NONCOMPRESSIVE CAUSES OF ACUTE MYELOPATHIES
The five groups of disorders that present as acute myelopathy are: demyelination, infections, other inflammatory disorders, vascular, and neoplastic and paraneoplastic. The first three are considered inflammatory disorders. Among these, demyelinating disorders are the most common. The initial task of the clinician is to determine which of these is most likely. In general, inflammatory disorders have an inflammatory cerebrospinal fluid (CSF) manifested by either pleocytosis, raised IgG index or both. Fig. [1] is an algorithm on the diagnosis and management of acute noncompressive myelopathies.
Figure 1 Diagnostic approach to acute myelopathy. MRI, magnetic resonance imaging; CSF, cerebrospinal fluid; NMO, neuromyelitis optica; MS, multiple sclerosis; IgG, immunoglobulin G; SS-A, Sjögren's syndrome antibody (anti-Ro).
Demyelinating Disorders
Typically, the onset of neurological symptoms in myelitis due to demyelination occurs over days with sensory motor symptoms and bladder and bowel disturbances, although occasionally necrotizing demyelinating myelopathies, including NMO, may progress over hours. They usually occur in individuals who are otherwise in good health and may be preceded by a nonspecific viral illness. Table [2] provides the differential diagnoses of demyelinating myelopathies and their clinical-radiological features.
Table 2 Causes of Acute Demyelinating Myelopathies and Diagnostic Clues
| Condition | Clinical Presentation | MRI Spinal Cord | MRI Brain | CSF |
| Multiple sclerosis | Partial myelopathy, e.g., Brown-Séquard; previous episodes of neurological dysfunction with recovery | Lesion less than 2 spinal cord segments, usually peripherally located; predilection for lateral and posterior funiculi | White matter lesions; Dawson's fingers; periventricular, juxtacortical, infratentorial lesions | OCB and raised IgG index |
| Neuromyelitis optica | 90% women; typically severe deficits; may have experienced previous myelitis or optic neuritis | Long cord lesion > 3 segments; cord swelling and gadolinium enhancement in acute lesions | Lesions present in up to 60% of patients, often subtle, usually periventricular; occasionally hypothalamic or brainstem lesions | Prominent CSF pleocytosis, occasionally with neutrophilic/eosinophilic predominance during acute attacks; no OCB in > 80%; usually normal or transiently elevated CSF IgG index |
| Acute disseminated encephalomyelitis | Monophasic; most commonly children; fever; encephalopathy; infectious (usually viral) prodrome | Variable lesion length | Large, often confluent white matter lesions; lesions of the same/similar duration (lacking evidence for “old” lesions) | Pleocytosis; OCB and IgG index that may be abnormal, often transiently |
| Postvaccinial | Monophasic; recent vaccination (preceding 3 wk) | Variable lesion length | Brain lesions possible | Pleocytosis; OCB and IgG index that may be abnormal, often transiently |
| Idiopathic transverse myelitis (Table [4]) | Monophasic; no cause after investigations; diagnosis of exclusion | Variable lesion length | No brain lesions | Pleocytosis OCB and IgG index that may be abnormal, often transiently |
| MRI, magnetic resonance imaging; CSF, cerebrospinal fluid; OCB, oligoclonal bands; IgG, immunoglobulin G. |
MULTIPLE SCLEROSIS
In MS, lesions are usually small (< 2 vertebral segments in length) and peripheral, and therefore cause asymmetric symptoms and signs (Fig. [2]). Lhermitte's sign (paresthesias spreading down the spine, often into the legs, on neck movement) is typical for a demyelinating lesion of the cervical posterior columns, but can be, although rarely, seen in other conditions that involve the same site. Other characteristic syndromes include isolated proprioceptive loss of an upper extremity (“sensory useless hand syndrome”),[1] Brown-Séquard syndrome, or, more commonly, incomplete versions thereof. Early in the relapsing phase of MS, before the development of fixed gliotic scars, symptoms usually resolve in a few weeks to months. CSF oligoclonal bands (OCBs) are present in more than 90% of patients, and a raised immunoglobulin (Ig)G index is seen in more than 60%. Subclinical optic nerve involvement may be evident on visually evoked response testing. At the first occurrence of a partial myelitis, the presence of two or more brain lesions indicates an 88% chance of conversion to MS in the next 20 years. With a normal MRI, the risk is only 19%.[2]
[3]
[4]
Figure 2 Cervical cord magnetic resonance imaging (MRI) from a 36-year-old woman with multiple sclerosis (MS). (A) Sagittal T2-weighted image shows discrete lesions without cord swelling. (B) Axial sections through the lower lesion show that the lesion is peripherally located within the cord.
