Gadolinium\p=m-\PenteticAcid Magnetic Resonance Imaging in Patients With Relapsing Remitting Multiple Sclerosis Ruggero Capra, MD; Nicoletta Marcian\l=o`\,MD; Luigi A. Vignolo MD; Antonio Chiesa, MD; Roberto Gasparotti, MD
patients with relapsing-remitting multiple sclerosis have been studied by serial gadolinium\p=m-\penteticacid magnetic resonance imaging (MRI) every 14 days for 3 months. At the end of the follow-up, seven relapses occurred in six patients; no therapy was administered during the study. Ninety-three enhancing lesions were collected in eight patients. With regard to the duration of the enhancement, 32 lesions were detected in only one MRI scan and 32 were found in more MRI scans (most of the lesions occurring in two serial examinations). Four old lesions increased their size with delayed enhancement. Correlation was found between the relapses and the gadolinium\p=m-\penteticacid\p=m-\ enhancing areas only for one brain-stem and two cervical spinal cord lesions. Gadolinium\p=m-\penteticacid MRI provides useful information about activity of the disease that cannot be obtained clinically even if the dynamic of the lesions may be undervalued in old plaques. (Arch Neurol. 1992;49:687-689)
PATIENTS AND METHODS
\s=b\ Ten
between the clinical course and the is notoriously poor in multiple Magnetic resonance imaging (MRI) is a well-established technique for the assessment of the MS lesions1-2 and gadolinium-pentetic acid (Gd-DTPA), a paramagnetic contrast medium, can show the increase of the blood-brain barrier (BBB) permeability, a sign of
correlation The pathologic process sclerosis (MS).
See editorial comment
on
685.
Gd-DTPA MRI. for
publication
October 21, 1991.
Departments of Neurology (Drs Capra, Marcian\l=o`\,and Vignolo) and Radiology (Drs Chiesa and Gasparotti), University of MedFrom the
icine, Brescia, Italy. Reprint requests to Piazza
2a Neurologia, Universit\l=a'\Deli Studi 25123 Brescia, Italia (Dr Capra).
Spedali Civili 1,
Patient Evaluation The patients underwent brain and spinal cord MRI without and with the injection of Gd-DTPA, every 14 days, for 3 months. At the end of every MRI examination, clinical examinations were used to evaluate symptoms and signs of neurologic dysfunction. The patients and the examining physician were "blinded" to the results of MRI. The occurrence of a symptom or sign of neurologic dysfunction lasting more than 24 hours was considered a relapse.
MRI Scans
Magnetic imaging was performed with a 1.5-T superconductor unit (Magnetom, Siemens, Erlangen, Germany). Spin-echo images of the brain were acquired using a head coil, resonance
256X256 matrix, 20-cm field of The in-plane spatial resolution
view, and 5-mm-thick sections.
was
0.75
mm.
The
p-weighted
(650/15/2 [repetition time/echo time/excitations]) and T2 axial images (2000/15 to70/l [repetition time/echo time]) with 20%
pathologie activity and plaque development.36 Gadolinium-pentetic acid MRI should be a useful tool in monitoring disease activity.7 Therefore, we have studied the course of the illness in patients with relapsingremitting MS, who are not receiving therapy, by means of Accepted
Patient Selection Ten patients with clinically definite MS according to the crite¬ ria of Poser et al8 were studied. Clinical selection criteria were as follows: no immunosuppressants before the study, no psychosis, no pregnancy, a score of less than 4 on the Expanded Disability Status Scale,9 a clinical relapsing-remitting course, and no evi¬ dence of secondary progression. The patients, three men and seven women, accepted to receive no steroid therapy in case of relapse during the study. Their ages were between 23 and 46 years (mean age, 30 years), with duration of illness between 2 and 10 years (mean duration, 6 years). At the beginning of the follow-up, Expanded Disability Status Scale scores ranged from 1 to 3 (mean, 2). All patients had an MRI without Gd-DTPA before the study.
