Transverse Myelitis

Immune-Mediated Demyelination and Axonal Injury

• Breakdown of blood-brain barrier (BBB) with infiltration of autoreactive T cells (predominantly CD8+) and B cells into the spinal cord parenchyma
• T cell-mediated cytotoxicity targeting oligodendrocytes and myelin antigens; activation of complement-mediated myelin destruction
• Secondary axonal degeneration occurs both acutely (excitotoxicity, oxidative stress) and chronically (mitochondrial dysfunction, persistent inflammation)
• Release of pro-inflammatory cytokines (TNF-α, IL-6, IL-17) perpetuates inflammation and increases BBB permeability

Gray Matter Involvement and Neurological Consequences

• Preferential early involvement of gray matter (especially anterior horns) with extension to white matter tracts, though full transverse involvement distinguishes TM from partial myelitis
• Disruption of corticospinal tract fibers causes upper motor neuron signs below the lesion level
• Spinothalamic tract involvement produces "sensory level" (dissociated sensory loss with preserved proprioception or vice versa depending on tract involvement)
• Autonomic fiber damage in intermediolateral columns results in bowel, bladder, and sexual dysfunction

Edema and Spinal Cord Swelling

• Cytotoxic edema (intracellular) and vasogenic edema (interstitial) lead to increased intramedullary pressure
• Spinal cord swelling may extend multiple segments rostral/caudal to the primary lesion on MRI, reflecting the extent of inflammation
• Microvascular occlusion and secondary ischemia contribute to gray matter necrosis in severe cases

Infectious Triggers

• Viral: Enterovirus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles, varicella-zoster virus (VZV), HIV, SARS-CoV-2
• Bacterial: Mycobacterium tuberculosis, Treponema pallidum, Lyme disease (Borrelia burgdorferi); post-bacterial vaccination
• Parasitic and fungal: Schistosoma, Toxoplasma, coccidioidomycosis (rare)

Demyelinating and Autoimmune Disorders

• Multiple sclerosis (MS): TM occurs in 5% of MS patients at presentation; conversely, 50% of isolated TM patients eventually develop MS
• Neuromyelitis optica spectrum disorder (NMOSD): Mediated by aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies; presents with severe, often longitudinally extensive myelitis
• Systemic lupus erythematosus, anti-phospholipid syndrome, Behçet's disease, vasculitis

Post-Vaccination and Molecular Mimicry

• Post-viral immunization (measles-mumps-rubella, hepatitis B, COVID-19 vaccines)
• Molecular mimicry between pathogenic antigens and CNS myelin proteins

Idiopathic Transverse Myelitis

• Approximately 30–50% of cases remain idiopathic after comprehensive workup
• No identifiable infectious, inflammatory, or structural cause

Risk Factors

• Female predominance (1.5–2:1)
• Age 10–19 and 40–60 years
• Preceding upper respiratory infection or systemic illness (weeks prior)

Cardinal Symptoms (Acute Onset over Hours to Days)

• Progressive paraplegia or tetraplegia (depending on level): rapid evolution to maximum deficit typically within 24–72 hours
• Bilateral sensory loss with a distinct "sensory level" (sharp demarcation at the level of spinal cord involvement)
• Painful paresthesias and dysesthesias: often severe, preceding motor weakness
• Acute urinary retention progressing to incontinence (autonomic involvement)
• Erectile dysfunction and fecal incontinence (in lower thoracic/lumbosacral lesions)

Motor Examination

• Spastic paraparesis or paraplegia with hyperreflexia and Babinski signs below the lesion level (upper motor neuron signs reflect central cord involvement)
• Initial flaccidity may occur in the first 24–48 hours before spasticity develops (spinal shock)
• Loss of abdominal reflexes at the lesion level
• Asymmetric weakness suggesting partial transverse myelitis rather than complete TM

Sensory Examination

• Dissociated sensory loss (selective loss of pain/temperature with preserved proprioception, or vice versa) reflecting gray matter predominance
• Sensory level: distinct boundary 1–2 levels below spinal cord lesion (due to rostral migration of fiber entry points)
• Sacral sparing is atypical in classical TM; if present, suggests alternative diagnosis (conus medullaris syndrome, cauda equina)

Systemic Features

• Preceding viral prodrome or constitutional symptoms (fever, malaise, myalgias) in 50% of cases
• Back pain at lesion level in 80% of patients
• Headache and meningeal signs (if associated meningitis)

Clinical Criteria for Transverse Myelitis (Proposed by International Panel)

1. 1.Bilateral signs/symptoms of spinal cord dysfunction (motor, sensory, autonomic)
2. 2.Clearly defined sensory level
3. 3.Inflammatory evidence (CSF pleocytosis and/or elevated IgG index, or contrast enhancement on MRI)
4. 4.Progression over ≤4 weeks (typically 24–72 hours)
5. 5.Exclusion of structural and systemic causes

Spinal Cord MRI (Gold Standard)

