ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY AND THALAMIC INFARCTION Jacob J. Yunker, MD,* Edgar L. Ready, IV, MD,*† Charles L. Tucker, MD,*† Robert E. Morris, MD,*† C. Douglas Witherspoon, MD*†
Objectives: To report a patient with acute posterior multifocal placoid pigment epitheliopathy (APMPPE) who developed a thalamic infarction and to discuss this unusual presentation. Design: Interventional case report and literature review. Methods: A 23-year-old man with APMPPE presented with acute confusion and memory loss. He underwent complete ophthalmologic and neurologic examination, with neuroimaging including magnetic resonance angiography (MRA). Main Outcome Measures: Clinical course and angiographic findings. Results: Magnetic resonance imaging (MRI) showed a left posteromedial thalamic infarction, with a corresponding filling defect of the left posterior communicating artery demonstrated by MRA. The patient underwent further treatment with intravenous corticosteroids followed by continued oral therapy with taper over several weeks. Conclusion: Although the association of APMPPE and cerebral vasculitis has been described, this patient is unique due to the subtle clinical presentation and anatomic location. This case emphasizes the importance of appropriate counseling of patients with APMPPE, as well as prompt recognition of clinical symptoms to enable timely intervention and treatment. RETINAL CASES & BRIEF REPORTS 2:209 –212, 2008
From the *Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama; and the †Helen Keller Foundation for Research and Education, Birmingham, Alabama.
in the third decade of life, with up to one third presenting with a gastrointestinal or respiratory viral prodrome. Characteristic funduscopic findings include multiple circumscribed, gray-white, flat lesions at the level of the retinal pigment epithelium. The clinical course is usually self-limited with gradual return of visual acuity over weeks to months; however, lifethreatening cerebral vasculitis and meningoencephalitis may occur.2 We describe an unusual case in one patient with APMPPE and cerebral vasculitis who had subtle neurologic symptoms and was found to have an acute thalamic infarction as demonstrated by magnetic resonance angiography. We suggest that this case indicates the importance of counseling patients with APMPPE and their families regarding possible cerebrovascular events, so that prompt evaluation and treatment can be provided should such complications occur.
A
cute posterior multifocal placoid pigment epitheliopathy (APMPPE) was first described by Gass1 in 1968 as an idiopathic, self-limited inflammatory disease of the choroidal vasculature. Affected patients are generally otherwise healthy young adults typically Supported in part by unrestricted departmental grants from Research to Prevent Blindness, Inc. (New York, NY), and by the Helen Keller Foundation for Research and Education (Birmingham, AL). Presented at the UAB Department of Ophthalmology Annual Clinical and Research Symposium; May 20 to 21, 2005. None of the authors have any proprietary interest in any of the content presented. Reprint requests: C. Douglas Witherspoon, MD, Retina Specialists of Alabama, 1201 11th Avenue South, Suite 300, Birmingham, AL 35205.
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Fig. 1. Color photographs showing placoid fundus lesions at the level of the retinal pigment epithelium: A, right eye; B, left eye.
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Fig. 2. Fluorescein angiograms of the right eye showing the characteristic pattern consistent with acute posterior multifocal placoid pigment epitheliopathy lesions. A, Early-phase angiogram demonstrating hypofluorescence (blocking) of fundus lesions. B, Late-phase angiogram showing hyperfluorescence of fundus lesions without leakage.
Case Report A 23-year-old man with no significant medical history presented with complaints of decreased vision and a paracentral scotoma in the left eye that had worsened over a period of 2 weeks. There were no other associated systemic symptoms. Ocular examination revealed visual acuity of 20/20 in the right eye and 20/200 in the left eye. Pupils were reactive with no relative afferent pupillary defect. Anterior segment examination results were unremarkable. Funduscopic examination revealed multiple slightly elevated hypopigmented lesions at the level of the retinal pigment epithelium involving the macula in both eyes. Fluorescein angiography demonstrated a mixture of lesions, some demonstrating early blocking of background choroidal fluorescence and others showing transmission defects (Fig. 1). Late-phase hyperfluorescence without leakage was noted in all areas of involvement (Fig. 2). On the basis of the clinical presentation and characteristic angiographic findings consistent with a diagnosis of APMPPE, therapy with oral prednisone was initiated (dose, 80 mg). Visual acuity (right eye, 20/20; left eye, 20/50) and clinical appearance were
improved at the 2-week follow-up, and a gradual taper of the corticosteroid dose was recommended. The patient’s condition continued to improve clinically until 7 weeks after initial presentation, when he developed confusion and disorientation. Family members reported that the patient seemed to have problems with short-term memory abilities. The patient was otherwise alert, had no focal weakness or sensory loss, and had no new visual changes or visual field loss. Visual acuity (right eye, 20/20; left eye, 20/25) and funduscopic examination results demonstrated an improved appearance, and the oral corticosteroid dosage had been decreased to 40 mg/d. Neurologic evaluation revealed a left posteromedial thalamic infarction by magnetic resonance imaging (Fig. 3), a corresponding filling defect with focal narrowing of the left posterior communicating artery by magnetic resonance angiography (Fig. 4), and lymphocytic pleocytosis consistent with vasculitis by cerebrospinal fluid examination. The patient was hospitalized and received a 3-day therapeutic course of intravenous methylprednisolone, which was followed by tapering
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Discussion
Fig. 3. Diffusion-weighted magnetic resonance image showing a left posteromedial thalamic infarction.
