A clinico-anatomical dissection of the magnocellular and parvocellular pathways in a patient with the Riddoch syndrome.

KEY MESSAGE: The Riddoch syndrome is thought to be caused by damage to the primary visual cortex (V1), usually following a vascular event. This study shows that damage to the anatomical input to V1, i.e., the optic radiations, can result in selective visual deficits that mimic the Riddoch syndrome. The results also highlight the differential susceptibility of the magnocellular and parvocellular visual systems to injury. Overall, this study offers new insights that will improve our understanding of the impact of brain injury and neurosurgery on the visual pathways. The Riddoch syndrome, characterised by the ability to perceive, consciously, moving visual stimuli but not static ones, has been associated with lesions of primary visual cortex (V1). We present here the case of patient YL who, after a tumour resection surgery that spared his V1, nevertheless showed symptoms of the Riddoch syndrome. Based on our testing, we postulated that the magnocellular (M) and parvocellular (P) inputs to his V1 may be differentially affected. In a first experiment, YL was presented with static and moving checkerboards in his blind field while undergoing multimodal magnetic resonance imaging (MRI), including structural, functional, and diffusion, acquired at 3 T. In a second experiment, we assessed YL's neural responses to M and P visual stimuli using psychophysics and high-resolution fMRI acquired at 7 T. YL's optic radiations were partially damaged but not severed. We found extensive activity in his visual cortex for moving, but not static, visual stimuli, while our psychophysical tests revealed that only low-spatial frequency moving checkerboards were perceived. High-resolution fMRI revealed strong responses in YL's V1 to M stimuli and very weak ones to P stimuli, indicating a functional P lesion affecting V1. In addition, YL frequently reported seeing moving stimuli and discriminating their direction of motion in the absence of visual stimulation, suggesting that he was experiencing visual hallucinations. Overall, this study highlights the possibility of a selective loss of P inputs to V1 resulting in the Riddoch syndrome and in hallucinations of visual motion.

[Bilateral visual pathway invasion of occipital astrocytoma: a case report].

A 33-year-old female presented to the ophthalmology clinic with right periorbital redness and pain for 12 hours. CT revealed right optic nerve thickening and enlargement. Cranial MRI demonstrated abnormalities in the corpus callosum, bilateral hippocampi, thalamus, basal ganglia, temporal-parietal lobes, and the left frontal lobe. Ocular B-scan ultrasound showed elevated optic disc and high echogenic signals in the right vitreous cavity. The patient had a history of surgical resection, radiation therapy, and chemotherapy for a left occipital glioma two years prior, with pathology indicating astrocytoma (World Health Organization Grade Ⅱ). Combining the patient's history and diagnostic findings, the confirmed diagnosis is bilateral occipital astrocytoma with invasion into the right transverse sinus, bilateral optic pathways involvement related to the left occipital astrocytoma, and seeding of astrocytoma in the right vitreous cavity.

Differential functional reorganization of ventral and dorsal visual pathways following childhood hemispherectomy.

Hemispherectomy is a surgical procedure in which an entire hemisphere of a patient's brain is resected or functionally disconnected to manage seizures in individuals with drug-resistant epilepsy. Despite the extensive loss of both ventral and dorsal visual pathways in one hemisphere, pediatric patients who have undergone hemispherectomy show a remarkably high degree of perceptual function across many domains. In the current study, we sought to understand the extent to which functions of the ventral and dorsal visual pathways reorganize to the contralateral hemisphere following childhood hemispherectomy. To this end, we collected fMRI data from an equal number of left and right hemispherectomy patients who completed tasks that typically elicit lateralized responses from the ventral or the dorsal pathway, namely, word (left ventral), face (right ventral), tool (left dorsal), and global form (right dorsal) perception. Overall, there was greater evidence of functional reorganization in the ventral pathway than in the dorsal pathway. Importantly, because ventral and dorsal reorganization was tested within the very same patients, these results cannot be explained by idiosyncratic factors such as disease etiology, age at the time of surgery, or age at testing. These findings suggest that because the dorsal pathway may mature earlier, it may have a shorter developmental window of plasticity than the ventral pathway and, hence, be less malleable after perturbation.

