Imaging Approach to Myelopathies

Myelopathy refers to spinal cord involvement from diverse etiologies resulting in neurologic symptoms. The presentation is variable, often posing a diagnostic challenge due to overlapping clinical and imaging features. Classification by symptom onset aids in the differential diagnosis and is based on hyperacute, acute/subacute, and chronic presentations, each carrying distinct prognoses. MR imaging is pivotal for diagnosis, providing detailed characterization of spinal cord involvement. This article offers a comprehensive overview of various diseases causing myelopathy, their imaging manifestations, differential diagnoses, and diagnostic algorithms, emphasizing the role of MR imaging in facilitating prompt identification of underlying causes and guiding optimal management.

Key points

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Myelopathies have diverse causes, including inflammatory, metabolic, vascular, and neoplastic diseases, necessitating thorough recognition for accurate diagnosis.
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MR imaging is crucial for diagnosing myelopathies, providing detailed characterization of spinal cord abnormalities and guiding treatment decisions.
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Compression is the primary cause of myelopathy and requires prompt evaluation with CT and MR imaging to determine its severity and guide intervention.
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Symptom onset, MR imaging findings, and laboratory tests aid in narrowing the differential diagnosis, while lesion distribution and extent provide additional diagnostic insights.

Abbreviations

ADEM	acute disseminated encephalomyelitis
AQP4	aquaporin-4 water channels
ATM	Acute transverse myelitis
AVF	arteriovenous fistulas
AVM	arteriovenous malformations
CAR	chimeric antigen receptor
CMV	cytomegalovirus
CRS	cytokine release syndrome
CSF	cerebrospinal fluid
CT	computed tomography
DWI	diffusion-weighted imaging
GRE	gradient echo
ICANS	immune effector cell-associated neurotoxicity syndrome
LETM	longitudinally extensive transverse myelitis
MOG	myelin oligodendrocyte glycoprotein
MOGAD	myelin oligodendrocyte glycoprotein antibody-associated disease
MS	multiple sclerosis
NMDA	N-methyl- d -aspartate
NMOSD	neuromyelitis optica spectrum disorders
SCD	subacute combined degeneration
STIR	short-tau inversion recovery
T1WI	T1-weighted imaging
T2WI	T2-weighted imaging

Introduction

Myelopathy is a term used to describe various processes that affect the spinal cord, resulting in a range of neurologic symptoms. Timely diagnosis is crucial for management but can be challenging due to variable pathogenesis and similar clinical presentations among different etiologies. A comprehensive evaluation, including clinical, imaging, and laboratory findings, is necessary to determine the underlying cause. ^,

Classification of myelopathies based on the timing of symptom onset (hyperacute, acute/subacute, or chronic) provides a framework for differential diagnosis, with different underlying mechanisms and prognostic implications associated with each category. Hyperacute myelopathies are characterized by sudden onset and rapid progression, while acute/subacute and chronic forms present with insidious symptoms. Compressive etiologies, including degenerative and neoplastic conditions, are the most common causes of myelopathy. Inflammatory disorders, such as multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica spectrum disorders (NMOSD), also contribute substantially to the myelopathy spectrum. Other causes of myelopathy include vascular disorders, infections, metabolic disorders, and trauma. Imaging studies, particularly MR imaging, play a crucial role in the diagnosis, providing detailed information about the spinal cord and surrounding structures and helping identify the underlying cause of myelopathy.

This article aims to delineate the clinical and imaging features of various myelopathies and provide a streamlined algorithm for differential diagnosis. Additionally, we emphasize the importance of MR imaging in elucidating key diagnostic clues, enabling timely identification of underlying etiologies and guiding appropriate management strategies and prognostication.

