Improving Understanding of Visual Snow by Quantifying its Appearance and Effect on Vision.

Purpose: Visual snow is the hallmark of the neurological condition visual snow syndrome (VSS) but the characteristics of the visual snow percept remain poorly defined. This study aimed to quantify its appearance, interobserver variability, and effect on measured visual performance and self-reported visual quality. Methods: Twenty-three participants with VSS estimated their visual snow dot size, separation, luminance, and flicker rate by matching to a simulation. To assess whether visual snow masks vision, we compared pattern discrimination thresholds for textures that were similar in spatial scale to visual snow as well as more coarse than visual snow, in participants with VSS, and with and without external noise simulating visual snow in 23 controls. Results: Mean and 95% confidence intervals for visual snow appearance were: size (6.0, 5.8-6.3 arcseconds), separation (2.0, 1.7-2.3 arcmin), luminance (72.4, 58.1-86.8 cd/m2), and flicker rate (25.8, 18.9-32.8 frames per image at 120 hertz [Hz]). Participants with finer dot spacing estimates also reported greater visibility of their visual snow (τb = -0.41, 95% confidence interval [CI] = -0.62 to -0.13, P = 0.01). In controls, adding simulated fine-scale visual snow to textures increased thresholds for fine but not coarse textures (F(1, 22) = 4.98, P = 0.036, ηp2 = 0.19). In VSS, thresholds for fine and coarse textures were similar (t(22) = 0.54, P = 0.60), suggesting that inherent visual snow does not act like external noise in controls. Conclusions: Our quantitative estimates of visual snow constrain its likely neural origins, may aid differential diagnosis, and inform future investigations of how it affects vision. Methods to quantify visual snow are needed for evaluation of potential treatments.

Exploring Factors That Prolong the Diagnosis of Myasthenia Gravis.

Background and Objectives: Myasthenia gravis (MG) is a condition with significant phenotypic variability, posing a diagnostic challenge to many clinicians worldwide. Prolonged diagnosis can lead to reduced remission rates and morbidity. This study aimed to identify factors leading to a longer time to diagnosis in MG that could be addressed in future to optimize diagnosis time. Methods: One hundred and ten patients from 3 institutions in Melbourne, Australia, were included in this retrospective cohort study. Demographic and clinical data were collected for these patients over the first 5 years from diagnosis and at 10 years. Nonparametric statistical analysis was used to identify factors contributing to a longer diagnosis time. Results: The median time for MG diagnosis was 102 (345) days. 90% of patients were diagnosed before 1 year. Female patients took longer than male patients to be diagnosed (p = 0.013). The time taken for first presentation after symptom onset contributed most to diagnosis time (median 17 [141] days), with female patients and not working as contributory factors. Neurology referral took longer if patients had diplopia (p = 0.022), respiratory (p = 0.026) symptoms, or saw an ophthalmologist first (p < 0.001). Outpatient management compared with inpatient was associated with a longer time to be seen by a neurologist from referral (p < 0.001), for the first diagnostic result to return (p = 0.001), and for the result to be reviewed (p < 0.001). Ocular MG had a median greater time to neurologist review than generalized MG (median 5 [25] days vs 1 [13] days, p = 0.035). Electrophysiology tests took longer for outpatients than inpatients (median 21 [35] days vs 2 [8] days, p < 0.001). Outpatients were also started on treatment later than inpatients (p < 0.001). There was no association of MG severity, ethnicity, age, medical and ocular comorbidities, and public or private health service on diagnosis time. There was also no impact of time to diagnosis on Myasthenia Gravis Foundation of America outcomes, number of follow-ups or hospitalizations, or prevalence of treatments used. This study is limited by low patient numbers and its retrospective nature. Discussion: This study identified several factors that can contribute to a prolonged diagnosis time of MG. Patient and clinician education about MG and outpatient diagnostic efficiency needs emphasis. Further studies are also needed to explore the delayed presentation time of women and nonworking patients in MG.

James Sharpe's Contributions to Neurology and Neuro-ophthalmology: A Posthumous Tribute 10 Years On.

