Magnetic Resonance Imaging of Radiation Optic Neuropathy Carol F. Zimmerman, M.D., Norman J. Schatz, M.D., and Joel S. Glaser, M.D. Three patients with delayed radiation optic neuropathy after radiation therapy for parasellar neoplasms underwent magnetic resonance imaging. The affected optic nerves and chiasms showed enlargement and focal gadopentetate dimeglumine enhancement. The magnetic resonance imaging technique effectively detected and defined anterior visual pathway changes of radionecrosis and excluded the clinical possibility of visual loss because of tumor recurrence. DELAYED RADIONECROSIS of cerebral tissues is a well known but rare complication after therapeutic radiation. With the evolution of irradiation as an effective primary treatment modality and an adjunct to surgery for pituitary adenomas, parasellar tumors, and other intracranial and extracranial tumors, delayed radiation necrosis of the optic nerves and chiasm is being recognized increasingly .1-4 The compu ted tomographic and magnetic resonance characteristics of delayed cerebral radionecrosis have been well documented.P" Guy and associates" reported magnetic resonance imaging findings of the optic nerves in delayed radiation optic neuropathy. We studied the magnetic resonance imaging findings in three patients with delayed radiation optic neuropathy.
Patients and Methods All three patients were referred to the Bascom Palmer Eye Institute between November 1988
Accepted for publication July 17, 1990. From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida. This study was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc. Reprints requests to Carol F. Zimmerman, M.D., Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9057. ©AMERICAN JOURNAL OF OPHTHALMOLOGY
110:389-394,
and June 1989, with acute visual loss occurring 13 to 21 months after radiation treatment for tumors in the parasellar region. All three patients were studied within a month of the onset of visual symptoms. One patient also had magnetic resonance imaging four months before and five months after the onset of symptoms. All patients were studied with a 1.5-T superconducting magnet, using a 256.0 x 256.0-cm matrix, 3.0- or 5.0-mm thin sections, and a field of view of 16.0 to 22.0 em. Two patients were studied with a General Electric Signa unit (General Electric, Milwaukee, Wisconsin), and one was studied with a Picker International Vista unit (Picker International, Cincinnati, Ohio). Spin echo pulse sequences producing the Tj-weighted images were obtained with repetition times (TR) of 500 to 600 msec and echo times (TE) of 20 to 26 msec. Two patients had Tj-weighted views before and after intravenous gadolinium diethylenetriamine pentaacetic acid (gadopentetate dimeglumine, 0.1 mmoly'kg of body weight).
Case Reports Case 1 A 63-year-old man with a pituitary adenoma invading the cavernous sinus had diplopia, a left third-nerve palsy, and normal optic nerve and chiasma 1 function. Two months after transsphenoidal surgery, he received 5,040 cGy to the pituitary region in fractions of 180 cGy over 28 days, using a free-field arrangement. The left eye motility improved and vision remained stable until 14 months later.' when the patient noticed abrupt loss of vision in the right eye. Visual acuity was R.E.: hand motions and L.E.: 20/25. There was a right afferent pupillary defect and bitemporal depression of the visual fields, especially to a red target. The right optic disk was pale, and the left optic disk was normal. Tj-weighted magnetic resonance imaging (TR, 600 msec; TE, 26 msec) showed no eviOCTOBER,
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Fig. 1 (Zimmerman, Schatz, and Glaser). Case 1. Magnetic resonance imaging. Top left, Tj-weighted coronal view (TR, 600 msec; TE, 26 msec). Prechiasmatic optic nerves (arrows) are isointense to cerebral gray matter, and the right optic nerve (curved arrow) cannot be clearly distinguished from surrounding tissue. Top right, Optic chiasm seen on sagittal view (arrow). Bottom left, Both prechiasmatic optic nerves enhance after gadopentetate dimeglumine infusion (coronal view, arrows). Bottom right, Sagittal view demonstrates enhancement of the chiasm (arrow) with gadopentetate dimeglumine.
