Clinical/Scientific Notes
Nicolae Sanda, MD Francoise Heran, MD Nicolas Daly-Schveitzer, MD, PhD Jose-Alain Sahel, MD, PhD Avinoam Bezalel Safran, MD
INCREASED OPTIC NERVE RADIOSENSITIVITY FOLLOWING OPTIC NEURITIS
Radiation-induced optic neuropathy (RION) is a late complication of radiotherapy, resulting in severe visual loss.1 We report a RION case following radiation therapy delivered at a dose widely considered as innocuous, occurring on a background of previous isolated optic neuritis. Increased brain sensitivity to radiation has been observed in patients with multiple sclerosis (MS),2–4 but we are not aware of previously reported cases solely involving the optic nerves (ONs). This aspect deserves consideration when defining therapeutic strategies. Case report. A 69-year-old woman with medical history of bilateral sequential optic neuritis 22 and 12 years previously in the right eye (RE) and left eye (LE), respectively, presented with progressive bilateral visual loss. Her visual acuity (VA) before visual loss was 0.7 in the RE and 0.8 in the LE. MS diagnosis based on 2010 McDonald criteria was ruled out by clinical course and multiple MRIs. Two years before presentation, a left maxillary sinus cystic adenoid carcinoma was diagnosed (T4aN0M0) and treated by surgery and external 6 MV fractioned radiotherapy. The right ON received an average dose of 19.9 Gy, while the left ON received an average dose of 53 Gy. Total dose per daily fraction was ,0.2 Gy. The patient noted progressive painless bilateral visual loss evolving over 4 months, starting 12 months after completion of the radiotherapy, and decided to consult. VA was 0.1 in the RE and 0.5 in the LE. Relative afferent pupillary defect and optic disc pallor were noted in the RE and a significant corticonuclear cataract in the LE. RE visual field was constricted and in addition showed a markedly reduced sensitivity in the central area. LE presented a diffuse reduction in sensitivity that was attributed to cataract (Humphrey perimetry mean deviation 23.34 dB P , 2%, pattern SD 1.53 dB). MRI performed to explore the anterior visual pathway showed T2 hyperintensity and postgadolinium T1 enhancement of the intracranial part of the right ON and of the right half of the chiasm (figure). In addition, nonspecific hyperintense T2 white matter lesions were noted. They were identical to those noted on successive MRI performed after the first episode of inflammatory optic neuropathy.
1474
Neurology 82
April 22, 2014
Careful analysis of the images ruled out local or distant recurrence of the maxillary tumor. CSF showed no oligoclonal immunoglobulin G (IgG) bands, elevated IgG index, or carcinomatous cell. Erythrocyte sedimentation rate, C-reactive protein, angiotensin-converting enzyme, as well as whole-body scan were unremarkable. Except for LE phacoemulsification that was refused by the patient, attending physicians advised no treatment and attentive follow-up was organized. RE VA progressed to light perception over an 8-month period, while LE VA stabilized at 0.4. Discussion. The vision loss in this case started 12 months after the radiotherapy and was produced by optic neuropathy in the RE and cataract in the LE. However, minimal optic neuropathy in the LE could not be excluded. The lavish localized contrast enhancement of the intracranial part of the right ON was highly suggestive of RION. Infiltrative, inflammatory, and tumoral etiologies were considered, although no clinical findings favored such hypotheses. The severity of the visual loss, its irreversible course, the timing between the radiation exposure and symptom onset, and major and stable MRI enhancement strongly supported the diagnosis of RION. Applied radiation, however, was much below doses considered potentially neurotoxic. Total doses of 50–63 Gy are reportedly associated with a 5% risk of RION occurrence at 5 years, while doses less than 50 Gy are considered to encompass a negligible risk.1,4 Fraction doses higher than 1.8–2 Gy are also associated with increased risk.1,5 Nevertheless, low doses of radiation may affect cell-to-cell communication mechanisms or tissue-level homeostatic processes.6 It is probable that the unexpected radiosensitivity of the patient’s ON was due to former episodes of optic neuritis, as several studies have demonstrated that patients with MS1–4 or compressive optic neuropathy1,7 show a lower threshold for radiation-induced neurotoxicity. It is conceivable that the damage of the ONs following demyelination was more extensive on the right than on the left ON, thus explaining the particular radiosensitivity of this structure. This suggestion is supported by the VA values, slightly worse in the RE than in the LE 3 months prior to radiation therapy. Data concerning the severity of visual impairment at the time of previous optic neuritis episodes were unavailable.
