The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis
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Abstract
Article abstract MRI is very sensitive in showing MS lesions throughout the CNS. Using MRI for diagnostic purposes, however useful, is a complex issue because of limited specificity of findings and a variety of options as to when, how, and which patients to examine. Comparability of data and a common view regarding the impact of MRI are needed. Following a review of the typical appearance and pattern of MS lesions including differential diagnostic considerations, we suggest economic MRI examination protocols for the brain and spine. Recommendations for referral to MRI consider the need to avoid misdiagnosis and the probability of detecting findings of diagnostic relevance. We also suggest MRI classes of evidence for MS to determine the diagnostic weight of findings and their incorporation into the clinical evaluation. These proposals should help to optimize and standardize the use of MRI in the diagnosis of MS.
MRI is by far the most sensitive technique for detecting MS lesions in vivo throughout the CNS. As a consequence, MRI has become an important tool for diagnosing MS and providing surrogate markers in therapeutic trials. Guidelines for the use of MRI in monitoring treatment efficacy have been issued.1-3 However, less work has been done toward developing consensus guidelines for diagnostic evaluation. This is for a variety of reasons. First, whereas MRI shows typical lesions in the majority of patients with clinically definite MS, and at times, such a finding is more robust than vague clinical symptoms, other disorders can also produce changes typical for MS. MS-like lesions may even be seen in asymptomatic individuals. Secondly, there are a few patients with clinically definite MS who do not show MRI abnormalities in either the brain or the spinal cord. Providing strict diagnostic criteria may therefore 1) overestimate the importance of MRI, 2) suggest a diagnosis of MS even in the absence of clinical findings, or 3) underestimate the frequency of this disorder if MRI changes do not meet certain criteria.4-6 Third, it is difficult to condense adequately the knowledge of experienced interpreters into simple diagnostic criteria. Finally, all MRI information should be viewed in the context of the clinical situation and complementary investigational results. Despite all these concerns, however, there is a need to standardize MRI as a diagnostic tool, especially with the rapid technical developments of recent years including hardware improvements and a wide choice of new sequences. There is need for a consensus on which MRI findings are of diagnostic support and to what extent. Economic concerns will also influence the diagnostic protocol.
A task force of the North Atlantic Collaboration in MS has reviewed the use of MRI as diagnostic tool for MS in clinical practice based on current literature and expert opinion. The review covered the range of MRI findings in MS lesions and comparison with other disorders. Based on this review, recommendations have been developed for 1) indications for referral for diagnostic MRI studies, 2) the examination protocol, and 3) interpretation of MRI findings in the context of MS diagnosis. The review and recommendations are presented here.
MRI characteristics of MS lesions.
Both acute and chronic MS lesions appear bright on proton density (PD)- and T2-weighted scans, as do other brain pathologies. Discrete MS lesions are relatively well circumscribed but may show a halo of less striking hyperintensity, probably consistent with edema in the very acute stage of inflammation. MS lesions tend to appear round or ovoid in shape and their size commonly ranges from a few millimeters to more than one centimeter in diameter.7 Differences in shape are partly a consequence of the angle of the imaging plane with the course of cerebral venules that frequently constitute the center of an MS lesion.8 Irregular areas of signal hyperintensity result from confluence of lesions. As a consequence, periventricular signal changes may take on a scalloped appearance. Rarely, disease foci can be very large, with a pseudotumor appearance. Slight signal alteration between or surrounding discrete lesions has also been observed on T2-weighted images of the brain and appears to represent a more diffuse component of the disease process.9 The term “dirty white matter” has been coined for such ill-defined abnormalities, which occur mainly in the deep and periventricular white matter and sometimes may be difficult to differentiate from the normal range of variability in white matter myelination. Whereas relatively static in extent, these regions have also been noted as a place for new, typical lesion formation at follow-up.10
Around 10 to 20% of T2 hyperintensities are also seen on T1-weighted images as areas of low signal intensity compared with normal white matter. In the acute phase, T1 hypointensity probably is a consequence of marked edema with or without matrix destruction, and can disappear as inflammation abates.11 Chronic foci of hypointensity also known as persisting “black holes” indicate areas with more severe tissue damage.12 On corresponding PD-weighted images, the center of these lesions, although more difficult to define, is also lower in signal intensity (because of a T1 saturation effect). This pattern becomes even more apparent using a sequence with T2 weighting but suppression of signal from CSF, such as fluid-attenuated inversion recovery (FLAIR).13 Large plaques are more likely to develop T1 hypointensity, both acutely as well as in their chronic stage.11 Infratentorially, MS-related signal abnormalities are often more diffuse and less bright, and there is a lower probability for “black holes” to develop in this region.11,14
