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Purpose: During the COVID-19 pandemic, clinicians and researchers have increasingly used remote online assessments to pursue their activities, but mostly with tests not validated for videoconference administration. This study aims to validate the remote online administration of picture description in Canadian French neurotypical speakers and to explore the thematic unit (TU) checklist recently developed. Method: Spoken discourse elicited through the picture description task of the Western Aphasia Battery–Revised (WAB-R) was collected from Canadian French neurotypical speakers from Québec aged between 50 and 79 years old. Forty-seven participants completed the task in person, and 49 participants completed the task by videoconference. Videos of each discourse sample were transcribed using CHAT conventions. Microstructural variables were extracted using the CLAN (Computerized Language ANalysis) program, whereas thematic informativeness was scored for each sample using TUs. Chi-square tests were conducted to compare both groups on each TU; t tests were also performed on the total score of TUs and microstructural variables. Results: Groups were matched on sex, age, and education variables. The t tests revealed no intergroup difference for the total TU score and for the microstructural variables (e.g., mean length of utterances and number of words per minute). Chi-square tests showed no significant intergroup difference for all 16 TUs. Conclusions: These findings support remote online assessment of the picnic scene of the WAB-R picture description in Canadian French neurotypical speakers. These results also validate the 16 TUs most consistently produced. The use of videoconference could promote and improve the recruitment of participants who are usually less accessible, such as people using assistive mobility technologies. Supplemental Material: https://doi.org/10.23641/asha.21476961

PURPOSE: To describe the clinical phenotype of a cohort of patients with Wolfram syndrome (WS), focusing on the pattern of optic atrophy correlated with brain magnetic resonance imaging (MRI) measurements, as compared with patients with OPA1-related dominant optic atrophy (DOA).center dot DESIGN: Retrospective, comparative cohort study.center dot METHODS: We reviewed 25 patients with WS and 33 age-matched patients affected by OPA1-related DOA. Ophthalmologic, neurologic, endocrinologic, and MRI data from patients with WS were retrospectively retrieved. Ophthalmologic data were compared with data from patients with OPA1-related DOA and further analyzed for age dependency dividing patients in age quartiles. In a subgroup of patients with WS, we correlated the structural damage assessed by optical coherence tomography (OCT) with brain MRI morphologic measurements. Visual acuity (VA), visual field mean defect (MD), retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thickness were assessed by OCT and MRI morphologic measurements of anterior and posterior visual pathways.center dot RESULTS: Optic atrophy was present in 100% of patients with WS. VA, MD, and RNFL thickness loss were worse in patients with WS with a faster decline since early age as compared with patients with DOA, who displayed a more stable visual function over the years. Conversely, GCL sectors were overall thinner in patients with DOA since early age compared to patients with WS, in which GCL thickness started to decline later in life. The neuroradiologic subanalysis on 11 patients with WS exhibited bilateral thinning of the anterior optic pathway, especially the prechiasmatic optic nerves and optic tracts. Optic tract thinning was significantly correlated with GCL thickness but not with RNFL parameters.center dot CONCLUSIONS: Our results showed a generally more severe and diffuse degeneration of both anterior and posterior visual pathways in patients with WS, with fast deterioration of visual function and structural OCT parameters since early age. The pattern observed with OCT suggests that retinal ganglion cell axonal degeneration (ie, RNFL) precedes cellular body atrophy (ie, GCL) by about a decade. This differs substantially from DOA, in which a more stable visual function is evident with predominant early loss of GCL, indirectly supporting the lack of a primary mitochondrial dysfunction in patients with WS. (Am J Ophthalmol 2022;241: 206-216. (c) 2022 Elsevier Inc. All rights reserved.)

Research on language processing requires language-specific norms of pictorial and linguistic experimental stimuli across different psycholinguistic variables. Such normative data have not yet been collected for Lebanese Arabic (LA), an Arabic dialect. Arabic languages are characterized by diglossia: while modern standard Arabic is their common means of formal communication, Arabic dialects are the medium of oral communication within each community. This claims for specific dialectal norms. Thus, the main goal of the present study was to collect normative LA data for 380 pictures taken from Cykowicz, Friedman, Rothstein, and Snodgrass (The Quarterly Journal of Experimental Psychology Section A 50(3):560-585; including the 260 pictures of SnodgrassVanderwart in Journal of experimental psychology: Human learning and memory 6(2):174-215, 1980) using a sample of 248 native LA speakers. Norms are reported for name agreement, conceptual familiarity, imageability and subjective frequency, together with word length in number of letters and syllables. We compared the obtained norms with the normative data of other Arabic dialects (Levantine, Tunisian and Gulf Arabic) and with English, French and Spanish. Results showed the distinction of LA from the other Arabic dialects. This provides support of specific dialectal Arabic norms and will allow researchers to rigorously select the stimuli to investigate language processing in LA-speaking populations.

The aim of this study was to investigate changes in macular perfusion in patients affected by diabetic macular edema (DME) and treated with ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg using optical coherence tomography angiography (OCTA).This was a retrospective cohort study that included patients aged18 years with type 2 non-proliferative diabetic retinopathy (DR) and DME at baseline. All patients were treated with the ILUVIEN® implant. A minimum of two 6 × 6-mm OCTA scans were required to ensure that all cases had a baseline OCTA and an OCTA performed at 4 months of follow-up. Qualitative and quantitative comparisons were performed.Ten eyes from ten subjects were included in the analysis. Mean (± standard deviation) age of the study cohort was 57.1 ± 8.3 years. Mean parafoveal perfusion density (PD) at baseline was 64.1 ± 1.8% at baseline, increasing to 66.1 ± 2.9% (p = 0.013) at the 4-month follow-up visit. Mean parafoveal PD at baseline was 64.4 ± 2.1%, increasing to 65.2 ± 2.6% (p = 0.024) after 4 months. In the qualitative assessment, 60 regions (10 areas for each subject) were graded to assess changes in retinal perfusion between the baseline and follow-up visits. This assessment revealed that 24 regions (40.0%) were characterized by a qualitative increase in perfusion after treatment, while 22 (36.7%) and 14 (23.3%) regions were featured by a stability and reduction in retinal perfusion, respectively.OCTA analysis detects improvements in macular perfusion after treatment with ILUVIEN®. This improvement in macular perfusion may be associated with corticosteroid-related beneficial effects on leukostasis.

