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Prognostic Value of Magnetic Resonance Imaging in Monosymptomatic Optic Neuritis
Prognostic Value of Magnetic Resonance Imaging in Monosymptomatic Optic Neuritis Stephan Dunker, MD, Wolfgang Wiegand, MD, PhD Purpose: Magnetic resonance imaging is able to depict lesions in the optic nerve in the acute stage of monosymptomatic optic neuritis. Most patients have lesions located intraorbitally, intracanalicularly, and/or intracranially. The goal of this study is to determine whether these lesions resolve after visual recovery, change in length or localization, or could be correlated to the visual function. Methods: Between 1987 and 1992, the authors examined 22 patients with acute optic neuritis using magnetic resonance imaging short-time inversion recovery sequences. Additionally, the authors determined visual acuity, visual field, color vision, contrast sensitivity, and visual-evoked responses. All patients were re-examined between 1993 and 1994 in the same manner. Visual recovery in the re-examination was divided into three groups: group 1 with complete visual recovery (visual acuity better than 20/ 25); group 2 with incomplete recovery (visual acuity better than 20/25 but defect in at least one of the other tests: visual field, color vision, and contrast sensitivity); and group 3 with partial recovery (visual acuity remained less than 20/25, defect in all the other tests). Results: All group 1 patients initially had lesions less than 17.5 mm, group 2 patients had lesions greater than 17.5 mm (44%) and/or lesions located intracanalicularly (66%), and most of group 3 patients initially had lesions greater than 17.5 mm '(79%). Conclusion: Eyes with lesions less than 17.5 mm in the optic nerve in acute optic neuritis have a good prognosis for visual recovery. Lesions greater than 17.5 mm or lesions involving the intracanalicular portion of the optic nerve lead to incomplete or partial visual recovery. Ophthalmology 1996; 103: 1768-1773
Optic neuritis is often the first manifestation of multiple sclerosis. Optic neuritis is a demyelinating disorder of the optic nerve. I - 4 Magnetic resonance imaging (MRI) can detect lesions of the brain in mUltiple sclerosis and lesions of the optic nerve in optic neuritis. Contrast-enhanced MRI can detect disruption of the blood-brain barrier that is associated with acute lesions. T2- w~ighted imaging can Originally received: September 18, 1995. Revision accepted: July 17, 1996. From the Department of Ophthalmology of the Philipps- University Marburg, Germany. Presented in part at the ARVO Annual Meeting, Ft Lauderdale, May 1995. Reprint requests to Stephan Dunker, MD, Philipps-Universitat, Medizinisches Zentrum fiir Augenheilkunde, Robert-Koch-Str. 4, 35037 Marburg, Germany.
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detect edema of acute lesions and the gliosis and demyelination of chronic lesions. s- s For imaging of the optic nerve, fat suppression is required. 9 In our MRI study, we used short-time inversion recovery sequences (STIR). With STIR, orbital fat has a low signal intensity, whereas inflammation, demyelination, and gliosis have a high signal intensity.lO,l1 We performed STIR in patients with optic neuritis to determine whether the lesions resolve after visual recovery or whether there is a change in length or localization that could be correlated to the visual function.
Materials and Methods Between 1987 and 1992, we examined 22 patients (13 women and 9 men) with acute monosymptomatic optic
Dunker and Wiegand . Prognostic Value of MRI
Results Acute Stage Initial visual acuity ranged from 20120 to less than 20/ 400. The results of visual-evoked responses and visual field are given in Figure 3. Magnetic resonance imaging depicted a lesion in the affected nerve in 77% of the patients. We classified the lesions into two subgroups regarding the length (lesions < 17.5 mm and those ~ 17.5 mm) and into three subgroups regarding the localization (intraorbital, intracanalicular, and intraorbital plus intracanalicular). In none of the patients did the prechiasmatic or chiasmatic (intracranial) part of the optic nerve show increased signal intensity of the affected nerve.
Clinical Course
Figure 1. Increased signal intensity of the right optic nerve in the acute stage of optic neuritis (September 1988) in a 21-year-old patient. Arrow = the affected optic nerve.