An unusual presentation of bilateral optic pathway glioma in Crouzon Syndrome.

Crouzon Syndrome is a genetic craniosynostosis disorder associated with a high risk of ophthalmologic sequelae secondary to structural causes. However, ophthalmologic disorders due to intrinsic nerve aberrations in Crouzon Syndrome have not been described. Optic pathway gliomas (OPGs) are low grade gliomas that are intrinsic to the visual pathway, frequently associated with Neurofibromatosis type 1 (NF-1). OPGs involving both optic nerves without affecting the optic chiasm are rarely seen outside of NF-1. We report an unusual case of bilateral optic nerve glioma without chiasmatic involvement in a 17-month-old male patient with Crouzon Syndrome without any clinical or genetic findings of NF-1. This case suggests that close ophthalmologic follow up and orbital MRIs may benefit patients with Crouzon Syndrome.

[Opportunities and challenges in the diagnosis and treatment of optic chiasm lesions: a clinical and research perspective].

The optic chiasm is a critical component of the visual pathway, and lesions in the pituitary and sellar regions can cause irreversible damage to a patient's visual function, resulting in a significant decrease in their quality of life. As a result, neuro-ophthalmology evaluation is a crucial part of the multidisciplinary treatment of pituitary diseases. However, due to the significant variation in the anatomical structure of the optic chiasm and the sellar region, as well as the complexity of the injury mechanism, chiasm injury can result in diverse manifestations and severity levels, which can make it difficult to correlate with anatomical parameters. In recent years, research has increasingly focused on the early recognition of optic chiasm compression, the prediction of visual function after intervention, and the long-term neurodegenerative effects, while optical coherence tomography (OCT), electrophysiological examinations, and functional magnetic resonance imaging are currently the most commonly used methods for evaluating sellar region lesions. However, the role of these methods, represented by OCT, in clinical diagnosis and treatment, still lacks high-level clinical evidence support, and the evaluation and prediction of optic chiasm function remain key areas for further study. In addition to compression lesions, lesions such as inflammation, infiltration, and demyelination in the sellar region, caused by systemic multi-system diseases, can also lead to visual function damage and require recognition in clinical practice.

Cross-subject variability of the optic radiation anatomy in a cohort of 1065 healthy subjects.

INTRODUCTION: Optic radiations are tracts of particular interest for neurosurgery, especially for temporal lobe resection, because their lesion is responsible for visual field defects. However, histological and MRI studies found a high inter-subject variability of the optic radiation anatomy, especially for their most rostral extent inside the Meyer's temporal loop. We aimed to better assess inter-subject anatomical variability of the optic radiations, in order to help to reduce the risk of postoperative visual field deficiencies. METHODS: Using an advanced analysis pipeline relying on a whole-brain probabilistic tractography and fiber clustering, we processed the diffusion MRI data of the 1065 subjects of the HCP cohort. After registration in a common space, a cross-subject clustering on the whole cohort was performed to reconstruct the reference optic radiation bundle, from which all optic radiations were segmented on an individual scale. RESULTS: We found a median distance between the rostral tip of the temporal pole and the rostral tip of the optic radiation of 29.2 mm (standard deviation: 2.1 mm) for the right side and 28.8 mm (standard deviation: 2.3 mm) for the left side. The difference between both hemispheres was statistically significant (p = 1.10-8). CONCLUSION: We demonstrated inter-individual variability of the anatomy of the optic radiations on a large-scale study, especially their rostral extension. In order to better guide neurosurgical procedures, we built a MNI-based reference atlas of the optic radiations that can be used for fast optic radiation reconstruction from any individual diffusion MRI tractography.

Development of an AAV-based model of tauopathy targeting retinal ganglion cells and the mouse visual pathway to study the role of microglia in Tau pathology.

