The Growing Role of Telerehabilitation and Teleassessment in the Management of Movement Disorders in Rare Neurological Diseases: A Scoping Review.

Background: People with rare neurological diseases (RNDs) often experience symptoms related to movement disorders, requiring a multidisciplinary approach, including rehabilitation. Telemedicine applied to rehabilitation and symptom monitoring may be suitable to ensure treatment consistency and personalized intervention. The objective of this scoping review aimed to emphasize the potential role of telerehabilitation and teleassessment in managing movement disorders within RNDs. By providing a systematic overview of the available literature, we sought to highlight potential interventions, outcomes, and critical issues. Methods: A literature search was conducted on PubMed, Google Scholar, IEEE, and Scopus up to March 2024. Two inclusion criteria were followed: (1) papers focusing on telerehabilitation and teleassessment and (2) papers dealing with movement disorders in RNDs. Results: Eighteen papers fulfilled the inclusion criteria. The main interventions were home-based software and training programs, exergames, wearable sensors, smartphone applications, virtual reality and digital music players for telerehabilitation; wearable sensors, mobile applications, and patient home video for teleassessment. Key findings revealed positive outcomes in gait, balance, limb disability, and in remote monitoring. Limitations include small sample sizes, short intervention durations, and the lack of standardized protocols. Conclusion: This review highlighted the potential of telerehabilitation and teleassessment in addressing movement disorders within RNDs. Data indicate that these modalities may play a major role in supporting conventional programs. Addressing limitations through multicenter studies, longer-term follow-ups, and standardized protocols is essential. These measures are essential for improving remote rehabilitation and assessment, contributing to an improved quality of life for people with RNDs.

Comparing the top 100 attacks in the Global Terrorism Database: high injury rate versus high fatality rate attacks.

BACKGROUND: Terrorist attacks have the potential to be mass casualty events, causing multiple injuries and deaths. High injury rate attacks will particularly place a high burden on emergency medical systems. This study aimed to assess if there is a difference between attacks with high injury rates and high fatality rates. METHODS: The top 100 terrorist events causing the highest number of fatalities versus the highest number of injuries were selected from the Global Terrorism Database. Analyses were performed on temporal factors, location, target type, attack and weapon type, and perpetrator type. RESULTS: The 9/11 attacks caused the highest number of both fatalities and injuries. With regards to injury rates, the sarin attacks in Tokyo, Japan ranked second. Events with high fatality rates were overrepresented in Sub-Saharan Africa, whereas events with high injury rates were predominant in the Middle East & North Africa. High fatality rates were most often associated with armed assaults and hostage takings. Bombings were responsible for the highest number of injuries. CBRN attacks were overrepresented in the top 100 injuries, and accounted for 11% of the incidents. CONCLUSION: High injury rate incidents place a heavy burden on the health care system as the number of injuries is nearly ten times as high as the number of injuries in high fatality rate incidents. Epidemiological analysis of high impact terrorist events may contribute to counter-terrorism preparedness, to an increased focus on dealing with CBRN-events, and thus to a proper medical response to future terrorist events.

50 Years of terrorism in Belgium: a review of 121 incidents in the global terrorism database.

OBJECTIVES: Belgium is not only prone to inland terrorism but also attracts terrorist factions aiming at various political, diplomatic, military, and/or religious targets. This study aimed to identify and characterize all documented terrorist attacks in Belgium reported to the Global Terrorism Database (GTD) over a period of 50 years. METHODS: The GTD was searched for all terrorist attacks in Belgium between 1970 and 2019. Analyses were performed on temporal factors, location, target type, attack and weapon type, attacker type, and number of casualties or hostages. RESULTS: In 50 years, 121 incidents accounted for 80 confirmed fatalities and 498 injured people. Bombings and explosions were the most frequently identified attack type (46.3%), followed by assassination (16.5%), infrastructure damage (15.7%) and armed or unarmed assaults (14.0%). Governmental and diplomatic institutions were the most frequent target (24.0%). For those perpetrators the GTD did have enough information we saw a timely change from far left and separatist dominating the early decades to Jihadi groups in the last decade, while anti-semitic factions were active in every decade. CONCLUSION: In contrast to other studies, this study did not show an increase over time. Left-wing perpetrators dominated the eighties. In 50 years of terrorist activity in Belgium, the health care system was spared. Devastating mass casualty attacks challenging the health care system are rare in Belgium.

Gait initiation in Parkinson's disease: comparison of timing and displacement during anticipatory postural adjustments as a function of motor severity and apathy in a large cohort.

