- •Transverse myelitis (TM) constitutes a pathobiologically heterogeneous syndrome that has significant neurologic implications and requires urgent attention.
- •Magnetic resonance imaging (MRI) evaluation of the entire spinal cord axis is mandatory in all myelopathic patients.
- •The length of the spinal cord lesion on MRI is an important discriminator with etiologic and prognostic significance; longitudinally extensive transverse myelitis (LETM) refers to lesions that extend over 3 or more vertebral segments.
- •Early and timely identification and immunotherapy are critical to minimize, or even prevent, future disability.
- •The long-term management should focus on neurorehabilitation and a multidisciplinary approach aimed at managing the various complications of spinal cord damage.
- Myelopathy: a broad, generic term referring to a lesion affecting the spinal cord
- Myelitis: refers to an inflammatory disease of the spinal cord
- Transverse myelitis (TM): classically describes a pathobiologically heterogeneous syndrome characterized by acute or subacute spinal cord dysfunction resulting in paresis, a sensory level, and autonomic impairment below the level of the lesion
- Acute Complete TM (ACTM): TM causing paresis of the lower and/or upper extremities, sensory dysfunction (characterized by a sensory level), and autonomic impairment below the level of the lesion. On magnetic resonance imaging (MRI), there is typically a single lesion spanning 1 or 2 vertebral segments; on axial sections, there is either full-thickness involvement, or the central portion of the spinal cord is maximally affected.
- Acute Partial TM (APTM): TM causing asymmetric neurologic impairment (localizable to the spinal cord) or deficits attributable to a specific anatomic tract. On MRI, it spans 1 or 2 vertebral segments; there is involvement of a small portion of the spinal cord on axial sections.
- Longitudinally-Extensive TM (LETM): a spinal cord lesion that extends over 3 or more vertebral segments on MRI. On axial sections, it typically involves the center of the cord over more than two-thirds of the spinal cord area.
- Secondary TM: TM related to a systemic inflammatory autoimmune disorder (eg, lupus, Sjögren syndrome, sarcoidosis). It is typically an ACTM.
- Idiopathic TM: TM without any clear etiology despite a thorough investigation. It should meet the criteria listed in Table 8.
|Syndrome||Tracts Involved||Clinical Manifestations|
|Complete transverse myelitis||All||Paresis, sensory loss, and autonomic impairment below the level of the lesion|
|Hemicord (Brown-Sequard)||Ipsilateral corticospinal; Ipsilateral dorsal columns; contralateral spinothalamic||Ipsilateral paresis and impaired dorsal column sensation; contralateral pain and temperature loss|
|Dorsal column||Bilateral dorsal columns||Bilateral loss of vibratory and proprioceptive sensation; Lhermitte phenomenon|
|Subacute Combined Degeneration||Bilateral dorsal columns and corticospinal tracts||Bilateral dorsal column dysfunction; paresis and upper motor neuron signs below the level of the lesion|
|Central cord||Crossing spinothalamic fibers, and corticospinal tracts||Dissociated sensory loss (diminished pain and temperature with normal dorsal column function) in a shawl-like pattern. Saddle-sparing sensory loss. Upper motor neuron weakness below the level of the lesion.|
|Conus medullaris||Sacral autonomic fibers||Early and prominent sphincter and sexual impairment; saddle pattern sensory loss; mild weakness|
|Tract-specific dysfunction||Depending on involved tract|
|Beevor sign||Describes the upward migration of the umbilicus during the act of sitting up from supine position owing to weakness of the lower half of the rectus abdominis (because the upper rectus segments pull in a direction opposite of the lower segments, the movement of the abdomen is upward).|
In some cases, downward migration of the umbilicus may be observed.
This sign indicates a lesion at the level of the T10–12 spinal cord and/or roots.
|Superficial abdominal reflexes||A lesion above T6 segmental cord level will abolish all superficial abdominal reflexes.|
A lesion at or below T10 spares the upper and middle abdominal reflexes.
All the reflexes are present with a lesion below T12.
|Cremasteric reflex||Lost in lesions at or above L2 segmental cord level.|
|Bulbocavernous reflex||Mediated by S2–4 nerve roots; hence, is abolished in lesions above S2 segmental cord level.|
|Anal wink reflex||Mediated by S2–4 nerve roots; hence, is abolished in lesions above S2 segmental cord level|
- 1.Apoplectic onset (reaching the nadir less than 4 hours from onset).
- 2.Insidious progressive course.
- 3.Older age of onset.
- 4.Preceding trauma, pain, and/or vertebral tenderness would suggest traumatic myelopathy.
- 5.Vascular instrumentation (in particular, aortic and cardiac surgery) or maneuvers that increase intra-abdominal pressure (eg, weight-lifting or straining) before the acute/subacute appearance of myelopathic features may implicate spinal cord infarction.
