Transverse Myelitis

Transverse myelitis is an acute inflammatory disorder of the spinal cord involving demyelination or necrosis across one or more vertebral segments, producing bilateral (though often asymmetric) motor, sensory, and autonomic deficits below the level of the lesion. The "transverse" descriptor refers to involvement spanning the full cross-sectional width of the cord at the affected level, not to horizontal orientation. It is a clinical-radiological syndrome rather than a single disease entity — the underlying cause ranges from idiopathic to multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), MOG antibody-associated disease (MOGAD), post-infectious or post-vaccination immune activation, and systemic autoimmune conditions. Identifying the underlying etiology, particularly AQP4-IgG and MOG-IgG serostatus, is essential because it fundamentally changes long-term relapse-prevention strategy and prognosis.

Overview
Epidemiology
Pathophysiology
Etiology and Classification
Clinical Presentation
Diagnosis
Treatment
Prognosis and Recovery
Rehabilitation
Prevention of Relapses
Recent Research
References

1. Overview

Transverse myelitis (TM) is characterized by acute or subacute onset of spinal cord dysfunction — typically evolving over hours to days — at one or more contiguous vertebral segments. The defining clinical triad is: (1) bilateral motor weakness, (2) bilateral sensory loss or dysesthesia, and (3) autonomic dysfunction (bladder, bowel, and/or sexual dysfunction), all below the spinal lesion level. A sensory "level" on examination — a band of altered sensation demarcating normal from abnormal — is the hallmark clinical finding and helps localize the lesion.

The Transverse Myelitis Consortium Working Group (2002) established widely adopted diagnostic criteria requiring all of the following: bilateral sensorimotor or autonomic dysfunction attributable to the spinal cord; a clearly defined sensory level; evidence of inflammation (CSF pleocytosis, elevated IgG index, or MRI gadolinium enhancement); and progression to nadir within 4 hours to 21 days. Cord compression, radiation-induced myelopathy, and vascular causes must be excluded.

Distinguishing TM associated with specific underlying disorders — particularly NMOSD (AQP4-IgG+), MOGAD (MOG-IgG+), or multiple sclerosis — from truly idiopathic TM is the central diagnostic challenge, because each carries different relapse risk and treatment implications. NMOSD-associated TM is typically longitudinally extensive (LETM: ≥3 vertebral segments), while MS-associated TM is usually short-segment (<2 segments). Idiopathic TM that meets LETM criteria carries a 60–90% risk of eventual NMOSD if AQP4-IgG is positive.

2. Epidemiology

The annual incidence of acute TM is estimated at 1.34–4.6 cases per million population, yielding a prevalence of approximately 33,000 affected individuals in the United States at any given time. TM is slightly more common in women (female-to-male ratio approximately 1.6:1), reflecting the female predominance of the autoimmune diseases that frequently underlie it. Peak incidence occurs in two age groups: young adults (20–39 years) and children (peak at 5–9 years and adolescence), though it can occur at any age.

Post-infectious TM shows seasonal clustering in spring and summer corresponding to enteroviral activity. NMOSD-associated TM has a higher prevalence in East Asian and African-descent populations, which parallels the geographic distribution of AQP4-IgG positivity. MS-associated TM is more common in Northern European-descent individuals and at higher latitudes — the standard MS epidemiological pattern. Approximately 15–30% of TM cases are eventually attributed to a specific systemic autoimmune disorder (lupus, Sjögren's, sarcoidosis, antiphospholipid syndrome).

3. Pathophysiology

Immune-Mediated Mechanisms

The final common pathway is T-cell and antibody-mediated attack on spinal cord myelin, oligodendrocytes, or astrocytes, resulting in focal inflammatory demyelination with variable degrees of axonal injury and necrosis. The specific cellular target differs by etiology:

MS-associated TM: CD4+ Th1 and Th17 cells infiltrate the cord, attacking oligodendrocyte myelin via MBP, MOG, and other myelin antigens; CD8+ cytotoxic T cells contribute to axonal loss; perivenular inflammation on pathology
NMOSD-AQP4+: Pathogenic IgG1 autoantibodies against aquaporin-4 (AQP4) — the predominant astrocytic water channel — bind astrocytic end-feet, activate complement (C5b-9 membrane attack complex), and trigger astrocyte destruction. This is the defining "outside-in" astrocytopathy distinguishing NMOSD from MS. Loss of astrocytes destabilizes the blood-brain barrier and triggers secondary oligodendrocyte and axonal injury. Lesions are characteristically large, centrally necrotic, and longitudinally extensive (LETM).
MOGAD: MOG-IgG (IgG4 class — not complement-fixing) targets myelin oligodendrocyte glycoprotein on the outermost lamellae of myelin sheaths; demyelination is prominent with relative axonal sparing; T-cell and Fc-mediated effector pathways contribute; pathologically resembles MS but with CD4+ T cell predominance and less axonal loss than NMOSD.
Post-infectious TM: Molecular mimicry between pathogen epitopes and myelin antigens activates autoreactive T cells; myelin-reactive antibodies may contribute; direct viral invasion of the cord is less common (poliomyelitis, West Nile, EV-D68 being exceptions where anterior horn infection dominates).

Structural Consequences

Acute inflammation causes edema, demyelination, and variable necrosis at the affected cord level. The degree of axonal injury — estimated by MRI diffusion restriction, N-acetylaspartate spectroscopy, and serum neurofilament light chain (NfL) levels — is the primary determinant of long-term neurological recovery. Gray matter involvement (central canal, anterior horns) predicts more severe motor deficits. Cystic necrosis, seen in severe NMOSD attacks, indicates irreversible damage and predicts persistent disability.

4. Etiology and Classification

Disease-Associated TM

NMOSD (AQP4-IgG+): The most important cause of LETM. Approximately 80% of NMOSD patients will experience TM; optic neuritis is the other hallmark attack. Seronegative NMOSD exists (AQP4-IgG−) and may be MOG-IgG+ or double-negative with stricter clinical criteria required.
Multiple sclerosis: TM is a common inaugural attack of MS; typically short-segment (<2 vertebral segments), posterolateral cord, incomplete deficits. The McDonald 2017 criteria apply: a second attack or MRI dissemination-in-time/space is required for definitive MS diagnosis after isolated TM.
MOGAD (MOG-IgG+): Increasingly recognized as a distinct entity from both MS and NMOSD; often causes LETM or conus lesions; opticospinal phenotype overlapping NMOSD but with better recovery per attack; higher relapse risk in adults than children.
Systemic lupus erythematosus (SLE): TM occurs in 1–2% of SLE patients; antiphospholipid antibodies and immune complex deposition contribute; often ischemic-inflammatory mixed mechanism.
Sjögren's syndrome: Primary Sjögren's can cause TM indistinguishable from NMOSD, sometimes with AQP4-IgG coexistence; SSA/Ro and SSB/La antibodies are present.
Sarcoidosis: Neurosarcoidosis causes TM via granulomatous inflammation of the cord; often accompanied by meningeal enhancement, cranial nerve involvement, or pulmonary/hilar lymphadenopathy.
Antiphospholipid syndrome (APS): Thrombotic mechanism (infarction) may mimic inflammatory TM; aCL, anti-β2GP1, and lupus anticoagulant testing required.

Post-Infectious and Post-Vaccination TM

Occurs 1–3 weeks after viral illness (influenza, Epstein-Barr virus, cytomegalovirus, herpes simplex, varicella-zoster, enteroviruses, SARS-CoV-2); thought to be immune-mediated molecular mimicry rather than direct viral infection of the cord
Post-vaccination TM is rare (<1 per million doses for most vaccines); temporal association requires rigorous causality assessment

Idiopathic TM

When all known causes are excluded and AQP4-IgG and MOG-IgG are negative, TM is classified as idiopathic. Idiopathic TM accounts for approximately 25–40% of cases in series where systematic antibody testing is performed. LETM that is antibody-negative carries a 10–20% risk of a future demyelinating event over 5 years; short-segment antibody-negative TM has a 10–30% risk of conversion to clinically definite MS over 10 years, depending on MRI brain lesion burden at onset.

5. Clinical Presentation

Onset and Progression

Symptoms typically evolve over 4 hours to 21 days (per diagnostic criteria). Hyperacute onset (minutes to hours) should raise concern for spinal cord infarction rather than inflammatory TM. A prodrome of back or limb pain at the level of the lesion is common, occurring in 40–60% of patients, and may precede neurological deficits by hours to days. Constitutional symptoms (fever, myalgia) suggest a post-infectious etiology.

