Neuroimmunology

Updated 12.10.2021
Released 05.08.1995
Expires For CME 12.10.2024

Transverse myelitis

Authors: Anthony T Reder MD, Sara Klein MD

Introduction

Overview

Transverse myelitis is inflammation that spans across both sides of at least one segment of the spinal cord. The inflammation leads to injury of the myelin, which protects the nerve fibers. There are multiple etiologies for transverse myelitis presentation. In this updated article, the author describes new developments in the diagnosis of subgroups of myelitis caused by myelin oligodendrocyte glycoprotein (MOG)-Ab and its comparison to multiple sclerosis and neuromyelitis optica.

Key points

	• Acute transverse myelitis, as defined here, is idiopathic and excludes other forms of myelitis [neuromyelitis optica, postinfectious and postvaccinal myelitis, multiple sclerosis, myelin oligodendrocyte glycoprotein (MOG)-Ab, etc.].
	• Cord symptoms evolve over hours to days and then typically resolve over several weeks or months.
	• The pathology is similar to multiple sclerosis, but only 40% will develop multiple sclerosis.
	• Cord lesions in neuromyelitis optica (NMO, Devic disease), MOG-Ab, and CNS Sjögren disease are longitudinal, down the center of the cord; in multiple sclerosis the lesions are shorter and acentric.
	• High-dose glucocorticosteroids hasten recovery but have no long-term benefit.

Historical note and terminology

Transverse lesions of the spinal cord were ascribed to thrombosis that was caused by arteriosclerosis, syphilis, and other infections by Bastian in the 1880s (53), and this concept persisted well into the next century. Foix and Alajouanine also believed that transverse myelitis had a vascular etiology (52). They described two patients with subacute necrosis in the sacral or thoracolumbosacral cord associated with massive dilatation and endomysial hypertrophy of the extramedullary veins and similar but less marked changes in the intramedullary vessels. The lumens were not obliterated, and the arteries were not involved. The term "angiodysgenetic necrotizing myelopathy" is sometimes applied to this condition (53). A similar syndrome is believed to be caused by spinal dural arteriovenous fistulae, although Mirich and colleagues found no arteriovenous malformations in 4 typical cases of subacute necrotizing myelopathy (117). Paine and Byers were the first to report a large clinical series with follow-up exams and used the term “transverse myelopathy” (131). They also postulated a vascular cause but did not present any pathological evidence. In most of these early reports, one or two patients were studied, and the autopsies were performed months to years after the original illness (77).

Autopsies from patients with acute transverse myelitis seldom show significant vascular alterations. Lipton's series of 34 contained only two cases with infarcts of unknown etiology and one with hemorrhage plus telangiectasias (107).

Other investigators assumed the condition was an inflammatory myelitis from an antigen-antibody reaction (139) or a hypersensitivity reaction to infection or vaccination (121). Histology showed demyelination, variable destruction of axons, and differing degrees of mononuclear cell infiltration. (There was loss of myelin in the cases of Foix and Alajouanine, but this does not prove that demyelination was the primary event.)

Several large series appeared in the 1960s and 1970s (04; 107; 148; 20). A consensus evolved that acute transverse myelitis was an inflammatory demyelinating disease of the cord. It sometimes followed infections, but usually had no antecedent. In a series of 33 cases of acute or subacute noncompressive myelopathy, 46% were parainfectious, 12% were associated with cord ischemia, 21% were multiple sclerosis exacerbations, and 21% were idiopathic (80). The underlying infection is seldom diagnosed.

Many types of cord lesion or systemic disease can cause a transverse spinal cord syndrome or myelopathy. Etiologies are infectious, neoplastic, compressive, traumatic, embolic, degenerative, or vitamin-substrate deficiency. However, acute transverse myelitis, as defined here, is an idiopathic disorder caused by inflammation of the spinal cord, associated with marked demyelination and often with significant axonal loss. The process that instigates the inflammation in transverse myelitis is unknown. (This includes the third of transverse myelitis patients with antecedent virus infections.)

Specific diagnostic criteria for transverse myelitis have been proposed (63). These include (1) neurologic symptoms attributable solely to the spinal cord, ie, negative brain MRI and no clinical brain symptoms, (2) bilateral signs or symptoms, (3) clearly defined sensory level, (4) MRI exclusion of compression, (5) inflammation in the spinal cord (CSF cells or IgG index, or MRI gadolinium enhancement) seen at onset or within 7 days, (6) progressive worsening with maxima from 4 hours to 21 days after onset, and (7) no other etiology. With these strict criteria, only 16% of 288 patients with acute transverse myelitis from all causes have idiopathic acute transverse myelitis (40). Scott and colleagues argue that inflammation is less common in transverse myelitis than in multiple sclerosis and, thus, inflammation should not be used as a criterion (159). Acute transverse myelitis can be split into complete or partial transverse myelitis, each with a different outcome (156).

These definitions are undergoing revision. A subset of transverse myelitis is associated with antibodies against aquaporin-4 (“NMO-IgG”, ie, neuromyelitis optica [NMO], Devic disease), and another partially overlapping subgroup is associated with Sjögren disease (78). These differ markedly from multiple sclerosis. Unfortunately, many of the classic treatises on idiopathic transverse myelitis include some of these patients.

Clinical manifestations

Presentation and course

Symptoms of transverse myelitis usually evolve over hours or sometimes over a week or two, but rarely will develop within minutes or stutter over a month (107; 148; 46; 63). Before the onset of neurologic dysfunction, there can be nonspecific complaints such as fever or muscle aches. Although the clinical signs are bilateral (ie, from "transverse" or horizontal cord lesions), there is usually also longitudinal expansion of cord pathology. Ascending symptoms are presumably from a lesion expanding both rostrally and caudally. In theory, lesions spreading centripetally from the meninges inward through somatotopic layers of the long tracts could cause ascending symptoms, but peripheral cord tracts are preserved compared to deeper fibers, making this unlikely.

Complete transverse myelitis (the main subject of this article) and partial transverse myelitis differ. The spinal cord damage in acute complete transverse myelitis generally affects all cord functions, and the symptoms are typically more severe than in typical cord lesions of multiple sclerosis. When inflammatory cord lesions are not transverse, the partial cord lesion causes a Brown-Sequard syndrome. Acute partial cord lesions cause unilateral or markedly asymmetric bilateral sensory and motor dysfunction (159; 156). This asymmetric picture is more often associated with multiple sclerosis (115; 54).

The first symptoms in transverse myelitis are ascending paresthesias or back pain at the level of the myelitis, plus leg weakness and sphincter dysfunction (04; 148; 46). Tingling or paresthesias in the feet soon progress to loss of pain, temperature, and vibration sensation, and then halt at a sensory level, usually thoracic (approximately 80%). There is an encircling band of hyperesthesia at the dermatome right above the sensory loss in one third of cases. Cervical levels are less commonly involved. There may be a dermatomal band of hyperesthesia two or three segments more rostrally, and pain is often interscapular. Weakness is usually flaccid at onset ("spinal shock"). In two thirds of cases, weakness is severe, with inability to walk, and often evolves to total leg paralysis and spasticity. The arms are weak in one fourth of cases and are occasionally involved before the legs. Later, deep tendon reflexes become brisk. Five percent of patients have respiratory weakness. Tonic spasms and Brown-Sequard symptoms can occur. Damage to autonomic pathways can cause a sweat level, adynamic ileus, anorgasmia, paroxysms of hypertension and sweating or poikilothermia, autonomic dysreflexia with paroxysms of sympathetic output due to renal denervation, myocardial ischemia, and orthostatic hypotension--especially with higher level lesions. Association with acute motor axonal neuropathy has appeared several times. Bladder and bowel function is frequently lost and is often heralded by urinary retention. Acute lumbosacral myelitis causes bladder symptoms and anogenital sensory loss. Neurogenic pruritis can appear with transverse myelitis. Ninety-two percent of patients with a diagnosis of neuromyelitis optica spectrum disorder and pruritus symptoms had the pruritus located within the dermatome innervated by the involved spinal cord area (69).

Symptoms typically begin to resolve in 2 to 17 days (46). The rate of resolution is most marked in the first few weeks after the symptoms have crested. Improvement is maximal in the first 3 to 6 months after disease onset but may continue for several years. Recovery can be complete, but many of the motor, sensory, and autonomic symptoms persist. Idiopathic acute transverse myelitis is commonly monophasic, with a low risk of reoccurrence. However, 0% to 30% of patients with acute transverse myelitis go on to develop multiple sclerosis over a 5- to 10-year period, making it a presenting feature of multiple sclerosis (51).

Children comprise approximately 20% of total cases of acute transverse myelitis (170). In children, acute transverse myelitis follows a similar clinical course. However, paresthesias are less common, and recovery is more frequent (131; 46). Fifty-eight percent report pain, 28% motor symptoms, and 11% numbness; 61% had T2 MRI brain lesions (171). In 27 children with non-Devic acute transverse myelitis, lesions were in the center of the cord, with a median length of five segments (03). Forty-three percent had swelling. Recurrences were only 6% over 5 years (03). Cognition is normal.

Recurrent transverse myelitis, without evidence of multiple sclerosis and with negative MRI and CSF studies, is unlikely to progress to multiple sclerosis but is sometimes part of the NMO/Devic disease spectrum (172; 174; 56; 92; 76; 28). Recurrent myelitis is associated with brucellosis and hepatitis C infection (62). Recurrent idiopathic myelitis is usually considered to be rare. However, recurrences were 6% over 5 years (03), and 17% over 1.4 years in Europe (38). It was recurrent in 31% of 13 transverse myelitis cases in Pavia, Italy (142), 31% of 34 cases in Baltimore (93), 47% of 30 patients with partial transverse myelitis over 5 years in Pennsylvania (159), 61% of 41 cases from Rio de Janeiro, Brazil (05), and 69% of 29 cases from Guangzhou, China (104). Risk of recurrence increases with African ancestry, female sex, CSF IgG index, oligoclonal bands, and low vitamin D levels (93).

Three patients selected from all spinal cord syndromes at Graz Medical University in Austria had relapsing acute transverse myelitis. All three had necrotizing inflammation and severe disability (160), and in retrospect they may have had Devic disease. Four of 17 tested in the Brazilians were positive for NMO-IgG, and three of these were recurrent, again suggesting significant mixing of transverse myelitis with Devic disease in a second series (05), and likely many other reported cases of recurrent myelitis. Neuromyelitis optica and CNS Sjögren disease are discussed in the differential diagnosis section.

Prognosis and complications

The sequelae of transverse myelitis are variable, even after severe paralysis. One third of patients recover completely, one third does not improve from their nadir, and one third has some degree of residual symptoms (107; 148; 20; 46). Patients with multiple sclerosis-like acute partial myelitis have a better short-term prognosis and are more likely to recover than patients with acute complete transverse myelitis. Recurrences are unusual in acute transverse myelitis compared to multiple sclerosis (172; 80). Some patients have lasting motor, sensory, or urologic complaints. Persistent genitourinary symptoms include detrusor hyperreflexia, detrusor-external sphincter dyssynergia, and erectile dysfunction (18).

