Magnetic Resonance Imaging 18 (2000) 1183–1186
Technical note
Serial gadolinium-DTPA of spinal cord MRI in multiple sclerosis: triple vs. single dose Indra Yousryb, Massimo Filippia, Ernst Waltherb, Claudio Gasperinic, Ruggero Caprad, Tarek A. Yousryb,* a
Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute Ospedale San Raffaele, University of Milan, Milan, Italy b Departments of Neuroradiology and Neurology Klinikum Grosshadern, Ludwig-Maximilians Universita¨t, Munich, Germany c Department of Neurology, Ospedale San Camillo, Rome, Italy d Department of Neurology, Spedali Civili, University of Brescia, Brescia, Italy Received 12 February 2000; accepted 27 August 2000
Abstract We compared the sensitivity of single and triple dose Gd-DTPA magnetic resonance imaging (MRI) in detecting enhancing lesions in the spinal cord (SC) from 15 patients with multiple sclerosis (MS). The patients were examined monthly on four occasions. We detected two enhancing lesions in two of 15 (13%) patients when a single dose of Gd-DTPA was used. No additional lesions were detected when a triple dose of Gd-DTPA was used. These results 1) confirm that enhanced spinal cord imaging does not significantly increase the detection of active lesions in MS, 2) they do not support the general application of triple dose Gd-DTPA when examining the SC but 3) suggest that further studies taking into account SC symptoms are necessary. © 2000 Elsevier Science Inc. All rights reserved. Keywords: Comparative studies; Multiple sclerosis; Spinal cord; Contrast enhancement; Gadolinium-DTPA; Triple dose
1. Introduction
2. Patients and methods
In multiple sclerosis (MS), lesions of the spinal cord (SC) are frequent and are likely to contribute to the disabling features of the disease. Therefore, considerable efforts have been undertaken for improving the detection of these lesions by magnetic resonance imaging (MRI). However, the results of previous studies that evaluated the role of enhanced MRI for detecting SC lesions are not definitive. Several longitudinal studies revealed that with the use of Gd-DTPA only a modest number of lesions can be seen [1–3]. On the other hand, a cross sectional study showed that the use of triple dose of Gd-DTPA increases the sensitivity of SC enhanced MRI significantly [4]. To evaluate the possible value of enhanced MRI after the injection of triple dose Gd-DTPA, we performed this longitudinal study, comparing triple versus single dose GdDTPA sensitivities in the detection of enhancing lesions in the SC of patients with MS.
2.1. Patients Fifteen consecutive out patients (4 men and 11 women) with clinically definite MS entered the study. Eight had relapsing-remitting and 7 had secondary progressive MS. Their mean age was 39 years (range ⫽ 30 –58 years), mean duration of the disease was 10.0 years (range ⫽ 2–21 years), and the mean Expanded Disability Status Scale (EDSS) score [5] was 3.7 (range ⫽ 1.0 –7.0). Patients who received corticosteroids during the preceding 3 months were excluded from the study. MRI examinations were performed on all patients every 28 ⫾ 5 days on four separate occasions, corresponding to a follow-up of 3 months duration. Written informed consent to participate in the study was obtained from all the patients.
* Corresponding author. Tel.: ⫹49-89-7095-2501; fax: ⫹49-89-70952509. E-mail address:
[email protected] (T.A. Yousry).
All MRI scans were performed using systems operating at 1.5T using a spine array coil. Imaging was performed in two centers (Munich and Milan) using two identical systems
2.2. SC MRI
0730-725X/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S 0 7 3 0 - 7 2 5 X ( 0 0 ) 0 0 1 9 1 - 0
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(Vision, Siemens, 30 MT gradient). On each scanning occasion, the MRI examination was split into two sessions, separated by an interval of 12–24 hours. Since it was shown that enhancement in MS lesions fades away after no more than 5 hours [6], the time interval was thought to be sufficient. The following sequences were obtained in the sagittal plane during the first session: 1) T1-weighted (TR ⫽ 642 ms, TE ⫽ 12 ms, 3-mm contiguous slices, echo train length ⫽ 15, FOV ⫽ 655 ⫻ 500 (phase encode ⫻ read-out), raw data matrix ⫽ 512 ⫻ 512, number of signal averages ⫽ 2, acquisition time ⫽ 4 minutes and 46 seconds) obtained before and 5 to 7 minutes after injection of Gd-DTPA. 2) Before Gd-DTPA was injected, T2-weighted turbo spin-echo (TSE) sequences were obtained (TR ⫽ 3817 ms, TE ⫽ 112 ms, echo train length ⫽ 15, FOV ⫽ 655 ⫻ 500 (phase encode ⫻ read-out), raw data matrix ⫽ 512 ⫻ 512, number of signal averages ⫽ 1, acquisition time ⫽ 2 minutes and 13 seconds). The dose of Gd-DTPA was randomized so that either a single dose (0.1 mmol/kg) or a triple dose (0.3 mmol/kg) was given in the first session, with the other dose given in the second session. 2.3. MRI evaluation Two of us, unaware of the Gd-DTPA dosage used, evaluated by consensus and in a random order the numbers of enhancing SC lesions present on scans obtained with two doses of Gd-DTPA. T2-weighted scans were always used as references to confirm the presence of enhancing lesions.
3. Results We detected two enhancing lesions in two of the 15 patients (13%) when the single dose of Gd-DTPA was used. One lesion was located in the cervical SC at the level of C2 and one in the thoracic SC at the level of T10. Both lesions were only seen in the 3rd session and both were detected on the T2-weighted sequence. The cervical lesion measured 5–10 mm, the thoracic lesion measured 5 mm in diameter. No additional lesions were detected and no increase of the lesion size was observed after a triple dose of Gd-DTPA injection (Fig. 1). The pre-contrast T1-weighted scans obtained on the second session never revealed any residual enhancement.