Background Discourse analysis has recently received much attention in the aphasia literature. Even if post-stroke language recovery occurs throughout the longitudinal continuum of recovery, very few studies have documented discourse changes from the hyperacute to the chronic phases of recovery. Aims To document a multilevel analysis of discourse changes from the hyperacute phase to the chronic phase of post-stroke recovery using a series of single cases study designs. Methods & Procedures Four people with mild to moderate post-stroke aphasia underwent four assessments (hyperacute: 0–24 h; acute: 24–72 h; subacute: 7–14 days; and chronic: 6–12 months post-onset). Three discourse tasks were performed at each time point: a picture description, a personal narrative and a story retelling. Multilevel changes in terms of macro- and microstructural aspects were analysed. The results of each discourse task were combined for each time point. Individual effect sizes were computed to evaluate the relative strength of changes in an early and a late recovery time frame. Outcomes & Results Macrostructural results revealed improvements throughout the recovery continuum in terms of coherence and thematic efficiency. Also, the microstructural results demonstrated linguistic output improvement for three out of four participants. Namely, lexical diversity and the number of correct information units/min showed a greater gain in the early compared with the late recovery phase. Conclusions & Implications This study highlights the importance of investigating all discourse processing levels as the longitudinal changes in discourse operate differently at each phase of recovery. Overall results support future longitudinal discourse investigation in people with post-stroke aphasia.

Older adults display impairments in accessing episodic, but not semantic details, when specifically requested to construct autobiographical events. How aging affects access to autobiographical information under conditions of low retrieval constraint remains unclear. We examined the production of episodic and "non-episodic" details in young (n = 25) and older (n = 24) adults on a novel autobiographical narrative task free from constraints on the type of information to be retrieved (Thoughts task), compared with the standard autobiographical memory and picture description tasks. Older adults generated fewer episodic and more non-episodic details on the memory task than young adults, however there was no age difference in detail profiles on the Thoughts task. Under these conditions of low retrieval constraint, narratives of young and older adults consisted of mostly personal and general semantic content. Young adults also provided less episodic and more semantic details on the Thoughts than the memory task, while older adults provided similar amounts of details across tasks. These results reveal that both young and older adults retrieve semantic autobiographical content under minimally constrained retrieval conditions. Moreover, aging may impact upon the ability to shift the detail types (episodic, semantic) provided in response to changing demands of different autobiographical narrative tasks.

Purpose: To report a case of endophthalmitis following bleb needling in a patient previously implanted with a PRESERFLO® MicroShunt. Methods: Case report. Results: A 40-year-old woman with bilateral malformative glaucoma repeatedly operated on in childhood underwent PRESERFLO® MicroShunt implantation in her right eye and six needling revisions (NRs) and a surgical revision due to unsatisfactory intraocular pressure (IOP) control due to bleb encapsulation. About 3 months after the surgical revision the bleb encapsulation relapsed and she underwent a further NR with betamethasone. About 4 days after the last NR, she experienced visual acuity reduction and was therefore advised to come immediately to the hospital for an unscheduled visit, showing up with hypopyon and diffuse vitreous haze. A clinical diagnosis of endophthalmitis (later confirmed by bacteria culture tests) was made and she was treated with pars-plana vitrectomy with silicone oil and intravitreal antibiotics. Preoperative visual function was luckily completely restored. Conclusions: Endophthalmitis can occur after NR in an eye with PRESERFLO® MicroShunt implant which therefore does not prevent reflux of bacteria from a filtering bleb to the anterior chamber.

To analyze the functional impact of ectopic inner foveal layers (EIFL), along with other clinical and optical coherence tomography biomarkers, on patients with epiretinal membrane (ERM) and preserved foveal layers’ segmentation undergoing ERM removal. Retrospective review of consecutive patients with ERM who underwent pars plana vitrectomy with ERM peeling from December 2018 to December 2019. Baseline factors including age, gender, lens status, phacoemulsification at the time of surgery, tamponade agent, dye used for ERM and internal limiting membrane (ILM) enhancement, ILM peeling, best-corrected visual acuity (BCVA) and central macular thickness (CMT), presence and thickness of EIFL, thickness of outer nuclear layer (ONL), presence of a cotton ball, subfoveal state of photoreceptors, and presence of cystoid macular edema were included in a multivariable model having the BCVA at 12 months as the main outcome. The changes in EIFL and ONL thickness over time were also analyzed. Fifty-one patients (58 eyes, 23 eyes in the no EIFL group, and 35 eyes in the EIFL group) were enrolled. The BCVA significantly improved over 12 months after surgery, regardless of the presence of EIFL (p < 0.001). Eyes with no EIFL had better BCVA at month 3 (p = 0.04), but this difference was no longer detectable at 6 and 12 months. The presence of EIFL was not associated with the final BCVA (p = 0.9), while the CMT at 12 months correlated with EIFL thickness (r = 0.8, p = 0.008). Patients with EIFL could reach optimal visual acuity in the absence of disorganization of the inner retinal layers but should be warned of potentially longer healing times. None of the morphologic signs included in this study precluded good visual recovery on long-term follow-up.