Bad prognostic indicators include a catastrophic onset, severe weakness, initial lancinating pain, sensory disturbance at cervical levels, spinal shock, incontinence, no recovery after 3 months, long cord lesions, and presence of 14-3-3 protein in the CSF (75). Pain is more common in neuromyelitis optica; misdiagnosed neuromyelitis optica patients could affect some epidemiological studies. Favorable prognostic signs include subacute progression of sensory or motor symptoms over days or weeks, youth, retention of posterior column function and deep tendon reflexes, and early recovery (107; 148). In addition, the chance of recovery is poor when somatosensory evoked potentials show a conduction block, but good when somatosensory evoked potentials are normal or only slightly delayed (178; 83). CSF cells or protein do not predict outcome (04; 148).

In 50 Japanese children, younger patients and those with hypotonia had a worse prognosis (120). Also ominous are need for respiratory support and high cord lesions (21). Many of these children (62%) had residual deficits. This contrasts with other studies with good functional outcomes in 50% (131), 56% (37), and 62% of children with myelitis (46).

The incidence of multiple sclerosis in transverse myelitis ranges from 0% over 6.5 years (37), 1% over 15 years (20), 5% over 8 years in children from Chongqing, China (29), 6% over 5 years (04), 3% after 5 years (107), 3% over 6 years (07), or 8% to 14% after an average of 5 years (148), 13% over 4.5 years—four fifths had brain lesions at presentation (171), 29% over 5 years (137), 40% of 20 patients over 12 to 30 months (35), or 45% over 6 years (36). The second attack, ie, multiple sclerosis, is most likely to occur 1 year later and unlikely if 2 years have passed (137).

Acute complete transverse myelitis, with long central lesions, only occasionally evolves into multiple sclerosis; acute partial transverse myelitis with short, acentric, asymmetric lesions evolves to multiple sclerosis more frequently (159). Partial cord lesions with negative MRI will evolve to multiple sclerosis in 2% to 25%, partial myelitis with multiple sclerosis-like brain lesions evolves to multiple sclerosis in 44% to 85% (156; 137; 161). Compared to patients with partial cord lesions, those with complete transverse myelitis have less frequent oligoclonal bands, relapses, and multiple sclerosis. In contrast, partial cervical myelopathy and transverse myelitis without initial brain MRI lesions often evolves into clinically definite multiple sclerosis, especially if evoked potentials and CSF are abnormal (16; 137). Many of the older series are likely to have included patients with neuromyelitis optica or CNS Sjögren disease.

The following features increase the risk of developing multiple sclerosis: (1) partial, rather than complete, transverse myelopathy and more than one cord lesion; (2) cranial MRI suggestive of multiple sclerosis after a transverse myelopathy, especially with multiple lesions, infratentorial plaques, high burden of disease, and development of new brain lesions on repeat scans (these suggest the myelitis is not the first episode of demyelination); (3) CSF IgG or IgM oligoclonal bands; (4) abnormal visual or sensory evoked potentials (less helpful than MRI); (5) HLA-DR2 positive status (16); and (6) family history of multiple sclerosis.

A hemicord lesion or disseminated lesions modify prognosis. In acute partial myelitis, the unilateral cord lesion is incomplete or patchy. It appears to be an entity separate from acute complete transverse myelitis. In slightly more than 3 years, 12 of 15 (80%) patients with acute partial myelitis developed multiple sclerosis (54). In a comparable study of acute partial cord syndromes, 14 of 38 patients developed multiple sclerosis within 18 months (115); 13 of these had disseminated MRI lesions at the onset of myelitis. Fourteen of 25 had positive oligoclonal bands at onset; 10 of them developed multiple sclerosis, but only 1 of 11 without oligoclonal bands progressed to multiple sclerosis. In 52 patients presenting with acute partial transverse myelitis, 30 developed multiple sclerosis over 3 years (34). Predictors of multiple sclerosis in acute partial transverse myelitis are the following: black Afro-American descent, initial sensory symptoms, lateral-posterior lesions, Gd-positive cord lesions, abnormal brain MRI, and positive CSF oligoclonal bands.

With a normal MRI, acute partial transverse myelitis seldom leads to multiple sclerosis, despite the fact that this type of lesion (one segment in length, acentric) is typical in multiple sclerosis. In the largest series, only three or four of 30 patients (10% to 13%) developed multiple sclerosis over 5 years (159); eight of 13 tested had oligoclonal bands, but only one of them developed multiple sclerosis. When the brain MRI is abnormal, however, the chance of developing multiple sclerosis is 80% to 90%. In other, smaller series in 1995 and one in 1997, eight of 24 patients had positive bands, and four developed multiple sclerosis over 2 years (159).

In established multiple sclerosis, when acute transverse myelitis appears, it is associated with later onset and optic neuritis, but with fewer brainstem, cerebral, or cerebellar symptoms and fewer lesions on MRI (55). (Note: These are Japanese patients. A Devic-like syndrome is more common in Japanese than in European patients.) In another series, 15 out of 16 patients with acute myelopathic multiple sclerosis had asymmetric motor or sensory symptoms, but 19 out of 20 acute transverse myelopathy patients had symmetric weakness and sensory symptoms (157). NMO-IgG is rare with short cord lesions in the United States; only 1 of 22 in acute partial transverse myelitis, but 3 of 4 in Devic disease, and none of 6 in multiple sclerosis (158).

Clinical vignette

A 30-year-old marathon runner and commodities broker developed a minor “cold,” and 10 days later noticed tingling in the middle of his trunk. The tingling was soon followed by paresthesias in his feet and then loss of sensation from below the mid-thoracic level with a 4 cm hyperesthetic band above. In conjunction, he developed profound weakness of both legs and urinary retention. He had no symptoms above the thoracic level. MRI scan of the brain was normal, but a spinal cord MRI showed swelling and diffuse abnormal T2 signal from the T-5 to the T-10 level. Spinal fluid had protein of 113 mg/100 ml, glucose of 66 mg/100 ml, 65 lymphocytes/mm3, and no oligoclonal bands. He refused therapy with glucocorticoids.

The symptoms lasted for 3 weeks and then began to resolve. Over the next 2 years, muscle strength gradually returned. He reported that improvements in a given muscle group were often heralded by muscle cramping and aches. At 2 years, sensation and bladder function was essentially normal, and he was running 4 miles per day.

Biological basis

Etiology and pathogenesis

Two thirds of acute transverse myelitis episodes are idiopathic. Virus infections seem to trigger one third of the cases of transverse myelitis in adults and at least half of the cases in children (107; 20; 171). In children, one half to two thirds have preceding infection (120). The pathological hallmark of transverse myelitis is the presence of lymphocytes and monocytes, plus astroglial and microglial activation in the spinal cord, with varying degrees of both axonal injury and demyelination. Transverse myelitis typically develops 3 to 15 days after an upper respiratory infection (131; 80). Some reported viral triggers include adenovirus; cat scratch fever; COVID-19; coxsackievirus strains A and B; cytomegalovirus; dengue 2; echovirus; enterovirus; Epstein-Barr virus; enteric cytopathogenic human orphan (ECHO) virus; hepatitis A; HSV types 1, 2, and 6; Herpes zoster; influenza; lymphocytic choriomeningitis virus; mumps; poliovirus; rubeola; rubella; Russian spring-summer encephalitis; and varicella (116; 95) (See differential diagnosis). There are occasional case reports of transverse myelitis following various immunizations, but a true disease association is not evident in controlled studies (below). Transverse myelitis with a more indolent course over several days or weeks has been described as a rare presentation of both HIV and HTLV-1 infections.

A virus could cause transverse myelitis through: (1) direct damage to parenchymal cells (eg, subacute sclerosing panencephalitis and possibly AIDS myelopathy); (2) a "bystander effect" damaging the cord during an immune response against the virus, or damage from release of virus-induced cytokines or superantigens that activate immune cells (eg, heat shock protein from mycoplasma); and (3) sensitization of the host to brain antigens during an inflammatory response, eg, release of damaged myelin (processed by antigen-presenting cells) or cross-reactivity between virus and myelin antigens. Examples of the latter include postinfectious encephalomyelitis (100) and postvaccinal encephalomyelitis, especially following rabies vaccination containing duck embryo CNS components and, arguably, following recombinant hepatitis B vaccine (169). The latter correlation does not hold in large series (10). Viruses trigger most episodes of acute disseminated encephalomyelitis, which is a true autoimmune, delayed-type hypersensitivity response against brain antigens. Similarly, postinfectious myelitis is seen after measles infection. Here, there is a clear host response to myelin basic protein, even when the virus is no longer present in the brain (81). Virus infections precede one third of multiple sclerosis relapses (133) and one third of episodes of transverse myelitis. The mechanism of the viral association with multiple sclerosis relapses is unknown.

In addition, some nonviral infections trigger acute transverse myelitis, including mycoplasma pneumoniae and, occasionally, pulmonary tuberculosis or Borrelia (95). Mycoplasma may induce neurotoxins or cause thrombosis or transient immunosuppression. It also induces interferons and polyclonal B-cell activation (02). Mycoplasma and brain antigens may cross-react and lead to anti-brain immune responses. The molecular mimicry between Campylobacter jejuni lipo-oligosaccharides on the surface of the agent and human gangliosides in the peripheral nervous system induce a cross-reactive immune response. Although this cross-reactivity is less common in the central nervous system, there have been cases of transverse myelitis after Campylobacter jejuni enteritis with associated antiganglioside antibodies (108). The previous literature has noted childhood acute transverse myelitis with positive anti-ganglioside GM1 antibodies (84).

At autopsy, the lesions in acute transverse myelitis are restricted to the cord. The histology differs somewhat from multiple sclerosis. In cord lesions from multiple sclerosis, many axons are usually preserved, and the lesions are scattered (primary demyelination). In acute transverse myelitis, although myelin loss does exceed axonal loss, axons are usually destroyed along with the demyelination, and secondary demyelination may result. In severe transverse myelitis, the lesions may be cavitary. Cases with scattered lesions are less common and this suggests multiple sclerosis. The lesions in acute idiopathic transverse myelitis are bilateral and somewhat symmetrical and are typically central, with relative preservation of tissue at the periphery; in multiple sclerosis, lesions often begin at the pial surface (Partial cord lesions, or transverse myelitis plus scattered CNS lesions on MRI, frequently evolve into multiple sclerosis or are exacerbations of established multiple sclerosis).

Transverse myelitis (MRI of central cord)

(Left) Proton density cross-section of thoracolumbar junction with suggestive increased signal intensity in central cord. (Right) T2-weighted image showing increased signal in central cord, surrounded by rim of normal signal, in t...

In transverse myelitis, there is perivascular spread of monocytes, lymphocytes infiltrate focal areas of the cord, and there is astroglial and microglial activation. In some acute cases of transverse myelitis, polymorphonuclear leukocytes and lymphocytes infiltrate the meninges, and macrophages infiltrate the parenchyma. The presence of polymorphonuclear leukocytes suggests high levels of IL-17, and a different immune etiology than in typical forms of transverse myelitis. The pattern of spread is difficult to discern based on autopsy findings, but at autopsy and on MRI there is relative preservation of subpial parenchyma. This suggests ischemia, possibly from small vessel arachnoid vasculitis, as the ultimate cause of the cord lesions in transverse myelitis and in the possibly related Devic disease.