NEUROMYELITIS OPTICA
Neuromyelitis optica is most commonly a relapsing demyelinating condition of the central nervous system (CNS) affecting predominantly the optic nerves and spinal cord. Table [3] lists the recently revised criteria for NMO. Lesions are centrally located and necrotic leading to more symmetric symptoms and signs, greater disability than seen in MS, and less complete recovery. The lesions in the cord are typically long (> 3 vertebral segments) (Fig. [3]). A history of severe optic neuritis should raise suspicion of NMO. NMO is relatively more common in Asian and African individuals, although the majority of patients with this condition in western countries are white. A variety of autoimmune conditions including SLE, Sjögren's syndrome, and thyroid autoimmune disorders may coexist with NMO. NMO-IgG is a recently identified serum antibody that is highly specific (> 90%) and sensitive (> 70%) for NMO.[5] It is also present in NMO spectrum disorders, including limited forms of NMO such as relapsing optic neuritis and relapsing myelitis. When identified at the first attack, NMO-IgG also predicts future episodes of myelitis or optic neuritis. In a prospective study, the risk of developing recurrent myelitis or new onset optic neuritis in patients with an isolated longitudinally extensive transverse myelitis was more than 50% among those who were NMO-IgG seropositive, compared with 0% in those who were NMO-IgG seronegative.[6] Brain MRI can be abnormal in NMO. Typically, lesions are periventricular, especially in regions of high concentration of aquaporin-4, the target antigen for the NMO-IgG.[7]
Table 3 Diagnostic Criteria for Neuromyelitis Optica
| Optic neuritis |
| Acute myelitis |
|
And at least two of three supportive criteria: |
| 1. Contiguous spinal cord MRI lesion extends over 3 vertebral segments. |
| 2. Brain MRI does not satisfy diagnostic criteria for multiple sclerosis. |
| 3. NMO-IgG is seropositive. |
| MRI, magnetic resonance imaging; NMO, neuromyelitis optica; IgG, immunoglobulin G. |
| From Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006;66(10):1485-1489. |
Figure 3 Cervical cord magnetic resonance imaging (MRI) from a 56-year-old woman with neuromyelitis optica (NMO). NMO-immunoglobulin (Ig)G was positive. (A) Sagittal T2-weighted MRI scan shows a longitudinally extensive T2 hyperintense lesion. (B) Axial image shows that the lesion is central within the cord.
ACUTE DISSEMINATED ENCEPHALOMYELTIS
Acute disseminated encephalomyelitis (ADEM) is a monophasic disorder that affects the brain and occasionally the spinal cord.[8] Often there is a history of preceding viral or other infectious illness. The brain and spinal cord show demyelinating lesions that are generally of the same age, although gadolinium enhancement may not be seen in all, and, occasionally, not in any of the lesions. ADEM may evolve over the course of up to 3 months. ADEM is more common in children, and is only reliably diagnosed in individuals who have concomitant encephalopathy. Follow-up of individuals with a clinical diagnosis of ADEM reveals that ~25% of cases eventually meet clinical criteria for MS.
POSTVACCINE MYELITIS
An acute transverse myelitis occurring in the 3 weeks following a vaccination has been linked to an immunological reaction to the vaccine, such as smallpox or rabies. In recent years vaccines such as hepatitis B, typhoid, influenza, rubella, and tetanus have been implicated,[9]
[10]
[11]
[12]
[13]
[14] but a causal relationship has not been established. Such cases may reflect chance occurrences of idiopathic transverse myelitis in patients who incidentally have had a vaccination.
ACUTE IDIOPATHIC TRANSVERSE MYELITIS
Inflammatory transverse myelitis (CSF inflammation with usual pleocytosis and occasionally elevated IgG index/OCBs) in the absence of a specific cause (such as MS, NMO, ADEM, connective tissue disease, etc.) is the most common cause of acute myelitis.[15]
[16] Criteria have been proposed for this entity[17] (Table [4]). However, the idiopathic nature is a diagnosis of exclusion. The bimodal peaks in onset ages are 10 to 19 years and 30 to 39 years. A preceding nonspecific fever, nausea, or muscle pain, possibly indicating a prior viral infection, is common, although one or more of these symptoms may also precede attacks of MS and NMO. The lesion length varies from less than one segment to the entire cord. Many of these large series of patients were reported before NMO-IgG was identified, and it is possible that many such patients may have an NMO spectrum disorder. The proportion of “idiopathic” inflammatory transverse myelitis is likely to decline with the increasing availability of newer autoimmune markers, imaging techniques, and microbiological tests capable of defining a specific etiology.