Tauopathy is a typical feature of Alzheimer's disease of major importance because it strongly correlates with the severity of cognitive deficits experienced by patients. During the pathology, it follows a characteristic spatiotemporal course which takes its origin in the transentorhinal cortex, and then gradually invades the entire forebrain. To study the mechanisms of tauopathy, and test new therapeutic strategies, it is necessary to set-up relevant and versatile in vivo models allowing to recapitulate tauopathy. With this in mind, we have developed a model of tauopathy by overexpression of the human wild-type Tau protein in retinal ganglion cells in mice (RGCs). This overexpression led to the presence of hyperphosphorylated forms of the protein in the transduced cells as well as to their progressive degeneration. The application of this model to mice deficient in TREM2 (Triggering Receptor Expressed on Myeloid cells-2, an important genetic risk factor for AD) as well as to 15-month-old mice showed that microglia actively participate in the degeneration of RGCs. Surprisingly, although we were able to detect the transgenic Tau protein up to the terminal arborization of RGCs at the level of the superior colliculi, spreading of the transgenic Tau protein to post-synaptic neurons was detected only in aged animals. This suggests that there may be neuron-intrinsic- or microenvironment mediators facilitating this spreading that appear with aging.

Impact of keratoprosthesis implantation on retinal and visual pathway function assessed by electrophysiological testing.

PURPOSE: To investigate the impact of Boston Type I Keratoprosthesis (BI-Kpro) implantation on retinal and visual pathway function, respectively, assessed by full-field electroretinography (ERG) and visually evoked potentials (VEPs). METHODS: This is a prospective interventional longitudinal study, and patients with BI-Kpro implantation were assessed preoperatively and at 3 and 12 months after surgery. ERG, flash, and pattern-reversal VEPs (15' and 60' checks) along with visual acuity (VA) were performed. RESULTS: A total of 13 patients (24 to 88 years of age) were included. Mean baseline VA (logMAR) improved from 2.30 to 1.04 at 3 months and to 1.00 at 12 months. Flash VEPs were normal in 6 (46%) patients and in 10 (77%) patients at the 12-month follow-up. PVEP was non-detectable in all patients preoperatively for both check sizes. For 15' check size, 6 (46%) patients showed responses after 3 and 12 months except for 1 patient with normal responses at 12 months with the remaining non-detectable. For 60' checks, 11 (85%) patients had responses 3 months after surgery with only 9 (70%) showing responses at 12 months. Abnormal full-field ERGs were found in all patients preoperatively. Amplitude improvement was found in 10 (77%) patients from baseline to 3 months and in 8 (62%) patients from the 3- to the 12-month follow-up. CONCLUSIONS: In this small cohort of patients with BI-Kpro implantation, a remarkable improvement on visual function quantitatively assessed by electrophysiological testing was found in the majority of cases. Visual electrophysiological testing can contribute to objectively assess functional outcomes in this population.

Evolution of flash visual evoked potentials to monitor visual pathway integrity during tumor resection: illustrative cases and literature review.

Flash visual evoked potentials (fVEPs) provide a means to interrogate visual system functioning intraoperatively during tumor resection in which the optic pathway is at risk for injury. Due to technical limitations, fVEPs have remained underutilized in the armamentarium of intraoperative neurophysiological monitoring (IONM) techniques. Here we review the evolution of fVEPs as an IONM technique with emphasis on the enabling technological and intraoperative improvements. A combined approach with electroretinography (ERG) has enhanced feasibility of fVEP neuromonitoring as a practical application to increase safety and reduce error during tumor resection near the prechiasmal optic pathway. The major advance has been towards differentiating true cases of damage from false findings. We use two illustrative neurosurgical cases in which fVEPs were monitored with and without ERG to discuss limitations and demonstrate how ERG data can clarify false-positive findings in the operating room. Standardization measures have focused on uniformity of photostimulation parameters for fVEP recordings between neurosurgical groups.

Neurovascular Compression in the Anterior Visual Pathway: A Case Series.

