that neurological involvement may result from endothelial dysfunction, neuroinflammation, immune-mediated injury, blood-brain barrier disruption, and, in selected cases, direct viral neuroinvasion. Greater clinical awareness is needed to improve recognition of neurological complications during hantavirus infection. Further prospective studies are required to better define the epidemiology, pathogenesis, and optimal diagnostic approaches of hantavirus-associated neurological disease.
2026-06-01 | Longitudinal Spinal Cord Atrophy in Patients With Neuromyelitis Optica Spectrum Disorder and Its Association With Rituximab Treatment.
Longitudinally extensive transverse myelitis (LETM) is a core feature of neuromyelitis optica spectrum disorder (NMOSD), which leads to spinal cord atrophy. We aim to determine annual spinal cord atrophy rates and influencing factors in NMOSD. Spinal cord structural metrics, including cross-sectional area (CSA), anteroposterior diameter (AP), and right-left diameter (RL), were calculated using the Spinal Cord Toolbox from brain 3D sagittal T1-weighted images covering the C1-C3 levels. Normative references were constructed based on healthy participants and used to derive the deviation scores (Z-scores). Annualized atrophy rates were estimated using a linear mixed-effects model. Associations with clinical measures, rituximab treatment, and neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were assessed using partial Pearson correlation, multivariate linear regression, and linear mixed-effects models. In this longitudinal study, 72 patients with NMOSD (233 MRI scans; mean age 40.0 years; 84.7% female) from the CLUE cohort and 2,162 healthy participants were included. In patients with NMOSD, annual atrophy rates were -0.27/y for CSA (95% CI -0.35 to -0.20, p < 0.001), -0.23/y for AP (95% CI -0.33 to -0.13, p < 0.001), and -0.14/y for RL (95% CI -0.20 to -0.09, p < 0.001). A faster AP atrophy rate was associated with longer T2 lesion length and a higher number of relapses (r = -0.35/-0.25, p < 0.05). Prolonged interval from initial LETM to baseline MRI was independently associated with a slower CSA atrophy rate (β = 4.62 × 10-5; 95% CI 0.25 to 9.00 × 10-5, p = 0.043), while older age (β = -25.17 × 10-5; 95% CI -39.12 to -11.22 × 10-5, p < 0.001) and lesion length (β = -55.66 × 10-5; 95% CI -104.50 to -6.83 × 10-5, p = 0.029) were related to faster RL atrophy. Rituximab was associated with slower RL atrophy compared with other immunosuppressive therapies (β = 0.02; 95% CI 0.01-0.05; p = 0.044). Elevated serum GFAP levels were correlated with accelerated CSA (r = -0.42/-0.45), AP (r = -0.49/-0.45), and RL (r = -0.37/-0.44) atrophy at baseline/follow-up (all p < 0.01). Increased NfL levels were correlated with faster CSA and RL atrophy at follow-up (p = 0.009, p = 0.031). Spinal cord atrophy in NMOSD progresses annually and is influenced by disease activity and duration. Rituximab was associated with attenuated progression of spinal cord atrophy. Moreover, serum NfL and GFAP may serve as potential biomarkers.
2026-05-31 | Para infectious myelitis with Conus medullaris immunotropism in the immune phase of leptospirosis infection: Clinical pattern and in silico molecular mimicry analysis based biological plausibility.
Neurological involvement in leptospirosis but increasingly recognized, with myelitis representing a disabling complication. Conus medullaris involvement has not been systematically described and may reflect region-specific vulnerability to immune-mediated injury, post leptospirosis infection. We report a case series of three patients with serologically confirmed leptospirosis who developed acute myelitis during the immune phase, with radiological involvement of the conus medullaris. Clinical, cerebrospinal fluid, and imaging features were analyzed. A proteome-wide in silico comparison was performed between human myelin oligodendrocyte glycoprotein and the Leptospira interrogans proteome to identify shared antigenic motifs. All patients presented with acute bladder dysfunction, lower limb weakness, or sensory symptoms following a febrile illness. Magnetic resonance imaging showed conus medullaris involvement, either isolated or as part of longitudinal cord lesions. Cerebrospinal fluid revealed inflammatory changes. Treatment with steroids, with adjunctive immunotherapy in severe cases, resulted in clinical improvement. In silico analysis did not demonstrate full-length homology but identified 19 shared peptide motifs with moderate sequence identity, several overlapping predicted B-cell and T-cell epitope regions. This series suggests a possible para-infectious conus-predominant myelitis pattern in leptospirosis. The identification of shared antigenic motifs provides biological plausibility for immune-mediated demyelination through molecular mimicry. Recognition of this pattern in endemic regions may facilitate early diagnosis and timely immunotherapy.
cell therapies
2026-08-05 | Association of therapeutic plasma exchange with functional outcomes in selected neurological disorders: a retrospective cohort study from a single tertiary center in Saudi Arabia.
Neurological disorders are associated with considerable morbidity and healthcare impact. Therapeutic plasma exchange (TPE) is an intervention that removes pathogenic antibodies, immune complexes, and other plasma constituents from circulation. Previous studies have suggested that TPE could be associated with improved outcomes in selected neurological disorders. To evaluate functional outcomes following therapeutic plasma exchange in patients with selected neurological disorders at National Guard Health Affairs (NGHA) in Jeddah, Saudi Arabia. This retrospective cohort study analyzes 133 patients diagnosed with various neurological disorders who received TPE between August 2015 and December 2022 at NGHA. Diagnoses included multiple sclerosis (MS), myasthenia gravis (MG), Guillain-Barré syndrome (GBS), neuromyelitis optica spectrum disorder (NMOSD), chronic inflammatory demyelinating polyneuropathy (CIDP), autoimmune encephalitis (AE), and other neurological conditions including amyotrophic lateral sclerosis (ALS), transverse myelitis, cerebellar ataxia, paraneoplastic neurologic syndrome, polymyositis, and central nervous system (CNS) infections. The effectiveness of TPE was assessed using the Modified Rankin Scale (mRS) before and 90 days following the final TPE session. Statistical analysis included Wilcoxon signed-rank tests and Mann-Whitney U test, with significance set at (p < 0.05). Significant improvements in mRS scores were observed following TPE for MS, MG, and GBS (all p < 0.001), as well as for NMOSD (p = 0.008), CIDP (p = 0.007), and AE (p = 0.018), but not in other neurological disorders (p = 0.234). Overall mortality was 6.8%, with no TPE-related deaths. Comorbidities among deceased patients included hypertension, diabetes mellitus, malignancy, chronic kidney disease, and cardiovascular disease. TPE was associated with improved functional outcomes in selected neurological disorders. Comorbidities were common among patients with poorer outcomes. Due to the retrospective design and potential confounding factors, causal inferences cannot be established. Further prospective studies are warranted to evaluate the role of TPE and optimize patient selection.