Table 4 Criteria for Idiopathic Acute Transverse Myelitis (modified from reference 17)
| Inclusion Criteria | Exclusion Criteria |
| • Sensory, motor, or autonomic dysfunction attributable to the spinal cord | • History of previous radiation to the spine within the past 10 years |
| • Bilateral signs and/or symptoms (though not necessarily symmetric) | • Clinical deficit consistent with thrombosis of the anterior spinal artery |
| • Clearly defined sensory level | • Abnormal flow voids on the surface of the spinal cord consistent with AVFs |
| • Exclusion of extra-axial compressive etiology by neuroimaging (MRI, myelography; CT of spine not adequate) | • Serologic or clinical evidence of connective tissue disease (sarcoidosis, Behçet's disease, Sjögren's syndrome, SLE, mixed connective tissue disorder, etc.)[*]
|
| • Inflammation within the spinal cord demonstrated by CSF pleocytosis or elevated IgG index or gadolinium enhancement | • Clinical or laboratory evidence for syphilis, Lyme disease, HIV, HTLV-1, Mycoplasma, other viral infection (e.g., HSV- 1, HSV-2, VZV, EBV, CMV, HHV-6, enterovirus)[*]
|
| • If none of the inflammatory criteria is met at symptom onset, repeat MRI and lumbar puncture evaluation between 2 and 7 days following symptom onset | • Brain MRI abnormalities suggestive of MS[*]
|
| • Progression to nadir between 4 hours and 21 days following the onset of symptoms (if patient awakens with symptoms, symptoms must become more pronounced from point of awakening) | • History of clinically apparent optic neuritis[*]
|
| AVFs, arteriovenous fistulas; MRI, magnetic resonance imaging; CT, computed tomography; CSF, cerebrospinal fluid; SLE, systemic lupus erythematosus; IgG, immunoglobulin G; HIV, human immunodeficiency virus; HTLV-1, human T-lymphotropic virus 1; HSV, herpes simplex virus; VZV, varicella zoster virus; EBV, Epstein-Barr virus; CMV, cytomegalovirus; HHV, human herpes virus. |
2 Do not exclude disease-associated acute transverse myelitis.
Assessment for Recurrence Risk in Demyelinating Myelopathies
After management of acute myelitis with steroids and/or plasma exchange, demyelinating myelopathies need to be evaluated for the risk of recurrence. The major decision point is whether a patient has complete or incomplete transverse myelitis (Fig. [1]). Complete transverse myelitis usually has more or less symmetrical findings and involvement of motor, sensory, and sphincter function. Incomplete transverse myelitis usually has asymmetric findings that may involve a limited number of tracts and does not typically result in loss of all motor, sensory, and sphincter function. In general, complete transverse myelitis is associated with a long spinal cord lesion exceeding three vertebral segments in length, often central within the cord, and an incomplete transverse myelitis is associated with a short spinal cord lesion, typically one to two segments in length and peripheral. However, there are exceptions to this general rule.
Patients with Complete Transverse Myelitis
Complete transverse myelitis patients, in general, are at low risk for future development of MS. However, they could have recurrences consistent with relapsing myelitis or NMO. Two autoimmune markers that may predict recurrence are anti-Sjögren's syndrome antibody (SS-A) and NMO-IgG.[18] NMO-IgG predicted each case of recurrence in a Mayo Clinic series, whereas anti-SS-A did not.[6] Thirty-eight percent of patients with a first episode of transverse myelitis were seropositive for NMO-IgG in a recent Mayo Clinic series; more than 50% of those followed for 1 year had recurrent myelitis or optic neuritis, whereas none of the seronegative patients experienced recurrence.[6] We currently advise testing for NMO-IgG in patients who have experienced a first episode of longitudinally extensive transverse myelitis, and instituting immunosuppressive therapy in those positive for NMO-IgG. We believe that monophasic inflammatory demyelinating transverse myelitis in patients seropositive for NMO-IgG is a limited form of NMO with a high risk of relapse, or an NMO spectrum disorder, and should be managed accordingly.