• T2-weighted sequences: Hyperintense intramedullary lesion spanning ≥3 vertebral segments in at least one plane (defines "longitudinally extensive myelitis" [LEM])
• Lesion characteristics:
• Central gray matter involvement (characteristic of idiopathic TM and MS)
• Peripheral white matter predominance (more common in NMOSD)
• Hemorrhage/necrosis indicates severe pathology
• Gadolinium enhancement (T1 post-contrast): Indicates active inflammation; enhancement pattern does not reliably distinguish etiologies
• Brain MRI: Essential to assess for demyelinating lesions suggestive of MS (40–60% of TM patients have asymptomatic brain lesions)
• Cervical/thoracic MRI: Complete imaging from foramen magnum to conus to exclude compressive or structural lesions

Cerebrospinal Fluid (CSF) Analysis

• Cell count: Lymphocytic pleocytosis (10–100 WBC/μL typical; higher counts suggest NMOSD or severe infection)
• Protein: Elevated (50–200 mg/dL); very high levels (>1000 mg/dL) suggest alternative diagnoses (spinal block, severe infection)
• Glucose: Normal (CNS glucose reflects serum glucose); low CSF glucose suggests infection or NMOSD
• Oligoclonal bands: Present in 50% of TM cases; more suggestive of MS when both serum and CSF bands present
• IgG index: Elevated in inflammatory demyelinating disease
• Microbiological studies: Viral PCR (enterovirus, EBV, CMV, VZV, SARS-CoV-2), bacterial cultures, acid-fast bacilli (AFB) stain, fungal studies as indicated
• Inflammatory markers: None specific; CSF IL-6 and TNF-α may be elevated but not routinely tested

Serological and Blood Testing

• Aquaporin-4 (AQP4) IgG antibody: Positive in ~50% of NMOSD; indicates poor prognosis and relapsing course
• Myelin oligodendrocyte glycoprotein (MOG) IgG antibody: Increasingly recognized in TM; associated with distinct phenotype
• Infectious serology/PCR: Syphilis (RPR, FTA-ABS), Lyme disease (Western blot if ELISA positive), HIV, viral cultures/PCR as indicated
• Systemic autoimmune panel: ANA, anti-dsDNA, complement levels, vasculitis markers (ANCA, cryoglobulins) to exclude SLE, antiphospholipid syndrome
• Chest imaging (CXR or CT): Exclude sarcoidosis, lymphoma, tuberculosis
• Vitamin B12, folate, copper: Deficiency can mimic but is distinguished by chronicity and CSF findings

Electrolyte Abnormalities

• Hyponatremia: May occur due to SIADH; monitor and correct cautiously to avoid osmotic demyelination

First-Line Immunotherapy

• Intravenous methylprednisolone (IVMP): 1 g daily × 3–5 days (or 30 mg/kg if weight-based dosing)
• Mechanism: Stabilizes BBB, inhibits leukocyte trafficking, anti-inflammatory cytokine effects
• Most evidence supports initiation as early as possible; efficacy diminishes after 2 weeks
• Transition to oral prednisone taper (1 mg/kg daily, then taper over 4–12 weeks) after IV therapy
• Rationale: Reduces inflammatory demyelination and improves motor recovery; standard of care for acute TM regardless of presumed etiology

Second-Line and Adjunctive Therapies

• Plasma exchange (PLEX): 5 sessions over 5–10 days for IVMP-refractory cases (no improvement after 2 weeks of high-dose corticosteroids) or fulminant presentations
• Particularly beneficial in NMOSD and MOG-positive disease; less evidence in idiopathic TM
• Mechanism: Removes pathogenic autoantibodies (AQP4, MOG) and complement components
• Intravenous immunoglobulin (IVIg): 2 g/kg over 3–5 days; alternative to PLEX if unavailable, though less robust evidence
• May be combined with corticosteroids for severe disease
• Immunosuppression (chronic): For NMOSD and MOG-positive TM
• Azathioprine (1–2.5 mg/kg/day) or mycophenolate mofetil (1–3 g/day): Standard steroid-sparing agents
• Rituximab: 375 mg/m² weekly × 4 weeks; B cell depletion particularly effective in AQP4-positive disease
• Eculizumab: Complement C5 inhibitor; recently FDA-approved for AQP4-NMOSD based on phase 3 trials

Symptomatic and Supportive Care

• Bowel/bladder management: Intermittent catheterization preferred over indwelling catheters; stool softeners, laxatives
• Spasticity management: Baclofen (titrate to 40–80 mg/day), tizanidine, or botulinum toxin injections
• Pain management: NSAIDs, gabapentin (300–3600 mg/day in divided doses), pregabalin, tricyclic antidepressants for neuropathic pain
• DVT/PE prophylaxis: LMWH or sequential compression devices during acute hospitalization (immobility risk)
• Rehabilitation: Physical therapy, occupational therapy, psychosocial support essential for long-term recovery

Monitoring During Treatment

• Clinical assessment: Neurological exams at baseline, day 3–5 (assess response to IVMP), and weekly during acute phase
• Repeat MRI: 4–8 weeks post-treatment to assess lesion resolution and confirm diagnosis
• CSF repeat: Not routinely needed unless diagnosis uncertain or no improvement
• Infectious disease consultation: If any concern for infectious etiology