diBrescia,
interslice gap were obtained with a complete coverage of the brain. In all patients, p-weighted images were also obtained af¬ ter intravenous administration of gadolinium-pentetic acid (Shering, Berlin, Germany) 0.2 mL/kg of body weight (0.1 mmol/kg). The contrast media was administered without changing the pa¬ tient's position. Contrast-enhanced ,-weighted images of the brain were collected 10 minutes after the injection. A mild T2 weighting was preferred for a better distinction of small periven¬ tricular demyelinating lesions. The spinal cord examination was based on ,-weighted sagittal spin-echo images (500/15 repeti¬ tion time in millisecond s/echo time in milliseconds) that were acquired after gadolinium-pentetic acid injection. Contiguous 3-mm-thick slices were obtained separately for the cervical and dorsal segments with a surface receiver coil. Serial examinations were performed with an accurate repositioning of the patient's head to obtain comparable sections at the same anatomic location. The position of the head was determined with the help of a laser
Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/16/2015
Findings on the Neuroradiologic and Neurologic Examinations* Neurologic Examination
Neuroradiologic Examination MRI, Patient No.
Symptoms
No. of Lesionst
Signs
Sequence
Sequence*
-
1 20
2
0
3
0
4
1
5
1
6
1
1
15
16
21
20
LLW,
15
LLW,
RLW LLW
LLW
LLW LLW
7
12
LLW
8
0
DIP
9
0
10
0
LLW
LLW
LLW
.
LLW
LLW
LLW
INO
LLW
LLW
.
PT
leg weakness; P, truncal and legs paresthesia; H, truncal and legs hypoesthesia; RLW, internuclear ophthalmoparesis; PT, paresthesias of the tongue; and MRI, magnetic resonance imaging. tNumber of gadolinium-pentetic acid lesions in each MRI examination. iSequence indicates the sequence number of the examination. *LLW indicates left
light. A sagittal midline section, on which a grid with vertical and horizontal numbered lines was superimposed, was taken as a reference image for a precise calculation of the correct head po¬ sition to ensure anatomic correspondence of the slices in subse¬
quent examinations. The MRI sequences were obtained before and after a bolus of gadolinium-pentetic acid, which was given to the patient, who was still in the scanner, over 2 minutes. Phe enhanced images were collected 10 minutes after the injection of gadolinium-pentetic acid. Phe largest diameter of the Gd-DPPAenhancing lesions was measured directly on the monitor using the conversion scale of the equipment. RESULTS
Patient Evaluations
Sixty clinical examinations were performed. lapses occurred in six patients: symptoms and
Seven re¬ results of
neurologic examinations were concordant in four patients. In three patients, relapses corresponded to Gd-DTPAenhancing lesions: paresthesia of the trunk and legs (patient 1) and left leg weakness (patient 7) occurred con¬ comitantly with two lesions in the cervical spinal cord, and diplopia (patient 8) occurred with one lesion in the brain stem. No relapse occurred without concomitant Gd-
DPPA-enhanced areas but Gd-DPPA enhancements were found without signs or symptoms of neurologic dysfunc¬ tion in the scans from 18 MRI examinations (Pable ). At the end of the follow-up, the Expanded Disability Status Scale score of the patients did not change.
TrWeighted MRI Characteristics forty-six hyperintense areas (123
One hundred
LLW
supra-
tentorial, 22 infratentorial, and one in the cervical spinal cord) were identified in T2-weighted images in the first
MRI examination. Periventricular confluence of the lesions was found in seven patients. One hundred fifty-four hyperintense areas (130 supratentorial, 22 infratentorial, and two in the cervical spinal cord) were identified in P2weighted scans in the last MRI examination. No correlation was found between the disability and MRI T2-weighted lesions at the beginning of the study.
right leg weakness; DIP, diplopia; INO,
,-Weighted Gd-DTPA MRI Characteristics Gd-DTPA MRI scans of the brain and of the spinal Sixty cord were performed. Ninety-three -weighted GdDTPA-enhanced areas were found in eight patients dur¬ ing the study: 82 lesions in the supratentorial areas, eight in the brain stem and cerebellum and three in the cervical spinal cord. No Gd-DTPA-enhanced areas were found in two patients. Sixty-five supratentorial Gd-DTPA enhance¬ ments occurred in T2-weighted hyperintense areas already found in previous examinations (Gd-DTPA enhancement of old lesions) and most of them were located in the periventricular confluence. Seventeen supratentorial en¬ hanced areas were new lesions and they were outside the periventricular area. All brain-stem and cerebellum GdDTPA enhancements occurred in previously found T2weighted hyperintense areas. Two of the three cervical spinal cord lesions were new. To determine the duration of the enhancement, Gd-DTPA-enhancing areas in the first and last scan were not included: 32 lesions were found in only one MRI scan and 32 lesions continued to enhance for more than one examination (21 were detected in two examinations, six were detected in three examinations, and five were detected in four examinations). Phese 64 GdDPPA-enhancing areas were divided by dimension: among the 32 single-appearance lesions, 18 were less than 5 mm in diameter, 13 were more than 5 mm, and one was more than 1 cm. Among the 32 lesions appearing in more than one examination, seven lesions were less than 5 mm in diameter, 21 were more than 5 mm, and four were more than 1 cm. One Gd-DPPA enhancement in the cervical spinal cord persisted from the first to the last scan. During the follow-up, three supratentorial Gd-DPPA-enhancing areas changed their enhancement into a ring shape before disappearing. Four Gd-DPPA supratentorial enhance¬ ments were preceded by the enlargement of the corre¬ sponding P2-weighted hyperintensity, detected in previ¬ ous serial examinations. Phe tendency of the plaques to enhance in temporal cluster was observed in three pa¬ tients.
Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/16/2015
COMMENT of MS, clinical studies may be the course assessing the as misleading activity of the immunopathologic pro¬ cess does not correlate with changes in disability.4,10'11 Multiple sclerosis lesions may be detected by MRI and the signal abnormalities correspond to the pathologic pro¬ cess112; moreover, the Gd-DTPA enhancement is a reliable marker of increased BBB permeability in patients with relapsing-remitting MS.3-7 In our study, Gd-DPPA MRI showed a continuous appearance and disappearance of BBB opening, often with unchanged results of clinical ex¬ aminations. During the follow-up, the supratentorialenhancing lesions did not correlate with the relapses. Only two of the three acute plaques of the cervical spinal cord and a brain-stem-enhancing lesion were symptomatic, al¬ though small lesions of the spinal cord could be missed by the less satisfactory MRI scanning of the spinal cord than of the brain. Phe absence of correlation between MRI and the clinical examination could be due to the fact that most of the Gd-DPPA-enhancing areas were located in the periventricular confluence of demyelination. Phe distribu¬ tion of the enhancing lesions also explains the slight increase of the number of the hyperintensities at the end of the study. However, the new supratentorial lesions were not symptomatic, even when located near the cortex or in the white matter, not adjacent to the ventricles. Our results are in accord with the study of Harris et al13 in patients with early, mild MS, except for the spinal cord that was not imaged. On the contrary, in a prospective monthly MRI study, Isaac et al14 found a larger number of new le¬ sions than old ones; Koopmans et al15 and Willoughby et al10 reported also that active lesions were more often out¬ side the periventricular location. Phe results of our study might be due to the Gd-DTPA that pointed out the BBB opening in areas of plaque confluence, where a modified lesion is noticed with difficulty. The Gd-DTPA also en¬ hanced small lesions (1 cm in diameter), the homo¬ geneous enhancement changed subsequently into a "ring" shape; later on, segments of the ring faded until complete disappearance as a progressive restoration of the BBB breakdown occurred. Phe ring enhancement was not a consequence of intensity changes made by a different scanning interval since the Gd-DPPA MRI scans were per¬ formed at the same time after contrast injection. In our study, Gd-DPPA enhancement appeared concomitantly or before the enlargement of lesions, but four old lesions, outside the border of the periventricular conflu¬ ence of demyelination, increased their size in the T2weighted images without any Gd-DTPA enhancement in the corresponding Prweighted sequences. Phe enhance¬ ment appeared subsequently in the follow-up. In contrast In
P2-weigthed
T2-weighted
from what is likely to happen in the new lesions, the en¬ largement of the old plaques might occur also without an active transport of Gd-DPPA through the endothelium, probably for a less active inflammation than in the new le¬ sions (Gd-DPPA diffusion not detectable by the scanner) or for a local immune activity that does not modify the BBB; likewise, Gd-DPPA MRI could undervalue the active inflammation in the central nervous system. In our pa¬ tients, the enhancement changed without concurrent ap¬ pearance or disappearance of all the Gd-DTPA-enhancing lesions. Phe simultaneously opposite state of lesion activ¬ ity and the disappearance of the enhanced segments of the ring plaques could be the sign of a modulation of the damage inside the central nervous system. In conclusion, the Gd-DPPA MRI provides useful infor¬ mation about lesion activity that cannot be obtained by a clinical evaluation; this technique might be a useful indi¬ cator of the pathologic process in monitoring therapeutic trials. However, this hypothesis must be considered with caution, since the dynamic of lesions may be undervalued for a limited active transport of the Gd-DPPA in old plaques and because of the resolution of the scanner. Fred D. Lublin,