Dr. Sharpe was a leading eye movement researcher who had also been the editor of this journal. We wish to mark the 10th anniversary of his death by providing a sense of what he had achieved through some examples of his research.

Eye movement characteristics are not significantly influenced by psychiatric comorbidities in people with visual snow syndrome.

Visual snow syndrome (VSS) is a neurological disorder primarily affecting the processing of visual information. Using ocular motor (OM) tasks, we previously demonstrated that participants with VSS exhibit altered saccade profiles consistent with visual attention impairments. We subsequently proposed that OM assessments may provide an objective measure of dysfunction in these individuals. However, VSS participants also frequently report significant psychiatric symptoms. Given that that these symptoms have been shown previously to influence performance on OM tasks, the objective of this study was to investigate whether psychiatric symptoms (specifically: depression, anxiety, fatigue, sleep difficulties, and depersonalization) influence the OM metrics found to differ in VSS. Sixty-one VSS participants completed a battery of four OM tasks and a series of online questionnaires assessing psychiatric symptomology. We revealed no significant relationship between psychiatric symptoms and OM metrics on any of the tasks, demonstrating that in participants with VSS, differences in OM behaviour are a feature of the disorder. This supports the utility of OM assessment in characterising deficit in VSS, whether supporting a diagnosis or monitoring future treatment efficacy.

Brain network dynamics in people with visual snow syndrome.

Visual snow syndrome (VSS) is a neurological disorder characterized by a range of continuous visual disturbances. Little is known about the functional pathological mechanisms underlying VSS and their effect on brain network topology, studied using high-resolution resting-state (RS) 7 T MRI. Forty VSS patients and 60 healthy controls underwent RS MRI. Functional connectivity matrices were calculated, and global efficiency (network integration), modularity (network segregation), local efficiency (LE, connectedness neighbors) and eigenvector centrality (significance node in network) were derived using a dynamic approach (temporal fluctuations during acquisition). Network measures were compared between groups, with regions of significant difference correlated with known aberrant ocular motor VSS metrics (shortened latencies and higher number of inhibitory errors) in VSS patients. Lastly, nodal co-modularity, a binary measure of node pairs belonging to the same module, was studied. VSS patients had lower modularity, supramarginal centrality and LE dynamics of multiple (sub)cortical regions, centered around occipital and parietal lobules. In VSS patients, lateral occipital cortex LE dynamics correlated positively with shortened prosaccade latencies (p = .041, r = .353). In VSS patients, occipital, parietal, and motor nodes belonged more often to the same module and demonstrated lower nodal co-modularity with temporal and frontal regions. This study revealed reduced dynamic variation in modularity and local efficiency strength in the VSS brain, suggesting that brain network dynamics are less variable in terms of segregation and local clustering. Further investigation of these changes could inform our understanding of the pathogenesis of the disorder and potentially lead to treatment strategies.

Early predictors of visual and axonal outcomes after acute optic neuritis.

Background: Predicting long-term visual outcomes and axonal loss following acute optic neuritis (ON) is critical for choosing treatment. Predictive models including all clinical and paraclinical measures of optic nerve dysfunction following ON are lacking. Objectives: Using a prospective study method, to identify 1 and 3 months predictors of 6 and 12 months visual outcome (low contrast letter acuity 2.5%) and axonal loss [retinal nerve fiber layer thickness and multifocal evoked potential (mfVEP) amplitude] following acute ON. Methods: In total, 37 patients of acute ON onset were evaluated within 14 days using between-eye asymmetry of visual acuity, color vision (Ishihara plates), optical coherence tomography, mfVEP, and optic nerve magnetic resonance imaging [magnetic transfer ratio (MTR) and diffusion tensor imaging (DTI)]. Results: Visual outcome at 6 and 12 months was best predicted by Ishihara asymmetry at 1 and 3 months following ON onset. Axonal loss at 6 and 12 months was reliably predicted by Ishihara asymmetry at 1 month. Optic nerve MTR and DTI at 3 months post-acute ON could predict axonal loss at 6 and 12 months. Conclusions: Simple Ishihara asymmetry testing 1 month after acute ON onset can best predict visual outcome and axonal loss at 6 and 12 months in a clinical or research setting.

