Transverse myelitis

Differential diagnosis
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By Anthony T Reder MD

Many processes can cause an acute transverse myelopathy and need to be differentiated from idiopathic demyelinating transverse myelitis, as therapy differs (Group TMCW 2002; Lennon et al 2004; Feng et al 2012). Pathology and workup of related diseases are discussed in the pathogenesis, pathophysiology, and diagnostic workup sections.

Transverse myelitis can be recurrent, but other diseases can also cause recurrent cord symptoms. These include hepatitis B with high-titer surface antigen (HBS Ag), systemic lupus erythematosus, antiphospholipid antibody syndrome, and connective tissue disease (Shyu et al 1993). Recurrent transverse myelitis has been seen in Sjögren syndrome (see below) and in anti-Ro (SSA) and antinuclear antibody-positive patients (77% of 13 recurrent idiopathic transverse myelitis cases were antibody-positive, but only 33% of 12 non-recurrent cases were positive) (Hummers et al 2004). Recurrence occurs with myasthenia gravis, thymic hyperplasia, and positive antinuclear antibodies (Tippett et al 1991; Lindsey et al 1992; Pandit and Rao 1996; Kahl et al 1998).

Diseases causing transverse myelopathy include the following:

  • Abscess of the spinal cord, intramedullary or epidural (usually Staphylococcus aureus) (DeSanto and Ross 2011). Spinal epidural abscess causes fever, local pain, and neurologic deficits, with systemic signs of infection and usually an enhancing MRI lesion. Agents are staphylococci, streptococci, and gram-negative bacteria, plus Candida, Aspergillus, and Blastomyces dermatitidis.
  • Acute disseminated encephalomyelitis, postvaccinal encephalomyelitis, and postinfectious encephalomyelitis are monophasic, and spinal cords are sometimes necrotic. Transverse myelitis in children is more often purely sensory and areflexic; acute disseminated encephalomyelitis more often involves multiple cord segments and has more severe demyelination (Yiu et al 2009).
  • Acute necrotizing hemorrhagic leukoencephalitis of Weston Hurst is usually seen in young adults, and occurs a few days after upper respiratory tract infection, occasionally after chickenpox or measles, or rarely after vaccination (rabies, smallpox) or drug exposure (arsphenamine, streptomycin, p-aminosalicylic acid, intra-arterial penicillin). The onset is explosive, with fever, peripheral leukocytosis, and neurologic symptoms. Spinal shock is caused by necrosis of the cord. At autopsy there are mononuclear and polymorphonuclear leukocyte infiltrates in the cord, with fibrin deposition in blood vessels and demyelination around the vessels. The CSF shows up to 2000 mononuclear cells early on, and polymorphonuclear leukocytes later (Helgason and Arnason 1987).
  • Acute partial myelitis (Ford et al 1992) is more likely to progress to multiple sclerosis than complete transverse myelitis.
  • Adrenomyeloneuropathy or adrenoleukodystrophy, where variable white matter abnormalities are seen in 14 of 16 patients on MRI (Aubourg et al 1992). Hereditary myelopathy is likely to be slowly progressive and cause spastic paraparesis and loss of vibratory sense in the legs.
  • AIDS-related myelopathy (Dodson 1990).
  • Allogeneic hematopoietic cell (stem cell) transplant has induced acute transverse myelitis in 3 patients. Symptoms have paralleled what is possibly an immune-mediated pancytopenia, presumably causing immune dysregulation (Perez-Montes et al 2001).
  • Amyloidosis, cerebral, shows MRI T2 white matter lesions, but iron on T2* images.
  • Arachnoiditis is usually more gradual in onset.
  • Atopic myelitis (idiopathic eosinophilic myelitis, hyperIgEaemic myelitis). In series from Japan and Korea, this is associated with high concentrations of IgE directed against mite antigens and eosinophilic infiltration of the cord (Kikuchi et al 2001; Yoon et al 2009). There are elevated eosinophils in blood, subacute onset of sensory symptoms, and extensive multi-segmental, usually thoracic, cord lesions with enhancement at the margins (Yoon et al 2009). CSF is usually normal. Steroids markedly reduce symptoms.
  • Barbotage of the cord during surgery (historical). Repeated injection and withdrawal of spinal fluid, possibly a rare mechanism for myelitis associated with intrathecal drug delivery systems.
  • Bariatric surgery can cause malabsorption of vitamins and other nutrients and a slowly progressive myelopathy.
  • Behçet disease causes recurring aphthous stomatitis, genital ulceration, arthropathy, and uveitis plus lesions in brainstem, basal ganglia, and occasional myelitis (in 10% of CNS Behçet disease). It may respond to type I interferon (Motomura et al 1980) or glucocorticoid therapy.
  • Cancer -- see neoplastic.
  • Cauda equina syndrome plus transverse myelitis in ankylosing spondylitis.
  • Compression of the spinal cord from abscess, herniated disc, synovial cyst, epidural or subdural hematoma (spontaneous or after lumbar puncture or trauma), ossification of the ligamentum flavum, tumor, tuberculoma, giant cell arteritis, ankylosing spondylitis, or rheumatoid arthritis with cervical spondylosis or atlantoaxial dislocation. T2 MRI lesions are common at the site of disc herniation (30% to 41%) but, of course, depend on the severity of the compression. Those without T1 lesions have better prognoses. Of those with T2 lesions, 32% to 52% improve after surgery, some by the end of surgery (Suri et al 2003; Mastronardi et al 2007).
  • Congenital and developmental defects (spina bifida, syrinx).

