Migrating Focal Seizures and Myoclonic Status in ARV1-Related Encephalopathy

ObjectiveTo report longitudinal clinical, EEG, and MRI findings in 2 sisters carrying compound heterozygous ARV1 mutations and exhibiting a peculiar form of developmental and epileptic encephalopathy (DEE). Neuropathologic features are also described in one of the sisters.MethodsClinical course description, video-EEG polygraphic recordings, brain MRI, skin and muscle biopsies, whole-exome sequencing (WES), and brain neuropathology.ResultsSince their first months of life, both girls exhibited severe axial hypotonia, visual inattention, dyskinetic movements, severe developmental delay, and slow background EEG activity. Intractable nonmotor seizures started in both at the eighth month of life, exhibiting the electroclinical characteristics of epilepsy of infancy with migrating focal seizures (EIMFS). In the second year of life, continuous epileptiform EEG activity of extremely high amplitude appeared in association with myoclonic status, leading to severely impaired alertness and responsiveness. Repeated brain MRI revealed progressive atrophic changes and severe hypomyelination. WES identified a compound heterozygous in the ARV1 gene [(p.Ser122Glnfs*7) and (p.Trp163*)] in one patient and was subsequently confirmed in the other. Both sisters died prematurely during respiratory infections. Postmortem neuropathologic examination of the brain, performed in one, revealed atrophic brain changes, mainly involving the cerebellum.ConclusionsThis report confirms that biallelic ARV1 mutations cause a severe form of DEE and adds epilepsy with migrating focal seizures and myoclonic status to the spectrum of epilepsy phenotypes. Considering the potential role of human ARV1 in glycosylphosphatidylinositol (GPI) anchor biosynthesis, this severe syndrome can be assigned to the group of inherited GPI deficiency disorders, with which it shares remarkably similar clinical and neuroimaging features. ARV1 should be considered in the genetic screening of individuals with EIMFS.

Unilateral Stroke: Computer-based Assessment Uncovers Non-Lateralized and Contralesional Visuoattentive Deficits

Objective: Patients with unilateral stroke commonly show hemispatial neglect or milder contralesional visuoattentive deficits, but spatially non-lateralized visuoattentive deficits have also been reported. The aim of the present study was to compare spatially lateralized (i.e., contralesional) and non-lateralized (i.e., general) visuoattentive deficits in left and right hemisphere stroke patients. Method: Participants included 40 patients with chronic unilateral stroke in either the left hemisphere (LH group, n = 20) or the right hemisphere (RH group, n = 20) and 20 healthy controls. To assess the contralesional deficits, we used a traditional paper-and-pencil cancellation task (the Bells Test) and a Lateralized Targets Computer Task. To assess the non-lateralized deficits, we developed a novel large-screen (173 × 277 cm) computer method, the Ball Rain task, with moving visual stimuli and fast-paced requirements for selective attention. Results: There were no contralesional visuoattentive deficits according to the cancellation task. However, in the Lateralized Targets Computer Task, RH patients missed significantly more left-sided than right-sided targets in bilateral trials. This omission distribution differed significantly from those of the controls and LH patients. In the assessment of non-lateralized attention, RH and LH patients missed significantly more Ball Rain targets than controls in both the left and right hemifields. Conclusions: Computer-based assessment sensitively reveals various aspects of visuoattentive deficits in unilateral stroke. Patients with either right or left hemisphere stroke demonstrate non-lateralized visual inattention. In right hemisphere stroke, these symptoms can be accompanied by subtle contralesional visuoattentive deficits that have remained unnoticed in cancellation task.

Vision Screening Assessment (VISA) tool: diagnostic accuracy validation of a novel screening tool in detecting visual impairment among stroke survivors

PurposeScreening for visual problems in stroke survivors is not standardised. Visual problems that remain undetected or poorly identified can create unmet needs for stroke survivors. We report the validation of a new Vision Impairment Screening Assessment (VISA) tool intended for use by the stroke team to improve identification of visual impairment in stroke survivors.MethodsWe conducted a prospective case cohort comparative study in four centres to validate the VISA tool against a specialist reference vision assessment. VISA is available in print or as an app (Medicines and Healthcare products Regulatory Agency regulatory approved); these were used equally for two groups. Both VISA and the comprehensive reference vision assessment measured case history, visual acuity, eye alignment, eye movements, visual field and visual inattention. The primary outcome measure was the presence or absence of visual impairment.ResultsTwo hundred and twenty-one stroke survivors were screened. Specialist reference vision assessment was by experienced orthoptists. Full completion of screening and reference vision assessment was achieved for 201 stroke survivors. VISA print was completed for 101 stroke survivors; VISA app was completed for 100. Sensitivity and specificity of VISA print was 97.67% and 66.67%, respectively. Overall agreement was substantial; K=0.648. Sensitivity and specificity of VISA app was 88.31% and 86.96%, respectively. Overall agreement was substantial; K=0.690. Lowest agreement was found for screening of eye movement and near visual acuity.ConclusionsThis validation study indicates acceptability of VISA for screening of potential visual impairment in stroke survivors. Sensitivity and specificity were high indicating the accuracy of this screening tool. VISA is available in print or as an app allowing versatile uptake across multiple stroke settings.