Tracking Eye Movements for Diagnosis in Myasthenia Gravis: A Comprehensive Review.

BACKGROUND: Around 60%--75% of myasthenia gravis (MG) patients initially present with nonspecific ocular symptoms. Failed recognition of these symptoms may delay the diagnosis of MG up to 5 years or more, leading to a reduced likelihood of remission and increased morbidity. Current diagnostic tests are either poorly sensitive for patients presenting with ocular symptoms alone or are time consuming, invasive, require a high level of technical expertise, and generally are universally difficult to obtain. This review will explore quantitative eye and pupil tracking as a potential noninvasive, time-effective, and less technically demanding alternative to current diagnostic tests of MG. EVIDENCE ACQUISITION: Comprehensive literature review. RESULTS: Thirty-two publications using oculography for the diagnosis of MG and 6 studies using pupillometry were evaluated. In MG patients, extra ocular muscle fatigue was evident in reports of intersaccadic, intrasaccadic and postsaccadic abnormalities, changes in optokinetic nystagmus, slow eye movements, disconjugate saccades, and pupillary constrictor muscle weakness. CONCLUSIONS: Our review identified several potentially useful variables that derive from oculography and pupillometry studies that could assist with a timely diagnosis of MG. Limitations of this review include heterogeneity in design, sample size, and quality of the studies evaluated. There is a need for larger, well-designed studies evaluating eye-tracking measures in the diagnosis of MG, especially for patients presenting with purely ocular symptoms.

Microstructure in patients with visual snow syndrome: an ultra-high field morphological and quantitative MRI study.

Visual snow syndrome is a neurological condition characterized by continuous visual disturbance and a range of non-visual symptoms, including tinnitus and migraine. Little is known about the pathological mechanisms underlying visual snow syndrome. Here, we assessed brain morphometry and microstructure in visual snow syndrome patients using high-resolution structural and quantitative MRI. Forty visual snow syndrome patients (22 with migraine) and 43 controls underwent 7-Tesla MRI (MP2RAGE, 0.75 mm isotropic resolution). Volumetric and quantitative T1 values were extracted for white and grey matter regions and compared between groups. Where regions were significantly different between groups (false discovery rate corrected for multiple comparisons), post hoc comparisons were examined between patients with and without migraine. For visual snow syndrome patients, significant MRI variables were correlated with clinical severity (number of visual symptoms, perceived visual snow intensity, disruptiveness, fatigue and quality of life) and psychiatric symptoms prevalent in visual snow syndrome (depression, anxiety and depersonalization). Finally, cortical regions and individual thalamic nuclei were studied. Compared with controls, visual snow syndrome patients demonstrated a trend towards larger brain and white matter volumes and significantly lower T1 values for the entire cortex (P < 0.001), thalamus (P = 0.001) and pallidum (P = 0.001). For the patient group, thalamic T1 correlated with number of visual symptoms (P = 0.019, r = 0.390) and perceived disruptiveness of visual snow (P = 0.010, r = 0.424). These correlations did not survive multiple comparison corrections. As for specificity in visual snow syndrome group, T1 changes were most evident in caudal regions (occipital cortices) followed by parietal, temporal and prefrontal cortices. T1 values differed between groups for most individual thalamic nuclei. No differences were revealed between patients with and without migraine. In visual snow syndrome patients, we observed no changes in morphometry, instead widespread changes in grey matter microstructure, which followed a caudal-rostral pattern and affected the occipital cortices most profoundly. Migraine did not appear to independently affect these changes. Lower T1 values may potentially result from higher neurite density, myelination or increased iron levels in the visual snow syndrome brain. Further investigation of these changes may enhance our understanding of the pathogenesis of visual snow syndrome, ultimately leading to new treatment strategies.

Corrigendum: Editorial: Visual Snow: Old Problem, New Understanding.

[This corrects the article DOI: 10.3389/fneur.2022.884752.].

