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.

Visuo-Cognitive Phenotypes in Early Multiple Sclerosis: A Multisystem Model of Visual Processing.

BACKGROUND: Cognitive impairment can emerge in the earliest stages of multiple sclerosis (MS), with heterogeneity in cognitive deficits often hindering symptom identification and management. Sensory-motor dysfunction, such as visual processing impairment, is also common in early disease and can impact neuropsychological task performance in MS. However, cognitive phenotype research in MS does not currently consider the relationship between early cognitive changes and visual processing impairment. OBJECTIVES: This study explored the relationship between cognition and visual processing in early MS by adopting a three-system model of afferent sensory, central cognitive and efferent ocular motor visual processing to identify distinct visuo-cognitive phenotypes. METHODS: Patients with clinically isolated syndrome and relapsing-remitting MS underwent neuro-ophthalmic, ocular motor and neuropsychological evaluation to assess each visual processing system. The factor structure of ocular motor variables was examined using exploratory factor analysis, and phenotypes were identified using latent profile analysis. RESULTS: Analyses revealed three ocular-motor constructs (cognitive control, cognitive processing speed and basic visual processing) and four visuo-cognitive phenotypes (early visual changes, efferent-cognitive, cognitive control and afferent-processing speed). While the efferent-cognitive phenotype was present in significantly older patients than was the early visual changes phenotype, there were no other demographic differences between phenotypes. The efferent-cognitive and cognitive control phenotypes had poorer performance on the Symbol Digit Modalities Test compared to that of other phenotypes; however, no other differences in performance were detected. CONCLUSION: Our findings suggest that distinct visual processing deficits in early MS may differentially impact cognition, which is not captured using standard neuropsychological evaluation. Further research may facilitate improved symptom identification and intervention in early disease.

Development and preliminary validation of a novel eating disorder screening tool for vegetarians and vegans: the V-EDS.

BACKGROUND: Eating disorders have one of the highest mortality of all mental illnesses but are associated with low rates of screening and early intervention. In addition, there remains considerable uncertainty regarding the use of current standardised screening tools in measuring eating pathology in vegetarians and vegans. With these groups presenting as potential at-risk groups for disordered eating development, the present study aimed to develop and preliminary validate a novel eating disorder screening tool, the Vegetarian Vegan Eating Disorder Screener (V-EDS). METHODS: We utilised a mixed-methods approach, comprising four phases. RESULTS: A conceptual framework was developed from 25 community, clinician, and lived experience interviews and used to derive a preliminary set of 163 items (Phase 1). Phase 2 piloted the items to establish face and content validity through cognitive debriefing interviews of 18 additional community, clinician, and lived experience participants, resulting in a reduced, revised questionnaire of 53 items. Phase 3 involved scale purification using Item Response Theory in analysis of 230 vegetarians and 230 vegans resulting in a further reduced 18-item questionnaire. Phase 4 validated the screening tool in a large community sample of 245 vegetarians and 405 vegans using traditional psychometric analysis, finding the V-EDS supports a unidimensional factor structure with excellent internal consistency (α = 0.95-0.96) and convergent validity (0.87-0.88), and moderate discriminate validity (0.45-0.55). CONCLUSIONS: This study provided strong initial support for the psychometric validity and theoretical assumptions of the novel V-EDS screening tool. The V-EDS has the potential to increase early intervention rates for vegetarians and vegans experiencing eating disorder symptoms, further supporting advocacy and treatment approaches for these expanding dietary groups.

The present study describes the development and preliminary validation of the first screening tool designed to uniquely assess eating disorder symptoms in individuals following a vegetarian or vegan diet. Following several development phases, the final version of the Vegetarian Vegan Eating Disorder Screener (V-EDS) comprises 18-items, with six dietary characteristic items and 12 eating disorder scored items. The current findings support excellent initial reliability and validity of the V-EDS. The V-EDS constitutes a promising tool that could potentially be integrated as a standalone measure for initial screening in clinical and research settings, but also for more comprehensive assessment when combined with other gold-standard eating disorder tools.