Patients with Incomplete Transverse Myelitis
This group of patients is currently regarded as having a clinically isolated syndrome (CIS), which places them at risk for developing other symptoms that will lead to a definite diagnosis of MS. Cranial MRI is used to determine the degree of risk of MS. Those with lesions consistent with MS (two or more) are at high risk, currently estimated at 88% within 20 years. Those with a normal brain on MRI have a much lower risk, ~19% at 20 years.[2]
[4] Some experts advocate prophylactic treatment with disease-modifying therapy for high-risk patients.[19] The prognosis for MS attacks may be much better than for NMO attacks, and some would argue that it would be worth waiting to determine if further disease activity occurs, given the highly variable and often favorable prognosis of MS.[20] This is a major point of controversy regarding management of CIS. Other predictors of recurrence include CSF OCBs.[21]
[22] MRI remains the single most potent predictor, although it is subject to problems of specificity of MRI-identified brain lesions for demyelinating disease.
Acute Infectious Myelopathies
Viral, bacterial, fungal, and parasitic agents can cause acute myelitis (Fig. [4]). Patients are systemically ill with fever and meningismus. Prominent CSF inflammation (pleocytosis, often neutrophilic and raised protein concentration) must prompt investigation for a causative agent, especially a treatable one. This is in contrast to parainfectious or idiopathic inflammatory myelitis where patients have recovered from a recent infection, usually viral. Table [5] lists clinical clues to an infectious cause, Table [6] lists the infectious agents, and Table [7] provides diagnostic studies. However, in most cases of acute viral myelitis, a specific viral cause is never determined.[23]
Figure 4 Sagittal T2-weighted magnetic resonance imaging (MRI) of the cervical cord in a 43-year-old man who developed herpes zoster in the upper limbs and simultaneously a longitudinally extensive cervical myelitis. (Image courtesy of Dr. Orhun Kantarci, Mayo Clinic, Rochester, MN.)
Table 5 Clinical Indications Suspicious of an Infectious Myelopathy
| Fever |
| Confusion |
| Meningismus |
| Rash |
| • Vesicular rash in the buccal mucosa and on the hands and feet in enterovirus 71 |
| • Herpes zoster rash in dermatomal distribution |
| • Erythema chronicum migrans of Lyme disease (rarely presents as acute myelitis) |
| Concurrent systemic infection |
| Immunocompromised state |
| Recurrent genital infection |
| Lymphadenopathy |
| Residence in area endemic for parasitic infections |
Table 6 Causes of Acute Myelopathies Resulting from Infectious Agent
| Specific Agents |
|
Viruses
|
DNA Viruses
|
RNA viruses
|
| Herpesviruses
| Flaviviruses
|
| Herpes simplex virus-2[*]
| Dengue virus |
| Varicella-zoster virus[*]
| Japanese encephalitis virus[†]
|
| Cytomegalovirus[*]
| St. Louis encephalitis virus |
| Human herpes viruses 6 and 7 | Tick-borne encephalitis virus[†]
|
| Epstein-Barr virus[36]
[*]
| West Nile virus[†]
|
| | Orthomyxoviruses
|
| | Influenza A virus |
| | Paramyxoviruses
|
| | Measles virus |
| | Mumps virus |
| | Picornaviruses
|
| | Coxsackieviruses A and B[†]
|
| | Echoviruses |
| | Enterovirus-70 and -71[†]
|
| | Hepatitis A, C[37]
|
| | Poliovirus types 1, 2, and 3[†]
|
|
Bacterial
| Spinal cord abscess due to hematogenous spread of systemic infection | |
| Mycoplasma, Borrelia burgdorferi (Lyme), Treponema pallidum (syphilis) | |
|
Mycobacterium tuberculosis
| |
|
Fungal
|
Actinomyces, Blastomyces dermatitidis, Coccidioides, Aspergillus
| |
|
Parasites
| Neurocysticercosis, Schistosoma, Gnathostoma, angiostrongylosis (eosinophilic myelitis) | |
| Note: HTLV-1 (human T-lymphotropic virus 1) and HIV can cause a chronic myelitis without brain involvement. |
3 Common causes.
4 Can cause acute poliomyelitis-like syndrome due to preferential, rather than selective, destruction of anterior horn cells and other motor pathways.
