Causes of Longitudinally Extensive Transverse Myelitis
The primary causes of LETM are MOG-antibody associated encephalomyelitis (MOG-EM) and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), which together account for the majority of cases, followed by idiopathic inflammatory causes, systemic autoimmune diseases (particularly SLE), infections, neoplasms, vascular disorders, and rarely multiple sclerosis. 1, 2
Primary Autoimmune/Inflammatory Causes
Antibody-Mediated Demyelinating Diseases
MOG-antibody associated encephalomyelitis (MOG-EM): LETM is common in MOG-EM, occurring in approximately 44-52% of patients at some point during their disease course 1. In pediatric MOG-EM patients, LETM is frequently present at disease onset (80% in examined cases) 1.
Aquaporin-4 antibody-positive NMOSD: LETM extending ≥3 vertebral segments is a hallmark feature and diagnostic criterion for AQP4-NMOSD 1. This represents one of the most common causes of LETM overall 2, 3.
Idiopathic LETM: Represents approximately 22% of LETM cases in some cohorts, where no specific antibody or underlying cause is identified despite thorough workup 3.
Systemic Autoimmune Diseases
Systemic lupus erythematosus (SLE): LETM can occur as a neuropsychiatric manifestation of SLE, though only 37 cases had been described in the literature as of 2015 4. These cases generally carry a poor prognosis and require prompt immunosuppressive treatment 4, 3.
Sjögren syndrome: Can present with LETM as part of CNS involvement 2.
Neurosarcoidosis: Sarcoidosis with CNS involvement can cause longitudinally extensive spinal cord lesions 2.
Other Inflammatory Conditions
Acute disseminated encephalomyelitis (ADEM): Can present with LETM, particularly in pediatric populations, often with concurrent brain involvement 1, 3, 5.
Multiple sclerosis (MS): LETM rarely if ever occurs in MS; when present, it should prompt consideration of alternative diagnoses 1. Non-contiguous lesions may occasionally mimic LETM in MS patients 1.
Infectious Causes
- Various infectious diseases with CNS involvement can cause LETM, though specific pathogens are not detailed in the provided guidelines 2, 6.
Neoplastic Causes
- Tumors: Both primary spinal cord tumors and metastatic disease can present with longitudinal spinal lesions mimicking LETM 2, 3. Neoplastic LETM is associated with poor recovery outcomes 3.
Vascular Causes
Dural arteriovenous fistula: Can cause longitudinal spinal cord signal abnormalities (7.4% of cases in one cohort) 3.
Ischemic myelopathy: Vascular compromise can produce longitudinally extensive lesions 3.
Metabolic Disturbances
- Metabolic disorders can occasionally present with longitudinally extensive spinal cord abnormalities 6.
Traumatic Causes
- Traumatic spinal cord injury can produce longitudinal spinal lesions on imaging 2.
Clinical Approach to Differential Diagnosis
When evaluating LETM, immediately test for both AQP4-IgG and MOG-IgG antibodies in parallel if cost is not prohibitive; if cost is a factor and the disease is stable, test AQP4-IgG first as it is more frequent 1.
Key Distinguishing Features:
Lesion extent ≥7 spinal segments: Associated with poor recovery at 3 months and suggests neoplastic, vascular, idiopathic, or lupus-related etiologies 3.
Brain MRI findings: Normal brain MRI in 59% of LETM cases; absence of Dawson's fingers, juxtacortical U-fiber lesions, and periventricular ovoid lesions argues against MS and supports MOG-EM 1, 3.
CSF analysis: Neutrophilic pleocytosis (64% of MOG-EM patients with pleocytosis) or WCC >50/μl suggests MOG-EM or AQP4-NMOSD rather than MS 1. Absence of oligoclonal bands (in 87-88% of MOG-EM patients) also distinguishes from MS 1.
Conus medullaris involvement: Particularly suggestive of MOG-EM, especially at disease onset 1.
Prognostic Indicators:
Patients with ≥7 affected spinal segments demonstrate significantly worse functional outcomes at 3 months and require more aggressive treatment considerations 3. The specific underlying etiology—particularly neoplastic, vascular, and lupus-related causes—carries distinct prognostic implications and treatment requirements 3.