Motor Deficits

Bilateral leg weakness is the most common motor presentation; arm involvement occurs with cervical lesions
Acute flaccid paraplegia (spinal shock) may initially mimic lower motor neuron disease due to areflexia and hypotonia; upper motor neuron signs (spasticity, hyperreflexia, Babinski response) emerge over days to weeks as spinal shock resolves
Asymmetric motor involvement is common, particularly in MS-associated TM and early MOGAD

Sensory Deficits

A sensory level — a dermatomal boundary below which sensation is abnormal — is the clinical hallmark; may be a band of hypersensitivity (allodynia, dysesthesia) or hypoesthesia
Lhermitte's sign (electric shock sensation down the spine on neck flexion) indicates posterior column involvement and is classically associated with cervical MS TM
Vibration and proprioception are disproportionately affected in posterior column lesions (dorsal columns); pain and temperature in spinothalamic tract lesions
In NMOSD, central cord involvement produces bilateral spinothalamic deficits; in MS, asymmetric dorsal column and corticospinal involvement is more typical (Brown-Séquard-like pattern)

Autonomic Dysfunction

Bladder: Urinary retention is the most common and often earliest autonomic symptom; detrusor-sphincter dyssynergia, urinary urgency, and incontinence occur as the cord lesion evolves; requires post-void residual measurement and catheterization if retention is present
Bowel: Constipation and fecal incontinence; bowel programs are required for cord lesions above the conus
Sexual dysfunction: Erectile dysfunction in men, reduced lubrication and orgasm in women; common but often under-reported
Autonomic dysreflexia: Life-threatening paroxysmal hypertension triggered by stimuli below the lesion level (full bladder, fecal impaction, pressure sores); occurs with thoracic lesions above T6; emergency management required
Thermoregulation: Impaired sweating below the lesion, poikilothermia in high thoracic/cervical lesions

6. Diagnosis

Emergency Priority: Rule Out Cord Compression

The first step in any patient with acute myelopathy is emergent MRI of the entire spine with and without gadolinium contrast to exclude structural cord compression (epidural abscess, hematoma, tumor, disc herniation). Cord compression is a neurosurgical emergency requiring immediate intervention. Lumbar puncture must NOT be performed until cord compression is excluded by MRI, as LP in the presence of a spinal block can precipitate tonsillar herniation or sudden neurological deterioration by shifting the CSF pressure gradient.

MRI Spinal Cord

T2-weighted sequences: The cornerstone finding is T2 hyperintensity within the cord at the affected level(s); best seen on sagittal T2 and axial T2 through the lesion
Lesion length (LETM vs. short-segment):
- NMOSD: typically ≥3 contiguous vertebral segments (LETM); often extends from cervical to thoracic cord; may involve the entire thoracic cord or conus; tends to be centrally located and bright
- MS: typically <2 vertebral segments; dorsal and/or lateral cord; asymmetric; small cross-sectional area (<50% of cord cross-section)
- MOGAD: often LETM but may be short-segment; conus involvement is characteristic
- Post-infectious/idiopathic: variable, often LETM in children
Gadolinium enhancement: Indicates active blood-brain barrier disruption and acute inflammation; patchy or homogeneous enhancement within the T2 lesion; absent in late presentations (>6 weeks) or very mild attacks
T1 hypointensity ("black holes"): Indicates significant axonal loss and predicts incomplete recovery in MS; cavitation or necrosis on T1 is characteristic of severe NMOSD attacks
DWI restriction: Acute diffusion restriction suggests cytotoxic edema from infarction or very acute severe inflammation; less common in purely inflammatory TM
Brain MRI: Essential in all TM cases — white matter lesions characteristic of MS or NMOSD (periaqueductal, area postrema, hypothalamic lesions in NMOSD; periventricular, juxtacortical, infratentorial in MS) guide etiological classification and satisfy McDonald 2017 dissemination criteria

