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Cerebrospinal Fluid In about one-third of all MS patients, particularly those with an acute onset or an exacerbation, there may be a slight to moderate mononuclear pleocytosis (usually in the range of 6 to 20 and in any case, less than 50 cells per cubic millimeter) In rapidly progressive cases of neuromyelitis optica (see above) and in certain instances of severe demyelinative disease of the brainstem, the total cell count may reach or exceed 100 and rarely 1000 cells per cubic millimeter; in the hyperacute cases, the greater proportion of these may be polymorphonuclear leukocytes This pleocytosis may in fact be the only measure of activity of the disease It has been shown that the gamma globulin proteins in the CSF of patients with MS are synthesized in the CNS (Tourtellotte and Booe) and that they migrate in agarose electrophoresis as abnormal discrete populations, so-called oligoclonal bands This is currently the most widely used CSF test for the con rmation of the diagnosis Determination of the IgG index and testing for oligoclonal IgG bands is done in most commercial and hospital labo-
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MAJOR CATEGORIES OF NEUROLOGIC DISEASE
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of Stewart and coworkers, who found multifocal lesions in the cerebrum in 80 percent of their established cases In a series of 114 patients with clinically de nite MS, Ormerod and colleagues detected T2-intense periventricular MRI abnormalities in all but 2 patients and discrete cerebral white matter lesions in all but 12 With newer imaging sequences, the proportion with lesions is even higher, greater than 90 percent in some series It is remarkable that even when there are a multitude of cerebral lesions, they tend to be asymptomatic; by contrast, spinal cord lesions are almost always symptomatic Also, attention has been drawn by Bot and colleagues to lesions in the spinal cord that allow for diagnosis based on the identi cation of a second involved site in the nervous system However, even in their series of 104 patients, only 3 had an abnormality in the cord and none in the cerebrum Several MRI features are characteristic of the chronic MS lesion; some of these are dependent on the eld strength of the magnet and the ratio of T1 and T2 weighting In general, chronic MS plaques are hyperintense (white) on T2-weighted images and even more strikingly obvious on FLAIR images (although we have seen the opposite pattern in some posterior fossa lesions) Lesions that have undergone some degree of cavitation, as happens only occasionally, are hypointense on T1-weighted images Longitudinal analyses reveal a slow increase over time in the total burden of hypointense T1 images; in one study, these increased with the numbers of enhancing lesions in untreated patients (Simon) The discrete cerebral lesions of MS do not always impart a speci c MRI appearance; but the nding on T2-weighted images of several asymmetrical, well-demarcated lesions immediately adjacent to the ventricular surface usually denotes MS Especially diagnostic are oval or linear regions of demyelination, oriented perpendicularly to the ventricular surface; they correspond to the radially oriented ber bundles of the white matter and periventricular veins When viewed in sagittal images, they extend outward from the corpus callosum in a mbriated pattern and have been termed Dawson ngers These areas may extend into the centrum semiovale and may reach the convolutional white matter (Fig 36-1) Even one highly characteristic lesion is sometimes enough to con rm the diagnosis in the proper clinical circumstances; multiple lesions are more convincing The presence of such lesions in the corpus callosum is diagnostically useful, as this structure is spared in many other disorders Early in the evolution of an MS lesion there is disruption of the blood-brain barrier, presumably as a consequence of in ammation The MRI correlate is enhancement following the administration of gadolinium Although usually readily apparent, this aspect may be exposed only by administration of double or triple the usual dose of gadolinium Gadolinium enhancement may last for 3 to 4 months following the development of the acute lesion Otherwise, the signal characteristics of MS lesions are not obviously dependent on the age of the lesions In advanced cases of MS, the lesions become con uent, usually at the poles of the ventricles The spectrum of these changes has been commented on by Berry and colleagues Infrequently, a large acute lesion may have a mass effect and a ring-like contrastenhancing border, resembling a glioblastoma or an infarct; the correct diagnosis may then be made only by biopsy A series of focal tumor-like lesions of the brain, the demyelinative nature of which became evident only after biopsy, has been reported by Kepes Serially performed MRIs can demonstrate the progress of the disease by the accumulation of increasing numbers of cerebral lesions; but even then they usually remain asymptomatic As mentioned,
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lesions in the spinal cord that are detected by MRI are more likely to be symptomatic, but there are striking exceptions As with other laboratory procedures, MRI changes assume maximal diagnostic signi cance when they are consistent with the clinical ndings Increasingly, other aspects of the pathology of MS lesions have been delineated using MRI studies, such as the processes of plaque remyelination, axonal degeneration and brain atrophy As assessed histologically in 36 brains with both autopsies and MRI studies, remyelinated foci were quite common and correlated well with persistent T2 hyperintensity; on the other hand, T1 hypointensity was inversely proportional to the degree of remyelination (Barkhof) Several studies have documented that slowly progressive brain atrophy, as gauged by volumetric MRI measurements, is a feature of long-standing MS This is demonstrable both early and late in the disease and correlates loosely with disability The basis for the atrophy is not fully de ned It probably re ects both the loss of glial cells and, importantly, wallerian degeneration and loss of axons triggered acutely by in ammation and more chronically by other neurodegenerative stimuli (Miller) In the investigation of brain atrophy in MS, volumetric studies have been supplemented by spectroscopic biochemical analyses; some studies have demonstrated a correlation between various measures of atrophy, levels of N-acetyl-aspartate (NAA, a marker of axons), and disability It should be stressed that foci of periventricular hyperintensity are observed with a variety of pathologic processes and even in normal persons, particularly older ones; in the older individuals, the periventricular changes are usually milder in degree, less dense, and smoother in outline than the lesions of MS Evoked Potentials and Other Con rmatory Tests When the clinical data point to only one lesion in the CNS, as often happens in the early stages of the disease or in the spinal form, a number of other sensitive physiologic and radiologic tests may establish the existence of additional asymptomatic lesions These include visual, auditory, and somatosensory evoked responses and the less standardized and infrequently tested perceptual delay on visual stimulation; electro-oculography; altered blink re exes; and a change in icker fusion of visual images At our hospitals, abnormal visual evoked responses have been found in 70 percent of patients with the clinical features of de nite MS and 60 percent of patients with probable or possible MS The corresponding gures for somatosensory evoked responses have been 69 percent and 51 percent, and for brainstem auditory evoked responses (usually prolonged interwave latency or decreased amplitude of wave 5), 47 percent and 20 percent, respectively according to our colleague K Chiappa (see Chap 2) CT scanning may also demonstrate cerebral lesions, often unexpectedly Doubling the dose of contrast material and delaying the scan for an hour postinfusion increases the yield of lesions during exacerbations of MS Two points worth noting about the CT scan are that acute plaques can appear as contrast-enhanced ring lesions, simulating abscess or tumor, and that some contrastenhanced periventricular lesions become radiologically inevident after steroid treatment, as occurs also with CNS lymphoma As mentioned earlier, the ancillary examinations in common use MRI, evoked potentials, and oligoclonal bands in the CSF have broadened the criteria for the diagnosis of MS Often these procedures disclose the presence of multiple plaques when clinical examination has failed to do so Stated differently, the time-honored rule that the diagnosis of MS requires evidence of lesions
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