of the oral corticosteroid dosage beginning at 80 mg/d and decreasing by 5 mg every 2 weeks. At the most recent follow-up, 4 months after initial presentation, visual acuity was 20/20 in both eyes with an improved funduscopic appearance and complete resolution of neurologic symptoms.
Fig. 4. Magnetic resonance angiography showing a filling defect in the left posterior communicating artery (arrow).
This case of cerebral vasculitis associated with APMPPE was characterized by the acute onset of confusion, disorientation, and memory problems. Neuroimaging demonstrated an acute left posteromedial thalamic infarction, corresponding anatomically and functionally with these clinical symptoms.3 Of interest is the observed onset of neurologic symptoms with tapering of the oral corticosteroid dose, a phenomenon noted by other investigators.4,5 Although the visual sequelae of APMPPE often resolve without permanent deficits in visual acuity, the condition may be associated with a wide range of central nervous system findings, including life-threatening cerebral vasculitis. The most common neurologic manifestation is headache accompanied by cerebrospinal fluid pleocytosis. Additional presenting symptoms of cerebral vasculitis associated with APMPPE include retrobulbar pain, nausea, vomiting, photophobia, ataxia, tremor, homonymous hemianopsia, limb and facial weakness, tonic seizure, and brain death.6 A high level of clinical awareness is thus necessary to follow patients with APMPPE closely, to identify a cerebrovascular event promptly should it occur. The need for such clinical acumen is further heightened by the sometimes insidious presenting symptoms, as in this case. Furthermore, such symptoms may be confused with mood-related side effects of systemic corticosteroid therapy (i.e., steroid psychosis). Gass1 initially attributed the primary lesion of APMPPE to the retinal pigment epithelium; however, indocyanine green angiography studies suggest that the disease involves a vasculitis process in the choriocapillaris.7 Further evidence of a primary choriocapillaris perfusion abnormality was provided by Deutman et al,8 who demonstrated partial nonperfusion of the choriocapillaris at the site of APMPPE lesions. Indocyanine green angiography studies by Dhaliwal et al9 demonstrated improved volume and extent of choroidal blood flow corresponding to improved visual acuity and resolution of pigment epithelial lesions. The association of APMPPE with both ocular vasculitis (episcleritis, anterior uveitis, retinal vasculitis, papillitis, and choroidal periphlebitis) and nonocular vasculitis, including cerebral vasculitis as in this case, further supports a vasculitic disease process involving the choroid. De Vries et al10 recently described a fatal case of cerebral vasculitis associated with APMPPE in a 23-year-old man. It is interesting that histopathologic findings at autopsy demonstrated no signs of vasculitis in the choriocapillaris. Instead, this patient was found to have choroidal granulomas as well as generalized systemic granulomas, including the lungs,
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lymph nodes, heart, liver, and spleen. Their report suggests that APMPPE may in fact represent a granulomatous inflammatory process. Evaluation of patients with APMPPE who have neurologic symptoms should include cerebrospinal fluid analysis, magnetic resonance imaging, and cerebral angiography. Given the potential morbidity and mortality of central nervous system complications, immunosuppressive treatment with corticosteroids, possibly in combination with other agents such as cyclophosphamide or azathioprine, is indicated.11 The onset of associated symptoms in this case corresponded with tapering of the corticosteroid dose. This is consistent with previous reports,5,6 illustrating the importance of a slow tapering regimen for patients with APMPPE. To our knowledge, this case is unique in its demonstration of the association of thalamic infarction with APMPPE-related cerebral vasculitis. Prompt intervention is critical to reduce potential morbidity and mortality that may accompany the associated neurologic complications. Key words: acute posterior multifocal placoid pigment epitheliopathy, cerebral vasculitis, thalamus, stroke. References 1. 2.