To investigate the associated features and the surgical outcomes in eyes with microcystoid macular edema (MME) and cone bouquet abnormalities (CBA) undergoing epiretinal membrane peeling.Retrospective study including patients who underwent pars plana vitrectomy for idiopathic epiretinal membrane. Factors associated with MME and CBA at baseline and their regression were identified with logistic regression models. Postoperative visual acuity was evaluated with linear mixed models from baseline to 12 months. Risk factors for new or worsened macular edema were explored with a Cox regression model.One hundred and eighty-seven eyes are included in this study; 30 eyes (16%) had MME and 53 eyes (28%) had CBA preoperatively. Microcystoid macular edema was associated with severe epiretinal membrane stage (odds ratio [95% confidence interval] = 3.6 [1.3-12.7], P = 0.02); CBA was inversely associated with ectopic inner foveal layer thickness (odds ratio [95% confidence interval] = 0.97 [0.97-0.99] for each 1- μ m EIFL increase, P = 0.006). Eyes with MME had worse visual acuity after epiretinal membrane peeling ( P = 0.01) and were at risk of macular edema worsening (hazard ratio [95% confidence interval] = 2.22 [1.01-5.16], P = 0.04). Older age was associated with MME persistence (odds ratio [95% confidence interval] = 2.46 [1.06-6.82] for each 10-year increase, P = 0.04). No significant associations were found for CBA.Although CBA had no prognostic consequences, MME was associated with suboptimal visual recovery and less efficient control of inflammation after surgery. Degeneration of Müller cells may have an alleged role, and further imaging and functional tests are warranted.

This study presents a comprehensive systematic review and meta-analysis of temporal processing in autism spectrum disorder (ASD) and developmental dyslexia (DD), two neurodevelopmental disorders in which temporal processing deficits have been highly researched. The results provide strong evidence for impairments in temporal processing in both ASD (g = 0.48) and DD (g = 0.82), as measured by judgments of temporal order and simultaneity. In individual analyses, multisensory temporal processing was impaired for both ASD and DD, and unisensory auditory, visual and tactile processing were all impaired in DD. In ASD, speech stimuli showed moderate impairment effect sizes, whereas nonspeech stimuli showed small effects. Greater reading and spelling skills in DD were associated with greater temporal precision. Temporal deficits did not show changes with age in either disorder. In addition to more clearly defining temporal impairments in ASD and DD, the results highlight common and distinct patterns of temporal processing between these disorders. Deficits are discussed in relation to existing theoretical models, and recommendations are made for future research.

Purposes: To describe the prevalence of ocular features among COVID-19 patients and their relationship with clinical data, inflammatory markers and respiratory support therapy (including CPAP); to investigate SARS-CoV-2 in ocular secretions of symptomatic patients. Methods: 172 COVID-19 patients were evaluated for presence of ocular manifestations. Clinical and laboratory data were also reviewed. Conjunctival swabs were analyzed for SARS-CoV-2 by RT-PCR. Results: Forty-five patients (26.2%) reported ocular manifestations. Patients treated with CPAP were more likely to have ocular abnormalities (p

The topological organization of the brain, governed by the capacity of brain regions to synchronize their activity, allows for cost-effective performance during everyday cognitive activity. Functional connectivity is an fMRI method deemed task-specific and demand-dependent. Although the brain undergoes significant changes during healthy aging, conceptual knowledge and word-production accuracy are generally preserved. The exploration of task-induced functional connectivity patterns during active picture naming may thus provide additional information about healthy functional cerebral mechanisms that are specifically adapted to the cognitive activity at hand. The goal of this study is to assess and describe age-related differences in functional connectivity during an overt picture-naming task, as well as to compare age-related differences under complex task demand, defined by lexical frequency. Results suggest both age-specific and task-specific mechanisms. In the context of preserved behavioral performance in a picture-naming task, older adults show a complex array of differences in functional connectivity architecture, including both increases and decreases. In brief, there is increased segregation and specialization of regions that are classically assigned to naming processes. Results also expand on previous word-production studies and suggest that motor regions are particularly subject to age-related differences. This study also provides the first indication that intrinsic task demand, as manipulated by lexical frequency, interacts little with the relationship between age and functional connectivity. Together, these findings confirm the value of task-induced functional connectivity analysis in revealing the brain organization that subserves task performance during healthy aging.

Diffusion imaging (DWI) is considered an optimal technique to detect hyperacute cerebral ischemia and has thus enriched the clinical management of patients with suspected stroke. Researchers have taken this technique beyond with Diffusion Tensor Imaging (DTI)-extracted measures, which have been proposed as biomarkers of stroke progression. A large body of literature report on the correlates between pathophysiological events, such as cytotoxic and vasogenic edema, and diffusion changes in the brain. However, a unified picture of these changes, and their exploration as stroke pathology progression biomarkers, remains to be done. We present here a narrative review on the different pathophysiological events underlying stroke from onset until late subacute stages and its relation to different brain edema forms. Studies included in this review used either DWI and/or DTI analysis in hyperacute (

Intrinsic connectivity networks (ICNs) identified through task-free fMRI (tf-fMRI) offer the opportunity to investigate human brain circuits involved in language processes without requiring participants to perform challenging cognitive tasks. In this study, we assessed the ability of tf-fMRI to isolate reproducible networks critical for specific language functions and often damaged in primary progressive aphasia (PPA). First, we performed whole-brain seed-based correlation analyses on tf-fMRI data to identify ICNs anchored in regions known for articulatory, phonological, and semantic processes in healthy male and female controls (HCs). We then evaluated the reproducibility of these ICNs in an independent cohort of HCs, and recapitulated their functional relevance with apost hocmeta-analysis on task-based fMRI. Last, we investigated whether atrophy in these ICNs could inform the differential diagnosis of nonfluent/agrammatic, semantic, and logopenic PPA variants. The identified ICNs included a dorsal articulatory-phonological network involving inferior frontal and supramarginal regions; a ventral semantic network involving anterior middle temporal and angular gyri; a speech perception network involving superior temporal and sensorimotor regions; and a network between posterior inferior temporal and intraparietal regions likely linking visual, phonological, and attentional processes for written language. These ICNs were highly reproducible across independent groups and revealed areas consistent with those emerging from task-based meta-analysis. By comparing ICNs' spatial distribution in HCs with patients' atrophy patterns, we identified ICNs associated with each PPA variant. Our findings demonstrate the potential use of tf-fMRI to investigate the functional status of language networks in patients for whom activation studies can be methodologically challenging.SIGNIFICANCE STATEMENTWe showed that a single, short, task-free fMRI acquisition is able to identify four reproducible and relatively segregated intrinsic left-dominant networks associated with articulatory, phonological, semantic, and multimodal orthography-to-phonology processes, in HCs. We also showed that these intrinsic networks relate to syndrome-specific atrophy patterns in primary progressive aphasia. Collectively, our results support the application of task-free fMRI in future research to study functionality of language circuits in patients for whom tasked-based activation studies might be methodologically challenging.

