Cerebral visual impairment: genetic diagnoses and phenotypic associations.

BACKGROUND: Cerebral visual impairment (CVI) is the most common form of paediatric visual impairment in developed countries. CVI can arise from a host of genetic or acquired causes, but there has been limited research to date on CVI in the context of genetic disorders. METHODS: We carried out a retrospective analysis of genotypic and phenotypic data for participants with CVI within the DECIPHER database and 100 000 Genomes Project (100KGP). RESULTS: 158 individuals with CVI were identified across both cohorts. Within this group, pathogenic or likely pathogenic sequence variants in 173 genes were identified. 25 of these genes already have known associations with CVI, while the remaining 148 are candidate genes for this phenotype. Gene ontology analysis of the CVI gene sets from both DECIPHER and 100KGP suggests that CVI has a similar degree of genetic heterogeneity to other neurodevelopmental phenotypes, and a strong association with genetic variants converging on ion channels and receptor functions. Individuals with a monogenic disorder and CVI have a higher frequency of epilepsies and severe neurodisability than individuals with a monogenic disorder but not CVI. CONCLUSION: This study supports the availability of genetic testing for individuals with CVI alongside other neurodevelopmental difficulties. It also supports the availability of ophthalmological screening for individuals with genetic diagnoses linked to CVI. Further studies could elaborate on the links between specific genetic disorders, visual maturation and broader neurodevelopmental characteristics.

A rare case of cortical blindness following vaccination against SARS-CoV-2.

A 61-year-old male presented with sudden loss of vision in both the eyes about 8 days after the first shot of coronavirus disease 2019 (COVID-19) vaccine (Covishield). On examination, the visual acuity was no perception of light in both the eyes. Contrast-enhanced magnetic resonance imaging (MRI) with diffusion-weighted imaging showed acute cerebral infarcts involving bilateral parieto-occipital region. Considering the temporal correlation with the vaccine shot and absence of any other precipitating factor, we hypothesized that this was probably an immunologic response to the vaccine.

Knowledge Assessment on Cortical Visual Impairment Among Ophthalmologists in Nepal.

INTRODUCTION: Cortical visual impairment (CVI) in children is a retro chiasmal visual tract disorder where there is with an impairment in the visual acuity and/or functionality of vision-guided task, including motor planning in the presence of normal ocular findings or minimal ocular morbidity. The study was conducted to assess the knowledge about CVI among ophthalmologists practicing in Nepal. MATERIALS AND METHODS: This was a cross sectional study. Data collection was done by administering a preformed, validated questionnaire that was sent via email to all the ophthalmologists registered under the Nepal Ophthalmic Society. The email mentioned the aim of the study along with the questionnaire. RESULTS: A total of 146 (37.82%) ophthalmologists responded to the questionnaire. Forty four percent of the participants were general ophthalmologists, 28% were pediatric ophthalmologists and 67% were ophthalmologists from other subspecialty. The median age of participants was 37.6 years. Most of the ophthalmologist had a good knowledge about the cause, common risk factors, clinical risk factors, management and prognosis of CVI. However only 29.5% of participants were aware of the investigation of choice for diagnosing CVI and 31.7% were aware of the leading causes of visual impairment in the developed countries. The study also established that the knowledge score was higher in pediatric ophthalmologists than the general ophthalmologist and ophthalmologists from other specialties. CONCLUSION: Most of the ophthalmologists had a good knowledge about the cause, common risk factors, clinical features, management and prognosis of CVI. However only a limited number of participants were aware of the investigation of choice for diagnosing CVI and the leading causes of visual impairment in the developed countries. Majority of the participants rarely examined patients with CVI which does not correlate with the high prevalence of perinatal hypoxia, the commonest cause of CVI, in our country.

Hepatic Encephalopathy Induced Transient Cortical Blindness.

Hepatic encephalopathy describes a spectrum of potentially reversible neuropsychiatric abnormalities seen in a patient with severe liver dysfunction with porto-systemic shunting. Cortical blindness can be a rare presentation of hepatic encephalopathy and can even precede the onset of altered sensorium. We report a case of 57 years female with chronic liver disease who presented with bilateral loss of vision, with no focal neurological deficits. From clinical and laboratory examination, a diagnosis of hepatic encephalopathy with cortical blindness was proposed. Her visual disturbances gradually improved with the treatment of hepatic encephalopathy. Keywords: Cortical blindness; end stage liver disease; hepatic encephalopathy; papilledema.