Working Memory Phenotypes in Early Multiple Sclerosis: Appraisal of Phenotype Frequency, Progression and Test Sensitivity.

Working memory (WM) impairments are common and debilitating symptoms of multiple sclerosis (MS), often emerging early in the disease. Predominantly, WM impairments are considered in a binary manner, with patients considered either impaired or not based on a single test. However, WM is comprised of different activated subcomponents depending upon the type of information (auditory, visual) and integration requirements. As such, unique WM impairment phenotypes occur. We aimed to determine the most frequent WM phenotypes in early MS, how they progress and which WM test(s) provide the best measure of WM impairment. A total of 88 participants (63 early relapsing-remitting MS: RRMS, 25 healthy controls) completed five WM tests (visual-spatial, auditory, episodic, executive) as well as the symbol digit modalities test as a measure of processing speed. RRMS patients were followed-up for two years. Factors affecting WM (age/gender/intelligence/mood) and MS factors (disease duration/disability) were also evaluated. Some 61.9% of RRMS patients were impaired on at least one WM subcomponent. The most subcomponents impaired were visual,-spatial and auditory WM. The most common WM phenotypes were; (1) visual-spatial sketchpad + episodic buffer + phonological loop + central executive, (2) visual-spatial sketchpad + central executive. The test of visual-spatial WM provided the best diagnostic accuracy for detecting WM impairment and progression. The SDMT did not achieve diagnostic accuracy greater than chance. Although this may be unsurprising, given that the SDMT is a measure of cognitive processing speed in MS, this does highlight the limitation of the SDMT as a general screening tool for cognitive impairment in early MS.

Longitudinal tracking of axonal loss using diffusion magnetic resonance imaging in multiple sclerosis.

Axonal loss in the CNS is a key driver of progressive neurological impairments in people with multiple sclerosis. Currently, there are no established methods for tracking axonal loss clinically. This study aimed to determine the sensitivity of longitudinal diffusion MRI-derived fibre-specific measures of axonal loss in people with multiple sclerosis. Fibre measures were derived from diffusion MRI acquired as part of a standard radiological MRI protocol and were compared (i) to establish measures of neuro-axonal degeneration: brain parenchymal fraction and retinal nerve fibre layer thickness and (ii) between different disease stages: clinically isolated syndrome and early/late relapsing-remitting multiple sclerosis. Retrospectively identified data from 59 people with multiple sclerosis (18 clinically isolated syndrome, 22 early and 19 late relapsing-remitting) who underwent diffusion MRI as part of their routine clinical monitoring were collated and analysed. Twenty-six patients had 1-year and 14 patients had a 2-year follow-up. Brain parenchymal fraction was calculated from 3D MRI scans, and fibre-specific measures were calculated from diffusion MRI using multi-tissue constrained spherical deconvolution. At each study visit, patients underwent optical coherence tomography to determine retinal nerve fibre layer thickness, and standard neurological assessment expanded the disability status scale. We found a significant annual fibre-specific neuro-axonal degeneration (mean ± SD = -3.49 ± 3.32%, P < 0.001) that was ∼7 times larger than the annual change of brain parenchymal fraction (-0.53 ± 0.95%, P < 0.001), and more than four times larger than annual retinal nerve fibre layer thinning (-0.75 ± 2.50% P = 0.036). Only fibre-specific measures showed a significant difference in annual degeneration between the disease stages (P = 0.029). Reduced brain parenchymal fraction, retinal nerve fibre layer thickness and fibre-specific measures were moderately related to higher expanded disability status scale (rho = -0.368, rho = -0.408 and rho = -0.365, respectively). Fibre-specific measures can be measured from data collected within a standard radiological multiple sclerosis study and are substantially more sensitive to longitudinal change compared with brain atrophy and retinal nerve fibre layer thinning.

Visual contrast perception in visual snow syndrome reveals abnormal neural gain but not neural noise.

