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The Uveo-Meningeal Syndromes

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The Uveo-Meningeal Syndromes ORIGINAL ARTICLE The Uveo-Meningeal Syndromes Paul W. Brazis, MD,* Michael Stewart, MD,* and Andrew G. Lee, MD† main clinical features being a meningitis or meningoenceph- Background: The uveo-meningeal syndromes are a group of disorders that share involvement of the uvea, retina, and meninges. alitis associated with uveitis. The meningeal involvement is Review Summary: We review the clinical manifestations of uveitis often chronic and may cause cranial neuropathies, polyra- and describe the infectious, inflammatory, and neoplastic conditions diculopathies, and hydrocephalus. In this review we define associated with the uveo-meningeal syndrome. and describe the clinical manifestations of different types of Conclusions: Inflammatory or autoimmune diseases are probably uveitis and discuss the individual entities most often associ- the most common clinically recognized causes of true uveo-menin- ated with the uveo-meningeal syndrome. We review the geal syndromes. These entities often cause inflammation of various distinctive signs in specific causes for uveo-meningeal dis- tissues in the body, including ocular structures and the meninges (eg, ease and discuss our evaluation of these patients. Wegener granulomatosis, sarcoidosis, Behc¸et disease, Vogt-Koy- anagi-Harada syndrome, and acute posterior multifocal placoid pig- ment epitheliopathy). The association of an infectious uveitis with an acute or chronic meningoencephalitis is unusual but occasionally the eye examination may suggest an infectious etiology or even a The uveo-meningeal syndromes are a specific organism responsible for a meningeal syndrome. One should consider the diagnosis of primary ocular-CNS lymphoma in heterogeneous group of disorders that share patients 40 years of age or older with bilateral uveitis, especially involvement of the uvea, retina, and meninges. with prominent vitritis, that fails to respond to treatment or who has associated neurologic findings. A paraneoplastic disorder has been described in patients who have combined optic neuritis and retinitis defined serologically by the presence of a paraneoplastic IgG auto- antibody CRMP-5-IgG. These patients may have an inflammatory UVEITIS vitritis and may have signs of cerebrospinal fluid inflammation. The uveal tract consists of the iris anteriorly, the ciliary Key Words: uveitis, vitritis, choroiditis, retinitis, uveo-meningeal body (the pars plicata anteriorly and the pars plana posteri- syndrome, meningitis orly) in the middle, and the choroid posteriorly (Fig. 1). Inflammation of any of these structures is called uveitis. The (The Neurologist 2004;10: 171–184) anatomic division of the uveal tract serves as the basis for classifying uveitis into anterior uveitis (iritis, anterior cyclitis, iridocyclitis), intermediate uveitis, or posterior uveitis (focal, he uveo-meningeal syndromes are a heterogeneous group multifocal, or diffuse choroiditis, retinochoroiditis, or neur- Tof disorders that share involvement of the uvea, retina, ouveitis with optic nerve inflammation), and panuveitis.1,2 and meninges. Etiologies of this syndrome include infectious, Anterior uveitis may be subdivided into acute or inflammatory, and neoplastic disorders (Table 1) with the chronic and granulomatous or nongranulomatous forms. Pa- tients with acute anterior uveitis present with eye pain, From the *Department of Ophthalmology, Mayo Clinic—Jacksonville, Jack- redness, tearing, photophobia, and decreased vision in the sonville, Florida; and the †Departments of Ophthalmology, Neurology, affected eye. There is a perilimbal flush caused by dilation of and Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, the circumcorneal conjunctival vessels and often clumps of Iowa. inflammatory cells called keratic precipitates on the posterior This work was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY. cornea (Fig. 2). The characteristic finding is inflammatory Reprints: Paul Brazis, MD, Department of Ophthalmology, Mayo Clinic— cells and protein in the aqueous humor (cell and flare). With Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224. E-mail: severe inflammation there may be a layering of inflammatory [email protected]. cells in the inferior anterior chamber (hypopyon). Chronic Copyright © 2004 by Lippincott Williams & Wilkins ISSN: 1074-7931/04/1004-0171 anterior uveitis often develops in a more gradual fashion with DOI: 10.1097/01.nrl.0000131145.26326.ff patients experiencing decreased vision. Affected eyes are The Neurologist • Volume 10, Number 4, July 2004 171 Brazis et al The Neurologist • Volume 10, Number 4, July 2004 TABLE 1. Etiologies of the Uveo-Meningeal Syndrome Infectious Bacterial Cat-scratch disease Whipple disease