Gass JDM. Acute posterior multifocal placoid pigment epitheliopathy. Arch Ophthalmol 1968;80:177–185. Comu S, Verstraeten T, Rinkoff JS, Busis NA. Neurological
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manifestations of acute posterior multifocal placoid pigment epitheliopathy. Stroke 1996;27:996–1001. 3. Pritchard TC, Alloway KD. Thalamocortical Organization. Medical Neuroscience. Madison, CT: Fence Creek Publishing; 1999:174. 4. Wilson CA, Choromokos EA, Sheppard R. Acute posterior multifocal placoid pigment epitheliopathy and cerebral vasculitis. Arch Ophthalmol 1988;106:796–800. 5. Kawi AA, Wang DZ, Kishore K, et al. A case of ischemic cerebral infarction associated with acute posterior multifocal placoid pigmentary epitheliopathy, CNS vasculitis, vitamin B12 deficiency and homocysteinemia. Cerebrovasc Dis 2004; 18:338–339. 6. Smith CH, Savino PJ, Beck RW, et al. Acute posterior multifocal placoid pigment epitheliopathy and cerebral vasculitis. Arch Neurol 1983;40:48–50. 7. Howe LJ, Woon H, Graham EM, et al. Choroidal hypoperfusion in acute posterior multifocal placoid pigment epitheliopathy: an indocyanine green angiography study. Ophthalmology 1995;102:790–798. 8. Deutman AF, Oosterhuis JA, Boen-tan TN, Aan de Kerk AL. Acute posterior multifocal placoid pigment epitheliopathy: pigment epitheliopathy or choriocapillaritis. Br J Ophthalmol 1972;56:863–874. 9. Dhaliwal RS, Maguire AM, Flower RW, Arribas NP. Acute posterior multifocal placoid pigment epitheliopathy: an indocyanine green angiographic study. Retina 1993;13:317–325. 10. De Vries JJ, den Dunnen WF, Timmerman EA, et al. Acute posterior multifocal placoid pigment epitheliopathy with cerebral vasculitis: a multisystem granulomatous disease. Arch Ophthalmol 2006;124:910–913. 11. O’Halloran HS, Berger JR, Lee WB, et al. Acute multifocal placoid pigment epitheliopathy and central nervous system involvement: nine new cases and a review of the literature. Ophthalmology 2001;108:861–868.
Objectives: To report a patient with acute posterior multifocal placoid pigment epitheliopathy (APMPPE) who developed a thalamic infarction and to discuss this unusual presentation. Design: Interventional case report and literature review. Methods: A 23-year-old man with APMPPE presented with acute confusion and memory loss. He underwent complete ophthalmologic and neurologic examination, with neuroimaging including magnetic resonance angiography (MRA). Main Outcome Measures: Clinical course and angiographic findings. Results: Magnetic resonance imaging (MRI) showed a left posteromedial thalamic infarction, with a corresponding filling defect of the left posterior communicating artery demonstrated by MRA. The patient underwent further treatment with intravenous corticosteroids followed by continued oral therapy with taper over several weeks. Conclusion: Although the association of APMPPE and cerebral vasculitis has been described, this patient is unique due to the subtle clinical presentation and anatomic location. This case emphasizes the importance of appropriate counseling of patients with APMPPE, as well as prompt recognition of clinical symptoms to enable timely intervention and treatment. RETINAL CASES & BRIEF REPORTS 2:209 –212, 2008
From the *Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama; and the †Helen Keller Foundation for Research and Education, Birmingham, Alabama.
in the third decade of life, with up to one third presenting with a gastrointestinal or respiratory viral prodrome. Characteristic funduscopic findings include multiple circumscribed, gray-white, flat lesions at the level of the retinal pigment epithelium. The clinical course is usually self-limited with gradual return of visual acuity over weeks to months; however, lifethreatening cerebral vasculitis and meningoencephalitis may occur.2 We describe an unusual case in one patient with APMPPE and cerebral vasculitis who had subtle neurologic symptoms and was found to have an acute thalamic infarction as demonstrated by magnetic resonance angiography. We suggest that this case indicates the importance of counseling patients with APMPPE and their families regarding possible cerebrovascular events, so that prompt evaluation and treatment can be provided should such complications occur.