- 6.Prior bariatric surgical procedures, malabsorption syndromes, dietary restrictions, malnutrition, use of zinc supplements, excessive use of zinc-containing denture cream, alcoholism, and/or drug/toxin exposure may implicate a metabolic or toxic etiology.
- 7.Prior radiation therapy.
- 8.Immunocompromised state (HIV/AIDS or immunosuppressive therapy).
- 9.Features of infection: fever, meningismus, rash, leukocytosis, burning dermatomal pain.
- 10.Paralysis with dissociated sensory loss (loss of pinprick and temperature but preserved dorsal column function) indicates an anterior spinal artery infarction.
- 11.The exacerbation of spinal pain with recumbency suggests malignancy.
- 12.Foix-Alajouanine syndrome (congestive venous myelopathy) is characterized by exacerbation of myelopathic features with exercise and relief with rest.
|Sjögren syndrome||Xerophthalmia, xerostomia, parotid gland enlargement, Raynaud phenomenon, dysphagia, and dry cough (owing to xerotrachea).|
A positive Schirmer test detects deficient tear production.
|Systemic lupus erythematosus||Joint pains, morning stiffness, myalgias, and integumentary manifestations (alopecia, unguium mutilans, perniotic lesions, leuconychia, splinter hemorrhages, nail-fold hyperkeratosis, ragged cuticles, malar rash, Raynaud phenomenon, photosensitivity, and/or discoid lupus).|
|Antiphospholipid syndrome||History of deep vein thromboses, pulmonary embolism, multiple miscarriages, and/or young-onset stroke.|
|Behcet disease||Classic triad of recurrent aphthous ulcers, genital ulcers, and uveitis.|
Other manifestations: ophthalmic (hypopyon and retinal vasculitis) and cutaneous (pseudofolliculitis, erythema nodosumlike lesions, or acneiform lesions).
Positive pathergy test.
|Ankylosing spondylitis||Back pain, enthesitis, and limited spinal flexion.|
Evaluation and diagnosis
- 1.Neuromyelitis optica (NMO) or NMO-spectrum disorders
- 2.Acute disseminated encephalomyelitis (ADEM)
- 3.Systemic autoimmune disorders: systemic lupus erythematosus (SLE), Sjögren syndrome (SS), neurosarcoidosis, neuro-Behcet disease
- 4.Parainfectious TM: Borrelia burgdorferi, Chlamydia psittaci, mumps virus, cytomegalovirus, coxsackie virus, Mycobacterium tuberculosis, Mycoplasma pneumoniae, enterovirus 71, hepatitis C virus, Brucella melitensis, Epstein-Barr virus, echovirus type 30, Ascaris suum, Toxocara canis, and Schistosoma species.
- 5.Paraneoplastic TM (in particular, anti-collapsin response-mediator protein [CRMP]-5 antibodies)
- 6.Mimics of TM
- a.Neoplasms: primary intramedullary spinal cord tumors, metastatic intramedullary tumors, lymphoma
- b.Radiation myelitis
- c.Metabolic myelopathies: B12 deficiency, copper deficiency, nitrous oxide toxicity
- d.Vascular myelopathies: anterior spinal artery infarction, spinal dural arteriovenous fistula
- 1.Magnetic resonance image (MRI) of the spine
- 2.Brain MRI
- 3.Cerebrospinal fluid (CSF): cells, differential, protein, glucose, Venereal Disease Research Laboratory (VDRL), immunoglobulin (Ig)G index, oligoclonal bands, cytologic analysis
- 4.Serum: B12, methylmalonic acid, HIV antibodies, syphilis serologies, thyroid stimulating hormone (TSH), Free T4, 25-hydroxyvitamin D
Must be obtained on all patients:
- 1.Serum NMO-IgG
- 2.Serum erythrocyte sedimentation rate, C-reactive protein, antinuclear antibodies, antibodies to extractable nuclear antigen, rheumatoid factor, antiphospholipid antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA)
- 3.Visual-evoked potentials
Must be obtained on all patients with LETM:
- 1.Neuro-ophthalmological evaluation
- 2.Paraneoplastic panel
- 3.Infectious serologies and CSF studies (cultures and viral polymerase chain reaction)
- 4.Serum copper and ceruloplasmin
- 5.Serum vitamin E level
- 6.Computed tomography of the chest
- 7.Nerve conduction studies and electromyography
- 8.Minor salivary gland biopsy
May need to be obtained:
Causes of TM
- 1.Acquired demyelinating disorders
- a.Multiple sclerosis
- 2.Systemic inflammatory autoimmune disorders
- c.Antiphospholipid syndrome
- d.Behcet disease
- e.Vogt-Koyanagi Harada disease
- f.Ankylosing spondylitis
- g.Mixed connective tissue disease
- h.Others: systemic sclerosis, anti-Jo-1 antibody, urticarial vasculitis, psoriatic arthritis, perinuclear ANCA systemic vasculitis, graft-versus-host disease, common variable immunodeficiency, celiac disease