Visual snow syndrome is a neurological condition characterized by a persistent visual disturbance, visual snow, in conjunction with additional visual symptoms. Cortical hyperexcitability is a potential pathophysiological mechanism, which could be explained by increased gain in neural responses to visual input. Alternatively, neural noise in the visual pathway could be abnormally elevated. We assessed these two potential competing neural mechanisms in our studies of visual contrast perception. Cortical hyperexcitation also occurs in migraine, which commonly co-occurs with visual snow syndrome. Therefore, to determine whether the effect of visual snow syndrome can be distinguished from interictal migraine, we recruited four participant groups: controls, migraine alone, visual snow syndrome alone and visual snow syndrome with migraine. In the first experiment, we estimated internal noise in 20 controls, 21 migraine participants and 32 visual snow syndrome participants (16 with migraine) using a luminance increment detection task. In the second experiment, we estimated neural contrast gain in 21 controls, 22 migraine participants and 35 visual snow syndrome participants (16 with migraine) using tasks assessing sensitivity to changes in contrast from a reference. Contrast gain and sensitivity were measured for the putative parvocellular and 'on' and 'off' magnocellular pathways, respectively. We found that luminance increment thresholds and internal noise estimates were normal in both visual snow syndrome and migraine. Contrast gain measures for putative parvocellular processing and contrast sensitivity for putative off magnocellular processing were abnormally increased in visual snow syndrome, regardless of migraine status. Therefore, our results indicate that visual snow syndrome is characterized by increased neural contrast gain but not abnormal neural noise within the targeted pathways.

Delayed Onset of Inhibition of Return in Visual Snow Syndrome.

Visual snow syndrome (VSS) is a complex, sensory processing disorder. We have previously shown that visual processing changes manifest in significantly faster eye movements toward a suddenly appearing visual stimulus and difficulty inhibiting an eye movement toward a non-target visual stimulus. We propose that these changes reflect poor attentional control and occur whether attention is directed exogenously by a suddenly appearing event, or endogenously as a function of manipulating expectation surrounding an upcoming event. Irrespective of how attention is captured, competing facilitatory and inhibitory processes prioritise sensory information that is important to us, filtering out that which is irrelevant. A well-known feature of this conflict is the alteration to behaviour that accompanies variation in the temporal relationship between competing sensory events that manipulate facilitatory and inhibitory processes. A classic example of this is the "Inhibition of Return" (IOR) phenomenon that describes the relative slowing of a response to a validly cued location compared to invalidly cued location with longer cue/target intervals. This study explored temporal changes in the allocation of attention using an ocular motor version of Posner's IOR paradigm, manipulating attention exogenously by varying the temporal relationship between a non-predictive visual cue and target stimulus. Forty participants with VSS (20 with migraine) and 20 controls participated. Saccades were generated to both validly cued and invalidly cued targets with 67, 150, 300, and 500 ms cue/target intervals. VSS participants demonstrated delayed onset of IOR. Unlike controls, who exhibited IOR with 300 and 500 ms cue/target intervals, VSS participants only exhibited IOR with 500 ms cue/target intervals. These findings provide further evidence that attention is impacted in VSS, manifesting in a distinct saccadic behavioural profile, and delayed onset of IOR. Whether IOR is perceived as the build-up of an inhibitory bias against returning attention to an already inspected location or a consequence of a stronger attentional orienting response elicited by the cue, our results are consistent with the proposal that in VSS, a shift of attention elicits a stronger increase in saccade-related activity than healthy controls. This work provides a more refined saccadic behavioural profile of VSS that can be interrogated further using sophisticated neuroimaging techniques and may, in combination with other saccadic markers, be used to monitor the efficacy of any future treatments.

The Psychiatric Symptomology of Visual Snow Syndrome.