Connective tissue diseases (lupoid sclerosis; lupus myelopathy; lupus myelitis). Transverse myelitis is seen with systemic lupus erythematosus (SLE), especially in association with anticardiolipin and antiphospholipid antibodies; mixed connective tissue disease, periarteritis nodosa, primary biliary sclerosis, scleroderma and systemic sclerosis (sometimes with conus lesions), and Sjögren disease (Helgason and Arnason 1987; Alarcon et al 1989; Barile and Lavalle 1992; Knebusch et al 1998; Kovacs et al 2000; Hummers et al 2004). Motor and sphincter dysfunction is typical in this spectrum, and outcome is poor. These diseases may cause recurrent longitudinal myelitis spanning several or many cord segments (Lehnhardt et al 2004). With lupus, the sometimes devastating lesions are usually thoracic but are much less frequent than the small white matter brain lesions in 50%, seen on T2 MRI. SLE myelopathy patients are often women and black, have elevated sedimentation rate and CSF IgG, and longer hospital stays.

Sjögren disease is somewhat similar to lupus--CSF cell counts are sometimes more than 30 per ml and oligoclonal bands are rare, but the large centromedullary lesions on MRI are usually in the cervical cord. CNS Sjögren lesions can be restricted to the cord (Chahin et al 2009). Rituximab has been used successfully in some cases of lupus myelopathy and in multiple cases of Sjögren myelopathy (Javed et al 2008).

The link of cord demyelination to connective tissue disease (and associated autoimmune disease and organ-specific antibodies) has been clarified by Dr. Javed. Sjögren disease is usually considered to be defined by serologic tests (SSA and SSB). However, it can be detected with a clinical history of sicca plus lip biopsies (minor salivary gland biopsy of internal oral mucosa) that show 4+/4 inflammation in minor salivary glands of the oral mucosa, even when serologic tests are negative. These patients have high serum interferon-alpha/beta levels and excessive response to interferon stimulation; both features are reduced in multiple sclerosis (Feng et al 2012). Transverse myelitis has not been studied. Approximately 5% of transverse myelitis cases have CNS Sjögren disease. They respond to rituximab better than to interferon or glatiramer therapy (Javed et al 2006).