2026-05-26 | Steroid Refractory and Plasma Exchange Partially Responsive Longitudinally Extensive Transverse Myelitis Due to Tumor Necrosis Factor-Alpha (Etanercept): A Case Report.
Background: Acute transverse myelitis (ATM) is an inflammatory disorder of the spinal cord with heterogeneous etiologies, including autoimmune, infectious, paraneoplastic, and drug-induced causes. Tumor necrosis factor-alpha (TNF-α) inhibitors have been infrequently associated with inflammatory central nervous system events, including transverse myelitis. TNF-inhibitor-associated myelitis typically presents with short-segment lesions, a normal brain MRI, and partial responsiveness to corticosteroids. Longitudinally extensive transverse myelitis (LETM) and steroid-refractory cases are uncommon. Case Presentation: A 39-year-old woman with psoriatic arthritis treated with etanercept for two years presented with subacute progressive bilateral lower-extremity sensory loss and weakness. MRI revealed a T2 hyperintense spinal cord lesion extending from T11 to L1 with gadolinium enhancement, consistent with transverse myelitis, while brain MRI was normal. Cerebrospinal fluid analysis showed lymphocytic pleocytosis, elevated protein, oligoclonal bands, and increased kappa free light chains. Extensive infectious, metabolic, paraneoplastic, and autoimmune testing, including aquaporin-4 and MOG antibodies, was negative. Despite high-dose intravenous corticosteroids and the discontinuation of etanercept, the patient experienced clinical worsening with lesion expansion, meeting criteria for LETM, and developed urinary retention. She subsequently underwent plasma exchange, resulting in radiologic improvement and moderate clinical recovery. Conclusions: This case highlights an atypical presentation of TNF-inhibitor-associated myelitis characterized by a biphasic course, longitudinally extensive spinal cord involvement, steroid refractoriness, and responsiveness to plasma exchange. These features suggest either an unusually severe TNF-inhibitor-related inflammatory phenotype or a TNF-inhibitor-triggered antibody-mediated demyelinating process. Reports of TNF-inhibitor-associated myelitis evolving into longitudinally extensive, steroid-refractory disease remain limited, and this presentation may broaden the recognized clinical spectrum of TNF-α-related CNS inflammatory events. Close neurologic follow-up and heightened awareness of severe CNS complications associated with TNF-α inhibitors are warranted.
2026-04-20 | Plasma Exchange as a Bridge to Recovery in Severe Pediatric Neurological Diseases in Pediatric Intensive Care.
Therapeutic plasma exchange (TPE) removes circulating pathogenic antibodies, immune complexes, cytokines, and complement components. While established in adult neurology, evidence on its safety and efficacy in pediatric neurocritical care remains limited. To evaluate the indications, clinical efficacy, and safety of TPE in children with acute or subacute immune-mediated neurological disorders admitted to the pediatric intensive care unit (PICU). A retrospective cohort of 24 pediatric patients (aged 1-18 years) treated with TPE between February 2023 and October 2025 was analyzed. Diagnoses included multiple sclerosis (n = 8), Guillain-Barré syndrome (n = 5), acute disseminated encephalomyelitis (n = 3), transverse myelitis (n = 3), autoimmune encephalitis (n = 3), optic neuritis (n = 1), and myasthenia gravis (n = 1). Patients received 3-7 TPE sessions. Clinical response was measured using the modified Rankin Scale (mRS) and GBS disability scores before and after treatment. A total of 130 sessions were performed. Clinical improvement occurred in 20 of 24 patients (83%)-moderate in 8 (33%) and mild in 12 (50%). Median mRS/GBS scores decreased from 4.0 to 3.0 (p = 0.001). Early initiation of TPE (≤ 7 days from symptom onset) was associated with a higher likelihood of neurological improvement in multivariable analysis. No life-threatening complications were observed. Transient, reversible events included hypocalcemia (2.3%), hypotension (1.5%), and urticaria (1.6%). TPE appears to be a safe and potentially beneficial intervention for severe or refractory pediatric neuroimmunological disorders. Earlier initiation of TPE was associated with improved neurological outcomes; however, these findings should be interpreted cautiously given the small sample size and heterogeneous disease groups. These findings support integrating TPE into multidisciplinary PICU management and add to the growing evidence supporting its use in pediatric neuroimmunology.
2025-11-18 | Efficacy and Safety of Plasmapheresis in Children With Acute Transverse or Flaccid Myelitis, and Guillain-Barré Syndrome.