dence of new neoplasm compared to previous studies (Fig. 1, top). After gadopentetate dimeglumine infusion, there was distinct enhancement of the intracranial segments of both optic nerves (Fig. 1, bottom). The patient received intravenous methylprednisolone, 250 mg every six hours for three days, with no improvement in vision or visual fields. He then underwent daily hyperbaric oxygen therapy for 14 days. Two months later, visual acuity, Goldmann visual fields, and optic disks remained unchanged. Case 2 A 57-year-old man was treated for poorly differentiated squamous cell carcinoma of the nasopharynx. The mass extended to the sphenoid sinus and invaded the middle cranial fossa. He underwent a six-week course of radiation
therapy with 5,040 cGy directed to the primary tumor, neck, and posterior cervical nodes in 180-cGy fractions. Additional radiation treatment was then delivered to the primary growth for a total of 7,560 cGy. The patient had a good response to treatment, with a reduction of the tumor noted on cranial computed tomography. Twenty-one months after treatment he noticed decreased vision of the left eye. Visual acuity was 20/25 in each eye, with a left afferent pupillary defect. There was a dense superior altitudinal defect in the left eye, and a superior arcuate defect in the right eye. The right conjunctiva was injected, and slit-lamp biomicroscopy disclosed bilateral filamentary keratopathy. The right optic disk was pale and swollen, with a small hemorrhage at the inferior margin. There was slight inferotemporal pallor of the left optic disk without edema. The
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retinal vessels, maculae, and fundi were otherwise normal. Tj-weighted magnetic resonance imaging (TR, 550 msec; TE, 20 msec) of the parasellar region showed no recurrence of the tumor mass in the area of the intracranial optic nerves and optic chiasm. The intracranial prechiasmatic portion of the left optic nerve was enlarged and enhanced with gadopentetate dimeglumine (Fig. 2). The patient was treated with intravenous methylprednisolone, 250 mg every six hours for five days, and began a 20-day course of daily hyperbaric oxygen treatment. Four weeks later, visual acuity was stable at R.E.: 20/25 and L.E.: 20/20 with only slight improvement of the visual field defects. Case 3
A 72-year-old man with a large intrasellar mass underwent trans sphenoidal hypophysectomy with subtotal resection of the tumor, which was confirmed to be a chordoma. Preoperative ocular examination recorded visual acuity of R.E.: 20/200 (chronic amblyopia) and L.E.: 20/40, with a small central scotoma in the left eye consistent with pre-existing age-related macular degeneration. Postoperatively, there was a right homonymous hemianopsia, with stable central visual acuity. The patient then had radiation treatment to the sella turcica consisting of 7,000 cGy in 68 fractions, twice daily over 52 elapsed days, using a free-field technique. Visual function was stable until 16 months later, when he noted sudden painless loss of vision in the left eye. Visual acuity was R.E.: 20/200 and L.E.: no
391
light perception, with an amaurotic left pupil reaction. The right temporal field defect noted postoperatively was unchanged. The left optic disk was pale, and the right optic disk was normal. Tj-weighted magnetic resonance imaging (TR, 500 msec; TE, 20 msec) showed enlargement of the optic chiasm and adjacent intracranial left optic nerve and tract, with no evidence of recurrent tumor (Fig. 3, top right and bottom left). The patient was treated with intravenous methylprednisolone, 250 mg every six hours for three days, with no improvement of visual function. Over the next six months, visual acuity remained L.E.: no light perception. The right optic disk became pale, but the visual acuity improved slowly to R.E.: 20/80, considered to be spontaneous improvement of an amblyopic eye. Follow-up magnetic resonance imaging obtained four months after the onset of symptoms showed marked reduction in the size of the chiasm, left optic nerve, and tract, with no evidence of recurrent tumor (Fig. 3, bottom right).
Discussion Late radionecrosis of neuronal structures is a rare but well-documented complication of radiation treatment for intracranial tumors, as well as some tumors of the head and neck. 2•4•IO White matter and hypothalamus appear to have lower tolerance to the effects of ionizing radiation than other cerebral tissues. I The clinical syn-
Fig. 2 (Zimmerman, Schatz and Glaser). Case 2. Magnetic resonance imaging. Left, Tj-weighted axial view (TR, 550 msec; TE, 20 msec). Right, Coronal view after gadopentetate dimeglumine infusion shows enhancement of the left prechiasmatic optic nerve (arrows).
