277 New Perspetives in Computed Tomography of Multiple Slerosis F. V. Vii'iuela 1. J. Fox 1 G. M. Debrun 1. 2 T. E. Feasby 3 G. C. Ebers 3 prospetive linial study was performed in 70 onseutive patients with known or strong linial suspiion of aute or relapsing multiple slerosis. The study was designed to ompare the results of standard omputed tomography and high-volume. ontrast-delayed sanning for the detetion of enhaning lesions. In 39 ases with linially definitive multiple slerosis, the onventional enhaned san was positive in 25 ases and the high-volume delay san in 32. The high-volume enhaned san added information in 23 of these 32 ases. In 21 ases, suspiious of multiple slerosis but not linially onfirmed, the standard enhaned san was positive in t wo ases and t he high-volume delay san in five. In these ases, omputed t omography was definitive in establishing the diagnosis by showing linially unsuspeted brain lesions. In 10 ases in whih the disease was eventually exluded, the sans were negative in all instanes. For the first time, by the high-volume delayed t ehnique, enhaning plaques in the ortial gray matter and in the gray/ white matter regions were demonstrated. This tehnique is a very useful diagnosti tool, not only for morphologi assessment when multiple slerosis is known, but for the positive diagnosis of this disease when the first linial presentation is diagnostially unertain. This artile appears in the May/ June 1982 issue of JNR and the July 1982 issue of JR. Reeived ugust 21, 1981; aepted after revision February 1, 1982 I Department of Diagnosti Radiology, Neuroradiology Setion, University Hospital, 339 Windermere Rd., London, Ontario, Canada N6 55. ddress reprint requests to F. V. Viriuela. 2 Present address: Department of Diagnosti Radiology, Massahusetts General Hospital, oston, M 02114. 3 Department of Clinial Neurologial Sienes, University Hospital, London, Ontario, Canada N61' 55. JNR 3:277-281, May/ June 1982 0 195-6108/82/0303-0277 $00.00 merian Roentgen Ray Soiety Neuroradiologi studies in patients with suspeted multiple slerosis (MS) have been traditionally used mainly for exlusion of other pathology. With th e introdution of omputed tomographi (CT) sanning of the brain, speifi details of the gray and white matter an now be evaluated. It is well known that MS has several different CT appearanes in patients with linial evidene of erebral involvement [1-4]. The CT san may be normal or it may show foal lesions with or without evidene of atrophy [1-6]. It is presumed that MS demyelinating plaques produe a " mild " blood-brain barrier () disruption, as manifested by a relatively slight elevation of erebrospinal fluid (CSF) protein. On the basis of that premise, it was thought that a prolonged exposure of MS lesions to a high-volume sustained blood-iod ine level (3-6 mg / dl) and delayed sanning might depit areas of enhanement in zones of disruption not visible on standard CT. The high-volume delayed (HVD) san was originall y desribed by Hayman et al. [7-9] for the assessment of other intraranial diseases. The potential usefulness of this tehnique for the assessment of MS was also suggested by Prendes [10] and Davis et al. [11]. Subjets and Methods Using a protool set up at University Hospital, University of Western Ontario, we examined 70 patients with known or strong linial suspiion of early aute or relapsing MS during a period of 14 months. Eah of the 70 patients was sanned before ontrast medium infusion. Then, 100 ml of Conray 400 (40 g iodine) were administered intravenously as a bolus injetion. Immediate ontrast CT sans were obtained. On ompletion of these sans, an additional rapid drip of 300 ml of Hypaque 30 (42 g iod ine) was given. Th e HVD
278 VINUEL ET L. JNR:3, May/ June 1982 sans were obtained 1 nr after tn e rapid drip infusion. None of these patients had diabetes or elevated reatinine levels. No relevant neurologi or systemi side effets after ontrast medium infusion (82 g iodine) were deteted. ll these studies were done on a GE 8800 sanner using a 9.6 se, high-resolution mode. Similar window settings were used for filming the standard and the high-volume delayed sans. The CT sans were evaluated by two staff neuroradiologists. Speial attenti on was given to differenes in information obtained in the highvolume delayed san when ompared with th e standard dose san. Results Pati ents were divided into three groups, depending on their eventual diagnosis, on the basis of standard li nial and laboratory inform ation. TLE 1: CT Findings in 70 Patients Examined for Multiple Slerosis Normal bnormal: Nonenhaned san Standard enhaned san High-volume delayed san Defi nite Suspiious Disease Di sease Disease Exluded (n = 39) (n = 2 1) (n = 10) 7 1 6 10 20 1 0 25 2 0 32 5 0 Group 1 : Definite Multiple Slerosis In 39 ases having definitive linial and laboratory evidene of MS, the CT san was positive in 32 ases (82%) and normal in seven (18 %) (table 1). The riteria of Shumaher et al. [12] were used for the linial diagnosis and the laboratory riteria were the CSF eletrophoreti hanges desribed by Ebers and Paty [13]. In the 32 CT-positive ases, the non enhaned san was abnormal in 20, the onventional enhaned san was abnormal in 25, and the HVD showed enhaning lesions in all 32. The latter tehnique showed important additional information in 23 (72%) of these ases. This additional information was: (1) reinforement of equivoal findings on standard CT san in 17 ases (fig. 1); (2) enhanement of lowdensity plaques not enhaned on standard CT in 13 ases (fig. 2); (3) enhanement of isodense plaques not enhaned on standard CT in nine ases (fig. 3); and (4) pereption of low-density plaques not disernible on standard CT in four ases (fig. 4). In none of the 32 positive ases was less information observed by HVD sanning than by onventional sanning. Group 2 : Suspeted Multiple Slerosis In the 21 ases of suspiious but not liniall y onfirmed intraranial MS, CT was positive in five. In these fi ve ases, Fig. 1.-Questionable enhanement on standard CT, rein fored on high-volume delay san., Nonontrast axial san. Low-density lesions in both entral semi ovale., Standard ontrast san. Small area of enhanement diffiult to differentiate from ortial vessel (arrow). C, Definitive enhaning plaque in right entrum semiovale with HVD. Fig. 2.-Enhanement of low-density plaque on high-volume delay san., Poorly defined low-density lesions in both enlra semiovale., Standard ontrast san. No abnormal enhanement. C, Enhaning lesion in right entrum semiovale.
