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Published online before print February 21, 2002, 10.1148/radiol.2231010707
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(Radiology 2002;223:46-56.)
© RSNA, 2002

Neuroradiology

Differentiation of Multiple Sclerosis from Other Inflammatory Disorders and Cerebrovascular Disease: Value of Spinal MR Imaging1

Joost C. J. Bot, MD, Frederik Barkhof, MD, PhD, Geert Lycklama à Nijeholt, MD, PhD, Dirkjan van Schaardenburg, MD, PhD, Alexandre E. Voskuyl, MD, PhD, Herman J. Ader, PhD, Jolanda A. L. Pijnenburg, MD, Chris H. Polman, MD, PhD, Bernard M. J. Uitdehaag, MD, PhD, Erik G. J. Vermeulen, MD and Jonas A. Castelijns, MD, PhD

1 From the Department of Radiology, MR Center for MS Research (J.C.J.B., F.B., G.L.N., J.A.C.), Rheumatology (D.v.S., A.E.V.), Biostatistics and Epidemiology (H.J.A.), Neurology (J.A.L.P., C.H.P., B.M.J.U.), and Vascular Surgery (E.G.J.V.), Vrije Universiteit (VU) Medical Centre, PO Box 7057, 1007 MB Amsterdam, the Netherlands. Received April 2, 2001; revision requested May 7; final revision received September 26; accepted October 9. Supported by Dutch MS society grant 97-307 from Sichting Vrienden MS Research. Address correspondence to J.C.J.B. (e-mail: J.Bot@VUMC.nl).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
PURPOSE: To determine the value of magnetic resonance (MR) imaging in the spinal cord to differentiate multiple sclerosis (MS) from other inflammatory disorders and cerebrovascular diseases (together, other neurologic disease [OND]).

MATERIALS AND METHODS: The study population included 66 patients with OND and 25 patients with MS, who were matched for age, sex, and symptom duration or severity. Brain MR imaging included gadolinium–enhanced T1-weighted and dual-echo T2-weighted spin-echo sequences to assess the number, size, and appearance of lesions, contrast enhancement, and compatibility with diagnostic criteria for MS. Spinal cord MR imaging included cardiac-triggered gadolinium-enhanced sagittal T1-weighted spin-echo and dual-echo T2-weighted sequences to assess the general appearance (normal, focal lesion, diffuse abnormality) and number or size of focal lesions. Images obtained in MS and OND patients were compared. Specificity, sensitivity, accuracy, and positive and negative predictive values with MR images were calculated.

RESULTS: Brain images were abnormal in all MS patients and in 65% of OND patients. Abnormal cord images were found in 92% of MS and 6% of OND patients. The combination of brain and spinal cord images increased accuracy of diagnosis compared with use of brain images alone.

CONCLUSION: In contrast to MS, cord lesions are very uncommon in OND. This finding can help differentiate these disorders.

© RSNA, 2002

Index terms: Brain, MR, 10.1214 • Connective tissue, diseases, 10.61, 30.61 • Lupus erythematosus, 10.612, 30.612 • Nervous system, diseases, 10.871 • Sarcoidosis, 10.22, 30.22 • Sclerosis, multiple, 10.871, 30.871 • Sjögren syndrome, 10.695, 30.695 • Spinal cord, MR, 31.1214, 32.1214


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Magnetic resonance (MR) images obtained in patients with multiple sclerosis (MS) depict the frequency, shape, and location of MS abnormalities in the brain (1). In as many as 98% of patients with clinically definite MS, brain MR images showed characteristic lesions. However, many other autoimmune-mediated inflammatory disorders (hereafter, inflammatory disorders) (ie, systemic lupus erythematosus, Sjögren disease, sarcoidosis, and intermediate uveitis) and cerebrovascular disease are known to produce brain lesions that mimic MS on T2-weighted MR images, which indicates that the sensitivity for brain involvement in MS is higher than the specificity (2). Therefore, the differential diagnosis between MS and inflammatory disorders or cerebrovascular disease can be difficult on T2-weighted brain MR images, especially when the patients also show clinical signs of central nervous system involvement (3).

