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.

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.

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.

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.

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.

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.

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.

Emotion processing in persons who respond vicariously towards others in pain: Disinhibited left-lateralized neural activity for threatening expressions.

We investigated emotional processing in vicarious pain (VP) responders. VP responders report an explicit sensory and emotional feeling of pain when they witness another in pain, which is greater in magnitude than the empathic processing of pain in the general population. In Study 1, 31 participants completed a chimeric faces task, judging whether emotional chimera in the left, or right, visual field was more intense. VP responders took longer to judge emotionality than non-responders, and fixated more on the angry hemiface in the right visual field, whereas non-responder controls had no lateralized fixation bias. In Study 2, blood-oxygen level-dependent signals were recorded during an emotional face matching task. VP intensity was correlated with increased insula activity and reduced middle frontal gyrus activity for angry faces, and with reduced activity in the inferior and middle frontal gyri for sad faces. Together, these findings suggest that VP responders are more reactive to negative emotional expressions. Specifically, emotional judgements involved altered left-hemisphere activity in VP responders, and reduced engagement of regions involved in emotion regulation.

Disassociation between brain activation and executive function in fragile X premutation females.

Executive dysfunction has been demonstrated among premutation (PM) carriers (55-199 CGG repeats) of the Fragile X mental retardation 1 (FMR1) gene. Further, alterations to neural activation patterns have been reported during memory and comparison based functional magnetic resonance imaging (fMRI) tasks in these carriers. For the first time, the relationships between fMRI neural activation during an interleaved ocular motor prosaccade/antisaccade paradigm, and concurrent task performance (saccade measures of latency, accuracy and error rate) in PM females were examined. Although no differences were found in whole brain activation patterns, regions of interest (ROI) analyses revealed reduced activation in the right ventrolateral prefrontal cortex (VLPFC) during antisaccade trials for PM females. Further, a series of divergent and group specific relationships were found between ROI activation and saccade measures. Specifically, for control females, activation within the right VLPFC and supramarginal gyrus correlated negatively with antisaccade latencies, while for PM females, activation within these regions was found to negatively correlate with antisaccade accuracy and error rate (right VLPFC only). For control females, activation within frontal and supplementary eye fields and bilateral intraparietal sulci correlated with prosaccade latency and accuracy; however, no significant prosaccade correlations were found for PM females. This exploratory study extends previous reports of altered prefrontal neural engagement in PM carriers, and clearly demonstrates dissociation between control and PM females in the transformation of neural activation into overt measures of executive dysfunction. Hum Brain Mapp 38:1056-1067, 2017. © 2016 Wiley Periodicals, Inc.

Long term verbal memory recall deficits in fragile X premutation females.

Carriers of a FMR1 premutation allele (between 55 and 199 CGG repeats) are at risk of developing a wide range of medical, psychiatric and cognitive disorders, including executive dysfunction. These cognitive deficits are often less severe for female premutation carriers compared to male premutation carriers, albeit similar in nature. However, it remains unclear whether female premutation carriers who exhibit executive dysfunction also report verbal learning and memory deficits like those of their male counterparts. Here we employed the CVLT to assess verbal learning and memory function in 19 female premutation carriers, contrasting performance with 19 age- and IQ-matched controls. Group comparisons revealed similar performance during the learning and short delay recall phases of the CVLT. However, after a long delay period, female premutation carriers remembered fewer words for both free and cued recall trials, but not during recognition trials. These findings are consistent with reports for male premutation carriers, and suggest that aspects of long term memory may be adversely affect in a subgroup of premutation carriers with signs of executive dysfunction.

Executive Dysfunction in Female FMR1 Premutation Carriers.

There is now growing evidence of cognitive weakness in female premutation carriers (between 55 and 199 CGG repeats) of the fragile X mental retardation gene, including impairments associated with executive function. While an age-related decline in assessments of executive function has been found for male premutation carriers, few studies have explored whether female carriers show a similar trajectory with age. A total of 20 female premutation carriers and 21 age- and IQ-matched healthy controls completed a battery of tasks assessing executive function tasks, including the behavioural dyscontrol scale (BDS), symbol digit modalities test (SDMT), paced auditory serial addition test (PASAT), Haylings sentence completion test and the digit span task (forward and backward). Performance was compared between premutation carriers and healthy controls, and the association between task performance and age was also ascertained. Compared to controls, female premutation carriers had significant impairment on the BDS, SDMT, PASAT, and Haylings sentence completion task, all of which rely on quick, or timed, responses. Further analyses revealed no significant association between age and task performance for either premutation carriers or controls. This study demonstrates that a cohort of female premutation carriers have deficits on a range of tasks of executive function that require the rapid temporal resolution of responses. We propose that the understanding of the phenotype of premutation carriers will be advanced through use of such measures.

