Hallucinatory Palinopsia in COVID-19-Induced Posterior Reversible Encephalopathy Syndrome

Visual perseveration or palinopsia is a nonspecific term that describes multiple types of visual symptoms char- acterized by persistence or recurrence of previously seen visual images, which are currently absent.

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Hallucinatory Palinopsia in COVID-19-Induced Posterior Reversible Encephalopathy Syndrome Ritwik Ghosh, MD, Durjoy Lahiri, MD, DM, Souvik Dubey, MD, DM, Biman K. Ray, MD, DNB, DM, Julián Benito-León, MD, PhD V isual perseveration or palinopsia is a nonspecific term that describes multiple types of visual symptoms characterized by persistence or recurrence of previously seen visual images, which are currently absent (1). Palinopsia has been associated with a wide variety of etiologies and mechanisms, such as drug-induced, idiopathic seizures, migraine, psychiatric conditions, metabolic alterations, head trauma, and structural lesions in the brain, mainly those affecting parietal and parieto-occipital connections (1). The high-resolution afterimages that are long-lasting, isochromatic, and unaltered by environmental conditioning and motion are typical of hallucinatory palinopsia, a category of palinopsia that represents a dysfunction in visual memory and is caused by posterior cortical lesions or seizures (1). By contrast, illusory palinopsia refers to afterimages that are unformed, indistinct, or of low resolution, and are affected by environmental conditioning. This type of palinopsia is due to a dysfunction in visual perception and is caused by migraines, prescription drugs, illicit drugs, or head trauma (1). Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder with various background risk factors, protean manifestations, and characteristic neuroimaging. Albeit several visual symptoms are commonly described in PRES (2), palinopsia is so far unheard of. Neuroimaging, in particular MRI, usually shows a distinctive parieto-occipital pattern with a symmetric distribution of changes reflecting vasogenic edema (2). Department of General Medicine (RG), Burdwan Medical College and Hospital, Burdwan, West Bengal, India; Department of Neuromedicine (DL, SD, BKR), Bangur Institute of Neurosciences, Kolkata, India; Department of Neurology (JB-L), University Hospital “12 de Octubre”, Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (JB-L), Madrid, Spain; and Department of Mediine (JB-L), Complutense University, Madrid, Spain. Supported by FEDER funds. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). Address correspondence to Julián Benito-León, MD, PhD, Deparment of Neurology, University Hospital “12 de Octubre”, Av. de Córdoba km. 5400 Madrid,, Spain; E-mail: [e-mail] Ghosh et al: J Neuro-Ophthalmol 2020; 40: 523-526 The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been enlisted as a cause of PRES (3–5). We herein report one patient who presented with hallucinatory palinopsia, as a predominant phenomenon, during coronavirus disease 2019 (COVID-19)-induced PRES. A 33-yer-old right-handed (laterality index of +100, as measured by Edinburgh’s Handedness Inventory) woman with 10 years of formal education visited the outpatient department with mild fever, headache, and visual symptoms. Her medical history was unremarkable. On detailed enquiry, she claimed to visualize short, previously viewed, stereotyped actions, continuously replaying for several minutes for the past 2 days. She specifically complained of seeing television images with the news anchor appearing abruptly in the field of vision in over backdrop of wall and persisting for 5–15 minutes. After the neuroophthalmological examination at the outpatient department, she started complaining of perceiving a superimposition of the examiner’s face shield and face mask on her visual field for next few hours. These incidents occurred minutes after the original visuals, with intact shape, architecture, color, and clarity, suggestive of hallucinatory palinopsia. There was no history of visual snow, micropsia, macropsia, teleopsia, akinetopsia, pelopsia, dysmetropsia, oscillopsia, phosphenes, and photopsias. She had no history of any drug intake, addictions, migraine, seizure disorders, diagnosed demyelinating disorder, and psychiatric ailments. She had no other cognitive deficits (i.e., neglect, visual perception, language, memory, and executive dysfunction). Other neurological and ophthalmological examination findings were noncontributory (See Supplemental