Tumoral Presentation of Homonymous Hemianopia and Prosopagnosia in Cerebral Amyloid Angiopathy-Related Inflammation

While cerebral amyloid angiopathy is a common cause of lobar hemorrhage, rarely it may be associated with an inflammatory response, thought to be incited by amyloid deposits. We report a 73-year-old woman with an extensive cancer history who presented with tumor-like lesions and symptoms of homonymous hemianopia and prosopagnosia. Found to have cerebral amyloid angiopathy-related inflammation proven by brain biopsy, she was treated successfully with immunosuppression.

Clinical Observation Tumoral Presentation of Homonymous Hemianopia and Prosopagnosia in Cerebral Amyloid Angiopathy-Related Inflammation Clotilde Hainline, MD, Janet C. Rucker, MD, David Zagzag, MD, PhD, John G. Golfinos, MD, Yvonne W. Lui, MD, Benjamin Liechty, MD, Floyd A. Warren, MD, Laura J. Balcer, MD, Steven L. Galetta, MD Abstract: While cerebral amyloid angiopathy is a common cause of lobar hemorrhage, rarely it may be associated with an inflammatory response, thought to be incited by amyloid deposits. We report a 73-year-old woman with an extensive cancer history who presented with tumor-like lesions and symptoms of homonymous hemianopia and prosopagnosia. Found to have cerebral amyloid angiopathy-related inflammation proven by brain biopsy, she was treated successfully with immunosuppression. Journal of Neuro-Ophthalmology 2017;37:48-52 doi: 10.1097/WNO.0000000000000474 © 2017 by North American Neuro-Ophthalmology Society C erebral amyloid angiopathy-related inflammation (CAA-I) is a disease characterized by inflammation with a perivascular or vascular infiltrate that colocalizes with amyloid in and around blood vessels (1). It affects individuals older than 40 years, and clinical features include headache, behavioral change, focal neurological signs, and seizures (2,3). MRI demonstrates patchy or confluent, typically asymmetric cortical-subcortical or deep white matter hyperintensities that, on occasion, can mimic an infiltrating neoplasm (3-5). Unlike most primary brain neoplasms, there is usually some evidence of past or present Departments of Neurology (CH, JCR, FAW, LJB, SLG), Pathology (DZ, BL), Neurosurgery (DZ, JGG), Otolaryngology-Head and Neck Surgery (JGG), Radiology (YWL), Ophthalmology (FAW, LJB, SLG), and Population Health (LJB), NYU Langone Medical Center, NYU School of Medicine, New York, New York. The authors report no conflicts of interest. Address correspondence to Clotilde Hainline, MD, Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Neurology C-3, Boston, MA 02118; E-mail: clotilde.hainline@ bmc.org 48 hemorrhage best appreciated on T2*-gradient echo or susceptibility-weighted imaging (SWI) (2,3). We report a case of CAA-I in a 73-year-old woman with homonymous hemianopia and prosopagnosia who presented a diagnostic challenge, initially thought to have a brain tumor. Histological evidence provided insight into the disease owing to the correlation of symptomatology and clinical imaging to histology. CAA-I is an increasingly recognized entity in the literature and clinical practice. It is critical to recognize as it is treatable with immunotherapy and, depending on the location of involvement, can present with visual symptoms (2,3,6,7). CASE REPORT A 73-year-old woman with no headache history was evaluated in the emergency department for several days of new-onset right-sided retrobulbar and vertex headaches and inability to see to her left side. One week before, she underwent successful left cataract surgery. Eight years before presentation, she had been diagnosed with Stage 1a lung adenocarcinoma and had undergone curative wedge resection. One year after being diagnosed with lung cancer, she was found to have metastatic bladder cancer, for which she underwent bladder resection and chemotherapy. She appeared to be in remission from both cancers as serial positron emission tomography scans had been negative to date. On examination, her vital signs were within normal limits. Visual acuity was 20/20, right eye, and 20/25, left eye, with normal color vision and pupillary testing. Slitlamp examination and ophthalmoscopy were unremarkable. She had an incongruous left homonymous hemianopia (Fig. 1). Her neurological examination was otherwise intact. Computed tomography (CT) of the brain revealed a 2-cm right occipitotemporal hemorrhage with Hainline et al: J Neuro-Ophthalmol 2017; 37: 48-52 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Observation FIG. 1. Automated (Humphrey 24-2) visual fields reveal an incongruous left homonymous hemianopia. surrounding edema (Fig. 2A). Brain MRI was also consistent with acute hematoma, showing subtle patchy rim enhancement and a suggestion of smooth, thin meningeal enhancement over the right hemisphere (Fig. 2B). SWI revealed a few adjacent punctate and linear foci, which were thought to represent a small amount of subarachnoid hemorrhage (Fig. 2C). Brain CT angiography and CT of the chest/abdomen/pelvis were noncontributory. Three weeks later, the patient noted that her face did not look real; her features appeared distorted, sunken, and swollen. She had difficulty recognizing other faces as well. Repeat brain MRI showed multiple areas of new hemorrhage adjacent to the original hemorrhage (Fig. 3). An echocardiogram and conventional cerebral angiography were normal. Although lung adenocarcinoma and bladder carcinoma are not typically hemorrhagic and the distribution and temporal evolution of the lesions were atypical for neoplasm, given the extensive history of malignancy, the clinical suspicion for metastases could not be ignored. A brain biopsy was performed and the preliminary pathology was negative for malignancy. Further analysis revealed an angiocentric mixed lympho-histiocytic inflammatory infiltrate (Fig. 4A). Leptomeningeal