Diagnostic criteria were developed to increase the specificity of cerebral MR imaging for MS. These criteria are based on size, number, contrast enhancement, and location of focal abnormalities (4–6). Nevertheless, the accuracy of such criteria is far from optimal, which results in a substantial number of misclassifications at diagnosis (6,7).

Technical advances enable high-quality sagittal imaging of the entire spinal cord within a reasonable acquisition time. Although fast sequences, such as fast spin-echo or fast short inversion time inversion recovery (or STIR), are available, the sensitivity of MR imaging for MS abnormalities is still highest with conventional spin-echo sequences incombination with cardiac triggering to reduce artifacts (8–13). The spinal cord is frequently involved in MS. In as many as 90% of MS patients, cord abnormalities are depicted on T2-weighted MR images (8,14–18). Spinal cord involvement in combination with no or few brain lesions is reported in as many as 10% of patients with clinically definite MS (19,20).

MS spinal cord abnormalities comprise two types. The first type, focal lesions, which consist of well-demarcated areas of high signal intensity (17), are seen equally well on intermediate- and T2-weighted MR images. The second, so-called diffuse abnormalities, comprise poorly demarcated areas of subtly increased signal intensity compared with cerebrospinal fluid on intermediate-weighted images; such diffuse abnormalities are difficult to recognize on T2-weighted images, since the signal intensity of the spinal cord is still lower than that of the surrounding cerebrospinal fluid (21,22). When focal and diffuse abnormalities are combined, as many as 97% of MS patients have abnormal spinal cord images (21).

In contrast to findings in the brain, MS-like abnormalities are seldom found in the spinal cord of healthy volunteers, even those older than 50 years (16,21). Spinal cord abnormalities have been reported in inflammatory disorders and cerebrovascular disease, though the appearance of such abnormalities may differ from those seen in MS (23–33). Little is known about the frequency of spinal cord abnormalities in inflammatory disorders and cerebrovascular disease. In one recent study (34), no focal cervical cord lesions were reported on MR images obtained in 44 patients with inflammatory disorders, even though 30% of the images showed brain abnormalities that mimicked MS (35). No comparison was made with patients with cerebrovascular disease, however, and the occurrence of diffuse spinal cord abnormalities was not analyzed. Moreover, these authors studied only the cervical cord. In other studies (23,24,36), spinal cord abnormalities in inflammatory disorders were often located in the thoracic region of the cord.

The purpose of this study was to determine the value of MR imaging in the spinal cord in the differentiation of MS from other neurologic disease (OND).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Study Groups
The brain and spinal cord in 25 patients with MS and 66 patients with inflammatory disorders or cerebrovascular disease (together, OND) were examined. The study population was selected from patients registered with the departments of neurology, rheumatology, and vascular surgery. Patients were excluded who had a familial history of more than one definite diagnosis and in whom neurologic involvement was not suspected. Those with inflammatory disorders represented all patients who met selection criteria, which included a definite diagnosis according to international criteria on the basis of clinical data and laboratory results (37–42). Seventy-five percent of the patients had experienced at least one episode of neurologic signs and symptoms that reflected central nervous system involvement.

Patients with cerebrovascular disease were randomly selected on the basis of the presence of cerebrovascular disease (minor stroke or transient ischemic attack) associated with at least two well-known vascular risk factors. The OND group comprised patients with systemic lupus erythematosus (n = 13); Sjögren disease (n = 7); sarcoidosis (n = 5); intermediate uveitis (n = 6); unspecified connective tissue diseases (n = 18); and cerebrovascular disease (n = 17), including seven patients with symptomatic familial hyperhomocystinemia.

Patients with clinically definite MS according to the criteria of Poser et al (43), who were matched for age, sex, symptom duration and severity, were selected from our center without prior knowledge of MR findings. For each patient, age, sex, disease symptoms, duration of symptoms, and clinical evidence for involvement of the spinal cord were recorded. All patients were scored for disability according to the Expanded Disability Status Scale of Kurtzke (44). The study was approved by the institutional ethics committee, and all patients gave informed consent.