Digital Content, Appendix 1, http://links.lww.com/ WNO/A449). Complete hemogram, electrolytes, arterial blood gas analysis, vitamin B12, liver, renal, and thyroid function tests (including antithyroid peroxidase) were normal. She tested seronegative for HIV, hepatitis B and C. Her nasopharyngeal and oropharyngeal swabs tested were positive for SARS-CoV-2. Brain MRI revealed hyperintense signal changes on T2-weighted and fluid attenuated inversion recovery (FLAIR)-weighted images, without diffusion restriction and signal blooming in susceptibilityweighted imaging, involving predominantly bilateral parieto-occipital regions and bilateral frontal, parietal, and 523 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence temporal gray–white interfaces, suggestive of PRES (Fig. 1). Magnetic resonance venography, angiography, computed tomography scan of thorax, cerebrospinal fluid study, and conventional (1 hour) 1–70 Hz electroencephalography were normal. After 5 days of therapy with azithromycin 500 mg daily and dexamethasone 24 mg daily (in divided doses), all the symptoms disappeared, and steroid was put off after fast tapering before discharging her on 15th day. The exact pathogenesis of COVID-19-associated PRES remains unclear. Among the possible mechanisms are (3–5): 1) cytokine storm-mediated disruption of blood–brainbarrier integrity; 2) interaction of viral spike protein S1 with angiotensin-converting enzyme-2 receptors, which are expressed abundantly on capillary endothelium, resulting in endothelial damage and increased permeability of blood– brain barrier; 3) SARS-CoV-2-mediated direct neurodegeneration and cerebral edema; and 4) SARS-CoV-2 pneumonia-associated hypoxemia, resulting in augmentation of systemic inflammatory response and deranged neuronal mitochondrial metabolism. All these mechanisms may destabilize autoregulation of cerebral circulation and may cause cerebral vasodilatation, neuronal swelling, and interstitial edema leading to PRES (2). The present case had features of hallucinatory palinopsia (i.e., categorical incorporation, scene preservation, and formed image preservation), indicative of a dysfunction in visual memory encoding, processing, or retrieval (1). Lesions involving both dominant and nondominant parietal, temporal, and occipital cortices can generate palinopsia (1). Because PRES has predilection toward the occipitoparietal regions of brain, disorders of higher visual function are common in this particular syndrome. However, palinopsia as a manifestation of PRES has never been reported before. PRES has been reported in COVID-19 (3–5). In our case, it could be caused by direct effect of SARS-CoV-2 on brain parenchyma because our patient did not have traditional risk factors, particularly metabolic abnormalities, known to be associated with PRES, unlike the previous reports (Table 1). Although commonest presentation of COVID-19-induced PRES is altered mental status, visual symptoms may be found at presentation as earlier depicted by Kaya et al. (5). The index case stands out as a genuinely rare manifestation of COVID-19. It adds to the tally of cases reporting PRES in COVID-19 and, more importantly, brings to FIG. 1. Brain MRI displaying multifocal hyperintense signal changes in bilateral occipital gray–white interface on axial T2weighted (A) and coronal T2-weighted (B) images. Axial FLAIR-weighted images (C, D) showing hyperintense signal changes suggestive of vasogenic edema in bilateral occipital and frontal gray–white interface. 524 Ghosh et al: J Neuro-Ophthalmol 2020; 40: 523-526 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence TABLE 1. Clinical-radiological spectrum of SARS-CoV-2-induced posterior reversible encephalopathy syndrome (PRES) Patient 1 (5) Age, sex Comorbidities 38 years, man None COVID-19 symptoms Fever, hypoxia Patient 2 (3) 48 years, man Obesity Patient 3 (3) 67 years, woman 58 years, man Dyslipidemia Arterial hypertension, Type 2 diabetes, coronary artery disease, gout and asthma None Fever, dry cough, malaise Fever, cough, breathing difficulty and circulatory shock Conventional Acutely raised blood Fluctuating blood Fluctuating blood risk factors of pressure pressure pressure PRES Altered mental Altered mental Symptoms of Acute confusional status status, lethargy PRES state, apathy, and confusion severe bilateral visual impairment and visual agnosia Neuroimaging Hyperintense signal Vasogenic edema Multiple areas of restricted in the posterior features changes on T2diffusion with