neuritis. Magnetic resonance imaging and clinical examinations were done within 1 to 5 days after the onset of visual loss or pain. Clinically, we examined visual acuity (Snellen charts), contrast-sensitivity (Pelly-Robson charts), color vision (Ishihara charts), visual field (static perimetry using a visual field analyzer (Ttibinger automatik perimeter, Oculus, Wetzlar, Germany), and kinetic perimetry using the Goldmann perimeter (Haag-Streit, Bern, Switzerland) were performed. Only static perimetry results and visual-evoked responses (pattern shift) are reported here. For MRI, we used a 0.5-Tesla instrument (Siemens Magnetom, Siemens, Erlangen, Germany) and STIR sequences (recovery time [TR] = 1800 mseconds; excitation time [TE] = 35 mseconds; inversion time [T] = 140 mseconds) (Fig 1). To show the whole length of the optic nerve, coronal sections from behind the globe up to the chiasm were performed. The brightening of the optic nerve was described in comparison with the contralateral optic nerve or the white matter of the brain. Every brightening of the optic nerve was judged by two independent examinators. Additionally, T2-weighted axial and coronal sections of the brain were performed. Between July 1993 and December 1994, we re-examined each patient using a 1.0-Tesla instrument (Siemens Magnetom Impact) for MRI and performing STIR sequences (TR = 2100 mseconds; TE = 20 mseconds; TI = 150 mseconds) with coronal sections (Fig 2). The age of the patients varied between 16 and 45 years (average, 31 years). The follow-up period between the first examination and the re-examination was between 2.5 and 8 years (average, 4.7 years). Table 1 shows the data of all 22 patients.
Most of the patients were treated with systemic corticosteroids starting with prednisolone equivalent (150 mg). After day 3, the dose was reduced to 120 mg prednisolone equivalent; after day 6, it was reduced to 100 mg prednisolone equivalent. Every second day after day 6, the dose was reduced by an additional 20 mg. Recovery of the visual acuity (>3 lines in the eye chart) was fast «4 weeks) in 30% of the patients and slow (4 weeks-1 year) in 60% of the patients. Two patients did not show any improvement of the visual acuity. In two patients, a relapse occurred in the same eye, and in two patients the contralateral eye was affected.
Figure 2. Same patient as in Figure 1. Increased signal intensity of the right optic nerve in the re-examination (May 1994). At that time, the patient was 26 years of age. Arrow = the affected optic nerve.
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Volume 103, Number 11, November 1996
Table l. Patient Characteristics
Case No.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 MRI
Visual Acuity in the Acute Stage
Age at Onset (yrs) Sex
<20/400 20/20 10/200 20/20 20/20 20/40 <20/400 < 20/400 10/200 20/80 <20/400 20/80 20/20 20/25 10/200 20/40 <20/400 < 20/400 20/200 < 20/400 20/200 < 20/400
37 38 45 23 25 35 28 21 28 38 28 24 32 27 26 37 30 44 16 31 23 29
F
M
F F
M M M M M
F F F F F
M M
F F F
M F
F
Date of First MRI
5/87 7/87 1/88 3/88 4/88 5/88 8/88 9/88 2/89 4/89 10/89 6/90 1/90 2/90 8/90 10/90 4/91 5/91 6/91 8/91 2/92 4/92
Time from Onset of First Visual First to Date of Length of Symptoms Initial Second MRI Lesion in Second (days) Length (yrs, mos) Examination Second MRI
3 5 3 4 5 4 3 3 3 2 1 1 2 3 1 4 1 Same day
2 2 2 1
21 0 21 10.5 0 31.5 31.5 10.5
14
0 7 7 3.5 0 10.5 21 28 21 0 14 10.5 31.5
7,4 6,11 6,3 5,3 5,4 6,4 4,10 5,8 4,8 5,6 4,7 3,2 4,10 4,8 2,11 3,7 3,6 2,10 3,2 3,3 2,10 2,8
9/94 6/94 4/94 6/93 8/93 9/94 6/93 5/94 10/93 10/94 5/94 8/93 11/94 10/94 7/93 5/94 10/94 3/94 8/94 11/94 12/94 12/94
31.5 0 21 0 17.5 38.5 21 38.5 0 17.5 7 0 3.5 0 0 28 28 21 0 14 10.5 31.5
Follow. up Visual Acuity
20/25 20/20 20/20 20/20 20/20 <20/400 20/30 20/50 20/20 20/20 20/25 20/20 20/20 20/20 20/20 20/30 20/25 20/30 20/20 20/25 20/20 20/25
Treatment Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral
= magnetic resonance imaging.
Re-examination Although visual acuity in most patients was good at the time of re-examination, defects of visual function could be demonstrated in many of the eyes (Fig 3). The length and localization of the lesions in MRI are demonstrated in Figures 4 and 5. Cases 6 and 8 showed increased signal intensity of the complete optic nerve (including the intracranial part). Correlations For further evaluation, we divided the visual recovery into three groups: group 1, eyes had complete visual recovery (visual acuity in this group was better than 20/25, and there were no defects in visual field, color vision, and contrast sensitivity tests); group 2, eyes had incomplete recovery at the time of control (visual acuity was better than 20/25, but there were defects in at least one of the other tests); and group 3, eyes had partial recovery (visual acuity remained less than 20125, and there were defects in all the other tests at the time of control). We investigated the following correlations using the Spearman rank correlation coefficient I 2: 1. The length of the lesions at the time of the first examination is compared with the length at the time of the re-examination (Fig 4).