Preliminary identification of clinical cut-off of the vegetarian vegan eating disorder screener (V-EDS) in a community and self-reported clinical sample of vegetarians and vegans.

BACKGROUND: The vegetarian vegan eating disorder screener (V-EDS) is an 18-item self-report screening tool designed to assess the unique elements of eating disorder symptomology in vegetarians and vegans. Previous results have suggested strong initial psychometric properties in non-clinical community samples of vegetarians and vegans. The present study sought to identify a preliminary threshold cut-off score to discriminate eating disorder pathology in a self-reported clinical and community sample. METHODS: This study involved secondary analysis using data collected in McLean et al. (Development and preliminary validation of a novel eating disorder screening tool for vegetarians and vegans: the V-EDS, 2023), comprising 599 non-clinical participants and 51 self-reported clinical participants. Receiver operating characteristic (ROC) curve analysis was used to compute possible cut-off values for the V-EDS. RESULTS: ROC analysis indicated good performance of the V-EDS (area under the curve = 0.87), with integration of the Youden index demonstrating a global score of ≥ 18 to be optimal in predicting clinical caseness with good sensitivity (0.804) and specificity (0.843). CONCLUSIONS: The present study fills an important gap as the first to investigate an optimal V-EDS score to discriminate level of impairment from eating disorder pathology in a sample of vegetarian and vegan community and self-reported clinical participants. We extend the utility of the V-EDS in discovering good discrimination power in classifying clinical caseness with a cut-off score of 18 shown to optimise the trade-off between sensitivity and specificity. Future research should focus on expanding the psychometric properties of the V-EDS in larger and more diverse participant groups, including gender, age, cultural identity, and eating disorder history.

This study builds on the preliminary validation of a novel eating disorder screening tool for people adhering to a vegetarian and vegan diet called the V-EDS. In this study, we set out to develop a cut-off score for the V-EDS to distinguish people needing further evaluation for a possible eating disorder within the community. We found a global V-EDS score of ≥ 18 to be ideal in distinguishing between eating disorder symptomatic and non-eating disorder groups. In future, the V-EDS may prove useful for initial screening and symptom progression of eating disorders across both clinical and research settings.

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.

Understanding the pathophysiology of idiopathic intracranial hypertension (IIH): a review of recent developments.

Idiopathic intracranial hypertension (IIH) is a condition of significant morbidity and rising prevalence. It typically affects young people living with obesity, mostly women of reproductive age, and can present with headaches, visual abnormalities, tinnitus and cognitive dysfunction. Raised intracranial pressure without a secondary identified cause remains a key diagnostic feature of this condition, however, the underlying pathophysiological mechanisms that drive this increase are poorly understood. Previous theories have focused on cerebrospinal fluid (CSF) hypersecretion or impaired reabsorption, however, the recent characterisation of the glymphatic system in many other neurological conditions necessitates a re-evaluation of these hypotheses. Further, the impact of metabolic dysfunction and hormonal dysregulation in this population group must also be considered. Given the emerging evidence, it is likely that IIH is triggered by the interaction of multiple aetiological factors that ultimately results in the disruption of CSF dynamics. This review aims to provide a comprehensive update on the current theories regarding the pathogenesis of IIH.

Ocular motility as a measure of cerebral dysfunction in adults with focal epilepsy.