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Fig. 3 (Zimmerman, Schatz, and Glaser). Case 3. Magnetic resonance imaging. Top left, Tj-weighted sagittal view (TR, 500 msec; TE, 20 msec) before acute onset of visual loss shows normal size of the optic chiasm (arrow). Top right, One month after onset of symptoms, sagittal view shows enlargement of the left optic nerve and chiasm (arrow). Bottom left, Coronal view shows enlarged optic chiasm, greater on the left (arrow) during acute phase. Bottom right, Coronal view four months later demonstrates reduction of the optic chiasm (arrow). Previous lacunar infarction is seen in the right temporal lobe (arrowhead). drome of radiation optic neuropathy, a subset of cerebral radionecrosis, is characteristic. Acute visual loss in one or both eyes occurs as early as six months to as late as three years after radiation treatment for a para sellar neoplasm, but the eight- to 13-month interval encompasses two thirds of all cases.' The visual loss may be profound, and although chiasmal visual field defects are reported, nerve fiber bundle defects are more typical. The optic disks are usually normal initially unless pre-existing compressive neuropathy has caused optic disk pallor, but disk edema has been noted." The disks then become pale within six to eight weeks after the onset of symptoms. Although it is most frequently seen after radiation treatment for pituitary adenomas, radiation optic neuropathy has also been reported after radiation treatment for clivus meningiomas, craniopharyngiomas,
metastatic breast carcinoma, opticohypothalamic glioma, malignant tumors of the maxillary and paranasal sinuses, and other neoplasms.':' The exact pathophysiologic mechanism of delayed radiation optic neuropathy is unclear. Most studies suggest a vascular cause with radiation-induced capillary endothelial damage and ischemic demyelinization, proliferation of glial elements, and microvascular occlusion with vasogenic edema. lO•ll An autoimmune mechanism has also been proposed." Risk factors for radiation damage include radiation doses greater than 4,800 cGy, a fractional dosage of greater than 200 cGy, timedose fractionation factor above 80, overlapping treatment fields, age younger than 12 years, and adjunctive chemotherapy.2.U:l.14 Hypertension has been shown to increase risk in animal
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models," although the role of hypertension or other systemic disorders that predispose to vasculopathy in humans is not well characterized. The diagnosis of radiation optic neuropathy is one of exclusion, and neurodiagnostic examination is mandatory to rule out other causes of postsurgical and postradiation visual loss, including recurrence of the primary tumor, occurrence of a radiation-induced second neoplasm, empty sella turcica syndrome with prolapse of the chiasm, or peri chiasmatic arachnoid adhesions. The computed tomographic and magnetic resonance changes in radiation-induced white matter injury have been studied extensively. Computed tomographic abnormalities include areas of decreased attenuation, with or without mass effect, with minimal contrast enhancement." Atrophy and frank necrosis may be seen. Magnetic resonance imaging findingsr" include edema, demyelinization, and tissue necrosis within the white matter, with prolongation of the Te and Tz-relaxation times of the involved structures. The lesions are seen as areas of decreased signal intensity on Tj-weighted studies and increased signal on Tz-weighted studies. These changes appear as well-demarcated areas with scalloped margins in the periventricular white matter and to a lesser extent in the subcortical white matter, with relative sparing of the adjacent cerebral cortex. Most series are composed of patients who received whole brain radiation, and recent studies have shown that magnetic resonance imaging is clearly more sensitive than computed tomography in detecting the white matter lesions that occur after whole brain radiation.v" In our Case 3, serial postoperative magnetic resonance studies had demonstrated normal optic nerves and chiasm, but with the onset of acute visual symptoms repeat magnetic resonance imaging showed enlargement of the intracranial left optic nerve and optic chiasm. These changes are probably caused by edema. Although Tz-weighted studies are more sensitive for detecting edema, such changes in the optic nerves or chiasm will be obscured by the intense white image of the surrounding cerebrospinal fluid. Gadopentetate dimeglumineenhanced magnetic resonance imaging was not performed. Five months later the left optic nerve and chiasm appeared shrunken, and no recurrent tumor or distortion of the perichiasmatic structures was identified. Gadopentetate dimeglumine is an intravenous paramagnetic contrast agent that shortens proton relaxation times to increase the radio
393
frequency signal in areas of breakdown of the blood-brain barrier or in abnormal vascular structures. Gadopentetate dimeglumine has been proven to be helpful in detecting the changes of acute inflammation in optic neuritis." 16-18 Gadopentetate dimeglumine enhancement of the intracranial optic nerves has been described in two patients with radiation-induced optic neuropathy." Our Cases 1 and 2 showed marked gadopentetate dimeglumine enhancement of the intracranial optic nerve on the side of the visual loss. In Case 2, there was enhancement of the intracranial optic nerve up to the chiasm on the affected side. The temporal visual field of the fellow eye was suppressed, consistent with chiasmal involvement. In both patients it is likely that gadopentetate dimeglumine partially defined areas of increased permeability of blood-brain barriers, consistent with inflammation, ischemic injury, or both. Although magnetic resonance imaging is undoubtedly more sensitive in demonstrating radiation damage that might be missed by computed tomography, when imaging residual or recurrent tumors neither technique is foolproof in distinguishing the precise mechanism of visual loss by radiologic criteria alone." Recent studies using positron emission tomography with 18- Fvdeoxyglucose" have demonstrated focal hypermetabolism in areas of known residual or recurrent tumor, and focal hypometabolism in areas of tumor necrosis. In these instances, the role of gadopentetate dimeglumine-enhanced magnetic resonance imaging has not been clearly established. Magnetic resonance imaging is becoming the preferred method of imaging the chiasm and parasellar structures. Magnetic resonance imaging is especially sensitive to changes in the water content of neural tissues and, thus, has unique soft tissue differentiation capabilities. In our patients, magnetic resonance imaging was useful in demonstrating irradiation-induced lesions of the optic nerve and chiasm, while simultaneously providing excellent anatomic detail of the parasellar area to rule out recurrent tumor or other alterations of parasellar structures.
