Woman presents with acute loss of bilateral vision

An MRI showed optic nerve enhancement and a hyperintense right paraclinoid mass.

Priti Batta

Namrata Nandakumar

A 64-year-old woman presented with bilateral vision loss that began about 2 weeks before presentation. She first noted peripheral vision loss in the left eye, which progressed to involve her central vision. Within a few days, she noted a decrease in vision in her right eye. She also described a right periorbital throbbing sensation that started earlier in the month.

The patient’s ocular history was remarkable for primary open-angle glaucoma that was diagnosed 10 years ago. Her medical history was significant for hypertension, type 2 diabetes mellitus and hyperlipidemia.

The patient’s best corrected visual acuity was 20/60 in the right eye and hand motion in the left eye. Pupils were 5 mm in the right eye and 3 mm in the left eye with a relative afferent pupillary defect in the left eye. When tested with Ishihara color plates, she was able to correctly answer 3 out of 8 plates in the right eye but no plates correctly in the left eye. Her extraocular motility was normal bilaterally, and her IOP was 20 mm Hg in each eye. Her anterior segment examination was significant only for mild cortical cataracts. Her fundus examination was relatively unremarkable aside from an increased cup-to-disc ratio with otherwise normal-appearing optic nerves (Figure 1).

Confrontation visual field testing showed severe constriction in both eyes with a dense inferior defect in the right eye. Humphrey visual fields were performed but were difficult to interpret due to a high number of false negative responses (Figure 2). Optical coherence tomography of the peripapillary nerve fiber layer showed only mild thinning temporally in the left eye but otherwise normal measurements and morphology. An MRI of the brain and orbits showed optic nerve enlargement and enhancement, left more so than right. It also revealed a hyperintense right paraclinoid mass (Figure 3).

Figure 1. Optic disc photographs of the right eye and left eye, revealing cupping of both optic nerves but otherwise well-defined margins and healthy rim color. Images: Liang M, Athappilly G

Figure 2. Humphrey visual fields (30-2). A central defect is seen in the right eye, and dense inferior and central defects are present in the left eye.

Figure 3. MRI of the orbits with gadolinium. Slightly enlarged optic nerves with infiltration is seen, as well as a hyperintense right paraclinoid mass.

What is your diagnosis?

Bilateral vision loss

The differential diagnosis for this patient with bilateral vision loss and enlargement of the optic nerves includes inflammatory, infectious and neoplastic etiologies. Inflammatory causes include sarcoidosis, Wegener’s granulomatosis and demyelinating optic neuritis. Possible infections include syphilis, Lyme disease and tuberculosis. Leukemic infiltration of the optic nerves is also in the differential.

Considering her acute onset of bilateral vision loss, the patient was admitted to the hospital for further work-up. Her blood work was significant for a normal ESR, CRP, ACE and ANCA. A lumbar puncture was also performed, which was significant for slightly elevated glucose and protein. Her cerebrospinal fluid (CSF) ACE level was normal, and CSF cytology was unremarkable. CT imaging revealed multiple enlarged lymph nodes throughout her chest, abdomen and pelvis, as well as a large lymph node under her left sternocleidomastoid muscle. While neurosurgery opted not to perform a biopsy of her brain lesion, a biopsy was obtained of the enlarged neck lymph node, which showed organizing granulomatous inflammation with sclerosis and scattered giant cells. It was negative for AFB, and cytology did not reveal neoplastic cells.

After the neck biopsy was performed, the patient was diagnosed with probable neurosarcoidosis with bilateral optic neuropathy and started on IV methylprednisolone 1 g/day. After five days of IV therapy, her vision improved to 20/20 in the right eye and 20/30 in the left eye. While she still had a left afferent pupillary defect, she was able to correctly answer all Ishihara color plates in the right eye and 4 out of 8 in the left eye. Her visual fields after treatment showed a central defect in the right eye and inferior and central changes in the left eye, but this was significantly improved from presentation.

After being discharged from the hospital, the patient’s prednisone dose had been tapered and she was also started on CellCept (mycophenolate mofetil, Genentech). While she had a great initial response to treatment, her course was complicated by another decrease in vision unresponsive to IV methylprednisolone and also IV infliximab. She then received IVIg for 5 days with much improvement in her vision in both eyes. She is currently still on oral prednisone and CellCept, with her prednisone being tapered 5 mg every 2 weeks.