Table 7 Cerebrospinal Fluid Evaluation in Suspected Infectious Myelitis
|
Stains and cultures
|
| • Gram's stain, bacterial culture |
| • Acid-fast bacilli smear and tuberculosis culture |
| • CSF India ink smear and fungal culture |
| • Viral cultures |
|
CSF polymerase chain reaction
|
| • Herpes simplex virus type 1 |
| • Herpes simplex virus type 2 |
| • Human herpesvirus 6 |
| • Varicella-zoster virus |
| • Cytomegalovirus |
| • Epstein-Barr virus |
| • Enteroviruses |
| • Herpes simplex virus |
| • Varicella-zoster virus |
| • Human T-lymphotropic virus type 1 |
| • Borrelia burgdorferi (Lyme) |
|
Serology |
| • Herpes simplex virus |
| • Varicella-zoster virus |
| • HIV |
| • Human T-lymphotrophic virus type 1 |
| • B. burgdorferi |
| • Syphilis |
| • Hepatitis A, B, C |
| • Mycoplasma |
| • Parasites |
|
Blood cultures
|
|
Chest radiograph/CT
|
| CSF, cerebrospinal fluid; HIV, human immunodeficiency virus; CT, computed tomography. |
Myelopathies Associated with Other Inflammatory Disorders
Connective tissue disorders and granulomatous disorders may present with acute or subacute myelitis. SLE, Sjögren's syndrome, scleroderma, mixed connective tissue disorder (MCTD), Behçet's disease, and sarcoidosis (Fig. [5]) have all been associated with myelitis.[24]
[25]
[26] However, it is rare for myelitis to be the presenting symptom. Almost invariably, classical systemic features, brain, or meningeal involvement, at least on MRI, will be present before development of myelitis. In general, established criteria for these disorders should be satisfied before the myelitis is attributed to these disorders. CSF is usually inflammatory, and MRI of the spinal cord may show enhancing lesions. The significance of an autoantibody (e.g., antinuclear antibody [ANA]) in isolation without consistent systemic clinical features is suspect. Table [8] lists the conditions that could cause acute inflammatory myelopathy and criteria needed to diagnose them. Recent evidence suggests that the presence of autoantibodies in patients with acute myelitis may suggest that the myelitis is an NMO spectrum disorder. This is because NMO-IgG is present in approximately half such cases, whereas it is absent in patients with connective tissue diseases, such as SLE and Sjögren's syndrome, who do not have a history of myelitis or optic neuritis.
Figure 5 Sagittal T2-weighted magnetic resonance imaging (MRI) of the thoracic cord of a 45-year-old woman with sarcoidosis who presented with a subacute myelopathy.
Table 8 Disorders that Could Cause Acute Inflammatory Myelopathy and Criteria to Diagnose Them
| Condition | Criteria |
|
SLE
|
The 1982 revised criteria; 4 of 11 needed for diagnosis:
[38]
|
| 1. Malar rash |
| 2. Discoid rash |
| 3. Photosensitivity |
| 4. Oral ulcers |
| 5. Arthritis |
| 6. Serositis |
| 7. Renal disorder |
| 8. Neurologic disorder: (a) seizures or (b) psychosis (both not due to drugs or metabolic abnormalities) |
| 9. Hematologic disorder |
| 10. Immunologic disorder (positive LE cell preparation/Anti-DNA/Anti-Sm/false-positive serologic test for syphilis |
| 11. Antinuclear antibody |
|
Primary Sjögren's syndrome
|
International consensus criteria; 4 of 6 any criteria or 3 of 4 objective criteria need to be present for diagnosis:
[39]
|
| 1. Dry eyes |
| 2. Dry mouth |
| 3. Objective evidence of dry eyes (at least one present): |
| Schirmer test, Rose-Bengal, lacrimal gland biopsy |
| 4. Histopathology of minor salivary glands focal lymphocytic sialoadenitis |
| 5. Objective evidence of salivary-gland involvement (at least one present): |
| Salivary-gland scintigraphy, parotid sialography, unstimulated whole sialometry (1.5 mL per 15 min) |
| 6. Laboratory abnormality (at least one present): |
| Anti-SS-A or anti-SS-B, ANA, IgM rheumatoid factor (anti-IgG Fc) |
|
MCTD
|
Diagnostic criteria:
[40]
|
| 1. Serological: High titer anti-U1RNP |
| 2. Clinical: Edema of hands/synovitis/myositis/Raynaud's phenomenon/acrosclerosis |
| 3. Serological criteria and at least three clinical criteria, including either synovitis or myositis required |
|
Systemic sclerosis (Scleroderma)
|
ARA Preliminary classification criteria 1980:
[41]
|
| Proximal skin scleroderma or two of the following three criteria: |
| • Sclerodactyly (fingers or toes) |
| • Digital pitting scars/pulp loss |
| • Bibasilar pulmonary fibrosis |
|
Neurosarcoidosis
|
Proposed criteria for diagnosis:
|
|
Definite: Clinical presentation suggestive of neurosarcoidosis with exclusion of other possible diagnoses and the presence of nervous system histology |
|
Probable: Clinical syndrome suggestive of neurosarcoidosis with: |
| • Laboratory support for CNS inflammation (elevated levels of CSF protein and/or cells, the presence of oligoclonal bands and/or MRI evidence compatible with neurosarcoidosis) |
| • Exclusion of alternative diagnoses |
| • Evidence for systemic sarcoidosis (either through positive histology, including Kveim test, and/or at least two indirect indicators from Gallium scan, chest imaging, elevated serum ACE) |
