Demyelinating disorders
Demyelinating disorders are a diverse group of diseases that show varying clinical and imaging features. They commonly present with features of myelopathy with altered spinal cord signal intensity on MR images. This group encompasses multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorder (NMOSD), and idiopathic transverse myelitis (TM) [2,3,4].
Multiple sclerosis (MS)
Multiple sclerosis is an immune-mediated demyelinating disease of the central nervous system which affects the brain and spinal cord. This is the most common demyelinating disease and affects females more commonly than males [3]. McDonald’s criteria that assist in the diagnosis of this condition are based on demonstrating the multiplicity of the clinical attacks and the radiologic evidence of lesions being disseminated in space and time along with the presence of oligoclonal bands in CSF [5, 6]. Although more than 90% of patients with MS show spinal cord affection, isolated spinal involvement can be seen in up to 20–25% of patients, with the cervical segment of spinal cord being typically affected [7]. The lesions are usually multiple, short (spanning over one to two vertebral body segments), asymmetric, peripheral, wedge-shaped or round and affect less than 50% of the cross-sectional area of the cord on axial sections (usually in the lateral and posterior aspect of the spinal cord) (Fig. 1) [3, 4, 8]. Contrast enhancement may be seen in active or acute disease. In the chronic stage, cord atrophy may be seen [4, 7]. In the brain, the lesions are characteristically located at the calloso-septal interface and in periventricular, perivenular, intracortical, and infratentorial locations. When present, typical sites of cerebral involvement can aid in the diagnosis [8].
Acute disseminated encephalomyelitis (ADEM)
This is an acute inflammatory demyelinating disease that most commonly affects children with a history of viral infection or vaccination. With a propensity to involve both the brain and spinal cord, the lesions in ADEM are similar to MS but are more ill-defined, confluent, and often involve the deep gray nuclei (basal ganglia and thalamus). Approximately one-third of patients with ADEM show brainstem and spinal cord involvement [8]. In the spine, lesions are found more commonly in the thoracic cord, demonstrate ill-defined margins, show larger cross-sectional area and longer craniocaudal extent than MS (Fig. 2) [4, 9]. ADEM lesions usually do not show enhancement; however variable enhancement and cord swelling may be present in the acute stage [4, 8]. Other clinical features which suggest a diagnosis of ADEM include the monophasic course of the illness, signs of encephalopathy, and CSF analysis showing pleocytosis without oligoclonal bands [10].
Neuromyelitis optica spectrum disease (NMOSD)
Neuromyelitis Optica spectrum disease, also known as Devic’s disease, is an autoimmune astrocytopathy that is more commonly seen in females. This is characterized by optic neuritis, myelitis, and the presence of autoantibody against the water channel protein aquaporin-4, also known as an anti-NMO-IgG antibody. Imaging shows a long segment T2 hyperintense signal of the cord traversing at least three vertebral body levels with predominant involvement of the central gray matter [11]. It frequently extends upward into the medulla [12]. NMOSD lesions tend to show more heterogeneity with poor definition of margins. About 50% of cases may show “bright spotty lesions” which are defined as focal internal areas of signal alteration showing hyperintense signal similar to that of CSF on T2 weighted images with corresponding low signal on T1, and this is highly specific to NMOSD [13]. In addition, the lesions can be expansile and often show enhancement on post-contrast images in acute settings [8]. Particularly, a ‘lens-shaped’ pattern of enhancement is observed on sagittal images in this disease [14].
Idiopathic acute transverse myelitis (ATM)
Idiopathic ATM is the most common acute inflammatory myelitis with the absence of a specific identifiable cause (such as MS, NMO, ADEM, connective tissue disease, infection, etc.) [15,16,17]. This is essentially a diagnosis of exclusion, which presents clinically with rapidly progressive, bilateral sensory and motor dysfunction with a distinct cord level. Pleocytosis and occasionally an elevated IgG index may be seen [15, 16]. It is more common in younger patients. On imaging, the lesions are typically located in the cervicothoracic spinal cord occupying at least two-thirds of the cross-sectional area of the cord with central cord predominance, with or without mild cord expansion (Fig. 3) [4, 15]. There is a variable length of cord involvement, with long segment involvement (longitudinally extensive TM) being more common than short segment involvement (acute partial TM) [17]. Enhancement is variable and is most commonly seen in the subacute stages. Enhancement patterns may be diffuse, poorly defined, heterogeneous, nodular, or peripheral [4].
Systemic inflammatory and immune-mediated disorders
Systemic lupus erythematosus (SLE), Sjögren syndrome, and sarcoidosis are the three common multisystemic inflammatory disorders affecting the spinal cord [3]. Central nervous system involvement including the spinal cord is uncommon in these disorders. Imaging morphology is nonspecific, and the diagnosis is established by considering the history and prior non-neurologic clinical manifestations. Imaging with MR shows a long-segment intramedullary T2 hyperintense area with variable enhancement and without significant expansion [3]. The distinctive features favouring neurosarcoidosis include dorsal spinal cord predominance, leptomeningeal enhancement, and the trident sign – crescentic-shaped subpial enhancement of the posterior cord with additional subtle enhancement in the region of the central canal [18].
