Progressive Vision Loss and Cognitive Decline as Presenting Manifestation of Adult Onset Subacute Sclerosing Panencephalitis

Photo and Video Essay Section Editors: Kimberly M. Winges, MD Michael J. Gilhooley, MA, MB, BChir, DPhil Progressive Vision Loss and Cognitive Decline as Presenting Manifestation of Adult Onset Subacute Sclerosing Panencephalitis Selvakumar Ambika, MBBS, DNB, Pranav S. Patil, MBBS, Veena Noronha, MBBS, DNB, Deepak Arjundas, MBBS, MD, Muna Bhende, MBBS, MS, Parthopratim Dutta Majumdar, MBBS, MS A 45-year-old apparently healthy man, an ophthalmologist by profession, presented to us with complaints of gradual painless progressive diminution of vision of both eyes, right followed by the left eye for the past 10 months. Initially, he was diagnosed and treated elsewhere as necrotizing viral macular retinitis in the right eye (Figs. 1,2). Vitreous biopsy at that time was negative for herpes simplex virus, varicella–zoster virus, and cytomegalovirus. He received a dose of intravitreal ganciclovir injection for the same. He also developed progressive psychiatric symptoms, and his MRI of the brain and orbit T2W fluid-attenuated inversion recovery (FLAIR) images revealed diffuse deep white matter lesions in both cerebral hemispheres. He was treated with antipsychotic medications by the local neurologist. Subsequently, there was further neurological deterioration such as cognitive decline, tics, right-sided rigidity, facial dystonia, walking difficulty, and speech disability, and he became wheelchair-bound with poor comprehension. He had a positive history of measles in childhood. On examination, he had hand movements close to face in both eyes with difficulty in comprehension. His anterior segment examination was within the normal limits. Indirect ophthalmoscopic examination of fundus revealed optic disc pallor with macular atrophy in the right eye and optic disc pallor with a normal macula in the left eye (Fig. 3). A repeat MRI of the brain showed confluent T2W FLAIR hyperintense signals in the periventricular white matter (L . R), which had increased compared with previous scans. MRI of the orbit showed subtle T2 hyperintense signal in the right optic nerve at the apex (Figs. 4,5). His routine hemogram, Departments of Neuro-Ophthalmology (SA) and Ophthalmology (PSP), Sankara Nethralaya (Medical Research Foundation), Chennai, India; Department of Radiology (VN), VRR Scans, Chennai, India; Vijaya Health Center (DA), Chennai, India; Shri Bhagwan Mahavir Department of Vitreo Retinal Services (MB), Sankara Nethralaya (Medical Research Foundation), Chennai, India; and Department of Uvea and Intraocular Inflammation (PDM), Sankara Nethralaya (Medical Research Foundation), Chennai, India. The authors report no conflicts of interest. Address correspondence to Pranav S. Patil, MBBS, Department of Ophthalmology, Sankara Nethralaya (Medical Research Foundation), Chennai 600006, India; E-mail: [e-mail] e194 C-reactive protein, rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibody, anti–double-stranded DNA antibody, serum copper, serum lead, liver and renal function tests, and neuromyelitis optica/myelin oligodendrocyte glycoprotein antibodies were within normal limits. He underwent lumbar puncture and cerebrospinal fluid (CSF) analysis, which showed normal CSF pressure and significantly raised measles immunoglobulin G titer in the CSF (.100). A diagnosis of subacute sclerosing panencephalitis (SSPE) was made. Optical coherence tomography findings at initial presentation were more suggestive of disruption of retinal layers and tissue loss in the right eye. There were subtle changes in the retinal nerve fiber layer and ganglion cell complex (GCC) which could have been due to chronic foveal tissue changes also. It may be difficult to differentiate whether GCC changes were due to isolated retinal changes or associated with white matter changes. However, the possibility of a retrograde transneuronal degeneration could not be ruled out. He was started on intravenous methyl prednisolone 1 g/day for 5 days along with oral sodium valproate, clonazepam, and isoprinosine. FIG. 1. Fundus photograph of the right eye at initial presentation showing a well-defined area of apparent tissue