Terminology, Etiology, Classification, and Diagnostic Approach

Terminology

Myelopathy refers to a wide range of pathologic conditions affecting the spinal cord, presenting with various clinical manifestations ranging from hyperacute to chronic. Hyperacute myelopathies are characterized by rapid symptom progression, peaking within minutes to 4 hours of onset. In contrast, acute/subacute and chronic myelopathies develop more slowly, with acute/subacute extending over 4 hours to 21 days and chronic presenting over months to years. ^, ^,

Acute transverse myelitis (ATM) refers to a distinct clinical presentation with bilateral spinal cord involvement leading to sensory or motor deficits. ATM does not represent a specific diagnosis but rather a syndrome that can originate from different underlying pathologies. Unlike ATM, partial myelitis is more localized, affecting only one side of the spinal cord or a specific tract, frequently observed in conditions such as MS. ^,

Classification and etiology

Myelopathies can be disease-associated or idiopathic, the latter being a diagnosis of exclusion after ruling out known causes. Disease-associated myelitis includes a wide range of conditions, such as inflammatory (localized or systemic), vascular, and infectious disorders. In addition, various conditions can mimic inflammatory myelopathies, including metabolic and toxic abnormalities, radiation-induced changes, and paraneoplastic disorders.

Myelopathies can develop as primary spinal cord disorders or from conditions that affect the cord secondarily, such as extrinsic compression. They can also be classified based on the timing of clinical onset into hyperacute, acute/subacute, or chronic, which is a useful first step in the clinical workup ( Table 1 ). ^, ^,

Table 1

Etiologic classification of myelopathy based on symptom acuity

Data from Refs. ^,^,

Hyperacute myelopathy (over minutes to 4 h)	Spinal cord infarction	• Hyperacute onset of symptoms → transfixing or belt-like acute pain, rapid and profound motor deficits. • Anterior pencil-like stripes on sagittal T2, H-shaped or butterfly-shaped signal abnormality of the central GM on axial T2 → anterior spinal artery infarction. • Diffusion restriction on DWI ± hemorrhage, without appreciable cord swelling. • Snake-eyes pattern at anterior horns of GM → watershed territory infarction.
Acute/subacute myelopathies (Over 4 h to 21 d)	Compressive myelopathy • Degenerative • Neoplasm • Trauma • Epidural collection ○ Abscess ○ Hematoma	• Mechanical compression of the spinal cord → weakness, sensory disturbances, and loss of motor function below the compression level. • MR imaging → gold standard for precise visualization of spinal cord compression and underlying pathologies. • CT → to evaluate bony anatomy and detect calcified lesions contributing to cord compression. • Traumatic myelopathies may present with hyperacute symptom onset. • Flat, pancake-like enhancement may be present at maximum pressure point.
	Demyelinating/inflammatory
	• MS	• Asymmetric, patchy, short segment, peripherally oriented T2 hyperintense lesions predominantly affecting posterior and lateral WM columns. • Rarely presents with LETM but can have a similar appearance in advanced disease when extensive lesions become confluent. • Active lesions may demonstrate cord swelling and enhancement.
	• NMOSD	• T2 hyperintense GM & WM lesions mostly with LETM pattern and optic neuritis. • ± diffuse cord expansion and patchy enhancement. • 75%–80% (+) serum AQP4 Ab, but may be Ab (−).
	• ADEM	• Affects both the brain and spinal cord and typically presents with encephalopathy → commonly affects children. • T2 hyperintense GM & WM lesions, mostly LETM pattern. • Cord expansion and variable patchy enhancement.
	• MOGAD	• T2 hyperintense GM & WM lesions, LETM and H-pattern on axial T2, ± optic neuritis. • Frequent leptomeningeal enhancement without cord enhancement. • (+) serum MOG Ab.
	• ITM	• Diagnosis of exclusion, nonspecific MR imaging findings
	Neurosarcoidosis	• Intra/extra medullary lesions → LETM and sheet/plaque-like enhancement along the spinal cord surface, wedge-like pattern with subpial involvement extending into spinal cord parenchyma along perivascular spaces. • ± myeloradicular enhancement in particular (+) respiratory disease. • Hilar lymphadenopathy is common; Serum and CSF ACE levels can be helpful but not sufficiently sensitive or specific in isolation.
	Connective tissue diseases • Lupus • Sjögren’s syndrome • BD • Scleroderma/SS	• Overlapping imaging characteristics predominantly presenting with an LETM pattern. • Varying degrees of contrast enhancement. • Lupus may manifest as hyperacute myelopathy → likely thrombotic mechanism. • Clinical and laboratory findings are helpful in the DDx.
	Infectious myelopathy • Viral (HSV, CMV, polio) • Parasite • Fungi • Bacterial, TB, Lyme	• Overlapping imaging findings → commonly LETM and diffuse cord edema. • CSF analysis, serologies, and PCR assays → to identify the causative pathogen. • Poliovirus and enterovirus strains → flaccid paralysis involving lower motor neurons along the GM → classic T2 hyperintensity of the anterior horn cells. • Bacterial infections → often associated with meningitis or discitis-osteomyelitis, can lead to intramedullary abscess → expansile ring-enhancing lesion.
	Vascular myelopathies • Spinal Dural AVF • Spinal AVM • Cavernoma	• Spinal dural AVFs → intradural extramedullary enlarged and tortuous flow void veins along dorsal > ventral surface of the cord. • LETM due to edema induced by venous hypertension. • Ill-defined cord enhancement → breakdown of the blood-spinal cord barrier. • DSA confirms diagnosis. • Cavernous malformation→ low-flow vascular lesion without arterial feeders, occult on DSA, T1 hyperintensity and blooming on T2∗ GRE due to blood products.
	Paraneoplastic & autoimmune myelopathy	• Overlapping imaging characteristics, commonly in a LETM pattern, tract specific distribution involving lateral, dorsal columns, and central GM.
Chronic myelopathy (Over 3 wk to months)	Metabolic & toxic myelopathy • Vit B12 and Cu deficiency • Zn, NO toxicity • Chemotherapy, CAR-T	• Posterior and occasionally lateral column involvement with T2 hyperintense inverted V sign . • Absent spinal cord expansion or enhancement. • CAR-T therapy may cause ICANS, CRS, cord expansion, LETM, and hemorrhage.
Chronic myelopathy (Over 3 wk to months)	Radiation myelitis	• History of RT, T1 hyperintense marrow signal of the adjacent vertebral bodies. • T2 signal abnormality, ± cord expansion and patchy enhancement.

