Demyelination of the Brain

SOURCE: spinwarp.ucsd.edu

This is not the whole article.

John R. Hesselink, MD, FACR

      MR imaging is exquisitely sensitive for detecting brain abnormalities. Particularly in the evaluation of white matter diseases, MR far outperforms any other imaging technique. Lesions that may be quite subtle or even invisible on CT are often clearly seen on the MR scan. The MR signal characteristics of white matter lesions are similar and relatively nonspecific, but other distinguishing features are often present to assist in diagnosis, such as the pattern of the abnormality, location, and enhancement features.

      The white matter is affected by many disease processes. The primary demyelinating disease is multiple sclerosis, but many other metabolic and inflammatory disorders result in deficient or abnormal myelination. Histologically, myelin abnormalities are either demyelin-ating or dysmyelinating. Demyelination implies destruction of myelin. Dysmyelination refers to defective formation or maintenance of myelin resulting from dysfunction of the oligodendrocytes. Most of the dysmyelinating disorders are caused by metabolic defects that present in infancy. White matter diseases in older children and adults are generally demyelinating or a combination of the two processes.


NORMAL WHITE MATTER

      The white matter of the brain is located in the central and subcortical regions of the cerebral and cerebellar hemispheres and accounts for about 60 % of the total brain volume. The white matter includes the major commissural tracts, the cortical association fibers, and all the cortical afferent and efferent fibers. Histologically, the white matter contains nerve fibers, supporting cells, interstitial space, and vascular structures. White matter consists mostly of axons with their envelope of myelin, along with two types of neuroglia: oligo-dendrocytes and astrocytes. Axons are extensions of neurons that reside within the gray matter of the brain, spinal cord, and ganglia. The myelin is produced and maintained by oligodendrocytes. Myelin functions as an insulator of the axons, and its structure facilitates rapid transmission of impulses.

      Myelin has relatively short T2 and T1 relaxation times, primarily owing to its lipid content. As a result, normal myelin is hypointense to gray matter on T2-weighted images and hyperintense on T1-weighted images. If a disease process reduces the myelin content, the white matter becomes less hydrophobic and takes on more water. Less myelin and more water protons prolong the relaxation times of both T1 and T2, resulting in more signal on T2-weighted and less signal on T1-weighted images. ,


MULTIPLE SCLEROSIS

      On histologic examination, acute MS plaques show partial or complete destruction and loss of myelin with sparing of axon cylinders. They occur in a perivenular distribution and are associated with a neuroglial reaction and infiltration of mononuclear cells and lymphocytes. The perivascular demyelination gives the appearance of a finger pointing along the axis of the vessel. In the pathologic literature these elongated lesions have been named "Dawson's fingers." Active demyelination is accompanied by transient breakdown of the blood-brain barrier. Chronic lesions show predominantly gliosis. MS plaques are distributed throughout the white matter of the optic nerves, chiasm and tracts, the cerebrum, the brain stem, the cerebellum and the spinal cord.


Imaging Features

      MS plaques are hyperintense on T2-weighted and FLAIR images and hypointense on T1-weighted scans. Specific signal intensities of MS lesions will vary depending on the magnetic field strength, the pulse sequence parameters, and partial volume effects. Occasionally, acute plaques may have a thin rim of relative T2 hypointensity or T1 hyperintensity. The T1 hyperintensity is attributed to free radicals, lipid-laden macrophages, and protein accumulations.

      MS plaques are usually discrete foci with well-defined margins. Most are small and irregular, but larger lesions can coalesce to form a confluent pattern. Multiple focal periventricular lesions can give a "lumpy-bumpy" appearance to the ventricular margins. As a result of their perivenular distribution, many periventricular plaques have an ovoid configuration, with their long axis oriented transversely on an axial scan. The ovoid lesion is the imaging correlate of "Dawson's finger." In general, MS plaques have a homogeneous texture without evidence of cystic or necrotic components. Hemorrhage is not a feature of MS lesions. Edema and mass effect are also uncommon.