Delayed-onset hypoxic cortical blindness: coming back from the abyss.

PURPOSE: To report a case of typical delayed-onset hypoxic cortical blindness that occurred few days after resuscitation from drowning in a young male. METHODS: Neurological and ophthalmological examination were performed including optical coherence tomography (OCT), Goldmann perimetry, pattern electroretinogram (pERG), pattern and flash visual evoked potentials (pVEP and fVEP) and brain magnetic resonance imaging (MRI). RESULTS: At presentation, at day 12 post-hypoxic incident, best corrected visual acuity (BCVA) was reduced to hand motion OU with an abolished optokinetic nystagmus, a normal fundus and no relative afferent pupillary defect. Macular and peripapillary OCT were normal. Goldmann perimetry revealed bilateral centrocecal scotoma. pERG was normal while pVEPs were undetectable and fVEPs were abnormal with delayed, decreased and disorganized responses, without interhemispheric asymmetry. Brain MRI disclosed a bilateral cortical-subcortical occipital hypersignal with laminar necrosis and thus confirmed the diagnosis of delayed-onset hypoxic cortical blindness. Visual rehabilitation, including visual stimulation in the scotomatous areas, was associated with a dramatic and rapid visual improvement with a BCVA of 20/32 OU, an ability to read after 2 weeks (day 30 post-hypoxic incident), and a reduction in the size of the scotoma. CONCLUSION: Delayed-onset hypoxic cortical blindness is a rare presentation of cortical blindness that develops few days after a cerebral hypoxic stress. While initial presentation can be catastrophic, visual improvement may be spectacular and enhanced with visual rehabilitation.

SARS-COV-2 infection during pregnancy, a risk factor for eclampsia or neurological manifestations of COVID-19? Case report.

BACKGROUND: There are no published cases of tonic-clonic seizures and posterior bilateral blindness during pregnancy and Severe Acute Respiratory Syndrome (SARS) Coronavirus (COV) 2 (SARS-COV-2) infection. We do not just face new and unknown manifestations, but also how different patient groups are affected by SARS-COV-2 infection, such as pregnant women. Coronavirus Disease 2019 (COVID-19), preeclampsia, eclampsia and posterior reversible leukoencephalopathy share endothelium damage and similar pathophysiology. CASE PRESENTATION: A 35-year-old pregnant woman was admitted for tonic-clonic seizures and SARS-COV-2 infection. She had a normal pregnancy control and no other symptoms before tonic-clonic seizures development. After a Caesarean section (C-section) she developed high blood pressure, and we initiated antihypertensive treatment with labetalol, amlodipine and captopril. Few hours later she developed symptoms of cortical blindness that resolved in 72 h with normal brain computed tomography (CT) angiography. CONCLUSION: The authors conclude that SARS COV-2 infection could promote brain endothelial damage and facilitate neurological complications during pregnancy.

Prenatal or Perinatal Injury? Diagnosing the Cortically Blind Infant.

PURPOSE: To document the association of prenatal brain disruption with secondary perinatal distress in children diagnosed as having cortical visual impairment (CVI). DESIGN: Retrospective case series. METHODS: Eight children with severe CVI and clinical history of perinatal events were included. Case histories and neuroimaging studies were reviewed. The main outcome measures were perinatal history, visual and neurologic findings, and magnetic resonance (MR) imaging. RESULTS: In our patient cohort, MR imaging showed signs of cortical dysgenesis leading to congenital brain malformations such as polymicrogyria consistent with a prenatal timing of CNS injury. Although subcortical white matter changes were common, signs of watershed injury to the visual cortex were absent, suggesting that the visual loss was attributable to a prenatal etiology with secondary birth complications. CONCLUSION: Some children with CVI and a history of perinatal distress have prenatal dysgenesis of the developing brain. Therefore, a clinical history of perinatal hypoxia-ischemia is nonspecific and merits neuroimaging to identify antecedent brain malformations and timing of injury, which can influence patient diagnosis and management.

Anton's Syndrome associated with autotopagnosia.

