Location, length, and enhancement: systematic approach to differentiating intramedullary spinal cord lesions

In demyelinating conditions, the underlying mechanism of myelopathy is that of inflammation damaging myelin sheath-forming cells. This can be primary, due to conditions such as multiple sclerosis (MS), or secondary, such as in post-infectious acute disseminated encephalomyelitis (ADEM) or transverse myelitis secondary to underlying viral infection [4]. MS is a primary demyelinating disease affecting the central nervous system with intracranial and spinal involvement (Figs. 4 and 5). The disease is twice as common in females and tends to occur in geographical regions farther away from the equator. MRI is the most important modality in both the diagnosis and clinical management of MS, demonstrating characteristic callososeptal and periventricular, perivenular demyelinating lesions in the brain [5]. Spinal cord involvement of MS frequently occurs along with brain involvement, although isolated spinal cord lesions can occur in 25% of patients. In Asian populations, who are more likely to present with the optic-spinal variant of MS, spinal cord involvement occurs more frequently, and the cord should be carefully evaluated in this subset of the population [6].

NMOSD (also known as Devic’s disease) is a relapsing disease with the typical triad of optic neuritis, myelitis, and positive NMO-IgG, an autoantibody to the protein channel aquaporin-4 (AQP4), which is expressed on foot processes of astrocytes (Fig. 6). The underlying pathophysiology is of autoimmune astrocytopathy [7], distinguishing this condition from MS and other demyelinating processes. The condition is much more common in females (5:1), and brain lesions are shown to occur much more frequently than previously thought. Among other diagnostic criteria, presence of longitudinally extensive spinal cord lesions (LESCL), which are characterised by T2 hyperintense signal of the cord traversing at least three vertebral body levels, is key to its diagnosis [8, 9].

ADEM is an acute, often monophasic post-infectious or inflammatory condition that most commonly occurs in children (Fig. 7). ADEM can involve both white and grey matter, and although it can demonstrate periventricular brain lesions similar to MS, it is more likely to have ill-defined, larger, and more rounded lesions, with a predilection for deep grey matter and the brainstem [10, 11]. Involvement of the brainstem and spinal cord occurs in approximately one-third of patients with ADEM and its spinal characteristics are helpful in differentiating this condition from MS [5].

Guillain-Barré syndrome (GBS) can be thought of as the peripheral nervous system counterpart to ADEM, with a post-infectious/inflammatory autoimmune pathophysiology (Fig. 8). It typically involves multiple peripheral nerves, most commonly the anterior nerve roots arising at the cauda equina. The classic clinical history consists of ascending weakness, which can progress to ascending paralysis, typically occurring after a bout of infection or after having received a vaccination. Most cases resolve within a few weeks without residual symptoms [12, 13].

Transverse myelitis is an inflammatory condition of the spinal cord with various underlying aetiologies. This condition may occur at any age; however, it is more common in younger patients. It typically presents with rapidly progressive bilateral sensory and motor dysfunction with a distinct cord level. Approximately one-third of affected patients recover fully while the remaining 60 % will have either moderate or profound neurological deficits. There are various underlying aetiologies of transverse myelitis, including MS, systemic autoimmune disorders such as systemic lupus erythematosus, vascular infarct, post-radiation, post-infectious, or idiopathic. MRI demonstrates a long segment T2 hyperintense cord lesion with bilateral cord involvement, occupying at least two-thirds of the cross-sectional area of the cord (Fig. 9) [14, 15].

HIV myelopathy is a late-onset complication of HIV (Fig. 10). Patients present with insidious onset myelopathy with lower extremity weakness and sensory abnormalities, impotence, and/or urinary symptoms. On MRI, spinal cord atrophy is typically present. Other findings can be seen, including symmetric dorsal column hyperintensity on T2-weighted images similar to subacute combined degeneration, though typically the signal abnormality is limited to the thoracic spine [16, 17]. The cervical spine is involved less commonly. On histology, there is vacuolization of the myelin-forming cells of the spinal cord [17].