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2. The localization at the time of the first examination is compared with the localization at the time of the re-examination (Fig 5). 3. The length at the time of the first examination is correlated with the visual function at the time of the re-examination (Fig 6). 4. The localization at the time of the first examination is correlated with visual function at the time of the re-examination (Fig 7). 5. The length of the lesion in the re-examination is correlated with the visual function at the time of the re-examination. 6. The localization of the lesion in the re-examination is correlated with the visual function at the time of the re-examination. Initial Examination Acute initial lesions smaller than 17.5 mm correlated with complete visual recovery (P < 0.005). Lesions initially longer than 17.5 mm correlated with partial recovery (P < 0.005) (Fig 6). Complete visual recovery (36%) occurred in patients with no detectable lesion in the optic nerve by MRI (P < 0.005) and in patients with intraorbital
Dunker and Wiegand . Prognostic Value of MRI
LATENCY < 120 56%
LATENCY> 120 44%
First examination
First examination
goA,
C.- IC. plus per.
~~
LATENCY> 120 LATENCY < 120
Reexamination
Reexamination
Visual evoked responses
Visual field
Figure 3. Visual-evoked responses (VER) during acute optic neuritis (a) and at the re-examination (h). Visual field during acute optic neuritis (c) and at the time of the re-examination (d). Visual-evoked response latency in mseconds c.-sc. plus per. sc. = central scotoma plus peripheral scotoma.
50 45 40 35
Number of 30 patients 25 In% 20
Number 01 4 patlents
15 10
I. 0.0
3.5
10.5
-
14
17.5
21
24.5
28
31.5
35
38.5
c:..;Ft..:;rsI.:;;.;examln==atIon=.;;;• .;.;Ree=xl:::m:::;lnaI=lo:::n:....J1 Increased Length of signal
L:I
Intensity In mm
Figure 4. Length of the increased signal intensity of the optic nerve on
magnetic resonance imaging in acute optic neuritis and at the time of the re-examination.
no lesion
intraorbi1aJ
intracanal.
Localization of the lesion
intraorbi1al
intracranial
plus intracanal.
10 First examination • Reexamination I Figure 5. Localization of the increased signal intensity of the optic nerve during acute optic neuritis on magnetic resonance imaging and at the time of the re-examination.
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Volume 103, Number 11, November 1996
Discussion
50 45 40 35 30
Number of patients 25 In% 20
15 10
I0 Complete recovery
Ellncomplete recovery _ Partial recovery
Figure 6. Correlation of the length of the increased signal intensity during the first examination and visual function at the time of the re-examination.
lesions (P < 0.05). Intracanalicular lesions correlated with incomplete visual recovery (P < 0.005) and intraorbital plus intracanalicular lesions with partial visual recovery (P < 0.005) (Fig 7). Follow,up Examination Lesions smaller than 17.5 mm at the time of re-examination correlated strongly (P < 0.0005) with complete visual recovery and lesions greater than 17.5 mm with partial visual recovery (P < 0.005). In eyes with complete visual recovery at the time of the re-examination (36%), there were no lesions of the optic nerve (P < 0.005) or intraorbital lesions (P < 0.001) on MRI. Visual recovery was incomplete in patients with intracanalicular lesions at the time of the re-examination (P < 0.005) and partial in patients with intraorbital plus intracanalicular lesions (P < 0.001).
25
20
Number of 15 patients in%
10
no lesion
in1raorbi1al
in1racanal.
Localization In first examination
I0 Complete recovery
intraorbi1al plus intracanal.
Ellncomplete recovery _ Partial recovery
Figure 7. Correlation of the localization of the increased signal intensity during the first examination and visual function at the time of the reexamination.
