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Primary Central Nervous System Vasculitis With Optic Nerve Involvement

Benson, Christy E. MD; Knezevic, Alexander MD; Lynch, Shannon C. MD

Journal of Neuro-Ophthalmology: June 2016 - Volume 36 - Issue 2 - p 174–177
doi: 10.1097/WNO.0000000000000328
Clinical Observation

Abstract: A 20-year-old woman presented with headache, decreased vision, eye pain, and urinary retention. During her clinical course, visual acuity declined to 20/800, right eye, and 20/50, left eye, associated with bilateral optic disc edema. Brain magnetic resonance imaging revealed enhancement of the leptomeninges, right optic nerve, and right side of the optic chiasm. Extensive evaluation of the central nervous system (CNS) for an infectious cause was negative. Brain biopsy showed a pattern consistent with vasculitis. The patient was treated with prednisone and cyclophosphamide, resulting in improvement of her vision and systemic symptoms. Primary CNS vasculitis is a rare condition that may affect the anterior visual pathways.

Department of Ophthalmology, University of Nebraska Medical Center, College of Medicine, Omaha, Nebraska.

Address correspondence to Christy E. Benson, MD, Truhlsen Eye Institute, UNMC Department of Ophthalmology, 3902 Leavenworth Street, 985540 Nebraska Medical Center, Omaha, NE 68198-5540; E-mail:

The authors report no conflicts of interest.

Primary central nervous system vasculitis (PCNSV) is a rare condition resulting in inflammation of small- to medium-sized blood vessels in the brain, spinal cord, and leptomeninges, with an incidence of 2.4 cases per 1 million persons per year (1). PCNSV occurs more commonly in women with median age of onset in the fourth decade (2,3). Although rare, there are documented cases of papilledema with elevated intracranial pressure in the setting of PCNSV (4–9). There is one a report of “bilateral optic atrophy” (10), one of branched retinal artery occlusions (11) and one of bilateral optic perineuritis with optic disc edema and relative sparing of visual acuity (12). Our patient seems unique in that optic neuritis was a presenting feature in her case.

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A 20-year-old woman was hospitalized with a 4-day history of worsening headache, left hemiparesis, and dysphasia. She had multiple blood tests to evaluate for an infectious or systemic inflammatory etiology. Specifically, the following diagnostic tests were performed and found to be noncontributory: cryoglobulin, antineutrophil cytoplasmic antibody, angiotensin-converting enzyme (ACE), myeloperoxidase, serine protease 3, extractable nuclear antigens, antinuclear antibody, serum immunofixation, C3/C4, total Ig, Brucella, cysticercosis, histoplasma, Ehrlichia, Rocky Mountain spotted fever, toxoplasmosis, blood parasites, TB quantiferon, hypercoagulable panel, West Nile, lyme, syphilis, Epstein–Barr virus, and HIV. Chest computed tomography (CT) was unremarkable. Opening pressure on lumbar puncture was 4 cm H2O with 3 white blood cells/mL, protein of 24 mg/dL (normal: 15–45 mg/dL), and glucose of 60 mg/dL. Electroencephalography was normal and brain magnetic resonance imaging (MRI) revealed mild right-sided leptomeningeal enhancement. Magnetic resonance angiography and venography were normal.

One week following discharge, the patient was readmitted to the hospital for persistent headache, decreased vision, eye pain, and urinary retention. Visual acuity was 20/80, right eye and 20/15, left eye with a right relative afferent pupillary defect. Extraocular movements were intact and the anterior segments were normal. Fundus examination revealed mild bilateral optic disc edema (Fig. 1).

FIG. 1

FIG. 1

Brain MRI revealed progressive right-sided leptomeningeal enhancement with new involvement of left cerebral hemisphere. In addition, there was enhancement of the right optic nerve and the right side of the optic chiasm (Fig. 2). MRI of the spine showed multiple intramedullary hyperintense lesions but without leptomeningeal enhancement (Fig. 3). Opening pressure on lumbar puncture was 31 cm of H2O. CSF protein was elevated at 78 mg/dL and there were 184 white blood cells per milliliter (29% polymorphonuclear leukocytes). N-methyl-D-aspartate receptor antibody, neuromyelitis optica IgG antibody, and paraneoplastic panel were negative.

FIG. 2

FIG. 2

FIG. 3

FIG. 3

Given the progression of symptoms and neuroimaging findings, a stereotactic brain biopsy was performed. Histology revealed perivascular lymphohistiocytic infiltrate involving small- and medium-sized vessels in a nonnecrotizing vasculitic pattern without granulomas (Fig. 4). Based on the biopsy results, the patient was diagnosed with PCNSV. She was treated with 1 g intravenous solumedrol per day for 5 days with complete resolution of symptoms and was discharged home on oral prednisone of 60 mg/d. Her prednisone was gradually tapered and her acuity returned to 20/20 bilaterally with resolution of her optic disc edema.