A retrospective review of 29 patients with neurovascular compression syndrome (NVCS) involving the anterior visual pathway was conducted. Various patterns of NVCS and visual defects were identified, most commonly involving the optic nerve and internal carotid artery. Most patients were stable, except one with progressive visual field defects. Although mostly asymptomatic, NVCS can rarely cause compressive optic neuropathy. NVCS should be kept in the differential diagnosis of normal tension glaucoma, especially with progressive visual loss despite treatment. Patients with progressive visual loss may require decompression surgery. Non-contrast computed tomography scan may miss NVCS, and magnetic resonance imaging is diagnostic.

Prognostic Value of Optical Coherence Tomography Characteristics in Anterior Visual Pathway Meningiomas.

BACKGROUND: Anterior visual pathway meningiomas (AVPM) represent 2.5%-18% of all meningiomas. They may affect visual function, including visual acuity (VA) and visual field (VF). The principal modes of treatment are surgery and radiotherapy. The prognostic value of macular ganglion cell complex count (GCC) thickness has not been assessed in the literature thus far. The purpose of this study was to evaluate the prognostic value of pre-treatment optical coherence tomography (OCT) parameters (retinal nerve fiber layer and GCC) for visual outcomes in patients with AVPM. METHODS: We retrospectively reviewed the medical records of all patients with AVPM who were treated in the Sheba Medical Center between 2011 and 2020. Included were patients with valid data containing preintervention OCT findings on the CIRRUS device and a minimum follow-up of 6 months. Preintervention and postintervention data on comprehensive ophthalmic examinations and OCT parameters of the affected eyes were retrieved. The correlation between preintervention OCT parameters and the visual outcome was assessed. The patients were also divided into 2 groups according to preintervention GCC (thin vs normal), and the visual outcome was compared between groups. RESULTS: In total, 186 patients' medical records were analyzed, and 38 patients who met the inclusion criteria were included in the study (mean age at diagnosis 52.8 ± 12.2 years, 28 women). Twenty-nine patients had 1 affected eye, and 9 had bilateral insult. A higher preinterventional average GCC was associated with better VA at 6 months, 1 year, and 2 years after intervention (r = -0.5, P ≤ 0.004, 0.005, and 0.03, respectively). There was a significant correlation between preinterventional GCC and VF mean deviation 2 years after intervention (r = 0.7, P ≤ 0.001). The thinner the GCC, the more prominent was the change in VA from before intervention to 2 years after intervention ( P ≤ 0.008). Correction for multiple comparisons with the Benjamini-Hochberg procedure did not change the significance of our findings. CONCLUSIONS: OCT parameters (GCC) have a predictive value in AVPM. There is strong correlation between preinterventional GCC and VA shortly after the intervention. Although a thin GCC is generally considered a negative prognostic factor, improvement in clinical parameters was also evident in patients with thin GCC. The potential of improvement despite preinterventional GCC thinning can add to the clinical discussion of the prognosis, and therefore, we recommend the patients with AVPM to undergo OCT and to be advised that GCC thinning alone should not be used as a major criterion in deciding whether treatment should be pursued.

Decussating axons segregate within the anterior core of the primate optic chiasm.

BACKGROUND: The axons of ganglion cells in the nasal retina decussate at the optic chiasm. It is unclear why tumours cause more injury to crossing nasal fibres, thereby giving rise to temporal visual field loss in each eye. To address this issue, the course of fibres through the optic chiasm was examined following injection of a different fluorescent tracer into each eye of a monkey. METHODS: Under general anaesthesia, cholera toxin subunit B-Alexa Fluor 488 was injected into the right eye and cholera toxin subunit B-Alexa Fluor 594 was injected into the left eye of a single normal adult male rhesus monkey. After a week's survival for anterograde transport, serial coronal sections through the primary optic pathway were examined. RESULTS: A zone within the core of the anterior and mid portions of the optic chiasm was comprised entirely of crossing fibres. This zone of decussation was delineated by segregated, interwoven sheets of green (right eye) and red (left eye) fibres. It expanded steadily to fill more of the optic chiasm as fibres coursed posteriorly towards the optic tracts. Eventually, crossed fibres became completely intermingled with uncrossed fibres, so that ocular separation was lost. CONCLUSIONS: A distinct, central compartment located within the anterior two-thirds of the optic chiasm contains only crossing fibres. Sellar tumours focus their compressive force on this portion of the structure, explaining why they so often produce visual field loss in the temporal fields.