  • Copper deficiency, seen after gastric, colon, and bariatric surgery, is often associated with high zinc consumption and low plasma ceruloplasmin. This causes progressive cervical myelopathy with gait ataxia, leg spasticity, sensory ataxia from dorsal column dysfunction, occasional optic neuropathy, neutropenia, and microcytic anemia. Copper deficiency myelopathy is a human analogue of “swayback” in ruminants (Kumar et al 2004) and, possibly, cuprizone-induced demyelination.
  • Cytomegalovirus can cause a radiculomyelitis that evolves over days to weeks.
  • Decompression sickness (dysbarism).
  • Devic disease (neuromyelitis optica, NMO) may have cord lesions similar to acute idiopathic transverse myelitis, but diagnosis requires optic nerve involvement, abnormal visual evoked potentials, or a subsequent episode of optic neuritis. Devic disease with optic nerve and cord involvement, simultaneously or sequentially (over months or years), will overlap clinically with acute transverse myelitis. It is not a form of multiple sclerosis, but a distinct variant with associated autoimmune features and excessive responses to interferon beta (Feng et al 2012).
  • Recurrent myelitis is typical in NMO. A United Kingdom study on neuromyelitis optica found a subgroup of 20 patients with relapsing myelitis without optic nerve involvement (Jacob et al 2004). Fifty-eight percent of relapsing cases were female (versus 76% in the overall neuromyelitis optica group). The average age of onset was 44 years. Fifty percent were significantly disabled (versus 87% overall). Oligoclonal bands were positive in 55% (versus 26% overall). Spinal cord lesions on MRI were long (6.5 cm), similar to neuromyelitis optica (4.5 cm), but were shorter in the oligoclonal band-positive group. Smaller cord MRI lesions (2.4 cm) were not inevitably central. Thus, there may be 3 related entities that cause transverse myelitis: (1) pure relapsing transverse myelitis, (2) neuromyelitis optica with early cord damage, but later optic nerve involvement and more frequent autoantibodies, and (3) a spinal variant of multiple sclerosis with positive CSF oligoclonal bands.
  • Fifteen Korean patients with recurrent cord symptoms were often male, presented with acute transverse myelitis, and had normal CSF indices (Kim 2003). Twenty of 32 Taiwanese patients with non-recurrent transverse myelitis were evenly divided between women and men, with mean length of damage = 1.6 vertebral segments (Chan et al 2006). All of the remaining cases were recurrent. All were women, and were later categorized as connective tissue disease (3), Devic variant (5), or idiopathic (3), with an average of 3.4 involved vertebral cord segments.
  • Neuromyelitis optica is marked by an antibody to aquaporin-4 on astrocyte foot processes (NMO-IgG) in 60% to 75% of cases; in multiple sclerosis, less than 10% are positive (Lennon et al 2004). Longitudinally extensive cord lesions, longer than 2 segments, are often associated with NMO-IgG. Other serum autoantibodies and other autoimmune diseases are frequent. Immunologically, there is more Th2 predominance compared to multiple sclerosis, leading to the autoantibodies. CSF oligoclonal bands are positive infrequently (approximately 25%), and disappear over time. NMO-IgG levels correlate with recurrent attacks. Some patients with CNS Sjögren disease and long cervical cord lesions are NMO-IgG negative.
  • Therapy differs between multiple sclerosis (interferon-beta, glatiramer, natalizumab, fingolimod, dimethylfumarate, teriflunomide, and mitoxantrone) and Devic disease (rituximab, mycophenolate mofetil, cyclophosphamide, and possibly lymphocytapheresis, but avoidance of interferon, especially in the CNS Sjögren variant).
  • Diskitis can cause local pain (DeSanto and Ross 2011).
  • Down syndrome with severe acute neuromyelitis optica may be linked to intrinsic Down abnormalities (Cabrera-Gomez et al 2007), such as hyperactive interferon responses.
  • Drugs. Based on clinical experience and the multiple sclerosis literature, there are theoretical reasons to avoid several drugs. Cimetidine, H2 blockers, and melatonin (Constantinescu 1995) enhance immune function (Anlar 1993). Beta-adrenergic blockers inhibit suppressor cell function (Karaszewski 1991). Occasionally, patients with demyelinating disease worsen with fluoroquinolone antibiotics (ie, ciprofloxacin), which induce inflammatory cytokines. Sulphamethazine, used to treat pneumonia in the mid-1900s, was implicated, but the pneumonia was a more likely trigger. Cigarette smoking is probably a risk factor.