MR Imaging Protocol
MR imaging was performed at 1.0 T (Magnetom Impact; Siemens Medical Systems, Erlangen, Germany) with a circularly polarized head coil and spinal phased-array coil. Brain MR imaging was performed with a gadolinium-enhanced (Magnevist; Schering, Erlangen, Germany) transverse T1-weighted spin-echo sequence (repetition time msec/echo time msec of 700/15, with two signals acquired) and a transverse dual-echo long repetition time spin-echo sequence (2,700/45, 90; with two signals acquired) with 25 sections, 5-mm section thickness, 0.5-mm intersection gap, 163 x 260-mm field of view, and 160 x 256 matrix. Spinal cord imaging was performed with a cardiac-triggered gadolinium-enhanced sagittal T1-weighted sequence (500/15, with two signals acquired) and a long repetition time dual-echo conventional spin-echo sequence (2,400–2,900/20, 80; with one signal acquired) with 13 sections, 3-mm section thickness, 0.3-mm intersection gap, 240 x 480-mm field of view, and 256 x 512 matrix.

Image Analysis
Images were printed as hard copies and evaluated in random order by two readers (F.B., J.A.C.), in consensus without knowledge of clinical findings or underlying disease, to determine the number and appearance of abnormalities and the presence and location of contrast enhancement. Brain lesions were defined as sharply demarcated areas of high signal intensity on both intermediate- and T2-weighted images.

Focal lesions were divided into four types on the basis of location: (a) juxtacortical, lesion touches or extends into the gray matter of the cortex; (b) periventricular, lesion is adjacent to ventricles or is less than 1 cm from them as measured from the center of the lesion; or (c) infratentorial. (d) Lesions that did not fulfill one of the previous criteria were classified as deep white matter lesions. Brain images were considered abnormal when they showed any of the previously mentioned abnormalities or enhancement.

Images were also scored according to the following diagnostic criteria for MS: Paty et al (5), presence of four focal brain lesions or presence of three focal brain lesions, one of which is periventricularly situated; Fazekas et al (4), presence of three or more brain lesions with two of the characteristics of periventricular location, infratentorial location, or size larger than 6 mm; and Barkhof et al (6), presence of three periventricular lesions, one of which is juxtacortical; one, infratentorial; and one, enhancing. For the latter criteria, a cut-off of at least three positive findings was used (45).

Spinal cord images were scored on the basis of MR appearance (normal, focal lesion, or diffuse abnormality), number of focal lesions, and presence and location of contrast enhancement. Focal lesions (ie, sharply delineated areas of increased signal intensity) were considered to be present when they were seen on both intermediate- and T2-weighted MR images. Focal lesion size was scored according to the number of vertebral segments involved. Diffuse abnormalities were defined as areas of subtle, poorly delineated increased signal intensity compared with cerebrospinal fluid on intermediate-weighted MR images (21). Spinal cord images were considered abnormal when they showed any of the previously mentioned abnormalities or enhancement.

Statistical Analysis
MS patients were compared with OND patients. Differences on the basis of matching criteria were assessed with the Student t test for normally distributed data and with the Mann-Whitney U test for nonnormal data. Frequencies of abnormal brain and spinal cord images were compared with the Pearson {chi}2 test. Differences on the basis of concordance of brain and spinal cord abnormalities were assessed with the Fisher exact test. Differences with P < .05 were considered significant.

Where TN is true-negative, TP is true- positive, FN is false-negative, and FP is false-positive, specificity was defined as TN/(TN + FP), sensitivity as TP/(TP + FN), accuracy as (TP + TN)/(TP + FN + TN + FP), positive predictive value as TP/(TP + FP), and negative predictive value as TN/(TN + FN).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Study Groups
All information concerning age, sex, and clinical findings for the MS and OND patients are listed in Table 1. The groups did not differ significantly for any of the matching parameters. Patients with MS and inflammatory disorders were mostly women (76% and 80%, respectively), whereas those with cerebrovascular disease were mostly men (53%).


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  		TABLE 1. Demographic and Clinical Data

 
Disease in the 66 OND patients was diagnosed as unspecified connective tissue disease (27%), cerebrovascular disease (26%), and systemic lupus erythematosus (20%). In total, 80% of OND patients had symptoms or signs that indicated cerebral involvement, and two (3%) patients with systemic lupus erythematosus had recent symptoms at the time of MR examination. In 6% of OND patients, evidence was found of clinical spinal cord involvement, which was not recent, at the time of MR examination.