A
cute posterior multifocal placoid pigment epitheliopathy (APMPPE) was first described by Gass1 in 1968 as an idiopathic, self-limited inflammatory disease of the choroidal vasculature. Affected patients are generally otherwise healthy young adults typically Supported in part by unrestricted departmental grants from Research to Prevent Blindness, Inc. (New York, NY), and by the Helen Keller Foundation for Research and Education (Birmingham, AL). Presented at the UAB Department of Ophthalmology Annual Clinical and Research Symposium; May 20 to 21, 2005. None of the authors have any proprietary interest in any of the content presented. Reprint requests: C. Douglas Witherspoon, MD, Retina Specialists of Alabama, 1201 11th Avenue South, Suite 300, Birmingham, AL 35205.
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Fig. 1. Color photographs showing placoid fundus lesions at the level of the retinal pigment epithelium: A, right eye; B, left eye.
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Fig. 2. Fluorescein angiograms of the right eye showing the characteristic pattern consistent with acute posterior multifocal placoid pigment epitheliopathy lesions. A, Early-phase angiogram demonstrating hypofluorescence (blocking) of fundus lesions. B, Late-phase angiogram showing hyperfluorescence of fundus lesions without leakage.
Case Report A 23-year-old man with no significant medical history presented with complaints of decreased vision and a paracentral scotoma in the left eye that had worsened over a period of 2 weeks. There were no other associated systemic symptoms. Ocular examination revealed visual acuity of 20/20 in the right eye and 20/200 in the left eye. Pupils were reactive with no relative afferent pupillary defect. Anterior segment examination results were unremarkable. Funduscopic examination revealed multiple slightly elevated hypopigmented lesions at the level of the retinal pigment epithelium involving the macula in both eyes. Fluorescein angiography demonstrated a mixture of lesions, some demonstrating early blocking of background choroidal fluorescence and others showing transmission defects (Fig. 1). Late-phase hyperfluorescence without leakage was noted in all areas of involvement (Fig. 2). On the basis of the clinical presentation and characteristic angiographic findings consistent with a diagnosis of APMPPE, therapy with oral prednisone was initiated (dose, 80 mg). Visual acuity (right eye, 20/20; left eye, 20/50) and clinical appearance were
improved at the 2-week follow-up, and a gradual taper of the corticosteroid dose was recommended. The patient’s condition continued to improve clinically until 7 weeks after initial presentation, when he developed confusion and disorientation. Family members reported that the patient seemed to have problems with short-term memory abilities. The patient was otherwise alert, had no focal weakness or sensory loss, and had no new visual changes or visual field loss. Visual acuity (right eye, 20/20; left eye, 20/25) and funduscopic examination results demonstrated an improved appearance, and the oral corticosteroid dosage had been decreased to 40 mg/d. Neurologic evaluation revealed a left posteromedial thalamic infarction by magnetic resonance imaging (Fig. 3), a corresponding filling defect with focal narrowing of the left posterior communicating artery by magnetic resonance angiography (Fig. 4), and lymphocytic pleocytosis consistent with vasculitis by cerebrospinal fluid examination. The patient was hospitalized and received a 3-day therapeutic course of intravenous methylprednisolone, which was followed by tapering
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Discussion
Fig. 3. Diffusion-weighted magnetic resonance image showing a left posteromedial thalamic infarction.
of the oral corticosteroid dosage beginning at 80 mg/d and decreasing by 5 mg every 2 weeks. At the most recent follow-up, 4 months after initial presentation, visual acuity was 20/20 in both eyes with an improved funduscopic appearance and complete resolution of neurologic symptoms.
Fig. 4. Magnetic resonance angiography showing a filling defect in the left posterior communicating artery (arrow).