loss at the fovea (Acknowledgment: Dr Raja Narayanan, Director and Network Head, Clinical Research at L V Prasad Eye Institute). Ambika et al: J Neuro-Ophthalmol 2024; 44: e194-e196 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay FIG. 2. Optical coherence tomography of the right macula at initial presentation showing a sharply defined area of the loss of retinal tissue at the macula with retained ILM. A small intraretinal cyst is seen adjacent to the area of the optically empty space. The loss of RPE is evidenced by the backscattering. The choroid appears normal (Acknowledgment: Dr Raja Narayanan, Director and Network Head, Clinical Research at L V Prasad Eye Institute). ILM, internal limiting membrane. SSPE, a progressive disease of the central nervous system, is more prevalent in countries with lower immunization rates against measles infections (1). Ocular involvement is seen in nearly 50% of cases of SSPE (1,2). Hallmark ophthalmoscopic lesions in patients with SSPE include optic disc edema, optic atrophy, and retinal pigment epithelium (RPE) changes secondary to chorioretinitis (3). The RPE and choroid show necrosis that most commonly affects the macula (2). Cochereau-Massin et al (4) reported 23 cases of ocular involvement in SSPE, one of the largest case series, which showed only 4 patients had ocular involvement before the onset of neurological manifestations. Cortical blindness has also been reported to be an initial presen- tation in SSPE (5). Studies have shown that neurological symptoms often precede ocular involvement (3,4). Hence, in patients presenting with ophthalmic complaints in the absence of neurological features, the diagnosis of SSPE can be challenging. Although on brain imaging, periventricular and subcortical white matter areas are most frequently involved, in the initial stages of the disease, there are reports of few patients with SSPE with normal MRI of the brain (2). Our patient was an otherwise normal adult who initially presented with acute-onset unilateral focal macular retinitis for which he received antiviral treatment; subsequently, he developed myoclonic jerks, dyspraxia, cognitive decline, aphasia, and rigidity. Adult onset SSPE has a more aggressive FIG. 3. Fundus photograph showing macular atrophy in the right eye and disk pallor in both eyes. Ambika et al: J Neuro-Ophthalmol 2024; 44: e194-e196 e195 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay FIG. 4. T2W fluid-attenuated inversion recovery image (FLAIR) axial scan at supraventricular region showing confluent, asymmetric T2 FLAIR hyperintense white matter lesions (L . R). course and a poorer prognosis with advancing age of onset (7). A combination of weekly intrathecal interferon-a and daily oral isoprinosine slows progression of the disease or prolongs survival but eventually has higher mortality (6). In developing countries, the diagnosis of SSPE should be kept in mind in patients who present with macular retinitis, in view of high prevalence of measles infection in these areas. SSPE is not an uncommon entity that is more rampant in countries with less measles immunization, and adult-onset form is devastatingly progressive with poor survival rates. STATEMENT OF AUTHORSHIP Conception and design: S. Ambika, P. S. Patil; Acquisition of data: S. Ambika, P. S. Patil; Analysis and interpretation of data: S. Ambika, P. S Patil, V. Noronha, D. Arjundas, M. Bhende, P. D. Majumdar. Drafting the manuscript: S. Ambika, P. S. Patil, M. Bhende, P. D. Majumdar; Revising the manuscript for intellectual content: S. Ambika, M. Bhende. Final approval of the completed manuscript: S. Ambika. e196 FIG. 5. T2W fat suppressed coronal section of orbit showing subtle increased T2 signal in the right optic nerve at the apex. REFERENCES 1. Colpak AI, Erdener SE, Ozgen B, Anlar B, Kansu T. Neuroophthalmology of subacute sclerosing panencephalitis: two cases and a review of the literature. Curr Opin Ophthalmol. 2012;23:466–471. 2. Garg RK. Subacute sclerosing panencephalitis. J Neurol. 2008;255:1861–1871. 3. Yuksel D, Sonmez PA, Yilmaz D, Senbil N, Gurer Y. Ocular findings in subacute sclerosing panencephalitis. Ocul Immunol Inflamm. 2011;19:135–138. 4. 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