Visual Pathway Involvement in NMDA Receptor Encephalitis: A Clinical, Optical Coherence Tomography, and 18-Fluorodeoxyglucose PET/CT Approach.

BACKGROUND: Anti-NMDA receptor (NMDAR) encephalitis patients have been reported to exhibit visual dysfunction without retinal thinning. The objective of our study was to examine the involvement of the visual pathway structure and function in anti-NMDAR encephalitis by assessing postrecovery visual function and retinal structure, and acute-phase occipital cortex function. METHODS: In this cross-sectional study, patients diagnosed with anti-NMDAR encephalitis per consensus criteria underwent postrecovery visual acuity (VA) testing and optical coherence tomography (OCT) with automated retinal layer segmentation. Clinical data and acute-phase brain 18F-fluorodeoxyglucose (FDG) PET/CT (performed within 90 days of symptom onset, assessed qualitatively and semi-quantitatively) were retrospectively analyzed. VA and OCT measures were compared between anti-NMDAR and age, sex, and race-matched healthy controls (HC). When available, FDG-PET/CT metabolism patterns were analyzed for correlations with VA, and OCT measures. RESULTS: A total of 16 anti-NMDAR (32 eyes) and 32 HC (64 eyes) were included in the study. Anti-NMDAR exhibited lower low-contrast VA (2.5% contrast: -4.4 letters [95% CI; -8.5 to -0.3]; P = 0.04, 1.25% contrast: -6.8 letters [95%CI; -12 to -1.7]; P = 0.01) compared with HC, but no differences were found on OCT-derived retinal layer thicknesses. Acute-phase FDG-PET/CT medial occipital cortex metabolism did not correlate with follow-up low-contrast VA or ganglion cell/inner plexiform layer thickness (GCIPL) (n = 7, 2.5% contrast: r = -0.31; P = 0.50, 1.25% contrast: r = -0.34; P = 0.45, GCIPL: r = -0.04; P = 0.94). CONCLUSIONS: Although the visual system seems to be involved in anti-NMDAR encephalitis, no retinal structural or occipital cortex functional abnormalities seem to be responsible for the visual dysfunction. When detected acutely, occipital lobe hypometabolism in anti-NMDAR encephalitis does not seem to associate with subsequent retrograde trans-synaptic degenerative phenomena, potentially reflecting reversible neuronal/synaptic dysfunction in the acute phase of the illness rather than neuronal degeneration.

A non-canonical retina-ipRGCs-SCN-PVT visual pathway for mediating contagious itch behavior.

Contagious itch behavior informs conspecifics of adverse environment and is crucial for the survival of social animals. Gastrin-releasing peptide (GRP) and its receptor (GRPR) in the suprachiasmatic nucleus (SCN) of the hypothalamus mediates contagious itch behavior in mice. Here, we show that intrinsically photosensitive retina ganglion cells (ipRGCs) convey visual itch information, independently of melanopsin, from the retina to GRP neurons via PACAP-PAC1R signaling. Moreover, GRPR neurons relay itch information to the paraventricular nucleus of the thalamus (PVT). Surprisingly, neither the visual cortex nor superior colliculus is involved in contagious itch. In vivo calcium imaging and extracellular recordings reveal contagious itch-specific neural dynamics of GRPR neurons. Thus, we propose that the retina-ipRGC-SCN-PVT pathway constitutes a previously unknown visual pathway that probably evolved for motion vision that encodes salient environmental cues and enables animals to imitate behaviors of conspecifics as an anticipatory mechanism to cope with adverse conditions.

Visual Field Defect Patterns Associated With Lesions of the Retrochiasmal Visual Pathway.