It could be argued that the pathology of transverse myelitis and optic neuritis is similar to that in multiple sclerosis. These are perhaps the earliest, and sometimes only, manifestations of multiple sclerosis, or could be related but limited demyelinating diseases.

Related syndromes show somewhat distinct pathology. In multiple sclerosis, lesions appear at different times and have different distributions. The lesions in acute disseminated encephalomyelitis are monophasic. In acute disseminated encephalomyelitis and associated conditions (perivenous encephalomyelitis, postinfectious encephalomyelitis, and postvaccinal encephalomyelitis), there is widespread perivenous lymphocytic-histiocytic inflammation, mostly within the white matter. There are small foci of demyelination (0.1 to 1 mm), but the contiguous demyelination of acute transverse myelitis is not seen (06).

Some other related conditions are necrotizing, in addition to having the inflammatory and demyelinating components, eg, acute hemorrhagic leukoencephalitis, progressive necrotizing myelopathy, and Devic disease. Distinction between these diseases rests on more than the degree of inflammation accompanying the demyelinating process. The clinical course, the histology, serum markers, and dissemination of lesions in space and time all differ.

Acute hemorrhagic leukoencephalitis is a monophasic, possibly post-viral syndrome that affects the cord, hemispheres, and brainstem. The CSF contains elevated protein and up to 3000 cells. Mononuclear cells appear first, followed by polymorphonuclear leukocytes. There are widespread perivascular cellular infiltrates, small perivascular hemorrhages, and necrosis, often to the point of liquefaction.

In Devic disease, as well as in transverse myelitis, axons and myelin are destroyed in the center of the cord; there is some preservation in subpial areas. In contrast to multiple sclerosis, in both Devic disease and transverse myelitis, the CSF contains elevated protein and tends to have transient or no oligoclonal bands, and a swollen cord is often visible on MRI. In an early study, antibodies to myelin-associated glycoprotein were present in all cases of neuromyelitis optica (66). A more specific marker, antibodies to aquaporin 4 (NMO-IgG), appears in two thirds of patients with neuromyelitis optica. This antibody defines a subpopulation of optic neuritis and myelitis cases separate from multiple sclerosis. Therapies differ between the two entities (102). (See Sjögren variant, section 12.)

Paraneoplastic necrotizing myelitis is acute or subacute and causes a necrotic "carcinotoxic myelodegeneration," with patchy bilateral destruction of myelin, axons, and neurons. Necrosis is massive and hemorrhagic. Inflammation is mild. The blood vessel walls are thickened and contain occasional fibrin thrombi (129).

The MRI appearance of acute transverse myelitis at times suggests arterial or venous ischemia in combination with demyelination (168). Another group of myelopathies has pronounced vascular changes (Foix-Alajouanine syndrome) (52). Many of these patients do have arteriovenous malformations.

Immune cells secrete inflammatory cytokines that affect spinal cord cells. For instance, IL-6 is increased in CSF in multiple sclerosis and inflammatory neurologic diseases (110); other cytokines, such as IL-8, IL-10, and matrix metalloproteases-2 and -9, are also increased. It is elevated 300-fold in idiopathic transverse myelitis compared to mixed neurologic controls (85). IL-6 is secreted by astrocytes, and to a lesser extent by microglia. It binds to oligodendroglia and axons and also induces more IL-6 production by astrocytes. High levels of IL-6 in the spinal cord directly cause death and dysfunction of CNS cells, and indirectly are toxic by inducing nitric oxide synthetase in microglia, which elevates nitric oxide. Moderate to high levels of IL-6 damage spinal cord cells in organotypic cultures. In contrast, brain cells are spared, and low IL-6 doses are actually neuroprotective, possibly because the brain has higher levels of the soluble IL-6 receptor that blocks IL-6 toxicity (85). IL-6 and IL-17 are secreted by peripheral blood cells at high levels in transverse myelitis (60).

High IL-6 levels correlate with tissue injury and with sustained clinical disability. IL-6 and other cytokines induced by interferon beta could similarly enhance spasticity, especially in multiple sclerosis patients with preexisting cord lesions (22). In parallel interferon-induced IL-6 levels correlate with fever (122). Interferon-beta induces IL-6 but also other members of the IL-6 superfamily, such as neurotrophic leukemia inhibitory factor and neuroprotective LIF (24). An “inverted U” effect of IL-6 induced by inflammation or interferon-beta could cause spinal cord repair, dysfunction, or damage depending on local IL-6 levels.

B cells are expanded in the blood and CSF in transverse myelitis (105). Immunoglobulins are also abnormal. There is extensive editing of immunoglobulins in multiple sclerosis and in transverse myelitis, but not in optic neuritis.

Whole-exome sequencing of sisters with idiopathic transverse myelitis compared to healthy siblings found a rare missense variant in VPS37A (c.700C> A, p.Leu234Ile), but the authors concluded that further studies are needed to determine the frequency of the variant in the patient population (113). VPS37A encodes a component of the endosomal sorting complex required for transport (ESCRT-1), which is one of several complexes that is involved in membrane remodeling.

Differential diagnosis

Many processes can cause an acute transverse myelopathy and need to be differentiated from idiopathic demyelinating transverse myelitis, as therapy differs (63; 102; 49). Pathology and workup of related diseases are discussed in the pathogenesis, pathophysiology, and diagnostic workup sections.

Transverse myelitis can be recurrent, but other diseases 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 (162). 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) (74). Recurrence occurs with myasthenia gravis, thymic hyperplasia, and positive antinuclear antibodies (172; 106; 132; 82).

Diseases causing transverse myelopathy include the following:

	• Abscess of the spinal cord, intramedullary or epidural (usually Staphylococcus aureus) (39). 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 (180).
	• 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 (70).
	• Acute partial myelitis (54) 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 (11). Hereditary myelopathy is likely to be slowly progressive and cause spastic paraparesis and loss of vibratory sense in the legs.
	• AIDS-related myelopathy (43).
	• Allogeneic hematopoietic cell (stem cell) transplant has induced acute transverse myelitis in three patients. Symptoms have paralleled what is possibly an immune-mediated pancytopenia, presumably causing immune dysregulation (136).
	• 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 (91; 181). There are elevated eosinophils in blood, subacute onset of sensory symptoms, and extensive multi-segmental, usually thoracic, cord lesions with enhancement at the margins (181). 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 (123) or glucocorticoid therapy. Hughes-Stovin syndrome (HSS) is a lymphocytic vasculitis that is a forme fruste of Behçet disease that can cause transverse myelitis.
	• Biotinidase deficiency.
	• Cancer--see neoplastic.
	• Cauda equina syndrome plus transverse myelitis in ankylosing spondylitis.
	• Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). In addition to brainstem lesions, about two thirds of patients have spinal cord lesions (167).
	• 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, surfer myelopathy from prolonged back hyperextension, 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 (166; 112).
	• Congenital and developmental defects (spina bifida, syrinx).
	• Connective tissue diseases (lupoid sclerosis; lupus myelopathy; lupus myelitis). Transverse myelitis is seen with systemic lupus erythematous (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 (70; 01; 15; 95; 96; 74; 183). 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 (101). 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. Patients with SLE myelopathy are often females and African Americans, 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 (27). Rituximab has been used successfully in some cases of lupus myelopathy and in multiple cases of Sjögren myelopathy (78).
	The link of cord demyelination to connective tissue disease (and associated autoimmune disease and organ-specific antibodies) has been clarified by Dr. A 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 (49). 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 (79).
	• 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 (97) 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 (49).
	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 (76). Fifty-eight percent of relapsing cases were female (vs. 76% in the overall neuromyelitis optica group). The average age of onset was 44 years. Fifty percent were significantly disabled (vs. 87% overall). Oligoclonal bands were positive in 55% (vs. 26% overall). Spinal cord lesions on MRI in transverse myelitis 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 (92). 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 (28). 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 (102). Aquaporin-4 is the most abundant water-channel protein in the central nervous system. 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.
	Steroids and plasma exchange are used for the treatment of an acute attack. 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 (39).
	• Down syndrome with severe acute neuromyelitis optica may be linked to intrinsic Down abnormalities (25), 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 (33) enhance immune function (09). Beta-adrenergic blockers inhibit suppressor cell function (86). 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) and imatinib (protein-tyrosine kinase inhibitor for Philadelphia chromosome abnormality in chronic myeloid leukemia). 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 (67). A potential mechanism is that anti-TNF-alpha agents create an imbalance between immune cell proliferation, regulation, and cell death, which can lead to a paradoxical activation of lymphocytes, macrophages, and microglia. This change in activation leads to inflammation and demyelination (145).
	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 (177). 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 (173). The CSF is normal. There is no associated viral syndrome. Recovery is unlikely.
	• Foix-Alajouanine syndrome, subacute necrotic myelitis of presumed vascular etiology (52); angiodysgenetic myelomalacia. These may have been lupus myelopathy.
	• Fungal infections with mass effect or thrombosis (39).
	• 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). There is a case report of Leber hereditary optic neuropathy with extensive myelopathy resembling longitudinally extensive transverse myelitis (23).
	• 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 one case and is in association with irradiation and high-dose chemotherapy in two 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) (144; 59; 64; 70; 48). 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 (125). Sacral radiculomyelitis can be triggered by HSV-2 infections (Elsberg syndrome).
	• Herpes zoster myelitis (varicella-zoster virus).
	• Hopkins syndrome: flaccid paralysis of one 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 (73).
	• 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 opportunistic 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 herpesvirus 7 reactivation causes myelitis in transplant recipients and during HIV infection (47).
	• Human herpesvirus 6 (causes progressive spastic paraparesis or acute multiple sclerosis–like episodes). There has been a case that was in addition to transverse myelitis opso-myoclonus syndrome.
	• IgG4-related disease typically presents with pachymeningitis and hypophysitis. Spinal cord involvement is rare, but there is a documented case of longitudinally extensive transverse myelitis (175).
	• Infection. Bacteria, abscess, acute meningitis with Borrelia, brucellosis, cat-scratch disease (Bartonella henselae), Campylobacter jejuni (see the “Pathogenesis and pathophysiology” section), chlamydia, erythema infectiosum (124; 95), 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, cryptococcosis in immunocompetent patient. 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 (87; 146). 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.
	• Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency (30).
	• 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).
	• Myelin oligodendrocyte glycoprotein autoantibody (MOG-IgG)–associated myelitis. The median age of onset is within the fourth decade of life with either a monophasic or relapsing course. Clinical features favoring MOG-IgG myelitis over AQP4-IgG myelitis include prodrome symptoms of optic neuritis and concurrent acute disseminated encephalomyelitis, with lack of enhancement. MOG-IgG–associated myelitis has MRI T2-signal abnormalities confined to the grey matter, multiple longitudinally extensive T2 cord lesions, and conus involvement.
	• Myasthenia gravis (see thymectomy, below)
	• Multiple sclerosis. These patients are typically younger and have patchy disseminated demyelination (13). 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 (126). 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 two 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, gastrointestinal tract, or renal; 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
	• Neurosarcoidosis is uncommon, with an incidence of approximately 5% to 15%. Cord symptoms, a transverse myelitis picture, may precede brain lesions but are less common than brain lesions. Spinal cord involvement occurs in less than 1% of all sarcoidosis cases. MRI often demonstrates hyperintensity on T2-weighted images and enhancement following Gd administration. Sarcoidosis can also include cauda equina syndrome, radiculopathy, syringomyelia, and arachnoiditis. With systemic sarcoidosis, hilar adenopathy may be present, along with constitutional symptoms. CSF lymphocytic pleocytosis, hypoglycorrhachia, and elevated angiotensin-converting enzyme are more common than in multiple sclerosis or neuromyelitis optica. The gold standard for diagnosis is biopsy of neurologic or non-neurologic tissue to document the presence of non-caseating granulomas.
	• 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 (129; 151). 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 (138) and underlying small cell lung cancer. Twenty-seven percent of patients with antibodies to amphiphysin IgG have inflammatory transverse myelitis (138). 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 (149). 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 (95; 39; 164), 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 (116), and other virus infections (below) as well as mycoplasma pneumoniae. Many of these viruses also cause primary invasion.
	• Postvaccinal encephalomyelitis (seen with rabies, especially with brain antigens in the vaccine preparation; smallpox) (50). Postvaccinal encephalomyelitis is most common in older subjects; young adults are affected more than infants (06). There are many reports of an association with recombinant hepatitis B vaccine (168); larger epidemiologic studies dispute this (10). Pertussis and influenza vaccination do not appear to cause acute transverse myelitis (50). 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 (179). 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).
	• 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 (44)
	• 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 (72).
	• 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 (94). This may be due to the underlying disease and not the thymectomy. Four women--two black, one white, and one 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 two of three, ANA in two of four, anti-acetylcholine receptor in four of four, and stiff-man syndrome in one. Interferon beta may have exacerbated disease in one. Because one in eight 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, 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. Chronic use of nitrous oxide can inactivate vitamin B12, causing demyelination of the dorsal columns of the spinal cord (103). A case of methanol intoxication presented with spinal cord involvement, likely necrosis with a clinical picture similar to transverse myelitis or myelopathy.
	• 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 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, CADASIL, cavernoma of conus medullaris, venous thrombosis, impaired venous drainage by a disc herniation or fibrocartilaginous embolism from a ruptured disc, 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 (63) 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. A case of spinal subarachnoid hemorrhage appeared in the setting of lupus vasculitis (57). 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 (128). 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, chikungunya, 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 (165), 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; primary or reactivation), West Nile flavivirus, and Zika virus (116; 32; 95).
	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 (162). 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 (141). SARS-CoV is associated with encephalopathy, stroke, seizures, Guillain-Barre syndrome, meningoencephalitis, and acute necrotizing hemorrhagic encephalopathy (127). 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 (109). CNS symptoms coexist with iridocyclitis, uveitis, and cutaneous abnormalities.