In differentiating spinal demyelinating processes, the location along the spine and degree of transverse cord involvement can be distinguishing features. In MS, lesions are more commonly located within the cervical spine and are often multifocal and asymmetric, involving a partial cross-sectional area of the cord, for example, involving a lateral or posterior aspect of the cord on an axial slice. This is in contrast to NMOSD and transverse myelitis, where there is central or more diffuse cord involvement on axial images [6]. MS lesions involve short segments (1–2 vertebral bodies), whereas in NMOSD, long segment and central involvement is more characteristic [11]. MS lesions appear more homogeneous, whereas NMOSD lesions tend to be more ill defined and heterogeneous in T2 hyperintensity [5]. ADEM will demonstrate diffuse T2 hyperintensity and expand the spinal cord; a long segment is commonly involved, and there is no enhancement [18]. If myelopathy is isolated to the conus medullaris/cauda equina, one must consider GBS, in which there is nerve root enhancement, particularly involving the anterior nerve roots [11]. Enhancing lesions in the cord may be seen with active demyelination in MS and NMOSD. The pattern of enhancement is variable with transverse myelitis, while ADEM lesions most commonly do not enhance. Ring-enhancing lesions, which are characteristically seen with tumefactive MS in the brain, can also rarely be present in the spinal cord. In NMOSD, a distinctive ‘lens-shaped’ pattern of enhancement on sagittal images is characteristic if present [18] (Table 1).

Subacute combined degeneration is the most common manifestation of metabolic derangements within the spinal cord. The condition presents clinically with loss of vibration and proprioception in the extremities, eventually leading to gait ataxia and extremity muscle weakness. The aetiology may be due to copper deficiency (Fig. 11) or nitric oxide use; however, the most common aetiology is vitamin B12 deficiency (Fig. 12). On MRI, the characteristic pattern is of long segment T2 hyperintensity involving the posterior spinal cord, classically involving the dorsal columns and producing a characteristic reversed “V” sign [19, 20] (Table 2).

Ependymomas are benign glial tumors that arise from ependymal cells lining the brain’s ventricles or the central canal of the spinal cord (Fig. 13). Although the majority of ependymomas occur intracranially, about 10% occur in the spinal cord and represent the most common intramedullary spinal cord tumor in adults. Spinal ependymomas most commonly occur in the cervical cord, though they can occur anywhere along the spinal cord. The myxopapillary subtype is confined to the filum terminale with rare extension into the conus medullaris. Their association with neurofibromatosis type II is explained by abnormality found within chromosome 22; the NF2 gene is located on chromosome 22q and patients with an ependymoma often have defects on the same chromosome [21‐24].

Hemangioblastomas are rare benign tumors that most commonly occur in the cerebellum and represent the third most common intramedullary spinal cord tumor (Fig. 14). They are associated with Von Hippel Lindau syndrome (VHL), particularly when seen within the cord, or if multiple lesions are detected. They are thought to arise from undifferentiated mesenchymal cells and are composed of densely packed capillaries lined with endothelial cells. There is no gender predilection, and they most commonly arise in the thoracic cord followed by the cervical cord [21‐23].

Intramedullary astrocytomas are most common in children and tend to occur more frequently in males (Fig. 15). They are likely to occur in the thoracic cord, followed by the cervical cord, involve multiple vertebral body levels and are infiltrative in nature. They are associated with neurofibromatosis type I. High-grade intramedullary astrocytomas are very rare, though glioblastoma multiforme has been reported, with which leptomeningeal involvement is commonly present [22‐24].

In intramedullary neoplasms, the length of involvement, location along the cord, and enhancement pattern are the most helpful in narrowing the differential diagnosis (Table 3). Spinal cord astrocytomas will involve a long segment, as will (but to a lesser extent) ependymomas, while hemangioblastomas and metastases typically involve short segments. The enhancement pattern is essential in differentiating these lesions. In ependymoma, a solid, mostly homogeneous pattern of enhancement is typical, while astrocytomas will exhibit more heterogeneous enhancement. Other distinguishing features of ependymoma include presence of tumoral and nontumoral cysts and identification of a “cap sign”, which is a rim of T2 hypointense hemosiderin secondary to associated hemorrhage that can occur in about one-third of cases [24]. More aggressive subtypes, such as the rare spinal cord glioblastoma multiforme, tend to exhibit areas of hemorrhage and non-uniform enhancement (Fig. 16). In hemangioblastomas, presence of a feeding vessel, detected as a flow void on T2-weighted images, and a focus of intense nodular enhancement are characteristic findings. When multiple and short segments of enhancement are involved, metastases should be considered (Fig. 17), and search for a primary malignancy should ensue if not already known.

Dural arteriovenous fistulas (dAVF) are the most common spinal cord vascular malformation (Figs. 18 and 19). These lesions are composed of a direct communication between a nerve root sleeve dural artery and vein and are categorised as a type I spinal vascular malformation. They are usually diagnosed late because of their prevalence in the elderly male population and nonspecific symptomatology, which often overlap with those of spondylosis or polyneuropathy [25]. A common pattern of diagnosis is in those with post-laminectomy syndrome, who exhibit persistent symptoms after spinal surgery for spondylosis. Although digital subtraction angiography is the gold standard study for definitive diagnosis, MRI and magnetic resonance angiography (MRA) techniques have become increasingly more sensitive for detection of this rare, but important spinal pathology. On MRI, serpentine flow voids on the surface of the cord with engorged venous structures and intramedullary hyperintensity on T2-weighted sequences are reliable clues to the diagnosis [26, 27]. The condition should be considered in patients with insidious myelopathy, as it can be reversible if diagnosed and treated early in the course of the disease.