    Therapeutic antibodies that modify immunity are occasionally associated with transverse myelitis, but rare reactions could be due to chance. Reports include efalizumab (anti-CD11a for psoriasis). Etanercept (TNF receptor-immunoglobulin fusion protein that blocks TNF) for ankylosing spondylitis is associated with transverse myelitis and other demyelinating diseases. After the drug is discontinued, there do not appear to be recurrences (Hartman et al 2010).

    Some patients are extremely sensitive to low doses of carbamazepine. It causes weakness, probably by blocking Na+ channels in demyelinated axons.
  • Epstein-Barr virus can cause an acute or subacute encephalomyeloradiculitis.
  • Fibrocartilaginous emboli. Rapid onset of spinal cord symptoms is from retrograde flow of emboli from a herniated nucleus pulposus into the anterior spinal artery or spinal veins during straining, causing an anterior spinal artery syndrome (Wilmshurst et al 1999). There is back or neck pain but often no history of trauma, followed by sudden (minutes to hours) onset of weakness and incontinence. This is more common in women than men and is associated with anterior cord lesions on MRI and anterior horn cell fallout on electrophysiologic testing. Cord swelling on MRI is associated with a collapsed disc at the level of the cord deficit, usually in the cervical region (Tosi et al 1996). The CSF is normal. There is no associated viral syndrome. Recovery is unlikely.
  • Foix-Alajouanine syndrome, subacute necrotic myelitis of presumed vascular etiology (Foix and Alajouanine 1926); angiodysgenetic myelomalacia. These may have been lupus myelopathy.
  • Fungal infections with mass effect or thrombosis (DeSanto and Ross 2011).
  • Genetic disorders with myelopathy include Friedreich ataxia (cerebellar symptoms), hereditary spastic paraparesis (predominantly motor, with bladder and dorsal column damage), leukodystrophies, and adrenomyelopathy (myelopathy, sometimes with affected cognition, vision, hearing, and cerebellar symptoms).
  • Granulocyte-colony stimulating factor given for immune reconstitution after autologous non-myeloablative stem cell transplantation for lupus is linked to recurrent transverse myelitis with neutrophil infiltration in 1 case and is in association with irradiation and high-dose chemotherapy in 2 others.
  • Granulomatous meningomyelitis (eg, tuberculosis).
  • Guillain-Barré syndrome (acute ascending polyradiculopathy, acute inflammatory demyelinating polyradiculopathy), which is largely a peripheral nerve disease, is more likely to cause autonomic damage, arm paresis, lost deep tendon reflexes, and cranial nerve weakness. Concomitant transverse myelitis has been reported.
  • Hematomyelia, hemorrhage; often associated with clotting deficiencies or trauma.
  • Heroin myelopathy (hypersensitivity) (Richter et al 1973; Goodhart et al 1982; Guidotti et al 1985; Helgason and Arnason 1987). Immune effects of opiates and autoantibodies as part of this myelitis have not been evaluated.
  • Herpes simplex virus myeloradiculitis (lumbosacral and bladder symptoms are prominent; myelitis may be recurrent and associated with genital Herpes lesions). Herpes simplex virus type 2 usually has an ascending pattern. A transverse myelopathy is more common with HSV-1 (Nakajima et al 1998). Sacral radiculomyelitis can be triggered by HSV-2 infections (Elsberg syndrome).
  • Herpes zoster myelitis (varicella-zoster virus).
  • Hopkins syndrome: flaccid paralysis of 1 or more limbs 4 to 7 days after an asthma attack. Anterior cord lesions in 1- to 12-year-old children with onset over 1 to 2 days are followed by permanent paralysis. CSF typically contains 20 lymphocytes and 20 polymorphonuclear neutrophils (Hopkins 1974).
  • HTLV-I–associated myelopathy (HAM) or tropical spastic paraparesis (TSP) is a slowly progressive myelopathy often with no brain involvement. It is typically ascending, but cervical cord lesions can predominate. The bladder is often hypotonic, and legs are spastic with loss of vibration sense.
  • Human immunodeficiency virus (HIV) causes (1) HIV-associated vacuolar myelopathy (a painless progressive spastic paraparesis without a discrete sensory level, with sensory ataxia and a neurogenic bladder), (2) direct infection causing a transverse myelitis, or (3) associated infections from other viruses, mycobacteria, or fungi. Immune restoration with effective HIV therapy can provoke transverse myelitis (immune reconstitution inflammatory syndrome; IRIS), sometimes in association with connective tissue disease.
  • Human Herpes virus 6 (causes progressive spastic paraparesis or acute multiple sclerosis-like episodes).
  • Infection: Bacteria, abscess, acute meningitis with Borrelia, brucellosis, cat-scratch disease (Bartonella henselae), Campylobacter jejuni (see the “Pathogenesis and pathophysiology” section), chlamydia, erythema infectiosum (Nagahama et al 1992; Knebusch et al 1998), Legionella pneumophila, psittacosis, rickettsia such as Coxiella burnetii (Q fever), R diaporica, and R tsutsugamushi (scrub typhus), Rochalimaea, Salmonella paratyphi B, non-typhi Salmonella, syphilis (especially tabes dorsalis), Toxocara canis (leg sensory, motor, and autonomic problems), leptospirosis, Lyme disease (neuroborreliosis). Mycoses, histoplasmosis; mycoplasma pneumoniae (the most frequent etiology of autoimmune neuroinflammation, is associated with anti-neuronal antibodies that appear 2 to 4 weeks after the infection). Tuberculous meningitis, tuberculoma (see “Parasites and virus infections,” below).