A high propensity of MS lesions for certain brain regions has been noted pathologically and in accordance is seen on MRI. Characteristic areas of involvement are the periventricular white matter including the corpus callosum, the cortico-subcortical regions, and the infratentorial brain regions. Discrete hyperintensities adjacent to the body or temporal horn of the lateral ventricles are frequent in MS and rarely seen with other disorders.15 Lesions around the frontal or posterior horns are also often seen but more difficult to separate from the phenomenon of hyperintense periventricular caps in normal subjects, at least in the early stage of the disease. Lesions of the corpus callosum are located preferentially at its inferior border toward the lateral ventricle or extend radiating toward the periphery.16-18 This appearance is the corollary to the pathologists’ eponym of Dawson’s fingers and can be best appreciated on PD/T2-weighted sagittal views. Pathologic examinations of MS brains report a high number of cortical lesions, but apparently this finding cannot yet be fully reproduced by MRI.19 Confounding factors are the small size of such abnormalities, less optimal contrast of MS lesions against adjacent gray compared to white matter, and partial volume effects with adjacent CSF. More recently developed segmentation algorithms promise a more comprehensive appreciation of cortical involvement in MS.20 Areas of signal hyperintensity adjacent to the cortex are more easily detected on conventional MRI. They are seen in around two thirds of patients with clinically definite MS21 and appear to be a rather characteristic finding in early stages of the disease.22 Detection of these lesions is facilitated by the use of FLAIR23,24 and the administration of contrast material.22,25 Preferred infratentorial locations of MS lesions are the floor of the fourth ventricle, the cerebellar peduncles, and the surface of the pons.15
MS lesions are further characterized by their dynamic evolution. In relapsing-remitting or secondary progressive MS, disease activity shown by MRI is 5 to 10 times higher than can be recognized clinically.1,2 The presence of blood–brain barrier disruption as indicated by contrast enhancement in new lesions serves best to delineate acute inflammation, and when present tends to persist for 2 to 6 weeks.25-27 Contrast enhancement also indicates the recurrence of inflammation within preexisting lesions. Steroid treatment of acute attacks shortens the period of enhancement.28 Acute lesions wax and wane in size and intensity, but some T2 abnormality will persist in most instances. Rarely, lesions disappear. Lesions falsely missed at follow-up are most likely those with a diameter below MRI slice thickness and infratentorial lesions because their signal intensity may barely exceed that of normal brain tissue in the chronic stage. Repair mechanisms, including remyelination, may contribute to signal normalization. With ongoing disease, new lesions or the enlargement of preexisting lesions can be seen to occur simultaneously with the shrinkage of other previously active plaques.
Spinal cord lesions in MS share a similar signal pattern as cerebral lesions except for the absence of “black holes.”14 On sagittal scans, spinal cord plaques characteristically have a cigar shape and may be located centrally, anteriorly, or posteriorly. Axial scans show their extension toward the periphery with a propensity for the dorsal columns. Spinal MS lesions rarely occupy more than half of the cross-sectional area of the cord or exceed two vertebral segments in length. Lesions are seen more often in the cervical than thoracic spinal cord and are most common in the midcervical region.29-31 Acute lesions, although infrequent, can produce mass effect with swelling of the cord and may enhance after the application of contrast material. Disease activity, including contrast enhancement and the development of new lesions, is much less frequent in the spine than in the brain.32 Global signal changes of the spinal cord have also been reported in MS.33 They consist of diffuse mild hyperintensity on PD-weighted scans and were seen most often in patients with a primary progressive course of the disease.33 However, this finding has yet to be replicated.
MRI also can detect MS lesions in the optic nerve. The challenge to delineate lesions within the nerve, despite its tortuosity and mobility and the surrounding orbital fat, can be solved with fat-suppression sequences and phased array coils.34,35 In optic neuritis, there is a moderately strong relation between lesion length and the rapidity and degree of visual recovery.36 When investigating cases of optic neuropathy, the diagnostic information provided by MRI clearly supersedes that of CT. This finding is partly due to the detection of coexisting demyelinating brain lesions as well as a high sensitivity of MRI for other intraorbital pathology.37 However, there is little need to detect demyelinating optic nerve lesions in routine diagnostic MRI—visual evoked potentials are an equally sensitive tool for such purpose.