References 1. Schatz, N. J., Lichtenstein,S., and Corbett, J. ].: Delayed radiation necrosis of the optic nerves and chiasm. In Glaser, J. 5., and Smith, J. L. (eds.): Neuro-Ophthalmology. Symposium of the Universi-
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ty of Miami and the Bascom Palmer Eye Institute. St. Louis, C. V. Mosby, 1975, pp. 131-139. 2. Kline, L. B., Kim, J. Y., and Ceballos, R.: Radiation optic neuropathy. Ophthalmology 92: 1118, 1985. 3. Warman, R., Glaser, J. 5., and Quencer, R. M.: Radionecrosis of optico-hypothalamic glioma. Neuro-ophthalmol. 9:219, 1989. 4. Roden, D., Bosley, T. M., Fowble, B., Clark, J., Savino, P. J., Sergott, R. c.. and Schatz, N. J.: Delayed radiation injury to the retrobulbar optic nerves and chiasm. Clinical syndrome and treatment with hyperbaric oxygen and corticosteroids. Ophthalmology 97:346,1990. 5. Constine, L. 5., Konski, A., Ekholm,S., McDonald,S., and Rubin, P.: Adverse effects of brain irradiation correlated with MR and CT imaging. J. Radiat. Oncol. BioI. Phys. 15:319, 1988. 6. Packer, R. J., Zimmerman, R. A., and Bilaniuk, L. T.: Magnetic resonance imaging in the evaluation of treatment related central nervous system damage. Cancer 58:635,1986. 7. Tsuruda, J. 5., Kortman, K. E., Bradley, W. G., Wheeler, D. c., Van Dalsern, W., and Bradley, T. P.: Radiation effects on cerebral white matter. MR evaluation. AJR 149:165, 1987. 8. Dooms, G. c., Hecht,S., Brant-Zawadzki, M., Berthiaume, Y., Norman, D., and Newton, T. H.: Brain radiation lesions. MR imaging. Radiology 158:149,1986. 9. Guy, J., Mancusco, A., Quisling, R. G., Beck, R., and Moster, M. L.: Gadolinium enhanced magnetic resonance imaging in optic neuropathies. Ophthalmology 97:592, 1990. 10. Rottenberg, D. A., Chernick, N. L., Deck, M. D. F., Ellis, F., and Posner, J. B.: Cerebral necrosis
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following radiotherapy of extracranial neoplasms. Ann. Neurol. 1:339, 1977. 11. Caveness, W. F.: Experimental observations. Delayed necrosis in normal monkey brain. In Gilbert, H. A., and Kagan, A. R. (eds.): Radiation Damage to the Nervous System. New York, Raven Press, 1980, pp. 1-38. 12. Crompton, M. R., and Layton, D. D.: Delayed radionecrosis of the brain following therapeutic xradiation of the pituitary. Brain 84:85,1961. 13. Aristizabal, 5., Caldwell, W. L., and Avila, J.: The relationship of time-dose fractionation factors to complications in the treatment of pituitary tumors by irradiation. J. Radiat. On col. BioI. Phys. 2:667, 1977. 14. Di Chiro, G., Oldfield, E., Wright, D. c.. De Michele, D., Katz, D. A., Patronas, N. J., Dopprnan. J. L., Larson, S. M., Ito, M., and Kufta, C. V.: Cerebral necrosis after radiotherapy and/or intraarterial chemotherapy for brain tumors. PET and neuropathologic studies. AJNR 8:1083, 1987. 15. Hopewell, J. W., and Wright, E. A.: The nature of latent cerebral irradiation damage and its modification by hypertension. Br. J. Radiol. 47:157, 1974. 16. Guy, J., Fitzsimmons, J., Ellis, E. A., and Mancusco, A.: Gadolinium-DTPA enhanced magnetic resonance imaging in experimental optic neuritis. Ophthalmology 97:601,1990. 17. Miller, D. H., Newton, M. R., van der Poel, J. c.. du Boulay, E. P. G. H., Halliday, A. M., Kendall, B. E., Johnson, G., MacManus, D. G., Moseley, I. F., and McDonald, W. I.: Magnetic resonance imaging of the optic nerve in optic neuritis. Neurology 38:175,1988. 18. Beck, R.: MRI in optic neuritis (letter to the editor). Arch. Ophthalmol. 107:789, 1989.
