Myelopathy in Multiple sclerosis

The author: Professor Yasser Metwally


April 30, 2010 — Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Recent data suggest that MS is a T-cell–mediated disease with secondary macrophage activation. The pathologic hallmark of MS is inflammatory demyelination, which can lead to irreversible tissue loss or partial demyelination in cases where reparative processes occur with subsequent remyelination. Three mechanisms of tissue injury in MS have been proposed: immunologic, excitotoxic, and metabolic [1]. The spinal cord is frequently involved in MS, with cord lesions found in up to 99% of autopsy cases [2,3]. The first pathologic descriptions of the macroscopic distribution of MS lesions in the spinal cord were by Carswell in 1838 [4] and Cruveilhier in 1841 [5]. In 70% to 80% of patients who have MS, cord abnormalities are detected on T2-weighted MR images [6]. MS spinal cord abnormalities can be divided into three main types: (1) focal, well demarcated areas of high signal intensity on T2-WI; (2) diffuse abnormalities seen as poorly demarcated areas of increased signal intensity on T2-WI; and (3) spinal cord atrophy and axonal loss.

  • Focal lesions

Macroscopically, spinal cord lesions appear elongated in the direction of the long axis of the cord and vary in length from a few millimeters to lesions that extend over multiple segments [7]. MR imaging is the most sensitive technique for detecting MS lesions in the brain and spinal cord. Its role as a tool in the diagnosis and longitudinal monitoring of patients who have MS has been well established in numerous studies [8,9,10,11,12]. The recent introduction of the McDonald [11] criteria has further strengthened the role of MR imaging in the diagnosis of MS. MS plaques are best seen with T2-weighted MR sequences and are hyperintense on T2-WI and iso-hypointense on T1-weighted MR images. Spinal cord demyelinating plaques present as well circumscribed foci of increased T2 signal that asymmetrically involve the spinal cord parenchyma. They are characteristically peripherally located, are less than two vertebral segments in length, and occupy less than half the cross-sectional area of the cord. On sagittal sections, plaques have a cigar shape and may be located centrally, anteriorly, and dorsally. On axial MR images, the lesions located in the lateral segments have a wedge shape with the basis at the cord surface or a round shape if there is no contact with the cord surface (Fig. 1). The distribution of MS lesions in the spinal cord closely corresponds to venous drainage areas. Cord swelling is usually found only in the relapsing-remitting form of MS [12,13,14]. Because acute lesions are associated with transient breakdown of the blood–brain barrier, enhancement may be seen on postcontrast images (Fig. 2, Fig. 3). The incidence of enhancing lesions is significantly lower than in the brain [7]. Sixty-two percent of the plaques occur in the cervical spinal cord. Chronic foci of hypointensity on T1-WI images, known in the brain as “black holes,” are not present in the spinal cord [15].

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Figure 1. Typical MS lesion in the cervical spinal cord. (A) Sagittal T2-weighted MR image showing hyperintense, dorsally located spinal cord lesion at the C2 level. (B) On axial T2-weighted MR image, a hyperintense, wedge-shaped lesion is located in the dorsal aspect of the spinal cord lesion, occupying less than half the cross-sectional area of the cord. (C) Axial fluid-attenuated, inversion-recovery–weighted MR image of the brain in the same patient showing hyperintense periventricular white matter lesions consistent with MS lesions. (Click to enlarge figure)

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Figure 2. Multiple spinal cord focal lesions in a patient who has MS. (A) Sagittal T2-weighted MR image showing several high-signal-intensity lesions in the spinal cord at levels C1/C2, T3, and from T6 to T8, consistent with spinal MS manifestation. (B) A sagittal gadolinium-enhanced, T1-weighted MR image demonstrating enhancement of the lesion at the T7 level, consistent with acute inflamed MS plaque. (C) Ring enhancement of the lesions located at the C2 level is observed on a sagittal postcontrast, T1-weighted MR image. (D) Axial T1-weighted, contrast-enhanced MR image of the brain showing a ring-like enhancing lesion in the left occipital white matter lesions. (Click to enlarge figure)