Acute transverse myelitis (ATM), acute flaccid myelitis with polio-like myeloradiculitis (AFM) and Guillain-Barré syndrome (GBS) are severe neuroimmune disorders associated with high morbidity. First-line treatments include corticosteroids and intravenous immunoglobulins (IVIg), but they may be insufficient. Therapeutic plasma exchange (TPE) and immunoadsorption (IA) are second- or third-line options in pediatrics, despite their recognized efficacy in adults. Data on pediatric use remain limited. This study aimed to evaluate the efficacy and safety of apheresis in children with ATM, GBS or AFM. We conducted a retrospective monocentric study at Necker University Hospital, including pediatric patients diagnosed with ATM, GBS or AFM who underwent TPE/IA between 2014 and 2024. Functional outcomes were assessed using the modified Rankin Scale (mRS) at five time points, from peak disease severity to last follow-up. Safety was evaluated based on severe adverse events. Among 23 children (6 years [Q1-Q3]), 20 received TPE and 3 IA. 17 of 23 patients (74%) showed significant improvement by the end of treatment. The median mRS was 5 (IQR 4-5) before apheresis, improving to 4 (IQR 2-4) at the end of TPE/IA, and decreasing to 2 at 6 months. Brainstem function fully recovered in all surviving patients. Among 14 children with sphincter dysfunction, 5 (36%) still required intermittent catheterization. No treatment discontinuations occurred, but two patients died, one from venous air embolism, one after life-sustaining treatment limitation. TPE and IA appear effective in pediatric ATM, AFM and GBS. Larger studies are needed to confirm long-term efficacy and refine treatment guidelines.
2025-11-17 | Effectiveness and safety of therapeutic plasma exchange in neurological disorders; measuring the response to treatment using Modified Rankin Scale - A single-center study.
Therapeutic plasma exchange (TPE) is commonly used as a treatment modality in varying neurological disorders. Response to TPE in neurological disorders is usually noted in "subjective" terms. We, measured response to treatment, objectively, using Modified Rankin Scale (MRS). This was an observational prospective study in patients diagnosed with autoimmune neurological disorders (AND) who underwent TPE, in addition to intravenous immunoglobulin, and/or prednisolone. This study was carried out at a tertiary care center. Demographic data, procedure details including adverse reactions, and clinical responses were collated. Clinical response was assessed by applying MRS, in different neurological disorders, before (pre-TPE) and after TPE (post-TPE). Pre- and post-TPE clinical conditions were compared using the Wilcoxon matched-pairs signed-ranks test. Fifty-three patients were included, with 15 females and 38 males, who had a median age of 48 years. Seven different AND were; myasthenia gravis (n = 11), Guillain-Barre syndrome (n = 18), neuromyelitis Optica spectrum disorders (n = 6); chronic inflammatory demyelinating polyneuropathy (n = 5); autoimmune encephalitis (n = 6); transverse myelitis (n = 6); and multiple sclerosis (n = 1). Patients received a median of 5 cycles of TPE and a mean 1.5 plasma volume was exchanged. The improvement in the MRS scale was significant when post-TPE scores were compared with pre-TPE scores. The most common adverse reaction was shivering (n = 5; 1.85%), which was managed conservatively. TPE was shown to be an effective and safe treatment modality in providing relief to patients with neurological disorders.
small molecules
2026-08-14 | Seronegative Longitudinally Extensive Transverse Myelitis in a Filipino Adult: Diagnostic Challenges and Characteristic Longitudinal MRI Findings.
Longitudinally extensive transverse myelitis (LETM) is a radiologic pattern of longitudinal spinal cord involvement most commonly associated with antibody-mediated autoimmune diseases such as neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease. Seronegative inflammatory cases remain diagnostically challenging because they require careful exclusion of infectious, autoimmune, vascular, neoplastic, metabolic, and structural etiologies. A 45-year-old Filipino female presented with a three-day history of severe upper back pain, followed by rapidly progressive bilateral upper and lower extremity weakness, sensory disturbances, and urinary retention. Neurologic examination revealed asymmetric quadriparesis, a sensory level at the fourth thoracic dermatome, preserved vibration and proprioception, and mixed hyperreflexia and hyporeflexia with bilateral Babinski signs. Spinal magnetic resonance imaging (MRI) demonstrated a poorly defined, non-expansile intramedullary T2-hyperintense lesion extending contiguously from C3 to T2 without discrete enhancement. Diffusion-weighted imaging demonstrated no restricted diffusion. Cerebrospinal fluid analysis showed mild lymphocytic pleocytosis with normal IgG index and absence of oligoclonal bands. Extensive infectious, inflammatory, autoimmune, and metabolic investigations were unrevealing, including negative serum aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies. Follow-up spinal MRI performed 3.5 months later demonstrated persistent longitudinal non-enhancing intramedullary T2 hyperintensity with evolution toward chronic myelomalacic change, providing important longitudinal imaging evidence supporting an inflammatory antibody-negative myelopathy over competing diagnostic considerations. The patient was treated with high-dose intravenous methylprednisolone, followed by an oral prednisone taper and subsequent initiation of azathioprine because of persistent severe deficits. Despite immunotherapy and rehabilitation, she remained wheelchair-dependent with persistent dysesthesias and neurogenic bladder at follow-up. Following comprehensive multidisciplinary evaluation and longitudinal follow-up, an inflammatory antibody-negative LETM was considered the most likely diagnosis after exclusion of competing etiologies. This case highlights the diagnostic complexity, therapeutic challenges, and potentially severe neurologic outcomes associated with seronegative LETM. It also underscores the importance of systematic exclusion of alternative etiologies, longitudinal follow-up, repeat serologic evaluation, and individualized consideration of escalation immunotherapy in patients with incomplete response to corticosteroid treatment.
2026-08-08 | Complement C3 inhibitory peptide AMY-101 ameliorates brain injury in a mouse model of NMOSD.
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease of the central nervous system, clinically characterized primarily by optic neuritis and transverse myelitis. This study aimed to investigate the therapeutic potential of the complement C3 inhibitory peptide AMY-101 in experimental models of NMOSD. In vitro experiments were performed using AQP4-transfected cells exposed to AQP4-IgG and human complement to assess complement-dependent cytotoxicity and membrane attack complex (MAC) deposition. In vivo efficacy was evaluated in an intracerebral injection mouse model of NMOSD, in which histopathological changes after AMY-101 treatment were compared with those in untreated controls. AMY-101 significantly attenuated AQP4-IgG- and complement-mediated cytotoxicity and inhibited MAC formation in vitro. In the NMOSD mouse model, AMY-101 treatment markedly reduced astrocyte loss, AQP4 depletion, and demyelination compared with controls. These findings demonstrate that complement C3 inhibition with AMY-101 effectively ameliorates key pathological features of NMOSD in experimental models, supporting its potential as a therapeutic strategy and providing a rationale for further preclinical and clinical investigation.