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The first clinical trial on lesions of the optic nerve in optic neuritis using MRI with STIR sequences was presented in 1988. 6 Clinically evident optic neuritis was correlated to an increased signal intensity of the optic nerve in 84% of these patients with acute optic neuritis. The localization of the increased signal intensity was intraorbital in 61 % of the patients and intracanalicular in 34% of the patients. Visual recovery was bad or slow in 50% of the intraorbital lesions and in 73% of the intracanalicular lesions. In addition, slow or bad visual recovery was more common in long lesions of the optic nerve. 6 In 1988, we started our study with STIR sequences because at that time it was the only technique available to suppress orbital fat. 9.1l We found lesions in the optic nerve in 77% of our patients with acute optic neuritis. With other MRI techniques for orbital fat suppression, increased signal intensity currently can be detected in nearly 100% of patients with acute optic neuritis. 13 The frequency-selected saturated pulse method detects increased signal intensity of the optic nerve in Tl- and T2weighted pictures. This method also is able to show signal enhancement with the use of intravenous gadoliniumDTPA (Gd-DTPA).14 Gadolinium-DTPA enhancement is found as long as blood-brain barrier breakdown existS. 13 - 16 In old demyelinated foci in optic neuritis, the blood-brain barrier is restored and Gd-DTPA enhancement cannot be detected. 17 For re-examination we used STIR for three reasons: (1) optic nerve lesions in chronic optic neuritis do not show Gd-DTPA enhancemene 6,17; (2) frequency-selected saturated pulse or other fat suppression techniques show increased signal intensity; in optic neuritis in different percentages than STIR (results from a re-examination with frequency-selected saturated pulse could not be correlated to the results from the first examination with STIR); and (3) studies showed that STIR is still of clinical interest wherever fat suppression is required, and the results do not differ significantly from other techniques. 18 •19 Of our patients, visual field recovery occurred in 77% In the acute stage of optic neuritis, 81 % of the patients did have visual field defects. The visual field profile of the Optic Neuritis Treatment Trial 20,21 detected visual field defects in the acute stage of optic neuritis in 78.7% of the affected eyes and normal visual fields in 68.6% of the affected eyes after 1 year. The group of patients reported in the Optic Neuritis Treatment Trial is much larger than in our study, but the percentage from the first examination matches with our examination and we speculate that recovery of the visual field after 4.7 years (average) is even better than after 1 year. Results of the Optic Neuritis Treatment Trial were reported in 1992,22 shortly after all the patients had been treated with oral prednisolone. Based on results of the Optic Neuritis Treatment Trial, oral prednisolone should not be used alone in treating patients with optic neuritis. We re-emphasize that, since late 1992, patients with acute
Dunker and Wiegand . Prognostic Value of MRI optic neuritis have been treated in our clinic with megadose intravenous methylprednisolone. In our study, we showed that MRI is able to give a prognosis about the visual recovery in monosymptomatic optic neuritis: If there is no increased signal intensity of the optic nerve or if a demyelinating focus is located directly behind the globe with a length less than 17.5 mm, the prognosis for fast and complete visual recovery is excellent. If the lesions in the optic nerve are greater than 17.5 mm or if the lesions are located in the intracanalicular part of the optic nerve, the prognosis is worse. In those eyes, deficits of the visual function or even loss of visual acuity are frequent. The worst prognostic results are obtained if lesions initially are located in the intraorbital plus intracanalicular part of the optic nerve. Additionally, long lesions of the optic nerve show no tendency to diminish. Lesions in the optic nerve in the late stage of optic neuritis also are morphologically different from lesions in the acute stage. In addition, lesions and edema in the intracanalicular portion of the optic nerve lead to compression because of the surrounding bone nonelastic structures, causing irreversible damage. Thus, MRI proves to be a useful tool for diagnosis as well as prognosis in acute optic neuritis.
8. 9. 10.
11.
12. 13.
14. 15 .
References 1. Lumsden CEo The neuropathology of mUltiple sclerosis. In: Vinken PJ, Bruyn GW, eds. Handbook of Clinical Neurology. Amsterdam: North-Holland Publishing Co; New York: Wiley Interscience Division, John Wiley, 1968-(1989); 9:217-309. 2. Barnes D, McDonald WI, Landon DN, Johnson G. The characterization of experimental gliosis by quantitative nuclear resonance imaging. Brain 1988; 111 :83-94. 3. McDonald WI. Pathophysiology of conduction in central nerve fibers. In: Desmedt JE, ed. Visual Evoked Potentials in Man, New Developments: Methodology at Patterned Visual Stimulation; Neurophysiology at Visual Functions in Man; Clinical Applications. Oxford, New York: Clarendon, 1977;427-37. 4. Guy J, Ellis EA, Hope GM, Rao NA. Antioxidant enzymes reduce loss of blood-brain barrier integrity in experimental optic neuritis. Arch Ophthalmol 1989; 107:1359-63. 5. Young IR, Hall AS, Pallis CA, et al. Nuclear magnetic resonance imaging of the brain in multiple sclerosis. Lancet 1981 ;2:1063-6. 6. Runge VM, Price AC, Kirshner HS, et al. Magnetic resonance imaging of multiple sclerosis: study of pulse-technique efficacy. AJR Am J Roentgenol 1984; 143:1015-26. 7. Sheldon JJ, Siddharthan R, Tobias J, et al. MR imaging of
16.