Cerebrospinal Fluid Analysis

Cell count: Pleocytosis (typically lymphocytic, 10–200 cells/mm³) in 50–80% of inflammatory TM cases; absent in mild or very acute cases; neutrophilic pleocytosis suggests bacterial infection or early viral TM
Protein: Mildly elevated (50–100 mg/dL) in most cases; markedly elevated protein (>100 mg/dL) with albuminocytologic dissociation suggests Guillain-Barré syndrome (peripheral, not cord)
Oligoclonal bands (OCBs): Present in 85–95% of MS patients with TM; typically absent or transiently present in NMOSD (an important distinguishing feature); absent in MOGAD and most post-infectious TM; presence in isolated first TM episode strongly suggests MS or subclinical demyelinating disease
IgG index: Elevated in MS (intrathecal IgG synthesis); normal in NMOSD
Glucose: Normal in viral/immune TM; low glucose suggests bacterial or fungal meningitis/myelitis
Cytology: Malignant cells in neoplastic myelopathy (leptomeningeal carcinomatosis, lymphoma)
Infectious studies: VDRL, herpes PCRs (HSV-1/2, VZV, EBV, CMV, enteroviruses), cryptococcal antigen, HTLV-1/2 serology, HIV in appropriate clinical contexts

Serology — Critical Testing

AQP4-IgG (NMO-IgG): Highly specific for NMOSD (specificity >99%); sensitivity 72–90% depending on assay (cell-based assay, CBA, is most sensitive); positive result in LETM context is diagnostic of NMOSD and mandates immediate relapse-prevention therapy
MOG-IgG: Tested by live cell-based assay (fixed-cell assays give false positives); identifies MOGAD — a distinct entity with different treatment approach than NMOSD and different prognosis than MS; positivity is especially common in children, bilateral optic neuritis, ADEM, and conus-predominant LETM
ANA, anti-dsDNA, anti-Smith: Screen for SLE
SSA/Ro, SSB/La: Screen for Sjögren's syndrome
ANCA (c-ANCA/p-ANCA): Neurosarcoidosis workup
Antiphospholipid antibodies (aCL, anti-β2GP1, LA): Screen for APS-related myelopathy
ACE level, chest CT/PET: Sarcoidosis workup (ACE has low sensitivity alone)
ESR, CRP: Non-specific markers of systemic inflammation
Vitamin B12, copper: Nutritional myelopathies can mimic TM; B12 deficiency causes subacute combined degeneration (posterior and lateral column; not typically inflammatory)

Evoked Potentials

Somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) can document subclinical cord involvement and confirm the physiological level of the lesion. Visual evoked potentials (VEPs) are important for detecting subclinical optic nerve involvement that would support MS or NMOSD diagnosis even before a clinical episode.

7. Treatment

Acute Phase: Corticosteroids

Intravenous methylprednisolone (IVMP) 1 g/day for 5 days is the standard first-line treatment for acute TM, based on its efficacy in MS relapses and extrapolation to other inflammatory TM subtypes. IVMP accelerates recovery speed but has less clear effect on long-term outcome. It is given regardless of the underlying etiology while workup proceeds, as rapid treatment of acute inflammation may limit axonal injury. Common side effects include hyperglycemia, insomnia, mood disturbance, and hypertension — monitor blood glucose and blood pressure during infusion.

Oral prednisolone taper after IVMP is commonly prescribed (e.g., 1 mg/kg/day for 10 days with taper) but evidence for the taper specifically in TM is limited; it is more established in optic neuritis and MS. High-dose oral steroids (1250 mg methylprednisolone equivalent) may be an alternative to IV for mild-to-moderate attacks when IV access is impractical.

Plasma Exchange (PLEX) for Steroid-Refractory TM

Plasma exchange (5–7 exchanges of 1–1.5 plasma volumes over 10–14 days) is the established second-line therapy for acute TM that fails to improve or continues to worsen after high-dose corticosteroids. The mechanism involves removal of pathogenic autoantibodies (AQP4-IgG, MOG-IgG, other complement-fixing antibodies) and inflammatory mediators. Response rates of 40–60% have been reported in steroid-refractory MS relapses and NMOSD attacks. PLEX is most effective when started within 2–3 weeks of attack onset; delayed initiation reduces efficacy. It is generally well tolerated; complications include hypocalcemia, coagulopathy, hypotension, and line-related infection.