JNR:3, May/ June 1982 CT OF MULTIPLE SCLEROSIS 279 Fig. 3.-Enhanement of isodense plaque on high-volume delay san. Normal standard nonenhaned () and enhaned () sans. C, Marked enhanement of right entrum semiovale isodense on HVD. Fig. 4.-Low-density plaque seen only on high-volume delay san. Normal standard non enhaned () and enhaned () sans. C, HVD san. Left entrum semiovale well defined low-density lesion (arrow). Normal enhanement of su rrounding white matter delineates plaque. Fig. 5.-Clinial diagnosis of aute transverse myelitis. Loalized enlargement of mid thorai ord was seen on metrizam ide myelography., Nonenhaned san. Low-density lesion (arrow )., Standard enhaned san. Lesion en hanes (arrow). C, HVD enhaning san. Large en haning lesion in right orona radiata ompatible with MS. the nonenhaned san was abnormal in one ase, the standard enhaned san was abnormal in two, and the highvolume delayed (HVD) san showed enhaning lesions in all five. ll the CT-positive ases also had positive oligolonal bands in the CSF. It is noteworthy that the intraranial lesions deteted by CT were unsuspeted and spatially separated from the linial topographi diagnosis (figs. 5 and 6). mong these five ases were three ases of trans- verse myelitis, one ase of opti neuritis, and one ase of a linial single brain lesion. gain, HVD showed important additional information in these ases (figs. 5 and 6). The other 16 ases with negative CT sans showed a wide spetrum of single or multiple neurologi symptoms suh as gait ataxia, bilateral opti atrophy, bilateral internulear ophthalm oplegia, generalized parathesia, bilateral/ lateral gaze nystagmus, et. This group of patients remains undiagnosed.
280 VINUEL ET L. JNR:3, May/ June 1982 Fig. 6. - Clinial diag nosis of aute opti neuritis. Standard nonontrast () and ontrast () sans were negative. C, HVD. Small enhanin g lesions in right entrum semiovale and left audate nuleus adjaent to lateral ve ntriular wall (arrows). Fig. 7.-Cortial and suborti al multiple slerosis., Nonontrast san. Small low-density lesion in left orona radiata (arrow). Large well defined lowdensity lesion lateral to it., Standard ontrast san. Questionable enhanement in right frontal white matter (small arrow). Definitive though mild enhanement in left oipital white matter (large arrow). No enhanement in low-density lesion. C, HVD san. Enhaning plaques in orti al gray matter (losed straight arrow), gray/ white matter juntion (urved arrow), and deep white matter (open arrows ). Group 3: Multiple Slerosis Exluded In the 10 patients in whom MS was eventually linially exluded, CT sans of all types were negative in all ases. Disussion Evidene that CT is a valuable diagnosti tool in MS has been extensively reported [1, 2, 4-6, 9, 14, 15]. CT sans have been an important soure of anatomi/ morphologi information in patients with known disease. Enhaning white matter lesions have been desribed in these patients. In most reports, a relatively low rate of enhaning lesions has been demonstrated: 24.5% [4], 20.8 % [6], 9% [15], and 12.5% [16]. Our detetion rate of enhaning lesions is substantially higher than that desribed previously. This dis repany may be explained by two fators: (1) all our patients were in a state of early aute or relapsing MS and (2) we used HVD sanning. HVD demonstrated additional MS enhaning lesions in 23 of the 32 positive ases, and it offered a positive diagnosis in nine ases (seven ases in group 1 and two ases in group 2), in whih the standard CT sans had been interpreted as normal or as showing no evidene of ative disease. HVD demonstrated areas of enhanement produed by blood-brain barrier disruption [17, 18] in low-density or isodense MS plaques that were not seen on standard CT. We also observed enhaning MS plaques in the erebral ortial and ortial/subortial regions (fig. 7). These findings are well known to neuropathologists [19, 20], but to our knowledge they have not been reported before in the CT literature of MS. There were strong positive linial/ CT orrelations in our aute or relapsing ases of MS reinforing the onept that the areas of enhanement are probably aute demyelinating plaques. Ultimate ertainty will require omparison of the CT enhaning lesions and the orresponding biopsies or postmortem histology. It is important to emphasize the essential role played by CT in the group of patients in whom MS was only suspeted but not linially onfirmed using standard riteria. In suh patients, CT suggested the diagnosis of MS by showing linially silent and spatially separated entral nervous system (CNS) lesions. Even at the time of the first linial presentation of a single lesion suh as opti neuritis (fig. 6), transverse myelitis (fig. 5), or a single intraranial asymptomati plaque, CT sanning showed additional lesions that were helpful in diagnosing the disease. CT should be added to the list of laboratory studies that an aid in the diagnosis of MS.
