Neuro-ophthalmology

Neuro-ophthalmology publications

Marsiglia M, Chwalisz BK, Maher M. Neuroradiologic Imaging of Neurologic and Neuro-Ophthalmic Complications of Coronavirus-19 Infection. J Neuroophthalmol 2021;41(4):452-460.Abstract
BACKGROUND: To review the literature and provide a summary of COVID-19-related neurologic and neuro-ophthalmic complications. METHODS: The currently available literature was reviewed on PubMed and Google Scholar using the following keywords for searches: CNS, Neuro-Ophthalmology, COVID-19, SARS-CoV-2, coronavirus, optic neuritis, pseudotumor cerebri, Acute Disseminated Encephalomyelitis, posterior reversible encephalopathy syndrome (PRES), meningitis, encephalitis, acute necrotizing hemorrhagic encephalopathy, and Guillain-Barré and Miller Fisher syndromes. RESULTS: Neuroradiologic findings of neurologic and neuro-ophthalmologic complications in relationship to COVID-19 infection were reviewed. Afferent visual pathway-related disorders with relevant imaging manifestations included fundus nodules on MRI, papilledema and pseudotumor cerebri syndrome, optic neuritis, Acute Disseminated Encephalomyelitis, vascular injury with thromboembolism and infarct, leukoencephalopathy, gray matter hypoxic injury, hemorrhage, infectious meningitis/encephalitis, acute necrotizing hemorrhagic encephalopathy, and PRES. Efferent visual pathway-related complications with relevant imaging manifestations were also reviewed, including orbital abnormalities, cranial neuropathy, Guillain-Barré and Miller Fisher syndromes, and nystagmus and other eye movement abnormalities related to rhombencephalitis. CONCLUSION: COVID-19 can cause central and peripheral nervous system disease, including along both the afferent and efferent components of visual axis. Manifestations of disease and long-term sequela continue to be studied and described. Familiarity with the wide variety of neurologic, ophthalmic, and neuroradiologic presentations can promote prompt and appropriate treatment and continue building a framework to understand the underlying mechanism of disease.
Douglas VP, Flores C, Douglas KA, Strominger MB, Kasper E, Torun N. OCULOMOTOR NERVE SCHWANNOMA: CASE SERIES AND LITERATURE REVIEW. Surv Ophthalmol 2021;Abstract
Oculomotor nerve schwannomas (ONS) are rare benign cranial nerve tumors. There are only a limited number of reports on this pathology in the literature, and there is currently no established management guidelines that aid providers in deciding on surgical versus non-surgical management. We assess the published literature on the topic to identify indications for treatment as well as outcome measures (e.g., local control rates, survival rates, and complication rates) that have been reported as associated with the various treatment modalities. We attempt to develop an algorithm for evaluation and treatment of ONS in order to establish consensus on how these tumors should be treated.
Bennett CR, Bauer CM, Bex PJ, Bottari D, Merabet LB. Visual search performance in cerebral visual impairment is associated with altered alpha band oscillations. Neuropsychologia 2021;161:108011.Abstract
Individuals with cerebral visual impairment (CVI) often present with deficits related to visuospatial processing. However, the neurophysiological basis underlying these higher order perceptual dysfunctions have not been clearly identified. We assessed visual search performance using a novel virtual reality based task paired with eye tracking to simulate the exploration of a naturalistic scene (a virtual toy box). This was combined with electroencephalography (EEG) recordings and an analysis pipeline focusing on time frequency decomposition of alpha oscillatory activity. We found that individuals with CVI showed an overall impairment in visual search performance (as indexed by decreased success rate, as well as increased reaction time, visual search area, and gaze error) compared to controls with neurotypical development. Analysis of captured EEG activity following stimulus onset revealed that in the CVI group, there was a distinct lack of strong and well defined posterior alpha desynchronization; an important signal involved in the coordination of neural activity related to visual processing. Finally, an exploratory analysis revealed that in CVI, the magnitude of alpha desynchronization was associated with impaired visual search performance as well as decreased volume of specific thalamic nuclei implicated in visual processing. These results suggest that impairments in visuospatial processing related to visual search in CVI are associated with alterations in alpha band oscillations as well as early neurological injury at the level of visual thalamic nuclei.