We mapped the left hemisphere cortical regions and fiber bundles involved in picture naming in adults by integrating task-based fMRI with dMRI tractography. We showed that a ventral pathway that “maps image and sound to meaning” involves the middle occipital, inferior temporal, superior temporal, inferior frontal gyri, and the temporal pole where a signal exchange is made possible by the inferior fronto-occipital, inferior longitudinal, middle longitudinal, uncinate fasciculi, and the extreme capsule. A dorsal pathway that “maps sound to speech” implicates the inferior temporal, superior temporal, inferior frontal, precentral gyri, and the supplementary motor area where the arcuate fasciculus and the frontal aslant ensure intercommunication. This study provides a neurocognitive model of picture naming and supports the hypothesis that the ventral indirect route passes through the temporal pole. This further supports the idea that the inferior and superior temporal gyri may play pivotal roles within the dual-stream framework of language.

Purpose: The main aim of this study is to provide French Canadian reference data for quantitative measures extracted from connected speech samples elicited by the Western Aphasia Battery–Revised picnic scene, a discourse task frequently used in clinical assessment of acquired language disorders. Method: Our sample consisted of 62 healthy French Canadian adults divided in two age groups: a 50- to 69-year-old group and a 70- to 90-year-old group. Results: High interrater reliability scores were obtained for most of the variables. Most connected speech variables did not demonstrate an age effect. However, the 70- to 90-year-old group produced more repetitions than the 50- to 69-year-old group and displayed reduced communication efficiency (number of information content units per minute). Conclusion: These findings contribute to building a reference data set to analyze descriptive discourse production in clinical settings.

Background: Rapid-eye-movement sleep behavior disorder (RBD) is a major risk factor for Parkinson’s disease and dementia with Lewy bodies. More than a third of RBD patients have mild cognitive impairment (MCI), but their specific structural brain alterations remain poorly understood. Objective: This study aimed to investigate the local deformation and volume of gray and white matter tissue underlying MCI in RBD. Methods: Fifty-two idiopathic RBD patients, including 17 with MCI (33%), underwent polysomnography, neuropsychological, neurological, and magnetic resonance imaging assessments. MCI diagnosis was based on a subjective complaint, cognitive impairment on the neuropsychological battery, and preserved daily functioning. Forty-one controls were also included. Deformation-based morphometry (DBM), voxel-based morphometry (VBM), and regional volume analyses of the corpus callosum and cholinergic basal forebrain were performed. Multiple regression models were also computed using anatomical, cognitive (composite z scores), and motor parameters. Results: Globally, patients with MCI displayed a widespread pattern of local deformation and volume atrophy in the cortical (bilateral insula, cingulate cortex, precuneus, frontal, temporal and occipital regions, right angular gyrus, and mid-posterior segment of the corpus callosum) and subcortical (brainstem, corona radiata, basal ganglia, thalamus, amygdala, and right hippocampus) regions compared to patients without MCI (DBM) or controls (DBM and VBM). Moreover, brain deformation (DBM) in patients were associated with lower performance in attention and executive functions, visuospatial abilities, and higher motor symptoms severity. Conclusion: The present study identified novel brain structural alterations in RBD patients with MCI which correlated with poorer cognitive performance. These results are consistent with those reported in patients with synucleinopathies-related cognitive impairment.

Background and ObjectivesSelf-reported language complaints, and more specifically word-finding difficulties, are among the most frequent cognitive complaints in cognitively normal older adults (CN). The clinical significance of elevated self-reported word-finding complaints in CN is still a matter of debate. The present study aims at characterizing word-finding complaints in CN, establish their sociodemographic and psychological correlates, determine if they are predictive of lower levels of cerebrospinal fluid Aβ levels and finally, investigate if they are associated with brain atrophy in regions associated with naming impairments.MethodsIn this observational case-control study, 239 CN from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were selected. All participants completed the self-reported version of the Everyday Cognition (ECog) questionnaire, as well as a lumbar puncture for Aβ and a MRI.ResultsWord-finding complaints were rated equally severe as a few other memory items and significantly more severe compared to all the other cognitive complaints. Ecog-Lang1 (Forgetting the names of objects) was not related to any demographic (age, sex, years of education) or psychological variable (depression-related symptoms, anxiety-related symptoms), while Ecog-Lang3 (Finding the right words to use in a conversation) was significantly negatively associated with years of education and positively associated with depression-related symptoms. Ecog-Lang1 severity significantly predicted CSF Aβ levels in CN, and this result remained significant even when controlling for all demographic and psychological variables as well as general level of cognitive complaint. Individuals with high Ecog-Lang1 complaints showed atrophy in the left fusiform gyrus and the left rolandic operculum in comparison to CN with no or low Ecog-Lang1 complaints.DiscussionOverall, our results support the fact that word-finding complaints are significant in CN and should be taken seriously. They have the potential to identify CN at risk of AD and support the need to include other cognitive domains in the investigation of subjective cognitive decline.