OBJECTIVE: Using objective oculomotor measures, we aimed to: (1) compare oculomotor performance in patients with drug-resistant focal epilepsy to healthy controls, and (2) investigate the differential impact of epileptogenic focus laterality and location on oculomotor performance. METHODS: We recruited 51 adults with drug-resistant focal epilepsy from the Comprehensive Epilepsy Programs of two tertiary hospitals and 31 healthy controls to perform prosaccade and antisaccade tasks. Oculomotor variables of interest were latency, visuospatial accuracy, and antisaccade error rate. Linear mixed models were performed to compare interactions between groups (epilepsy, control) and oculomotor tasks, and between epilepsy subgroups and oculomotor tasks for each oculomotor variable. RESULTS: Compared to healthy controls, patients with drug-resistant focal epilepsy exhibited longer antisaccade latencies (mean difference = 42.8 ms, P = 0.001), poorer spatial accuracy for both prosaccade (mean difference = 0.4°, P = 0.002), and antisaccade tasks (mean difference = 2.1°, P < 0.001), and more antisaccade errors (mean difference = 12.6%, P < 0.001). In the epilepsy subgroup analysis, left-hemispheric epilepsy patients exhibited longer antisaccade latencies compared to controls (mean difference = 52.2 ms, P = 0.003), while right-hemispheric epilepsy was the most spatially inaccurate compared to controls (mean difference = 2.5°, P = 0.003). The temporal lobe epilepsy subgroup displayed longer antisaccade latencies compared to controls (mean difference = 47.6 ms, P = 0.005). SIGNIFICANCE: Patients with drug-resistant focal epilepsy exhibit poor inhibitory control as evidenced by a high percentage of antisaccade errors, slower cognitive processing speed, and impaired visuospatial accuracy on oculomotor tasks. Patients with left-hemispheric epilepsy and temporal lobe epilepsy have markedly impaired processing speed. Overall, oculomotor tasks can be a useful tool to objectively quantify cerebral dysfunction in drug-resistant focal epilepsy.

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.

Discriminating spatialised speech in complex environments in multiple sclerosis.

People with multiple sclerosis (pwMS) frequently present with deficits in binaural processing used for sound localization. This study examined spatial release from speech-on-speech masking in pwMS, which involves binaural processing and additional higher level mechanisms underlying streaming, such as spatial attention. 26 pwMS with mild severity (Expanded Disability Status Scale score <3) and 20 age-matched controls listened via headphones to pre-recorded sentences from a standard list presented simultaneously with eight-talker babble. Virtual acoustic techniques were used to simulate sentences originating from 0°, 20°, or 50° on the interaural horizontal plane around the listener whilst babble was presented continuously at 0° azimuth, and participants verbally repeated the target sentence. In a separate task, two simultaneous sentences both containing a colour and number were presented, and participants were required to report the target colour and number. Both competing sentences could originate from 0°, 20°, or 50° on the azimuthal plane. Participants also completed a series of neuropsychological assessments, an auditory questionnaire, and a three-alternative forced-choice task that involved the detection of interaural time differences (ITDs) in noise bursts. Spatial release from masking was observed in both pwMS and controls, as response accuracy in the two speech discrimination tasks improved in the spatially separated conditions (20° and 50°) compared with the co-localised condition. However, pwMS demonstrated significantly less spatial release (18%) than controls (28%) when discriminating colour/number coordinates. At 50° separation, pwMS discriminated significantly fewer coordinates (77%) than controls (89%). In contrast, pwMS had similar performances to controls when sentences were presented in babble, and for the basic ITD discrimination task. Significant correlations between speech discrimination performance and standardized neuropsychological scores were observed across all spatial conditions. Our findings suggest that spatial hearing is likely to be implicated in pwMS, thereby affecting the perception of competing speech originating from various locations.

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.

Monitoring the acute and subacute recovery of cognitive ocular motor changes after a sports-related concussion.

