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, occur- ring 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 (T 4a N 0 M 0 ) 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 cortico- nuclear 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 sen- sitivity that was attributed to cataract (Humphrey perim- etry mean deviation 23.34 dB P , 2%, pattern SD 1.53 dB). MRI performed to explore the anterior visual pathway showed T2 hyperintensity and postgadoli- nium T1 enhancement of the intracranial part of the right ON and of the right half of the chiasm (fig- ure). 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. Careful analysis of the images ruled out local or dis- tant 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 phacoemulsifica- tion that was refused by the patient, attending physicians advised no treatment and attentive follow-up was orga- nized. 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 etiol- ogies 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 pa- tients with MS 1–4 or compressive optic neuropathy 1,7 show a lower threshold for radiation-induced neurotoxi- city. It is conceivable that the damage of the ONs fol- lowing demyelination was more extensive on the right than on the left ON, thus explaining the particular radiosensitivity of this structure. This suggestion is sup- ported 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. 1474 Neurology 82 April 22, 2014