Infectious myelitis
Infectious myelopathy can be caused by various viral, bacterial, and fungal pathogens. MRI shows nonspecific diffuse non-expansile T2 hyperintense signal [4, 8].
Tubercular myelitis
Compressive myelopathy due to tubercular spondylodiscitis is a common entity; however, isolated intramedullary involvement by tuberculosis is relatively rare. There are various manifestations of tubercular myelitis which include acute myelitis, longitudinally extensive transverse myelitis, radiculomyelitis, arachnoiditis, and tuberculomas (intramedullary or intradural-extramedullary) [19]. Both acute partial transverse myelitis and longitudinally extensive transverse myelitis have been described in patients with tuberculous meningitis (Fig. 4). The latter is indistinguishable from NMOSD through imaging, hence necessitating the need for relevant clinical and laboratory details. The most commonly affected areas include the thoracic and cervical segments of the cord [20]. Intradural extramedullary tubercular spinal granulomas without bony involvement and intramedullary spinal tuberculomas are rare and show morphological characteristics similar to intracranial tuberculomas i.e. iso-intense on T1W and iso to hypointense on T2W with ring or nodular enhancement on post-contrast images (Fig. 5). Intramedullary granulomas may show fusiform cord swelling with surrounding T2 hyperintense edema [4]. Spinal arachnoiditis is a frequent presentation in these infections, which shows exudates and clumping of cauda equina nerve roots (along with resultant empty thecal sac) which may show enhancement on post-contrast images [19].
Human immunodeficiency virus (HIV) myelopathy
Myelopathy is a late-onset complication of HIV infection. MR can demonstrate varying appearances ranging from normal to diffuse T2 hyperintensity within the central spinal cord with accompanying cord atrophy. Additional findings include symmetrical non-enhancing T2 hyperintense areas in the dorsal columns of the spinal cord similar to subacute combined degeneration, although the signal abnormality is typically limited to the thoracic spine [20].
Ischemic myelopathy
Spinal cord ischemia and infarction usually have an acute presentation, with symptoms onset and progression in less than 4 h [2]. It can be arterial or venous, with the former being more common. Multiple radiculomedullary arteries form the anterior and posterior spinal arteries perfusing the anterior two-thirds and posterior one-third of the spinal cord, respectively. Ischemia most commonly affects the territory of the anterior spinal artery and typically affects the lower thoracic cord [2]. Underlying aetiologies include severe atherosclerotic aortic disease, aortic dissection or aneurysm, and aortic surgery/stenting. On MR imaging, characteristic findings include long segment T2 hyperintense signal within the central gray matter, producing an “H-shaped” or “butterfly-shaped” pattern with corresponding restricted diffusion on diffusion-weighted images [2]. Watershed territory infarction may cause abnormalities in the ventral horns of the gray matter only, producing the typical “snake-eyes” or “owl’s-eyes” appearance [21]. Imaging morphology of long segment involvement, central gray matter predominance, and absence of expansion, together with the hyperacute onset of symptoms, are highly suggestive of ischemia and help to discriminate it from other causes of acute myelopathy [2, 22].
Spinal vascular malformation
The most common vascular malformation is a dural arteriovenous fistula (d AVF), which represents approximately 80% of all spinal vascular malformations [23]. This comprises an abnormal direct communication between the dural artery and vein of a nerve root sleeve. It is usually prevalent in the elderly male population and presents with nonspecific symptoms overlapping with spondylosis or polyneuropathy. A dural arteriovenous fistula is most commonly found at the mid and lower spinal levels, from T4 to L3 [2]. MRI characteristically shows numerous serpentine flow voids on the dorsal surface of the cord due to associated venous engorgement, which shows marked post-contrast enhancement. The spinal cord demonstrates long segment intramedullary T2 hyperintensity due to edema caused by venous hypertension often extending to the conus medullaris (Fig. 6). Ill-defined parenchymal contrast enhancement of the spinal cord can be seen. The gold standard study for localization of fistula and demonstration of arterial supply is digital subtraction angiography. MR angiography, however, can be useful in localizing the fistula site, allowing for a more focused catheter angiogram [2].
Intramedullary arteriovenous malformation (AVM) consists of an arteriovenous capillary nidus supplied by an enlarged feeding artery and drained via a tumid venous plexus. AVMs demonstrate intramedullary serpiginous flow voids and a short segment of signal change within the cord (representing the nidus) on T2W MRI, which shows enhancement on post-contrast images [2, 3]. If there is venous congestion, cord edema is seen as ill-defined intramedullary T2 hyperintensity with cord expansion. In contrast to AVF, these lesions more commonly show haemorrhage, which is a useful discriminating feature on MRI. Haemorrhage may be either intramedullary or subarachnoid in location and shows variable signal intensities depending upon the age of blood products [23].