All 25 MS patients had central nervous system involvement, and 60% had clinical suspicion of cord involvement. None of the MS patients were examined during a relapse.

Brain MR Findings
All 25 (100%) MS patients had abnormal brain MR images, and 26 of 49 (53%) patients with inflammatory disorders and 16 of 17 (94%) patients with cerebrovascular disease had focal abnormalities (Table 2). Among patients with abnormal brain MR images, all but six with inflammatory disorders (one with intermediate uveitis, three with unspecified connective tissue disease, and two with Sjögren disease) had neurologic signs and symptoms that reflect central nervous system involvement. The locations of focal lesions in the brain were as follows: Periventricular lesions were present in all 25 MS patients (Fig 1), 31% of patients with inflammatory disorders, and 71% of patients with cerebrovascular disease (Fig 2). Juxtacortical lesions were present in 80% of MS patients, 18% of patients with inflammatory disorders, and 41% of patients with cerebrovascular disease. Infratentorial lesions were present in 84% of MS patients, 12% of patients with inflammatory disorders, and 35% of patients with cerebrovascular disease. Deep white matter lesions were present in 96% of MS patients, 49% of patients with inflammatory disorders, and 82% of patients with cerebrovascular disease. Enhancing focal lesions were observed 32% of MS patients, 6% of patients with inflammatory disorders, and 6% of patients with cerebrovascular disease (Table 2). Leptomeningeal and basal ganglia enhancement, which were not observed in patients with MS or cerebrovascular disease, were each found in 4% of patients with inflammatory disorders.


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  		TABLE 2. Imaging Findings

 


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  		Figure 1. MR images in a 29-year-old female MS patient with neurologic symptoms and clinical evidence for involvement of the spinal cord for 2 years and an Expanded Disability Status Scale (44) score of 2. Left: Transverse intermediate-weighted (top) and T2-weighted (bottom) brain images (spin-echo; 2,700/45, 90; with two signals acquired) show multiple white matter lesions, two (solid arrows) of which are located periventricularly and one (open arrow), juxtacortically. Brain images met all MS brain criteria. Right: On sagittal intermediate-weighted (left) and T2-weighted (right) cord images (cardiac-triggered spin-echo; 2,400-2,900/20, 80; with one signal acquired), multiple focal lesions (arrows) are visible. Owing to slight scoliosis during positioning, the full length of the spinal cord could not be shown. Adjacent cord images (not shown) depicted no abnormalities.

 


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  		Figure 2. MR images in a 73-year-old female patient with cerebrovascular disease with neurologic symptoms for 2 years and an Expanded Disability Status Scale score of 1. Left: Transverse intermediate-weighted (top) and T2-weighted (bottom) brain images (spin-echo; 2,700/45, 90; with two signals acquired) show three focal lesions (arrows) around the ventricles. The brain images met the MS criteria of both Paty et al (5) and Fazekas et al (4) but not the criteria of Barkhof et al (6). Right: Sagittal intermediate-weighted (left) and T2-weighted (right) cord images (cardiac-triggered spin-echo; 2,400-2,900/20, 80; with one signal acquired) show no abnormalities. Adjacent cord images (not shown) also showed no abnormalities.

 
Classification of brain MR findings according to the MS criteria of Paty et al (5), Fazekas et al (4), and Barkhof et al (6) is listed in Table 3. Thirty-three OND patients (false-positive findings) and all MS patients (true-positive findings) met criteria of Paty et al, which resulted in an accuracy of 64% (positive predictive value, 43%; negative predictive value, 100%) (Fig 3). Criteria of Fazekas et al were fulfilled in 14 OND patients (Fig 4) and 23 MS patients (two false-negative findings), with an accuracy of 82% (positive predictive value, 62%; negative predictive value, 96%). Criteria of Barkhof et al were fulfilled in five OND patients (Fig 5) and 19 MS patients (six false-negative findings) with accuracy of 88% (positive predictive value, 79%; negative predictive value, 91%) (Table 4).