Shi L, Yuan T, Fan S, Zheng J, Diao Y, Qin G, Liu D, Zhu G, Qin K, Liu H, Zhang H, Yang A, Meng F, Zhang J. Comparison of cognitive performance between patients with Parkinson's disease and dystonia using an intraoperative recognition memory test. Sci Rep 2021;11(1):20724.Abstract
Neuroscientific studies on the function of the basal ganglia often examine the behavioral performance of patients with movement disorders, such as Parkinson's disease (PD) and dystonia (DT), while simultaneously examining the underlying electrophysiological activity during deep brain stimulation surgery. Nevertheless, to date, there have been no studies comparing the cognitive performance of PD and DT patients during surgery. In this study, we assessed the memory function of PD and DT patients with the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). We also tested their cognitive performance during the surgery using a continuous recognition memory test. The results of the MoCA and MMSE failed to reveal significant differences between the PD and DT patients. Additionally, no significant difference was detected by the intraoperative memory test between the PD and DT patients. The intraoperative memory test scores were highly correlated with the MMSE scores and MoCA scores. Our data suggest that DT patients perform similarly to PD patients in cognitive tests during surgery, and intraoperative memory tests can be used as a quick memory assessment tool during surgery.
Winter CC, He Z, Jacobi A. Axon Regeneration: A Subcellular Extension in Multiple Dimensions. Cold Spring Harb Perspect Biol 2021;Abstract
Axons are a unique cellular structure that allows for the communication between neurons. Axon damage compromises neuronal communications and often leads to functional deficits. Thus, developing strategies that promote effective axon regeneration for functional restoration is highly desirable. One fruitful approach is to dissect the regenerative mechanisms used by some types of neurons in both mammalian and nonmammalian systems that exhibit spontaneous regenerative capacity. Additionally, numerous efforts have been devoted to deciphering the barriers that prevent successful axon regeneration in the most regeneration-refractory system-the adult mammalian central nervous system. As a result, several regeneration-promoting strategies have been developed, but significant limitations remain. This review is aimed to summarize historic progression and current understanding of this exciting yet incomplete endeavor.
Ahangari N, Munoz DG, Coulombe J, Gray DA, Engle EC, Cheng L, Woulfe J. Nuclear IMPDH Filaments in Human Gliomas. J Neuropathol Exp Neurol 2021;Abstract
The analysis of nuclear morphology plays an important role in glioma diagnosis and grading. We previously described intranuclear rods (rods) labeled with the SDL.3D10 monoclonal antibody against class III beta-tubulin (TUBB3) in human ependymomas. In a cohort of adult diffuse gliomas, we identified nuclear rods in 71.1% of IDH mutant lower-grade gliomas and 13.7% of IDH wild-type glioblastomas (GBMs). The presence of nuclear rods was associated with significantly longer postoperative survival in younger (≤65) GBM patients. Consistent with this, nuclear rods were mutually exclusive with Ki67 staining and their prevalence in cell nuclei inversely correlated with the Ki67 proliferation index. In addition, rod-containing nuclei showed a relative depletion of lamin B1, suggesting a possible association with senescence. To gain insight into their functional significance, we addressed their antigenic properties. Using a TUBB3-null mouse model, we demonstrate that the SDL.3D10 antibody does not bind TUBB3 in rods but recognizes an unknown antigen. In the present study, we show that rods show immunoreactivity for the nucleotide synthesizing enzymes inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase. By analogy with the IMPDH filaments that have been described previously, we postulate that rods regulate the activity of nucleotide-synthesizing enzymes in the nucleus by sequestration, with important implications for glioma behavior.
Douglas VP, Douglas KA, Cestari DM. Ophthalmic manifestations of dementing disorders. Curr Opin Ophthalmol 2021;32(6):515-520.Abstract
PURPOSE OF REVIEW: Dementia is a term for loss of memory, language, problem-solving, and other thinking abilities, which significantly interferes with daily life. Certain dementing conditions may also affect visual function. The eye is an accessible window to the brain that can provide valuable information for the early diagnosis of people who suffer from Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies as well as from more rare causes of dementias, such as Creutzfeldt-Jacob and Huntington's diseases. Herein, we present the ocular manifestations of neurocognitive disorders focusing on the neuro-ophthalmic ones and further discuss potential ocular biomarkers that could help in early detection of these disorders. RECENT FINDINGS: Ophthalmic examination along with the recent developments in in-vivo testing have provided a strong foundation of useful knowledge about brain disorder in neurodegenerative diseases without the need for invasive studies. Currently, a number of visual measures, such as visual acuity, contrast sensitivity, pupil response, and saccades in addition to various ophthalmic tests, such as electroretinogram, visual evoked potential, optical coherence tomography (OCT), and OCT-angiography have been widely used and evaluated as potential biomarkers for different stages of dementia. SUMMARY: Ophthalmologic and neuro-ophthalmic evaluation is evolving as an important part of the early diagnosis and management of people with dementia. A particular focus on ocular biomarkers in dementing illnesses has arisen over the past few years and there are several promising measures and imaging tools that have been proposed as potential biomarkers for these diseases.