Metabolic causes
Subacute combined degeneration of the spinal cord
This condition is the most common presentation of spinal cord involvement due to metabolic derangements and affects the dorsal columns, hence presenting clinically with gait ataxia and loss of vibration and proprioception in the extremities [8]. Most of the cases invariably occur due to Vitamin B12 deficiency [8]. Other aetiologies for this manifestation include copper deficiency and nitric oxide inhalation. MR imaging shows almost exclusive involvement of the dorsal columns in the cervical and thoracic spinal cord which show a non-expansile, long segment T2 hyperintensity producing a characteristic reversed V sign on axial images (Fig. 7) [24].
Neoplastic causes
Intramedullary neoplastic lesions can manifest as focal T2 hyperintensity within the spinal cord. Typically, expansion of the spinal cord on imaging and a subacute to chronic onset distinguish neoplastic from nonneoplastic conditions [25]. Astrocytoma, ependymoma, and hemangioblastoma are the common lesions in this group. Less commonly, lymphoma and metastases can also manifest as intramedullary lesions.
On MR imaging, location along the cord, the length of involvement, and enhancement characteristics are valuable for determination of the plausible causes [8]. Astrocytomas and hemangioblastomas more commonly affect the thoracic cord, whereas ependymomas and metastasis commonly affect the cervical cord. Myxopapillary ependymoma is typically restricted to the filum terminale with rare involvement of the conus medullaris. Long segment involvement is seen in astrocytomas (4–7 vertebral bodies) and ependymomas (up to 4 vertebral bodies), while hemangioblastomas and metastases typically involve short segments of the cord [8]. Ependymomas typically show homogeneous enhancement as opposed to astrocytomas which exhibit more heterogeneous enhancement. Additional differentiating features of ependymoma include the presence of peritumoral cysts, hemorrhage, and identification of the hemosiderin “cap sign”, consisting of a rim of T2 hypointensity at one or both poles, which occurs in about one-third of cases (Fig. 8) [25]. Peculiar findings of hemangioblastomas include the presence of a feeding vessel, detectable as a flow void on T2W images, and a focus of intense nodular enhancement on post-contrast images. Metastases merit consideration when dealing with multiple and short segment enhancing lesions [8].
Miscellaneous causes
Guillain–Barré syndrome (GBS)
GBS is a post-infectious/inflammatory autoimmune disease typically involving multiple peripheral nerves, most commonly the ventral nerve roots arising at the cauda equina. Although, this is essentially radiculopathy, ascending myelopathic changes can occur in some cases. CSF findings typically reveal albumin-cytologic dissociation, referring to an elevation of CSF protein without pleocytosis [26]. The clinical history of ascending paralysis and areflexia characteristically occurring post-infection or a vaccination along with typical CSF findings and electrophysiological examination can aid in diagnosis. Characteristic findings on MR imaging include thickening and contrast enhancement of conus medullaris and cauda equina nerve roots (predominantly anterior) (Fig. 9) [26]. Sometimes the more cephalad ventral gray matter horns and nerve roots may show enhancement.
Motor neuron disease
This consists of an uncommon group of fatal progressive neurodegenerative diseases which includes primary lateral sclerosis, spinocerebellar ataxia, iron neurodegeneration, Friedreich ataxia, and amyotrophic lateral sclerosis (ALS). ALS is the most common type of motor neuron disease. Typical findings comprise of long segment T2 hyperintensity involving the anterolateral columns with or without associated spinal cord atrophy. Associated intracranial extension of the abnormal signal along the cortico-spinal tracts can also be observed in some cases [27].
Radiation myelitis
Radiation myelitis presents as slowly progressive myelopathy with a variable latent period. Imaging characteristically demonstrates extensive long-segment T2 hyperintensity involving the irradiated field. A variable degree of enhancement may be appreciated in the acute stage. In the chronic stage, features of atrophy predominate with or without cystic necrosis [28]. Accompanying fatty bone marrow replacement in the adjacent vertebral bodies further increases the diagnostic confidence [28].
Myelopathy with normal MRI
Findings of normal spinal MRI in settings of clinically suspected acute myelopathy are not uncommon. There are several explanations for this: (1) the syndrome is not myelopathy rather an inflammatory radiculopathy; Guillain–Barre´s syndrome may be mistaken as myelitis, especially considering the abnormal CSF protein concentration and ascending symptoms that may mimic those seen in myelitis. (2) MRI performed during the convalescence period (if scanned after recovery from an acute attack of transverse myelitis and after resolution of spinal cord changes). (3) Many cases of acute myelitis/myelopathy may not demonstrate any altered intramedullary signal intensity. Newer MR techniques like tractography and fractional anisotropy have shown promising results in early detection of cord changes as compared to conventional MRI and may provide valuable information in such scenarios [15, 29]. History and clinical features should be reviewed carefully and correlated with CSF findings for arriving at a specific diagnosis. In some cases, MRI brain may be abnormal and that may help formulate the differential diagnosis [29].