Prevalence of Eye Problems among Young Infants of Rohingya Refugee Camps: Findings from a Cross-Sectional Survey

Early detection of pediatric eye problems can prevent future vision loss. This study was to estimate the prevalence of common eye problems among infants born in a resource-constrained emergency setting with a broader aim to prevent future vision loss or blindness among them through early detection and referral. We conducted a cross-sectional survey among 670 infants (0–59 days old) born in Rohingya refugee camps in Bangladesh between March and June of 2019. The most common eye problem found was watering from the eye and accumulation of discharge by which 14.8% of the children were suffering (95% CI: 12.2–17.7). More than 5% of the infants had visual inattention (95% CI: 3.5–7.0), and 4% had redness in their eyes (95% CI: 2.7–5.8). Only 1.9% of infants (95% CI: 1–3.3) had whitish or brown eyeballs, and 1.8% of children might have whitish pupillary reflex (95% CI: 0.9–3.1). None of the eye problems was associated with the gender of the infants. The prevalent eye problems demand eye care set up for the screening of eye problems in the camps with proper referral and availability of referral centres with higher service in the districts.

Predicting Drivers’ Eyes-Off-Road Duration in Different Driving Scenarios

Drivers consecutively direct their gaze to various areas to select relevant information from the traffic environment. The rate of crash risk increases with different off-road glance durations in different driving scenarios. This paper proposed an approach to identify current driving scenarios and predict driver’s eyes-off-road durations using Hidden Markov Model (HMM). A moving base driving simulator study with 26 participants driving in three driving scenarios (urban, rural, and motorway) was conducted. Three different fixed occlusion durations (0-s, 1-s, and 2-s) were applied to quantify eyes-off-road durations. Participants could initiate each occlusion for certain duration by pressing a microswitch on a finger. They were instructed to occlude their vision as often as possible while still driving safely. Drivers’ visual behavior and occlusion behavior were captured and analyzed based on manually frame by frame coding. Visual behaviors in terms of glance duration and glance location in time series were used as input to train HMMs. The results showed that current driving scenarios could be identified ideally using glance location sequences, the accuracy achieving up to 89.3%. And motorway was relatively distinguishable easily with over 90% accuracy. Moreover, HMM-based algorithms that fed up with both glance duration and glance location sequences resulted in a highest accuracy of 92.7% in driver’s eyes-off-road durations prediction. And higher accuracy achieved in longer eyes-off-road durations prediction. It indicates that time series of glance allocations could be used to predict driving behavior and indentify driving environment. The developed models in this study could contribute to the development of scenario sensitive visual inattention prewarning system.

Visual Impairment Screening Assessment (VISA) tool: pilot validation

ObjectiveTo report and evaluate a new Vision Impairment Screening Assessment (VISA) tool intended for use by the stroke team to improve identification of visual impairment in stroke survivors.DesignProspective case cohort comparative study.SettingStroke units at two secondary care hospitals and one tertiary centre.Participants116 stroke survivors were screened, 62 by naïve and 54 by non-naïve screeners.Main outcome measuresBoth the VISA screening tool and the comprehensive specialist vision assessment measured case history, visual acuity, eye alignment, eye movements, visual field and visual inattention.ResultsFull completion of VISA tool and specialist vision assessment was achieved for 89 stroke survivors. Missing data for one or more sections typically related to patient’s inability to complete the assessment. Sensitivity and specificity of the VISA screening tool were 90.24% and 85.29%, respectively; the positive and negative predictive values were 93.67% and 78.36%, respectively. Overall agreement was significant; k=0.736. Lowest agreement was found for screening of eye movement and visual inattention deficits.ConclusionsThis early validation of the VISA screening tool shows promise in improving detection accuracy for clinicians involved in stroke care who are not specialists in vision problems and lack formal eye training, with potential to lead to more prompt referral with fewer false positives and negatives. Pilot validation indicates acceptability of the VISA tool for screening of visual impairment in stroke survivors. Sensitivity and specificity were high indicating the potential accuracy of the VISA tool for screening purposes. Results of this study have guided the revision of the VISA screening tool ahead of full clinical validation.

Rhythmic Activity and Individual Variability in Recognition Memory: Theta Oscillations Correlate with Performance whereas Alpha Oscillations Correlate with ERPs

During study trials of a recognition memory task, alpha (∼10 Hz) oscillations decrease, and concurrently, theta (4–8 Hz) oscillations increase when later memory is successful versus unsuccessful (subsequent memory effect). Likewise, at test, reduced alpha and increased theta activity are associated with successful memory (retrieval success effect). Here we take an individual-differences approach to test three hypotheses about theta and alpha oscillations in verbal, old/new recognition, measuring the difference in oscillations between hit trials and miss trials. First, we test the hypothesis that theta and alpha oscillations have a moderately mutually exclusive relationship; but no support for this hypothesis was found. Second, we test the hypothesis that theta oscillations explain not only memory effects within participants, but also individual differences. Supporting this prediction, durations of theta (but not alpha) oscillations at study and at test correlated significantly with d′ across participants. Third, we test the hypothesis that theta and alpha oscillations reflect familiarity and recollection processes by comparing oscillation measures to ERPs that are implicated in familiarity and recollection. The alpha-oscillation effects correlated with some ERP measures, but inversely, suggesting that the actions of alpha oscillations on memory processes are distinct from the roles of familiarity- and recollection-linked ERP signals. The theta-oscillation measures, despite differentiating hits from misses, did not correlate with any ERP measure; thus, theta oscillations may reflect elaborative processes not tapped by recollection-related ERPs. Our findings are consistent with alpha oscillations reflecting visual inattention, which can modulate memory, and with theta oscillations supporting recognition memory in ways that complement the most commonly studied ERPs.