MD, gave technical assistance. References
et al. The role of imaging in the assessment of multiple sclerosis and isolated neurological lesions. Brain. 1987;110:1579-1616. 2. Reider-Groswasse I, Kott E, Benmair J, Huberman M, Matchey Y, Gelernter I. MRI parameters in multiple sclerosis patients. Neuroradiology. 1988;30:219-223. 3. Poser CM. Controversies in the pathogenesis of multiple sclerosis. In: Behan WMH, ed. Clinical Neuroimmunology. Boston, Mass: Blackwell Scientific Publications Inc; 1987:179-191. 4. Miller DH, Rudge P, Johnson G, et al. Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis. Brain. 1988;111:927-939. 5. Kermode AG, Tofts PS, Thompson AJ, et al. Heterogeneity of blood\x=req-\ brain barrier changes in multiple sclerosis. Neurology. 1990;40:
1. Ormerod
IEC, Miller DH, McDonald WI,
229-235. 6. Kermode AG, Thompson AJ, Tofts P, et al. Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Brain. 1990;113:1477-1489. 7. Hawkins CP, Munro PMG, Mackenzie F, et al. Duration and selectivity of blood-brain barrier breakdown in chronic relapsing experimental allergic encephalomyelitis studied by gadolinium-DTPA and protein markers. Brain.
1990;113:365-378. 8. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983;13: 227-231. 9. Kurtzke JF.
Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444-1452. 10. Willoughby EW, Grochowski E, Li DKB, Oger J, Kastrukoff LF, Paty DW. Serial magnetic resonance scanning in multiple sclerosis: a second prospective study in relapsing patients. Ann Neurol. 1989;25:43-49. 11. Koopmans RA, Li DKB, Grochowski E, Cutler PJ, Paty DW. Benign versus chronic progressive multiple sclerosis: magnetic resonance imaging
features. Ann Neurol. 1989;25:74-81. 12. Stewart WA, Hall LD, Berry K, et al. Magnetic resonance imaging (MRI) in multiple sclerosis (MS): pathological correlation studies in eight cases. Neurology. 1986;36(suppl 1):320. 13. Harris JO, Frank JA, Patronas N, McFarlin DE, McFarland HF. Serial gadolinium-enhanced magnetic resonance imaging scans in patients with early, relapsing-remitting multiple sclerosis: implications for clinical trials and natural history. Ann Neurol. 1991;29:548-555. 14. Isaac C, Li DKB, Genton M, Jardine C, et al. Multiple sclerosis: a serial study using MRI in relapsing patients. Neurology. 1988;38:1511-1515. 15. Koopmans RA, Li DKB, Oger JJF, Mayo J, Paty DW. The lesion of multiple sclerosis: imaging of acute and chronic stages. Neurology. 1989;39: 959-963.
Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/16/2015
patients with relapsing-remitting multiple sclerosis have been studied by serial gadolinium\p=m-\penteticacid magnetic resonance imaging (MRI) every 14 days for 3 months. At the end of the follow-up, seven relapses occurred in six patients; no therapy was administered during the study. Ninety-three enhancing lesions were collected in eight patients. With regard to the duration of the enhancement, 32 lesions were detected in only one MRI scan and 32 were found in more MRI scans (most of the lesions occurring in two serial examinations). Four old lesions increased their size with delayed enhancement. Correlation was found between the relapses and the gadolinium\p=m-\penteticacid\p=m-\ enhancing areas only for one brain-stem and two cervical spinal cord lesions. Gadolinium\p=m-\penteticacid MRI provides useful information about activity of the disease that cannot be obtained clinically even if the dynamic of the lesions may be undervalued in old plaques. (Arch Neurol. 1992;49:687-689)
PATIENTS AND METHODS
\s=b\ Ten
between the clinical course and the is notoriously poor in multiple Magnetic resonance imaging (MRI) is a well-established technique for the assessment of the MS lesions1-2 and gadolinium-pentetic acid (Gd-DTPA), a paramagnetic contrast medium, can show the increase of the blood-brain barrier (BBB) permeability, a sign of
correlation The pathologic process sclerosis (MS).
