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Machado Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disease. Mentalizing is the ability to think and understand the mental state of the other and of the self in terms of thoughts, feelings, and intentions. The aim of this study is to fill the gap in our understanding of mentalizing in MJD since there is currently very little and inconsistent research on MJD and mentalizing. A total of 18 Jews of Yemenite origin with clinically and genetically confirmed MJD, 5 pre-symptomatic MJD with a positive genetic test, and 17 Jews of Yemenite origin healthy controls, underwent a battery of tests consisting of reading the mind in the eyes (RME), Toronto Alexithymia Scale (TAS-20), and false belief test (FBt). The MJD group scored lower on the RME and FBt, and higher on TAS-20 test compared to control. A significant negative correlation was found between disease duration and RME score. All the pre-symptomatic participants scored within the normal clinical range in all tests. MJD patients demonstrated a widespread deficiency in the ability to mentalizing on a clinical level with autistic characteristics. These impairments may impact the patient's interpsychic experience and daily life interactions and have important clinical implication. Pre-symptomatic participants demonstrated normal mentalizing in all tests, suggesting that the mentalizing impairments do not precede the symptoms of ataxia and are part of the clinical picture of MJD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Because of the crucial importance of finding a useful biomarker for further clinical trials in Machado-Joseph disease (MJD), and based on our previous studies, we aimed to evaluate whether the horizontal vestibulo-ocular reflex (VOR) gain could be a reliable neurophysiological biomarker for the clinical onset, severity, and progression of the disease. Thirty-five MJD patients, 11 pre-symptomatic genetically confirmed MJD subjects, and 20 healthy controls underwent a detailed epidemiological and clinical neurological examination including the Scale for the Assessment and Rating of Ataxia (SARA). Their VOR gain was measured using the video Head Impulse Test system. Twenty of the MJD patients were re-tested after a period of 1-3 years. Horizontal VOR gain was abnormal in 92% of MJD, 54% pre-symptomatic, and 0% healthy controls. Horizontal VOR gain in the MJD group was significantly negatively correlated with SARA score in the first (r=0.66, p<0.001) and second (r=0.61, p<0.001) examinations. There was also a significant negative correlation between the percentage of change in horizontal VOR gain and the percentage of change in SARA score across both examinations (r=-0.54, p < 0.05). A regression model of the SARA score with the horizontal VOR gain and disease duration as predictors demonstrated that both the horizontal VOR gain and the disease duration had an independent contribution to the prediction of the SARA score. The horizontal VOR gain seems to be a reliable biomarker for the clinical onset, severity, and progression of MJD and could be used in further clinical studies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a slowly progressing autosomal recessive ataxic disorder linked to an abnormal biallelic intronic (most commonly) AAGGG repeat expansion in the replication factor complex subunit 1 (RFC1). While the clinical diagnosis is relatively straightforward when the three components of the disorder are present, it becomes challenging when only one of the triad (cerebellar ataxia, neuropathy or vestibular areflexia) manifests. Isolated cases of Bilateral Vestibulopathy (BVP) or vestibular areflexia that later developed the other components of CANVAS have not been documented. We report four cases of patients with chronic imbalance and BVP that, after several years, developed cerebellar and neuropathic deficits with positive genetic testing for RFC1. Our report supports the concept that CANVAS should be considered in every patient with BVP of unknown etiology, even without the presence of the other triad components. This is especially important given that about 50% of cases in many BVP series are diagnosed as idiopathic, some of which may be undiagnosed CANVAS., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The vestibulo-ocular reflex (VOR) stabilizes vision during head movements. VOR disorders lead to symptoms such as imbalance, dizziness, and oscillopsia. Despite similar VOR dysfunction, patients display diverse complaints. This study analyses saccades, balance, and spatial orientation in chronic peripheral and central VOR disorders, specifically examining the impact of oscillopsia., Methods: Participants involved 15 patients with peripheral bilateral vestibular loss (pBVL), 21 patients with clinically and genetically confirmed Machado-Joseph disease (MJD) who also have bilateral vestibular deficit, and 22 healthy controls. All pBVL and MJD participants were tested at least 9 months after the onset of symptoms and underwent a detailed clinical neuro-otological evaluation at the Dizziness and Eye Movements Clinic of the Meir Medical Center., Results: Among the 15 patients with pBVL and 21 patients with MJD, only 5 patients with pBVL complained of chronic oscillopsia while none of the patients with MJD reported this complaint. Comparison between groups exhibited significant differences in vestibular, eye movements, balance, and spatial orientation. When comparing oscillopsia with no-oscillopsia subjects, significant differences were found in the dynamic visual acuity test, the saccade latency of eye movements, and the triangle completion test., Discussion: Even though there is a significant VOR gain impairment in MJD with some subjects having less VOR gain than pBVL with reported oscillopsia, no individuals with MJD reported experiencing oscillopsia. This study further supports that subjects experiencing oscillopsia present a real impairment to stabilize the image on the retina, whereas those without oscillopsia may utilize saccade strategies to cope with it and may also rely on visual information for spatial orientation. Finding objective differences will help to understand the causes of the oscillopsia experience and develop coping strategies to overcome it., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Geisinger, Elyoseph, Zaltzman, Mintz and Gordon.)