2026-07-30 | Area postrema syndrome and longitudinally extensive transverse myelitis masquerading as leptomeningeal carcinomatosis.
Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune demyelinating disease of the central nervous system commonly associated with aquaporin-4 (AQP4) antibodies. Area postrema syndrome (APS), characterized by intractable nausea, vomiting, and hiccups, is a core clinical feature but is frequently misdiagnosed as a gastrointestinal disorder, leading to delays in diagnosis and treatment. A 63-year-old woman with a history of treated breast cancer presented with one week of intractable nausea, vomiting, progressive left lower extremity weakness, and sensory changes. Initial evaluation was unrevealing. MRI demonstrated longitudinally extensive transverse myelitis and an enhancing dorsal medullary lesion consistent with APS, along with diffuse leptomeningeal enhancement raising concern for neoplastic or inflammatory etiologies. Cerebrospinal fluid analysis showed lymphocytic pleocytosis and elevated protein. The patient developed respiratory failure requiring intensive care support. Empiric treatment with high-dose intravenous methylprednisolone and plasma exchange was initiated. AQP4-IgG serology returned positive, confirming NMOSD. Following treatment, nausea and mental status improved, with partial neurological recovery, although significant residual left leg weakness and neurogenic bladder persisted. The patient was discharged to rehabilitation with plans for long-term immunosuppressive therapy. This case highlights APS as an important early manifestation of NMOSD that may mimic gastrointestinal or neoplastic conditions, particularly in patients with complex medical histories. Early recognition of APS and prompt immunotherapy are critical to prevent severe neurological disability and improve outcomes.
2026-07-03 | Longitudinally extensive transverse myelitis with encephalopathy following acute dengue infection
Dengue is a common arboviral infection in tropical/subtropical regions; neurologic complications occur in ~5% of cases, usually as encephalopathy from systemic illness (1). Viral neurotropism and immune-mediated injury are rare and mimic infectious/inflammatory etiologies (2,3). Although corticosteroids are not routinely recommended, case reports describe high-dose steroids usage with favorable outcomes (4,5). A previously healthy 25-year-old man in Brazil developed fever and retro-orbital headache followed by disorientation, hallucinations, abdominal pain, urinary retention, and rapidly progressive areflexic paraparesis. CSF showed lymphocytic pleocytosis (140 cells/µL); infectious and autoimmune/demyelinating tests were negative. MRI revealed longitudinally extensive intramedullary hyperintensity from upper cervical cord to conus with leptomeningeal enhancement. Dengue IgM with IgM/IgG seroconversion confirmed acute infection. IV methylprednisolone (1 g/day) improved symptoms within 72h; he walked by day 5 and fully recovered within 1 year. In endemic settings, neurodengue is a possibility when alternatives are excluded. Once infection is ruled out, immunotherapy should be considered.
2026-06-22 | Spinal Cord Involvement in Neurosarcoidosis: A Case of Longitudinally Extensive Transverse Myelitis at Disease Onset.
Acute-onset neurological deficits in otherwise healthy individuals warrant a broad differential diagnosis. Neurosarcoidosis presenting as longitudinally extensive transverse myelitis is rare, mimicking demyelinating, infectious, or neoplastic disorders. Early recognition, histopathological confirmation, and timely immunosuppressive therapy are crucial. Further research is mandatory in optimizing treatment regimens, especially for refractory neurosarcoidosis cases.
proteins
2025-08-27 | Telitacicept Inhibits the Maturation and Differentiation of B Lymphocytes in NMOSD.
Telitacicept, a novel recombinant fusion protein comprising the ligand-binding domain of the TACI receptor and the Fc component of human IgG, has rarely been studied for the treatment of neuromyelitis optica spectrum disorders (NMOSD). This study aimed to explore the effects of telitacicept in NMOSD mice. An NMOSD mouse model was constructed. Fifty microliters of 0.8 mg/mL telitacicept was injected intravenously on Days 4, 8, 12 and 16 postimmunization (p.i.). Behavioral scoring, magnetic resonance imaging and histopathological evaluation were conducted on Day 19. B lymphocytes and their subgroups were analyzed by flow cytometry. Concentration of serum IgM was measured using an ELISA kit. Concentrations of B lymphocyte stimulator (BLyS) and IL-6 were measured via LEGENDplex. Differentially expressed genes of B lymphocytes were screened via mRNA sequencing and verified by qPCR. Behavioral score of telitacicept-treated NMOSD mice significantly decreased (p < 0.0001). Inflammation, demyelination, loss of AQP4 and GFAP in the spinal cord were markedly alleviated (p < 0.05). B lymphocytes and their subsets were reduced to varying degrees (p < 0.05). Telitacicept treatment significantly reduced serum IgM levels (p < 0.01), as well as BLyS and IL-6 concentrations (p < 0.05). Telitacicept induced differential gene expression in B lymphocytes, inhibiting the expression of transcription factors related to B lymphocyte maturation, such as IRF8, BLIMP1, and Pou2af1, as well as cell surface receptors such as CD19 and CD21. Telitacicept has a therapeutic effect on NMOSD mice by regulating the differentiation of B lymphocyte subsets and inhibiting the production of pathogenic antibodies.
2024-10-28 | Overview of emerging therapies for demyelinating diseases.
This paper provides an overview of autoimmune disorders of the central nervous system, specifically those caused by demyelination. We explore new research regarding potential therapeutic interventions, particularly those aimed at inducing remyelination. Remyelination is a detailed process, involving many cell types-oligodendrocyte precursor cells (OPCs), astrocytes, and microglia-and both the innate and adaptive immune systems. Our discussion of this process includes the differentiation potential of neural stem cells, the function of adult OPCs, and the impact of molecular mediators on myelin repair. Emerging therapies are also explored, with mechanisms of action including the induction of OPC differentiation, the transplantation of mesenchymal stem cells, and the use of molecular mediators. Further, we discuss current medical advancements in relation to many myelin-related disorders, including multiple sclerosis, optic neuritis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, transverse myelitis, and acute disseminated encephalomyelitis. Beyond these emerging systemic therapies, we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries. Despite these aforementioned scientific advancements, this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients' quality of life.