Prevalence of MRI findings according to stage and course of MS.
Patients who present with a first symptom suggestive of MS may show a normal scan or one or more signal hyperintensities on MRI of the brain. The probability of developing clinically definite MS is strongly influenced by the number of lesions at first presentation.38-41 In a prospective study, infratentorial, juxtacortical, and periventricular lesion location and gadolinium enhancement were the four features which in a regression model were able to predict conversion to clinically definite MS with a sensitivity of 82% and a specificity of 78%.22 The long-term evolution of MRI changes has not yet been analyzed in detail. Obviously, continuing accumulation of new lesions should increase both the total area of signal abnormality and the number of brain regions involved and ultimately can lead to confluent hyperintensity extending from the lateral ventricles toward the periphery and down into the brainstem as frequently seen in later stages of MS. Except at the clinical onset, the correlation of lesion load with clinical disability is generally limited but statistically significant.42 With advancing disease, atrophy of the brain and spinal cord may also become apparent.43,44
Lesion patterns of patients with relapsing-remitting or secondary progressive MS are rather similar. In comparison, patients with a primary progressive course of the disease tend to have fewer and smaller lesions.45 This holds true for periventricular and nonperiventricular regions.46 Disease activity as shown by the number of new and enhancing lesions is also much lower in patients with primary progressive MS than in the two other groups.45,47
MS lesions within the spinal cord are more difficult to detect than in the brain because of a lower conspicuity and greater technical challenges for their delineation. Therefore, patients presenting with spinal cord symptoms may well have a negative MRI of the spine but can show cerebral lesions that are typical for MS.30,48 However, the inverse can also occur. Patients with suspected MS may have a normal or equivocal MRI examination of the brain but can show characteristic lesions in the spinal cord.6 Such findings are more common for patients with primary progressive MS, but can be seen in classic relapsing-remitting MS.
Differential diagnosis and diagnostic criteria for MS.
Disorders that can cause MRI signal hyperintensities of the white matter are numerous. Fortunately, the pattern of signal abnormalities associated with these diseases is rather different from MS in most disorders. Moreover, the possibility of a false positive interpretation of non-MS hyperintensities strongly depends on their prevalence within the “suspected MS population.” Therefore, the following categories of disorders that need to be considered in the differential diagnosis include more frequent or representative examples of diseases only. Overall, they are much less common than MS, except for incidental or microangiopathy-related hyperintensities.
Brain.
Incidental hyperintensities/hypoxic-ischemic disorders.
Punctate or patchy white matter signal hyperintensities are frequently seen with normal aging. They are noted in about half of the normal population around the age of 50 years.7 Occurrence of incidental MRI lesions is not restricted to the elderly brain, however, and can also be seen in younger individuals and even in children. Cerebrovascular risk factors such as hypertension and migraine are associated with a higher frequency of such lesions. “Incidental” hyperintensities are randomly distributed throughout the deep and subcortical white matter. Infratentorial regions are usually spared. Small symmetric periventricular caps predominantly around the frontal horns are a normal morphologic variation and smooth lining or bands of periventricular hyperintensity in the absence of obstructed CSF pathways are a nonspecific finding.49
Irregular and sometimes extensive periventricular hyperintensity is seen in patients with subcortical arteriosclerotic encephalopathy. Confluent signal changes typically spare the subcortical U-fibers. Clearly demarcated lacunar lesions within the areas of white matter signal abnormality and in the basal ganglia are frequent and characteristic50 and may even be seen within the corpus callosum. In contrast to MS lesions, the center of a lacune tends to appear isointense to CSF on all sequences because of complete tissue destruction. Ill-defined hyperintensity may also be seen in the pons but is usually confined to its central parts. As subcortical arteriosclerotic encephalopathy usually does not develop before the fifth decade, this problem of differential diagnosis is encountered primarily when MS is suspected later in life.
Immune-mediated vasculopathies.
Vasculitis and immune-mediated vasculopathies are important to consider in the differential diagnosis of MS and need not be associated with a typical pattern of infarction. Systemic lupus erythematosus and the antiphospholipid syndrome can cause nonspecific focal white matter hyperintensities.51,52 These lesions are located primarily in the deep and subcortical white matter. Behçet’s disease involves primarily the brainstem and the diencephalon.53
Infectious and inflammatory diseases.