The authors report a case of a male patient affected by macular hole. In particular, a hyperreflective tissue was found on optical coherence tomography (OCT) examination in macular region, just above the retinal pigment epithelium (RPE). OCT angiography (OCTA) did not show the presence of vascular tissue, thus the hyperreflective material was ascribed to primary gliotic tissue. This case highlights the ability for Müller cells placed near macular holes to migrate up to the RPE and to produce gliotic tissue.

The aim of this study was to explore whether rotational three-dimensional (3D) visualization of optical coherence tomography angiography (OCTA) volume data may yield valuable information regarding diabetic retinal microaneurysm (MA) characteristics. In this retrospective, observational study, we collected data from 20 patients (20 eyes) with diabetic retinopathy. Subjects were imaged with the SS-OCTA system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). The OCTA volume data were processed with a volume projection removal algorithm and then exported to imageJ in order to obtain a 3D visualization of the analyzed MAs. The rotational three-dimensional OCTA images were qualitatively and quantitatively investigated. A total of 52 MAs were included in the analysis. On rotational 3D OCTA images, the number of vessels associated with each MA varied between 1 and 4, and most MAs (59.6%) were associated with 2 vessels. Moreover, in 20 MAs (38.4%) these vessels seem to originate from the SCP, while 26 MAs (50.0%) had associated vessels originating from the DVC, and 6 MAs had associated vessels arising from both the SCP and DVC (11.6%). Most MAs (31/52) had a ‘saccular’ shape. The number of retinal layers occupied by each MA ranged between 1 and 3 and the inner nuclear layer was the retinal layer most frequently occupied by MAs. In conclusion, this study used an algorithm to obtain rotational three-dimensional visualization of retinal MAs. The MAs’ architecture is complex and 3D visualization may clarify the true vascular origin of these lesions, which is often mistaken using en face OCTA images.

Choroideremia (CHM) is an X-linked chorioretinal dystrophy characterized by progressive degeneration of the choroid, retinal pigment epithelium and retina. This disease is caused by mutations in the X-linked CHM gene encoding a Ras-related GTPase Rab escort protein (REP)-1, which is extremely important for the retinal function. Clinically, male-affected patients have a progressive reduction in visual acuity. This disease is formally considered incurable, although new promising treatments have been recently introduced. In this article, a review of the salient pathogenetic features of choroideremia, essential for the proper interpretation of therapeutic approaches, is followed by a discussion of the fundamental clinical features of this hereditary disease. Finally, relevant new therapeutic approaches in this disease will be discussed, including gene therapy, stem cells, small molecules, and retinal prosthesis.

The goal of the study was to determine whether the semantic variant of primary progressive aphasia (svPPA) affects the intrinsic connectivity network anchored to left and right anterior hippocampus, but spares the posterior hippocampus. A resting-state functional connectivity MRI (rs-fcMRI) study was conducted in a group of patients with svPPA and in controls, using a seed-to-voxel approach. In comparison to controls, massively reduced connectivity was found in the anterior hippocampus, mainly the left one, for svPPA patients but not in the left or right posterior hippocampus. In svPPA, the anterior hippocampus showed reduced functional connectivity with regions implicated in the semantic memory network. Significant correlation was also found between the functional connectivity strength of the left anterior hippocampus and the ventromedial cortex, and performance in semantic tasks. These findings indicate that the functional disconnection of the anterior hippocampus may be a promising in vivo biomarker of svPPA and illustrate the role of this hippocampal subregion in the semantic memory system.

Despite a well-documented pattern of semantic memory (SM) impairment, the patterns of brain activation during semantic processing in svPPA still remain poorly understood. The current study aimed to investigate the neural substrates of residual semantic processing in the context of this significant but selective SM impairment, through the case study of one svPPA patient. One svPPA patient (EC) and six elderly controls carried out a general-level semantic categorization task (biological and manufactured objects) while their brain activity was recorded using magnetoencephalography (MEG). Despite similar behavioral performance, EC showed hyperactivation of the left inferior temporal gyrus (ITG) and right anterior temporal lobe (ATL) relative to controls. This suggests that periatrophic regions within the ATL region may support preserved semantic abilities in svPPA. These results thus contribute to our understanding of the brain regions which are recruited to compensate for bilateral atrophy of the ATL and ensure residual semantic processing in svPPA.

Background: Connected speech (CS) deterioration appears early in the progression to Alzheimer’s disease (AD) and in mild cognitive impairment (MCI). As such, CS assessment may prove a quick, clinic...

International audience; Perceptual experience plays a critical role in the conceptual representation of words. Higher levels of semantic variables such as imageability, concreteness, and sensory experience are generally associated with faster and more accurate word processing. Nevertheless, these variables tend to be assessed mostly on the basis of visual experience. This underestimates the potential contributions of other perceptual modalities. Accordingly, recent evidence has stressed the importance of providing modality-specific perceptual strength norms. In the present study, we developed French Canadian norms of visual and auditory perceptual strength (i.e., the modalities that have major impact on word processing) for 3,596 nouns. We then explored the relationship between these newly developed variables and other lexical, orthographic, and semantic variables. Finally, we demonstrated the contributions of visual and auditory perceptual strength ratings to visual word processing beyond those of other semantic variables related to perceptual experience (e.g., concreteness, imageability, and sensory experience ratings). The ratings developed in this study are a meaningful contribution toward the implementation of new studies that will shed further light on the interaction between linguistic, semantic, and perceptual systems.

To report a case of endophthalmitis following bleb needling in a patient previously implanted with a PRESERFLOCase report.A 40-year-old woman with bilateral malformative glaucoma repeatedly operated on in childhood underwent PRESERFLOEndophthalmitis can occur after NR in an eye with PRESERFLO

International audience; Consistent with embodied cognition, a growing evidence in young adults show that sensorimotor processing is at the core of cognition. Considering that this approach predicts direct interaction between sensorimotor processing and cognition, embodied cognition may thus be particularly relevant to study aging, since this population is characterized by concomitant changes in sensorimotor and cognitive processing. The present perspective aims at showing the value and interest to explore normal aging throughout embodiment by focusing on the neurophysiological and cognitive changes occurring in aging. To this end, we report some of the neurophysiological substrates underpinning the perceptual and memory interactions in older adults, from the low and high perceptual processing to the conjunction in the medial temporal lobe. We then explore how these changes could explain more broadly the cognitive changes associated with aging in terms of losses and gains.