OPHTHALMIC MINIATURE
"We see asquint, like those whose twisted sight can make out only the far-off," he said, "for the King of All still grants us that much light .... r r Dante Alghieri, The Inferno, translated by John Ciardi New York, New American Library, p. 99
Patients and Methods All three patients were referred to the Bascom Palmer Eye Institute between November 1988
Accepted for publication July 17, 1990. From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida. This study was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc. Reprints requests to Carol F. Zimmerman, M.D., Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9057. ©AMERICAN JOURNAL OF OPHTHALMOLOGY
110:389-394,
and June 1989, with acute visual loss occurring 13 to 21 months after radiation treatment for tumors in the parasellar region. All three patients were studied within a month of the onset of visual symptoms. One patient also had magnetic resonance imaging four months before and five months after the onset of symptoms. All patients were studied with a 1.5-T superconducting magnet, using a 256.0 x 256.0-cm matrix, 3.0- or 5.0-mm thin sections, and a field of view of 16.0 to 22.0 em. Two patients were studied with a General Electric Signa unit (General Electric, Milwaukee, Wisconsin), and one was studied with a Picker International Vista unit (Picker International, Cincinnati, Ohio). Spin echo pulse sequences producing the Tj-weighted images were obtained with repetition times (TR) of 500 to 600 msec and echo times (TE) of 20 to 26 msec. Two patients had Tj-weighted views before and after intravenous gadolinium diethylenetriamine pentaacetic acid (gadopentetate dimeglumine, 0.1 mmoly'kg of body weight).
Case Reports Case 1 A 63-year-old man with a pituitary adenoma invading the cavernous sinus had diplopia, a left third-nerve palsy, and normal optic nerve and chiasma 1 function. Two months after transsphenoidal surgery, he received 5,040 cGy to the pituitary region in fractions of 180 cGy over 28 days, using a free-field arrangement. The left eye motility improved and vision remained stable until 14 months later.' when the patient noticed abrupt loss of vision in the right eye. Visual acuity was R.E.: hand motions and L.E.: 20/25. There was a right afferent pupillary defect and bitemporal depression of the visual fields, especially to a red target. The right optic disk was pale, and the left optic disk was normal. Tj-weighted magnetic resonance imaging (TR, 600 msec; TE, 26 msec) showed no eviOCTOBER,
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Fig. 1 (Zimmerman, Schatz, and Glaser). Case 1. Magnetic resonance imaging. Top left, Tj-weighted coronal view (TR, 600 msec; TE, 26 msec). Prechiasmatic optic nerves (arrows) are isointense to cerebral gray matter, and the right optic nerve (curved arrow) cannot be clearly distinguished from surrounding tissue. Top right, Optic chiasm seen on sagittal view (arrow). Bottom left, Both prechiasmatic optic nerves enhance after gadopentetate dimeglumine infusion (coronal view, arrows). Bottom right, Sagittal view demonstrates enhancement of the chiasm (arrow) with gadopentetate dimeglumine.
