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Neuroradiology Case of the Week

Case 395

March 2009

Ashwani K. Sharma, MD, and PL Westesson, MD, PhD, DDS

Clinical Presentation: A 34-year-old female presented with progressive right arm and left leg numbness and weakness.

Imaging Findings: On magnetic resonance (MR) imaging, typical multiple sclerosis (MS) lesions appear as T2 hyperintensities in the periventricular regions; they have an ovoid appearance with their largest axis oriented perpendicular to the ventricular surface and they also involve corpus callosum.
     The most common infratentorial locations for plaque formation are the surface of the pons, the cerebellar peduncles, and white matter regions adjacent to the fourth ventricle.
Hypointensity of lesions in T1 images may reflect some degree of axonal damage or more chronic tissue damage resulting in gliosis.
     Lesions that enhance with gadolinium are thought to reflect active disease, as enhancement may correspond to breakdown of the blood-brain barrier from an ongoing subacute inflammatory process.

Diagnosis: Multiple Sclerosis

Discussion: Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). MS lesions, characterized by perivascular infiltration of monocytes and lymphocytes, appear as indurated areas in pathologic specimens; hence, the term "sclerosis in plaques." The disease can present in different forms, such as primary progressive, relapsing remitting, relapsing progressive, and secondary progressive phenotypes.
     The favorable clinical responses to the disease-modifying immunomodulatory agents (i.e., interferon beta-1a and beta-1b, glatiramer acetate) suggest that these medications modify disease progression on the basis of their ability to counteract the proinflammatory phenotype of immune cells. Other disease-modifying treatments for MS include mitoxantrone (a DNA intercalator) and natalizumab (a monoclonal antibody against the adhesion molecule VLA-4).

Enhancement patterns in multiple sclerosis: The acute enhancing MS lesion is visualized as a result of abnormal leakage and accumulation of contrast material across disrupted tight junctions of the vascular endothelium that are a crucial component of the blood-brain barrier [1].
     The duration of enhancement can range from less than 1 week to about 16 weeks. The time course for enhancement in MS parallels that for inflammation, but more accurately enhancement measures the integrity of the blood-brain barrier [2].
     The enhancement pattern (size, shape, solid versus ring) may be strikingly variable within and more so between patients, which is highly suggestive of a heterogeneous pathology, possibly related to the host response and severity [3,4]. Ring enhancement, for example, may suggest a more severe pathology [4]. Enhancement seen only after high (triple dose) MR imaging contrast infusion tends to be smaller and may indicate less destruction than that detected by single (standard) dose MR imaging contrast [5].
     Schwartz, et al. [6] reviewed 221 ring-enhancing lesions seen on MR images and reported that 40% were gliomas; 30%, metastases; 8%, abscesses; and 6%, demyelinating disease. In their series, 45% of metastases and 77% of gliomas were single lesions, whereas abscesses and multiple sclerosis lesions were multiple in 75% and 85% of patients, respectively [6].
     The cause of the enhancement in demyelination is inflammation, usually perivascular, which most often is limited to the venous side (i.e., "perivenular" inflammation); there is no neovascularity, no angiogenesis, and no necrosis [7]. For this reason, enhancement of multiple sclerosis plaques may be faint, the lesions usually do not produce any perilesional vasogenic edema, and the enhancing rim is thin and often incomplete [6,8,9]. An "incomplete ring" may be seen in active demyelination, both in multiple sclerosis and in tumefactive demyelination [8,9].
     If MS is suspected, MR imaging of the spinal cord may demonstrate additional lesions to help support the diagnosis [10].
     MR spectroscopy uses the characteristic spectra of specific biochemical markers to quantitate organic compounds in vivo. N-acetylaspartate (NAA) is a relatively specific neuronal marker that is in sufficient concentrations in the brain to be revealed on MR spectroscopic images. By comparing the spectral signal of NAA with that of creatinine (Cr), MR spectroscopic can be useful in assessing neuronal and axonal loss.

Clinical Diagnosis: A diagnosis of MS is made on the basis of clinical findings by using supporting evidence from ancillary tests such as cerebrospinal fluid (CSF) examination for oligoclonal banding and MRI.
     Clinically, MS has historically been diagnosed with the demonstration of white matter dysfunction disseminated in time and space (Schumacher, 1965) [11]. With the advent of diagnostic laboratory investigations and imaging techniques, the Poser criteria (Poser, 1983) [12] were proposed to establish a degree of certainty of diagnosis in the absence of the two clinical attacks by using terms such as possible MS and probable MS.
     Even more recently, with increasing treatment options for MS, and better imaging techniques, newer diagnostic criteria have been suggested that allow diagnosis after a single attack coupled with appropriate positive test results. These criteria have been coined the McDonald criteria [13].
     Dissemination in space based on the criteria of McDonald and colleagues [13], Barkhof and colleagues [14], and Tintore and colleagues [15] consisted of three of four of the following:
       1.  At least one gadolinium-enhancing or nine T2 lesions.
       2.  At least one infratentorial lesion.
       3.  At least one juxtacortical lesion.
       4.  At least three periventricular lesions.
One cord lesion was allowed to replace one brain lesion.
     Dissemination in time consisted of either one or more gadolinium-enhancing lesions at least 3 months after the attack or one or more T2 lesions subsequent to a scan at least 3 months after the attack.

References:

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