Anterior ischemic optic neuropathy (AION) may be a presenting sign of giant cell arteritis (GCA). The diagnosis of GCA in such cases usually is suspected on the basis of associated systemic symptoms (headache, scalp tenderness, jaw claudication, ear pain) combined with an elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or both and is confirmed with a biopsy of one or both superficial temporal arteries. Several patients have been reported in whom arteritic AION was associated with magnetic resonance imaging (MRI) evidence of optic nerve sheath enhancement (1–31–31–3). We report a patient with unilateral AION due to biopsy-proven GCA and bilateral optic nerve sheath enhancement on MRI.
A 67-year-old man, with medically controlled hypertension and hyperlipidemia, was evaluated in the emergency room for decreased vision in his left eye. He first noticed superior visual field loss in his left eye about 5 days earlier, and 2 days before presentation, he started seeing “fireworks” accompanied by a decline in central vision of his left eye. His right eye was asymptomatic. On review of systems, he had been feeling well and denied headache, scalp tenderness, fatigue, or decrease in appetite; however, he did report bilateral jaw claudication that had begun about 2 weeks earlier.
On examination, visual acuity was 20/30 in the right eye and 20/100 in the left eye. Color vision using Ishihara plates was 10/10 in the right eye and 1/10 in the left eye. The visual field of the right eye was full by confrontation while the left field showed a superior nasal defect. The pupils were isocoric, with a small left relative afferent pupil defect. Extraocular movements were full and slit lamp examination revealed no abnormalities except for mild bilateral nuclear sclerosis. Ophthalmoscopy revealed no abnormalities in the right eye, but the left optic disc was moderately swollen and pale. There was no tenderness to palpation in the region of the superficial temporal arteries. A Westergren ESR was 27 mm/h. CRP was 0.7 mg/dL (normal: <0.5 mg/dL).
Because of concern for possible GCA, the patient was given 1 dose of 1 g methylprednisolone intravenously. MRI of the brain and orbits showed bilateral optic nerve sheath enhancement (Fig. 1). Given the patient's relatively young age, unremarkable inflammatory markers, lack of convincing GCA symptoms, and imaging results, it was thought that GCA was unlikely. Instead, there were concerns for central nervous system lymphoma. As a result, steroids were discontinued, and the patient underwent an extensive evaluation for an underlying neoplastic process. Computed tomography of the chest, abdomen, and pelvis revealed no evidence of primary malignancy. Lumbar puncture revealed an elevated protein concentration of 91 mg/dL (normal: 15–45 mg/dL), and the cerebrospinal fluid was acellular. Hematologic studies including ANA, c-ANCA and p-ANCA, RF, dRVVT, anti-dsDNA ab, anti-Ro/La ab, complement levels, LDH, peripheral blood smear, NMO-IgG, TSH, B12/MMA, B1, copper, zinc, RPR, HIV, Lyme, and HbA1C gave negative or normal results.
By day 3 of his hospitalization, the patient's left eye vision had declined to 20/400. Automated visual field testing was normal in the right eye while field of the left eye showed generalized reduction in sensitivity.
Positron emission tomography (PET) demonstrated abnormal uptake in the ophthalmic, temporal, and occipital arteries concerning for GCA (Fig. 2). A temporal artery biopsy was performed that showed changes consistent with active GCA. The patient was placed on prednisone 60 mg by mouth daily with a slow taper.
Our patient represented an interesting diagnostic challenge. He presented with an acute left anterior optic neuropathy characterized by pallid optic disc swelling in the setting of recent onset of jaw claudication. Although we initially considered a diagnosis of GCA, the finding of bilateral optic nerve sheath enhancement on MRI prompted an extensive workup for neoplastic or other inflammatory etiologies, which was unrevealing until PET scan showed abnormal uptake in the ophthalmic, temporal, and occipital arteries consistent with GCA. This diagnosis was confirmed with temporal artery biopsy.
It is not unusual to see very mild optic nerve sheath enhancement on MRI in normal individuals with no evidence of optic nerve dysfunction, whereas significant enhancement has been described in patients with idiopathic optic perineuritis (4), herpes zoster (5), sarcoidosis (6), granulomatosis with polyangitis (7), syphilis (8), GCA (1–31–31–3), and systemic malignancy (9,109,10).