Diagnostic workup

Transverse myelitis is a clinical syndrome with many inflammatory and noninflammatory causes. The first step is to rapidly rule out cord compression (MRI), then vascular or connective tissue disease (serology), and then define whether the inflammation is restricted to the cord (brain MRI). The history and exam should exclude connective tissue disease and Behçet disease by focusing on rashes, joint pain, pleuritis, night sweats, shortness of breath, hematuria, anemia, adenopathy, orogenital ulcers, organomegaly, uveitis, and retinitis. Labs should include CBC and differential, CRP, ANA, and other infectious workups (ie, QuantiFERON-TB gold) to differentiate disease-related from idiopathic transverse myelitis.

Spinal cord inflammation is a sine qua non for idiopathic acute transverse myelitis, so a Gd-enhanced MRI and CSF analysis strengthen the diagnosis. An MRI of the spinal cord shows increased signal density on T2-weighted images in 50% to 90% of adults (114; 12; 83) and 50% to 83% of children (95; 120) presenting with acute transverse myelitis. T1-weighted MRI scans are isointense or mildly hypointense, with swelling of the cord over several segments. Normal MRIs occur in 50% of patients with devastating, localized cord symptoms, suggesting that there are different disease mechanisms or etiologies. Moreover, extensive cord involvement often does not correlate with clinical severity or outcome (08).

The abnormal MRI T2 or FLAIR signal is centrally located or holocord and extends over multiple cord segments (168; 58). It may reach several segments above the clinically determined sensory level (14; 31). The thoracic cord is typically involved, but some series show cervical predominance (74% of lesions in 20 young French patients) (35). Lupus myelopathy is typically thoracic, Sjögren myelopathy is cervical. Lesions restricted to the conus medullaris can follow virus infections. The spinal cord is sometimes swollen in transverse myelitis (40%), whereas swelling on MRI is rarely seen in multiple sclerosis (80). MRI lesions are all of the same age in acute transverse myelitis, but the signal resolves in some areas before others. More extensive MRI lesions and persistent enhancement after gadolinium infusion herald residual clinical deficits in some cases (153; 134), but MRI severity does not always correlate with clinical deficits (140). Diffusion tensor imaging shows abnormalities in distal, normal-appearing white matter and may be more sensitive than conventional MRI. Associated brain lesions suggest acute disseminated encephalomyelitis or multiple sclerosis, by definition. However, there is one report of brain MRI abnormalities in 17 of 30 patients and oligoclonal bands in 12 of 25 patients who had "acute transverse myelitis" without clinical signs above the foramen magnum (114). Patients with CSF abnormalities and brain MRI lesions are more likely to eventually develop multiple sclerosis, as are those with heterogeneous spinal cord involvement on MRI (163).

The spinal fluid has elevated protein (often 100 to 120 mg/100 ml; normal less than 50 mg%) and moderate pleocytosis (50 to 100 lymphocytes/mm3) in one third to one half of adult patients (04; 107; 20; 172; 12; 80) and in up to 80% of children (120). Glucose and opening pressure are normal (04; 148). Seventy percent of children have elevated spinal fluid myelin basic protein (120). The spinal fluid in transverse myelitis typically lacks oligoclonal bands and, thus, differs from the typical picture in multiple sclerosis (12) (note: with a low-resolution assay) (80). The bands, if present, do not persist (90). IgG (35% to 52%), IgG index (42%, the most specific of these measures of inflammation), and immunoglobulin synthesis rate (33%) are sometimes increased, but not as frequently as in multiple sclerosis (148; 42; 80). The axonal 14-3-3 protein is present in only 10% of patients with transverse myelitis and multiple sclerosis (41). In seven patients with acute transverse myelitis, the four that had 14-3-3 in their CSF did poorly (75). In 19 Japanese patients with multiple sclerosis, 14-3-3 was present with more damage, progression, and optico-spinal disease (154). In another series, none of the six patients with transverse myelitis were positive (41). High CSF IL-6 predicted recurrent transverse myelitis and disability (99; 85). Nonspecific enolase (NSE), myelin basic protein, and S-100 are also potential predictors of severity.

Related syndromes have a different MRI and CSF picture. In acute necrotizing hemorrhagic leukoencephalomyelitis, there is fever and peripheral blood neutrophilia. The CSF is xanthochromic, contains variable amounts of protein and often red blood cells as well as up to 2000 polymorphonuclear lymphocytes. In milder cases the cell count is lower and largely mononuclear. In progressive necrotizing myelopathy, from spinal vascular malformations (52; 117) or from a remote effect of cancer (53), the cord is swollen on myelography and the CSF is xanthochromic with high protein (150), a normal cell count or a few lymphocytes or polymorphonuclear lymphocytes, and no oligoclonal bands. In acute disseminated encephalomyelitis, MRI lesions are all of the same age and are widespread in brain and cord, often with bilateral optic nerve or basal ganglia lesions. These disappear with the passage of time (184; 90). There is moderate pleocytosis, moderately increased protein, and occasional but transient oligoclonal bands. In chronic progressive myelopathy, 44% have oligoclonal bands, and 44% have abnormal visual evoked potentials (135), suggesting that many of these patients have multiple sclerosis. In 20 patients with "myelopathy" developing over days to years, 65% had T2-weighted MRIs compatible with multiple sclerosis, and an additional 25% had abnormal visual evoked potentials or CSF oligoclonal bands (118).

MRI and lumbar puncture, which are sensitive and specific, have largely obviated other tests. Myelograms are usually normal (107; 20) although cord swelling may be present on CT myelography (150). CT provides less information than MRI. MRI sometimes (two of five cases) shows cord swelling when myelograms are normal (14).

Lesions in transverse myelitis (MRI)

Transverse myelitis in a 53-year-old woman. Lesions are typical of transverse myelitis, but symptoms began 2 weeks after a hepatitis B vaccination, suggesting postvaccinal encephalomyelitis. Patchy foci of enhancement at T11-L1 on...
Transverse myelitis (MRI of central cord)

(Left) Proton density cross-section of thoracolumbar junction with suggestive increased signal intensity in central cord. (Right) T2-weighted image showing increased signal in central cord, surrounded by rim of normal signal, in t...

Electrophysiologic tests of spinal cord function are sensitive for detecting spinal cord damage. Visual and brainstem evoked potentials help exclude CNS dissemination (which would suggest multiple sclerosis) and nerve conduction velocity and in some cases excludes damage to the peripheral nervous system. In parainfectious and idiopathic transverse myelitis, one-fourth of patients have evidence of peripheral damage (eg, abnormal motor unit action potentials, sensory nerve action potentials, and nerve conduction velocities) (68), unlike multiple sclerosis.

There is slowed central motor conduction time to the lower limbs (abnormal in 90%) after magnetic stimulation. Electrically induced motor evoked potentials are even more sensitive, but this test can be painful. Painless magnetically evoked potential, transcranial magnetic stimulation, is abnormal in 96% of children with myelitis (176). Somatosensory evoked potentials are abnormal in up to 85% (147; 178; 83); normal potentials suggest a better prognosis. Absent or reduced sensory action potentials could also indicate peripheral nervous system damage. F waves may be absent on electrodiagnostic testing, and this raises the possibility of Guillain-Barré syndrome. Electromyography of the lower limb muscles showing neuropathic potentials suggests demyelination in the ventral root zone. These indicate a poor outcome (119), as do abnormalities of peripheral nervous function (68).

NMO-IgG, MOG-IgG, angiotensin-converting enzyme, and serum tests for connective tissue disease are important, especially if cord lesions are contiguous or extend for more than two segments

Management

Transverse myelitis is a diagnosis of exclusion. Potentially treatable diseases such as cord compression, local tumor, paraneoplastic disease, infection, vascular causes, and connective tissue diseases must be ruled out.

Symptom management. Most patients with transverse myelitis will have paraplegia of the lower limbs for weeks or months, and in some the paresis is permanent. Prevention of deep vein thrombosis and decubitus ulcers is essential. Spastic legs can be relaxed with physical therapy with active and passive range of motion exercises and stretching plus baclofen, tizanidine, benzodiazepines, or dantrolene (removed from some markets including the United States). Intrathecal baclofen is useful for severe spasticity unrelieved by oral drugs. Weakness may be improved with amantadine, methylphenidate, and 4-aminopyridine and 3,4-diaminopyridine (fampridine). In idiopathic acute transverse myelitis, extended-release dalfampridine (D-ER) improved walking speed in 85% of the treated arm compared to 69% of the placebo group (155).