Abbreviations: Ab, antibody; CAR-T, chimeric antigen receptor T-cell; Cu, copper; DDx, differential diagnosis; GM, gray matter; HSV, herpes simplex virus; ITM, idiopathic transverse myelitis; NO, nitrous oxide; RT, radiotherapy; SS, systemic sclerosis; TB, tuberculosis; WM, white matter; Zn, zinc.

Algorithm for diagnosis

The diagnostic process for myelopathies typically includes a thorough evaluation of demographic information, timing of symptom onset, and a comprehensive clinical/neurologic examination. Classifying myelopathies by symptom onset offers a practical approach for differential diagnosis and determining the need for urgent intervention. Hyperacute myelopathies demand immediate imaging, typically MR imaging, to identify reversible or emergent conditions such as spinal cord infarction or trauma, and to prevent or mitigate further damage. The differential diagnosis for acute/subacute myelopathies is more extensive and includes compressive and noncompressive pathologies such as infectious, inflammatory, and neoplastic disease. Chronic myelopathies often indicate long-standing conditions such as degenerative spinal disease or metabolic disorders.

While MR imaging is the mainstay for characterizing myelopathies, computed tomography (CT) is the first-line technique in trauma patients and can help identify spinal canal stenosis due to fracture retropulsion or dislocations. CT is also the preferred modality for depicting ligamentous ossifications and other osseous causes of spinal canal stenosis. CT is helpful in evaluating postsurgical changes and may help identify other complications such as hematomas and abscesses, although its ability to detect intraspinal collections is limited without intrathecal contrast. Although CT cannot provide sufficient characterization of spinal cord parenchyma, CT myelography can help identify intrathecal pathologies resulting in myelopathy, such as dorsal arachnoid webs and arachnoid cysts.