Objective: To characterise the psychiatric symptoms of visual snow syndrome (VSS), and determine their relationship to quality of life and severity of visual symptoms. Methods: One hundred twenty-five patients with VSS completed a battery of questionnaires assessing depression/anxiety, dissociative experiences (depersonalisation), sleep quality, fatigue, and quality of life, as well as a structured clinical interview about their visual and sensory symptoms. Results: VSS patients showed high rates of anxiety and depression, depersonalisation, fatigue, and poor sleep, which significantly impacted quality of life. Further, psychiatric symptoms, particularly depersonalisation, were related to increased severity of visual symptoms. The severity/frequency of psychiatric symptoms did not differ significantly due to the presence of migraine, patient sex, or timing of VSS onset (lifelong vs. later onset). Conclusion: Psychiatric symptoms are highly prevalent in patients with VSS and are associated with increased visual symptom severity and reduced quality of life. Importantly, patients with lifelong VSS reported lower levels of distress and milder self-ratings of visual symptoms compared to patients with a later onset, while being equally likely to experience psychiatric symptoms. This suggests that the psychiatric symptoms of VSS are not solely due to distress caused by visual symptoms. While no consistently effective treatments are available for the visual symptomology of VSS, psychiatric symptoms offer an avenue of treatment that is likely to significantly improve patient quality of life and ability to cope with visual symptoms.

Eye movement characteristics provide an objective measure of visual processing changes in patients with visual snow syndrome.

Visual snow syndrome (VSS) is a poorly understood neurological disorder that features a range of disabling sensory changes. Visual processing changes revealed previously in VSS appear consistent with poor attentional control, specifically, with difficulty controlling environmentally driven shifts of attention. This study sought to confirm this proposal by determining whether these changes were similarly evident where attention is internally driven. Sixty seven VSS patients and 37 controls completed two saccade tasks: the endogenously cued saccade task and saccadic Simon task. The endogenously cued saccade task correctly (valid trial) or incorrectly (invalid trial) pre-cues a target location using a centrally presented arrow. VSS patients generated significantly shorter saccade latencies for valid trials (p = 0.03), resulting in a greater magnitude cue effect (p = 0.02), i.e. the difference in latency between valid and invalid trials. The saccadic Simon task presents a peripheral cue which may be spatially congruent or incongruent with the subsequent target location. Latencies on this task were comparable for VSS patients and controls, with a normal Simon effect, i.e. shorter latencies for saccades to targets spatially congruent with the preceding cue. On both tasks, VSS patients generated more erroneous saccades than controls towards non-target locations (Endogenously cued saccade task: p = 0.02, saccadic Simon task: p = 0.04). These results demonstrate that cued shifts of attention differentially affect saccade generation in VSS patients. We propose that these changes are not due to impairment of frontally-mediated inhibitory control, but to heightened saccade-related activity in visual regions. These results contribute to a VSS ocular motor signature that may provide clinical utility as well as an objective measure of dysfunction to facilitate future research.

Ocular motor measures of visual processing changes in visual snow syndrome.

OBJECTIVE: To determine whether changes to cortical processing of visual information can be evaluated objectively using 3 simple ocular motor tasks to measure performance in patients with visual snow syndrome (VSS). METHODS: Sixty-four patients with VSS (32 with migraine and 32 with no migraine) and 23 controls participated. Three ocular motor tasks were included: prosaccade (PS), antisaccade (AS), and interleaved AS-PS tasks. All these tasks have been used extensively in both neurologically healthy and diseased states. RESULTS: We demonstrated that, compared to controls, the VSS group generated significantly shortened PS latencies (p = 0.029) and an increased rate of AS errors (p = 0.001), irrespective of the demands placed on visual processing (i.e., task context). Switch costs, a feature of the AS-PS task, were comparable across groups, and a significant correlation was found between shortened PS latencies and increased AS error rates for patients with VSS (r = 0.404). CONCLUSION: We identified objective and quantifiable measures of visual processing changes in patients with VSS. The absence of any additional switch cost on the AS-PS task in VSS suggests that the PS latency and AS error differences are attributable to a speeded PS response rather than to impaired executive processes more commonly implicated in poorer AS performance. We propose that this combination of latency and error deficits, in conjunction with intact switching performance, will provide a VS behavioral signature that contributes to our understanding of VSS and may assist in determining the efficacy of therapeutic interventions.

There's something in the air.