Autonomic instability from disruption of sympathetic feedback may increase sensitivity to pain. Central neuropathic pain in multiple sclerosis, and presumably in some cases of transverse myelitis, is strongly linked to T1-T6 cord lesions. These lesions disrupt the longitudinally extensive intermediomedial nucleus that surrounds the midthoracic central canal (130). Pain is usually not a problem after the initial symptoms resolve, but pain may be relieved with muscle stretching or by therapy with gabapentin, carbamazepine, phenytoin, amitriptyline, or oral or intrathecal baclofen (71). Orthostatic hypotension can be treated with compression stockings, hydration, salt supplementation, and fludrocortisone or midodrine.

Anticholinergics can reduce urinary frequency caused by a spastic bladder but can lead to or worsen urinary retention. Self-catheterization is far superior to indwelling catheters for treatment of incontinence. Recurrent urinary tract infections after apparent recovery should be investigated; they suggest a second insult from multiple sclerosis. Acute and chronic rehabilitation is helpful for recovery from transverse myelitis (99). Maximization of load bearing in affected limbs, optimization of sensory cues, and patterned nonspecific training, as well as functional electrical stimulation and neurotrophin induction have been detailed (152).

Treating the underlying disease process. Transverse myelitis has traditionally been treated with oral or intravenous glucocorticoids or intravenous adrenocorticotropic hormone. The aim of initial immunotherapy is to stop disease progression. High-dose intravenous steroid therapy is associated with prompt clinical improvement (45; 89). The second line of immunotherapy used to treat idiopathic transverse myelitis is intravenous immunoglobulin or plasma exchange (51). Oral and intravenous steroids and IVIG had no effect on eventual outcome in a retrospective study of 50 Japanese children (120). Lessons from the treatment of other demyelinating diseases may also be relevant because they share many of the clinical and pathological facets of transverse myelitis. In multiple sclerosis, glucocorticoid or adrenocorticotropic hormone therapy shortens the duration of symptoms but glucocorticoids do not change the long-term outlook. In optic neuritis, high-dose intravenous methylprednisolone improves vision and appears to prevent recurrences compared to oral prednisone alone or placebo (17). A more prolonged steroid taper than that described by Beck and colleagues may be advisable based on a rat model of postvaccinal encephalomyelitis (143), hard data in humans are lacking. Similarly, acute disseminated encephalomyelitis responds dramatically to glucocorticoids, but symptoms flare up on sudden withdrawal (184), so a taper is advised. Idiopathic transverse myelitis, however, may have a different pathogenesis than these diseases.

A number of studies from the Mayo Clinic and other case reports suggest that plasma exchange can benefit severe attacks of CNS demyelination (88; 61). Cyclophosphamide, mycophenolate, azathioprine, and rituximab have been used for chronic disease or because of resistance to multiple other treatments. Anecdotal evidence has suggested azathioprine or cyclophosphamide therapy is helpful (61), but this sample included many cases of other autoimmune diseases that cause transverse myelitis (98). These drugs are not FDA-approved for therapy of either multiple sclerosis or transverse myelitis.

Recurrent transverse myelitis would appear to be a form of multiple sclerosis, although according to Scott it infrequently develops into multiple sclerosis when the brain MRI is negative (156). Approved disease-modifying drugs are likely to be most effective in preventing further attacks in multiple sclerosis.

If serum NMO-IgG antibodies are positive, the disease is different from multiple sclerosis or idiopathic transverse myelitis. Treatment of the initial attack includes intravenous high-dose corticosteroids and plasma exchange. Because of the likelihood of recurrence, maintenance therapy is recommended to suppress the immune system. The following medications are FDA-approved for NMO-IgG neuromyelitis optica spectrum disorder: eculizumab (complement inhibitor), inebilizumab (anti-CD19), and satrilizumab (anti-IL6). In the past, rituximab, mycophenolate mofetil, and azathioprine were used. Interferon beta is unhelpful or dangerous in patients with positive NMO-IgG or CNS Sjögren disease because they already have high endogenous type I interferon levels (78). For MOG-IgG disease, there are no current FDA-approved medications for maintenance therapy. The primary therapies in current use are mycophenolate mofetil, rituximab, azathioprine, and repeated intravenous immunoglobulin infusions.

One patient may have improved with intrathecal acidic fibroblast growth factor.

Tumor necrosis factor blockers, effective in rheumatoid arthritis, have precipitated transverse myelitis and other demyelinating syndromes.

Outcomes

In pediatric transverse myelitis, motor function and urinary dysfunction improve the most when there is minimal delay from symptom onset to initiation of immunotherapy and rehabilitation (26). Outcomes are also discussed in the Clinical manifestations section.

