Incidence and Types of Cortical Lesions

Several studies have described the incidence of cerebral cortical lesions in MS. A histological study by Brownell and Hughes (1962) reported that 26% of the brain lesions in MS involved the gray matter. The majority of gray matter lesions (~65%) was located at the leukocortical junction and affected both the cortex and white matter. The remaining 35% of the lesions were located either in the central gray matter (15%) or completely within in the cortex (~19%). Another histological study of 60 MS brains reported cortical lesions in 93% of cases, with 59% of the cerebral lesions affecting the cortex (Lumsden, 1970). In one brain there was extensive involvement of the cerebral cortex, which contained an incredible 465 gyral plaques.

Despite the identification of cortical involvement, which can be quite extensive in some patients with MS, this aspect of the disease has been overlooked for the last 30 years. Recently, there has been renewed interest in the involvement of cerebral cortex in MS (Filippi, 2001). MRI allows the in vivo detection of white matter lesions, which sometimes correlate with neurological symptoms; however, MS patients often display neurological symptoms that cannot be explained by the identified white matter pathology. A recent immunocytochemical study identified and characterized 112 cortical lesions in 110 tissue blocks from 50 MS brains (Peterson et al., 2001). Based on the distribution of the demyelinated areas, three general types of cortical lesions were described (Fig. 8). Type I lesions, which demyelinated both white matter and cortex, made up 34% of the cortical lesions. Demyelinating lesions that were intracortical were called Type II lesions and consisted of 16% of the cortical lesions. The remaining 50% of the cortical lesions extended into the cortex from the pial surface and were defined as Type III lesions. All three lesion types were often identified in tissue from the same MS brains. Although no single pattern of cortical demyelination appears to predominate in individual patients, it remains to be determined whether sub-grouping patients with variable pathogenesis (Lucchinetti et al., 2000) can identify a prevalence of subtypes. Each subtype may be informative regarding mechanisms of demyelination and characteristics of the immune response or demyelinating inflammatory environment. Cortical lesions were identified in

Figure 8 Three types of cortical demyellnatlon are prominent in MS. Type I lesions occur at the leukocortical junction affecting both white and gray matter. Type II lesions are small, circular intracortical lesions most often centered around vessels. Type III lesions extend from the pial surface midway into the cortex and often involve multiple gyri. Cortex is white, white matter is gray, and orange represents demyelination.

Figure 8 Three types of cortical demyellnatlon are prominent in MS. Type I lesions occur at the leukocortical junction affecting both white and gray matter. Type II lesions are small, circular intracortical lesions most often centered around vessels. Type III lesions extend from the pial surface midway into the cortex and often involve multiple gyri. Cortex is white, white matter is gray, and orange represents demyelination.

tissue samples from all 50 of the MS brains, suggesting that cortical involvement in MS is common. The extent of cortical demyelination was more carefully analyzed in another recent immunocytochemical study that prospectively selected the frontal, parietal, and temporal cortices along with cingulate gyrus for analysis from postmortem MS brains. The study determined that on average approximately 27% of the sampled cortices was demyelinated, indicating significant involvement of the cortices in MS (Bo et al., 2003b).

Although these studies suggest that cortical demyelination is significant in MS brains, the precise incidence and dynamics of cortical demyelination remain to be elucidated. Cortical lesions are often missed in sections stained histologically for myelin with luxol fast blue (LFB) because the protocol recommends destaining LFB sections until the cerebral cortex is no longer blue. This may explain why the earlier histological studies (Brownell and Hughes, 1962; Lumsden, 1970) identified fewer cortical only lesions, which would be harder to detect than lesions that also affected the white matter. However, myelin protein immunocytochemistry has proven to be highly sensitive and reliable for identifying cortical lesions in paraffin, free floating, and frozen tissue sections (Peterson et al., 2001; Bo et al., 2003b). A more practical approach to determine the cortical lesion load is the possibility of using MRI scans. In a combined MRI/histology study the use of gadolinium-enhancement increased the detection of cortical lesions on MRI scans by 140% (Kidd et al., 1999). In addition, 26% of all active brain lesions identified in this study were within or adjacent to the cerebral cortex. Although the use of gadolinium with T2-weighted MRI scans improved detection of cortical lesions, histologi-cal examination of the same brains revealed that MRI analysis still underestimated the presence of cortical lesions. Although standard MRI and MRS protocols are relatively insensitive for detection of cortical lesions (Kidd et al., 1999; Sharma et al., 2001), specialized pulse sequences or spec troscopy with 3 Tesla scanners may provide the higher resolution necessary for detection of cortical lesions.

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