See editorial comment
on
685.
Gd-DTPA MRI. for
publication
October 21, 1991.
Departments of Neurology (Drs Capra, Marcian\l=o`\,and Vignolo) and Radiology (Drs Chiesa and Gasparotti), University of MedFrom the
icine, Brescia, Italy. Reprint requests to Piazza
2a Neurologia, Universit\l=a'\Deli Studi 25123 Brescia, Italia (Dr Capra).
Spedali Civili 1,
Patient Evaluation The patients underwent brain and spinal cord MRI without and with the injection of Gd-DTPA, every 14 days, for 3 months. At the end of every MRI examination, clinical examinations were used to evaluate symptoms and signs of neurologic dysfunction. The patients and the examining physician were "blinded" to the results of MRI. The occurrence of a symptom or sign of neurologic dysfunction lasting more than 24 hours was considered a relapse.
MRI Scans
Magnetic imaging was performed with a 1.5-T superconductor unit (Magnetom, Siemens, Erlangen, Germany). Spin-echo images of the brain were acquired using a head coil, resonance
256X256 matrix, 20-cm field of The in-plane spatial resolution
view, and 5-mm-thick sections.
was
0.75
mm.
The
p-weighted
(650/15/2 [repetition time/echo time/excitations]) and T2 axial images (2000/15 to70/l [repetition time/echo time]) with 20%
pathologie activity and plaque development.36 Gadolinium-pentetic acid MRI should be a useful tool in monitoring disease activity.7 Therefore, we have studied the course of the illness in patients with relapsingremitting MS, who are not receiving therapy, by means of Accepted
Patient Selection Ten patients with clinically definite MS according to the crite¬ ria of Poser et al8 were studied. Clinical selection criteria were as follows: no immunosuppressants before the study, no psychosis, no pregnancy, a score of less than 4 on the Expanded Disability Status Scale,9 a clinical relapsing-remitting course, and no evi¬ dence of secondary progression. The patients, three men and seven women, accepted to receive no steroid therapy in case of relapse during the study. Their ages were between 23 and 46 years (mean age, 30 years), with duration of illness between 2 and 10 years (mean duration, 6 years). At the beginning of the follow-up, Expanded Disability Status Scale scores ranged from 1 to 3 (mean, 2). All patients had an MRI without Gd-DTPA before the study.
diBrescia,
interslice gap were obtained with a complete coverage of the brain. In all patients, p-weighted images were also obtained af¬ ter intravenous administration of gadolinium-pentetic acid (Shering, Berlin, Germany) 0.2 mL/kg of body weight (0.1 mmol/kg). The contrast media was administered without changing the pa¬ tient's position. Contrast-enhanced ,-weighted images of the brain were collected 10 minutes after the injection. A mild T2 weighting was preferred for a better distinction of small periven¬ tricular demyelinating lesions. The spinal cord examination was based on ,-weighted sagittal spin-echo images (500/15 repeti¬ tion time in millisecond s/echo time in milliseconds) that were acquired after gadolinium-pentetic acid injection. Contiguous 3-mm-thick slices were obtained separately for the cervical and dorsal segments with a surface receiver coil. Serial examinations were performed with an accurate repositioning of the patient's head to obtain comparable sections at the same anatomic location. The position of the head was determined with the help of a laser
Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/16/2015
Findings on the Neuroradiologic and Neurologic Examinations* Neurologic Examination
Neuroradiologic Examination MRI, Patient No.
Symptoms
No. of Lesionst
Signs
Sequence
Sequence*
-
1 20
2
0
3
0
4
1
5
1
6
1
1
15
16
21
20
LLW,
15
LLW,
RLW LLW
LLW
LLW LLW
7
12
LLW
8
0
DIP
9
0
10
0
LLW
LLW
LLW
.
LLW
LLW
LLW
INO
LLW
LLW
.
