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

Abstract

Visual 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). 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 neuro-ophthalmological 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, https://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 susceptibility-weighted imaging, involving predominantly bilateral parieto-occipital regions and bilateral frontal, parietal, and 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.FIG. 1.: Brain MRI displaying multifocal hyperintense signal changes in bilateral occipital gray–white interface on axial T2-weighted (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.The exact pathogenesis of COVID-19-associated PRES remains unclear. Among the possible mechanisms are (3–5): 1) cytokine storm-mediated disruption of blood–brain-barrier 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 occipito-parietal 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). TABLE 1. - Clinical-radiological spectrum of SARS-CoV-2-induced posterior reversible encephalopathy syndrome (PRES) Patient 1 (5) Patient 2 (3) Patient 3 (3) Patient 4 (4) Patient 5 (4) Patient 6 Age, sex 38 years, man 48 years, man 67 years, woman 58 years, man 67 years, woman 33 years, woman Comorbidities None Obesity Arterial hypertension, Type 2 diabetes, coronary artery disease, gout and asthma Dyslipidemia Hypertension, Type 2 diabetes and obesity None COVID-19 symptoms Fever, hypoxia Fever, cough, breathing difficulty and circulatory shock None Fever, dry cough, malaise Breathing difficulty, fever, myalgia, vomiting and diarrhea Fever and headache Conventional risk factors of PRES Acutely raised blood pressure Fluctuating blood pressure Fluctuating blood pressure Acutely raised blood pressure and sepsis Acutely raised blood pressure None Symptoms of PRES Acute confusional state, apathy, severe bilateral visual impairment and visual agnosia Altered mental status Altered mental status, lethargy and confusion Altered mental status Altered mental status Hallucinatory palinopsia Neuroimaging features Hyperintense signal changes on T2-weighted and FLAIR-weighted images with diffusion restriction revealing vasogenic edema involving bilateral, especially left occipital, frontal cortical white matter and splenium of corpus callosum, compatible with PRES Vasogenic edema in the posterior parieto-occipital regions with subacute blood products suggestive of hemorrhagic PRES Multiple areas of restricted diffusion with associated edema, most extensive in the posterior parieto-occipital lobes, but also in the right frontal lobe, basal ganglia, and cerebellar hemispheres. In addition, extensive superimposed hemorrhages in the parieto-occipital region along with abnormal enhancement Scattered Hyperintense signal changes on T2-weighted images involving the subcortical white matter of both occipital and temporal lobes with effacement of the adjacent sulci, compatible with PRES with subarachnoid hemorrhage Hyperintense signal changes on T2-weighted images involving the subcortical white matter of the right occipital lobe and the left cerebellar hemisphere with effacement of the adjacent sulci, compatible with PRES, with scattered parenchymal petechial hemorrhages Hyperintense signal changes on T2-weighted and FLAIR-weighted images, without diffusion restriction and signal blooming in susceptibility-weighted imaging, involving predominantly bilateral parieto-occipital regions and bilateral frontal, parietal and temporal gray–white interfaces, suggestive of PRES CT thorax features Multiple, multilobar, peripheral ground-glass opacifications in both lungs — Bilateral multifocal ground-glass opacities. — — None Ancillary tests Highly elevated C-reactive protein, ferritin and marked lymphopenia High D-dimer, lactate dehydrogenase, C-reactive protein and ferritin Lactic acidosis, raised creatinine and mild hyponatremia High D-dimer,lactate dehydrogenase, C-reactive protein, ferritin,leukocytopenia and coagulopathy High D-dimer,lactate dehydrogenase, C-reactiveprotein, ferritin,and coagulopathy None Treatment received Hydroxychloroquine,azithromycin, andoseltamivircombined withoxygen anddexamethasone — — Tocilizumab,hydroxychloroquine,azithromycin,cefepime,vancomycinmetronidazole, and nicardipine Hydroxychloroquine,azithromycinceftriaxone andnicardipine Azithromycin anddexamethasone History of blood pressurefluctuationduring hospitalstay Yes Variations in blood pressure, ranging from 70/30 to 180/90 mm Hg Variations in blood pressure, ranging from 115/72 to 178/83 mm Hg Variations in blood pressure, ranging from 86/52 to 189/122 mm Hg Variations in blood pressure, ranging from 79/44 to 193/97 mm Hg None Intensive care unit admission Yes Yes Not commented, likely no Yes Yes No Required ventilator support Yes, non-invasive mechanical ventilatory support Yes, invasive mechanical ventilatory support No Yes, invasive mechanical ventilatory support Yes, invasive mechanical ventilatory support No Outcome Recovered fully Recovered fully Recovered fully Recovered fully Recovered fully Recovered fully 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 attention a pure visual cognitive dysfunction in the clinical spectrum of COVID-19.

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