Intramedullary spinal arteriovenous malformations (AVM) are significantly rarer than dAVFs, representing about 25% of vascular lesions within the spine. They can present as a spinal subdural hemorrhage or progressive myelopathy in which patients initially experience spastic paralysis followed by flaccid paralysis of the extremities, accompanied by sensory deficits and sphincter dysfunction. This clinical presentation has been termed the Foix-Alanjouanine syndrome [28]. Spinal arteriovenous malformations contain a true arteriovenous capillary nidus fed by an enlarged feeding artery and drained via an enlarged venous plexus on the cord surface (Fig. 20). They are categorised as type II spinal vascular malformations and most commonly occur within the cervical or thoracic cord [28‐31].

Most commonly found in the thoracic cord, spinal cavernomas (also known as cavernous malformations) are rare lesions that commonly present intracranially. They consist of endothelial-lined lacunae filled with blood and surrounded by thick walls. They are occult on angiography as they do not communicate with the cord vasculature and have similar imaging characteristics as their intracranial counterparts [32, 33] (Fig. 21).

Spinal cord infarctions occur very rarely, accounting for less than 1% of strokes. However, appropriate diagnosis of this entity is critical, as its symptoms overlap with other causes of myelopathy, such as demyelinating processes. There are many underlying aetiologies of spinal cord infarction, and they are classified according to the transverse involvement of the cord, which corresponds to the insulted vascular territory. MRI is the gold standard for diagnosis. All cases involve a long segment of the cord, and the majority of infarcts will involve the anterior spinal artery, resulting in anterior or central cord involvement [34] (Fig. 22).

Segment length involvement is a very important distinguishing factor in spinal vascular lesions. Long-segment cord T2 hyperintensity should raise the suspicion of a dAVF or spinal cord infarct, while short segment involvement raises the possibility of a cavernoma or arteriovenous malformation. Cavernous malformations usually do not cause cord edema or expansion. “Popcorn-like” heterogeneity from blood products of differing ages, a hemosiderin perimeter (low T2 signal rim), and susceptibility or blooming on gradient echo sequences are classic findings. DAVFs almost always demonstrate T2 hyperintensity at the conus medullaris because of dependent cord edema, and identification of serpiginous flow voids on the surface of the cord is immensely helpful in making the diagnosis. This is in contrast to finding intramedullary serpentine flow voids and a short segment of intramedullary signal change, which should point to the presence of a nidus in an AVM. A long segment “owl-eye” appearance of bilateral ventral horn hyperintensity on T2-weighted images is concerning for the presence of anterior spinal artery infarction and should prompt a search for a possible underlying aetiology, such as severe atherosclerotic aortic disease, an aortic dissection or aneurysm (Table 4). Although rarely present, signal changes in the adjacent vertebral body manifesting as marrow edema or osseous infarction can be helpful in confirming the diagnosis of a spinal cord infarct [35].

A common cause of weakness and sensory deficits in older patients is cervical compressive myelopathy or myelopathic spondylosis, which can occur secondary to spondylotic changes in the cervical spine and less commonly because of congenital abnormalities. The mechanism of injury involves decreased canal diameter and spinal stenosis, with resultant focal signal abnormality within the affected cord (Fig. 23). Ossification of the posterior longitudinal ligament (OPLL) is a common contributor. Compressive myelopathy typically demonstrates focal T2 hyperintensity in the cord at a level of spinal stenosis (at the level of a disc) with or without associated enhancement [36, 37] (Table 5).

Hirayama disease is a disease of young males, mostly recognised in Japan and India. It presents with unilateral upper extremity weakness. The disease is related to a lax dura mater, which changes position with flexion and extension. Resulting repetitive circulatory changes in the anterior spinal artery due to cord compression cause atrophy and eventual necrosis in the anterior horns. MRI plays an essential role in the diagnosis of this rare disease (Fig. 24). Neutral cervical spine images are not very sensitive in showing the pertinent changes, and if there is clinical concern for this condition, flexion images should be obtained. Forward displacement of the dura mater is seen, with anterior cord compression and enlargement of the posterior epidural space, which may enhance post contrast. On transverse sections, there is atrophy of the anterior horns, which is typically asymmetric [38, 39] (Table 5).