Background: Machado Joseph Disease (MJD) is an autosomal dominant neurodegenerative disease. In previous studies, we described significant bilateral horizontal Vestibulo-Ocular Reflex (VOR) deficit within this population without any reference to the presence of vestibular symptomatology., Objective: To evaluate whether, beyond cerebellar ataxia complaints, MJD patients have typical vestibular symptomatology corresponding to the accepted diagnostic criteria of Bilateral Vestibulopathy (BVP) according to the definition of the International Barany Society of Neuro-Otology., Methods: Twenty-one MJD, 12 clinically stable chronic Unilateral Vestibulopathy (UVP), 15 clinically stable chronic BVP, and 22 healthy Controls underwent the video Head Impulse Test (vHIT) evaluating VOR gain and filled out the following questionnaires related to vestibular symptomatology: The Dizziness Handicap Inventory (DHI), the Activities-specific Balance Confidence Scale (ABC), the Vertigo Visual Scale (VVS) and the Beck Anxiety Inventory (BAI)., Results: The MJD group demonstrated significant bilateral vestibular impairment with horizontal gain less than 0.6 in 71% of patients (0.54±0.17). Similar to UVP and BVP, MJD patients reported a significantly higher level of symptoms than Controls in the DHI, ABC, VVS, and BAI questionnaires., Conclusions: MJD demonstrated significant VOR impairment and clinical symptoms typical of BVP. We suggest that in a future version of the International Classification of Vestibular Disorders (ICVD), MJD should be categorized under a separate section of central vestibulopathy with the heading of bilateral vestibulopathy. The present findings are of importance regarding the clinical diagnosis process and possible treatment based on vestibular rehabilitation.

Objective: Stimulation of the peripheral visual field has been previously reported as beneficial for cognitive performance in ADHD. This study assesses the safety and efficacy of a novel intervention involving peripheral visual stimuli in managing attention deficit hyperactivity disorder (ADHD)., Methods: One hundred and eight adults, 18-40 years old, with ADHD, were enrolled in a two-month open-label study. The intervention (i.e., Neuro-glasses) consisted of standard eyeglasses with personalized peripheral visual stimuli embedded on the lenses. Participants were assessed at baseline and at the end of the study with self-report measures of ADHD symptoms (the Adult ADHD Self-Report Scale; ASRS), and executive functions (The Behavior Rating Inventory of Executive Function Adult Version; BRIEF-A). A computerized test of continuous performance (The Conners' Continuous Performance Test-3; CPT-3) was tested at baseline with standard eyeglasses and at the end of study using Neuro-glasses. The Clinical Global Impression-Improvement scale (CGI-I) was assessed at the intervention endpoint. Safety was monitored by documentation of adverse events., Results: The efficacy analysis included 97 participants. Significant improvements were demonstrated in self-reported measures of inattentive symptoms (ASRS inattentive index; p  = 0.037) and metacognitive functions concerning self-management and performance monitoring (BRIEF-A; p  = 0.029). A continuous-performance test (CPT-3) indicated significant improvement in detectability (d'; p  = 0.027) and reduced commission errors ( p  = 0.004), suggesting that the Neuro-glasses have positive effects on response inhibition. Sixty-two percent of the participants met the response criteria assessed by a clinician (CGI-I). No major adverse events were reported., Conclusion: Neuro-glasses may offer a safe and effective approach to managing adult ADHD. Results encourage future controlled efficacy studies to confirm current findings in adults and possibly children with ADHD. Clinical trial registration : https://www.clinicaltrials.gov/, Identifier NCT05777785., Competing Interests: YR, CG, DG, NM-K, and CB-M are employees of VIZO-Specs Ltd. ZE and GV are consultants for VIZO-Specs Ltd. The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study received funding from VIZO-Specs Ltd. The funder had the following involvement with the study: study design, data collection, analysis, interpretation of data, the writing of this article, and the decision to submit it for publication., (Copyright © 2023 Richter, Gordon, Vainstein, Bublil-Mor, Geisinger, Meital-Kfir and Elyoseph.)