PT
leg weakness; P, truncal and legs paresthesia; H, truncal and legs hypoesthesia; RLW, internuclear ophthalmoparesis; PT, paresthesias of the tongue; and MRI, magnetic resonance imaging. tNumber of gadolinium-pentetic acid lesions in each MRI examination. iSequence indicates the sequence number of the examination. *LLW indicates left
light. A sagittal midline section, on which a grid with vertical and horizontal numbered lines was superimposed, was taken as a reference image for a precise calculation of the correct head po¬ sition to ensure anatomic correspondence of the slices in subse¬
quent examinations. The MRI sequences were obtained before and after a bolus of gadolinium-pentetic acid, which was given to the patient, who was still in the scanner, over 2 minutes. Phe enhanced images were collected 10 minutes after the injection of gadolinium-pentetic acid. Phe largest diameter of the Gd-DPPAenhancing lesions was measured directly on the monitor using the conversion scale of the equipment. RESULTS
Patient Evaluations
Sixty clinical examinations were performed. lapses occurred in six patients: symptoms and
Seven re¬ results of
neurologic examinations were concordant in four patients. In three patients, relapses corresponded to Gd-DTPAenhancing lesions: paresthesia of the trunk and legs (patient 1) and left leg weakness (patient 7) occurred con¬ comitantly with two lesions in the cervical spinal cord, and diplopia (patient 8) occurred with one lesion in the brain stem. No relapse occurred without concomitant Gd-
DPPA-enhanced areas but Gd-DPPA enhancements were found without signs or symptoms of neurologic dysfunc¬ tion in the scans from 18 MRI examinations (Pable ). At the end of the follow-up, the Expanded Disability Status Scale score of the patients did not change.
TrWeighted MRI Characteristics forty-six hyperintense areas (123
One hundred
LLW
supra-
tentorial, 22 infratentorial, and one in the cervical spinal cord) were identified in T2-weighted images in the first
MRI examination. Periventricular confluence of the lesions was found in seven patients. One hundred fifty-four hyperintense areas (130 supratentorial, 22 infratentorial, and two in the cervical spinal cord) were identified in P2weighted scans in the last MRI examination. No correlation was found between the disability and MRI T2-weighted lesions at the beginning of the study.
right leg weakness; DIP, diplopia; INO,
,-Weighted Gd-DTPA MRI Characteristics Gd-DTPA MRI scans of the brain and of the spinal Sixty cord were performed. Ninety-three -weighted GdDTPA-enhanced areas were found in eight patients dur¬ ing the study: 82 lesions in the supratentorial areas, eight in the brain stem and cerebellum and three in the cervical spinal cord. No Gd-DTPA-enhanced areas were found in two patients. Sixty-five supratentorial Gd-DTPA enhance¬ ments occurred in T2-weighted hyperintense areas already found in previous examinations (Gd-DTPA enhancement of old lesions) and most of them were located in the periventricular confluence. Seventeen supratentorial en¬ hanced areas were new lesions and they were outside the periventricular area. All brain-stem and cerebellum GdDTPA enhancements occurred in previously found T2weighted hyperintense areas. Two of the three cervical spinal cord lesions were new. To determine the duration of the enhancement, Gd-DTPA-enhancing areas in the first and last scan were not included: 32 lesions were found in only one MRI scan and 32 lesions continued to enhance for more than one examination (21 were detected in two examinations, six were detected in three examinations, and five were detected in four examinations). Phese 64 GdDPPA-enhancing areas were divided by dimension: among the 32 single-appearance lesions, 18 were less than 5 mm in diameter, 13 were more than 5 mm, and one was more than 1 cm. Among the 32 lesions appearing in more than one examination, seven lesions were less than 5 mm in diameter, 21 were more than 5 mm, and four were more than 1 cm. One Gd-DPPA enhancement in the cervical spinal cord persisted from the first to the last scan. During the follow-up, three supratentorial Gd-DPPA-enhancing areas changed their enhancement into a ring shape before disappearing. Four Gd-DPPA supratentorial enhance¬ ments were preceded by the enlargement of the corre¬ sponding P2-weighted hyperintensity, detected in previ¬ ous serial examinations. Phe tendency of the plaques to enhance in temporal cluster was observed in three pa¬ tients.
Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/16/2015
COMMENT of MS, clinical studies may be the course assessing the as misleading activity of the immunopathologic pro¬ cess does not correlate with changes in disability.4,10'11 Multiple sclerosis lesions may be detected by MRI and the signal abnormalities correspond to the pathologic pro¬ cess112; moreover, the Gd-DTPA enhancement is a reliable marker of increased BBB permeability in patients with relapsing-remitting MS.3-7 In our study, Gd-DPPA MRI showed a continuous appearance and disappearance of BBB opening, often with unchanged results of clinical ex¬ aminations. During the follow-up, the supratentorialenhancing lesions did not correlate with the relapses. Only two of the three acute plaques of the cervical spinal cord and a brain-stem-enhancing lesion were symptomatic, al¬ though small lesions of the spinal cord could be missed by the less satisfactory MRI scanning of the spinal cord than of the brain. Phe absence of correlation between MRI and the clinical examination could be due to the fact that most of the Gd-DPPA-enhancing areas were located in the periventricular confluence of demyelination. Phe distribu¬ tion of the enhancing lesions also explains the slight increase of the number of the hyperintensities at the end of the study. However, the new supratentorial lesions were not symptomatic, even when located near the cortex or in the white matter, not adjacent to the ventricles. Our results are in accord with the study of Harris et al13 in patients with early, mild MS, except for the spinal cord that was not imaged. On the contrary, in a prospective monthly MRI study, Isaac et al14 found a larger number of new le¬ sions than old ones; Koopmans et al15 and Willoughby et al10 reported also that active lesions were more often out¬ side the periventricular location. Phe results of our study might be due to the Gd-DTPA that pointed out the BBB opening in areas of plaque confluence, where a modified lesion is noticed with difficulty. The Gd-DTPA also en¬ hanced small lesions (1 cm in diameter), the homo¬ geneous enhancement changed subsequently into a "ring" shape; later on, segments of the ring faded until complete disappearance as a progressive restoration of the BBB breakdown occurred. Phe ring enhancement was not a consequence of intensity changes made by a different scanning interval since the Gd-DPPA MRI scans were per¬ formed at the same time after contrast injection. In our study, Gd-DPPA enhancement appeared concomitantly or before the enlargement of lesions, but four old lesions, outside the border of the periventricular conflu¬ ence of demyelination, increased their size in the T2weighted images without any Gd-DTPA enhancement in the corresponding Prweighted sequences. Phe enhance¬ ment appeared subsequently in the follow-up. In contrast In
P2-weigthed
T2-weighted
from what is likely to happen in the new lesions, the en¬ largement of the old plaques might occur also without an active transport of Gd-DPPA through the endothelium, probably for a less active inflammation than in the new le¬ sions (Gd-DPPA diffusion not detectable by the scanner) or for a local immune activity that does not modify the BBB; likewise, Gd-DPPA MRI could undervalue the active inflammation in the central nervous system. In our pa¬ tients, the enhancement changed without concurrent ap¬ pearance or disappearance of all the Gd-DTPA-enhancing lesions. Phe simultaneously opposite state of lesion activ¬ ity and the disappearance of the enhanced segments of the ring plaques could be the sign of a modulation of the damage inside the central nervous system. In conclusion, the Gd-DPPA MRI provides useful infor¬ mation about lesion activity that cannot be obtained by a clinical evaluation; this technique might be a useful indi¬ cator of the pathologic process in monitoring therapeutic trials. However, this hypothesis must be considered with caution, since the dynamic of lesions may be undervalued for a limited active transport of the Gd-DPPA in old plaques and because of the resolution of the scanner. Fred D. Lublin,
MD, gave technical assistance. References
et al. The role of imaging in the assessment of multiple sclerosis and isolated neurological lesions. Brain. 1987;110:1579-1616. 2. Reider-Groswasse I, Kott E, Benmair J, Huberman M, Matchey Y, Gelernter I. MRI parameters in multiple sclerosis patients. Neuroradiology. 1988;30:219-223. 3. Poser CM. Controversies in the pathogenesis of multiple sclerosis. In: Behan WMH, ed. Clinical Neuroimmunology. Boston, Mass: Blackwell Scientific Publications Inc; 1987:179-191. 4. Miller DH, Rudge P, Johnson G, et al. Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis. Brain. 1988;111:927-939. 5. Kermode AG, Tofts PS, Thompson AJ, et al. Heterogeneity of blood\x=req-\ brain barrier changes in multiple sclerosis. Neurology. 1990;40:
1. Ormerod
IEC, Miller DH, McDonald WI,
229-235. 6. Kermode AG, Thompson AJ, Tofts P, et al. Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Brain. 1990;113:1477-1489. 7. Hawkins CP, Munro PMG, Mackenzie F, et al. Duration and selectivity of blood-brain barrier breakdown in chronic relapsing experimental allergic encephalomyelitis studied by gadolinium-DTPA and protein markers. Brain.
1990;113:365-378. 8. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983;13: 227-231. 9. Kurtzke JF.
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