17. 18.
19.
20.
21. 22.
multiple sclerosis: comparison with clinical and CT examinations in 74 patients. AJR Am J Roentgenol 1985; 145:957-64. Bydder GM, Steiner RE, Young IR, et al. Clinical NMR imaging of the brain: 140 cases. Am J Roentgenol 1982; 139:215-36. Miller DH, Newton MR, van der Poel JC, et al. Magnetic resonance imaging of the optic nerve in optic neuritis. Neurology 1988; 38:175-9. Wiegand W. Erkrankungen des Sehnervs. In: Naumann GOH, Merte HJ, Hollwich F, Gloor B, eds. Kernspintomographie von Auge, Orbita und Sehnerv. Biicherei des Augenarztes. Band 122. Enke Verlag 1990;104-12. Wiegand W. Kernspintomographie des Sehnervs bei Retrobulbameuritis und Optikusatrophie: Darstellung von Entziindung und Entmarkung. Ophthalmologica 1988;197:193201. Sachs L. AbhangigkeitsmaBe und Korrelation. In: Sachs L, ed. Angewandte Staisik 7. Auftage. New York, Berlin: Springer Verlag, 1992;510-5. Guy J, Mao J, Bidgood WD Jr, et al. Enhancement and demyelination of the intraorbital optic nerve. Fat suppression magnetic resonance imaging. Ophthalmology 1992; 99:713-9. Guy J, Mancuso A, Quisling RG, et al. Gadolinium-DTPAenhanced magnetic resonance imaging in optic neuropathies. Ophthalmology 1990;97:592-600. Guy J, Fitzsimmons J, Ellis EA, et al. Intraorbital optic nerve and experimental optic neuritis. Correlation of fat suppression magnetic resonance imaging and electron microscopy. Ophthalmology 1992;99:720-5. Guy J, McGorray S, Fitzsimmons J, et al. Reversals of blood-brain barrier disruption by catalase: a serial magnetic resonance imaging study of experimental optic neuritis. Invest Ophthalmol Vis Sci 1994;35:3456-65. Christianson P, Frederikson JL, Henriksen 0 , et al. GdDTP A-enhanced lesions in the brain of patients with acute optic neuritis. Acta Neurol Scand 1992; 85: 141-6. Miller DH, MacManus DG, Bartlett PA, et al. Detection of optic nerve lesions in optic neuritis using frequency selective fat-saturation sequences. Neuroradiology 1993; 35: 156-8. Mirowitz SA, Apicella P, Reinus WR, et al. MR imaging of bone marrow lesions: relative conspiciousness on Tlweighted, fat-suppressed T2-weighted, and STR images. AJR Am J Roentgenol 1994; 162:215-21. Keltner JL, Johnson CA, Spurr JO, et al. Baseline visual field profile of optic neuritis. The experience of the optic neuritis treatment trial. Arch Ophthalmol 1993; 111:2314. Keltner JL, Johnson CA, Spurr JO, et al. Visual field profile of optic neuritis. One-year follow-up trial in the optic neuritis treatment trial. Arch Ophthalmol 1994; 112:946-53 . Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med 1992;326:581-8.
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Optic neuritis is often the first manifestation of multiple sclerosis. Optic neuritis is a demyelinating disorder of the optic nerve. I - 4 Magnetic resonance imaging (MRI) can detect lesions of the brain in mUltiple sclerosis and lesions of the optic nerve in optic neuritis. Contrast-enhanced MRI can detect disruption of the blood-brain barrier that is associated with acute lesions. T2- w~ighted imaging can Originally received: September 18, 1995. Revision accepted: July 17, 1996. From the Department of Ophthalmology of the Philipps- University Marburg, Germany. Presented in part at the ARVO Annual Meeting, Ft Lauderdale, May 1995. Reprint requests to Stephan Dunker, MD, Philipps-Universitat, Medizinisches Zentrum fiir Augenheilkunde, Robert-Koch-Str. 4, 35037 Marburg, Germany.
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detect edema of acute lesions and the gliosis and demyelination of chronic lesions. s- s For imaging of the optic nerve, fat suppression is required. 9 In our MRI study, we used short-time inversion recovery sequences (STIR). With STIR, orbital fat has a low signal intensity, whereas inflammation, demyelination, and gliosis have a high signal intensity.lO,l1 We performed STIR in patients with optic neuritis to determine whether the lesions resolve after visual recovery or whether there is a change in length or localization that could be correlated to the visual function.