Figure
Dose distribution plan and MRI
Increased ON radiosensitivity following inflammatory disorders1,4 deserves a particular consideration and warrants more precise determination of radiation values potentially deleterious in such conditions. From the Institut de la Vision/Université Pierre et Marie Curie (N.S., J.-A.S., A.B.S.); CHNO des Quinze-Vingts (N.S., J.-A.S., A.B.S.), Paris; Foch Hospital (N.S.), Suresnes; Fondation Ophtalmologique Adolphe de Rothschild (F.H.), Paris; Institut Gustave Roussy (N.D.-S.), Villejuif, France; and Geneva University School of Medicine (A.B.S.), Switzerland. Author contributions: N. Sanda: drafting/revising the manuscript for content, including medical writing for content; study concept or design; acquisition, analysis or interpretation of data. F. Heran: drafting/revising the manuscript for content, including medical writing for content; analysis or interpretation of data. N. Daly-Schveitzer: analysis or interpretation of data. J.A. Sahel: drafting/revising the manuscript for content, including medical writing for content. A.B. Safran: critical revision of the manuscript for important intellectual content, study concept, acquisition and interpretation of data. Study funding: No targeted funding reported. Disclosure: The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures. Received August 7, 2013. Accepted in final form January 8, 2014. Correspondence to Dr. Sanda: [email protected] © 2014 American Academy of Neurology 1. 2.
3.
4.
5. (A) Dose distribution plan: right optic nerve (ON) average dose 19.9 Gy (median 19.1 Gy, minimal 9.6 Gy, maximal 53.8 Gy for a 0.1 cm3 volume); left ON average dose 53 Gy (median 59.2 Gy, minimal 21.4 Gy, maximal 67.5 Gy for a 0.2 cm3 volume). Initial MRI (B, C, D): the intracranial right ON segment and the right half of the optic chiasm (arrows) show enlargement, lavish T1 gadolinium enhancement (B, C), and T2 hyperintensity. Follow-up MRI (E, F) 3 months later shows (arrows) atrophy of the right ON and the right part of the optic chiasm (E, F), reduced but persistent gadolinium enhancement (E), and moderate T2 hyperintensity (F). Strong initial gadolinium enhancement of an enlarged ON and its remote persistence (for months) coupled with subsequent optic atrophy are in the appropriate clinical context, highly suggestive of radiation-induced optic neuropathy.
6.
7.
Danesh-Meyer HV. Radiation-induced optic neuropathy. J Clin Neurosci 2008;15:95–100. Miller RC, Lachance DH, Lucchinetti CF, et al. Multiple sclerosis, brain radiotherapy, and risk of neurotoxicity: the Mayo Clinic experience. Int J Radiat Oncol Biol Phys 2006;66:1178–1186. Peterson K, Rosenblum MK, Powers JM, Alvord E, Walker RW, Posner JB. Effect of brain irradiation on demyelinating lesions. Neurology 1993;43:2105–2112. Daniels TB, Pollock BE, Miller RC, Lucchinetti CF, Leavitt JA, Brown PD. Radiation-induced optic neuritis after pituitary adenoma radiosurgery in a patient with multiple sclerosis: case report. J Neurooncol 2009;93:263–267. Bhandare N, Monroe AT, Morris CG, Bhatti MT, Mendenhall WM. Does altered fractionation influence the risk of radiation-induced optic neuropathy? Int J Radiat Oncol Biol Phys 2005;62:1070–1077. Brechignac F, Paquet F. Radiation-induced risks at low dose: moving beyond controversy towards a new vision. Radiat Environ Biophys 2013;52:299–301. Siddiqui JD, Loeffler JS, Murphy MA. Radiation optic neuropathy after proton beam therapy for optic nerve sheath meningioma. J Neuroophthalmol 2013;33:165–168.