2024-09-02 | Effects of intravenous pulse methylprednisolone in neuromyelitis optica during the acute phase.
Neuromyelitis optica spectrum disorder (NMOSD) is an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. While intravenous pulse methylprednisolone (IVMP) is the recommended initial treatment option for acute onset NMOSD, its therapeutic mechanism remains unclear. We hypothesized that IVMP would reduce the expression of pro-inflammatory factors and increase the resolution of inflammation in patients with NMOSD. Mendelian randomization (MR) analysis was used to screen meaningful inflammatory and resolution factors for inclusion. Three MR methods with inverse variance weighting (IVW) were primarily used to identify positive results. Interleukin (IL)-10, IL-1β, IL-6, C-X-C motif chemokine ligand 12 (CXCL12), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were screened from 41 inflammatory factors, and resolvin D1 (RvD1), maresin 1 (MaR1), and lipoxin A4 (LXA4) were screened from 6 resolution markers for inclusion. Subsequently, 12 patients with NMOSD were enrolled and treated with IVMP. Serum levels of the aforementioned inflammatory and resolution markers were measured by enzyme-linked immunosorbent assay before and after IVMP treatment. High levels of TRAIL, CXCL12, and IL-1β were associated with an increased risk of NMOSD (TRAIL: odds ratio [OR], 1.582; 95% confidence interval [CI], 1.003-2.495; CXCL12: OR, 3.610; 95% CI, 1.011-12.889; IL-1β: OR, 4.500; 95% CI, 1.129-17.927). High levels of RvD1, MaR1, and LXA4 were associated with a reduced risk of NMOSD (RvD1: OR, 0.725; 95% CI, 0.538-0.976; MaR1: OR, 0.985; 95% CI, 0.970-0.999; LXA4: OR, 0.849; 95% CI, 0.727-0.993). Among patients with NMOSD, serum levels of IL-6, CXCL12, and TRAIL significantly decreased following IVMP treatment, compared with pretreatment levels, while levels of IL-1β, LXA4, and MaR1 significantly increased after IVMP treatment (p < 0.05). A significant positive correlation was observed between CXCL12 levels and Expanded Disability Status Scale (EDSS) scores (r = 0.451, p < 0.05). Several systemic inflammatory regulators associated with the pathogenesis of NMOSD were identified. The protective roles of LXA4 and MaR1 may be indispensable components of glucocorticoid treatment. Therefore, the use of resolution markers may be a potential strategy for improving central nervous system injury in individuals with NMOSD.
2012-10-02 | Botulinum toxin A in the treatment of spasticity - An open label study.
To assess the efficacy of botulinum toxin type A in spasticity in upper-motor neuron syndromes. Twenty-three patients with spasticity resulted from stroke-related hemiplegia, transverse myelitis and multiple sclerosis took part in the study. Following the history and physical examinations of the patients, injections of botulinum toxin-A were applied. The dose ranged from 80 to 400 mouse unit (MU) depending on the size of the muscle injected. In all patients, spasticity, spasms and pain were measured using the Ashworth Scale, Spasm Frequency Score, and Visual Analogue Scale prior to the therapy, at the 1st week, 1st month and 3rd month of the therapy. In all patients, botulinum toxin type A led to a significant decrease in spasticity, spasms and pain after the 1st week, 1st and 3 rd months of the treatment when compared to the baseline values (p<0.001). No significant side effects or complications were observed. Our results have demonstrated that botulinum toxin type A is effective in the management of patients with spasticity due to stroke-related hemiplegia, transverse myelitis and multiple sclerosis, without major adverse effects.
2007-07-03 | Successful treatment with botulinum toxin A after failed augmentation ileocystoplasty.
A 49-year old man initially underwent clam ileocystoplasty 14 years ago. A revision of this original procedure was required 11 years ago for intractable detrusor overactivity secondary to transverse myelitis; he experienced only temporary symptomatic improvement that lasted 6 months after each procedure. Despite the use of oral anticholinergic drugs, the patient subsequently needed to perform clean intermittent self-catheterization approximately 10 times every 24 h, and when he presented to our department, he still suffered from occasional episodes of urgency incontinence that required the regular use of a penile sheath. Symptom severity was assessed using a 4-day bladder diary. Cystometry confirmed the presence of terminal detrusor overactivity. After the patient provided his informed consent, he was treated as an outpatient with intradetrusor injections of botulinum toxin A, delivered under local anesthesia by a minimally invasive technique that used a flexible cystoscope. A significant improvement was noted in the patient's lower urinary tract symptoms, urodynamic parameters and quality of life, measured at 4 and 16 weeks after treatment. The patient was completely dry at both follow-up visits and was able to discontinue the use of anticholinergic drugs and the penile sheath for a total of 11 months.
antibodies
2026-08-13 | AQP4-IgG-positive myelitis occurring in a patient with small cell lung cancer: a case report.
Acute myelopathy in patients with small cell lung cancer (SCLC) is often attributed to metastatic spinal cord involvement. However, non-compressive inflammatory conditions, particularly aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD), can produce similar clinical and radiologic features, creating substantial diagnostic uncertainty. A male aged 65 years with extensive-stage SCLC presented with acute urinary retention followed by rapidly progressive paraplegia. Spinal magnetic resonance imaging (MRI) revealed longitudinally extensive intramedullary T2-hyperintense lesions affecting the cervical and thoracic spinal cord, with patchy contrast enhancement and no evidence of vertebral destruction, epidural mass, or spinal cord compression. Cerebrospinal fluid (CSF) examination demonstrated inflammatory abnormalities without malignant cells, and infectious causes were excluded. Serum and CSF testing were strongly positive for AQP4-IgG, establishing a diagnosis of AQP4-IgG-positive NMOSD. The patient received high-dose intravenous methylprednisolone followed by adjunctive intravenous immunoglobulin (IVIG). Plasma exchange was not performed because of advanced malignancy and concerns regarding procedural risks. Satralizumab was initiated during corticosteroid tapering for maintenance immunotherapy. Neurological function subsequently stabilized, and partial recovery of independence in activities of daily living was achieved. This case highlights that AQP4-IgG-positive myelitis can occur in patients with SCLC. In patients presenting with non-compressive longitudinally extensive transverse myelitis (LETM), particularly when imaging shows no evidence of compression and CSF cytology is negative for malignant cells, prompt AQP4-IgG testing is critical to prevent misdiagnosis and enable early initiation of appropriate immunotherapy.