A 20-year-old woman presented with bilateral constant positive visual phenomenon since she was 9 years old. The symptoms had been worsening and becoming more intrusive in the last 3 years. Recently she has also had a migrainous episode. All ophthalmic and neurological investigations were normal. Her symptoms met the diagnostic criteria for visual snow. The diagnosis was explained, and the patient was reassured. Ophthalmologists and neurologists need to be aware of this condition to avoid over investigation and worsening of patient anxiety.

Visual Snow: Visual Misperception.

BACKGROUND: Visual snow (VS) is a constant visual disturbance described as flickering dots occupying the entire visual field. Recently, it was characterized as the defining feature of a VS syndrome (VSS), which includes palinopsia, photophobia, photopsias, entoptic phenomena, nyctalopia, and tinnitus. Sixty percent of patients with VSS also experience migraine, with or without aura. This entity often is considered psychogenic in nature, to the detriment of the patient's best interests, but the high frequency of similar visual symptoms argues for an organic deficit. The purpose of this review is to clarify VSS as a true entity and elaborate the nature of individual symptoms and their relationship to each other. EVIDENCE ACQUISITION: The literature was reviewed with specific regard to the clinical presentation and psychophysical, neurophysiological, and functional imaging studies in patients with defined visual disturbances that comprise VSS. RESULTS: Consideration of the individual symptoms suggests that multiple factors are potentially involved in the development of VSS, including subcortical network malfunction and cortical hyperexcitation. Although there is substantial overlap between VSS and migraine syndromes in terms of co-occurring symptoms, both neurophysiological and neuroimaging studies provide substantial evidence of separate abnormalities of processing, supporting these as separate syndromes. CONCLUSIONS: VSS is likely associated with either hyperactive visual cortices or, alternatively, impaired processing of simultaneous afferent information projecting to cortex. VSS likely results from widespread disturbance of sensory processing resulting in sensory misperception. There may be a number of syndromes associated with impaired sensory processing resulting in sensory misperception, including migraine, persistent perceptual postural dizziness, and tinnitus, which overlap with VSS. Elucidation of abnormality in one defined syndrome may provide a path forward for investigating all.

Retinal ganglion cell loss in neuromyelitis optica: a longitudinal study.

OBJECTIVES: Neuromyelitis optica spectrum disorders (NMOSD) are inflammatory conditions of the central nervous system and an important differential diagnosis of multiple sclerosis (MS). Unlike MS, the course is usually relapsing, and it is unclear, if progressive neurodegeneration contributes to disability. Therefore, we aimed to investigate if progressive retinal neuroaxonal damage occurs in aquaporin4-antibody-seropositive NMOSD. METHODS: Out of 157 patients with NMOSD screened, 94 eyes of 51 patients without optic neuritis (ON) during follow-up (F/U) and 56 eyes of 28 age-matched and sex-matched healthy controls (HC) were included (median F/U 2.3 years). The NMOSD cohort included 60 eyes without (EyeON -) and 34 eyes with a history of ON prior to enrolment (EyeON+). Peripapillary retinal nerve fibre layer thickness (pRNFL), fovea thickness (FT), volumes of the combined ganglion cell and inner plexiform layer (GCIP) and the inner nuclear layer (INL) and total macular volume (TMV) were acquired by optical coherence tomography (OCT). RESULTS: At baseline, GCIP, FT and TMV were reduced in EyeON+ (GCIP p<2e-16; FT p=3.7e-4; TMV p=3.7e-12) and in EyeON - (GCIP p=0.002; FT p=0.040; TMV p=6.1e-6) compared with HC. Longitudinally, we observed GCIP thinning in EyeON- (p=0.044) but not in EyeON+. Seven patients had attacks during F/U; they presented pRNFL thickening compared with patients without attacks (p=0.003). CONCLUSION: This study clearly shows GCIP loss independent of ON attacks in aquaporin4-antibody-seropositive NMOSD. Potential explanations for progressive GCIP thinning include primary retinopathy, drug-induced neurodegeneration and retrograde neuroaxonal degeneration from lesions or optic neuropathy. pRNFL thickening in the patients presenting with attacks during F/U might be indicative of pRNFL susceptibility to inflammation.