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  		TABLE 3. Number of Patients with Diagnostic Brain MR Criteria for MS

 


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  		Figure 3. MR images in a 43-year-old female patient with unspecified connective tissue disease with neurologic symptoms for 11/2 years and an Expanded Disability Status Scale score of 2. Left: Transverse intermediate-weighted (top) and T2-weighted (bottom) brain images (spin-echo; 2,700/45, 90; with two signals acquired) show multiple small white matter lesions, four (arrows) of which are located periventricularly. Brain images met the MS criteria of only Paty et al (5); they depicted 47 lesions. Since the lesions were very small and most were located in deep white matter, the criteria of Fazekas et al (4) and Barkhof et al (6) were not met. Right: Sagittal intermediate-weighted (left) and T2-weighted (right) cord images (cardiac-triggered spin-echo; 2,400-2,900/20, 80; with one signal acquired) show no abnormalities. Adjacent cord images (not shown) also did not depict any abnormalities.

 


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  		Figure 4. MR images in a 74-year-old female patient with Sjögren disease with neurologic symptoms for 6 years and an Expanded Disability Status Scale score of 1. Left: Transverse intermediate-weighted (top) and T2-weighted (bottom) brain images (spin-echo; 2,700/45, 90; with two signals acquired) show multiple ovoid white matter lesions (arrows) located in the corpus callosum. Brain images met the MS criteria of both Paty et al (5) and Fazekas et al (4) but not the criteria of Barkhof et al (6). Right: Sagittal intermediate-weighted (top) and T2-weighted (bottom) cord images (cardiac-triggered spin-echo; 2,400-2,900/20, 80; with one signal acquired) show no abnormalities. Owing to severe scoliosis during positioning, the spinal cord could not be shown in full length. Adjacent cord images (not shown) depicted no abnormalities.

 


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  		Figure 5. MR images in a 53-year-old female patient with hyperhomocysteine with neurologic symptoms for 7 years and an Expanded Disability Status Scale score of 1. Left: Transverse intermediate-weighted (top) and T2-weighted (bottom) brain images (spin-echo; 2,700/45, 90; with two signals acquired) show two white matter lesions, one (arrow) of which is situated juxtacortically. Brain images met all MS brain criteria. Right: Sagittal intermediate-weighted (left) and T2-weighted (right) cord images (cardiac-triggered spin-echo; 2,400-2,900/20, 80; with one signal acquired) show no abnormalities. Adjacent cord images (not shown) also showed no abnormalities.

 

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  		TABLE 4. Diagnostic Value of MS Brain Criteria for MS without and with Abnormal Spinal MR Image

 
MR Imaging Spinal Cord Abnormalities in MS Compared with Those in Inflammatory Disorders and Cerebrovascular Disease
In 23 (92%) of 25 MS patients, spinal cord images were abnormal, with only focal lesions in 14 cases (median, 2.5 lesions; range, 1–16 lesions) (Fig 1). In nine (36%) images, both focal lesions and diffuse abnormalities were present (Fig 6); diffuse abnormalities only were not seen in any MS patient (Table 2). In the inflammatory disorders group, three (6%) of 49 spinal cord images showed diffuse cord abnormalities (Fig 7), and none showed focal spinal cord lesions (Table 2). In the cerebrovascular disease group, only one of 17 spinal cord images was abnormal, showing a single focal lesion in the spinal cord, and none showed diffuse abnormalities (Table 2). Spinal cord MR images showed enhancing focal lesions in only one MS patient. No gadolinium enhancement (either focal or leptomeningeal) was observed on spinal cord images in patients with inflammatory disorders or cerebrovascular disease.



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  		Figure 6. MR images in a 46-year-old female MS patient with neurologic symptoms for 26 years and an Expanded Disability Status Scale score of 7.5. Left: Transverse intermediate-weighted (top) and T2-weighted (bottom) brain images (spin-echo; 2,700/45, 90; with two signals acquired) show multiple white matter lesions, most of which are located periventricularly (solid arrows) and in the corpus callosum (open arrow). Brain images met the MS criteria of both Paty et al (5) and Fazekas et al (4) but not the criteria of Barkhof et al (6), because no juxtacortical or enhancing lesions were found. Right: On sagittal intermediate-weighted (left) and T2-weighted (right) cord images (cardiac-triggered spin-echo; 2,400-2,900/20, 80; with one signal acquired), diffuse abnormalities can be seen in the cervical part of the cord (open arrows). Furthermore, one focal lesion (solid arrows) is present at T9.