A few patients with Lyme disease have shown a lesion pattern similar to MS but such finding is uncommon. Neurosarcoidosis can be associated with multiple lesions throughout the CNS. Almost exclusively cortico-subcortical location of lesions and frequently associated granulomatous leptomeningitis as evidenced using gadolinium are different from MS in most cases. Progressive multifocal leukoencephalopathy, HIV encephalitis, subacute sclerosing panencephalitis, and other inflammatory disorders of the brain may cause nonspecific white matter changes but will usually not mimic a lesion pattern that is typical for MS.
Early on, acute disseminated encephalomyelitis (ADEM) may not be separable from MS. Areas of inflammation in ADEM may share all the features of acute MS lesions. At the beginning of the disease, extensive perifocal edema and contrast enhancement of most lesions suggest a rather aggressive process and lesion uniformity attests to a monophasic event, even though a mix of enhancing and nonenhancing lesions can sometimes be found. Some patients with ADEM exhibit symmetric lesions in cerebellar peduncles or cerebral white matter—a pattern unlike MS. Chronic lesions characterized by tissue destruction with atrophy should be absent. Lesions tend to resolve at follow-up and new lesions should not occur.54,55
Leukodystrophies and toxic metabolic diseases.
These disorders are very rare and include various types of dysmyelination or demyelination caused by inborn metabolic errors and damage to the white matter from toxins including radiation therapy. Most of these diseases are associated with a rather symmetric and confluent pattern of white matter signal abnormality that lacks the discrete multifocality of lesions common to MS. It must be noted, however, that MS-like lesions have been reported for individuals with Leber’s hereditary optic neuropathy, a mitochondrial disease,56 and patients with vitamin B12 deficiency.57
Malignancies.
Brain tumors such as a glioma can cause an area of signal hyperintensity that may be indistinguishable from demyelination presenting as a solitary or mass lesion. Lymphoma or even metastatic disease may have to be considered with multiple lesions. Short-term lesion evolution usually suffices to make a clear diagnosis if morphologic features are not sufficiently specific at first, but sometimes biopsy is required for a definitive diagnosis.
The differences in lesion distribution, shape, and size between the above disorders and MS have stimulated the development of criteria for MRI differential diagnosis.7,58 More recently, the pattern of features typical for MS lesions was expanded in a search for predictors of conversion to clinically definite MS following a first symptom22 (table 1). All three sets of criteria appear valid but the different purposes for which they were developed should be recognized. The criteria of Paty et al.58 were defined to determine MRI’s capability of predicting the development of clinically definite MS in patients with suspected MS, whereas the criteria of Fazekas et al.7 were developed in an attempt to separate MRI signal abnormalities of MS patients from incidental signal hyperintensities of the normal population. Both rely on features readily apparent on PD/T2-weighted scans. Retrospective comparison in a series of 1,500 consecutive MRI scans showed a somewhat higher specificity of the Fazekas criteria (96% versus 92%) at the cost of a lower sensitivity (81% versus 87%).15 The criteria of Barkhof et al. include findings on contrast enhanced T1-weighted MRI and are clearly of value in predicting those patients who will go on to develop clinically definite MS following an isolated first clinical symptom.22 How these criteria would perform in the distinction from other white matter diseases has not been tested.
Composite features of brain lesions characteristic for MS
Caution is advised not to use any of these criteria too rigidly. They all attempt to expand rather than to replace experienced image interpretation and must be viewed in the context of clinical and other investigative findings; e.g., on the one hand, just one single lesion of typical shape and location can serve to support the clinical suspicion of MS, whereas, on the other hand, it would be possible to have a patient with vascular lesions or even cerebral metastases fulfill all MRI criteria for MS but clearly not have the disease.
Spinal cord.
In contrast to the brain, there is no evidence for the occurrence of incidental intramedullary hyperintensities related to aging or cerebrovascular risk factors.59 Otherwise, the differential diagnosis of single or multiple spinal cord signal abnormalities has to consider similar etiologies as in the brain; i.e., vasculitis and immune-mediated vasculopathies, infectious and inflammatory diseases such as viral myelitis, neurosarcoidosis60 or ADEM, and glioma. Dural arteriovenous fistulas may also present with waxing and waning of focal intramedullary hyperintensity and can usually be detected on good quality MR images; in the case of suboptimal MRI studies or remaining clinical uncertainty they may have to be excluded by spinal angiography.