References

01: Alarcon-Segovia D, Deleze M, Oria CV, et al. Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients. Medicine 1989;68:353-65. PMID 2811661
02: Albucher JF, Lauque D, Geyer I, et al. Myelite transverse induite par une infection a mycoplasma pneumoniae. Rev Neurol (Paris) 1995;151:350-3. PMID 7481396
03: Alper G, Petropoulou KA, Fitz CR, Kim Y. Idiopathic acute transverse myelitis in children: an analysis and discussion of MRI findings. Mult Scler 2011;17(1):74-80. PMID 20858691
04: Altrocchi PH. Acute transverse myelopathy. Arch Neurol 1963;9:111-9. PMID 14048158
05: Alvarenga MP, Thuler LC, Neto SP, et al. The clinical course of idiopathic acute transverse myelitis in patients from Rio de Janeiro. J Neurol 2010. PMID 20127351
06: Alvord EC Jr. Disseminated encephalomyelitis: its variations in form and their relationships to other diseases of the nervous system. In: Vinken PJ, Bruyn GW, Klawans HL, Koetsier JC, editors. Handbook of clinical neurology. Amsterdam: North Holland, 1985:467-502.
07: Andersen O. Myelitis. Curr Opin Neurol 2000;13:311-6. PMID 10871257
08: Andronikou S, Albuquerque-Jonathan G, Wilmshurst J, Hewlett R. MRI findings in acute idiopathic transverse myelopathy in children. Pediatr Radiol 2003;33:624-9. PMID 12879317
09: Anlar B, Gucuyener K, Imir T, Yalaz K, Renda Y. Cimetidine as an immunomodulator in subacute sclerosing panencephalitis: a double blind, placebo-controlled study. Pediatr Infect Dis 1993;12:578-81. PMID 8346000
10: Asherio A, Zhang SM, Hernan MA, et al. Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med 2001;344:327-32. PMID 11172163
11: Aubourg P, Adamsbaum C, Lavallard-Rousseau MC, et al. Brain MRI and electrophysiologic abnormalities in preclinical and clinical adrenomyeloneuropathy. Neurology 1992;42:85-91. PMID 1734328
12: Austin SG, Zee CS, Waters C. The role of magnetic resonance imaging in acute transverse myelitis. Can J Neurol Sci 1992;19:508-11. PMID 1423048
13: Bakshi R, Kinkel PR, Mechtler LL, et al. Magnetic resonance imaging findings in 22 cases of myelitis: comparison between patients with and without multiple sclerosis. Eur J Neurol 1998;5:35-48. PMID 10210810
14: Barakos JA, Mark AS, Dillon WP, Norman D. MR imaging of acute transverse myelitis and AIDS myelopathy. J Comput Assist Tomogr 1990;14:45-50. PMID 2298996
15: Barile L, Lavalle C. Transverse myelitis in systemic lupus erythematosus--the effect of IV pulse methylprednisolone and cyclophosphamide. J Rheumatol 1992;19:370-2. PMID 1578449
16: Bashir K, Whitaker JN. Importance of paraclinical and CSF studies in the diagnosis of multiple sclerosis patients presenting with partial cervical transverse myelopathy: cranial MRI. Mult Scler 2000;6:312-6. PMID 11064439
17: Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med 1992;326:581-8. PMID 1734247
18: Berger Y, Blaivas JG, Oliver L. Urinary dysfunction in transverse myelitis. J Urol 1990;144:103-5. PMID 2359154
19: Berghella V, Spector T, Trauffer P, Johnson A. Pregnancy in patients with preexisting transverse myelitis. Obstet Gynecol 1996;87:809-12. PMID 8677096
20: Berman M, Feldman S, Alter M, Zilber N, Kahana E. Acute transverse myelitis: incidence and etiologic considerations. Neurology 1981;31:966-71. PMID 7196523
21: Borchers AT, Gershwin ME. Transverse myelitis. Autoimmun Rev 2012;11(3):231-48. PMID 21621005
22: Bramanti P, Sessa E, Rifici C, et al. Enhanced spasticity in primary progressive multiple sclerosis patients treated with interferon beta-1b. Neurology 1998;51:1720-3. PMID 9855531
23: Bursle C, Riney K, Stringer J, et al. Leber hereditary optic neuropathy and longitudinally extensive transverse myelitis. JIMD Rep 2018;42:53-60. PMID 29249004
24: Byskosh PV, Reder AT. Interferon-beta effects on cytokine mRNA in peripheral mononuclear cells in multiple sclerosis. Mult Scler 1996;1:262-9. PMID 9345428
25: Cabrera-Gomez JA, Galarraga-Inza J, Coro-Antich RM, et al. Down's syndrome and neuromyelitis optica (Devic's disease): an autopsy-proven case. Mult Scler 2007;13:433-6. PMID 17439915
26: Celik H, Aksoy E, Oztoprak U, et al. Longitudinally extensive transverse myelitis in childhood: clinical features, treatment approaches, and long-term neurological outcomes. Clin Neurol Neurosurg 2021;207:106764. PMID 34171586
27: Chahin S, Garwood MD, St Louis EK, Shivapour ET, Kelkar PM, Granner MA. Intramedullary Sjögren syndrome. Neurology 2009;73(23):2041-2. PMID 19996081
28: Chan KH, Tsang KL, Fong GCY, Ho SL, Cheung RTF, Mak W. Idiopathic inflammatory demyelinating disorders after acute transverse myelitis. Eur J Neurol 2006;13:862-8. PMID 16879297
29: Chen L, Li J, Guo Z, Liao S, Jiang L. Prognostic indicators of acute transverse myelitis in 39 children. Pediatr Neurol 2013;49(6):397-400. PMID 24112847
30: Chinello M, Mauro M, Cantalupo G, et al. Acute cervical longitudinally extensive transverse myelitis in a child with lipopolysaccharide-responsive-beige-like-anchor-protein (LRBA) deficiency: a new complication of a rare disease. Front Pediatr 2020;8:580963. PMID 33178652
31: Choi KH, Lee KS, Chung SO, et al. Idiopathic transverse myelitis: MR characteristics. Am J Neuroradiol 1996;17(6):1151-60. PMID 8791931
32: Christensen PB, Wermuth L, Hinge HH, Bomers K. Clinical course and long-term prognosis of acute transverse myelopathy. Acta Neurol Scand 1990;81:431-5. PMID 2375246
33: Constantinescu CS. Melanin, melatonin, melanocyte-stimulating hormone, and the susceptibility to autoimmune demyelination: a rationale for light therapy in multiple sclerosis. Med Hypotheses 1995;45(5):455-8. PMID 8748085
34: Cordonnier C, de Seze J, Breteau G, et al. Prospective study of patients presenting with acute partial transverse myelopathy. J Neurol 2003;250:1447-52. PMID 14673577
35: Dalecky A, Pelletier J, Cherif AA, Levrier O, Khalil R. Myelopathies aigues du sujet jeune et sclerose en plaques: Etude prospective de 20 cas. Rev Neurol 1997;153:569-78. PMID 9684021
36: Debette S, de Sèze J, Pruvo JP, et al. Long-term outcome of acute and subacute myelopathies. J Neurol 2009;256(6):980-8. PMID 19252779
37: Defresne P, Hollenberg H, Husson B, et al. Acute transverse myelitis in children: clinical course and prognostic factors. J Child Neurol 2003;18:401-6. PMID 12886975
38: Deiva K, Absoud M, Hemingway C, et al. Acute idiopathic transverse myelitis in children: early predictors of relapse and disability. Neurology 2015;84(4):341-9. PMID 25540303
39: DeSanto J, Ross JS. Spine infection/inflammation. Radiol Clin North Am 2011;49(1):105-27. PMID 21111132
40: de Seze J, Lanctin C, Lebrun C, et al. Idiopathic acute transverse myelitis: application of the recent diagnostic criteria. Neurology 2005;65:1950-3. PMID 16380618
41: de Seze J, Peoc’h K, Ferriby D, Stojkovic T, Laplanche JL, Vermersch P. 14-3-3 protein in the cerebrospinal fluid of patients with acute transverse myelitis and multiple sclerosis. J Neurol 2002;249:626-7. PMID 12021955
42: Deuskar NJ, Thakare JP, Gore MM, Wadia RS, Ghosh SN. Cerebrospinal fluid immunoglobulins in acute transverse myelitis. Indian J Med Res 1983;77:854-60. PMID 6642583
43: Dodson D. Transverse myelitis and spastic paraparesis in a patient with HIV infection [letter]. N Engl J Med 1990;322:1322. PMID 2325730
44: Donati E, Bargnani C, Besana R, Locatelli P, Faggi L, DeMarinis S. Subacute myelo-optic neuropathy (SMON) induced by antituberculous treatment in uremia. Funct Neurol 1990;5:151-4. PMID 2172103
45: Dowling PC, Bosch VV, Cook SD. Possible beneficial effect of high-dose intravenous steroid therapy in acute demyelinating disease and transverse myelitis. Neurology 1980;30:33-6. PMID 6248819
46: Dunne K, Hopkins IJ, Shield LK. Acute transverse myelopathy in childhood. Dev Med Child Neurol 1986;28:198-204. PMID 3709989
47: Escobar-Villalba A, Sainz de la Maza S, Pérez Torre P, et al. Acute myelitis by human herpes virus 7 in an HIV-infected patient. J Clin Virol 2016;77:63-5. PMID 26906233
48: Eyas M, Jahinover M, Abhiram N, Michael TM. Acute cervical-transverse myelitis following intranasal insufflation of heroin. Radiol Case Rep 2020;15(11):2136-8. PMID 32952750
49: Feng X, Reder NP, Yanamandala M, et al. Type I interferon signature is high in lupus and neuromyelitis optica but low in multiple sclerosis. J Neurol Sci 2012;313(1-2):48-53. PMID 22036215
50: Fenichel GM. Neurological complications of immunization. Ann Neurol 1982;12:119-28. PMID 6751212
51: Fiani B, Covarrubias C, Jarrah R. Neuroimmunology and novel methods of treatment for acute transverse myelitis. Cureus 2021;13(8):e17043. PMID 34522521
52: Foix C, Alajouanine T. La myélite nécrotique subaigue: myélite centrale angéio-hypertrophique à évolution progressive. Paraplégie amyotrophique lentement ascendante, d'abord spasmodique, puis flasque, s'accompagnant de dissociation albumino-cytologique. Rev Neurol 1926;2:3-42.
53: Follis AH, Netsky MG. Progressive necrotic myelopathy. In: Vinken PJ, Bruyn GW, editors. Handbook of clinical neurology. Multiple sclerosis and other demyelinating diseases. New York: Wiley Interscience, 1970:452-68.
54: Ford B, Tampieri D, Francis G. Long-term follow-up of acute partial transverse myelopathy. Neurology 1992;42:250-2. PMID 1285728
55: Fukazawa T, Hamada T, Tashiro K, Moriwaka F, Yanagihara T. Acute transverse myelopathy in multiple sclerosis. J Neurol Sci 1990;100:217-22. PMID 2089136
56: Garcia-Merino A, Blasco MR. Recurrent transverse myelitis with unusual long-standing Gd-DTPA enhancement. J Neurol 2000;247:550-1. PMID 10993498
57: Glynn RM, Garza MR, Campanella FM. Evaluation and management of spinal subarachnoid hemorrhage in a patient with lupus vasculitis. Am J Case Rep 2018;19:114-7. PMID 29382812
58: Goh C, Phal PM, Desmond PM. Neuroimaging in acute transverse myelitis. Neuroimaging Clin N Am 2011;21(4):951-73. PMID 22032509
59: Goodhart LC, Loizou LA, Anderson M. Heroin myelopathy. J Neurol Neurosurg Psychiatry 1982;45:562-3. PMID 7119822
60: Graber JJ, Allie SR, Mullen KM, et al. Interleukin-17 in transverse myelitis and multiple sclerosis. J Neuroimmunol 2008;196(1-2):124-32. PMID 18417225
61: Greenberg BM, Thomas, KP, Krishnan C, Kaplin AI, Calabresi PA, Kerr DA. Idiopathic transverse myelitis; corticosteroids, plasma exchange, or cyclophosphamide. Neurology 2007;68:1614-17. PMID 17485649
62: Grewal AK, Lopes MB, Berg CL, Bennett AK, Alves VA, Trugman JM. Recurrent demyelinating myelitis associated with hepatitis C viral infection. J Neurol Sci 2004;224:101-6. PMID 15450779
63: Transverse Myelitis Consortium Working Group. Proposed diagnostic criteria and nosology of acute transverse myelitis. Neurology 2002;59:499-505. PMID 12236201
64: Guidotti M, Passerini D, Brambilla M, Landi G. Heroin myelopathy: a case report. Ital J Neurol Sci 1985;6:99-100. PMID 3997468
65: Gutowski NJ, Davies AO. Transverse myelitis following general anaesthesia. Anaesthesia 1993;48:44-5. PMID 8240476
66: Haase CG, Schmidt S. Detection of brain-specific autoantibodies to myelin oligodendrocyte glycoprotein, S100beta and myelin basic protein in patients with Devic’s neuromyelitis optica. Neurosci Lett 2001;307:131-3. PMID 11427318
67: Hartman E, Reder AT, Bernard J, et al. Spectrum of adverse neurological events with biologic therapies in autoimmune disease. CMSC/ACTRIMS, San Antonio, Texas, June 5, 2010.
68: Harzheim M, Schlegel U, Urbach H, et al. Discriminatory features of acute transverse myelitis: a retrospective analysis of 45 patients. J Neurol Sci 2004;217:217-23. PMID 14706227
69: He Z, Ren M, Wang X, Guo Q, Qi X. Pruritus may be a common symptom related to neuromyelitis optica spectrum disorders. Mult Scler Relat Disord 2017;13:1-3. PMID 28427688
70: Helgason CM, Arnason BW. Demyelinating diseases affecting the spinal cord. In: Davidoff RA. Handbook of the Spinal Cord. New York: Marcel Dekker, 1987:559-606.
71: Herman RM, D'Luzansky SC, Ippolito R. Intrathecal baclofen suppresses central pain in patients with spinal lesions. A pilot study. Clin J Pain 1992;8:338-45. PMID 1493344
72: Hiz F, Kokes U, Eyiipgil T, Sari SO, Erdogan A. Akut transvers miyelite neden olan tersiyer spinal sifiliz tablosu: Olgu sunumu. [Acute transverse myelitis with tertiary spinal syphilis.] Turk Noroloji Dergisi 2008;14:121-7.
73: Hopkins IJ. A new syndrome: poliomyelitis-like illness associated with acute asthma in childhood. Aust Paediatr J 1974;10:273-6. PMID 4447516
74: Hummers LK, Krishnan C, Casciola-Rosen L, et al. Recurrent transverse myelitis associates with anti-Ro (SSA) autoantibodies. Neurology 2004;62:147-9. PMID 14718721
75: Irani DN, Kerr DA. 14-3-3 protein in the cerebrospinal fluid of patients with acute transverse myelitis. Lancet 2000;355:901. PMID 10752712
76: Jacob A, Nicholas R, Das K, et al. Exploring the relationship of relapsing myelitis with neuromyelitis optica (Devic's disease) and multiple sclerosis. Ann Neurol 2004;56(Suppl 8):S33, A88.
77: Jaffe D, Freeman W. Spinal necrosis and softening of obscure origin. Arch Neurol Psychiatry 1943;49:683-707.
78: Javed A, Balabanov R, Arnason BGW, et al. Minor Salivary gland inflammation in Devic’s disease and longitudinally extensive myelitis. Mult Scler 2008;14:809-14. PMID 18573828
79: Javed A, Kelly T, Walsh R, Reder AT. Longitudinally extensive transverse myelitis: Treatment outcome of patients with features of Sjögren’s disease and positive NMO antibody. Ann Neurol 2006;60(Suppl 10):S38, M-13.
80: Jeffery DR, Mandler RN, Davis LE. Transverse myelitis. Retrospective analysis of 33 cases, with differentiation of cases associated with multiple sclerosis and parainfectious events. Arch Neurol 1993;50:532-5. PMID 8489410
81: Johnson RT, Griffin DE, Hirsch RL, et al. Measles encephalomyelitis: clinical and immunologic studies. N Engl J Med 1984;310:137-41. PMID 6197651
82: Kahl KG, Naumann M, Oertele E, Warmuth-Metz M, Toyka KV. Recurrent transverse myelitis. 2 cases and review of the literature. Nervenarzt 1998;69:1115-22. PMID 9888150
83: Kalita J, Misra UK, Mandal SK. Prognostic predictors of acute transverse myelitis. Acta Neurol Scand 1998;98:60-3. PMID 9696529
84: Kalra V, Sharma S, Sahu J, et al. Childhood acute transverse myelitis: clinical profile, outcome, and association with antiganglioside antibodies. J Child Neurol 2009;24(4):466-71. PMID 19196873
85: Kaplin AI, Deshpande DM, Scott E, et al. IL-6 induces regionally selective spinal cord injury in patients with the neuroinflammatory disorder transverse myelitis. J Clin Invest 2005;115:2731-41. PMID 16184194
86: Karaszewski JW, Reder AT, Anlar B, Kim WC, Arnason BG. Increased lymphocyte beta-adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28- suppressor cell. Ann Neurol 1991;30:42-7. PMID 1656847
87: Kastenbauer S, Winkler F, Fesl G, et al. Acute severe spinal cord dysfunction in bacterial meningitis in adults. Arch Neurol 2001;58:806-10. PMID 11346376
88: Keegan M, Pineda AA, McClelland RL, et al. Plasma exchange for severe attacks of CNS demyelination: Predictors of response. Neurology 2002;58:143-6. PMID 11781423
89: Kennedy PG, Weir AI. Rapid recovery of acute transverse myelitis treated with steroids. Postgrad Med J 1988;64:384-5. PMID 3200781
90: Kesselring J, Miller DH, Robb SA, et al. Acute disseminated encephalomyelitis: MRI findings and the distinctions from multiple sclerosis. Brain 1990;113:291-302. PMID 2328406