2026-08-06 | Case Report: Anti-GQ1b antibody–positive overlap syndrome: a pediatric case involving the brainstem, spinal cord, and peripheral nerves
Disorders associated with anti-GQ1b antibodies predominantly encompass Bickerstaff brainstem encephalitis (BBE), Guillain–Barré syndrome (GBS), and Miller Fisher syndrome. Concurrent presentation of BBE, GBS, and acute transverse myelitis is exceptionally rare and presents significant diagnostic and therapeutic challenges. This report describes an 8-year-old boy who exhibited clinical features consistent with all three conditions, including impaired consciousness, ophthalmoplegia, ataxia, and limb weakness. Laboratory investigations revealed positive serum anti-GQ1b IgG antibodies, elevated cerebrospinal fluid protein levels with mild lymphocytic pleocytosis, and neurophysiological findings indicative of peripheral nerve demyelination. Magnetic resonance imaging of the brain and spinal cord demonstrated evidence of brainstem encephalitis and extensive spinal cord involvement. Following treatment with intravenous immunoglobulin and corticosteroid pulse therapy, marked neurological improvement was observed, and follow-up evaluations demonstrated favorable resolution of radiological abnormalities. This case highlights that anti-GQ1b antibody–associated syndrome may simultaneously affect the brainstem, spinal cord, and peripheral nerves. Early recognition and prompt initiation of combined immunotherapy may be critical for optimizing clinical outcomes.
2026-06-26 | Hantavirus infection: Neurologic manifestations should not be overlooked.
Hantavirus infection is primarily associated with hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), with predominant renal and pulmonary involvement. However, neurological manifestations affecting both the central nervous system (CNS) and peripheral nervous system (PNS) are increasingly recognized. We conducted a narrative review of the literature to summarize the current evidence regarding hantavirus-associated neurological involvement. Reported CNS manifestations included encephalitis, encephalopathy, seizures, meningitis, neurocognitive alterations, posterior reversible encephalopathy syndrome, transverse myelitis, and cerebral hemorrhage. PNS involvement appeared less frequent and included Guillain-Barré syndrome, cranial nerve palsies, neuropathic pain, and sensory disturbances. Neuroimaging findings were heterogeneous, while cerebrospinal fluid analysis often demonstrated nonspecific inflammatory changes. Advanced molecular techniques such as metagenomic next-generation sequencing may improve diagnostic sensitivity, particularly in immunocompromised patients. Current evidence suggests that neurological involvement may result from endothelial dysfunction, neuroinflammation, immune-mediated injury, blood-brain barrier disruption, and, in selected cases, direct viral neuroinvasion. Greater clinical awareness is needed to improve recognition of neurological complications during hantavirus infection. Further prospective studies are required to better define the epidemiology, pathogenesis, and optimal diagnostic approaches of hantavirus-associated neurological disease.
2026-06-01 | Longitudinal Spinal Cord Atrophy in Patients With Neuromyelitis Optica Spectrum Disorder and Its Association With Rituximab Treatment.
Longitudinally extensive transverse myelitis (LETM) is a core feature of neuromyelitis optica spectrum disorder (NMOSD), which leads to spinal cord atrophy. We aim to determine annual spinal cord atrophy rates and influencing factors in NMOSD. Spinal cord structural metrics, including cross-sectional area (CSA), anteroposterior diameter (AP), and right-left diameter (RL), were calculated using the Spinal Cord Toolbox from brain 3D sagittal T1-weighted images covering the C1-C3 levels. Normative references were constructed based on healthy participants and used to derive the deviation scores (Z-scores). Annualized atrophy rates were estimated using a linear mixed-effects model. Associations with clinical measures, rituximab treatment, and neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were assessed using partial Pearson correlation, multivariate linear regression, and linear mixed-effects models. In this longitudinal study, 72 patients with NMOSD (233 MRI scans; mean age 40.0 years; 84.7% female) from the CLUE cohort and 2,162 healthy participants were included. In patients with NMOSD, annual atrophy rates were -0.27/y for CSA (95% CI -0.35 to -0.20, p < 0.001), -0.23/y for AP (95% CI -0.33 to -0.13, p < 0.001), and -0.14/y for RL (95% CI -0.20 to -0.09, p < 0.001). A faster AP atrophy rate was associated with longer T2 lesion length and a higher number of relapses (r = -0.35/-0.25, p < 0.05). Prolonged interval from initial LETM to baseline MRI was independently associated with a slower CSA atrophy rate (β = 4.62 × 10-5; 95% CI 0.25 to 9.00 × 10-5, p = 0.043), while older age (β = -25.17 × 10-5; 95% CI -39.12 to -11.22 × 10-5, p < 0.001) and lesion length (β = -55.66 × 10-5; 95% CI -104.50 to -6.83 × 10-5, p = 0.029) were related to faster RL atrophy. Rituximab was associated with slower RL atrophy compared with other immunosuppressive therapies (β = 0.02; 95% CI 0.01-0.05; p = 0.044). Elevated serum GFAP levels were correlated with accelerated CSA (r = -0.42/-0.45), AP (r = -0.49/-0.45), and RL (r = -0.37/-0.44) atrophy at baseline/follow-up (all p < 0.01). Increased NfL levels were correlated with faster CSA and RL atrophy at follow-up (p = 0.009, p = 0.031). Spinal cord atrophy in NMOSD progresses annually and is influenced by disease activity and duration. Rituximab was associated with attenuated progression of spinal cord atrophy. Moreover, serum NfL and GFAP may serve as potential biomarkers.