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Figure 3. Active (enhancing) focal spinal cord lesion in two patients who have MS. (A) Sagittal T2-weighted MR image of the thoracic spine showing a focal hyperintense spinal cord lesion consistent with a focal MS lesion in the spinal cord. (B) On sagittal postcontrast, T1-weighted MR image, subtle nodular enhancement of the MS lesion is observed. (C, D) In another patient, a wedge-shaped, high-signal-intensity lesion located in the lateral aspect of the cord (D) extending from C2 to C4 with mild cord expansion is demonstrated on a sagittal T2-weighted MR image (C). (E) Peripheral enhancement of the lesion is demonstrated on an axial postcontrast T1-weighted MR image with fat suppression. (Click to enlarge figure)

  • Diffuse abnormalities

Diffuse abnormalities are more common in primary progressive MS and secondary progressive MS. Diffuse signal changes of the spinal cord are recognized on images as mild intramedullary hyperintensities on T2-weighted MR images (Figure 4).

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Figure 4. Diffuse abnormalities in the cervical spinal cord in a patient who has primary progressive multiple sclerosis. (A) Sagittal T2-weighted MR-image showing increased signal intensity on T2-WI in the cervical spinal cord, extending to multiple segments with cord enlargement. (B) Sagittal T1-weighted, gadolinium-enhanced MR images showing diffuse, poorly demarcated enhancement of the spinal cord lesions. (C) On axial T2-weighted MR image, the lesion involves almost the whole area of the spinal cord. (Click to enlarge figure)

  • Spinal cord atrophy

In addition to plaques and diffuse spinal cord abnormalities, spinal cord atrophy has been recognized for many years (Fig. 5). Axonal degeneration, or an alternative atrophic process, may be responsible for spinal cord atrophy in MS. One recent study has shown that the degree of atrophy varies in different parts of the cord, being more prominent in upper parts of the cord [16]. Studies have also shown that spinal cord atrophy correlates with clinical disability [16]. Analysis of the amount of atrophy revealed a correlation between upper cervical cord and cerebral white matter atrophy and an expanded disability status scale [17]. Significant cerebral and spinal cord volume reductions have been found in all patient subgroups of MS compared with control subjects [17]. Higher rates of atrophy have been reported in relapsing-remitting MS than in secondary progressive forms of the disease [17]. Plaques associated with cord atrophy are more likely to occur with the relapsing-progressive form of MS.

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Figure 5. A marked decrease of the spinal cord diameter is demonstrated on a sagittal T2-WI MR image in a patient who has MS. (Click to enlarge figure)

  • Axonal loss

Postmortem studies have shown convincingly that cord damage is not limited to lesions visible on T2-WI [18]. According to the neuropathologic studies about MS of the spinal cord, axonal loss can be found in 60% to 70% of chronic MS lesions. Magnetic Resonance Spectroscopy studies have shown reduced N-acetyl aspartate in areas of the cord that were normal on conventional MR images. Significant abnormalities in normal-appearing spinal cord have also been observed [19]. Decreased small fiber density was found in one study in the lateral column of the cervical spinal cord of patients who have MS compared with control subjects [20]. Data from recent neuropathologic studies suggest that extensive axonal damage occurs during plaque formation soon after the onset of demyelination [21]. Furthermore, during that process, significant axonal injury is found in the normal white matter. Ongoing, low-burning axonal destruction has also been found in inactive demyelinated lesions in the brain [21].

The entire spinal cord should be imaged in patients who have spinal symptoms and who have a known or presumptive diagnosis of MS. Slice thickness should not exceed 3 mm, with a maximum interslice gap of 10% [10]. The imaging protocol should include the following sequences: sagittal T2-WI, T1-WI, axial T2-WI for exact anatomic location of the lesion, and contrast-enhanced T1-WI. Studies have shown the superiority of short-tau inversion-recovery sequences to Fast Spin Echo sequences in the detection of MS lesions in the spinal cord (Fig. 6) [22,23]. Fast fluid inversion recovery was rated unsatisfactory [22].