 


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  		Figure 7. MR images in a 25-year-old female patient with systemic lupus erythematosus with neurologic symptoms for 21/2 years and an Expanded Disability Status Scale score of 2. Left: Transverse intermediate-weighted (top) and T2-weighted (bottom) brain images (spin-echo; 2,700/45, 90; with two signals acquired) show periventricularly located lesions (arrows). Brain images showed seven focal lesions and met MS criteria of only Paty et al (5). Right: Sagittal intermediate-weighted (left) cord image (cardiac-triggered spin-echo; 2,400-2,900/20, 80; with one signal acquired) shows a diffusely increased signal intensity throughout the cord (arrows), but the patient did not have clinical evidence for involvement of the spinal cord. Note that diffuse abnormalities are difficult to appreciate on the T2-weighted image (right). No focal cord lesions are present.

 
With use of only spinal cord images for differentiating MS from OND, accuracy was 93% on the basis of the presence of any abnormality (positive predictive value, 85%; negative predictive value, 97%).

With the combination of brain and spinal cord MR images, accuracy of differentiating MS from OND was 95% (positive predictive value, 89%; negative predictive value, 97%) with positive criteria of Paty et al (4) and any spinal cord abnormality (three false-positive findings in OND patients and two false-negative findings in MS patients). When an abnormal cord was combined with the criteria of Fazekas et al (4), accuracy was 93% (positive predictive value, 91%; negative predictive value, 94%). For an abnormal cord with the criteria of Barkhof et al (g), accuracy was 93% (positive predictive value, 100%; negative predictive value, 92%) (Table 4, Fig 8).



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  		Figure 8. MR images in a 51-year-old female patient with unspecified connective tissue disease with neurologic symptoms for 2 years and an Expanded Disability Status Scale score of 1.5. Left: Transverse intermediate-weighted (top) and T2-weighted (middle) brain images (spin-echo; 2,700/45, 90; with two signals acquired) show multiple focal lesions around the occipital horns of the ventricles (solid arrows) and juxtacortical lesions (open arrows) in the right temporal lobe on the detailed images (bottom). Brain images met all MS brain criteria. Right: Sagittal intermediate-weighted (top) and T2-weighted (bottom) cord images (cardiac-triggered spin-echo; 2,400-2,900/20, 80; with one signal acquired) show no abnormalities. Owing to motion artifacts and partial volume averaging, T2-weighted images are slightly degraded. Since intermediate-weighted images do not depict sharp contrast between cerebrospinal fluid and normal cord, artifacts have less effect on image quality. On intermediate-weighted images, no increase in signal intensity is depicted at the location of the cord; thus, no diffuse abnormalities or focal lesions are present. Owing to severe scoliosis during positioning, the spinal cord could not be shown in full length. Adjacent cord images (not shown) depicted no abnormalities.

 
Spinal cord imaging versus clinical signs of spinal cord involvement.—Fifteen (60%) of 25 MS patients had clinical signs that reflected possible spinal cord involvement, even though 23 (92%) spinal cords were abnormal at MR examination (Fig 9). One of 15 MS patients with clinical signs that reflected spinal cord involvement had a normal spinal cord on MR images. Four (6%) OND patients had clinical signs that reflected possible spinal cord involvement, although none had abnormalities on their MR images. Four OND patients had abnormalities on spinal cord images, although they did not have clinical signs that indicated spinal cord involvement (Tables 1, 2).



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  		Figure 9. MR images in a 24-year-old female MS patient with neurologic symptoms for 21/2 years and an Expanded Disability Status Scale score of 1. Left: Transverse intermediate-weighted (top) and T2-weighted (bottom) brain images (spin-echo; 2,700/45, 90; with two signals acquired) show multiple white matter lesions, most of which are located periventricularly (solid arrows) and one located juxtacortically (open arrow). Brain image met all MS brain criteria. Right: Sagittal intermediate-weighted (left) and T2-weighted (right) cord images (cardiac-triggered spin-echo; 2,400-2,900/20, 80; with one signal acquired) depict a focal lesion at C3 (arrows); however, no clinical evidence for involvement of the spinal cord was found.