Zhang M, Chen T, Zhong Y. Demographic and prognostic factors of optic nerve astrocytoma: a retrospective study of surveillance, epidemiology, and end results (SEER). BMC Cancer 2021;21(1):976.Abstract
BACKGROUND: Optic nerve astrocytomas (ONAs) are neurological neoplasms in the central nervous system (CNS), and they have the highest incidence rate among all the tumor types in the visual pathway. In this study, we conducted a Surveillance, Epidemiology, and End Results (SEER) -based research to explore the demographic, survival, and prognostic factors of patients diagnosed with ONAs. METHODS: Utilizing the SEER database, we retrospectively evaluated data of patients diagnosed with ONAs of all ages from 1984 to 2016. We used the Student's t distribution to test variables of patients and various characteristics, and Kaplan-Meier curve to illustrate overall survival (OS) with 95.0% confidence intervals (CIs). We also performed univariate and multivariate analyses to evaluate various variables' validity on overall survival. RESULTS: A total of 1004 cases were analyzed, and revealed that age (P<0.001, hazard ratio (HR) = 8.830, 95% CI: 4.088-19.073), tumor grade (P<0.001, HR = 1.927, 95% CI: 1.516-2.450), diagnostic confirmation (P<0.001, HR = 2.444, 95% CI: 1.632-3.660), and histology type (P = 0.046, HR = 1.563, 95% CI: 1.008-2.424) of the tumor were associated with decreased survival. CONCLUSIONS: From this large, comparative study of ONAs, we found that younger age may be considered as a protective indicator, while high-grade astrocytic tumors have a worse prognosis. We also found that diagnostic confirmation and tumor grade were independent prognostic factors in this patient population.
Gowrisankaran S, Shah AS, Roberts TL, Wiecek E, Chinn RN, Hawash KK, O'Brien MJ, Howell DR, Meehan WP, Raghuram A. Association between post-concussion symptoms and oculomotor deficits among adolescents. Brain Inj 2021;:1-11.Abstract
PURPOSE: To examine the association between Post-Concussion Symptom Scale (PCSS) scores, Convergence Insufficiency Symptom Survey (CISS) scores, and oculomotor deficits post-concussion. METHODS: Records of adolescent patients examined in a multidisciplinary concussion clinic between July 2014 and May 2019 were reviewed. PCSS and CISS scores, results of eye examination and oculomotor assessment, concussion history, and demographics were abstracted. RESULTS: One hundred and forty patient records (median age, 15.3 years; 52 males, presented 109 days (median) from their most recent concussion) met inclusion criteria. Mean total scores on PCSS and CISS were 46.67 ± 25.89 and 27.13 ± 13.22, respectively, and were moderately correlated with each other (r = 0.53, p < .001). Oculomotor deficits were observed in 123 (88%) patients. Step-wise linear regression identified increased PCSS total score to be significantly associated with decreased amplitude of accommodation (p < .001). Increased CISS total score was significantly associated with receded near point of convergence, developmental eye movement test error scores, and cause of concussion. CONCLUSION: High PCSS scores may indicate an accommodation deficit and thus prompt an oculomotor assessment in patients following a concussion. Using the CISS and a detailed oculomotor assessment may reveal underlying oculomotor deficits, which may benefit from treatment.
Pamir Z, Bauer CM, Bennett CR, Kran BS, Merabet LB. Visual perception supported by verbal mediation in an individual with cerebral visual impairment (CVI). Neuropsychologia 2021;160:107982.Abstract
Cerebral visual impairment (CVI) often presents with deficits associated with higher order visual processing. We report a case of an individual with CVI who uses a verbal mediation strategy to perceive and interact with his visual surroundings. Visual perceptual performance was assessed using a virtual reality based visual search task combined with eye tracking. Functional magnetic resonance imaging (fMRI) was employed to identify the neural correlates associated with this strategy. We found that when using verbal mediation, the individual could readily detect and track the target within the visual scene which was associated with robust activation within a network of occipito-parieto-temporal visual cortical areas. In contrast, when not using verbal mediation, the individual was completely unable to perform the task, and this was associated with dramatically reduced visual cortical activation. This unique compensatory strategy may be related to the individual's use of verbal working memory for the purposes of understanding complex visual information.