|
Possible: Clinical presentation suggestive of neurosarcoidosis with exclusion of alternative diagnoses where the above criteria are not met |
|
Behçet's Disease
|
International Study Group for Behçet's Disease; 1990 criteria:
[42]
|
| Recurrent oral ulceration should occur at least three times in 1 y, accompanied by any two of the following: |
| 1. Recurrent genital ulcers |
| 2. Anterior or posterior uveitis or retinal vasculitis |
| 3. Skin lesions (erythema nodosum, acneiform nodules, pseudofolliculitis, and papular lesions) |
| 4. Positive pathergy test |
| SLE, systemic lupus erythematosus; LE, lupus erythematosus; SS-A, Sjögren's syndrome antibody A (anti-Ro); SS-B, Sjögren's syndrome antibody B (anti-La); ANA, antinuclear antibody; Ig, immunoglobulin; Fc, fragment, crystallizable (of immunoglobulin); MCTD, mixed connective tissue disorder; ARA, American Rheumatism Association; CNS, central nervous system; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; ACE, angiotensin-converting enzyme. |
Vascular Disorders
The arterial supply of the spinal cord consists of a single anterior spinal artery and two posterior spinal arteries (that course vertically over the surface of the cord) and their penetrating branches.[27] Acute vascular occlusion can lead to spinal cord infarction mimicking myelitis (Fig. [6]). Arterial occlusions are rare and develop acutely over minutes. However, arteriovenous fistulas (AVFs) usually progress slowly due to gradual ischemia resulting from venous congestion. Sudden decompensation of myelopathy caused by AVFs or bleeding into vascular malformations may also mimic myelitis (Fig. [7]). CSF is usually normal, although spinal AVF can lead to elevated CSF protein concentration without pleocytosis. Causes of acute vascular myelopathies and diagnostic clues are listed in Table [9].
Figure 6 Sagittal T2-weighted cervical magnetic resonance imaging (MRI) of a 49-year-old woman who developed acute paraparesis and a thoracic sensory level to pain following heavy physical exertion. Arrow points to the linear lesion in the anterior cord-presumed anterior spinal artery occlusion. (Image courtesy of Mark Keegan, Mayo Clinic, Rochester MN.)
Figure 7 A 49-year-old man who presented with acute myelopathy. (A) T1-weighted image shows no definite abnormality. (B) T2-weighted image shows hyperintense longitudinally extensive lesion. (C) Gadolinium-enhanced T1-weighted image reveals dilated blood vessels on the surface of the cord.
Table 9 Causes of Acute Vascular Myelopathies and Diagnostic Clues[27]
[43]
[44]
| Condition | Clinical Presentation | MRI Spinal Cord |
| Anterior spinal artery occlusion[27] (spinal radicular artery occlusion is clinically indistinguishable) | Anterior cord syndrome especially in the following settings: | Elongated “pencil-like” lesion in the anterior cord[43]
|
| • Aortic surgery | |
| • Spinal angiography | |
| • Vasculitis | |
| • Embolic source (e.g., cardiac; cholesterol) | |
| • Aortic/vertebral dissection | |
| • Hypotension | |
| • Prothrombotic states (e.g., sickle cell; protein C or S deficiency; activated protein C resistance/Factor V Leiden; antiphospholipid syndromes) | |
| Posterior spinal artery occlusion | Posterior column dysfunction | Triangular lesion in posterior cord |
| • Etiology as above | |
| Sulcocommissural artery[27]
| Brown Séquard syndrome | Lateral cord lesion |
| • Etiology as above | |
| Arteriovenous fistulas | • Stepwise progressive or recurrent episodes of weakness related to upright posture or walking, accompanied by upper motor neuron or lower motor neuron syndrome or both | Long spinal cord lesion often extending into the conus on T2 images; tortuous vessels seen on the surface of the cord; if highly suspected, despite normal MRI proceed to spinal angiogram |
| • Due to ischemia or congestion | |
| Hematomyelia | • Bleeding diathesis (coagulation/platelet) | Appearance of blood products (exact appearance depends on stage) |
| • Cavernomas | Flow voids in the cord |
| • Arteriovenous malformations of the cord | |
| • Osler-Rendu-Weber syndrome (hereditary hemorrhagic telangiectasia) | |
| Fibrocartilaginous disc embolism[45]
| • Back pain and history of physical exertion | Loss of vertical intervertebral disc height and T2 signal abnormality in corresponding level cord; microfractures of the vertebral endplates |
| • Features of anterior spinal artery occlusion | |
| MRI, magnetic resonance imaging. |
Neoplasia and Myelopathy
Intramedullary metastatic disease and intradural extramedullary compressive tumors (neurofibromas and meningiomas) are common causes of acute or acute-on-chronic myelopathy. Primary intramedullary cord tumors (ependymomas, astrocytomas, hemangioblastomas) or metastatic intramedullary tumors usually present over weeks. This is not a difficult diagnosis when there is an enhancing heterogenous lesion on MRI, especially with known systemic cancer. However, certain situations may cause diagnostic dilemmas.