Technical considerations and imaging protocol.
The sensitivity of an MRI examination for detecting MS lesions will depend on the choice of the imaging protocol and the quality of its performance. Despite numerous comparisons of pulse sequences, protocol recommendations need to be rather general because of variations in the feasibility, quality, and utility of pulse sequences on different scanners. Overall, there is a trend toward using faster pulse sequences to shorten the examination times, but this may be at the cost of sensitivity. A detailed description and evaluation of the various pulse sequences is obtained from recent reviews.3,42,61 Development of a standardized imaging protocol including uniform slice thickness and imaging planes for patients with suspected MS should help to optimize the examination procedure at multiple sites and aid the comparison of serial examinations that may be needed in difficult diagnostic settings. Imaging at high field strengths (≥1 tesla) is preferable because high signal can be used to facilitate the detection of even small lesions. This is especially true for imaging of the spine.
Brain imaging.
Maximal slice thickness should be 5 mm with an interslice gap of ≤10%. Axial scans should be obtained perpendicular to the interhemispheric fissure and parallel to either the bicommisural line or a line connecting the lower borders of the genu and splenium of the corpus callosum. To follow these landmarks, axial scanning must be planned from both coronal (position of interhemispheric fissure) and sagittal (delineation of corpus callosum) scout views using appropriate angulations. Implementation of this procedure in clinical practice ensures comparable scanning planes and thus facilitates the interpretation of follow-up studies. However, the use of MRI in follow-up of patients to make treatment decisions cannot be recommended at this time.
T2-weighted sequences (long echo time [TE] and long repetition time [TR]) are most sensitive for the parenchymal changes of MS because of the longer T2 of lesions versus normal white matter. However, it may be difficult to separate bright lesions in a periventricular or cortico-subcortical location from the high signal intensity of CSF on purely T2-weighted scans. If the signal of CSF is darker, a much better lesion–CSF contrast is obtained. This is achieved by so-called PD-weighted images (short TE and long TR). Both PD and T2 weighting can be achieved with a conventional dual spin-echo sequence or a rapid acquisition relaxation enhanced (RARE) dual spin-echo sequence. RARE sequences have been also designated as turbo or fast spin-echo techniques.
Another approach to facilitate lesion discrimination in the proximity of CSF spaces can be taken with a T2-weighted sequence that includes suppression of signal from water, such as FLAIR. Some FLAIR sequences appear less sensitive for infratentorial lesions, which is a drawback in view of the diagnostic importance of infratentorial lesions. On the other hand, FLAIR provides an apparent better delineation of signal hyperintensities in cortico-subcortical locations.23,24 Therefore, combination of a RARE T2-weighted sequence with a FLAIR sequence is another option.
To obtain scans in a second plane takes advantage of MRI’s multiplanar imaging capability and conveys further diagnostic information. T1-weighted scans are frequently used in this context as they show the anatomy of important midline structures such as the corpus callosum, optic chiasm, pituitary gland, brainstem including the aqueduct, and the craniovertebral junction. PD/T2-weighted sagittal scans add to the detection of lesions in the corpus callosum that are rather characteristic for MS16,17 but at the cost of anatomic detail. Sagittal FLAIR has the advantage of better visualization of lesions at the inferior borders of the corpus callosum but at this time may be prone to pulsation artifacts.18,61
Contrast enhancement is a means to increase diagnostic certainty. First, it may provide additional proof for the dissemination of lesions in time; i.e., the combined presence of acute contrast-enhancing and old nonenhancing lesions.22,62 In this context, it is important to note that “incidental” or microangiopathy-related white matter hyperintensities typically do not enhance. Secondly, contrast enhancement may help to clarify atypical T2 abnormalities and to visualize structural abnormalities that are not seen or may go undetected on noncontrast scans, such as leptomeningeal/cortical disease including sarcoidosis and neoplastic infiltration; vascular malformations, particularly capillary telangiectasia; dural arteriovenous malformations or venous angiomas; and meningiomas. In addition, contrast enhancement may indicate a level of disease activity that has prognostic implications.63-65 Contrast-enhanced scans may be of less additional diagnostic value if 1) clinical uncertainty is low and 2) PD/T2 scans are characteristic.