Motor and Sensory Sequelae

• Chronic weakness and spasticity: Occurs in 50–70% of patients despite treatment; permanent paraparesis most common residual deficit
• Chronic pain: Neuropathic pain syndromes, including central post-stroke pain (CPSP)-like syndrome, affect 40–50% at 1 year
• Lhermitte's sign: Brief electric-shock sensation with neck flexion; reflects persisting demyelination

Autonomic and Visceral Dysfunction

• Neurogenic bladder: Detrusor hyperreflexia or areflexia requiring long-term catheterization management
• Bowel incontinence/constipation: Often refractory to medical management
• Sexual dysfunction: Erectile dysfunction and loss of sensation in 60% of patients

Secondary Complications (Life-Threatening)

• Respiratory failure: Occurs with high cervical lesions (above C3); requires mechanical ventilation; may necessitate tracheostomy
• Sepsis from urinary tract infection: Common in catheterized patients; associated with mortality if not promptly treated
• Pulmonary embolism (PE): Immobility and spasticity increase VTE risk; use prophylactic anticoagulation
• Severe autonomic dysreflexia: Sudden hypertension, bradycardia, headache triggered by bladder/bowel distention; life-threatening in high spinal lesions

Disease-Related Complications

• Recurrent demyelinating episodes: 5–20% risk of relapse, higher with positive AQP4 or MOG antibodies; indicates conversion to relapsing condition
• Conversion to MS: 30% of patients with isolated idiopathic TM later develop MS within 5 years (especially if brain MRI lesions present or CSF oligoclonal bands positive)
• Tethered spinal cord: Rare sequela of healing; can cause delayed worsening

Natural History and Recovery Timeline

• Maximum neurological deficit: Typically reached within 24–72 hours of symptom onset
• Early recovery phase: 50–60% of patients show some improvement within 1–3 months, especially with early IVMP
• Late recovery: Slow, incremental improvement continues up to 12 months; some recovery documented even at 2 years
• Plateau phase: Most functional recovery achieved by 6 months; further improvement unlikely after 12 months

Prognostic Factors (Favorable)

• Young age at presentation
• Incomplete myelitis (preserved motor/sensory function in some myotomes)
• Rapid initiation of immunotherapy (<2 weeks)
• Absence of severe spinal cord necrosis/hemorrhage on MRI
• Negative AQP4 and MOG antibodies (idiopathic TM has better prognosis than NMOSD)

Prognostic Factors (Unfavorable)

• Older age (>40 years)
• Fulminant presentation with rapid progression to complete paraplegia
• Severe spinal cord edema extending >4 segments
• MRI evidence of necrosis or hemorrhage
• High CSF pleocytosis (>100 cells/μL) or very high protein (>500 mg/dL)
• Positive AQP4 IgG antibody (predicts 50–80% relapse rate within 5 years)
• Delayed treatment initiation (>2 weeks)

Functional Outcomes at 12 Months

• Ambulation: 50–66% achieve independent ambulation; 10–15% remain non-ambulatory
• Disability: EDSS score ranges from 2–7 at 1 year; mean

The stem that means transverse myelitis

• Triad to recognize: bilateral weakness + a crisp sensory level + early bowel/bladder dysfunction evolving over hours to days. A sensory level is the single most discriminating physical finding on exam questions.
• Best next step is always imaging: emergent MRI of the spine with and without gadolinium to exclude a compressive lesion (epidural abscess, metastasis, hematoma) — a neurosurgical emergency. Lumbar puncture and steroids come after compression is excluded; below a complete block, LP can also worsen deficits.

The association examiners test

• Longitudinally extensive lesion (≥3 vertebral segments) → check AQP4-IgG (NMOSD) and MOG-IgG; per the International Panel for NMO Diagnosis criteria, AQP4 seropositivity plus myelitis establishes NMOSD and mandates chronic immunosuppression rather than MS therapy.
• Short-segment, partial, dorsolateral cord lesion with periventricular brain lesions and CSF oligoclonal bands → clinically isolated syndrome heading toward multiple sclerosis.
• Do not treat NMOSD as MS: interferon-beta and natalizumab can worsen AQP4-positive disease.

Distractors to avoid

• Spinal shock: early flaccid, areflexic paralysis does not mean a lower motor neuron process — hyperreflexia and Babinski appear days later.
• Guillain–Barré syndrome: ascending weakness with global areflexia, no sensory level, sphincters usually spared, and albuminocytologic dissociation (high protein, few cells) rather than pleocytosis.
• Anterior spinal artery infarction: onset over seconds to minutes with abrupt back pain, loss of pain/temperature with preserved vibration and proprioception (dorsal columns spared) — infarct, not inflammation.
• Subacute combined degeneration (B12): weeks-to-months course, dorsal column plus corticospinal signs, no enhancement.

Treatment reflex

• High-dose IV methylprednisolone first; plasma exchange for steroid-refractory or fulminant disease — the American Academy of Neurology's plasmapheresis guideline supports PLEX in severe acute CNS demyelinating attacks.