Materials and Methods Between 1987 and 1992, we examined 22 patients (13 women and 9 men) with acute monosymptomatic optic
Dunker and Wiegand . Prognostic Value of MRI
Results Acute Stage Initial visual acuity ranged from 20120 to less than 20/ 400. The results of visual-evoked responses and visual field are given in Figure 3. Magnetic resonance imaging depicted a lesion in the affected nerve in 77% of the patients. We classified the lesions into two subgroups regarding the length (lesions < 17.5 mm and those ~ 17.5 mm) and into three subgroups regarding the localization (intraorbital, intracanalicular, and intraorbital plus intracanalicular). In none of the patients did the prechiasmatic or chiasmatic (intracranial) part of the optic nerve show increased signal intensity of the affected nerve.
Clinical Course
Figure 1. Increased signal intensity of the right optic nerve in the acute stage of optic neuritis (September 1988) in a 21-year-old patient. Arrow = the affected optic nerve.
neuritis. Magnetic resonance imaging and clinical examinations were done within 1 to 5 days after the onset of visual loss or pain. Clinically, we examined visual acuity (Snellen charts), contrast-sensitivity (Pelly-Robson charts), color vision (Ishihara charts), visual field (static perimetry using a visual field analyzer (Ttibinger automatik perimeter, Oculus, Wetzlar, Germany), and kinetic perimetry using the Goldmann perimeter (Haag-Streit, Bern, Switzerland) were performed. Only static perimetry results and visual-evoked responses (pattern shift) are reported here. For MRI, we used a 0.5-Tesla instrument (Siemens Magnetom, Siemens, Erlangen, Germany) and STIR sequences (recovery time [TR] = 1800 mseconds; excitation time [TE] = 35 mseconds; inversion time [T] = 140 mseconds) (Fig 1). To show the whole length of the optic nerve, coronal sections from behind the globe up to the chiasm were performed. The brightening of the optic nerve was described in comparison with the contralateral optic nerve or the white matter of the brain. Every brightening of the optic nerve was judged by two independent examinators. Additionally, T2-weighted axial and coronal sections of the brain were performed. Between July 1993 and December 1994, we re-examined each patient using a 1.0-Tesla instrument (Siemens Magnetom Impact) for MRI and performing STIR sequences (TR = 2100 mseconds; TE = 20 mseconds; TI = 150 mseconds) with coronal sections (Fig 2). The age of the patients varied between 16 and 45 years (average, 31 years). The follow-up period between the first examination and the re-examination was between 2.5 and 8 years (average, 4.7 years). Table 1 shows the data of all 22 patients.
Most of the patients were treated with systemic corticosteroids starting with prednisolone equivalent (150 mg). After day 3, the dose was reduced to 120 mg prednisolone equivalent; after day 6, it was reduced to 100 mg prednisolone equivalent. Every second day after day 6, the dose was reduced by an additional 20 mg. Recovery of the visual acuity (>3 lines in the eye chart) was fast «4 weeks) in 30% of the patients and slow (4 weeks-1 year) in 60% of the patients. Two patients did not show any improvement of the visual acuity. In two patients, a relapse occurred in the same eye, and in two patients the contralateral eye was affected.
Figure 2. Same patient as in Figure 1. Increased signal intensity of the right optic nerve in the re-examination (May 1994). At that time, the patient was 26 years of age. Arrow = the affected optic nerve.
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Ophthalmology
Volume 103, Number 11, November 1996
Table l. Patient Characteristics
Case No.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 MRI
Visual Acuity in the Acute Stage
Age at Onset (yrs) Sex
<20/400 20/20 10/200 20/20 20/20 20/40 <20/400 < 20/400 10/200 20/80 <20/400 20/80 20/20 20/25 10/200 20/40 <20/400 < 20/400 20/200 < 20/400 20/200 < 20/400
37 38 45 23 25 35 28 21 28 38 28 24 32 27 26 37 30 44 16 31 23 29
F
M
F F
M M M M M
F F F F F
M M
F F F
M F
F
Date of First MRI
5/87 7/87 1/88 3/88 4/88 5/88 8/88 9/88 2/89 4/89 10/89 6/90 1/90 2/90 8/90 10/90 4/91 5/91 6/91 8/91 2/92 4/92
Time from Onset of First Visual First to Date of Length of Symptoms Initial Second MRI Lesion in Second (days) Length (yrs, mos) Examination Second MRI
3 5 3 4 5 4 3 3 3 2 1 1 2 3 1 4 1 Same day
2 2 2 1
21 0 21 10.5 0 31.5 31.5 10.5
14
0 7 7 3.5 0 10.5 21 28 21 0 14 10.5 31.5
7,4 6,11 6,3 5,3 5,4 6,4 4,10 5,8 4,8 5,6 4,7 3,2 4,10 4,8 2,11 3,7 3,6 2,10 3,2 3,3 2,10 2,8
9/94 6/94 4/94 6/93 8/93 9/94 6/93 5/94 10/93 10/94 5/94 8/93 11/94 10/94 7/93 5/94 10/94 3/94 8/94 11/94 12/94 12/94
31.5 0 21 0 17.5 38.5 21 38.5 0 17.5 7 0 3.5 0 0 28 28 21 0 14 10.5 31.5
Follow. up Visual Acuity
20/25 20/20 20/20 20/20 20/20 <20/400 20/30 20/50 20/20 20/20 20/25 20/20 20/20 20/20 20/20 20/30 20/25 20/30 20/20 20/25 20/20 20/25
Treatment Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral Oral
= magnetic resonance imaging.