dence of new neoplasm compared to previous studies (Fig. 1, top). After gadopentetate dimeglumine infusion, there was distinct enhancement of the intracranial segments of both optic nerves (Fig. 1, bottom). The patient received intravenous methylprednisolone, 250 mg every six hours for three days, with no improvement in vision or visual fields. He then underwent daily hyperbaric oxygen therapy for 14 days. Two months later, visual acuity, Goldmann visual fields, and optic disks remained unchanged. Case 2 A 57-year-old man was treated for poorly differentiated squamous cell carcinoma of the nasopharynx. The mass extended to the sphenoid sinus and invaded the middle cranial fossa. He underwent a six-week course of radiation
therapy with 5,040 cGy directed to the primary tumor, neck, and posterior cervical nodes in 180-cGy fractions. Additional radiation treatment was then delivered to the primary growth for a total of 7,560 cGy. The patient had a good response to treatment, with a reduction of the tumor noted on cranial computed tomography. Twenty-one months after treatment he noticed decreased vision of the left eye. Visual acuity was 20/25 in each eye, with a left afferent pupillary defect. There was a dense superior altitudinal defect in the left eye, and a superior arcuate defect in the right eye. The right conjunctiva was injected, and slit-lamp biomicroscopy disclosed bilateral filamentary keratopathy. The right optic disk was pale and swollen, with a small hemorrhage at the inferior margin. There was slight inferotemporal pallor of the left optic disk without edema. The
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retinal vessels, maculae, and fundi were otherwise normal. Tj-weighted magnetic resonance imaging (TR, 550 msec; TE, 20 msec) of the parasellar region showed no recurrence of the tumor mass in the area of the intracranial optic nerves and optic chiasm. The intracranial prechiasmatic portion of the left optic nerve was enlarged and enhanced with gadopentetate dimeglumine (Fig. 2). The patient was treated with intravenous methylprednisolone, 250 mg every six hours for five days, and began a 20-day course of daily hyperbaric oxygen treatment. Four weeks later, visual acuity was stable at R.E.: 20/25 and L.E.: 20/20 with only slight improvement of the visual field defects. Case 3
A 72-year-old man with a large intrasellar mass underwent trans sphenoidal hypophysectomy with subtotal resection of the tumor, which was confirmed to be a chordoma. Preoperative ocular examination recorded visual acuity of R.E.: 20/200 (chronic amblyopia) and L.E.: 20/40, with a small central scotoma in the left eye consistent with pre-existing age-related macular degeneration. Postoperatively, there was a right homonymous hemianopsia, with stable central visual acuity. The patient then had radiation treatment to the sella turcica consisting of 7,000 cGy in 68 fractions, twice daily over 52 elapsed days, using a free-field technique. Visual function was stable until 16 months later, when he noted sudden painless loss of vision in the left eye. Visual acuity was R.E.: 20/200 and L.E.: no
391
light perception, with an amaurotic left pupil reaction. The right temporal field defect noted postoperatively was unchanged. The left optic disk was pale, and the right optic disk was normal. Tj-weighted magnetic resonance imaging (TR, 500 msec; TE, 20 msec) showed enlargement of the optic chiasm and adjacent intracranial left optic nerve and tract, with no evidence of recurrent tumor (Fig. 3, top right and bottom left). The patient was treated with intravenous methylprednisolone, 250 mg every six hours for three days, with no improvement of visual function. Over the next six months, visual acuity remained L.E.: no light perception. The right optic disk became pale, but the visual acuity improved slowly to R.E.: 20/80, considered to be spontaneous improvement of an amblyopic eye. Follow-up magnetic resonance imaging obtained four months after the onset of symptoms showed marked reduction in the size of the chiasm, left optic nerve, and tract, with no evidence of recurrent tumor (Fig. 3, bottom right).
Discussion Late radionecrosis of neuronal structures is a rare but well-documented complication of radiation treatment for intracranial tumors, as well as some tumors of the head and neck. 2•4•IO White matter and hypothalamus appear to have lower tolerance to the effects of ionizing radiation than other cerebral tissues. I The clinical syn-
Fig. 2 (Zimmerman, Schatz and Glaser). Case 2. Magnetic resonance imaging. Left, Tj-weighted axial view (TR, 550 msec; TE, 20 msec). Right, Coronal view after gadopentetate dimeglumine infusion shows enhancement of the left prechiasmatic optic nerve (arrows).
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Fig. 3 (Zimmerman, Schatz, and Glaser). Case 3. Magnetic resonance imaging. Top left, Tj-weighted sagittal view (TR, 500 msec; TE, 20 msec) before acute onset of visual loss shows normal size of the optic chiasm (arrow). Top right, One month after onset of symptoms, sagittal view shows enlargement of the left optic nerve and chiasm (arrow). Bottom left, Coronal view shows enlarged optic chiasm, greater on the left (arrow) during acute phase. Bottom right, Coronal view four months later demonstrates reduction of the optic chiasm (arrow). Previous lacunar infarction is seen in the right temporal lobe (arrowhead). drome of radiation optic neuropathy, a subset of cerebral radionecrosis, is characteristic. Acute visual loss in one or both eyes occurs as early as six months to as late as three years after radiation treatment for a para sellar neoplasm, but the eight- to 13-month interval encompasses two thirds of all cases.' The visual loss may be profound, and although chiasmal visual field defects are reported, nerve fiber bundle defects are more typical. The optic disks are usually normal initially unless pre-existing compressive neuropathy has caused optic disk pallor, but disk edema has been noted." The disks then become pale within six to eight weeks after the onset of symptoms. Although it is most frequently seen after radiation treatment for pituitary adenomas, radiation optic neuropathy has also been reported after radiation treatment for clivus meningiomas, craniopharyngiomas,