2026-05-31 | Para infectious myelitis with Conus medullaris immunotropism in the immune phase of leptospirosis infection: Clinical pattern and in silico molecular mimicry analysis based biological plausibility.
Neurological involvement in leptospirosis but increasingly recognized, with myelitis representing a disabling complication. Conus medullaris involvement has not been systematically described and may reflect region-specific vulnerability to immune-mediated injury, post leptospirosis infection. We report a case series of three patients with serologically confirmed leptospirosis who developed acute myelitis during the immune phase, with radiological involvement of the conus medullaris. Clinical, cerebrospinal fluid, and imaging features were analyzed. A proteome-wide in silico comparison was performed between human myelin oligodendrocyte glycoprotein and the Leptospira interrogans proteome to identify shared antigenic motifs. All patients presented with acute bladder dysfunction, lower limb weakness, or sensory symptoms following a febrile illness. Magnetic resonance imaging showed conus medullaris involvement, either isolated or as part of longitudinal cord lesions. Cerebrospinal fluid revealed inflammatory changes. Treatment with steroids, with adjunctive immunotherapy in severe cases, resulted in clinical improvement. In silico analysis did not demonstrate full-length homology but identified 19 shared peptide motifs with moderate sequence identity, several overlapping predicted B-cell and T-cell epitope regions. This series suggests a possible para-infectious conus-predominant myelitis pattern in leptospirosis. The identification of shared antigenic motifs provides biological plausibility for immune-mediated demyelination through molecular mimicry. Recognition of this pattern in endemic regions may facilitate early diagnosis and timely immunotherapy.
cell therapies
2026-08-05 | Association of therapeutic plasma exchange with functional outcomes in selected neurological disorders: a retrospective cohort study from a single tertiary center in Saudi Arabia.
Neurological disorders are associated with considerable morbidity and healthcare impact. Therapeutic plasma exchange (TPE) is an intervention that removes pathogenic antibodies, immune complexes, and other plasma constituents from circulation. Previous studies have suggested that TPE could be associated with improved outcomes in selected neurological disorders. To evaluate functional outcomes following therapeutic plasma exchange in patients with selected neurological disorders at National Guard Health Affairs (NGHA) in Jeddah, Saudi Arabia. This retrospective cohort study analyzes 133 patients diagnosed with various neurological disorders who received TPE between August 2015 and December 2022 at NGHA. Diagnoses included multiple sclerosis (MS), myasthenia gravis (MG), Guillain-Barré syndrome (GBS), neuromyelitis optica spectrum disorder (NMOSD), chronic inflammatory demyelinating polyneuropathy (CIDP), autoimmune encephalitis (AE), and other neurological conditions including amyotrophic lateral sclerosis (ALS), transverse myelitis, cerebellar ataxia, paraneoplastic neurologic syndrome, polymyositis, and central nervous system (CNS) infections. The effectiveness of TPE was assessed using the Modified Rankin Scale (mRS) before and 90 days following the final TPE session. Statistical analysis included Wilcoxon signed-rank tests and Mann-Whitney U test, with significance set at (p < 0.05). Significant improvements in mRS scores were observed following TPE for MS, MG, and GBS (all p < 0.001), as well as for NMOSD (p = 0.008), CIDP (p = 0.007), and AE (p = 0.018), but not in other neurological disorders (p = 0.234). Overall mortality was 6.8%, with no TPE-related deaths. Comorbidities among deceased patients included hypertension, diabetes mellitus, malignancy, chronic kidney disease, and cardiovascular disease. TPE was associated with improved functional outcomes in selected neurological disorders. Comorbidities were common among patients with poorer outcomes. Due to the retrospective design and potential confounding factors, causal inferences cannot be established. Further prospective studies are warranted to evaluate the role of TPE and optimize patient selection.
2026-05-26 | Steroid Refractory and Plasma Exchange Partially Responsive Longitudinally Extensive Transverse Myelitis Due to Tumor Necrosis Factor-Alpha (Etanercept): A Case Report.
Background: Acute transverse myelitis (ATM) is an inflammatory disorder of the spinal cord with heterogeneous etiologies, including autoimmune, infectious, paraneoplastic, and drug-induced causes. Tumor necrosis factor-alpha (TNF-α) inhibitors have been infrequently associated with inflammatory central nervous system events, including transverse myelitis. TNF-inhibitor-associated myelitis typically presents with short-segment lesions, a normal brain MRI, and partial responsiveness to corticosteroids. Longitudinally extensive transverse myelitis (LETM) and steroid-refractory cases are uncommon. Case Presentation: A 39-year-old woman with psoriatic arthritis treated with etanercept for two years presented with subacute progressive bilateral lower-extremity sensory loss and weakness. MRI revealed a T2 hyperintense spinal cord lesion extending from T11 to L1 with gadolinium enhancement, consistent with transverse myelitis, while brain MRI was normal. Cerebrospinal fluid analysis showed lymphocytic pleocytosis, elevated protein, oligoclonal bands, and increased kappa free light chains. Extensive infectious, metabolic, paraneoplastic, and autoimmune testing, including aquaporin-4 and MOG antibodies, was negative. Despite high-dose intravenous corticosteroids and the discontinuation of etanercept, the patient experienced clinical worsening with lesion expansion, meeting criteria for LETM, and developed urinary retention. She subsequently underwent plasma exchange, resulting in radiologic improvement and moderate clinical recovery. Conclusions: This case highlights an atypical presentation of TNF-inhibitor-associated myelitis characterized by a biphasic course, longitudinally extensive spinal cord involvement, steroid refractoriness, and responsiveness to plasma exchange. These features suggest either an unusually severe TNF-inhibitor-related inflammatory phenotype or a TNF-inhibitor-triggered antibody-mediated demyelinating process. Reports of TNF-inhibitor-associated myelitis evolving into longitudinally extensive, steroid-refractory disease remain limited, and this presentation may broaden the recognized clinical spectrum of TNF-α-related CNS inflammatory events. Close neurologic follow-up and heightened awareness of severe CNS complications associated with TNF-α inhibitors are warranted.