Neurology 82
April 22, 2014
1475
Increased optic nerve radiosensitivity following optic neuritis Nicolae Sanda, Francoise Heran, Nicolas Daly-Schveitzer, et al. Neurology 2014;82;1474-1475 Published Online before print March 21, 2014 DOI 10.1212/WNL.0000000000000339 This information is current as of March 21, 2014 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/82/16/1474.full.html
References
This article cites 7 articles, 1 of which you can access for free at: http://www.neurology.org/content/82/16/1474.full.html##ref-list-1
Subspecialty Collections
This article, along with others on similar topics, appears in the following collection(s): MRI http://www.neurology.org//cgi/collection/mri Optic nerve http://www.neurology.org//cgi/collection/optic_nerve Optic neuritis; see Neuro-ophthalmology/Optic Nerve http://www.neurology.org//cgi/collection/optic_neuritis Radiation therapy-tumor http://www.neurology.org//cgi/collection/radiation_therapytumor Visual loss http://www.neurology.org//cgi/collection/visual_loss
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
Nicolae Sanda, MD Francoise Heran, MD Nicolas Daly-Schveitzer, MD, PhD Jose-Alain Sahel, MD, PhD Avinoam Bezalel Safran, MD
INCREASED OPTIC NERVE RADIOSENSITIVITY FOLLOWING OPTIC NEURITIS
Radiation-induced optic neuropathy (RION) is a late complication of radiotherapy, resulting in severe visual loss.1 We report a RION case following radiation therapy delivered at a dose widely considered as innocuous, occurring on a background of previous isolated optic neuritis. Increased brain sensitivity to radiation has been observed in patients with multiple sclerosis (MS),2–4 but we are not aware of previously reported cases solely involving the optic nerves (ONs). This aspect deserves consideration when defining therapeutic strategies. Case report. A 69-year-old woman with medical history of bilateral sequential optic neuritis 22 and 12 years previously in the right eye (RE) and left eye (LE), respectively, presented with progressive bilateral visual loss. Her visual acuity (VA) before visual loss was 0.7 in the RE and 0.8 in the LE. MS diagnosis based on 2010 McDonald criteria was ruled out by clinical course and multiple MRIs. Two years before presentation, a left maxillary sinus cystic adenoid carcinoma was diagnosed (T4aN0M0) and treated by surgery and external 6 MV fractioned radiotherapy. The right ON received an average dose of 19.9 Gy, while the left ON received an average dose of 53 Gy. Total dose per daily fraction was ,0.2 Gy. The patient noted progressive painless bilateral visual loss evolving over 4 months, starting 12 months after completion of the radiotherapy, and decided to consult. VA was 0.1 in the RE and 0.5 in the LE. Relative afferent pupillary defect and optic disc pallor were noted in the RE and a significant corticonuclear cataract in the LE. RE visual field was constricted and in addition showed a markedly reduced sensitivity in the central area. LE presented a diffuse reduction in sensitivity that was attributed to cataract (Humphrey perimetry mean deviation 23.34 dB P , 2%, pattern SD 1.53 dB). MRI performed to explore the anterior visual pathway showed T2 hyperintensity and postgadolinium T1 enhancement of the intracranial part of the right ON and of the right half of the chiasm (figure). In addition, nonspecific hyperintense T2 white matter lesions were noted. They were identical to those noted on successive MRI performed after the first episode of inflammatory optic neuropathy.
1474
Neurology 82
April 22, 2014
Careful analysis of the images ruled out local or distant recurrence of the maxillary tumor. CSF showed no oligoclonal immunoglobulin G (IgG) bands, elevated IgG index, or carcinomatous cell. Erythrocyte sedimentation rate, C-reactive protein, angiotensin-converting enzyme, as well as whole-body scan were unremarkable. Except for LE phacoemulsification that was refused by the patient, attending physicians advised no treatment and attentive follow-up was organized. RE VA progressed to light perception over an 8-month period, while LE VA stabilized at 0.4. Discussion. The vision loss in this case started 12 months after the radiotherapy and was produced by optic neuropathy in the RE and cataract in the LE. However, minimal optic neuropathy in the LE could not be excluded. The lavish localized contrast enhancement of the intracranial part of the right ON was highly suggestive of RION. Infiltrative, inflammatory, and tumoral etiologies were considered, although no clinical findings favored such hypotheses. The severity of the visual loss, its irreversible course, the timing between the radiation exposure and symptom onset, and major and stable MRI enhancement strongly supported the diagnosis of RION. Applied radiation, however, was much below doses considered potentially neurotoxic. Total doses of 50–63 Gy are reportedly associated with a 5% risk of RION occurrence at 5 years, while doses less than 50 Gy are considered to encompass a negligible risk.1,4 Fraction doses higher than 1.8–2 Gy are also associated with increased risk.1,5 Nevertheless, low doses of radiation may affect cell-to-cell communication mechanisms or tissue-level homeostatic processes.6 It is probable that the unexpected radiosensitivity of the patient’s ON was due to former episodes of optic neuritis, as several studies have demonstrated that patients with MS1–4 or compressive optic neuropathy1,7 show a lower threshold for radiation-induced neurotoxicity. It is conceivable that the damage of the ONs following demyelination was more extensive on the right than on the left ON, thus explaining the particular radiosensitivity of this structure. This suggestion is supported by the VA values, slightly worse in the RE than in the LE 3 months prior to radiation therapy. Data concerning the severity of visual impairment at the time of previous optic neuritis episodes were unavailable.