Re-examination Although visual acuity in most patients was good at the time of re-examination, defects of visual function could be demonstrated in many of the eyes (Fig 3). The length and localization of the lesions in MRI are demonstrated in Figures 4 and 5. Cases 6 and 8 showed increased signal intensity of the complete optic nerve (including the intracranial part). Correlations For further evaluation, we divided the visual recovery into three groups: group 1, eyes had complete visual recovery (visual acuity in this group was better than 20/25, and there were no defects in visual field, color vision, and contrast sensitivity tests); group 2, eyes had incomplete recovery at the time of control (visual acuity was better than 20/25, but there were defects in at least one of the other tests); and group 3, eyes had partial recovery (visual acuity remained less than 20125, and there were defects in all the other tests at the time of control). We investigated the following correlations using the Spearman rank correlation coefficient I 2: 1. The length of the lesions at the time of the first examination is compared with the length at the time of the re-examination (Fig 4).
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2. The localization at the time of the first examination is compared with the localization at the time of the re-examination (Fig 5). 3. The length at the time of the first examination is correlated with the visual function at the time of the re-examination (Fig 6). 4. The localization at the time of the first examination is correlated with visual function at the time of the re-examination (Fig 7). 5. The length of the lesion in the re-examination is correlated with the visual function at the time of the re-examination. 6. The localization of the lesion in the re-examination is correlated with the visual function at the time of the re-examination. Initial Examination Acute initial lesions smaller than 17.5 mm correlated with complete visual recovery (P < 0.005). Lesions initially longer than 17.5 mm correlated with partial recovery (P < 0.005) (Fig 6). Complete visual recovery (36%) occurred in patients with no detectable lesion in the optic nerve by MRI (P < 0.005) and in patients with intraorbital
Dunker and Wiegand . Prognostic Value of MRI
LATENCY < 120 56%
LATENCY> 120 44%
First examination
First examination
goA,
C.- IC. plus per.
~~
LATENCY> 120 LATENCY < 120
Reexamination
Reexamination
Visual evoked responses
Visual field
Figure 3. Visual-evoked responses (VER) during acute optic neuritis (a) and at the re-examination (h). Visual field during acute optic neuritis (c) and at the time of the re-examination (d). Visual-evoked response latency in mseconds c.-sc. plus per. sc. = central scotoma plus peripheral scotoma.
50 45 40 35
Number of 30 patients 25 In% 20
Number 01 4 patlents
15 10
I. 0.0
3.5
10.5
-
14
17.5
21
24.5
28
31.5
35
38.5
c:..;Ft..:;rsI.:;;.;examln==atIon=.;;;• .;.;Ree=xl:::m:::;lnaI=lo:::n:....J1 Increased Length of signal
L:I
Intensity In mm
Figure 4. Length of the increased signal intensity of the optic nerve on
magnetic resonance imaging in acute optic neuritis and at the time of the re-examination.
no lesion
intraorbi1aJ
intracanal.
Localization of the lesion
intraorbi1al
intracranial
plus intracanal.
10 First examination • Reexamination I Figure 5. Localization of the increased signal intensity of the optic nerve during acute optic neuritis on magnetic resonance imaging and at the time of the re-examination.
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Ophthalmology
Volume 103, Number 11, November 1996
Discussion
50 45 40 35 30
Number of patients 25 In% 20
15 10
I0 Complete recovery
Ellncomplete recovery _ Partial recovery
Figure 6. Correlation of the length of the increased signal intensity during the first examination and visual function at the time of the re-examination.
lesions (P < 0.05). Intracanalicular lesions correlated with incomplete visual recovery (P < 0.005) and intraorbital plus intracanalicular lesions with partial visual recovery (P < 0.005) (Fig 7). Follow,up Examination Lesions smaller than 17.5 mm at the time of re-examination correlated strongly (P < 0.0005) with complete visual recovery and lesions greater than 17.5 mm with partial visual recovery (P < 0.005). In eyes with complete visual recovery at the time of the re-examination (36%), there were no lesions of the optic nerve (P < 0.005) or intraorbital lesions (P < 0.001) on MRI. Visual recovery was incomplete in patients with intracanalicular lesions at the time of the re-examination (P < 0.005) and partial in patients with intraorbital plus intracanalicular lesions (P < 0.001).