Inhibitory saccadic dysfunction is associated with cerebellar injury in multiple sclerosis.

Cognitive dysfunction is common in patients with multiple sclerosis (MS). Saccadic eye movement paradigms such as antisaccades (AS) can sensitively interrogate cognitive function, in particular, the executive and attentional processes of response selection and inhibition. Although we have previously demonstrated significant deficits in the generation of AS in MS patients, the neuropathological changes underlying these deficits were not elucidated. In this study, 24 patients with relapsing-remitting MS underwent testing using an AS paradigm. Rank correlation and multiple regression analyses were subsequently used to determine whether AS errors in these patients were associated with: (i) neurological and radiological abnormalities, as measured by standard clinical techniques, (ii) cognitive dysfunction, and (iii) regionally specific cerebral white and gray-matter damage. Although AS error rates in MS patients did not correlate with clinical disability (using the Expanded Disability Status Score), T2 lesion load or brain parenchymal fraction, AS error rate did correlate with performance on the Paced Auditory Serial Addition Task and the Symbol Digit Modalities Test, neuropsychological tests commonly used in MS. Further, voxel-wise regression analyses revealed associations between AS errors and reduced fractional anisotropy throughout most of the cerebellum, and increased mean diffusivity in the cerebellar vermis. Region-wise regression analyses confirmed that AS errors also correlated with gray-matter atrophy in the cerebellum right VI subregion. These results support the use of the AS paradigm as a marker for cognitive dysfunction in MS and implicate structural and microstructural changes to the cerebellum as a contributing mechanism for AS deficits in these patients.

Saccade reprogramming in Friedreich ataxia reveals impairments in the cognitive control of saccadic eye movement.

Although cerebellar dysfunction has known effects on motor function in Friedreich ataxia (FRDA), it remains unclear the extent to which the reprogramming of eye movements (saccades) and inhibition of well-learned automatic responses are similarly compromised in affected individuals. Here we examined saccade reprogramming to assess the ability of people with FRDA to respond toward unexpected changes in either the amplitude or direction of an "oddball" target. Thirteen individuals with genetically confirmed FRDA and 12 age-matched controls participated in the study. The saccade reprogramming paradigm was used to examine the effect of an unpredictable "oddball" target on saccade latencies and accuracy when compared to a well-learned sequence of reciprocating movements. Horizontal eye movements were recorded using a scleral search coil eye tracking technique. The results showed a proportionally greater increase in latencies for reprogrammed saccades toward an oddball-direction target in the FRDA group when compared to controls. The FRDA group were also less accurate in primary saccade gain (i.e. ratio of saccade amplitude to target amplitude) when reprogramming saccades toward an unexpected change in direction. No significant group differences were found on any of the oddball-amplitude targets. Significant correlations were revealed between latency and disease severity as measured by the Friedreich Ataxia Rating Scale. These findings provide further support to the view that cognitive changes in FRDA may arise from disruption of cerebellar connections to cortical structures.

Exploring inhibitory deficits in female premutation carriers of fragile X syndrome: through eye movements.

There is evidence which demonstrates that a subset of males with a premutation CGG repeat expansion (between 55 and 200 repeats) of the fragile X mental retardation 1 gene exhibit subtle deficits of executive function that progressively deteriorate with increasing age and CGG repeat length. However, it remains unclear whether similar deficits, which may indicate the onset of more severe degeneration, are evident in female PM-carriers. In the present study we explore whether female PM-carriers exhibit deficits of executive function which parallel those of male PM-carriers. Fourteen female fragile X premutation carriers without fragile X-associated tremor/ataxia syndrome and fourteen age, sex, and IQ matched controls underwent ocular motor and neuropsychological tests of select executive processes, specifically of response inhibition and working memory. Group comparisons revealed poorer inhibitory control for female premutation carriers on ocular motor tasks, in addition to demonstrating some difficulties in behaviour self-regulation, when compared to controls. A negative correlation between CGG repeat length and antisaccade error rates for premutation carriers was also found. Our preliminary findings indicate that impaired inhibitory control may represent a phenotype characteristic which may be a sensitive risk biomarker within this female fragile X premutation population.