Figure
Dose distribution plan and MRI
Increased ON radiosensitivity following inflammatory disorders1,4 deserves a particular consideration and warrants more precise determination of radiation values potentially deleterious in such conditions. From the Institut de la Vision/Université Pierre et Marie Curie (N.S., J.-A.S., A.B.S.); CHNO des Quinze-Vingts (N.S., J.-A.S., A.B.S.), Paris; Foch Hospital (N.S.), Suresnes; Fondation Ophtalmologique Adolphe de Rothschild (F.H.), Paris; Institut Gustave Roussy (N.D.-S.), Villejuif, France; and Geneva University School of Medicine (A.B.S.), Switzerland. Author contributions: N. Sanda: drafting/revising the manuscript for content, including medical writing for content; study concept or design; acquisition, analysis or interpretation of data. F. Heran: drafting/revising the manuscript for content, including medical writing for content; analysis or interpretation of data. N. Daly-Schveitzer: analysis or interpretation of data. J.A. Sahel: drafting/revising the manuscript for content, including medical writing for content. A.B. Safran: critical revision of the manuscript for important intellectual content, study concept, acquisition and interpretation of data. Study funding: No targeted funding reported. Disclosure: The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures. Received August 7, 2013. Accepted in final form January 8, 2014. Correspondence to Dr. Sanda: [email protected] © 2014 American Academy of Neurology 1. 2.
3.
4.
5. (A) Dose distribution plan: right optic nerve (ON) average dose 19.9 Gy (median 19.1 Gy, minimal 9.6 Gy, maximal 53.8 Gy for a 0.1 cm3 volume); left ON average dose 53 Gy (median 59.2 Gy, minimal 21.4 Gy, maximal 67.5 Gy for a 0.2 cm3 volume). Initial MRI (B, C, D): the intracranial right ON segment and the right half of the optic chiasm (arrows) show enlargement, lavish T1 gadolinium enhancement (B, C), and T2 hyperintensity. Follow-up MRI (E, F) 3 months later shows (arrows) atrophy of the right ON and the right part of the optic chiasm (E, F), reduced but persistent gadolinium enhancement (E), and moderate T2 hyperintensity (F). Strong initial gadolinium enhancement of an enlarged ON and its remote persistence (for months) coupled with subsequent optic atrophy are in the appropriate clinical context, highly suggestive of radiation-induced optic neuropathy.
6.
7.
Danesh-Meyer HV. Radiation-induced optic neuropathy. J Clin Neurosci 2008;15:95–100. Miller RC, Lachance DH, Lucchinetti CF, et al. Multiple sclerosis, brain radiotherapy, and risk of neurotoxicity: the Mayo Clinic experience. Int J Radiat Oncol Biol Phys 2006;66:1178–1186. Peterson K, Rosenblum MK, Powers JM, Alvord E, Walker RW, Posner JB. Effect of brain irradiation on demyelinating lesions. Neurology 1993;43:2105–2112. Daniels TB, Pollock BE, Miller RC, Lucchinetti CF, Leavitt JA, Brown PD. Radiation-induced optic neuritis after pituitary adenoma radiosurgery in a patient with multiple sclerosis: case report. J Neurooncol 2009;93:263–267. Bhandare N, Monroe AT, Morris CG, Bhatti MT, Mendenhall WM. Does altered fractionation influence the risk of radiation-induced optic neuropathy? Int J Radiat Oncol Biol Phys 2005;62:1070–1077. Brechignac F, Paquet F. Radiation-induced risks at low dose: moving beyond controversy towards a new vision. Radiat Environ Biophys 2013;52:299–301. Siddiqui JD, Loeffler JS, Murphy MA. Radiation optic neuropathy after proton beam therapy for optic nerve sheath meningioma. J Neuroophthalmol 2013;33:165–168.
Neurology 82
April 22, 2014
1475
Increased optic nerve radiosensitivity following optic neuritis Nicolae Sanda, Francoise Heran, Nicolas Daly-Schveitzer, et al. Neurology 2014;82;1474-1475 Published Online before print March 21, 2014 DOI 10.1212/WNL.0000000000000339 This information is current as of March 21, 2014 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/82/16/1474.full.html
References
This article cites 7 articles, 1 of which you can access for free at: http://www.neurology.org/content/82/16/1474.full.html##ref-list-1
Subspecialty Collections
This article, along with others on similar topics, appears in the following collection(s): MRI http://www.neurology.org//cgi/collection/mri Optic nerve http://www.neurology.org//cgi/collection/optic_nerve Optic neuritis; see Neuro-ophthalmology/Optic Nerve http://www.neurology.org//cgi/collection/optic_neuritis Radiation therapy-tumor http://www.neurology.org//cgi/collection/radiation_therapytumor Visual loss http://www.neurology.org//cgi/collection/visual_loss
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