FIG. 4

FIG. 4

Three months after discharge, although still on 15 mg of prednisone, she complained of recurrent blurry vision. Visual acuity was 20/800, right eye and 20/50, left eye. Lumbar puncture showed opening pressure of 16 mm H2O with normal CSF analysis. MRI of the brain and orbit revealed continued leptomeningeal and right optic nerve enhancement, whereas cervical and thoracic spine MRI was normal. Owing to recurrence, despite glucocorticoid therapy, she was started on cyclophosphamide 1,200 mg IV. Two weeks later, acuity was 20/20 bilaterally and fundus examination showed mild bilateral optic atrophy. Since that time, she has had relapses including an episode of vision loss in the left eye which has improved. At the time of her last examination, her vision remained 20/20 in each eye and while she remained on 5 mg of prednisone daily, she was transitioned to mycophenolate mofetil 1 g twice a day.

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Although there are no consensus guidelines for diagnosis of PCNSV, criteria proposed in 1988 are most commonly used (13). First, the patient must have history or clinical findings of an acquired unexplained neurological deficit after initial basic evaluation. Next, the patient must have either classic angiographic findings with imaging or histopathologic features on brain biopsy. Finally, systemic vasculitis or a condition in which angiographic or pathologic features could be secondary must be excluded.

PCNSV presents with a broad set of nonspecific symptoms. Headache is the most common initial complaint and can occur acutely or chronically with a wide range of severity. Altered cognition and persistent neurological deficits are also common manifestations. Constitutional symptoms such as weight loss or fever may suggest a more systemic disease (14). Visual symptoms include visual field defects, diplopia, and decreased acuity (1–3).

As the clinical findings of PCNSV are often nonspecific, there is a wide differential diagnosis. Systemic vasculitides involving the central nervous system include Taikayasu arteritis, giant cell arteritis, polyarteritis nodosa, Kawasaki disease, granulomatosis with polyangiitis, Churg–Strauss syndrome, microscopic polyangiitis, Henoch–Schonlein purpura, and Behcet disease. Secondary causes must be ruled out and include systemic lupus erythematosus, Sjogren disease, infections, and malignancy (2). Our patient's extensive evaluation excluded these disorders. In particular, neurosarcoidosis was ruled out with the absence of hilar adenopathy on chest CT, negative ACE levels in both the serum and CSF, and pathology specimen showing vasculitis without granulomas.

Establishing the diagnosis of PCNSV can be challenging. Laboratory testing is frequently normal but useful in terms of ruling out other disorders which may present with similar symptoms. The findings on MRI typically are nonspecific and multifocal, and may include areas of cerebral infarction, leptomeningeal enhancement, and intracranial hemorrhage (3). Leptomeningeal enhancement can occur as an isolated finding (15). Angiography, conventional or magnetic resonance, shows alternating narrowing and dilation of cerebral arteries (16). It is uncommon to have spinal cord involvement in addition to cerebral involvement, but it has been documented in 5% of patients (17).

Brain biopsy is considered the gold standard for diagnosis. Histopathology characteristically demonstrates transmural inflammation of the vascular wall of the cerebral arteries with a cellular infiltrate typically composed of lymphocytes. CSF analysis is abnormal in most cases, frequently with a mild increase in both white cell count and protein concentration (2).

Treatment of PCNSV is generally the same as for systemic primary small- and medium-sized vessel vasculitis (14), although no controlled trials have been performed. Current guidelines based on observational data and experts' opinion by the European League Against Rheumatism recommend a combination of pulsed cyclophosphamide and glucocorticoids (18). The combination therapy achieves better control of disease compared with glucocorticoids alone.

We present this case to illustrate that PCNSV should be considered in the differential diagnosis of patients who present with optic neuritis.


Category 1: a. conception and design: Christy E Benson; Alexander Knezevic; Shannon C Lynch; b. acquisition of data: Christy E Benson; Alexander Knezevic; Shannon C Lynch; c. analysis and interpretation of data: Christy E Benson; Alexander Knezevic; Shannon C Lynch. Category 2: a. drafting the manuscript: Christy E Benson; Alexander Knezevic; b. revising it for intellectual content: Christy E Benson; Shannon C Lynch. Category 3: a. final approval of the completed manuscript: Christy E Benson; Alexander Knezevic; Shannon C Lynch.

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