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:
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.
2026-08-13 | 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.
2026-08-08 | 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.
2026-08-06 | 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.
2026-08-05 | 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.
2026-08-14 | 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.
2026-08-13 | 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.
2026-08-08 | 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.
2026-08-06 | 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.
2026-08-05 | 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.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
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. |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.