Persistent Placoid Maculopathy Complicated by Cerebral Vasculitis

Persistent placoid maculopathy (PPM) is a bilateral inflammatory chorioretinopathy characterized by long-standing plaque-like macular lesions. No systemic manifestations have been reported to date. We describe a case of PPM complicated by cerebral vasculitis, suggesting that neurological symptoms, including headache, should be enquired about in all PPM subjects.

Clinical Observation Persistent Placoid Maculopathy Complicated by Cerebral Vasculitis Eva Lenassi, MD, PhD, Maja Kojovic, MD, PhD, Polona Jaki Mekjavi c, MD, PhD, Sasa Sega, MD, PhD, Natasa Vidovi c Valentin ci c, MD, PhD Abstract: Persistent placoid maculopathy (PPM) is a bilateral inflammatory chorioretinopathy characterized by long-standing plaque-like macular lesions. No systemic manifestations have been reported to date. We describe a case of PPM complicated by cerebral vasculitis, suggesting that neurological symptoms, including headache, should be enquired about in all PPM subjects. Journal of Neuro-Ophthalmology 2017;37:273-275 doi: 10.1097/WNO.0000000000000399 © 2016 by North American Neuro-Ophthalmology Society W hite dot syndromes are a heterogeneous group of inflammatory chorioretinopathies characterized by the presence of yellow-white fundus lesions. Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and persistent placoid maculopathy (PPM) are 2 of the diagnoses within this group. The latter typically presents with bilateral symmetrical plaque-like lesions that persist in the same location beyond 3 months. It may superficially resemble APMPPE, although PPM presents later in life (fifth-seventh decade) and has a much poorer prognosis (1,2). To date, 18 cases of PPM have been reported, with 11 of them developing choroidal neovascularization (1-5). Typically, white dot syndromes show no systemic manifestations, although a few patients with APMPPE and associated cerebral vasculitis have been described (6). Here, we report what is, to our knowledge, the first case of cerebral vasculitis associated with PPM. Eye Hospital (EL, PJM, NVV), University Medical Centre, Ljubljana, Slovenia; and Department of Neurology (MK, SS), University Medical Centre, Ljubljana, Slovenia. Supported by a grant from the Slovenian research agency (ARRS P3-0333). The authors report no conflicts of interest. Address correspondence to Eva Lenassi, MD, PhD, Eye Hospital, University Medical Centre, Grabloviceva ulica 46, Ljubljana 1000, Slovenia; E-mail: [e-mail] Lenassi et al: J Neuro-Ophthalmol 2017; 37: 273-275 CASE REPORT A 57-year-old woman reported a 3-day history of bilateral visual loss, headaches, and fever. Besides leg varicose veins and a healed leg ulcer, her medical history was unremarkable. Visual acuity at presentation was 20/100, right eye, and 20/60, left eye. Anterior segment and vitreous examination were normal. Funduscopy revealed multiple yellow-white plaque-like lesions in both maculae (Fig. 1A). On fundus autofluorescence, these lesions demonstrated hyperautofluorescene centrally with hypoautofluorescent margins (Fig. 1B). Fluorescein angiography revealed early central hypofluorescence and increasing hyperfluorescence over time (Fig. 1C). Indocyanine green angiography showed sharply delineated central hypofluorescence that persisted in the late stages of the angiogram (Fig. 1D). Optical coherence tomography (OCT) demonstrated outer retinal abnormalities, including hyperreflectivity of the outer nuclear layer and disruption of the ellipsoid zone; the inner choroid appeared homogenously reflective and thickened (Fig. 2). Uveitic workup excluded an infectious etiology (including tuberculosis and syphilis), and vasculitic screen was negative. The diagnosis of PPM was suspected. As the patient complained of headaches, cerebrospinal fluid (CSF) analysis was performed revealing protein level of 0.42 g/L (normal: 0.15-0.45 g/L), glucose of 3.2 mmol/L (normal: 2.5-3.9 mmol/L), and 8 white blood cells/mL. Brain magnetic resonance imaging (MRI) and angiography (MRA) were normal (Fig. 3A), and the patient was treated with three 500 mg pulses of intravenous methylprednisolone followed by oral methylprednisolone (1 mg/kg per day). There was symptomatic improvement and the steroids were tapered. Two months after presentation, the patient discontinued treatment against instructions. Two days later, she developed dysarthria and left