Discussion

Sarcoidosis is a chronic multisystem inflammatory disorder characterized by granulomas in various organs. It can affect anyone at any age but is most commonly found in African-American women between the ages of 20 years and 40 years. The etiology is unknown, and it affects primarily the lungs, but 5% to 10% of cases involve the central nervous system. Of these cases, facial nerve involvement is most common, but the optic nerves can be affected as well. Manifestations of neurosarcoidosis are usually related to cranial nerve involvement, but other presentations include seizures, aseptic meningitis, and CSF obstruction and mass effect due to granuloma formation. Overall, the prevalence of sarcoid is 40 out of 100,000. Only 1% of these cases are neurosarcoidosis without other organ involvement.

Definite diagnosis of neurosarcoidosis is only possible with a positive central nervous system (CNS) biopsy. As this is often hard to obtain, other studies are often employed. Brain MRI with gadolinium is helpful in outlining mass lesions or enhancement of the optic nerves and meninges. The CSF is often noted to have elevated protein and pleocytosis, although it can be normal in 30% of cases. ACE levels can also be elevated in both the CSF and serum in more than 50% of patients and can be followed over time to assess disease activity, although these levels can also be elevated due to other disease. Other possible studies include a PET scan, which can pinpoint any hypermetabolic areas of the body, and visual and brainstem evoked potentials, which can often be abnormal before symptoms arise. As it can be difficult to diagnose neurosarcoid, certain criteria have been developed. Definite neurosarcoid includes plausible symptoms, a positive biopsy and no other possible causes. Probable neurosarcoid, as in our patient, includes suggestive symptoms, signs of CNS inflammation (by CSF and MRI) and exclusion of other diagnoses. Possible neurosarcoid includes symptoms not due to other conditions but the above criteria not met. Tissue biopsy shows granulomas rich in epithelioid cells, surrounded by other immune system cells such as lymphocytes and multinucleated giant cells.

There is no treatment for sarcoidosis; however, not all patients with systemic sarcoid need to be treated. Patients with neurosarcoid, though, tend to have a chronic course, so treatment is typically initiated at presentation, usually with 40 mg to 60 mg of oral prednisone, depending on severity. Pulsed IV steroids (1 g IV for 3 days) can also be used. A slow taper of steroids is usually required (5 mg every 2 weeks), and patients are often not able to tolerate less than 10 mg or 20 mg of prednisone without recurrence of symptoms. Other treatment options include immunosuppressants and immunomodulators, specifically methotrexate, Plaquenil (hydroxychloroquine, sanofi-aventis), cyclophosphamide, azathioprine, CellCept and thalidomide. IV infliximab and IVIg have also been successful, especially in refractory cases. Radiation therapy has been performed in the past in unresponsive cases, and neurosurgical intervention is required for patients who have CSF obstruction or mass effect. Overall, patients with neurosarcoid have a chronic variable course and often require long-term steroids in addition to adjunctive therapy.

References:

• Barrack S. Neurosarcoidosis.http://knol.google.com/k/neurosarcoidosis#.
• Baughman RP, Lower EE. Therapy for sarcoidosis. Eur Respir Mon. 2005;32:301-315.
• Menninger MD, Amdur RJ, Marcus RB Jr. Role of radiotherapy in the treatment of neurosarcoidosis. Am J Clin Oncol. 2003;26(4):115-118.
• Moravan M, Segal BM. Treatment of CNS sarcoidosis with infliximab and mycophenolate mofetil. Neurology. 2009;72(4):337-340.
• Pawate S, Moses H, Sriram S. Presentations and outcomes of neurosarcoidosis: A study of 54 cases. Q J Med. 2009;102(7):449-460.
• Stern BJ, Corbett J. Neuro-ophthalmic manifestations of sarcoidosis. Curr Treat Options Neurol. 2007;9(1):63-71.
• Zajicek JP, Scolding NJ, Foster O, et al. Central nervous system sarcoidosis — diagnosis and management. Q J Med. 1999;92(2):103-117.

• Michelle Liang, MD, and Geetha Athappilly, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.

• Edited by Priti Batta, MD, and Namrata Nandakumar, MD. Drs. Batta and Nandakumar can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.