metastatic breast carcinoma, opticohypothalamic glioma, malignant tumors of the maxillary and paranasal sinuses, and other neoplasms.':' The exact pathophysiologic mechanism of delayed radiation optic neuropathy is unclear. Most studies suggest a vascular cause with radiation-induced capillary endothelial damage and ischemic demyelinization, proliferation of glial elements, and microvascular occlusion with vasogenic edema. lO•ll An autoimmune mechanism has also been proposed." Risk factors for radiation damage include radiation doses greater than 4,800 cGy, a fractional dosage of greater than 200 cGy, timedose fractionation factor above 80, overlapping treatment fields, age younger than 12 years, and adjunctive chemotherapy.2.U:l.14 Hypertension has been shown to increase risk in animal
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models," although the role of hypertension or other systemic disorders that predispose to vasculopathy in humans is not well characterized. The diagnosis of radiation optic neuropathy is one of exclusion, and neurodiagnostic examination is mandatory to rule out other causes of postsurgical and postradiation visual loss, including recurrence of the primary tumor, occurrence of a radiation-induced second neoplasm, empty sella turcica syndrome with prolapse of the chiasm, or peri chiasmatic arachnoid adhesions. The computed tomographic and magnetic resonance changes in radiation-induced white matter injury have been studied extensively. Computed tomographic abnormalities include areas of decreased attenuation, with or without mass effect, with minimal contrast enhancement." Atrophy and frank necrosis may be seen. Magnetic resonance imaging findingsr" include edema, demyelinization, and tissue necrosis within the white matter, with prolongation of the Te and Tz-relaxation times of the involved structures. The lesions are seen as areas of decreased signal intensity on Tj-weighted studies and increased signal on Tz-weighted studies. These changes appear as well-demarcated areas with scalloped margins in the periventricular white matter and to a lesser extent in the subcortical white matter, with relative sparing of the adjacent cerebral cortex. Most series are composed of patients who received whole brain radiation, and recent studies have shown that magnetic resonance imaging is clearly more sensitive than computed tomography in detecting the white matter lesions that occur after whole brain radiation.v" In our Case 3, serial postoperative magnetic resonance studies had demonstrated normal optic nerves and chiasm, but with the onset of acute visual symptoms repeat magnetic resonance imaging showed enlargement of the intracranial left optic nerve and optic chiasm. These changes are probably caused by edema. Although Tz-weighted studies are more sensitive for detecting edema, such changes in the optic nerves or chiasm will be obscured by the intense white image of the surrounding cerebrospinal fluid. Gadopentetate dimeglumineenhanced magnetic resonance imaging was not performed. Five months later the left optic nerve and chiasm appeared shrunken, and no recurrent tumor or distortion of the perichiasmatic structures was identified. Gadopentetate dimeglumine is an intravenous paramagnetic contrast agent that shortens proton relaxation times to increase the radio
393
frequency signal in areas of breakdown of the blood-brain barrier or in abnormal vascular structures. Gadopentetate dimeglumine has been proven to be helpful in detecting the changes of acute inflammation in optic neuritis." 16-18 Gadopentetate dimeglumine enhancement of the intracranial optic nerves has been described in two patients with radiation-induced optic neuropathy." Our Cases 1 and 2 showed marked gadopentetate dimeglumine enhancement of the intracranial optic nerve on the side of the visual loss. In Case 2, there was enhancement of the intracranial optic nerve up to the chiasm on the affected side. The temporal visual field of the fellow eye was suppressed, consistent with chiasmal involvement. In both patients it is likely that gadopentetate dimeglumine partially defined areas of increased permeability of blood-brain barriers, consistent with inflammation, ischemic injury, or both. Although magnetic resonance imaging is undoubtedly more sensitive in demonstrating radiation damage that might be missed by computed tomography, when imaging residual or recurrent tumors neither technique is foolproof in distinguishing the precise mechanism of visual loss by radiologic criteria alone." Recent studies using positron emission tomography with 18- Fvdeoxyglucose" have demonstrated focal hypermetabolism in areas of known residual or recurrent tumor, and focal hypometabolism in areas of tumor necrosis. In these instances, the role of gadopentetate dimeglumine-enhanced magnetic resonance imaging has not been clearly established. Magnetic resonance imaging is becoming the preferred method of imaging the chiasm and parasellar structures. Magnetic resonance imaging is especially sensitive to changes in the water content of neural tissues and, thus, has unique soft tissue differentiation capabilities. In our patients, magnetic resonance imaging was useful in demonstrating irradiation-induced lesions of the optic nerve and chiasm, while simultaneously providing excellent anatomic detail of the parasellar area to rule out recurrent tumor or other alterations of parasellar structures.