91: Kikuchi H, Osoegawa M, Ochi H, et al. Spinal cord lesions of myelitis with hyperIGEemia and mite antigen specific IgE (atopic myelitis) manifest eosinophilic inflammation. J Neuro Sci 2001;183:73-8. PMID 11166798
92: Kim KK. Idiopathic recurrent transverse myelitis. Arch Neurol 2003;60:1290-4. PMID 12975297
93: Kimbrough DJ, Mealy MA, Simpson A, Levy M. Predictors of recurrence following an initial episode of transverse myelitis. Neurol Neuroimmunol Neuroinflamm 2014;1(1):e4. PMID 25340060
94: Kister I, Gulati S, Boz C, et al. Neuromyelitis optica in patients with myasthenia gravis who underwent thymectomy. Arch Neurol 2006;63:851-6. PMID 16769866
95: Knebusch M, Strassburg HM, Reiners K. Acute transverse myelitis in childhood: nine cases and review of the literature. Dev Med Child Neurol 1998;40:631-9. PMID 9766742
96: Kovacs B, Lafferty TL, Brent LH, DeHoratius RJ. Transverse myelopathy in systemic lupus erythematosus: an analysis of 14 cases and review of the literature. Ann Rheum Dis 2000;59:120-4. PMID 10666167
97: Kumar N, Gross JB Jr, Ahlskog JE. Copper deficiency myelopathy produces a clinical picture like subacute combined degeneration. Neurology 2004;63:33-9. PMID 15249607
98: Kumar S, Sandhya G, Rajshekher G, Reddy R, Prabhakar S. Idiopathic transverse myelitis: corticosteroids, plasma exchange, or cyclophosphamide. Neurology 2008;70:160. PMID 18180448
99: Krishnan C, Kaplin AI, Deshpande DM, et al. Transverse myelitis: pathogenesis, diagnosis and treatment. Front Biosci 2004;9:1483-99. PMID 14977560
100: Label LS, Batts DH. Transverse myelitis caused by duck embryo rabies vaccine. Arch Neurol 1982;39:426-30. PMID 7103777
101: Lehnhardt FG, Impekoven P, Rubbert A, et al. Recurrent longitudinal myelitis as primary manifestation of SLE. Neurology 2004:63:1976. PMID 15557531
102: Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364:2106-12. PMID 15589308
103: Lewis B, Nelson G, Vu T, Judge B. No laughing matter - myeloneuropathy due to heavy chronic nitrous oxide abuse. Am J Emerg Med 2021;46:799.e1-2. PMID 33597094
104: Li R, Qiu W, Lu Z, et al. Acute transverse myelitis in demyelinating diseases among the Chinese. J Neurol 2011; 258(12):2206-13. PMID 21590279
105: Ligocki AJ, Rounds WH, Cameron EM, et al. Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation. Genes Immun 2013;14(5):291-301. PMID 23594958
106: Lindsey JW, Albers GW, Steinman L. Recurrent transverse myelitis, myasthenia gravis, and autoantibodies. Ann Neurol 1992;32:407-9. PMID 1416813
107: Lipton HL, Teasdall RD. Acute transverse myelopathy in adults. A follow-up study. Arch Neurol 1973;28:252-7. PMID 4688431
108: Llamas Y, Hazel K, Nicholson P, Costelloe L. Longitudinally extensive transverse myelitis after Campylobacter jejuni enteritis. Pract Neurol 2018;18(2):143-5. PMID 29273615
109: Lubin JR, Loewenstein JI, Frederick AJ. Vogt-Koyanagi-Harada syndrome with focal neurologic signs. Am J Ophthalmol 1981;91:332-41. PMID 7211990
110: Maimone D, Reder AT, Gregory S. T cell lymphokine-induced secretion of cytokines by monocytes from patients with multiple sclerosis. Cell Immunol 1993;146:96-106. PMID 8425234
111: Marabani M, Zoma A, Hadley D, Sturrock RD. Transverse myelitis occurring during pregnancy in a patient with systemic lupus erythematosus. Ann Rheum Dis 1989;48:160-2. PMID 2930267
112: Mastronardi L, Elsawaf A, Roperto R, et al. Prognostic relevance of the postoperative evolution of intramedullary spinal cord changes in signal intensity on magnetic resonance imaging after anterior decompression for cervical spondylotic myelopathy. J Neurosurg Spine 2007;7(6):615-22. PMID 18074686
113: Mealy MA, Nam TS, Pardo SJ, et al. Familial monophasic acute transverse myelitis due to the pathogenic variant in VPS37A. Neurol Genet 2018;4(1):e213. PMID 29473047
114: Miller DH, McDonald WI, Blumhardt LD, et al. Magnetic resonance imaging in isolated noncompressive spinal cord syndromes. Ann Neurol 1987;22:714-23. PMID 3435080
115: Miller DH, Ormerod IC, Rudge P, Kendall BE, Moseley IF, McDonald WI. The early risk in multiple sclerosis following isolated acute syndromes of the brainstem and spinal cord. Ann Neurol 1989;26:635-9. PMID 2817838
116: Miller HG, Stanton JB, Gibbons JL. Para-infectious encephalomyelitis and related syndromes. Q J Med 1956;25:427-505. PMID 13379602
117: Mirich DR, Kucharczyk W, Keller MA, Deck J. Subacute necrotizing myelopathy: MR imaging in four pathologically proved cases. Am J Neuroradiol 1991;12:1077-83. PMID 1763730
118: Miska RM, Pojunas KW, McQuillen MP. Cranial magnetic resonance imaging in the evaluation of myelopathy of undetermined etiology. Neurology 1987;37:840-3. PMID 3574687
119: Misra UK, Kalita J. Can electromyography predict the prognosis of transverse myelitis. J Neurol 1998;245(11):741-4. PMID 9808244
120: Miyazawa R, Ikeuchi Y, Tomomasa T, Ushiku H, Ogawa T, Morikawa A. Determinants of prognosis of acute transverse myelitis in children. Pediatr Int 2003;45:512-6. PMID 14521523
121: Moersch FP, Kernohan JW. Progressive necrosis of the spinal cord. Arch Neurol Psychiatry 1934;31:504.
122: Montalban X, Duran I, Rio J, Saez-Torres I, Tintore M, Martinez-Caceres EM. Can we predict flu-like symptoms in patients with multiple sclerosis treated with interferon-beta. J Neurol 2000;247:259-62. PMID 10836616
123: Motomura S, Tabira T, Kuroiwa Y. A clinical comparative study of multiple sclerosis and neuro-Behçet’s syndrome. J Neurol Neurosurg Psychiatry 1980;43:210-3. PMID 7373318
124: Nagahama Y, Shimohama S, Kaji R, Akiguchi I, Kimura J. An adult case of transverse myelitis with erythema infectiosum. Rinsho Shinkeigaku 1992;32:1035-7. PMID 1300262
125: Nakajima H, Furutama D, Kimura F, et al. Herpes simplex virus myelitis: clinical manifestations and diagnosis by the polymerase chain reaction method. Eur Neurol 1998;39:163-7. PMID 9605393
126: Nakashima I, Fujihara K, Takase S, Itoyama Y. Decrease in multiple sclerosis with acute transverse myelitis in Japan. Tohoku J Exp Med 1999;188:89-94. PMID 10494904
127: Needham EJ, Chou SHY, Coles AJ, Menon DK. Neurological implications of COVID-19 infections. Neurocrit Care 2020;32(3):667-71. PMID 32346843
128: Novy J, Carruzzo A, Maeder P, Bogousslavsky J. Spinal cord ischemia: clinical and imaging patterns, pathogenesis, and outcomes in 27 patients. Arch Neurol 2006;63:1113-20. PMID 16908737
129: Ojeda VJ. Necrotizing myelopathy associated with malignancy. Cancer 1984;53:1115-23. PMID 6362838
130: Okuda DT, Melmed K, Matsuwaki T, Blomqvist A, Craig AD. Central neuropathic pain in MS is due to distinct thoracic spinal cord lesions. Annals of Clinical and Translational Neurology 2014;1(8):554-61.** PMID 25356427
131: Paine RS, Byers RK. Transverse myelopathy in childhood. Am J Dis Child 1953;85:151-63. PMID 13007166
132: Pandit L, Rao S. Recurrent myelitis. J Neurol Neurosurg Psychiatry 1996;60:336-8. PMID 8609515
133: Panitch HS, Bever CT Jr, Katz E, Johnson KP. Upper respiratory tract infections trigger attacks of multiple sclerosis in patients treated with interferon. J Neuroimmunol 1991;Suppl 1:125.
134: Pardatscher K, Fiore DL, Lavano A. MR imaging of transverse myelitis using Gd-DTPA. J Neuroradiol 1992;19:63-7. PMID 1564531
135: Paty DW, Blume WT, Brown WF, et al. Chronic progressive myelopathy: investigation with CSF electrophoresis, evoked potentials, and CT scan. Ann Neurol 1978;6:419-24. PMID 92910
136: Perez-Montes R, Richard C, Baro J, Pascual J, Varela R, Zubizarreta A. Acute transverse myelitis and autoimmune pancytopenia after unrelated hematopoietic cell transplantation. Haematologica 2001;86:556-7. PMID 11410429
137: Perumal J, Zabad R, Caon C, et al. Acute transverse myelitis with normal brain MRK: Long-term risks of multiple sclerosis. J Neurol 2008;255:89-93. PMID 18080852
138: Pittock SJ, Lucchinetti CF. Inflammatory transverse myelitis: evolving concepts. Curr Opin Neurol 2006;19:362-8. PMID 16914974
139: Plum F, Olson ME. Myelitis and myelopathy. In: Baker AB, Baker LH, editors. Clinical neurology. Philadelphia: 1973:1-49.
140: Poser CM. Magnetic resonance imaging in asymptomatic disseminated vasculomyelinopathy. J Neurol Sci 1989;94:69-77. PMID 2614477
141: Pradhan S, Gupta RK, Kapoor R, et al. Parainfectious conus myelitis. J Neurol Sci 1998;161:156-62. PMID 9879697
142: Ravaglia S, Bastianello S, Franciotta D, et al. NMO-IgG-negative relapsing myelitis. Spinal Cord 2009;47(7):531-7. PMID 19104509
143: Reder AT, Thapar M, Jensen M. A reduction in serum glucocorticoids provokes experimental allergic encephalomyelitis: implications for treatment of inflammatory brain disease. Neurology 1994;44:2289-94. PMID 7991114
144: Richter RW, Pearson J, Bruun B, Challenor YB, Brust JC, Baden MM. Neurological complications of addiction to heroin. Bull N Y Acad Med 1973;49:3-21. PMID 4344820
145: Rimkus CM, Schoeps VA, Boaventura M, et al. Drug-related demyelinating syndromes: understanding risk factors, pathophysiological mechanisms and magnetic resonance imaging findings. Mult Scler Relat Disord 2021;55:103146. PMID 34332456
146: Roos KL. Acute severe spinal cord dysfunction in bacterial meningitis in adults. Arch Neurol 2001;58:717-8. PMID 11346365
147: Ropper A, Miett T, Chiappa K. Absence of evoked potential abnormalities in acute transverse myelopathy. Neurology 1982;32:80-2. PMID 6275306
148: Ropper AH, Poskanzer DC. The prognosis of acute and subacute transverse myelopathy based on early signs and symptoms. Ann Neurol 1978;4:51-9. PMID 697326
149: Ross AG, McManus DP, Farrar J, Hunstman RJ, Gray DJ, Li YS. Neuroschistosomiasis. J Neurol 2012;259(1):22-32. PMID 21674195
150: Rowe A, Gorman WP. Transverse myelitis and myelography. Bristol Med Chir J 1986;101:58-9. PMID 3664312
151: Rudnicki SA, Dalmau J. Paraneoplastic syndromes of the spinal cord, nerve, and muscle. Muscle Nerve 2000;23:1800-18. PMID 11102903
152: Sadowsky CL, Becker D, Bosques G, et al. Rehabilitation in transverse myelitis. Continuum (Minneap Minn) 2011;17(4):816-30. PMID 22810933
153: Sanders KA, Khandji AG, Mohr JP. Gadolinium-MRI in acute transverse myelopathy. Neurology 1990;40:1614-6. PMID 2215955
154: Satoh J, Yukitake M, Kurohara K, Takashima H, Kuroda Y. Detection of the 14-3-3 protein in the cerebrospinal fluid of Japanese multiple sclerosis patients presenting with severe myelitis. J Neurol Sci 2003;212:11-20. PMID 12809994
155: Schwartz K, Wymbs NF, Huang H, et al. Randomized, placebo-controlled crossover study of dalfampridine extended-release in transverse myelitis. Mult Scler J Exp Transl Clin 2017;3(4):2055217317740145. PMID 29270309
156: Scott TF. Nosology of idiopathic transverse myelitis syndromes. Acta Neurol Scand 2007;115:371-6. PMID 17511844
157: Scott TF, Bhagavatula K, Snyder PJ, Chieffe C. Transverse myelitis. Comparison with spinal cord presentations of multiple sclerosis. Neurology 1998;50:429-33. PMID 9484367
158: Scott TF, Kassab SL, Pittock SJ. Neuromyelitis optica IgG status in acute partial transverse myelitis. Arch Neurol 2006;63:1398-1400. PMID 17030654
159: Scott TF, Kassab SL, Singh S. Acute partial transverse myelitis with normal cerebral magnetic resonance imaging: transition rate to clinically definite multiple sclerosis. Mult Scler 2005;11:373-7. PMID 16042216
160: Seifert T, Enzinger C, Ropele S, Storch MK, Strasser-Fuchs S, Fazekas F. Relapsing acute transverse myelitis: a specific entity. Eur J Neurol 2005;12:681-4. PMID 16128868
161: Sellner J, Luthi N, Buhler R, et al. Acute partial transverse myelitis: risk factors for conversion to multiple sclerosis. Eur J Neurol 2008;15:398-405. PMID 18312402
162: Shyu WC, Lin JC, Chang BC, Harn HJ, Lee CC, Tsao WL. Recurrent ascending myelitis: an unusual presentation of herpes simplex virus type 1 infection. Ann Neurol 1993;34:625-7. PMID 8215253
163: Simnad VI, Pisani DE, Rose JW. Multiple sclerosis presenting as transverse myelopathy: clinical and MRI features. Neurology 1997;48:65-73. PMID 9008496
164: Sireesha Y, Uppin MS, Bohra K, Alugolu R, Neeharika ML, Kanikannan A. Longitudinally extensive transverse myelitis due to toxoplasma: an autopsy study. Ann Indian Acad Neurol 2018;21(2):161-3. PMID 30122845
165: Stubgen JP. Immune-mediated myelitis associated with hepatitis virus infections. J Neuroimmunol 2011;239(1-2):21-7. PMID 21945641
166: Suri A, Chabbra RP, Mehta VS, Gaikwad S, Pandey RM. Effect of intramedullary signal changes on the surgical outcome of patients with cervical spondylotic myelopathy. Spine J 2003;3(1):33-45. PMID 14589243
167: Taieb G, Allou T, Labauge P. Therapeutic approaches in CLIPPERS. Curr Treat Options Neurol 2017;19(5):17. PMID 28386850
168: Tartaglino LM, Croul SE, Flanders AE, et al. Idiopathic acute transverse myelitis: MR imaging findings. Radiology 1996;201:661-9. PMID 8939212
169: Tartaglino LM, Heiman-Patterson T, Friedman DP, Flanders AE. MR imaging in a case of postvaccination myelitis. AJNR Am J Neuroradiol 1995;16:581-2. PMID 7793384
170: Tavasoli A, Tabrizi A. Acute transverse myelitis in children, literature review. Iran J Child Neurol 2018;12(2):7-16. PMID 29696041
171: Thomas T, Branson HM, Verhey LH, et al. The demographic, clinical, and magnetic resonance imaging (MRI) features of transverse myelitis in children. J Child Neurol 2012;27(1):11-21. PMID 21968984
172: Tippett DS, Fishman PS, Panitch HS. Relapsing transverse myelitis. Neurology 1991;41:703-6. PMID 2027486
173: Tosi L, Rigoli G, Beltramello A. Fibrocartilaginous embolism of the spinal cord: a clinical and pathogenetic reconsideration. J Neurol Neurosurg Psychiatry 1996;60:55-60. PMID 8558152
174: Ungurean A, Palfi S, Dibo G, Tiszlavicz L, Vecsei L. Chronic recurrent transverse myelitis or multiple sclerosis. Funct Neurol 1996;11(4):209-14. PMID 8934153
175: Vakrakou AG, Evangelopoulos ME, Boutzios G, et al. Recurrent myelitis and asymptomatic hypophysitis in IgG4-related disease: case-based review. Rheumatol Int 2020;40(2):337-43. PMID 31898763
176: Voitenkov VB, Klimkin AV, Skripchenko NV, Pulman NF, Ivanova MV. Diagnostic transcranial magnetic stimulation as a prognostic tool in children with acute transverse myelitis. Spinal cord 2016;54(3):226-8. PMID 26238314
177: Wilmshurst JM, Walker MC, Pohl KR. Rapid onset transverse myelitis in adolescence: implications for pathogenesis and prognosis. Arch Dis Child 1999;80:137-42. PMID 10325728
178: Wulff CH. Evoked potentials in acute transverse myelopathy. Dan Med Bull 1985;32:282-6. PMID 4053703
179: Yamada S, Hoshi A, Takai Y, et al. Radiation tolerance dose of the spinal cord following conventionally fractionated irradiation. Gan No Rinsho 1987;33:1189-92. PMID 3669312
180: Yiu EM, Kornberg AJ, Ryan MM, Coleman LT, Mackay MT. Acute transverse myelitis and acute disseminated encephalomyelitis in childhood: spectrum or separate entities. J Child Neurol 2009;24(3):287-96. PMID 19258287
181: Yoon JH, Joo IS, Li WY, Sohn SY. Clinical and laboratory characteristics of atopic myelitis: Korean experience. J Neurol Sci 2009;285(1-2):154-8. PMID 19628231
182: Young J, Quinn S, Hurrell M, Taylor B. Clinically isolated acute transverse myelitis: prognostic features and incidence. Mult Scler 2009;15(11):1295-302. PMID 19812117
183: Zhao M, Zhang M, Zhou S, et al. Transverse myelitis associated with primary biliary cirrhosis: clinical, laboratory, and neuroradiological features. Int J Neurosci 2020:1-8. PMID 32842840
184: Ziegler DK. Acute disseminated encephalitis. Some therapeutic and diagnostic considerations. Arch Neurol 1966;14:476-88. PMID 5911246