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Figure 6. Comparison of a T2-WI MR image and short-tau inversion-recovery MR image in the detection of spinal cord MS lesions. (A) On the sagittal T2-WI MR image of the cervical spinal cord, intramedullary high-signal-intensity lesions have been detected at the C2 and C4-C5 levels. Note the mild increase in signal intensity. (B) On the sagittal short-tau inversion-recovery MR sequence, focal lesions in the cord show a marked increase in signal intensity and are much more easily appreciated. (Click to enlarge figure)

The value of spinal MR imaging in the differentiation of MS from other inflammatory or cerebrovascular disorders has been evaluated in a recent study [24]. Specificity, sensitivity, and positive and negative predictive values for MR imaging were calculated for 66 patients who had other neurologic diseases and 25 patients who had MS. Brain images were abnormal in all patients who had MS but in only 65% of patients who had other brain disorders. Spinal cord abnormality was found in 92% of patients who had MS but in only 6% of patients who had other diseases. With the combination of brain and spinal cord MR imaging in that study, the accuracy of differentiating MS from other disorders reached 95% based on the criteria of Paty and colleagues [25], 93% based on the criteria of Fazekas and colleagues [26], and 93% based on the criteria of Barkhof and colleagues [27].

Diffusion-weighted MR imaging (DWI) has been increasingly used for the evaluation of spinal cord diseases, especially in spinal cord ischemia [28,29]. Clark and colleagues [30] were the first to use a conventional, cardiac-gated, navigation diffusion-sensitized spin-echo sequence for in vivo DW imaging of the spinal cord. MS lesions were found to have increased rates of diffusivity, with a significantly higher isotropic diffusion coefficient, compared with healthy control subjects. Differences in diffusion anisotropy did not reach statistical significance. The decrease in anisotropy is probably due to several factors, such as loss of myelin from white matter fiber tracts, expansion of the extracellular space fraction, and perilesional inflammatory edema. Reduced anisotropy is also seen in MS brain lesions [31,32,33]. A large standard deviation in the lesion values was observed by Clark and colleagues, which could be explained by lesion heterogeneity. On postmortem high-resolution MR imaging of the spinal cord in MS, two main types of lesions have been found: lesions with marked signal intensity (SI) changes that corresponded with complete demyelination and lesions with mild SI abnormalities where only partial demyelination was found histologically [34].

To assess whether diffusion tensor-derived measures of cord tissue damage are related to clinical disability, mean diffusivity (MD) and fractional anisotropy (FA) histograms were acquired from the cervical cords obtained from a large cohort of patients who had MS [35]. In that study, diffusion-weighted, echo planar images of the spinal cord and brain DW images were acquired from 44 patients who had MS and from 17 healthy control subjects. The study showed that average cervical cord FA was significantly lower in patients who had MS compared with control subjects. Good correlation was found between the average FA and average MD and the degree of disability. In another recently published study, axial diffusion tensor MR imaging (DTI) was performed in 24 patients who had relapsing-remitting MS and 24 age- and sex-matched control subjects [36]. FA and MD were calculated in the anterior, lateral, and posterior spinal cord bilaterally and in the central spinal cord at the C2-C3 level. Significantly lower FA values were found in the lateral, dorsal, and central parts of the normal-appearing white matter in patients who had MS. The results of this study show that significant changes in DTI metrics are present in the cervical spinal cord of patients who have MS in the absence of spinal cord signal abnormality at conventional MR examination [36]. The exact value of DW imaginging and DTI in MS of the spinal cord has not been completely evaluated [37].

Studies have been performed to evaluate the usefulness of T1 relaxation time and magnetization transfer ratio [38,39,40]. In one study of 90 patients who had MS and 20 control subjects, reduced histogram magnetization transfer ratio values were found in patients who had MS [39]. Although the results were encouraging, the long acquisition times are clinically questionable.

Table 1. MRI criteria for relapsing remitting multiple sclerosis and progressive multiple sclerosis

MRI criteria

MS type

Focal spinal cord lesions

Relapsing-progressive form of MS

Plaques associated with cord atrophy

Relapsing-progressive form of MS

Diffuse abnormalities (mild intramedullary hyperintensities on T2-weighted MR images)

Primary progressive MS and secondary progressive MS


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