- 4.Parainfectious TM
- a.Viral: hepatitis A, hepatitis B, hepatitis C, hepatitis E, measles, mumps, rubella, varicella zoster, Epstein-Barr, cytomegalovirus, herpes simplex, influenza A/B, lymphocytic choriomeningitis virus, chikungunya, Hanta virus, HIV, human T-cell lymphotropic virus, human herpes virus 6, Japanese encephalitis, Murray Valley encephalitis, St Louis encephalitis, tick-borne encephalitis, vaccinia, Rocky Mountain spotted fever, dengue virus, enterovirus 71, coxsackievirus A and B, West Nile virus, parvovirus B19, human corona virus, and echovirus
- b.Bacterial: Mycoplasma pneumoniae, Campylobacter jejuni, Borrelia burgdorferi, Acinetobacter baumanii, Coxiella burnetii, Bartonella henselae, Chlamydia psittaci, Leptospira, Chlamydia pneumoniae, Legionella pneumonia, Orientia tsutsugamushi (scrub typhus), Salmonella paratyphi B, Mycobacterium tuberculosis, Treponema pallidum, Brucellosis melitensis, and groups A and B streptococci
- c.Fungal: Actinomyces, Blastomyces, Coccidioides, Aspergillus, Cryptococcus, and Cladophialophora bantiana
- d.Parasitic: Toxocara species, Schistosoma species, Gnasthostoma spinigerum, Echinococcus granulosus, Taenia solium, Toxoplasma gondii, Acanthamoeba species, Paragonimus westermani, and Trypanosoma brucei
- 5.Paraneoplastic syndromes
- a.Anti-Ri (ANNA-2) antibody
- b.CRMP-5-IgG antibody
- c.Anti-amphiphysin IgG antibody
- d.Anti-GAD65 antibody
- e.NMDAR antibody
- 6.Atopic myelitis
- 7.Drugs and toxins
- a.Tumor necrosis factor-alpha inhibitors
- c.Epidural anesthesia
- d.Chemotherapeutic agents: gemcitabine, cytarabine, cisplatin
- g.Brown recluse spider toxin
- 8.Idiopathic TM
Systemic Lupus Erythematosus
|Gray Matter Myelitis||White Matter Myelitis|
|Presentation||Lower motor neuron features with urinary retention (urinary retention always heralds paraplegia)||Upper motor neuron features|
|Prodrome (fever, nausea, vomiting)||Very frequent||Infrequent|
|Clinical course||More rapid deterioration; more severe weakness at nadir.|
Lower motor neuron features persist beyond the time expected for spinal shock.
More aggressive immunosuppression needed.
|Less severe clinical deterioration; longer time to reach nadir; less severe weakness at nadir.|
|CSF||Neutrophilic pleocytosis; higher protein; hypoglycorrachia||Mild pleocytosis; mildly elevated protein; normal glucose|
|MRI||Cord swelling; frequent LETM; less frequent gadolinium-enhancement||Infrequent cord swelling; less frequent LETM; More frequent gadolinium-enhancement|
|Recurrence||Very rare||More than 70% of patients|
|Prior optic neuritis||Absent||Frequent|
|Coexisting NMO and/or NMO-IgG seropositivity||None||Frequent|
|Higher SLE disease activity||Frequent||Infrequent|
TM in Other Rheumatologic Diseases
|Ankylosing spondylitis||Neurologic involvement is rare and is almost always attributable to compressive myelopathy. Noncompressive myelopathy is exceptionally rare with only 2 clearly documented cases of TM.|
|Mixed connective tissue disease||Female preponderance; predilection for the thoracic cord.|
|Systemic sclerosis||Rare and typically compressive in etiology. Progressive myelopathy, subacute TM, and NMO-IgG positive LETM have been reported.|
|Anti-Jo-1 antibody||A single report of TM preceding the development of polymyositis and pulmonary fibrosis in a patient with anti-Jo-1 antibody.|
|Urticarial vasculitis||Urticarial vasculitis may be primary disorder or coexist with other autoimmune diseases.|
|pANCA seropositivity||Perinuclear antineutrophil cytoplasmic antibody (pANCA) seropositivity has been reported to cause TM associated with CSF pleocytosis and increased protein with typically absent OCBs.|
|Celiac disease||Celiac disease is an immune-mediated disorder characterized by intolerance to dietary gluten.|
|Thymic follicular hyperplasia||Recurrent multifocal TM associated with thymic follicular hyperplasia that resolved following thymectomy.|
|Graft-vs-host disease||TM may be a rare manifestation of graft-vs-host disease following hematopoietic cell transplantation.|
|Common variable immunodeficiency||A primary immune deficiency disorder characterized by hypogammaglobulinemia, antibody deficiency, and recurrent infections.|