Gadolinium chelates in a dosage of 0.1 mmol/kg body weight suffice for diagnostic MRI. A minimum time interval of 5 minutes between the injection of contrast material and the postcontrast T1-weighted series should be employed. To use this interval, a T2-weighted sequence such as in the sagittal plane can be performed during this “waiting” period. Injection via a long IV line may also help to save time and to avoid patient movement. For the sake of comparison it is advisable to obtain contrast-enhanced T1-weighted scans in the axial plane and with an identical image geometry to the PD/T2 series. Magnetization transfer (MT) weighting should not be used to increase conspicuity of contrast-enhancing lesions unless a precontrast T1-weighted scan with the same technique has been obtained beforehand; otherwise, there is a high risk of falsely labeling lesions as contrast enhancing, especially when using MT saturation pulses.66 Table 2 summarizes suggestions for a routine examination protocol of the brain.
MRI protocol suggestions for diagnostic workup of clinically suspected MS
Spinal cord imaging.
Spinal cord imaging is even more quality-dependent than that of the brain. Slice thickness should not exceed 3 mm with a maximum interslice gap of 10%. The entire spinal cord should be imaged in patients with spinal cord syndromes and especially when intending to rule out compression of the spinal cord. MS lesions can be found at all levels in the cord, but more often in the cervical region.6,29 Surface coils help to increase signal to noise ratio and phased array coils are particularly useful in providing images of the whole spinal cord without moving the patient.59
Sagittal images should be performed with a T2-weighted sequence (RARE, cardiac or peripheral gated conventional spin-echo). The sensitivity of fast FLAIR has been disappointing.67,68 Complementary T1-weighted sagittal images are recommended. Axial T2-weighted images help to define lesions suspected from sagittal scans and to outline anatomic lesion location clearly. Gadolinium-enhanced scans are less likely to show contrast material uptake in MS lesions of the spinal cord69 but may be useful in the differential diagnosis, e.g., by demonstrating leptomeningeal enhancement in sarcoidosis or extramedullary disorders, such as arteriovenous malformations or neoplasms. Addition of fat suppression techniques has no direct diagnostic impact in MS but can serve to reduce artifacts from fat with more complex imaging sequences.
Imaging the uncooperative patient.
With the introduction of very fast imaging techniques such as turbo gradient spin-echo, echoplanar imaging–FLAIR, or half-fourier acquisition single-shot turbo spin-echo–FLAIR, scanning time can be reduced to a few seconds.70 These sequences minimize motion artifacts in uncooperative patients. Although limitations in signal to noise, contrast, and spatial resolution are drawbacks of these techniques, large lesions will be seen. Differences in lesion contrast compared to conventional sequences and between scanners due to different technologic implementation must also be considered. More detailed evaluation of the advantages and disadvantages of these ultrafast methods is underway.71
Follow-up studies.
Difficulties in diagnosis will sometimes necessitate repeat MRI examinations. Wherever possible, field strength and the imaging protocol should be kept identical to the preceding study if the same region of the CNS is examined. This concerns not only the pulse sequence but also image geometry such as slice position, thickness and interslice gap, field of view, and matrix.
Suggestions for referral to MRI examination.
The clinical symptoms and signs in a given patient will guide the clinician’s decisions as to when to order an MRI and what region of the CNS to have examined (table 3).
Proposals for MRI examination regarding the clinical setting of suspected or definitive MS
Clinically isolated symptom suggestive of MS.
MRI of the brain is suggested in any patient presenting with a clinically isolated symptom possibly attributable to MS to collect supportive evidence and to rule out other structural disorders. Whereas the use of gadolinium may be superfluous in typical cases, its overall use is strongly recommended. A complementary MRI examination of the spine is not necessary in the absence of spinal cord symptoms although cord lesions have been seen even in patients with isolated optic neuritis72 or in those with normal brain imaging.6 Unlike the “incidental” occurrence of cerebral hyperintensities with aging, they are a pathologic finding at all ages,59 and thus increase the specificity of MRI especially in older patients.
MRI along the entire length of the spinal cord is suggested in patients presenting with cord symptoms. This is both to exclude compression or other treatable conditions and to search for support of MS. Whereas demonstration of the symptomatic lesion alone is not evidence for lesion dissemination in space, it may nevertheless intuitively contribute to diagnostic confidence. In this situation and in the absence of any cord lesion, imaging of the brain to detect additional lesions is worthwhile.30,48 Demonstration of more widespread affection of the CNS, i.e., supportive evidence for MS, may become even more important if the results of early treatment trials are in favor of initiating immunomodulatory treatment as soon as possible after the first clinical event. These results will also affect the clinical need for application of contrast material in patients with isolated symptoms. Number and extent of cerebral lesions have been repeatedly shown to parallel the risk of conversion to clinically definite MS in patients with clinically isolated symptoms whether they occur in the brain, spinal cord, or optic nerves.38-41 Presence of a contrast-enhancing lesion adds further predictive power22 and helps to satisfy the MS criterion of lesion dissemination in time.