Identifying when recovery from a sports-related concussion (SRC) has occurred remains a challenge in clinical practice. This study investigated the utility of ocular motor (OM) assessment to monitor recovery post-SRC between sexes and compared to common clinical measures. From 139 preseason baseline assessments (i.e. before they sustained an SRC), 18 (12 males, 6 females) consequent SRCs were sustained and the longitudinal follow-ups were collected at 2, 6, and 13 days post-SRC. Participants completed visually guided, antisaccade (AS), and memory-guided saccade tasks requiring a saccade toward, away from, and to a remembered target, respectively. Changes in latency (processing speed), visual-spatial accuracy, and errors were measured. Clinical measures included The Sports Concussion Assessment Tool, King-Devick test, Stroop task, and Digit span. AS latency was significantly longer at 2 days and returned to baseline by 13-days post-SRC in females only (P < 0.001). Symptom numbers recovered from 2 to 6 days and 13 days (P < 0.05). Persistently poorer AS visual-spatial accuracy was identified at 2, 6 and 13 days post-SRC (P < 0.05) in both males and females but with differing trajectories. Clinical measures demonstrated consistent improvement reminiscent of practice effects. OM saccade assessment may have improved utility in tracking recovery compared to conventional measures and between sexes.

Video game training in traumatic brain injury patients: an exploratory case report study using eye tracking.

Remediation of attentional impairments is an essential component of cognitive rehabilitation after traumatic brain injury (TBI). Evidence from healthy participants has demonstrated attentional improvement following playing an action video game. This exploratory study investigated its application in TBI participants in a multiple baselines single case experimental design (SCED). Saccadic eye movements, recognized as the visible indicators of visual attention, were assessed to evaluate the effectiveness of the game training. Three severe TBI participants were trained in an action game for 10 hours. Saccadic eye movements during a self-paced saccade and an abstract visual search task were investigated during baseline, mid training and post-training. Using Percentage of Non-overlapping Data (PND), analysis showed consistent increase in the rate of the self-paced saccades in participants 1 (PND=80%) and 2 (PND=70%). In abstract search, fixation duration showed a minimally effective decrease for participant 2 (PND= 60%) and a moderately effective reduction in participant 3 (PND= 80%). Search time showed a highly effective reduction in participant 2 (PND = 100%) and moderately effective decrease in participant 3 (PND=70%). Overall, video game training might modify allocation of attention in eye movements. More evidence is required to validate the usefulness of this novel method of the cognitive training.

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.

Hallucinogenic Persisting Perception Disorder: A Case Series and Review of the Literature.

Background: Hallucinogen persisting perception disorder (HPPD) is characterized by the re-emergence of perceptual symptoms experienced during acute hallucinogen intoxication following drug cessation. The underlying pathophysiology is poorly understood. We report the clinical characteristics and investigation findings of a series of HPPD cases with a literature review of previous case reports. We draw parallels between the features of HPPD and Visual Snow Syndrome (VSS). Methods: Retrospective case series of 13 patients referred from neuro-ophthalmologists. Literature review with 24 HPPD case reports were identified through database search using the terms "hallucinogenic persisting perception disorder" OR "hallucinogen persisting perception disorder." Results: Lysergic acid diethylamide (LSD), 3,4-Methyl enedioxy methamphetamine (MDMA) and cannabinoid use was common. Cannabinoids and MDMA were mostly used in association with classical hallucinogens. The most frequent symptoms in our patients were visual snow, floaters, palinopsia, photophobia and nyctalopia. In the literature other symptoms included visual hallucinations altered motion perception, palinopsia, tracers and color enhancement. Ophthalmic and neurologic investigations were mostly normal. The majority of patients had ongoing symptoms. Two of our patients fully recovered-one after treatment with benzodiazepine and one without treatment. Twenty-five percent of cases from the literature fully recovered. Conclusions: HPPD presents with heterogeneous visual phenomena on a background of previous classic and non-classic hallucinogen use. Ophthalmic investigations are typically normal. The symptoms of HPPD in our case series overlap with the typical features of Visual Snow Syndrome (VSS). Patients presenting with VSS should be screened for past recreational drug use. The DSM-5 description of HPPD does not include visual snow, nyctalopia, photophobia or floaters. A revision of the diagnostic criteria to include these symptoms may better reflect the typical clinical phenotype. Increased awareness of HPPD as a secondary cause of VSS can avoid extensive investigations. Controlled trials comparing primary and secondary VSS patients are needed to understand the pathophysiology better and optimize treatment for HPPD.

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.