    M pneumoniae, M tuberculosis, mumps, and non-specific respiratory infections may cause rapid onset of severe, progressive necrotizing myelopathy. Bacterial meningitis can present with hyperintensities of the central cord (Kastenbauer et al 2001; Roos 2001). Many of these are case reports, so spurious associations, and amplification of preexisting symptoms by fever, are possible.
  • Intermittent claudication of the cauda equina is caused by narrowing of the lumbar spinal cord. Rarely, claudication of the cord is caused by spinal AVM, atherosclerosis, thrombosis of terminal aorta, syphilitic arteritis, or lumbar spondylosis with disc protrusion.
  • Lupus myelopathy. See connective tissue disease.
  • Lyme disease (borreliosis, erythema chronicum migrans; Bannwarth syndrome, lymphocytic meningoradiculitis) in both acute and chronic stages of infection. A lymphocytic meningitis is associated with myelitis alone or with acute radiculoneuritis.
  • Metabolic and nutritional (chronic liver disease or hepatic shunt myelopathy, diabetes mellitus, vitamin B12 or vitamin E deficiency, pellagra).
  • Metachromatic leukodystrophy (slowly progressive peripheral nervous system and supratentorial signs).
  • Myasthenia gravis (see thymectomy, below).
  • Multiple sclerosis. These patients are typically younger and have patchy disseminated demyelination (Bakshi et al 1998). Transverse myelitis can be the first sign of multiple sclerosis or can appear as an exacerbation. The incidence of this overlap syndrome of acute transverse myelitis in multiple sclerosis has dropped from 60% to 5% in Japan over 30 years, strongly suggesting that environment influences the clinical profile of these demyelinating diseases (Nakashima et al 1999). The cord lesion in multiple sclerosis, however, is more often patchy (not contiguous over many segments), partial (not transverse and bilateral), and multiple with skipped, normal segments. A longitudinally extensive cord lesion of more than 2 segments suggests it is not multiple sclerosis; cord MRI abnormalities are usually more extensive in transverse myelitis. CSF abnormalities such as oligoclonal bands are more common in multiple sclerosis. A slowly evolving myelopathy is typical in primary progressive multiple sclerosis--but some of these patients may be misdiagnosed and actually have neuromyelitis optica or CNS Sjögren disease. Autoimmune disease and connective tissue disease are seldom if ever associated with multiple sclerosis; associations in many studies are likely from epidemiologic contamination with Devic or Sjögren variants.
  • Neoplastic. Extramedullary tumors are often painful and easily seen with MRI (meningeal spread from melanoma, lung, breast, or gastrointestinal tract; metastatic invasion or compression of the cord). However, an intramedullary tumor can mimic transverse myelitis (astrocytoma, dermoid, ependymoma, intramedullary glioma, hemangioblastoma, schwannoma, B cell lymphoma, intravascular lymphomatosis). A tumor typically has symptoms lasting weeks to months, enhances after Gd infusion on MRI, and less frequently causes CSF pleocytosis. (see below--paraneoplastic, eg, with small cell lung cancer.)
  • Neuromyelitis optica (NMO) see Devic disease.
  • Paraneoplastic myelopathy, on a background of lymphoma, oat cell, non-small cell lung cancer, or other tumors, causes subacute necrotizing encephalomyelopathy. Also called necrotic myelitis, spinal necrosis, and myelomalacia. Some cases have associated hypertrophy of the cauda equina. The course is acute or subacute, and the ascending paraplegia is followed by rapid deterioration and death (Ojeda 1984; Rudnicki and Dalmau 2000). Thoracic onset in the center of the cord progresses rostrally and caudally over days to weeks. Anti-Ri is associated with paraneoplastic myelitis. Antibodies to collapsin response-mediator protein-5 (CRMP-5-IgG, aka CV2) are associated with a constellation of optic neuritis, vitreous inflammation with CD4 lymphocytes, CSF oligoclonal bands, and occasionally with extensive or patchy cord lesions (Pittock and Lucchinetti 2006) and underlying small cell lung cancer. Twenty-seven percent of patients with antibodies to amphiphysin IgG have inflammatory transverse myelitis (Pittock and Lucchinetti 2006). Antibodies to amphiphysin syndrome are associated with breast cancer and also stiff-man syndrome.
  • Parasitic. Schistosomiasis, typically S mansoni or S haematobium, causes myelopathy with lumbar pain, lower limb radicular pain, muscle weakness, sensory loss and bladder dysfunction, and lesions at T12-L1 and the conus (Ross et al 2012). Rarely causing cord symptoms are Ascaris suum or Toxocara canis (visceral larva migrans), cysticercosis, echinococcosis, gnathostomiasis, malaria, paragonimiasis, toxocara canis (cord lesions are several segments long), toxoplasmosis (Knebusch et al 1998; DeSanto and Ross 2011), and trypanosomiasis.
  • Pelizaeus-Merzbacher disease (early onset, slow progression, supratentorial symptoms, family history).