Introduction Positron emission tomography (PET) amyloid imaging has become an important part of the diagnostic workup for patients with primary progressive aphasia (PPA) and uncertain underlying pathology. Here, we employ a semi-automated analysis of connected speech (CS) with a twofold objective. First, to determine if quantitative CS features can help select primary progressive aphasia (PPA) patients with a higher probability of a positive PET amyloid imaging result. Second, to examine the relevant group differences from a clinical perspective. Methods 117 CS samples from a well-characterised cohort of PPA patients who underwent PET amyloid imaging were collected. Expert consensus established PET amyloid status for each patient, and 40% of the sample was amyloid positive. Results Leave-one-out cross-validation yields 77% classification accuracy (sensitivity: 74%, specificity: 79%). Discussion Our results confirm the potential of CS analysis as a screening tool. Discriminant CS features from lexical, syntactic, pragmatic, and semantic domains are discussed.

AimTo characterise macular neovascularisation (MNV) developing in eyes affected by geographic atrophy (GA).MethodsIn this multicentric longitudinal study involving three retina referral centres, patients previously affected by GA who developed an active MNV were included. Patients were investigated using structural optical coherence tomography (OCT), fundus autofluorescence, OCT-angiography and dye angiographies. Patients were treated with ProReNata antivascular endothelial growth factor (VEGF) injections and were revaluated after treatment.ResultsAmong 512 patients previously diagnosed with GA, 40 eyes of 40 patients (mean age 80.8±7.9 years, mean GA area 8.73±7.39 mm2) presented with treatment-naïve exudative MNV (accounting for an estimated prevalence of 7.81%; 5.49 to 10.13, 95% CIs) and thus were included in the analysis. 67.5% of MNVs were classified as type 2 MNV, 25% as type 1, 2.5% as type 3 and 5% as mixed phenotype. In 92.5% of cases, active MNV in GA showed subretinal hyperreflective material with or without evidence of subretinal/intraretinal hyporeflective exudation. During a mean follow-up of 28±25 months, patients were treated with 6.6±6.3 anti-VEGF injections, with 2.9±1.4 injections in the first year of treatment. No patient developed GA enlargement in the area of MNV.ConclusionsMNVs in GA showed different features and therapeutic response in comparison to previously reported features of MNV in age-related macular degeneration (AMD) without GA. For these reasons, the combined phenotype (ie, GA with neovascular AMD) should be considered as a distinct entity in the research and clinical setting.

Introduction: Stargardt disease (STGD) is heterogeneous in terms of severity and rate of progression. New advancements in genetic testing and retinal imaging have improved prognostication in the disease. Areas covered: A PubMed-based search was carried out using the terms ‘Stargardt dystrophy’, ‘Stargardt disease’, ‘Fundus flavimaculatus’, and ‘ABCA4’. All studies published in English up to August 2020 were reviewed. Data from international multicenter trials were also considered in the discussion. Expert opinion: Genotype-phenotype correlations represent a challenge in STGD, as other epigenetic and environment modifiers participate in defining the clinical outcome and the long-term prognosis. Earlier age of onset and deleterious ABCA4 variants are the main determinants of severe progression. Quantitative imaging approaches are potentially useful for following-up STGD patients. Non-invasive biomarkers are needed to predict the natural history of the disease or drug effectiveness in future therapeutic trials.

Systemic hypertension is related to a variety of retinal manifestations. Reported herein is a case of malignant hypertension associated with bilateral foveal neurosensory detachment in a middle age woman with stenosis of the left renal artery. The present case outlines the importance of recognizing ocular manifestations as a possible consequence of life-threatening systemic disease.

Background: Previous findings have demonstrated the importance of discourse analysis in post-stroke aphasia, as it allows for in-depth examination of language impairment and represents key components of functional communication. However, little is known about the recovery of discourse over time. Aims: The main aim of this study is to measure the longitudinal changes in descriptive discourse production from the acute to chronic stages of post-stroke aphasia recovery. The secondary aim is to explore the association between discourse measures and overall language impairment severity measures at different testing points. Methods & Procedure: Seventeen French Canadian speakers with various types and severities of aphasia following a first left middle cerebral artery stroke participated in this study. They underwent three language assessments (acute: 0 to 72 hours; subacute: 7 to 14 days; chronic: 6 to 12 months post-onset). The picture description from the Western Aphasia Battery was analyzed at three time points. Changes in terms of thematic informativeness and microstructural variables were analyzed. Outcomes & Results: Regarding the micro-structural variables, the mean length of utterances (MLU) and the number of words per minute showed significant positive changes between the acute and chronic phases. For the thematic informativeness measures, the number of thematic units (TUs), the number of thematic units per minute (TUs/min) and the number of thematic units per utterance (TUs/utt) 4 increased significantly between the acute and chronic phases. Positive correlations between TUs and MLU in the acute phase and a general language impairment severity measure in the acute and chronic phases suggest a relationship between these measures and global language performance suggesting the potential predictive value of these variables in the acute phase. Conclusions & Implications: These findings support the use of thematic units in descriptive discourse analysis during an acute clinical examination of language as they require minimal additional time to score and track changes in post-stroke aphasia recovery. They capture long-term changes in discourse abilities and appear related to overall language measures in both the acute and chronic stages of recovery. The interpretation of the changes in MLU and the number of words per minute is less straightforward, as improvements in these measures carry different interpretations depending on the type of aphasia. Nonetheless, further studies are required to investigate test-retest reliability and the effect of therapy on the changes observed over time when using thematic units to document change in discourse.