JNR:3, May/ June 1982 CT OF MULTIPLE SCLEROSIS 281 On the basis of our experiene, we regard the highvolume delayed (HVD) CT san as the examination of hoie for the detetion of MS enhaning lesions. It not only inreases the number of enhaning lesions deteted by standard CT but demonstrates new lesions with a topography otherwise rarely observed, that is, ortial gray matter and gray matter/ white matter juntion. It may suggest the diagnosis by showing linially silent and spatially separated CNS lesions. The sequential use of CT sanning may help in understanding the morphologi evolution of enhaning, " ative" MS plaques and the effets of treatment on them. REFERENCES 1. Cole M, Ross RH. Plaques of MS seen on omputerized transaxial tomograms. Neurology (NY) 1977;27 : 890-891 2. yldensted C. Computer tomography of the erebrum in multiple slerosis. Neuroradiology 1976; 12: 33-42 3. Jaobs L, Kinkel WR. Computerized axial transverse tomography in multiple slerosis (abstr). Neurology (NY) 1976;26: 390-391 4. Weinstein M, Lederman R, Rothner 0, et al. Interval omputed tomography in MS. Radiology 1978;129: 689-694 5. Haughton VM, Ho KC, Williams, Eldevik OP. CT detetion of demyelinated plaques in MS. JR 1979;132: 213-215 6. Mikol F, ouhareine, ubin ML, Vignaud J. La Tomodensitometrie dans la slerose en plaques. Rev Neurol (Paris) 1980;6 : 481-490 7. Hayman L, Evans R, Hink VC. Rapid high dose (RHO) ontrast omputed tomography of peri sellar vessels. Radiology 1979;131 : 121-123 8. Hayman L, Evans R, Hink VC. Rapid high dose ontrast omputed tomography of isodense subdural hematoma and erebral swelling. Radiology 1979; 131 : 381-383 9. Hayman L, Evans R, Hink VC. Rapid high dose (RHO) ontrast ranial omputed tomography: a onise revi ew of normal anatomy. J Comput ssist Tomogr 1979;312 : 147-154 10. Prendes JL. Letter to th e editor. rh Neuro/1981 ;38: 67-68 11. Davis J, Davis K, Newhouse J. Expanded high iodine dose in omputed ranial tomography; a preliminary test report. Radiology 1979;131 :372-380 12. Shumaher G, eebe G, Kibler RF, et al. Problems of experimental trials of therapy in multiple slerosis: report by the panel of the evaluation of experim ental trials of therapy in multiple slerosis. nn NY ad Si 1973; 122: 552-568 13. Ebers GC, Paty OW. CSF eletrophoresis in one thousand patients. Can J Neurol Si 1980;7: 275-280 14. Hukman M, Fox J, Ramsey R. Computed tomography in the diagnosis of degenerative diseases of the brain. Semin Roentgeno/1977;12 :63-76 15. Hersey L, Gado MH, Trotter JL. Computerized tomography in the diagnosti evaluation of multiple slerosis. nn Neurol 1979;5: 32-39 16. Radve EW, Kendall E. Iodide and xenon enhanement of CT in MS. Neuroradiology 1978;15: 153-158 17. Wuthrih R, Gigli H, Wiggli V, Muller HR. CT sanning in demyelinating disease for ranial omputerized tomography. erlin: Springer, 1976: 239-243 18. roman T. lood-brain barrier damage in MS: supravital test observation. ta Neurol Sand 1964;40: 21-24 19. lakwood W, MMenemey WH, Meyer, Norman RM. Greenfield 's neuropathology, 3d ed. Chiago: Yearbook Medial, '1 976 20. Esourolle R, Poirier J. Manual of basi neuropathology (transl). Philadelphia: Saunders, 1973