The combination of IVMP followed immediately by PLEX (rather than waiting for steroid failure) is practiced at some centers for severe NMOSD attacks (complete paraplegia, bilateral visual loss), given the poor recovery seen in untreated severe NMOSD attacks, though this approach has not been studied in a randomized controlled trial.

Intravenous Immunoglobulin (IVIG)

IVIG (2 g/kg total dose over 2–5 days) is sometimes used for post-infectious TM (particularly in children) or as an alternative when PLEX is unavailable or contraindicated. Evidence is limited to case series and small retrospective studies; IVIG has not been shown in randomized trials to be superior to IVMP for acute TM. Its mechanisms include neutralization of pathogenic antibodies, Fc receptor blockade, and immunomodulation.

Symptomatic Management

Bladder

Urinary retention: Intermittent self-catheterization (ISC) every 4–6 hours is the gold standard for neurogenic bladder management; maintains bladder volumes below 400–500 mL to prevent upper tract damage; preferable to indwelling catheter (lower UTI and stone risk)
Detrusor overactivity / urgency incontinence: Oxybutynin 5 mg twice daily to three times daily (anticholinergic); solifenacin, mirabegron (β3-adrenergic agonist) as alternatives with better tolerability; botulinum toxin A cystoscopic injection for refractory detrusor overactivity
UTI prevention: Adequate hydration, aseptic ISC technique, cranberry extract (modest evidence), prophylactic antibiotics reserved for recurrent UTIs (≥3/year); regular urine cultures if symptomatic

Bowel

Neurogenic bowel program: scheduled defecation at consistent times, digital rectal stimulation, suppositories (bisacodyl) to trigger reflexic bowel in upper motor neuron lesions; manual evacuation for lower motor neuron lesions (conus/cauda equina)
Stimulant laxatives (senna, bisacodyl) for constipation; osmotic agents (macrogol, lactulose) for stool softening; adequate fiber (25–35 g/day) and fluid intake
Avoid routine daily enemas — bowel program achieves predictable continence without dependency

Spasticity

Baclofen (GABA-B agonist): starting dose 5 mg three times daily, titrated to 60–80 mg/day; most effective oral antispastic; intrathecal baclofen pump for severe refractory spasticity
Tizanidine (α2-agonist): 2–4 mg at bedtime, titrated to 36 mg/day; useful for nighttime spasticity; hepatotoxicity monitoring required
Diazepam, clonazepam: Useful for nocturnal spasms but sedating; dependence potential limits long-term use
Physiotherapy: Stretching, passive range-of-motion, and progressive resistance exercises are essential adjuncts to pharmacological spasticity management

Neuropathic Pain

Gabapentin: 300–3600 mg/day in divided doses; first-line for neuropathic pain, dysesthesias, and burning sensations below the lesion; also reduces spasms
Pregabalin: 75–300 mg twice daily; similar efficacy to gabapentin with more predictable pharmacokinetics
Duloxetine: 60–120 mg/day SNRI; effective for neuropathic pain, also treats comorbid depression common in TM
Amitriptyline: 10–75 mg at bedtime; TCA with dual analgesic and sleep benefit; anticholinergic effects may worsen bladder dysfunction
Opioids: Reserved for severe refractory pain; risk of tolerance, constipation (worsens neurogenic bowel), and respiratory depression

Autonomic Dysreflexia

In patients with lesions above T6: recognize immediately (pounding headache, flushed face, sweating above, pallor/piloerection below, severe hypertension ≥150/100 mmHg). Remove the trigger (full bladder first — catheterize immediately; then bowel, pressure areas, tight clothing). Sit patient upright (drops blood pressure). If hypertension persists: sublingual nifedipine (10 mg) or nitropaste; IV labetalol for severe crisis. Educate patient and caregivers — recurrent dysreflexia episodes indicate need for optimized bowel and bladder programs.

8. Prognosis and Recovery

Recovery from TM follows the rule of thirds: approximately one-third of patients achieve full or near-full neurological recovery, one-third have partial recovery with residual deficits, and one-third have no meaningful recovery and remain with significant permanent disability. Recovery mostly occurs within the first 3–6 months, with most gains made in the initial 2 months; further slow improvement can continue up to 2 years.