The aim of this study was to measure macular perfusion in patients with type 1 diabetes and no signs of diabetic retinopathy (DR) using volume rendered three-dimensional (3D) optical coherence tomography angiography (OCTA). We collected data from 35 patients with diabetes and no DR who had OCTA obtained. An additional control group of 35 eyes from 35 healthy subjects was included for comparison. OCTA volume data were processed with a previously presented algorithm in order to obtain the 3D vascular volume and 3D perfusion density. In order to weigh the contribution of different plexuses’ impairment to volume rendered vascular perfusion, OCTA en face images were binarized in order to obtain two-dimensional (2D) perfusion density metrics. Mean ± SD age was 27.2 ± 10.2 years [range 19–64 years] in the diabetic group and 31.0 ± 11.4 years [range 19–61 years] in the control group (p = 0.145). The 3D vascular volume was 0.27 ± 0.05 mm3 in the diabetic group and 0.29 ± 0.04 mm3 in the control group (p = 0.020). The 3D perfusion density was 9.3 ± 1.6% and 10.3 ± 1.6% in diabetic patients and controls, respectively (p = 0.005). Using a 2D visualization, the perfusion density was lower in diabetic patients, but only at the deep vascular complex (DVC) level (38.9 ± 3.7% in diabetes and 41.0 ± 3.1% in controls, p = 0.001), while no differences were detected at the superficial capillary plexus (SCP) level (34.4 ± 3.1% and 34.3 ± 3.8% in the diabetic and healthy subjects, respectively, p = 0.899). In conclusion, eyes without signs of DR of patients with diabetes have a reduced volume rendered macular perfusion compared to control healthy eyes.

We report a case of ocular drug toxicity consistent with bilateral Vogt-Koyanagi-Harada (VKH) like disease in a patient with cutaneous melanoma treated with Dabrafenib/Trametinib therapy. A 53-year-old man with a history of metastatic cutaneous melanoma, treated with Dabrafenib/Trametinib, developed a severe acute panuveitis with granulomatous anterior uveitis and multiple serous retinal detachments. The ocular inflammatory reaction was classified as a bilateral Vogt-Koyanagi-Harada disease. Intraocular inflammation resolved after discontinuation of chemotherapeutic agents and aggressive topical and systemic corticosteroid therapy. The present case outlines the importance of recognizing VKH-like syndrome as a possible consequence of therapy with dabrafenib and trametinib.

Objective The present study aims to assess the relationship between quantitative measures of connected speech production and performance in confrontation naming in early post-stroke aphasia (8-14 days post-stroke). Method: We collected connected speech samples elicited by a picture description task and administered a confrontation naming task to 20 individuals with early post-stroke aphasia and 20 healthy controls. Transcriptions were made in compliance with the CHAT format guidelines. Several micro- (i.e. duration, total number of words, words per minute, mean length of utterances, ratio of open- to closed-class words and noun-to-verb ratio, VOC-D, repetitions, self-corrections, and phonological and semantic errors) and macrolinguistic (i.e. informativeness and efficiency) measures were extracted. Results: We provide evidence for the presence of impairments in an array of micro- and macrolinguistic measures of speech in individuals with early post-stroke aphasia. We show that in the patient group, confrontation naming abilities most strongly relate to informativeness in a picture description task. Conclusion: Our findings contribute to a better understanding of the relationship between performance in confrontation naming and in connected speech production in the first days after stroke onset and also suggest that discourse analysis may provide unique, possibly more complex information.

To report our five-year experience on vitreoretinal lymphoma (VRL) as a single-center tertiary hospital.The ophthalmic, cytopathology, and onco-hematologic records of patients with VRL consecutivel...

The aim of this study was to report normal measurements of green-emitting fluorophores in the macula of healthy young individuals and to assess the repeatability of these quantitative metrics. To do so, healthy young volunteers were imaged twice (7 &plusmn, 3 days apart) using a confocal blue-light fundus autofluorescence (FAF) device with a shorter excitation wavelength (peak at 450 nm) and the capability for separately detecting the red and green components of the emission spectrum. The main outcome measure was the percentage of area occupied by green-emitting fluorophores in the macula. In addition, this measure was performed in separate regions providing a topographical assessment in the foveal, parafoveal and perifoveal regions. Furthermore, the level of agreement between repeated measurements was evaluated. Thirty eyes from 30 healthy volunteers were included in this analysis. Mean age was 26.2 &plusmn, 2.8 years (median: 25.0 years, range: 23.0&ndash, 32.0 years). Median (interquartile range&mdash, IQR) area occupied by green-emitting fluorophores was 3.6% (1.9&ndash, 4.7%) in the macular region. In the topographical analysis, this percentage was higher in the foveal area (median = 33.3%, IQR = 21.9&ndash, 41.2%), as compared with both the parafoveal (median = 5.3%, IQR = 2.4&ndash, 8.1%, p &lt, 0.0001) and perifoveal (median = 0.5%, IQR = 0.2&ndash, 0.8%, 0.0001) regions. The coefficient of variation (CV, ranging from 1.1% to 1.7% in the analyzed regions) and the intraclass correlation coefficient (ICC, ranging from 0.93 to 0.97) indicated high levels of repeatability. In conclusion, the assessment of green-emitting fluorophores is repeatable. The distribution of these fluorophores is highest in the foveal region. Assuming that flavin adenine dinucleotide (FAD) emits in the green autofluorescence spectrum, this variability could be secondary to an increased quantity of mitochondria in the foveal region.