ACUTE PRESENTATIONS OF SPINAL TUMORS
Hemorrhage or infarction of tumors resulting in acute swelling can mimic myelitis. Intramedullary cord lymphomas may respond symptomatically and radiologically to corticosteroids, which can further confuse the diagnosis. If serial imaging, CSF studies, and a search for a primary neoplasm are inconclusive, cord biopsy may be necessary. OCBs in CSF may be seen with tumors, but persistence of the bands is unusual.[28] Persisting gadolinium enhancement months after treatment of an acute myelitis should alert physicians to a potential neoplasm.[28]
RADIATION-ASSOCIATED MYELOPATHY
Radiation-induced myelopathies are usually slowly progressive but may occur up to 15 years after the end of radiation treatment, which may obscure the role of radiation therapy in causing the myelopathy. Early in the course, cord swelling or enhancement may be seen, but later atrophy may be the only finding.[29] Myokymia may be evident on electromyography (EMG) in affected muscles. MRI may show cord lesions indistinguishable from inflammatory lesions, but the simultaneous involvement of the adjacent vertebrae (usually hyperintense on T2-weighted scans) in the same field of radiation is an important clue to the etiology (Fig. [8]).
Figure 8 Radiation myelopathy. Sagittal T2-weighted image of the thoracic cord of a 34-year-old man with Hodgkin's lymphoma who received radiotherapy and presented 2 years later with subacute myelopathy and thoracic sensory level. Long arrow points to the longitudinally extensive T2 hyperintense intramedullary lesion. The short arrow points to the vertebral changes in the field of radiation. The vertebra immediately below seems normal. (Image courtesy of Dr Orhun Kantarci, Mayo Clinic, Rochester, MN.)
Paraneoplastic Disorders and Myelopathy
When paraneoplastic antibodies are identified in neurological syndromes, they usually predict an underlying cancer and not necessarily a specific neurological syndrome.[30] Several paraneoplastic antibodies are associated with subacute myelopathies, and a search for such antibodies and an underlying malignancy is warranted if other etiologies for the myelopathy are not apparent (Table [10]). Autoimmunity to CRMP5 may lead to myelopathy and optic neuropathy that may mimic NMO,[31] and when present, should spur a search for an underlying small cell lung carcinoma. Amphiphysin-specific antibodies raise the possibility of breast cancer. Detection of a longitudinally extensive tract-specific lesion, usually symmetrically involving both sides of the cord, may occur with diverse cancers. We have recently recognized this finding, particularly when accompanied by gadolinium enhancement, as a specific radiological sign of a paraneoplastic myelopathy (Fig. [9]). Some paraneoplastic conditions may mimic a myelopathy, although they are more likely “neurochemical” (e.g., GAD65 autoimmunity and stiff man syndrome-associated spasms may mimic spasticity; amphiphysin and rigidity/myoclonus may mimic spasticity).[32]
[33]
[34]
[35]
Table 10 Myelopathy Associated with Paraneoplastic Antibodies and Cancers
| Cancers Associated with Possible Paraneoplastic Myelopathies | Paraneoplastic Antibodies Associated with Myelopathies |
| Small cell lung carcinoma | Amphiphysin-IgG |
| CRMP-5 IgG |
| GAD |
| Cation channel antibodies[*]
|
| Breast cancer | PCA 2 |
| Ovarian cancer | ANNA 2 |
| Non-small cell lung cancer | Neuronal and muscle AChR antibodies |
| Ig, immunoglobulin; CRMP, collapsin response-mediator protein; GAD, glutamic acid decarboxylase; PCA, Purkinje cell antibody; ANNA, antineuronal nuclear antibodies; AChR, acetylcholine receptor. |
5 P/Q or N-type calcium channel, KC voltage-gated potassium channel.
Figure 9 Paraneoplastic tractopathy. Axial T2 sections through the cord of a 69-year-old woman with melanoma and high titres of amphiphysin-immunoglobulin (Ig)G. Arrow points to hyperintensity in the region of the corticospinal tracts. (Reproduced with permission from Pittock SJ, Lucchinetti CF, Parisi JE, et al. Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol 2005;58[1]:96-107.)