4. Discussion In this longitudinal MRI study, we compared the sensitivities of single and triple dose of Gd-DTPA for detecting enhancing lesions in the SC of MS patients. We found no difference between the two techniques. Our study as well as most studies evaluating enhance-
ment in the SC of patients with MS showed that the number of enhancing lesions was low [1–3,7]. We only detected 2 lesions in 15 patients scanned monthly for 3 months. In one study, only 12 enhancing SC lesions were detected over one year from 10 patients with monthly scanning [3]. Similarly, 19 enhancing SC lesions were detected on 79 serial scans from 29 patients [2], and only one enhancing lesion was detected from 19 patients with monthly scanning [7]. Increasing the scanning frequency up to 2 scans per month did not increase the number of detected lesions. Capra et al. detected only 3 lesions on 60 scans from 10 patients who underwent serial imaging every 2 weeks for 3 months [1]. The number of enhancing lesions in the SC was considerably higher in only one study. Trop et al. studied 25 patients presenting with signs and symptoms of myelopathy over one year on four occasions (at baseline and at months 2, 6 and 12) [8]. On the baseline scans, they found 15 enhancing lesions in 13 patients (52%), and detected 9 additional enhancing lesions in 6 patients on the follow-up scans [8]. When using delayed scanning the number of enhancing lesions increased from 13 to 15 and 4 lesions were more conspicuous [8]. The latter finding is probably the reason why the authors thought that a double dose of Gd-DTPA could be helpful in improving the detection of enhancing lesions [8]. The different results of this study compared to the others are most probably due to a sampling difference. The main inclusion criteria in those studies reporting a low detection rate of enhancing SC lesions in MS [1–3,7, present study] was the presence of definite MS, while in the study by Trop et al. only patients with definite MS and myelopathic symptomatology were studied. The importance of the clinical presentation is underlined by the fact that 71% of the patients presenting with new clinical manifestations of myelopathy had enhancing lesions in the cord [8]. The reported differences in the enhancement of SC lesions suggest that concerning the site of disease activity various subgroups of patients exist. The extremes would be a disease activity that is confined either to the brain or to the SC. Between these two groups there would be patients with a disease activity in both the SC and the brain with a predominance in one of these two sites. Uldry et al. studied 28 patients and found that 3 had only lesions in the SC, 14 had lesions in the SC and in the brain and 9 patients had lesions confined to the brain only [9]. In autopsy studies up to 13% of 70 randomly selected MS patients lesions were restricted to the SC without brain involvement [10]. To date, only one study examined the sensitivity of triple dose of Gd-DTPA for the detection of enhancing lesions in the SC [4]. Using this approach in 13 patients, the number of lesions detected, increased from 2 lesions in 2 patients to 12 lesions in 5 patients [4]. These results were not replicated in the present longitudinal study. Even though the time interval between the contrast doses was shorter in this study than in the previous one, no additional lesions were seen on the second scan. The difference in the results obtained in the
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Fig. 1. a) 43-years old patient with relapsing remitting MS. In the 4th session no enhancing lesions on the T1-weighted single dose enhanced sequence was detected. b) T1 weighted triple dose enhanced sequence revealing no enhancing lesions.
previous and in the present study are partially related to the difference in patient selection. The present study enrolled a higher number of patients with secondary progressive MS (7 out of 15 patients) as compared to the previous study (4 out of 13 patients). Given the fact that cerebral lesions reveal a lower enhancement in secondary progressive MS as compared to relapsing remitting MS [11], part of the discrepancy can be related to the different proportion of secondary progressive MS patients. Finally, the proportion of myelopathic patients was probably also reduced in the present study as compared to the previous one, which could be the most important factor contributing to the discrepancy of results. Nevertheless, the present study indicates that the low sensitivity of conventional enhanced MRI for detecting MS lesions in the SC of an unselected MS population cannot be significantly increased by the general use of a triple dose of Gd-DTPA. Rather a concentration on a subgroup of patients presenting with SC symptoms would be necessary. Contrary to the SC, the role of triple dose of Gd-DTPA for detecting MS lesions in the brain has been settled by multiple studies that all confirm its supremacy over the
standard approach [12,13]. To establish the role of triple dose Gd-DTPA in the evaluation of the spinal cord in myelopathic patients, a longitudinal study focusing on these patients is warranted. References [1] Capra R, Marciano N, Vignolo LA, Chiesa A, Gasparotti R. Gadolinium-penletic acid magnetic resonance imaging in patients with relapsing remitting multiple sclerosis. Arch Neurol 1992;49:687–9. [2] Wiebe S, Lee DH, Karlik SJ, Hopkins M, Vandervoort MK, Womg CJ, Hewitt L, Rice GP, Ebers GC, Noseworthy JH. Serial cranial and spinal cord magnetic resonance imaging in multiple sclerosis. Ann Neurol 1992;32:643–50. [3] Thorpe JW, Kidd D, Moseley IF, Kenndall BE, Thompson AJ, MacManus DG, McDonald WI, Miller DH. Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis. Neurology 1996;46:373– 8. [4] Yousry TA, Fesl G, Walther E, Voltz R, Filippi M. Triple dose of gadolinium-DTPA increases the sensitivity of spinal cord MRI in detecting enhancing lesions in multiple sclerosis. J Neurol Sci 1998; 158:221–5. [5] Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444 –52.
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