Mycobacterial—tuberculosis Syphilis Lyme disease Fungal Toxoplasmosis Viral Gnathostomiasis Inflammatory Wegener granulomatosis Sarcoidosis Behc¸et disease VKH syndrome APMPPE Neoplastic Lymphoma Metastatic disease Paraneoplastic syndrome of combined optic neuritis and retinitis defined serologically by CRMP-5-IgG FIGURE 1. This cross-section drawing of the eye shows the uveal tract (highlighted in brown) with its 4 anatomic compo- nents: iris, ciliary body (pars plicata), pars plana, and choroid. often not gray (ie, they are “quiet”) but may have pigmented keratic precipitates, aqueous cells and flare, and areas where the iris has become adherent to the anterior lens capsule (posterior synechiae). Iris nodules may occur on the pupillary margin (Koeppe nodules) or away from the pupillary margin (Busacca nodules). When large keratic precipitates (“mutton fat” precipitates) are present with nodules on the iris, the inflammation is said to be granulomatous. If these iris nod- ules or mutton fat keratic precipitates are absent, the uveitis is called nongranulomatous. Posterior subcapsular cataracts of- ten occur with chronic anterior uveitis. Inflammatory medi- ated scarring between the iris and peripheral cornea (anterior synechiae) may lead to chronic glaucoma. Inflammation of the ciliary body (cyclitis and pars planitis) presents with the gradual onset of blurred vision or floaters in a quiet eye. The anterior chamber may have a few cells but there are diffuse cells in the vitreous. Clumps of FIGURE 2. Peri-limbal flush, seen here as fine red lines on the vitreous inflammatory cells may cause vitreous “snowballs.” sclera just outside the iris, indicates dilated capillaries and small Mounds of inflammatory white exudates may accumulate arterioles resulting from iritis. The multifocal accumulation of because of gravity on the inferior pars plana (“snow banks”). protein and inflammatory cells on the corneal endothelial The release of vasoactive agents lead to macular edema surface forms keratic precipitates (KPs). which may cause decreased or distorted vision. Patients with posterior segment inflammation (choroid- itis and retinitis) present with reduced vision, distorted vision, arterioles and venules causes sheathing, focal vascular nar- and floaters of acute or insidious onset. Pain, redness, tearing, rowing and irregularity. Exudates may cluster along vessels and photophobia are often absent. Inflammation of the retinal appearing as “candle wax drippings” (tache d’bougie). With 172 © 2004 Lippincott Williams & Wilkins The Neurologist • Volume 10, Number 4, July 2004 Uveo-Meningeal Syndromes choroidal and retinal inflammation, cells are often noted in outlined in Table 2. Only infectious agents known to cause a the vitreous (vitritis). The macula and optic nerve may also meningeal syndrome possibly associated with uveitis will be become swollen or ischemic. Retinitis is characterized by discussed. areas of retinal whitening and thickening, while choroiditis is characterized by deeper yellow or cream-colored lesions BACTERIAL INFECTIONS beneath the retinal pigment epithelium. Vascular leakage The major bacterial etiologies for uveo-meningeal syn- from choroidal inflammation may cause exudative retinal drome include cat scratch disease, Whipple disease, syphilis, detachment. The association of retinitis or choroiditis with a tuberculosis, and Lyme disease. swollen optic disc is referred to as neuroretinitis. Cat scratch disease is usually manifested by a regional The evaluation of uveitis thus requires thorough oph- lymphadenopathy following the scratch or bite of a kitten or thalmologic examination including assessment of visual acu- adult cat and is a result of infection by Bartonella henselae. ity and color vision, external examination (for conjunctival or A common ophthalmologic manifestation of cat scratch dis- episcleral injection), slit-lamp biomicroscopy (cell and flare, ease is optic disc edema (Fig. 3) with a macular star keratic precipitates, iris atrophy, iris nodules, syneciae, cata- (ODEMS).6 This neuroretinitis may be associated with ante- ract, etc.), measurement of intraocular pressures, and dilated rior uveitis. Cat scratch disease may cause a focal, multifocal, fundus examination.2,3 Fluorescein angiography is often use- or diffuse retinitis or choroiditis (Fig. 4).7–9 In a study of 24 ful to confirm retinal vasculitis, macular edema, and areas of patients (35 eyes) with choroidal, retinal, or optic disc man- retinitis, choroiditis, ischemia, or retinal detachment. ifestations of cat scratch disease, discrete white retinal or choroidal lesions were the most common posterior segment finding (46% of eyes, 63% of patients) followed by macular star (43% of eyes, 63% of patients).9 Some patients with cat It is important to identify the predominant
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