      The periventricular white matter is a favorite site for MS plaques, particularly along the lateral aspects of the atria and occipital horns. The corpus callosum, corona radiata, internal capsule, visual pathways, and centrum semiovale are also commonly involved. When more than a few lesions are present, symmetric involvement of the cerebral hemispheres seems to be the rule. Any structures that contain myelin can harbor MS plaques, including the brain stem, spinal cord, subcortical U-fibers, and even within the gray matter of the cerebral cortex and basal ganglia. A distinctive site in the brain stem is the ventrolateral aspect of the pons at the fifth nerve root entry zone. Brain stem and cerebellar plaques are more prevalent in the adolescent age group.

      Lesions of the corpus callosum have been a special focus of study. On axial sections, plaques in the corpus callosum above the lateral ventricles have a transverse orientation along the course of the nerve fiber tracts and vessels. Sagittal FLAIR images are especially helpful to depict the small callosal lesions closely apposed to the superior ependymal surface of the lateral ventricles. Early edema and demyelination along subependymal veins produce a striated appearance. Atrophy of the corpus callosum is common in long-standing, chronic MS and is seen best on T1-weighted sagittal images.

      Involvement of the visual pathways, particularly the optic nerves, frequently occurs sometime during the course of disease. Patients may present with optic neuritis, although in about half of those cases, MRI will unveil other silent lesions in the brain. Imaging plaques in the optic nerves is a challenge even for MRI. Unenhanced spin-echo sequences are not very sensitive, and generally some type of fat suppression is required. Probably the most sensitive method for detecting acute MS of the optic nerves is the combination of gadolinium enhancement and fat suppression.

      The spinal cord is commonly involved by MS, and patients may present with a transverse myelitis. All levels of the cord can be affected, but most plaques are found in the cervical region. Since the white matter fiber tracts are positioned along the outer aspects of the cord, MS plaques are often based along a pial surface and have an elongated configuration. Signal characteristics are similar to lesions in the brain. Edema associated with acute plaques may lead to cord swelling, simulating an intramedullary tumor. In chronic MS, cord atrophy can result from focal lesions or axonal degeneration from distal disease.

      Nonenhanced MR cannot judge lesion activity, because plaques almost always remain evident after the acute clinical episode. Although the water content of acute plaques decreases over time, the T1 and T2 relaxation times of acute and chronic plaques have sufficient overlap that quantitative MR cannot distinguish between old and new lesions. Quantitative brain analyses of MS patients have shown that the T1 and T2 relaxation times are prolonged not only in acute and chronic plaques but also in normal-appearing white matter.  Occasionally, a “dirty white matter” appearance can be seen on T2-weighted images. Diffuse white matter involvement has been confirmed further with magnetization transfer (MT) measurements.


Gadolinium enhancement

      Since acute MS plaques are associated with transient breakdown of the blood-brain barrier, gadolinium contrast agents will produce enhancement of these lesions on T1-weighted images. Enhancement will be observed for 8 to 12 weeks following acute demyelination. Thus, Gd-enhanced MR can be used to assess lesion activity just like contrast-enhanced CT. Either nodular or ringlike enhancement may be seen early after contrast injection, but the central areas tend to fill in and become more homogeneous on delayed scans. Immediate postcontrast scans are most sensitive for detecting MS, and delayed scanning is not necessary. Contrast-enhanced MR can be used to follow the progression of disease and to assess the response to the response to therapy.

      Occasionally, large plaques, also called tumefactive MS, may produce mass effect and simulate other mass lesions. However, compared with neoplastic or inflammatory processes, MS plaques have minimal surrounding edema and relatively less mass effect for the overall size of the white matter lesions. Balo's concentric sclerosis has a unique MR appearance. Like tumefactive MS, the plaques usually are quite large, but in addition, a concentric laminated pattern is seen on T2 and T1-weighted images. Similarly, post-contrast images often show rings of enhancement alternating with non-enhancing regions during the acute phase.
 

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