25
20
Number of 15 patients in%
10
no lesion
in1raorbi1al
in1racanal.
Localization In first examination
I0 Complete recovery
intraorbi1al plus intracanal.
Ellncomplete recovery _ Partial recovery
Figure 7. Correlation of the localization of the increased signal intensity during the first examination and visual function at the time of the reexamination.
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The first clinical trial on lesions of the optic nerve in optic neuritis using MRI with STIR sequences was presented in 1988. 6 Clinically evident optic neuritis was correlated to an increased signal intensity of the optic nerve in 84% of these patients with acute optic neuritis. The localization of the increased signal intensity was intraorbital in 61 % of the patients and intracanalicular in 34% of the patients. Visual recovery was bad or slow in 50% of the intraorbital lesions and in 73% of the intracanalicular lesions. In addition, slow or bad visual recovery was more common in long lesions of the optic nerve. 6 In 1988, we started our study with STIR sequences because at that time it was the only technique available to suppress orbital fat. 9.1l We found lesions in the optic nerve in 77% of our patients with acute optic neuritis. With other MRI techniques for orbital fat suppression, increased signal intensity currently can be detected in nearly 100% of patients with acute optic neuritis. 13 The frequency-selected saturated pulse method detects increased signal intensity of the optic nerve in Tl- and T2weighted pictures. This method also is able to show signal enhancement with the use of intravenous gadoliniumDTPA (Gd-DTPA).14 Gadolinium-DTPA enhancement is found as long as blood-brain barrier breakdown existS. 13 - 16 In old demyelinated foci in optic neuritis, the blood-brain barrier is restored and Gd-DTPA enhancement cannot be detected. 17 For re-examination we used STIR for three reasons: (1) optic nerve lesions in chronic optic neuritis do not show Gd-DTPA enhancemene 6,17; (2) frequency-selected saturated pulse or other fat suppression techniques show increased signal intensity; in optic neuritis in different percentages than STIR (results from a re-examination with frequency-selected saturated pulse could not be correlated to the results from the first examination with STIR); and (3) studies showed that STIR is still of clinical interest wherever fat suppression is required, and the results do not differ significantly from other techniques. 18 •19 Of our patients, visual field recovery occurred in 77% In the acute stage of optic neuritis, 81 % of the patients did have visual field defects. The visual field profile of the Optic Neuritis Treatment Trial 20,21 detected visual field defects in the acute stage of optic neuritis in 78.7% of the affected eyes and normal visual fields in 68.6% of the affected eyes after 1 year. The group of patients reported in the Optic Neuritis Treatment Trial is much larger than in our study, but the percentage from the first examination matches with our examination and we speculate that recovery of the visual field after 4.7 years (average) is even better than after 1 year. Results of the Optic Neuritis Treatment Trial were reported in 1992,22 shortly after all the patients had been treated with oral prednisolone. Based on results of the Optic Neuritis Treatment Trial, oral prednisolone should not be used alone in treating patients with optic neuritis. We re-emphasize that, since late 1992, patients with acute
Dunker and Wiegand . Prognostic Value of MRI optic neuritis have been treated in our clinic with megadose intravenous methylprednisolone. In our study, we showed that MRI is able to give a prognosis about the visual recovery in monosymptomatic optic neuritis: If there is no increased signal intensity of the optic nerve or if a demyelinating focus is located directly behind the globe with a length less than 17.5 mm, the prognosis for fast and complete visual recovery is excellent. If the lesions in the optic nerve are greater than 17.5 mm or if the lesions are located in the intracanalicular part of the optic nerve, the prognosis is worse. In those eyes, deficits of the visual function or even loss of visual acuity are frequent. The worst prognostic results are obtained if lesions initially are located in the intraorbital plus intracanalicular part of the optic nerve. Additionally, long lesions of the optic nerve show no tendency to diminish. Lesions in the optic nerve in the late stage of optic neuritis also are morphologically different from lesions in the acute stage. In addition, lesions and edema in the intracanalicular portion of the optic nerve lead to compression because of the surrounding bone nonelastic structures, causing irreversible damage. Thus, MRI proves to be a useful tool for diagnosis as well as prognosis in acute optic neuritis.
8. 9. 10.
11.
12. 13.
14. 15 .
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