Highlights • Both svPPA and AD manifest hippocampal atrophy. • svPPA and AD have similar pattern of hippocampal shape deformation as detected by deformation-based shape analysis. • Both diseases are characterized by a lateral displacement of the central part (body) of the hippocampus. • Morphological hippocampal changes are part of the early anatomical profile of patients with svPPA., Background Increasing evidence shows that the semantic variant of primary progressive aphasia (svPPA) is characterized by hippocampal atrophy. However, less is known about disease-related morphological hippocampal changes. The goal of the present study is to conduct a detailed characterization of the impact of svPPA on global hippocampus volume and morphology compared with control subjects and patients with Alzheimer’s disease (AD). Methods We measured hippocampal volume and deformation-based shape differences in 22 patients with svPPA compared with 99 patients with AD and 92 controls. Multiple Automatically Generated Templates Brain Segmentation Algorithm (MAGeT-Brain) was used on MRI images obtained at the diagnostic visit. Results Comparable left and right hippocampal atrophy were observed in svPPA and AD. Deformation-based shape analysis showed a common pattern of morphological deformation in svPPA and AD compared with controls. More specifically, both svPPA and AD showed inward deformations in the dorsal surface of the hippocampus, from head to tail on the left side, and more limited to the anterior portion of the body in the right hemisphere. These results also pointed out that both diseases are characterized by a lateral displacement of the central part (body) of the hippocampus. Discussion Our study provides critical new evidence of hippocampal morphological changes in svPPA, similar to those found in AD. These findings highlight the importance of considering morphological hippocampal changes as part of the anatomical profile of patients with svPPA.

Background: The greatest degree of language recovery in post-stroke aphasia takes place within the first weeks. Aphasia severity and lesion measures have been shown to be good predictors of long-term outcomes. However, little is known about their implications in early spontaneous recovery. The present study sought to determine which factors better predict early language outcomes in individuals with post-stroke aphasia. Methods: Twenty individuals with post-stroke aphasia were assessed

Purpose: To evaluate demographic, clinical, imaging, and genetic factors associated with retinal pigment epithelium enlargement in Stargardt disease (STGD1) and to measure the agreement between short-wavelength fundus autofluorescence (SW-FAF) and near-infrared fundus autofluorescence (NIR-FAF). Methods: Retrospective cohort study of patients with STGD1 with >2 gradable SW- FAF images. RPE-atrophy areas were measured on SW-FAF and NIR-FAF at each visit and regressed against time to obtain the rate of RPE-atrophy enlargement. Agreement between SW-FAF and NIR-FAF with regards to baseline atrophic areas and rates of enlargement was evaluated. Baseline factors predictive of faster SW-FAF RPE-atrophy enlargement were investigated with linear mixed models. Results: Fifty-four eyes of 28 patients (median age: 45 years; 13 males) were included. SW-FAF and NIR-FAF agreed well for slow rates of RPE-atrophy progression, but agreement decreased as the rate increased. Median (interquartile range [IQR]) rate of RPE-atrophy expansion was 0.18 (0.10-0.85) mm2/year on SW-FAF and 0.24 (0.08-0.33) mm2/year on NIR-FAF. Larger baseline RPE-atrophy area (estimate: 0.057 mm'/year, P < 0.001), worse visual acuity (0.305 mm'/year, P = 0.005), multifocal disease (0.401 mm"7year, P = 0.02), and SW-FAF pattern (0.534 mnWyear, P =0.03) were associated with a faster rate of progression (predictive R?: 0.65).Conclusions: SW-FAF and NIR-FAF are not interchangeable in the evaluation of RPEatrophy enlargement, and both imaging modalities may be required for optimal detection of disease progression. A multivariable model based on baseline clinical and imaging information may identify patients at higher risk of fast disease progression. Translational Relevance: The knowledge of the agreement of different FAF modalities, the estimated rates of RPE-atrophy enlargement, and factors predictive of faster anatomic decay in STGD1 may allow tailored clinical management and better clinical trials design.

Background Structural and functional brain imaging methods have identified age-related changes in brain structures involved in gait control. This cross-sectional study aims to investigate gray matter networks associated with gait control in aging using structural covariance analysis. Methods Walking speed were measured in 326 nondemented older community-dwellers (age 71.3 ± 4.5; 41.7% female) under three different walking conditions: normal walking and two challenging tasks: motor (ie, fast speed) and an attention-demanding dual task (ie, backward counting). Results Three main individual gray matter regions were positively correlated with walking speed (ie, slower walking speed was associated with lower brain volumes): right thalamus, right caudate nucleus, and left middle frontal gyrus for normal walking, rapid walking, and dual-task walking condition, respectively. The structural covariance analysis revealed that prefrontal regions were part of the networks associated with every walking condition; the right caudate was associated specifically with the hippocampus, amygdala and insula for the rapid walking condition, and the left middle frontal gyrus with a network involving the cuneus for the dual-task condition. Conclusion Our results suggest that brain networks associated with gait control vary according to walking speed and depend on each walking condition. Gait control in aging involved a distributed network including regions for emotional control that are recruited in challenging walking conditions.

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a major risk factor for Parkinson's disease and dementia with Lewy bodies. Anatomical gray matter abnormalities in the motor cortico-subcortical loop areas remain under studied in iRBD patients. We acquired T1-weighted images and administrated quantitative motor tasks in 41 patients with polysomnography-confirmed iRBD and 41 healthy subjects. Cortical thickness and voxel-based morphometry (VBM) analyses were performed to investigate local cortical thickness and gray matter volume changes, vertex-based shape analysis to investigate shape of subcortical structures, and structure-based volumetric analyses to investigate volumes of subcortical and brainstem structures. Cortical thickness analysis revealed thinning in iRBD patients in bilateral medial superior frontal, orbitofrontal, anterior cingulate cortices, and the right dorsolateral primary motor cortex. VBM results showed lower gray matter volume in iRBD patients in the frontal lobes, anterior cingulate gyri, and caudate nucleus. Shape analysis revealed extensive surface contraction in the external and internal segments of the left pallidum. Clinical and motor impaired features in iRBD were associated with anomalies of the motor cortico-subcortical loop. In summary, iRBD patients showed numerous gray matter structural abnormalities in the motor cortico-subcortical loop, which are associated with lower motor performance and clinical manifestations of iRBD.

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