parieto-occipital weighted and associated regions with FLAIR-weighted edema, most subacute blood images with extensive in the products diffusion posterior parietosuggestive of restriction occipital lobes, hemorrhagic revealing but also in the PRES vasogenic edema right frontal lobe, involving basal ganglia, bilateral, and cerebellar especially left hemispheres. In occipital, frontal addition, cortical white extensive matter and superimposed splenium of hemorrhages in corpus callosum, the parietocompatible with occipital region PRES along with abnormal enhancement — Bilateral multifocal CT thorax Multiple, multilobar, ground-glass features peripheral opacities. ground-glass opacifications in both lungs Lactic acidosis, High D-dimer, Ancillary tests Highly elevated Craised creatinine lactate reactive protein, and mild dehydrogenase, ferritin and hyponatremia C-reactive marked protein and lymphopenia ferritin Ghosh et al: J Neuro-Ophthalmol 2020; 40: 523-526 Patient 4 (4) Patient 5 (4) Patient 6 67 years, woman Hypertension, Type 2 diabetes and obesity 33 years, woman None Breathing difficulty, fever, myalgia, vomiting and diarrhea Fever and headache Acutely raised blood Acutely raised blood None pressure and pressure sepsis Altered mental Altered mental Hallucinatory status status palinopsia Hyperintense signal Hyperintense signal Scattered changes on T2changes on T2Hyperintense weighted and weighted images signal changes FLAIR-weighted involving the on T2-weighted images, without subcortical white images involving diffusion matter of the right the subcortical restriction and occipital lobe and white matter of signal blooming the left cerebellar both occipital and in susceptibilityhemisphere with temporal lobes weighted effacement of the with effacement imaging, involving adjacent sulci, of the adjacent predominantly compatible with sulci, compatible bilateral parietoPRES, with with PRES with occipital regions scattered subarachnoid and bilateral parenchymal hemorrhage frontal, parietal petechial and temporal hemorrhages gray–white interfaces, suggestive of PRES — — None None High D-dimer, High D-dimer, lactate dehydr lactate ogenase, Cdehydrogenase, reactive C-reactive protein, ferritin, protein, ferritin, and coagulopathy leukocytopenia and coagulopathy 525 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence (Continued ) Patient 1 (5) Patient 2 (3) Patient 3 (3) Treatment received Hydroxychloroquine, azithromycin, and oseltamivir combined with oxygen and dexamethasone — — History of blood pressure fluctuation during hospital stay Intensive care unit admission Required ventilator support Yes Outcome Patient 5 (4) Patient 6 Hydroxychloroquine, Azithromycin and Tocilizumab, dexame azithromycin hydroxy thasone ceftriaxone and chloroquine, nicardipine azithromycin, cefepime, vancomycin metronidazole, and nicardipine Variations in blood Variations in blood Variations in blood Variations in blood None pressure, ranging pressure, ranging pressure, ranging pressure, from 79/44 to from 86/52 to from 115/72 to ranging from 193/97 mm Hg 189/122 mm Hg 178/83 mm Hg 70/30 to 180/ 90 mm Hg Yes Yes Not commented, likely no Yes Yes No Yes, non-invasive mechanical ventilatory support Recovered fully Yes, invasive mechanical ventilatory support Recovered fully No Yes, invasive mechanical ventilatory support Recovered fully Yes, invasive mechanical ventilatory support Recovered fully No Recovered fully attention a pure visual cognitive dysfunction in the clinical spectrum of COVID-19. ACKNOWLEDGMENTS Dr. Julián Benito-León is supported by the National Institutes of Health, Bethesda, MD, USA (NINDS #R01 NS39422), European Commission (grant ICT-2011287739, NeuroTREMOR), the Ministry of Economy and Competitiveness (grant RTC-2015-3967-1, NetMD—platform for the tracking of movement disorder), and the Spanish Health Research Agency (grant FIS PI12/01602 and grant FIS PI16/00451). 526 Patient 4 (4) Recovered fully REFERENCES 1. Gersztenkorn D, Lee AG. Palinopsia revamped: a systematic review of the literature. Surv Ophthalmol. 2015;60:1–35. 2. Fischer M, Schmutzhard E. Posterior reversible encephalopathy syndrome. J Neurol. 2017;264:1608–1616. 3. Franceschi AM, Ahmed O, Giliberto L, Castillo M. Hemorrhagic posterior reversible encephalopathy syndrome as a manifestation of COVID-19 infection. AJNR Am J Neuroradiol. 2020;41:1173–1176. 4. Kishfy L, Casasola M, Banankhah P, Parvez A, Jen Jan Y, Shenoy A, Thomson C, AbdelRazek MA. 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