  • Postinfectious encephalomyelitis is an autoimmune, parainfectious and not a primary virus infection. This is seen in children and young adults after measles (incidence = 3 in 100,000), chickenpox/varicella, dengue, rubella, mumps, scarlet fever (Miller et al 1956), and other virus infections (below) as well as mycoplasma. Many of these viruses also cause primary invasion.
  • Postvaccinal encephalomyelitis (seen with rabies, especially with brain antigens in the vaccine preparation; smallpox) (Fenichel 1982). Postvaccinal encephalomyelitis is most common in older subjects; young adults are affected more than infants (Alvord 1985). There are many reports of an association with recombinant hepatitis B vaccine (Tartaglino et al 1996); larger epidemiologic studies dispute this (Asherio et al 2001). Pertussis and influenza vaccination do not appear to cause acute transverse myelitis (Fenichel 1982). There are scattered reports following millions of vaccinations for cholera, influenza, Japanese encephalitis, DPT, measles, mumps, rubella, polio, and typhoid. However, epidemiologic studies have not established a causal link.
  • Radiation myelopathy (with exposure over 50 Gy). Damage is delayed up to 15 years after exposure but is typically 10 to 16 weeks later (Yamada et al 1987). Radiation myelopathy causes vasculopathic and sometimes anterior horn cell, changes with high MRI T2 signal and swelling.
  • Referred pain (cervical rib, brachial plexus tumor or plexitis, visceral mass, myocardial ischemia).
  • Sarcoidosis enhances with Gd on MRI. Cord symptoms may precede brain lesions but are uncommon.
  • Serum sickness (anti-tetanus serum or others). Local neuritis or polyneuritis is much more common than acute transverse myelitis.
  • Sjögren disease--(see connective tissue disease).
  • Spider bite (brown recluse).
  • Stiff-person syndrome, most common in women, is lowly progressive spasticity, stiffness, and cramps described by Moersch and Woltman in 1956. It is associated with antibodies to glutamic acid decarboxylase (GAD65) on a background of diabetes mellitus, or occasionally with antibodies to amphiphysin on a background of adenocarcinoma of breast.
  • Subacute combined degeneration (from vitamin B12 deficiency; funicular myelopathy—European terminology for long tract degeneration). Affects dorsal columns, corticospinal tact, and peripheral nerves. Serum B12 levels are usually low, but confirmation may be necessary with elevated serum homocysteine and methylmalonic acid--which are more specific.
  • Subacute myelo-opticoneuropathy; iodochlorohydroxyquinoline toxicity (Donati et al 1990).
  • SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) has occurred in association with Devic disease.
  • Syphilis. The relevant classic syndrome is tabes dorsalis, but tertiary syphilis (meningomyelitis) can cause acute paraparesis (Hiz et al 2008).
  • Syrinx. Syringomyelia can cause slowly evolving symptoms. Extensive central cord plaques could also evolve into a transient or chronic syrinx.
  • Systemic lupus erythematosus--see connective tissue disease.
  • Tetanus causes spasticity.
  • Thymectomy for myasthenia gravis increases the risk of neuromyelitis optica by 150-fold (Kister et al 2006). This may be due to the underlying disease and not the thymectomy. Four women--2 black, 1 white, and 1 Chinese--developed Devic disease 1, 5, 2, and 10 years after thymectomy. Longitudinal lesions were 5.5 cord segments at onset and at least 10.5 later. NMO-IgG was positive in 2/3, ANA in 2/4, anti-acetylcholine receptor in 4/4, and stiff-man syndrome in 1. Interferon beta may have exacerbated disease in one. Because 1/8 thymectomized patients develop autoimmune diseases, it is postulated that elimination of thymic suppressor cells leads to overactive T and B cell responses.
  • Toxins include arsenic, clioquinol, diethylene glycol [Sterno] with delayed ascending paralysis 8 days after injection, intrathecal chemotherapy, intrathecal radiological contrast media, nitrous oxide abuse, and orthocresol phosphate. Nitrous oxide abuse inactivates methylcobalamin. In medical and dental settings, “anesthesia paresthetica” can develops up to weeks after exposure to nitrous oxide.
  • Trauma to the cord.
  • Tropical ataxic neuropathy (in Mozambique this is from cyanide in cassava roots).
  • Tuberculosis. Compression arises from a dural tuberculoma, intramedullary tuberculoma, tuberculous spondylitis (Pott’s disease), spinal cord infarction, or tuberculous myelitis.
  • Tumor -- see neoplastic.
  • Ulcerative colitis associated with transverse myelitis.
  • Vaccinations (see postvaccinal encephalomyelitis, above).
  • Vascular lesions from arterial occlusion, especially anterior spinal artery of Adamkiewicz, rarely posterior spinal artery, and acute occlusion of terminal aorta; arteriovenous malformation (AVM), spinal dural arteriovenous fistula, cavernoma of conus medullaris, venous thrombosis, impaired venous drainage by a disc herniation or fibrocartilaginous embolism from a ruptured disk, percutaneous embolization; or postsurgical—aortic reconstruction with hypotension during surgery). Cobb syndrome, with skin and spinal cord angiomas.