We describe an unusual case of a 68-year-old male affected by cerebral amyloid angiopathy and cortical blindness associated with Anton's syndrome. In addition, our patient presented with autotopagnosia, a form of agnosia characterized by loss of body spatial representation. Neuropsychological assessment evidenced cognitive impairment. Magnetic Resonance Imaging showed hemorrhagic foci in the left occipital and right occipito-parietal lobe, paratrigonal white matter, and post-ischemic parenchymal gliosis. The pattern-reversal of visual evoked potentials were indicative bilateral visual pathway of integrity of the. After a neurological damage, patients could show a denial of their own deficit; however, the association between anosognosia and autotopagnosia represents a rare neurological condition. The simultaneous onset of unusual neuropsychological syndromes could be related to involvement of a complex brain network.

Final versus referral diagnosis of childhood visual impairment in an Italian tertiary low vision rehabilitation centre.

PURPOSE: To compare the final diagnosis of the causes of low vision in children attending a tertiary rehabilitation centre for visually impaired children versus referral diagnosis. METHODS: Retrospective review of clinical charts of all children referred to the Robert Hollman Foundation, a tertiary centre for visually impaired children, between January 2010 and June 2011. The following clinical data were analysed: entry diagnosis made by the referral ophthalmologist and final diagnosis made at Robert Hollman Foundation based on a complete ophthalmic evaluation. RESULTS: Ninety-two consecutive children (mean age = 2.37 ± 1.98 years, range = 0-9) were included. A referral diagnosis was retrieved in 76 cases (82.6%), including cerebral visual impairment (14.1%), retinopathy of prematurity (14.1%), hereditary retinal diseases (10.9%), nystagmus (8.7%) and other rarer diseases (34.8%). In the remaining 16 children (17.4%), a precise referral diagnosis was unavailable. Final clinical diagnosis made at Robert Hollman Foundation was normal visual function in 8.7%, cerebral visual impairment in 30.4%, retinopathy of prematurity in 10.9%, hereditary retinal disease in 9.8% and other in 40.2%. In 17 cases (18.5%), the diagnosis made at the Robert Hollman Foundation did not confirm the entry diagnosis. Among patients where measurement of visual acuity was possible (84), 66.7% were blind or seriously visual impaired, and the main causes were cerebral visual impairment (32.1%) and retinopathy of prematurity (16.1%). CONCLUSION: The most frequent diseases were cerebral visual impairment, retinopathy of prematurity and hereditary retinal diseases. Approximately one-third of referred children had not a correct diagnosis at baseline. The activity of an ophthalmic tertiary centre is essential to offer a precise diagnosis to visually impaired (sometimes with other deficits) children.

Understanding low functioning cerebral visual impairment: An Indian context.

For several reasons, cerebral visual impairment (CVI) is emerging as a major cause of visual impairment among children in the developing world and we are seeing an increasing number of such children in our clinics. Owing to lack of early training about CVI and it being a habilitation orientated subject, we need to become equipped to optimally help the affected children. In this paper we have explained our pragmatic approach in addressing children who present with low functioning CVI. Initially we explain briefly, how vision is processed in the brain. We then present what should be specifically looked for in these children in regular clinics as a part of their comprehensive ophthalmic examination. We discuss the process of functional vision evaluation that we follow with the help of videos to explain the procedures, examples of how to convey the conclusions to the family, and how to use our findings to develop intervention guidelines for the child. We explain the difference between passive vision stimulation and vision intervention, provide some common interventions that may be applicable to many children and suggest how to infuse interventions in daily routines of children so that they become relevant and meaningful leading to effective learning experiences.

Patterns of Cortical Visual Field Defects From Embolic Stroke Explained by the Anastomotic Organization of Vascular Microlobules.

The cerebral cortex is supplied by vascular microlobules, each comprised of a half dozen penetrating arterioles that surround a central draining venule. The surface arterioles that feed the penetrating arterioles are interconnected via an extensively anastomotic plexus. Embolic occlusion of a small surface arteriole rarely produces a local infarct, because collateral blood flow is available through the vascular reticulum. Collateral flow also protects against infarct after occlusion of a single penetrating arteriole. Cortical infarction requires blockage of a major arterial trunk, with arrest of blood flow to a relatively large vascular territory. For striate cortex, the major vessels compromised by emboli are the inferior calcarine and superior calcarine arteries, as well as the distal branches of the middle cerebral artery. Their vascular territories have a fairly consistent relationship with the retinotopic map. Consequently, occlusion by emboli results in stereotypical visual field defects. The organization of the arterial supply to the occipital lobe provides an anatomical explanation for a phenomenon that has long puzzled neuro-ophthalmologists, namely, that of the myriad potential patterns of cortical visual field loss, only a few are encountered commonly from embolic cortical stroke.