This case of cerebral vasculitis associated with APMPPE was characterized by the acute onset of confusion, disorientation, and memory problems. Neuroimaging demonstrated an acute left posteromedial thalamic infarction, corresponding anatomically and functionally with these clinical symptoms.3 Of interest is the observed onset of neurologic symptoms with tapering of the oral corticosteroid dose, a phenomenon noted by other investigators.4,5 Although the visual sequelae of APMPPE often resolve without permanent deficits in visual acuity, the condition may be associated with a wide range of central nervous system findings, including life-threatening cerebral vasculitis. The most common neurologic manifestation is headache accompanied by cerebrospinal fluid pleocytosis. Additional presenting symptoms of cerebral vasculitis associated with APMPPE include retrobulbar pain, nausea, vomiting, photophobia, ataxia, tremor, homonymous hemianopsia, limb and facial weakness, tonic seizure, and brain death.6 A high level of clinical awareness is thus necessary to follow patients with APMPPE closely, to identify a cerebrovascular event promptly should it occur. The need for such clinical acumen is further heightened by the sometimes insidious presenting symptoms, as in this case. Furthermore, such symptoms may be confused with mood-related side effects of systemic corticosteroid therapy (i.e., steroid psychosis). Gass1 initially attributed the primary lesion of APMPPE to the retinal pigment epithelium; however, indocyanine green angiography studies suggest that the disease involves a vasculitis process in the choriocapillaris.7 Further evidence of a primary choriocapillaris perfusion abnormality was provided by Deutman et al,8 who demonstrated partial nonperfusion of the choriocapillaris at the site of APMPPE lesions. Indocyanine green angiography studies by Dhaliwal et al9 demonstrated improved volume and extent of choroidal blood flow corresponding to improved visual acuity and resolution of pigment epithelial lesions. The association of APMPPE with both ocular vasculitis (episcleritis, anterior uveitis, retinal vasculitis, papillitis, and choroidal periphlebitis) and nonocular vasculitis, including cerebral vasculitis as in this case, further supports a vasculitic disease process involving the choroid. De Vries et al10 recently described a fatal case of cerebral vasculitis associated with APMPPE in a 23-year-old man. It is interesting that histopathologic findings at autopsy demonstrated no signs of vasculitis in the choriocapillaris. Instead, this patient was found to have choroidal granulomas as well as generalized systemic granulomas, including the lungs,
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lymph nodes, heart, liver, and spleen. Their report suggests that APMPPE may in fact represent a granulomatous inflammatory process. Evaluation of patients with APMPPE who have neurologic symptoms should include cerebrospinal fluid analysis, magnetic resonance imaging, and cerebral angiography. Given the potential morbidity and mortality of central nervous system complications, immunosuppressive treatment with corticosteroids, possibly in combination with other agents such as cyclophosphamide or azathioprine, is indicated.11 The onset of associated symptoms in this case corresponded with tapering of the corticosteroid dose. This is consistent with previous reports,5,6 illustrating the importance of a slow tapering regimen for patients with APMPPE. To our knowledge, this case is unique in its demonstration of the association of thalamic infarction with APMPPE-related cerebral vasculitis. Prompt intervention is critical to reduce potential morbidity and mortality that may accompany the associated neurologic complications. Key words: acute posterior multifocal placoid pigment epitheliopathy, cerebral vasculitis, thalamus, stroke. References 1. 2.
Gass JDM. Acute posterior multifocal placoid pigment epitheliopathy. Arch Ophthalmol 1968;80:177–185. Comu S, Verstraeten T, Rinkoff JS, Busis NA. Neurological
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manifestations of acute posterior multifocal placoid pigment epitheliopathy. Stroke 1996;27:996–1001. 3. Pritchard TC, Alloway KD. Thalamocortical Organization. Medical Neuroscience. Madison, CT: Fence Creek Publishing; 1999:174. 4. Wilson CA, Choromokos EA, Sheppard R. Acute posterior multifocal placoid pigment epitheliopathy and cerebral vasculitis. Arch Ophthalmol 1988;106:796–800. 5. Kawi AA, Wang DZ, Kishore K, et al. A case of ischemic cerebral infarction associated with acute posterior multifocal placoid pigmentary epitheliopathy, CNS vasculitis, vitamin B12 deficiency and homocysteinemia. Cerebrovasc Dis 2004; 18:338–339. 6. Smith CH, Savino PJ, Beck RW, et al. Acute posterior multifocal placoid pigment epitheliopathy and cerebral vasculitis. Arch Neurol 1983;40:48–50. 7. Howe LJ, Woon H, Graham EM, et al. Choroidal hypoperfusion in acute posterior multifocal placoid pigment epitheliopathy: an indocyanine green angiography study. Ophthalmology 1995;102:790–798. 8. Deutman AF, Oosterhuis JA, Boen-tan TN, Aan de Kerk AL. Acute posterior multifocal placoid pigment epitheliopathy: pigment epitheliopathy or choriocapillaritis. Br J Ophthalmol 1972;56:863–874. 9. Dhaliwal RS, Maguire AM, Flower RW, Arribas NP. Acute posterior multifocal placoid pigment epitheliopathy: an indocyanine green angiographic study. Retina 1993;13:317–325. 10. De Vries JJ, den Dunnen WF, Timmerman EA, et al. Acute posterior multifocal placoid pigment epitheliopathy with cerebral vasculitis: a multisystem granulomatous disease. Arch Ophthalmol 2006;124:910–913. 11. O’Halloran HS, Berger JR, Lee WB, et al. Acute multifocal placoid pigment epitheliopathy and central nervous system involvement: nine new cases and a review of the literature. Ophthalmology 2001;108:861–868.