MR imaging protocols to evaluate myelopathy should include T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), short-tau inversion recovery (STIR), T2∗ gradient echo (GRE), diffusion-weighted imaging (DWI), and gadolinium-enhanced T1WI. Although myelopathic changes are difficult to visualize on noncontrast T1WI, T1 hyperintensity can sometimes be seen with hemorrhage due to the presence of methemoglobin. T2WI and the more sensitive STIR sequence usually show hyperintense signal corresponding to edema and inflammatory changes. T2∗ GRE sequences are useful for detecting hemorrhage from various causes, including trauma, underlying tumors, and vascular malformations. DWI usually demonstrates diffusion restriction in spinal cord ischemia and abscesses, whereas inflammatory myelopathies may rarely show diffusion restriction during the acute phase. ^,

Sagittal imaging is instrumental in establishing the presence of longitudinally extensive transverse myelitis (LETM), characterized by involvement of more than 3 vertebral segments. Axial imaging is essential for differentiating between ATM, which affects most of the spinal cord cross-section, and partial myelitis, which is limited to less than 50%. ^, Six different MR imaging patterns of axial involvement can be described: central, centripetal, dorsal column, gray matter, anterior horn, and peripheral patterns ( Fig. 1 ). ^, The presence and pattern of contrast enhancement, such as nonenhancing, diffuse, patchy, or peripheral, may also be helpful in the differential diagnosis. However, lesion patterns commonly overlap, necessitating additional information such as cerebrospinal fluid (CSF) analysis and a comprehensive serum workup, including autoantibodies, metabolic, and microbiology tests. Brain MR imaging is also essential for assessing the spatial distribution of underlying pathology. Depending on the context and MR imaging findings, further studies may be required, such as body CT, PET, angiography, or ophthalmologic examination.

Hyperacute Presentation

Spinal cord infarction

Cord ischemia is a rare cause of myelopathy, requiring a high index of suspicion for diagnosis in the appropriate clinical setting. It is characterized by an abrupt onset of symptoms that often reach their peak severity in less than 4 hours, presenting with distinctive features such as transfixing or belt-like pain, coupled with rapid and profound motor deficits. Cord ischemia can be caused by a variety of conditions, ranging from arteriosclerosis to prothrombotic states, aortic surgery/stenting, hypotension, aortic or vertebral artery dissection, and fibrocartilaginous embolism. Other rare causes include diving decompression accidents or surfer’s myelopathy due to hyperextension of the thoracic spine, also described in gymnasts. ^, ^, Ischemia most commonly affects the anterior spinal artery, which supplies a substantial portion of the central gray matter. This region relies on a limited number of vessels, particularly in the lower thoracic cord, where infarction is most common.

MR imaging may reveal anterior pencil-like stripes on sagittal imaging and an H-shaped or butterfly-shaped signal abnormality of the central gray matter on axial images, indicative of anterior spinal artery involvement. As opposed to inflammatory myelopathies, there is no appreciable cord swelling or enhancement. ^, ^, DWI is useful for revealing diffusion restriction and can show different imaging patterns, such as dorsal column involvement in posterior spinal artery infarction or a snake-eyes or owl-eyes pattern selectively involving the anterior horns of the gray matter in watershed anterior spinal artery territory infarction ( Fig. 2 ). ^, Associated bone marrow signal abnormalities suggestive of vertebral body infarction may be useful in challenging cases.

Acute/Subacute Presentation

Compressive myelopathy

Compressive myelopathy arises secondary to mass effect on the spinal cord and leads to neurologic deficits and symptoms below the level of compression. The cervical spine is most commonly affected and patients commonly present with hand numbness, arm paresthesias, ataxia, Lhermitte phenomenon, and weakness. Compressive myelopathy is most commonly caused by degenerative spinal stenosis from disc herniations, osteophyte formation, and facet arthrosis but can also be seen with ossification of the posterior longitudinal ligament. Traumatic injuries, such as vertebral fractures or epidural hematomas, are also a common cause of spinal cord compression. Rarely, compressive myelopathy may be caused by a dorsal thoracic arachnoid web ( Fig. 3 ).