BACKGROUND: Perimetry is widely used in the localization of retrochiasmal visual pathway lesions. Although macular sparing, homonymous paracentral scotomas, and quadrantanopias are regarded as features of posterior retrochiasmal visual pathway lesions, incongruous hemianopia is regarded as a hallmark of anterior lesions. Recent studies have questioned the specificity of these defect patterns. METHODS: Retrospective record review conducted in a single, academic, medical center using an electronic search engine with the terms ""homonymous hemianopia," "optic tract," "temporal lobectomy," "visual field defect," and "MRI." Patients were included if they had reliable, automated, static visual fields, high-quality reviewable MRI scans, and pertinent lesions. MRI lesions were assigned to 1 of 6 retrochiasmal visual pathway segments by the study neuroradiologist. Two study authors independently reviewed the visual fields and designated 10 different defect patterns. RESULTS: From an original cohort of 256 cases, only 83 had MRI-defined lesions that were limited to particular retrochiasmal segments and had visual field defect patterns that allegedly permitted localization to those particular segments. The 5 contralateral nerve fiber bundle defects were exclusive to optic tract tumors with rostral extension. Pie-in-the-sky defects were exclusive to Meyer loop lesions. Among 22 fields with macular sparing, 86% arose from the visual cortex or posterior optic radiations. Among 31 fields with homonymous quadrantanopias, 77% arose from Meyer loop, visual cortex, or posterior optic radiations. Among 13 fields with homonymous paracentral scotomas, 69% arose from visual cortex or posterior optic radiations. Optic tract lesions accounted for 70% of incongruous hemianopias but that pattern occurred uncommonly. CONCLUSION: In correlating discrete MRI-defined retrochiasmal lesions with visual field defect patterns identified on static perimetry, this study showed that macular sparing, homonymous paracentral scotomas, and quadrantanopias localized to the visual cortex and posterior optic radiations segments but not exclusively. It has differed from an earlier study in showing that incongruous hemianopias occur predominantly from optic tract lesions.

Caracterización de las lesiones compresivas de la vía visualanterior / Characterization of Compressive Lesions of the Anterior VisualPathway

Objetivo: Determinar las características clínico-epidemiológicas de los pacientes diagnosticados con lesiones compresivas de la vía visual anterior. Métodos: Se realizó un estudio descriptivo transversal durante el período comprendido entre mayo de 2018 y marzo de 2020 con 41 pacientes con diagnóstico de síndrome compresivo de la vía visual anterior atendidos en el Servicio de Neuroftalmología del Instituto Cubano de Oftalmología "Ramón Pando Ferrer". Resultados: La mayor frecuencia en cuanto a síntomas fue la disminución progresiva de la visión central. Se encontraron lesiones de tipo tumoral en 39 pacientes para el 95,1 por ciento. Los defectos hemianópticos se detectaron en el campo visual del 45 por ciento de la muestra y el 33 por ciento presentó disminución difusa de la sensibilidad retiniana. Conclusiones: La mayoría de los pacientes fueron del sexo femenino en edades medias de la vida. Predominaron las lesiones tumorales sobre las vasculares. Los macroadenomas de hipófisis y los meningiomas fueron las etiologías más frecuentes y el sitio de compresión más encontrado fue el quiasma óptico. Se detectó disminución del grosor del complejo de células ganglionares maculares en la tomografía de coherencia óptica de la mayoría de los enfermos(AU)

Objective: To determine the clinical-epidemiological characteristics of patients diagnosed with compressive lesions of the anterior visual pathway. Methods: A cross-sectional descriptive study was conducted during the period from May 2018 to March 2020 with 41 patients diagnosed with compressive syndrome of the anterior visual pathway attended at the Neurophthalmology Service of the Cuban Institute of Ophthalmology "Ramón Pando Ferrer". Results: The most frequent symptom was the progressive decrease of central vision. Tumor type lesions were found in 39 patients for 95.1 percent. Hemianoptic defects were detected in the visual field of 45 percent of the sample and 33 percent presented diffuse decrease of retinal sensitivity. Conclusions: The majority of patients were female at middle ages of life. Tumor lesions predominated over vascular lesions. Pituitary macroadenomas and meningiomas were the most frequent etiologies and the most frequent site of compression was the optic chiasm. Decreased thickness of the macular ganglion cell complex was detected in the optical coherence tomography of most of the patients(AU)