Predictors of Poor Outcome

Complete paralysis at nadir (complete TM vs. incomplete TM — most important prognostic factor)
Rapid onset (hours rather than days)
NMOSD-AQP4+ etiology (severe axonal injury; 80% of NMOSD attacks cause permanent disability if untreated)
Extensive T2 lesion length and T1 hypointensity on MRI
High serum neurofilament light chain (NfL) — a marker of axonal injury
Delayed treatment (onset to IVMP >72 hours)
Older age at onset

Predictors of Good Outcome

Incomplete neurological deficit at nadir
MOGAD etiology (better per-attack recovery than NMOSD, though relapse risk remains)
Post-infectious etiology (often good recovery)
Short-segment lesion (<3 vertebral segments)
Absence of T1 hypointensity (no black holes) on MRI
Rapid improvement within 1 week of IVMP

Relapse Risk

Truly idiopathic monophasic TM has a relapse rate of approximately 10–15% over 5 years. AQP4-IgG positive TM (NMOSD) carries a 90% cumulative relapse probability over 5 years without maintenance therapy; untreated relapses in NMOSD cause cumulative severe disability. MOG-IgG positive TM: relapse rate approximately 50% over 5 years in adults, lower in children; each relapse carries better recovery odds than NMOSD. MS-associated TM: standard MS natural history (without disease-modifying therapy, approximately 50% relapse rate at 2 years after first attack).

9. Rehabilitation

Neurorehabilitation is essential for maximizing functional recovery in TM and begins in the acute phase once medically stable. The Functional Independence Measure (FIM) and the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI/ASIA impairment scale) are the standard outcome measures used in TM rehabilitation. Goals are individualized based on lesion level, completeness of deficit, and patient priorities.

Physical Therapy (PT)

Gait retraining: body-weight-supported treadmill training (BWSTT), robotic-assisted gait (Lokomat) for non-ambulatory patients, overground walking therapy
Strengthening: progressive resistance exercises for preserved motor function above and at the lesion level; electrical stimulation (NMES, FES) for denervated muscles
Spasticity management: daily stretching program, positioning, splinting; hydrotherapy for pain relief and range-of-motion
Transfer and mobility training: bed mobility, wheelchair propulsion, car transfers; essential for patients with incomplete recovery

Occupational Therapy (OT)

Activities of daily living (ADLs): adaptive strategies for bathing, dressing, grooming, cooking in patients with persistent motor deficits
Upper extremity function: fine motor retraining for cervical TM with arm involvement; adaptive equipment (grab bars, long-handled tools, voice-activated technology)
Home modification assessment: ramp access, roll-in showers, stair lifts; work reintegration planning

Vocational and Psychological Rehabilitation

Depression and anxiety are prevalent in TM (up to 40% of patients with persistent deficits); targeted psychological support, cognitive-behavioral therapy, and pharmacological treatment (SSRIs/SNRIs) are integral to comprehensive rehabilitation. Sexual health counseling, fatigue management programs, and peer support networks (Transverse Myelitis Association) significantly improve quality of life. Return to work is achievable for many patients with incomplete recovery, particularly with cognitive accommodation and ergonomic modification.

Pain Rehabilitation

Chronic central neuropathic pain — particularly at-level dysesthesias and below-level burning pain — is reported in 60–80% of TM survivors and is a major determinant of quality of life. A multidisciplinary pain program incorporating pharmacotherapy (gabapentin/pregabalin/duloxetine), psychological interventions (acceptance and commitment therapy, mindfulness), and physical modalities (TENS, heat/cold) produces better outcomes than any single approach.

10. Prevention of Relapses

Relapse prevention is not relevant for truly monophasic TM, but is the cornerstone of long-term management for NMOSD, MOGAD, and MS. The choice of agent depends on etiology — which is why AQP4-IgG and MOG-IgG serology are mandatory before committing to any maintenance therapy.