hemiparesis. Brain MRI showed widespread acute ischemic lesions and MRA revealed focal narrowing in posterior cerebral arteries, confirming the diagnosis of cerebral vasculitis (Fig. 3B). Further diagnostic 273 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Observation FIG. 1. Fundus of right eye. A. Yellow-white plaque-like lesions are observed in the macula. B. On fundus autofluorescence, the lesions are hyperautofluorescent centrally with hypoautofluorescent margins. C. On fluorescein angiography, the macular lesions are initially hypofluorescent but gradually become hyperfluorescent. D. On indocyanine green angiography, there is sharply delineated hypofluorescence associated with the placoid areas. tests, including thrombophilia screen, carotid Doppler, cardiology examination, and cardiac Holter monitoring, were unremarkable. Oral methylprednisolone (1 mg/kg per day) and intravenous cyclophosphamide treatment (1 g per month) were initiated, and no further ischemic events were observed. At 7-month follow-up, there was complete resolution of the patient's neurological symptoms. Retinal morphology and visual symptoms also improved (Fig. 2), and visual acuity was 20/50, right eye, and 20/40, left eye. Eighteen months after presentation, the placoid lesions were still present at the same location and fundus FIG. 2. Optical coherence tomography (OCT) of the right fundus. A. At presentation, there is hyperreflectivity of the outer nuclear layer, disruption of the ellipsoid zone, and thickening of the inner choroid. B. At 7-month follow-up, the OCT changes appear to be resolving. C. Association between a hypofluorescent lesion on indocyanine green angiography (arrow) and increased inner choroidal thickening (arrow) is shown on enhanced-depth imaging OCT (D). Seven months later, the inner choroidal thickness (arrow) has normalized (E). 274 Lenassi et al: J Neuro-Ophthalmol 2017; 37: 273-275 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Observation FIG. 3. Neuroimaging. A. At presentation, there is a normal appearance on magnetic resonance angiography (left) and axial fluid-attenuated inversion recovery images (center, right). B. Two months later, there is segmental narrowing (arrow) of the right posterior cerebral artery (left) and evidence of infarction (arrows) involving the right occipital lobe (center), the right putamen and right caudate nucleus (right). autofluorescence findings remained consistent with PPM. DISCUSSION Cerebral vasculitis is an uncommon, life-threatening complication of both APMPPE (6,7) and PPM. Neurological symptoms, including headache, should be enquired about, and CSF analysis and neuroimaging should be considered in the diagnostic workup. If neurological symptoms persist, close multidisciplinary monitoring is required. Little is known about optimal management of PPM but there is some evidence that high-dose corticosteroids may provide short-term benefit (2,3,5). This is in keeping with our findings: aggressive immunosuppression helped control not only the ocular disease but also the cerebrovascular complications. The primary site of inflammation in PPM is unclear (2,3). Serial enhanced-depth OCT imaging in our patient suggests that the inflammatory process likely begins at the level of the inner choroid with secondary involvement of the retinal pigment epithelium and outer retina (Fig. 2C-E). We speculate that the hallmark of PPM is choroidal vasculitis leading to ischemic choroidal infarcts. A similar mechanism has been previously proposed for APMPPE (8). The MRA appearance and response to steroids in our patient coupled with the reported findings in cases of APMPPE with central nervous system involvement (6,7) suggest that PPM-associated inflammation also can affect the cerebral vasculature. Lenassi et al: J Neuro-Ophthalmol 2017; 37: 273-275 STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: E. Lenassi and N. Vidovi c Valentin ci c; b. Acquisition of data: E. Lenassi, M. Kojovic, S. Sega, and N. Vidovi c Valentin ci c; c. Analysis and interpretation of data: E. Lenassi, M. Kojovic, and N. Vidovi c Valentin ci c. Category 2: a. Drafting the manuscript: E. Lenassi; b. Revising it for intellectual content: M. Kojovic, P. Jaki Mekjavi c, S. Sega, and N. Vidovi c Valentin ci c. Category 3: a. Final approval of the completed manuscript: E. Lenassi, M. Kojovic, P. 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