    An ischemic or hemorrhagic vascular etiology is likely if symptoms peak within 4 hours (Group TMCW 2002) or stepwise. Acute myelitis is mimicked by occlusion of the anterior cerebral artery (loss of sphincter function, but no loss of pain sensation augurs a poor outcome). AVMs are rare but can lead to subarachnoid hemorrhage or focal cord lesions. Hemorrhage into the cord or subarachnoid space presents with sudden severe back pain, spreading to different levels and nerve roots, with meningeal irritation. Chronic AVM damage is slowly progressive, occasionally stepwise. Venous congestion causes diffuse high T2 MRI signal and flow voids in vessels on dorsum of cord. Central or transverse infarcts are linked to peripheral vascular disease and arterial hypotension (Novy et al 2006). Oligoclonal bands are usually negative, and patients often are older than 50
  • Virus infections. The most common viruses causing myelitis are enterovirus, HSV-2, and Varicella-zoster. There are scattered case reports of associations with adenovirus, cat scratch fever, Coxsackie strains A and B, cytomegalovirus, dengue 2 virus, echovirus types 2, 5, 6, 11, 18, 19, 25, and 30, enterovirus 71, Epstein-Barr virus, ECHO virus, hepatitis A, B, C, and E (Stubgen 2011), HIV, HTLV 1 and 2, herpes simplex (HSV) types 1, 2, and 6, Herpes zoster with or without shingles, influenza, Japanese encephalitis virus, lymphocytic choriomeningitis virus, mumps, Murray Valley encephalitis virus, parvovirus b19, poliovirus 1, 2, and 3, rubeola, rubella, Russian spring-summer encephalitis, St Louis encephalitis virus, acute varicella (VZV), and West Nile flavivirus (Miller et al 1956; Christensen et al 1990; Knebusch et al 1998).