Clinically definite MS.
Brain MRI is suggested at least once in every patient with MS. A scan will help to avoid admittedly rare but possible and potentially treatable misdiagnosis. In addition, considering the costs of modern MS therapies, it is also socioeconomically justified to avoid treatment of non-MS patients by ensuring maximal diagnostic certainty. If and how extent or pattern of lesions could influence treatment decisions or serve to extract prognostic information is a matter of debate.3,42 Complementary MRI of the spine may be considered for patients with equivocal brain findings and if spinal cord symptomatology is predominant, such as is often the case in primary progressive MS.
MRI follow-up examinations during the course of MS will be needed rarely but can be important if diagnostic issues arise. Again, they may be used to clarify equivocal findings both in the brain and spine. Spinal MRI is also recommended in patients with clinically definite MS who develop first or progressive spinal cord symptoms possibly attributable to a different etiology.
Proposals for diagnostic interpretation.
MRI of the CNS is a very sensitive instrument for depicting MS-related lesions. However, because of the variety of other etiologies of MRI signal changes, the mere presence of lesions cannot suffice this purpose. Limitations of previously suggested criteria for the interpretation of MRI have been discussed above and elsewhere.42,61 To circumvent these problems without abstaining from a more MS-directed image interpretation, we suggest indicating classes of evidence for MS from MRI of the brain, spine, or both.
Class A: Supportive findings.
This class comprises MRI lesions typical for MS based on their location, shape, size, and contrast enhancement including previously suggested sets of criteria (see table 1).7,22,58 The respective criteria that have served to label an MRI examination as consistent with Class A findings should always be indicated.
Class B: Equivocal findings.
This class comprises MRI changes that cannot be clearly attributed to any one CNS disorder.
Class C: Normal findings.
This class comprises scans without any structural abnormality including the absence of focal and diffuse signal changes.
Class D: Clinically significant “non-MS” findings. This class comprises MRI abnormalities typical for another CNS disorder that can also explain the patient’s symptoms, e.g. infarct, tumor, etc.
These classes can be used for relating MRI abnormalities of the brain or the spine to a referral diagnosis of suspected or definite MS with following diagnostic implications:
-
Class A is in support of MS (in the setting of clinical suspicion).
-
Class B and C neither refute nor support a diagnosis of MS. A normal MRI of the brain, however, is clearly uncommon for MS.6
-
Class D rules against a diagnosis of MS.
This categorization does not obviate the need for relating image interpretation to the clinical situation. A review of the MRI by the neurologist is always recommended for this purpose. Patients also tend to appreciate and understand their situation better if they have been shown the films. Judging the probability of an MRI class in a given situation and hence the plausibility of certain findings is impossible without knowledge of duration, stage, and course of the disease. As an example, normal findings will be expected more often in a patient with a first clinical symptom suggestive of MS than in a patient with an established course of relapsing-remitting disease of several years’ duration. Categorization of findings especially between Classes A and B will also tend to vary somewhat with patient characteristics such as age. In addition, equivocal findings of the brain and spine can supplement each other to become supportive.
By intention, proposed categories provide rather loose rules on how to handle MRI findings. This is in order not to endanger the needed interaction between clinician and interpreter by first steps to formally integrate MRI into the entire process of MS diagnosis. For research purposes, more strictly defined and detailed MRI criteria can be formulated, which will be the subject of a future review.
Footnotes
-
Based on a meeting of the North Atlantic Collaboration on Multiple Sclerosis (NATOMS); Cambridge, UK; November 21–23, 1997. Coordinators were D.H.M. and H.F.M. Participants were supported by the United States and Canadian MS Societies and the European Community (ERBCHRXCT 940684—European Magnetic Resonance Network in Multiple Sclerosis). The authors constitute the NATOMS Task Force on the Diagnostic Use of MRI in MS.
- Received November 18, 1998.
- Accepted April 29, 1999.
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Dr. Babak Hooshmand and Dr. David Smith
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