 
Discordant or concordant brain and spinal cord MR examinations in relation to criteria for MS.—In 41% of patients with inflammatory disorders, 6% of patients with cerebrovascular disease, and no MS patients, both brain and spinal cord MR images were normal. MR images that were abnormal for both brain and spinal cord were obtained in 92% of MS patients (Fig 6) and 6% of OND patients, in whom positive findings on brain images were combined with a normal spinal cord in 59% (Fisher exact test, P < .001) (Table 5). All patients with abnormal spinal cord images also had abnormal brain images, irrespective of the patient group. With regard to the 27 examinations in which both the brain and spinal cord images were abnormal—which were obtained in 23 patients with MS, three patients with inflammatory disorders, and one patient with cerebrovascular disease—all 23 MS brain examinations met the criteria of Paty et al (5), 21 (91%) met the criteria of Fazekas et al (4), and 19 (83%) met criteria of Barkhof et al (6). Among the three patients with inflammatory disorders, one did not meet any criteria, two met the criteria of Paty et al, one met the criteria of Fazekas et al, and none met the criteria of Barkhof et al. In the patient with cerebrovascular disease in whom both brain and spinal cord MR images were abnormal, brain abnormalities met the criteria of both Paty et al and Fazekas et al but not those of Barkhof et al.


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  		TABLE 5. Value of Spinal Cord MR Imaging in Patients with Abnormal Findings in Brain MR Examinations (n = 68)

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
In this study, MR images in all MS patients showed focal brain abnormalities (2,5). MR images in 64% of patients with OND (especially those with inflammatory disorders) showed significantly fewer brain abnormalities than did those in MS patients (P = .001, Pearson {chi}2 test). As reported in the literature (35,46–51), the frequency of central nervous system involvement in OND patients varies between diseases and ranges from 5% to 92% depending on the disease, patient selection criteria, and study design. The relatively high frequency of brain abnormalities in the OND patients reflects the design of our study, in which we mainly selected patients with symptoms indicative of central nervous system involvement.

The frequency of spinal cord abnormalities in MS patients found in this study (92%) is comparable with values as high as 90% reported in the literature (8,15–18). In contrast, MR images in only four (6%) of 66 OND patients in our study showed spinal cord abnormalities (P < .001, Fisher exact test). In a recent MR study of the cervical spine by Rovaris et al (34), no abnormalities were described. However, Rovaris et al acquired only T2-weighted MR images of the cervical spine to detect focal spinal cord lesions in patients with inflammatory diseases. In our study, diffuse abnormalities were found in three patients with inflammatory disorders. These abnormalities are best seen on intermediate-weighted MR images and may be difficult to appreciate on T2-weighted MR images (21). Moreover, Rovaris et al studied only the cervical cord, whereas it has been reported that spinal cord abnormalities in inflammatory disorders are often located in the thoracic region of the cord (23,24,36), and they included a patient population in which 50% of patients had central nervous system involvement. To our knowledge, the frequency of spinal cord lesions has not been studied systematically in patients with cerebrovascular disease.

When MS and OND patients are compared, adequate matching of both study populations is important, because severe neurologic involvement is more frequent in MS compared with OND patients, especially those with inflammatory disorders. In our study, we successfully matched MS patients with OND patients, with no significant difference regarding disability and clinical status. On average, as a result of the matching procedure, the MS group comprised patients with mild disability for MS patients and the OND group comprised patients with a high frequency of disability for OND patients.