Myelopathy with Normal Magnetic Resonance Imaging
Occasionally, the MRI is normal in the setting of an acute myelopathy. There are several potential explanations. First, the syndrome may not be a myelopathy. Guillain-Barré syndrome may be mistaken as myelitis, especially considering the abnormal CSF protein concentration and ascending symptoms that may mimic those seen in myelitis. Enhancing nerve roots on MRI may be a clue to an inflammatory radiculopathy (Fig. [10]). It is uncommon to find an acellular CSF in acute inflammatory myelitis. Second, it may not be an acute problem. It is well known that trivial trauma or environmental or physiological stressors like viral illnesses may decompensate a longstanding myelopathy, making it symptomatic to the patient. Friedreich's ataxia, motor neuron disease, vitamin B12 or copper deficiency myelopathy, hereditary spastic paraparesis, human immunodeficiency virus (HIV), human T-lymphotropic virus 1 (HTLV-1)-myelopathy, and adrenomyeloneuropathy may all have such “pseudo-acute” presentations. MRI scans are more often normal than not in these disorders.
Figure 10 A 67-year-old woman with presumed acute myelopathy and markedly elevated cerebrospinal (CSF) protein. (A) T2-weighted sagittal magnetic resonance imaging is normal; (B) T1-weighted, gadolinium-enhanced axial section through the cauda equina with gadolinium showed enhancing nerve roots. Nerve conduction studies confirmed acute inflammatory demyelinating polyneuropathy.
Imaging performed during the convalescent phase may miss a cord lesion. The quality of the images may have been suboptimal, especially in terms of resolution of an intramedullary lesion. Repeat imaging using sedation, if necessary, to prevent movement-related artifact may be needed if suspicion of myelopathy is high. Table [11] lists the various other possibilities for myelopathy with normal MRI.
Table 11 Approach to ‘Myelopathy’ with Normal Magnetic Resonance Imaging
| Alternative Explanations | Examples |
| Has a compressive cause been missed? | Epidural lipomatosis |
| Dynamic compression on flexion extension only[46]
[47]
|
| Is it really a myelopathy? | Ganglionopathy, e.g., Sjögren's, paraneoplastic, toxins |
| Peripheral nerve disease, e.g., acute inflammatory polyradiculoneuropathy |
| Plexopathy, e.g., neoplastic or idiopathic inflammatory |
| Neuromuscular junction, e.g., myasthenia gravis |
| Muscle, e.g., periodic paralysis |
| Motor neuronopathy, e.g., ALS/primary lateral sclerosis |
| Is there a cerebral cause for the deficit? | Parasagittal meningioma |
| Cerebral venous thrombosis |
| Anterior cerebral artery thrombosis |
| Normal pressure hydrocephalus |
| Hydrocephalus |
| Small vessel disease (vascular lower limb predominant parkinsonism) |
| Other extrapyramidal disorders |
| Is it an acute presentation of an underlying chronic metabolic, degenerative, or infective myelopathy? | B12, folate, copper deficiency |
| Nitrous oxide inhalation |
| HTLV-1 |
| HIV |
| Syphilis |
| Motor neuron disease (ALS) |
| Adrenomyeloneuropathy |
| Hereditary spastic paraplegia |
| Friedreich's ataxia |
| Lathyrism |
| Is the image quality adequate? | Motion artifact |
| Low-strength magnet (0.5 T) |
| Were the images taken too early or too late in time and therefore “missed” the lesion (i.e., before it appeared or after it resolved)? | Long lesions of NMO may appear patchy or short, and hence nondiagnostic, if imaging is performed in the convalescent phase |
| Is the lesion too small to be seen on MRI? | |
| Is the weakness not organic (“functional”)? | |
| ALS, amyotrophic lateral sclerosis; HTLV-1, human T-lymphotropic virus 1; HIV, human immunodeficiency virus; NMO, neuromyelitis optica. |