2026-04-20 | Plasma Exchange as a Bridge to Recovery in Severe Pediatric Neurological Diseases in Pediatric Intensive Care.
Therapeutic plasma exchange (TPE) removes circulating pathogenic antibodies, immune complexes, cytokines, and complement components. While established in adult neurology, evidence on its safety and efficacy in pediatric neurocritical care remains limited. To evaluate the indications, clinical efficacy, and safety of TPE in children with acute or subacute immune-mediated neurological disorders admitted to the pediatric intensive care unit (PICU). A retrospective cohort of 24 pediatric patients (aged 1-18 years) treated with TPE between February 2023 and October 2025 was analyzed. Diagnoses included multiple sclerosis (n = 8), Guillain-Barré syndrome (n = 5), acute disseminated encephalomyelitis (n = 3), transverse myelitis (n = 3), autoimmune encephalitis (n = 3), optic neuritis (n = 1), and myasthenia gravis (n = 1). Patients received 3-7 TPE sessions. Clinical response was measured using the modified Rankin Scale (mRS) and GBS disability scores before and after treatment. A total of 130 sessions were performed. Clinical improvement occurred in 20 of 24 patients (83%)-moderate in 8 (33%) and mild in 12 (50%). Median mRS/GBS scores decreased from 4.0 to 3.0 (p = 0.001). Early initiation of TPE (≤ 7 days from symptom onset) was associated with a higher likelihood of neurological improvement in multivariable analysis. No life-threatening complications were observed. Transient, reversible events included hypocalcemia (2.3%), hypotension (1.5%), and urticaria (1.6%). TPE appears to be a safe and potentially beneficial intervention for severe or refractory pediatric neuroimmunological disorders. Earlier initiation of TPE was associated with improved neurological outcomes; however, these findings should be interpreted cautiously given the small sample size and heterogeneous disease groups. These findings support integrating TPE into multidisciplinary PICU management and add to the growing evidence supporting its use in pediatric neuroimmunology.
2025-11-18 | Efficacy and Safety of Plasmapheresis in Children With Acute Transverse or Flaccid Myelitis, and Guillain-Barré Syndrome.
Acute transverse myelitis (ATM), acute flaccid myelitis with polio-like myeloradiculitis (AFM) and Guillain-Barré syndrome (GBS) are severe neuroimmune disorders associated with high morbidity. First-line treatments include corticosteroids and intravenous immunoglobulins (IVIg), but they may be insufficient. Therapeutic plasma exchange (TPE) and immunoadsorption (IA) are second- or third-line options in pediatrics, despite their recognized efficacy in adults. Data on pediatric use remain limited. This study aimed to evaluate the efficacy and safety of apheresis in children with ATM, GBS or AFM. We conducted a retrospective monocentric study at Necker University Hospital, including pediatric patients diagnosed with ATM, GBS or AFM who underwent TPE/IA between 2014 and 2024. Functional outcomes were assessed using the modified Rankin Scale (mRS) at five time points, from peak disease severity to last follow-up. Safety was evaluated based on severe adverse events. Among 23 children (6 years [Q1-Q3]), 20 received TPE and 3 IA. 17 of 23 patients (74%) showed significant improvement by the end of treatment. The median mRS was 5 (IQR 4-5) before apheresis, improving to 4 (IQR 2-4) at the end of TPE/IA, and decreasing to 2 at 6 months. Brainstem function fully recovered in all surviving patients. Among 14 children with sphincter dysfunction, 5 (36%) still required intermittent catheterization. No treatment discontinuations occurred, but two patients died, one from venous air embolism, one after life-sustaining treatment limitation. TPE and IA appear effective in pediatric ATM, AFM and GBS. Larger studies are needed to confirm long-term efficacy and refine treatment guidelines.
2025-11-17 | Effectiveness and safety of therapeutic plasma exchange in neurological disorders; measuring the response to treatment using Modified Rankin Scale - A single-center study.
Therapeutic plasma exchange (TPE) is commonly used as a treatment modality in varying neurological disorders. Response to TPE in neurological disorders is usually noted in "subjective" terms. We, measured response to treatment, objectively, using Modified Rankin Scale (MRS). This was an observational prospective study in patients diagnosed with autoimmune neurological disorders (AND) who underwent TPE, in addition to intravenous immunoglobulin, and/or prednisolone. This study was carried out at a tertiary care center. Demographic data, procedure details including adverse reactions, and clinical responses were collated. Clinical response was assessed by applying MRS, in different neurological disorders, before (pre-TPE) and after TPE (post-TPE). Pre- and post-TPE clinical conditions were compared using the Wilcoxon matched-pairs signed-ranks test. Fifty-three patients were included, with 15 females and 38 males, who had a median age of 48 years. Seven different AND were; myasthenia gravis (n = 11), Guillain-Barre syndrome (n = 18), neuromyelitis Optica spectrum disorders (n = 6); chronic inflammatory demyelinating polyneuropathy (n = 5); autoimmune encephalitis (n = 6); transverse myelitis (n = 6); and multiple sclerosis (n = 1). Patients received a median of 5 cycles of TPE and a mean 1.5 plasma volume was exchanged. The improvement in the MRS scale was significant when post-TPE scores were compared with pre-TPE scores. The most common adverse reaction was shivering (n = 5; 1.85%), which was managed conservatively. TPE was shown to be an effective and safe treatment modality in providing relief to patients with neurological disorders.
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Drug Discovery Landscape
2 orphan drug designations for Acute transverse myelitis.
2 orphan drug designations for Acute transverse myelitis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
dalfampridine | small molecules | FDA | 2019-11-25 | — | Magnum Therapeutics |
human glial restricted progenitor cells and their progeny | cell therapies | FDA | 2018-04-11 | — | Q Therapeutics, Inc. |
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