Background: Comorbid Balance, Anxiety, and Spatial symptoms are observed in neurodevelopmental disorders and aging. Each of these symptoms was studied separately in association with vestibular hypofunction. We aimed to investigate whether such a diffuse range of symptoms has common vestibular pathophysiology. Specifically, we tested whether this Triad of dysfunctions is associated with central or peripheral vestibular hypofunction. We also assessed the possible contribution of semicircular canals (SCCs) vs. saccular function., Methods: We tested patients with Peripheral bilateral and unilateral Vestibular Hypofunction (PVH), Machado Joseph Disease (MJD) with cerebellar and central bilateral vestibular hypofunction, and healthy controls. SCCs and sacculi functioning were evaluated by the video Head Impulse Test (vHIT) and cervical Vestibular Evoked Myogenic Potentials (cVEMP), respectively. Balance was assessed by the Activities-specific Balance Confidence scale (ABC), anxiety by the Hamilton Anxiety Rating Scale (HAM-A), and spatial orientation by the Object Perspective Taking test (OPT-t)., Results: PVH patients with vestibular SCCs and saccular hypofunction presented the Triad of symptoms, imbalance, anxiety, and spatial disorientation. MJD patients with SCCs-related vestibular hypofunction but preserved saccular-related vestibular function presented with a partial profile of imbalance and spatial disorientation., Conclusions: The present study provides evidence that peripheral vestibular hypofunction is associated with the Triad of dysfunctions, i.e., imbalance, anxiety, and spatial disorientation. The combination of SCCs and saccular hypofunction seems to contribute to the emergence of the Triad of symptoms., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Machado-Joseph disease (MJD) is an inherited neurodegenerative disease with progressive cerebellar ataxia manifested through lack of coordination and balance. MJD patients also present significant Vestibulo-Ocular Reflex (VOR) deficit but their whole vestibular features have not been previously evaluated. We aimed to evaluate whether MJD patients have vestibular features fitting the diagnostic criteria of Bilateral Vestibulopathy established by the International Society for Neuro-otology., Methods: Sixteen MJD patients and 21 healthy controls underwent a detailed clinical neuro-otological examination including a quantitative evaluation of the VOR gain using the video Head Impulse Test (vHIT). Vestibular-related symptoms were evaluated by the Dizziness Handicap Inventory (DHI), the Activities-specific Balance Confidence Scale (ABC), the Vertigo Visual Scale (VVS). In addition, anxiety that is frequently present in vestibular disorders, was evaluated by the Beck Anxiety Inventory (BAI)., Results: MJD patients had significantly reduced horizontal VOR gain with significantly higher scores in all vestibular-related symptoms questionnaires. These symptoms scores were like those reported in studies evaluating patients with bilateral peripheral vestibular loss., Conclusions: Beyond the cerebellar deficits, MJD patients have vestibular signs and symptoms fitting the diagnostic criteria of Bilateral Vestibulopathy established by the International Society for Neuro-otology. These findings are of relevance not only for the diagnosis and evaluation of progressive cerebellar diseases but also for the possible beneficial effect of vestibular rehabilitation techniques on dizziness, balance and the emotional, physiological and functional aspects of MJD.

Background: Psychiatric Depersonalization/Derealization (DPDR) symptoms were demonstrated in patients with peripheral vestibular disorders. However, only semicircular canals (SCCs) dysfunction was evaluated, therefore, otoliths' contribution to DPDR is unknown. Also, DPDR symptoms in patients with central vestibular dysfunction are presently unknown. DPDR was also studied in the context of spatial disorientation and anxiety, but the relation of these cognitive and emotional functions to vestibular dysfunction requires clarification., Methods: We tested patients with peripheral Bilateral Vestibular Hypofunction (pBVH), Machado Joseph Disease (MJD) with cerebellar and central bilateral vestibular hypofunction, and healthy controls. Participants completed the video Head Impulse Test (vHIT) for SCCs function, cervical Vestibular Evoked Myogenic Potentials test (cVEMPt) for sacculi function, Body Sensation Questionnaire (BSQ) for panic anxiety, Object Perspective-Taking test (OPTt) for spatial orientation and Cox & Swinson DPDR inventory for DPDR symptoms., Results: pBVH patients showed significant SCCs and sacculi dysfunction, spatial disorientation, elevated panic anxiety, and DPDR symptoms. MJD patients showed significant SCCs hypofunction but preserved sacculi function, spatial disorientation but normal levels of panic anxiety and DPDR symptoms. Only pBVH patients demonstrated a positive correlation between the severity of the DPDR and spatial disorientation and panic anxiety., Conclusions: DPDR develops in association with sacculi dysfunction, either with or without SSCs dysfunction. Spatial disorientation and anxiety seem to mediate the transformation of vestibular dysfunction into DPDR symptoms. DPDR does not develop in MJD with central vestibular hypofunction but a normal saccular response. We propose a three-step model that describes the development of DPDR symptoms in vestibular patients., Competing Interests: Declaration of Competing Interest Zohar Elyoseph, Dario Geisinger, Roy Zaltzman, Carlos R. Gordon, and Matti Mintz have nothing to declare and have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)