NMOSD-AQP4+ Relapse Prevention

Three approved complement and B-cell targeted therapies have transformed NMOSD prognosis:

Eculizumab (Soliris): Humanized monoclonal antibody inhibiting complement component C5, blocking formation of the membrane attack complex (C5b-9) — the primary effector of AQP4-IgG-mediated astrocyte injury. FDA-approved 2019 for AQP4-IgG+ NMOSD. PREVENT trial: 94.2% reduction in annualized relapse rate versus placebo. Requires meningococcal vaccination ≥2 weeks before initiation. Ravulizumab (Ultomiris) — longer-acting anti-C5 — is now FDA-approved as a more convenient alternative (monthly infusion vs. biweekly).
Inebilizumab (Uplizna): Anti-CD19 monoclonal antibody depleting B cells and plasmablasts (CD19+ cells, which include plasmablasts that produce AQP4-IgG and are CD20-negative). FDA-approved 2020. N-MOmentum trial: 73% reduction in relapse risk vs. placebo. Given as two IV infusions 2 weeks apart, then every 6 months.
Satralizumab (Enspryng): Anti-IL-6 receptor monoclonal antibody (recombinant humanized IgG2); inhibits IL-6 signaling, reducing plasmablast survival and AQP4-IgG production. FDA-approved 2020. SAkuraStar trial: 55% reduction in relapse risk in AQP4-IgG+ patients; subcutaneous injection every 4 weeks after loading doses.
Rituximab: Off-label anti-CD20 depleting B cells; widely used before approved agents and in resource-limited settings; 375 mg/m² × 4 doses or 1000 mg × 2 doses; re-treated when CD19+ cells repopulate (>1% or at 6-month intervals)
Azathioprine + prednisone: Traditional immunosuppression; still used in resource-limited settings; inferior to biologic therapies in head-to-head comparisons; AZA 2–3 mg/kg/day; TPMT testing before initiation

MOGAD Relapse Prevention

No agent is currently FDA-approved specifically for MOGAD. Options used in practice (based on observational data and expert consensus):

Long-term low-dose prednisone (10–20 mg/day maintenance) — most commonly used; risk of metabolic complications with prolonged use
Azathioprine or mycophenolate mofetil — steroid-sparing immunosuppression; azathioprine 2–3 mg/kg/day; MMF 1–1.5 g twice daily
IVIG maintenance (0.4–0.8 g/kg every 4–8 weeks) — particularly considered in pediatric MOGAD and patients unable to tolerate chronic immunosuppression
Rituximab — used for refractory relapsing MOGAD though less evidence than in NMOSD; some data suggest MOG-IgG may persist on B-cell depletion as it can be produced by CD20-negative long-lived plasma cells

MS-Associated TM

MS disease-modifying therapies (DMTs) are indicated after a second demyelinating attack or after a first attack (clinically isolated syndrome) with MRI features meeting McDonald 2017 dissemination criteria. First-line high-efficacy DMTs (ofatumumab, ocrelizumab, natalizumab, alemtuzumab, cladribine) are increasingly preferred over platform therapies (interferons, glatiramer acetate) for patients with active lesions or severe first attack, given superior efficacy demonstrated in randomized trials.

11. Recent Research

Advances in TM research have focused on precision etiological diagnosis, novel therapeutic targets, and biomarker-guided prognosis. A landmark development was the clinical availability of MOG-IgG testing (CBA method, 2016 onwards), which reclassified a significant proportion of formerly "seronegative NMOSD" and "atypical MS" as MOGAD — with distinct treatment implications. Ongoing work is characterizing the role of GFAP (glial fibrillary acidic protein) as a serum biomarker of astrocyte injury in NMOSD, complementing neurofilament light chain (NfL) as a marker of axonal damage; both are being evaluated as tools to predict attack severity and guide treatment escalation decisions.

The PREVENT trial (2019) demonstrated that eculizumab reduces the annualized relapse rate in NMOSD-AQP4+ by 94% versus placebo, establishing complement inhibition as the first pathophysiology-directed therapy for NMOSD. Subsequent real-world registry data from the NMOSD-FAR study confirmed sustained efficacy over 4 years. Research into tozinameran-associated TM following COVID-19 mRNA vaccination has been published (predominantly MOGAD or LETM phenotype, good recovery), providing regulatory-grade safety signal data. Emerging research on type I interferons and JAK inhibition in MOGAD (notably baricitinib) is under active investigation following observation of interferon pathway dysregulation in MOGAD brains.

Neuroprotection trials — examining whether early high-dose methylcobalamin, erythropoietin, or riluzole can protect axons during acute TM attacks — are ongoing but have not yet produced practice-changing results. Patient-derived stem cell therapy (iPSC-derived oligodendrocyte precursor transplantation) remains in preclinical stages for chronic TM sequelae.

12. References

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