    Coxsackie, enterovirus, poliovirus, and West Nile virus can cause acute flaccid paralysis. HSV-2 can cause sacral radiculomyelitis sometimes associated with genital lesions; HSV-1 can cause recurrent ascending myelitis (Shyu et al 1993). Hepatitis viruses appear to cause an autoimmune myelitis, probably not from direct invasion. Parainfectious conus myelitis causes bladder hesitancy and retention, occasional sacral and lumbar sensory loss, and motor weakness (Pradhan et al 1998). Recent infection, rash, stiff neck, acute onset, and elevated CSF cell count are suggestive of a virus infection
  • Vitamin deficiency. Low vitamin B12 causes subacute combined degeneration (see above). Low folate may cause symptoms similar to B12 deficiency, but is often not clearly associated with neurologic problem. Vitamin E deficiency causes progressive spinocerebellar problems and damages dorsal columns, corticospinal tract, and peripheral nerves.
  • Vogt-Koyanagi-Harada disease, uveomeningoencephalitis, a disorder of melanin-forming cells (Lubin et al 1981). CNS symptoms coexist with iridocyclitis, uveitis, and cutaneous abnormalities.

In This Article

Historical note and nomenclature
Clinical manifestations
Clinical vignette
Pathogenesis and pathophysiology
Differential diagnosis
Diagnostic workup
Prognosis and complications
References cited