References 1. Schatz, N. J., Lichtenstein,S., and Corbett, J. ].: Delayed radiation necrosis of the optic nerves and chiasm. In Glaser, J. 5., and Smith, J. L. (eds.): Neuro-Ophthalmology. Symposium of the Universi-
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ty of Miami and the Bascom Palmer Eye Institute. St. Louis, C. V. Mosby, 1975, pp. 131-139. 2. Kline, L. B., Kim, J. Y., and Ceballos, R.: Radiation optic neuropathy. Ophthalmology 92: 1118, 1985. 3. Warman, R., Glaser, J. 5., and Quencer, R. M.: Radionecrosis of optico-hypothalamic glioma. Neuro-ophthalmol. 9:219, 1989. 4. Roden, D., Bosley, T. M., Fowble, B., Clark, J., Savino, P. J., Sergott, R. c.. and Schatz, N. J.: Delayed radiation injury to the retrobulbar optic nerves and chiasm. Clinical syndrome and treatment with hyperbaric oxygen and corticosteroids. Ophthalmology 97:346,1990. 5. Constine, L. 5., Konski, A., Ekholm,S., McDonald,S., and Rubin, P.: Adverse effects of brain irradiation correlated with MR and CT imaging. J. Radiat. Oncol. BioI. Phys. 15:319, 1988. 6. Packer, R. J., Zimmerman, R. A., and Bilaniuk, L. T.: Magnetic resonance imaging in the evaluation of treatment related central nervous system damage. Cancer 58:635,1986. 7. Tsuruda, J. 5., Kortman, K. E., Bradley, W. G., Wheeler, D. c., Van Dalsern, W., and Bradley, T. P.: Radiation effects on cerebral white matter. MR evaluation. AJR 149:165, 1987. 8. Dooms, G. c., Hecht,S., Brant-Zawadzki, M., Berthiaume, Y., Norman, D., and Newton, T. H.: Brain radiation lesions. MR imaging. Radiology 158:149,1986. 9. Guy, J., Mancusco, A., Quisling, R. G., Beck, R., and Moster, M. L.: Gadolinium enhanced magnetic resonance imaging in optic neuropathies. Ophthalmology 97:592, 1990. 10. Rottenberg, D. A., Chernick, N. L., Deck, M. D. F., Ellis, F., and Posner, J. B.: Cerebral necrosis
October, 1990
following radiotherapy of extracranial neoplasms. Ann. Neurol. 1:339, 1977. 11. Caveness, W. F.: Experimental observations. Delayed necrosis in normal monkey brain. In Gilbert, H. A., and Kagan, A. R. (eds.): Radiation Damage to the Nervous System. New York, Raven Press, 1980, pp. 1-38. 12. Crompton, M. R., and Layton, D. D.: Delayed radionecrosis of the brain following therapeutic xradiation of the pituitary. Brain 84:85,1961. 13. Aristizabal, 5., Caldwell, W. L., and Avila, J.: The relationship of time-dose fractionation factors to complications in the treatment of pituitary tumors by irradiation. J. Radiat. On col. BioI. Phys. 2:667, 1977. 14. Di Chiro, G., Oldfield, E., Wright, D. c.. De Michele, D., Katz, D. A., Patronas, N. J., Dopprnan. J. L., Larson, S. M., Ito, M., and Kufta, C. V.: Cerebral necrosis after radiotherapy and/or intraarterial chemotherapy for brain tumors. PET and neuropathologic studies. AJNR 8:1083, 1987. 15. Hopewell, J. W., and Wright, E. A.: The nature of latent cerebral irradiation damage and its modification by hypertension. Br. J. Radiol. 47:157, 1974. 16. Guy, J., Fitzsimmons, J., Ellis, E. A., and Mancusco, A.: Gadolinium-DTPA enhanced magnetic resonance imaging in experimental optic neuritis. Ophthalmology 97:601,1990. 17. Miller, D. H., Newton, M. R., van der Poel, J. c.. du Boulay, E. P. G. H., Halliday, A. M., Kendall, B. E., Johnson, G., MacManus, D. G., Moseley, I. F., and McDonald, W. I.: Magnetic resonance imaging of the optic nerve in optic neuritis. Neurology 38:175,1988. 18. Beck, R.: MRI in optic neuritis (letter to the editor). Arch. Ophthalmol. 107:789, 1989.
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"We see asquint, like those whose twisted sight can make out only the far-off," he said, "for the King of All still grants us that much light .... r r Dante Alghieri, The Inferno, translated by John Ciardi New York, New American Library, p. 99
