Atypical Lymphocytic Angiitis of the Optic Nerve and Central Nervous System

Primary angiitis of the central nervous system (PACNS), also known as primary vasculitis of the central nervous system, is a rare, poorly understood, and often fatal disorder.^1,2 Although the association of PACNS with optic neuropathy has been documented,^3-5 this is the first report to our knowledge of visual loss with histopathologic involvement of the optic nerves.

Our patient developed decreasing visual acuity and right-sided weakness in his 40s after falling from a height of 3 m. Neuroimaging revealed normal blood vessels on computed tomographic angiography and irregular large areas of hyperintensity in the brain and cervical spine on magnetic resonance imaging, consistent with demyelinating processes of different ages. He was treated for multiple sclerosis with interferon beta-1a (Avonex, Rebif) and natalizumab (Tysabri) for 4 years but then experienced altered mental status and left-sided weakness. He developed bowel and bladder incontinence, monoplegia of the left lower extremity, spasticity, and loss of vision in the left eye. During the last month of life, he was treated for multiple urinary tract infections and died of acute aspiration bronchopneumonia.

The brain was normal sized with multiple circular granular lesions ranging in diameter from 1 to 3 mm. The largest lesion was in the mid–corpus callosum at the level of the caudate nucleus, and multiple small lesions surrounded the calcarine fissure. Both eyes had indistinct borders of the optic nerve, suggestive of optic edema.

Microscopic examination of the brain revealed no multiple sclerosis plaques. Instead, there were prominent eosinophilic (Figure 1A), well-circumscribed nodules of fibrotic tissue (Figure 1B) in the white and gray matter of the right occipital lobe and medulla. The nodules had a central, cellular core containing a mixture of macrophages and CD3⁺ T lymphocytes (Figure 1C) and CD20⁺ B lymphocytes (Figure 1D), with T cells predominating. Lymphocytic vasculitis (angiitis) involved arterioles. Reactive astrocytes surrounded arterioles within the nodules. Reactive microgliosis with a few macrophages surrounded the nodules. We interpreted the nodules as representing areas of fibrosis secondary to chronic inflammation, consistent with a partial response to immunosuppressive therapy.

Both eyes had bilateral lymphocytic angiitis with vascular fibrosis of the optic nerve as well as optic nerve demyelination (Figure 2). There was a scant mononuclear infiltrate in the optic nerve meninges bilaterally, similar to that in the leptomeninges of the brain.

The diagnosis of PACNS is extremely challenging owing to the limited diagnostic performance of current neuroradiologic studies and the large number of conditions that can mimic PACNS.^1,2 The diagnostic criteria for PACNS are the presence of an acquired neurological or psychiatric deficit, the classic angiographic or histopathological features of PACNS, and no evidence of systemic vasculitis or any disorder that can cause or mimic this condition.¹ Only histopathology can definitively confirm the diagnosis of PACNS.^1,2

Visual loss has rarely been described in PACNS, but without corresponding histopathologic analysis. Four cases of bilateral visual loss have been reported secondary to cortical infarction.³ Optic disc edema has also been rarely reported in patients with PACNS, most commonly in association with increased intracranial pressure,³ which was not documented in our patient. In another case of PACNS with bilateral optic disc edema, a relative sparing of the visual acuity suggested an optic perineuritis pattern.³ The histopathologic picture of nongranulomatous PACNS in our patient resembles that described by Solis et al⁵ in the absence of a clinical history of decreased visual acuity.

In conclusion, visual loss may be associated with involvement of the optic nerve in PACNS. Primary angiitis of the central nervous system and optic nerve should be considered in the differential diagnosis of optic disc edema and magnetic resonance imaging findings resembling a primary demyelinating illness.

Corresponding Author: Eleonora M. Lad, MD, PhD, Department of Ophthalmology, Duke University Medical Center, DUMC 3802, Durham, NC 27710 (nora.lad@duke.edu).

Published Online: August 21, 2014. doi:10.1001/jamaophthalmol.2014.2786.

Author Contributions: Dr Lad had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Lad, Proia.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Lad, Proia.

Critical revision of the manuscript for important intellectual content: All authors.

Administrative, technical, or material support: Lad, Proia.

Study supervision: Proia.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.