Douglas VP, Douglas KA, Reinshagen KL, Chwalisz BK. Case 292: Lyme Neuroborreliosis. Radiology 2021;300(2):484-488.Abstract
History A 24-year-old right-handed woman presented to a neuro-ophthalmology clinic in Massachusetts in the summer with acute binocular diplopia when looking down and to the left, which started about 1 month earlier. Her medical history was notable for Raynaud syndrome, recurrent streptococcal pharyngitis, and an allergy to amoxicillin. Three days prior to developing diplopia, she presented to an outside emergency department due to fever, chills, and back pain. She received ciprofloxacin for presumed urinary tract infection based on urinalysis, which demonstrated few bacteria and was negative for leukocyte esterase, nitrites, and white blood cells. She then presented again to an outside emergency department for diplopia evaluation. Initial MRI and MR angiography of the brain at that time did not demonstrate any relevant findings, and the patient was referred to our department for neuro-ophthalmic evaluation, where she was seen 4 weeks later. Neuro-ophthalmic examination revealed 20/20 visual acuity in both eyes, and a right hypertropia in left gaze, downgaze and right head tilt, with right eye excyclotorsion. There were no ocular signs of myasthenia gravis or thyroid eye disease, nor did the patient report ocular or systemic symptoms. She denied recent travel. High-spatial-resolution MRI of the brain and orbit were performed.
Bouffard MA, M Mallery R, Liao YJ, Torun N. Variation in Evolving Optic Neuritis. J Neuroophthalmol 2021;41(4):476-479.Abstract
BACKGROUND: The typical natural history of optic neuritis is subjected to important exceptions. Recognition of these exceptions has led to valuable insights regarding specific etiologies of optic neuritis. Exceptions to the natural history of recovering optic neuritis are well-defined (e.g., chronic relapsing inflammatory optic neuropathy), but exceptions to the natural history of evolving optic neuritis are less so. METHODS: Medical records of patients illustrating an atypical course of evolving optic neuritis were reviewed in a retrospective manner. Each patient was treated by at least one of the authors. RESULTS: Four patients were identified who illustrated an atypical natural history of incipient optic neuritis. Diagnoses included idiopathic optic neuritis, seropositive neuromyelitis optica spectrum disease, anti-myelin oligodendrocyte glycoprotein antibody disease, and multiple sclerosis in 1 patient each. Features of interest included an atypical temporal relationship between development of pain and onset of clinical optic neuropathy, an unusually protracted duration of pain, and an unusually long duration of worsening optic neuropathy before stabilization. CONCLUSIONS: This case series illustrates the substantial clinical heterogeneity which may be observed in the evolution of optic neuritis. The temporal relationship between development of pain and onset of clinical optic neuropathy, the duration of pain, and duration of worsening optic neuropathy before stabilization are all subjected to significant variability. Although most patients with optic neuritis present with painful vision loss which progresses over 1 week or less, careful attention to the exceptions described herein may facilitate earlier recognition of diagnostically challenging cases.
Jacobs HIL, Schoemaker D, Torrico-Teave H, Zuluaga Y, Velilla-Jimenez L, Ospina-Villegas C, Lopera F, Arboleda-Velasquez JF, Quiroz YT. Specific Abnormalities in White Matter Pathways as Interface to Small Vessels Disease and Cognition in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Individuals. Brain Connect 2021;Abstract
Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by leukoencephalopathy leading to cognitive impairment. Subtle cognitive deficits can be observed early in the course of the disease, before the occurrence of the first stroke. Therefore, markers that can predict disease progression at this early stage, when interventions are likely to alter disease course, are needed. We aimed to examine the biological cascade of microstructural and macrostructural white matter (WM) abnormalities underlying cognitive deficits in CADASIL. Methods: We examined 20 nondemented CADASIL mutation carriers and 23 noncarriers who underwent neuropsychological evaluation and magnetic resonance imaging. Using probabilistic tractography of key WM tracts, we examined group differences in diffusivity measures and WM hyperintensity volume. Successive mediation models examined whether tract-specific WM abnormalities mediated subtle cognitive differences between CADASIL mutation carriers and noncarriers. Results: The largest effect size differentiating the two groups was observed for left superior longitudinal fasciculus-temporal (SLFt) diffusivity (Cohen's f = 0.49). No group differences were observed with a global diffusion measure. These specific microstructural differences in the SLFt were associated with higher WM hyperintensities burden, and subtle executive deficits in CADASIL mutation carriers. Discussion: Worse diffusivity in the left SLFt is related to greater severity of small vessel disease and worse executive functioning in the asymptomatic stage of the disease. Worse diffusivity of the left SLFt may potentially hold promise as an indicator of disease progression.

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