vessels were thickened and showed immunoreactivity for amyloid antibody (Fig. 4B-D). Congo red FIG. 2. A. Noncontrast axial brain computed tomography shows a right occipitotemporal hemorrhage with surrounding edema. B. Postcontrast axial T1 MRI demonstrates rim enhancement of the lesion and a suggestion of smooth thin dural or leptomeningeal enhancement over the right hemisphere (arrows). C. Susceptibility-weighted imaging reveals an area of hemorrhage and a few adjacent foci of punctate and linear susceptibility. Hainline et al: J Neuro-Ophthalmol 2017; 37: 48-52 49 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Observation FIG. 3. Brain MRI 3 weeks after the initial study. Precontrast (A) and postcontrast (B) axial T1 scans reveal new areas of hemorrhage with enhancement inferior and medial to the original lesion. staining confirmed apple-green birefringence confirming amyloidosis (Fig. 4E). Extensive polymerase chain reaction tissue analysis for infectious agents was negative. A diagnosis of CAA-I was made. The patient was treated with prednisone 60 mg/day for several weeks and transitioned to mycophenolate mofetil. Over the following year, she had a subjective improvement in her ability to recognize faces but retains a residual left hemifield deficit. Radiologically, there has been involution of the hemorrhagic lesions and no development of new lesions. DISCUSSION We report a patient with CAA-I who developed purely visual manifestations of homonymous hemianopia followed by prosopagnosia. Prosopagnosia is a cortically based visual agnosia for faces without visual agnosia for other objects. It has been localized to the occipitotemporal region of the brain, specifically the fusiform face area (8). Although input is bilateral, several cases have demonstrated a unilateral lesion on the right side sufficient to cause prosopagnosia (9). A homonymous hemianopia usually is present as well; although due to the occipitotemporal location, superior altitudinal or upper quandrantanopias also may occur (10). Definite CAA is a pathologic diagnosis. It is common among the elderly, increasing with age. Population-based autopsy studies estimate a prevalence of 20%-40% in nondemented and 50%-60% in demented individuals (11). CAA may broadly include those patients with abnormal amyloid deposition in their cerebral blood vessels with or without associated inflammation. CAA manifests with amyloid-beta (Ab) deposition in small-to-medium-sized arteries in the cerebral cortex and leptomeninges, and presents with lobar intracerebral hemorrhages (11). Very 50 rarely, there can be a secondary inflammatory response: hence, the term CAA-I. In 2005, this clinical entity was first defined and named Ab-related angiitis by Scolding et al (1), drawing from a group of cases with similar clinical, neuroradiological, and neuropathological features. The literature has since varied in terms of whether pathologic subtypes of the disease are further delineated. Some label the perivascular form as CAA-I (12,13), and the vasculitic, transumural, often granulomatous inflammatory form as Ab-related angiitis (1,7,14). More recent reports simply refer to CAA-I, encompassing the range of inflammatory responses from perivascular infiltrate to vessel wall inflammation with granulomatous destruction (2,4,7). The Ab protein in the vessel wall is thought to incite the inflammatory response. This hypothesis is supported by the occurrence of clinicoradiologic similarities to CAA-I developed by a subset of patients with Alzheimer disease who received bapineuzumab, a humanized, monoclonal antibody to Ab (15,16). CAA-I lies on a spectrum between CAA and primary angiitis of the central nervous system (PACNS), the latter with no known antigen triggering the vasculitic reaction. Neuropathologically, in PACNS, Ab deposits are typically absent, and if coincidentally present, do not colocalize with the inflammatory changes as they do in CAA-I. In addition, patients with PACNS tend to present at a younger age (on average ,50 years), with more infarcts, fewer hemorrhages, and sometimes myelopathy (7,17). Diagnostic criteria for CAA-I have been proposed (3) and recently refined with clinicoradiologic validation (Table 1). Although these criteria may aid the clinician, a definitive diagnosis requires neuropathologic validation. Because of the rarity of the disease, there are no clinical trials to guide treatment, but a variety of immune-modulating therapies Hainline et al: J Neuro-Ophthalmol 2017; 37: 48-52 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Observation TABLE 1. Criteria for the diagnosis of probable cerebral amyloid angiopathy-related inflammation 1. Age $40 yr 2. Presence of $1 clinical feature Headache Decrease in consciousness Behavioral change Focal neurological signs and seizures Presentation not directly attributable to ICH 3. MRI shows unifocal or multifocal white matter hyperintense lesions (cortical-subcortical or deep) that are asymmetric and extend to the immediate subcortical white matter; asymmetry is not due to past ICH 4. Presence of $1 of the following cortical-subcortical hemorrhagic lesions Cerebral macrobleed Cerebral microbleed Cortical superficial siderosis 5. Absence of neoplastic, infectious, or other causes ICH, intracerebral hemorrhage. Modified from Ref. (2). have been shown to help arrest disease activity, typically corticosteroids, often combined with additional immunosuppressive therapy (3,7,18). While clinical improvement is universally expected, the response to therapy can be dramatic and sustained (1,3,14). However, mortality has been reported to range between 7% and 44%, further reinforcing the importance of recognition and treatment (1,7,18). Our case demonstrates how CAA-I may present initially with a neuro-ophthalmic syndrome. 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