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Transverse myelitis

Associated Disorders

Acute disseminated encephalomyelitis
Acute necrotizing hemorrhagic leukoencephalitis
Devic disease (neuromyelitis optica)
Inflammatory myelinoclastic diffuse sclerosis
MOG-IgG disease
- Multiple sclerosis
- Parainfectious conus myelitis
- Postinfectious encephalomyelitis
- Postvaccinal encephalomyelitis
- Schilder disease
- Schilder myelinoclastic diffuse sclerosis

Differential Diagnosis

AIDS-related myelopathy
angiodysgenetic myelomalacia
arteriovenous malformation
Balo concentric sclerosis
Behçet disease
- Foix-Alajouanine syndrome
- Guillain-Barré syndrome
- heroin myelopathy
- herpes simplex myeloradiculitis
- herpes zoster myelitis
- HTLV-1 associated myelopathy
- Intermittent claudication of the cord
- Lyme disease
- lymphoma
- metastatic epidural spinal cord compression
- mixed connective tissue disease
- necrotizing myelopathy (lupus-related)
- neurosarcoidosis
- paraneoplastic myelopathy
- pellagra
- polyarteritis nodosa
- progressive necrotizing myelopathy
- progressive systemic sclerosis
- psychogenic neurologic disorders
- radiation myelopathy
- Sjögren disease
- spinal abscess
- spinal astrocytoma
- spinal cord compression
- stiff-person syndrome
- subacute combined degeneration
- syrinx
- tick paralysis
- vascular disorders of the spinal cord

Also Relevant

Brucellosis of the nervous system
Clinically isolated syndrome
Epstein-Barr virus infections of the nervous system
Hepatitis viruses: neurologic complications
Intramedullary spinal cord metastatic tumors
- Multiple sclerosis: presentation and course
- Neurologic complications of vaccination
- Neuromyelitis optica spectrum disorders

Content Categories

Neuroimmunology

Transverse myelitis …

Transverse myelitis

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Authors

Patient Profile

ICD & OMIM codes

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Also in This Category

Acute inflammatory demyelinating polyradiculoneuropathy

Guillain-Barre syndrome in children

Tumefactive demyelinating lesions

Acquired human cytomegalovirus

Nonparaneoplastic autoimmune cerebellar ataxias

Motor and multifocal motor neuropathies

Radiologically isolated syndrome

Sarcoidosis neuropathy

Transverse myelitis

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Acute inflammatory demyelinating polyradiculoneuropathy

Guillain-Barre syndrome in children

Tumefactive demyelinating lesions

Acquired human cytomegalovirus

Nonparaneoplastic autoimmune cerebellar ataxias

Motor and multifocal motor neuropathies

Radiologically isolated syndrome

Sarcoidosis neuropathy

This is an article preview.
Start a Free Account
to access the full version.