Concurrent motor and cognitive function in multiple sclerosis: a motor overflow and motor stability study.

OBJECTIVE AND BACKGROUND: The interplay between motor and cognitive functions during performance of concurrent tasks is not fully understood but is known to vary depending on task characteristics and across clinical populations. Our controlled study examined how a concurrent digit span task affected a motor stability and motor overflow task in patients with multiple sclerosis (MS). METHOD: We asked 22 patients with MS and 22 matched controls to exert force on a transducer using 1 index finger at a time. We measured their motor stability (accuracy of voluntary force production) and motor overflow (involuntary force produced by the opposite, inactive finger). During half of the trials, the participants concurrently performed a digit span task. RESULTS: Overall, the patients with MS had more motor overflow and less motor stability than the controls; these measures correlated with the patients' disease severity. Adding the concurrent task affected motor stability; this relationship varied with the required level of exerted force. Motor overflow was lower during trials with the concurrent task. The concurrent task affected patients and controls similarly for both motor stability and overflow. CONCLUSIONS: This study demonstrates preserved motor function in a concurrent-task paradigm in patients with MS, and sheds further light on the relationship between attention and motor function in both the patients and controls. This research may help to inform rehabilitation for everyday life situations in which patients routinely perform cognitive and motor tasks simultaneously.

Movement planning and online control in multiple sclerosis: assessment using a Fitts law reciprocal aiming task.

OBJECTIVE: We sought to quantify subtle changes in motor control in multiple sclerosis (MS) using a Fitts law reciprocal aiming task presented on a computer touchscreen. BACKGROUND: Upper-limb motor control is impaired in MS. However, many commonly used motor assessments do not detect subtle changes in motor function or differentiate between aspects of movement such as planning and online control. Fitts law states that movement time varies as a function of task difficulty, with smaller targets and greater distances making the task more difficult. METHODS: We gave a Fitts aiming task to 22 patients with MS and 22 matched controls. We manipulated movement difficulty by changing the targets' size and distance apart. RESULTS: The patients spent a significantly longer time than the controls stationary in each target before starting the next movement, and had a lower peak velocity, suggesting deficits in movement planning. The patients also spent longer in the deceleration phase of each movement, indicating deficits in the online control of movement. CONCLUSIONS: The computerized Fitts task allows quick, easy, and sensitive measurement of subtle aspects of movement. This task should be useful in clinical and research settings for assessing MS motor symptoms, disease progression, and treatment efficacy.

Impaired response inhibition is associated with self-reported symptoms of depression, anxiety, and ADHD in female FMR1 premutation carriers.

Fragile X Mental Retardation 1 (FMR1) premutation carriers (PM-carriers) have a defective trinucleotide expansion on the FMR1 gene that is associated with continuum of neuropsychological and mental disorders. Currently, little is known about the distinct subcomponents of executive function potentially impaired in female PM-carriers, and there have been no investigations into associations between executive function and incidences of mental disorders. A total of 35 female PM-carriers confirmed by Asuragen triple primed PCR DNA testing and 35 age- and intelligence-matched controls completed tests of executive function (i.e., response inhibition and working memory) and self-reported on social anxiety, depression, and ADHD predominantly inattentive (ADHD-PI) symptoms. Compared to controls, PM-carriers were significantly elevated on self-reported social anxiety and ADHD-PI symptoms. Irrespective of mental symptoms, female PM-carries performed significantly worse than controls on a response inhibition test, and further investigations revealed significant correlations between executive function performance and self-reported symptoms of anxiety, depression and ADHD-PI. Critically, among PM-carriers with good executive function performance, no women exceeded threshold markers for probable caseness of mental disorder. However, rates of probable caseness were elevated in those with average performance (response inhibition: social anxiety: 41.7%; depression: 20%; ADHD: 44.4%; working memory: social anxiety: 27.3%; depression: 9.1%; ADHD: 18.2%) and highly elevated for those with poor executive function performance (response inhibition: social anxiety: 58.3%; depression: 80%; ADHD: 55.6%; working memory: social anxiety: 100%; depression: 50%; ADHD: 83.3%). These data suggest that subtle executive dysfunction may be a useful neuropsychological indicator for a range of mental disorders previously reported in female PM-carriers.

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.

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.

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.