Application of the criteria of Paty et al (5) to our study population yielded a sensitivity of 100% and a specificity of 50% for MS. With the criteria of Fazekas et al (4), sensitivity decreased to 92%, and specificity increased to 79%. With the criteria of Barkhof et al (6), sensitivity decreased to 76%, but specificity increased to 92%. The criteria of Paty et al, which are known to be very sensitive for MS, seem to be well suited to exclude MS (negative predictive value, 100%). With use of the findings at only brain MR imaging, the criteria of Barkhof et al were most predictive for MS (positive predictive value, 79%). On the basis of the criteria of Paty et al, brain MR images in 50% of OND patients showed abnormalities compatible with MS; Fazekas et al, 21%; and Barkhof et al, 8%. Rovaris et al (35) found a pattern that resembled MS in 30% of non-MS patients on brain MR images, although no criteria were mentioned.

Whatever criteria were applied, disease in a significant number of patients was misclassified on the basis of brain MR findings alone. Owing to significant difference in frequency of spinal cord abnormalities between MS and OND patients (P < .001, Pearson {chi}2 test), spinal cord MR images may help differentiate MS from OND. MS can be confirmed with high certainty when the spinal cord is abnormal on MR images. With a sensitivity for MS (92%) comparable to that with the criteria of Fazekas et al (4) and a specificity for MS (94%) higher than that with the criteria of Barkhof et al (6), accuracy for differentiating MS from OND (93%) was higher on the basis of an abnormal spinal MR image than on the basis of any brain criteria. When a spinal cord image was normal, MS was almost always absent (negative predictive value for MS, 97%); when a spinal cord image was positive, MS was frequently present (positive predictive value for MS, 85%).

Diagnostic certainty can be further increased when results of brain and spinal cord MR are combined to help differentiate between MS and OND. With use of both brain and spinal cord images, accuracy to diagnose MS increased to 95% and positive predictive value for MS increased to 89% when criteria of Paty et al (5) were positive and the spinal cord MR image was abnormal; this combination also yielded a very high (97%) negative predictive value for MS. For criteria of Fazekas et al (4) and the presence of any spinal cord abnormality, accuracy was 93%. For criteria of Barkhof et al (6) and any cord abnormality, accuracy was 93%; this combination yielded the highest positive predictive value for MS, 100%.

Almost all spinal cord MR images in MS patients were abnormal, regardless of the presence of spinal symptoms; this finding confirms that clinically silent spinal cord lesions are common in MS (52,53). Until now, little has been known about the frequency of spinal cord abnormalities in OND patients. Authors of several small studies, mostly with patients with one disease, report the presence of cord lesions in patients with typical cord syndromes, such as transverse myelitis (24,26,28,31,54–56). Findings in our study show that the frequency of cord abnormalities is extremely low in the absence of such typical cord syndromes, which indicates infrequent subclinical lesions. The very high diagnostic yield found in this study, however, applies to only patients without a clear-cut cord syndrome. Another caveat is that we selected patients with a certain disease duration, although, at first presentation, the diagnostic yield may be lower. Finally, we can not rule out the presence of cord abnormalities during the first clinical presentation, since all patients had established (and stable) disease at the time of imaging.

Contrary to findings on brain MR images, the frequency of spinal cord abnormalities seen on spinal MR images in OND patients is very low compared with that in MS patients. Therefore, spinal cord MR imaging is a powerful tool to help differentiate between MS and OND, even in the presence of an abnormal brain MR examination.


   FOOTNOTES
 
Abbreviations: MS = multiple sclerosis, OND = other neurologic disease

Author contributions: Guarantors of integrity of entire study, F.B., C.H.P., J.A.C.; study concepts, F.B., G.L.N., C.H.P., J.A.C.; study design, J.C.J.B., F.B., C.H.P., J.A.C.; literature research, J.C.J.B., F.B., C.H.P., J.A.C.; clinical studies, D.v.S., A.E.V., J.A.L.P., C.H.P., B.M.J.U., E.G.J.V.; data acquisition, J.C.J.B., F.B., D.v.S., A.E.V., J.A.L.P., C.H.P., B.M.J.U., J.A.C.; data analysis/interpretation, J.C.J.B., H.J.A., F.B., J.A.C.; statistical analysis, J.C.J.B., H.J.A.; manuscript preparation, J.C.J.B.; manuscript definition of intellectual content and editing, J.C.J.B., F.B., C.H.P., J.A.C.; manuscript revision/review, J.C.J.B., F.B., G.L.N., C.H.P., J.A.C.; manuscript final version approval, all authors.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
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