Using PubMed, we were able to identify 4 cases of optic nerve sheath enhancement in patients with biopsy-proven GCA (Table 1). Lee et al (1) reported an 82-year-old woman with typical symptoms of GCA, elevated inflammatory markers, bilateral optic neuropathies, right optic nerve enhancement, and left optic nerve sheath enhancement. Liu et al (2) reported 2 similar cases. The first patient was an 83-year-old woman who presented with headache and bilateral vision loss. She was found to have bilateral optic neuropathies associated with bilateral optic nerve sheath enhancement. The second patient was a 69-year-old woman with vision loss in the left eye, a left optic neuropathy, and enhancement of the left optic nerve sheath. Morgenstern et al (3) reported an 83-year-old man with bilateral vision loss, elevated inflammatory markers, bilateral optic neuropathies, and bilateral optic nerve sheath enhancement. In contrast, our patient had bilateral optic nerve sheath enhancement despite unilateral left optic neuropathy. This unique combination of clinical and imaging findings has not been reported previously.
Our case illustrates that optic nerve sheath enhancement can be seen in patients with clinically silent GCA. The fact that our patient had bilateral optic nerve sheath enhancement but only unilateral optic neuropathy raises interesting questions regarding the pathophysiology of the disease and vision loss. Our hypothesis is that in this subset of GCA patients, the ischemic optic neuropathy and the enhancement of the optic nerve sheath (presumably due to break down of the blood-tissue barrier within the sheath itself) are associated but not causally related to each other.
In the patient reported by Morgenstern et al (3), there was granulomatous inflammation in the vessel walls in both the optic nerve sheath and temporal artery biopsy specimens, a finding that suggests that inflammation of the blood vessels within the optic nerve sheath is a parallel process to the vasculitis seen in the larger vessels in the rest of the body.
If the breakdown in the blood-tissue barrier of the nerve sheath was directly causing the optic neuropathy, one would expect not only the enhancement of the optic nerve sheath but also enhancement of the nerve itself, a prediction inconsistent with the previously reported cases and our patient. It also would not explain why there was bilateral optic nerve sheath enhancement and yet only unilateral optic neuropathy in our patient. Hence, we hypothesize that in GCA patients with optic neuropathy and optic nerve sheath enhancement, the optic neuropathy is due to ischemia from reduced blood flow in the vessels proximal to the optic nerve and the enhancement of the optic nerve sheath is due to inflammation of the vessels inside the sheath itself.
An alternative hypothesis is that the bilateral optic nerve sheath enhancement in our patient was a manifestation of involvement of the ophthalmic arteries by vasculitis (11) (i.e., not due to inflammation within the sheath itself). The reason that our patient did not have a right optic neuropathy was that he was treated with corticosteroids before the right optic nerve became ischemic.
Although we are not recommending MRI as part of the routine evaluation for possible GCA, there is a developing literature on using MRI to assist in making the diagnosis (12). Specifically, it has been shown that a significant percentage of patients with biopsy-proven GCA have pathologic vessel enhancement on MRI (13,1413,14). On review of our patient's MRI, there was abnormal enhancement of both temporal arteries, left more than right. This finding initially was not recognized. Although the use of noninvasive vascular studies is of great interest, establishment of the diagnosis of GCA still requires temporal artery biopsy.
In conclusion, optic nerve sheath enhancement can be seen in various disorders, including GCA. Optic nerve sheath enhancement in the appropriate clinical setting should not delay either the evaluation or empiric steroid treatment for GCA.
STATEMENT OF AUTHORSHIP
Category 1: a. Conception and design: T. Y. A. Liu and N. Miller; b. Acquisition of data: T. Y. A. Liu and N. Miller; c. Analysis and interpretation of data: T. Y. A. Liu and N. Miller. Category 2: a. Drafting the manuscript: T. Y. A. Liu and N. Miller; b. Revising it for intellectual content: T. Y. A. Liu and N. Miller. Category 3: a. Final approval of the completed manuscript: T. Y. A. Liu and N. Miller.
We thank Rick Wray, MD, for assistance with positron emission tomography in our patient.
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