Introduction: Gait initiation is preceded by three anticipatory postural adjustment (APA) phases. In Parkinson's disease (PD) generated force, displacement and timing during APA differ from healthy controls. APA might be influenced by disease status, weight or emotion. It is unknown how motor severity, disease duration or presence of apathy influences APA timing and displacement. Methods: We included 99 people with PD and 50 healthy controls (HC) to perform five gait initiation trials following an auditory cue. Force plates measured timing and center of pressure (CoP) displacement during APA phases. Results: Time to gait initiation (tGI) was higher in the PD group (p < 0.001, t = 2.74, 95%CI (0.008, 0.066)). The first two APA phases (APA1 and APA2a) lasted longer in PD (respectively p < 0.001, t = 3.87, 95%CI (0.091, 0.28) and p < 0.001, t = 4.1, 95%CI (0.031, 0.091)). Mean CoP displacement, variability in timing and displacement did not differ. A multiple regression model was used to determine if clinical variables were related to gait initiation parameters. tGI was predicted by age (p < 0.001) and weight (p = 0.005). The duration of APA1 was predicted by weight (p = 0.006) and APA2a by age (p < 0.001). Variability in duration of the locomotor phase (LOC) was predicted by age (p < 0.001). Conclusion: tGI and initial APA phases are longer in PD than in HC. There are no significant differences in variability of timing or displacement between the two groups. Gait initiation parameters are independent of disease duration, motor severity, medication usage or apathy in PD. Our findings suggest that cueing does not speed up gait initiation but reduces variability.

Evidence of Vestibular and Balance Dysfunction in Patients With Mild Cognitive Impairment and Alzheimer's Disease.

OBJECTIVES: Given the expected rise in dementia prevalence, early diagnosis is vital. As a growing body of literature has identified a potential association between vestibular function and cognition, vestibular assessment may aid in early screening. The aim of the study was to better comprehend the proposed association between vestibular function and Alzheimer's disease (AD) by comparing vestibular parameters (vestibular function testing and clinical balance measures) between a group with mild cognitive impairment (MCI), AD, and healthy controls with age-normal cognition. DESIGN: Cross-sectional analysis of the GECkO study, an ongoing prospective single-center longitudinal cohort study. This study included 100 older adults (55 to 84 years). A total of 33 participants with MCI, 17 participants with AD, and 50 participants of age, sex, and hearing-matched healthy controls were included. RESULTS: Participants with AD demonstrated a delayed latency of the p13 component measured by cervical vestibular-evoked myogenic potentials (cVEMP) compared with healthy controls and participants with MCI. Other measures including n23 latency, presence of intact responses, rectified amplitude, mean rectified voltage (measured by cVEMP) and lateral vestibulo-ocular reflex gain (measured by video Head Impulse Test [vHIT]) did not differ between groups. The Timed Up and Go (TUG), Performance-Oriented Mobility Assessment-Balance subscale (POMA-B), and Functional Gait Assessment (FGA) differed significantly between the three groups. Here, more cognitively impaired groups were associated with worse clinical balance scores. CONCLUSIONS: Vestibular and balance deficits were more prevalent in groups with increasing cognitive decline. Regarding vestibular function testing, p13 latency as measured by cVEMP was delayed in participants with AD. Other cVEMP or vHIT measures did not differ between groups. All three clinical balance assessments (TUG, POMA-B, and FGA) resulted in worse scores along the AD continuum. Future research integrating vestibular parameters that add value (including otolith function testing, balance, and spatial navigation) is recommended to validate the association between vestibular function and cognition while avoiding redundant testing.

The 2022 European postgraduate (residency) programme in neurology in a historical and international perspective.

BACKGROUND AND PURPOSE: Neurology residency programmes, which were first established at the beginning of the 20th century, have become mandatory all over Europe in the last 40-50 years. The first European Training Requirements in Neurology (ETRN) were published in 2005 and first updated in 2016. This paper reports the most recent revisions of the ETRN. METHODS: Members of the EAN board performed an in depth revision of the ETNR 2016-version, which was reviewed by members of the European Board and Section of Neurology of the UEMS, the Education and Scientific Panels, the Resident and Research Fellow Section and the Board of the EAN, as well as the presidents of the 47 European National Societies. RESULTS: The new (2022) ETRN suggest a 5-year training subdivided in three phases: a first phase (2 years) of general neurology training, a second phase (2 years) of training in neurophysiology/neurological subspecialties and a third phase (1 year) to expand clinical training (e.g., in other neurodisciplines) or for research (path for clinical neuroscientist). The necessary theoretical and clinical competences as well as learning objectives in diagnostic tests have been updated, are newly organized in four levels and include 19 neurological subspecialties. Finally, the new ETRN require, in addition to a programme director, a team of clinician-educators who regularly review the resident's progress. The 2022 update of the ETRN reflects emerging requirements for the practice of neurology and contributes to the international standardization of training necessary for the increasing needs of residents and specialists across Europe.

Is vestibular function related to human hippocampal volume?

BACKGROUND: Recent studies implicate the effect of vestibular loss on cognitive decline, including hippocampal volume loss. As hippocampal atrophy is an important biomarker of Alzheimer's disease, exploring vestibular dysfunction as a risk factor for dementia and its role in hippocampal atrophy is of interest. OBJECTIVE: To replicate previous literature on whole-brain and hippocampal volume in semicircular canal dysfunction (bilateral vestibulopathy; BV) and explore the association between otolith function and hippocampal volume. METHODS: Hippocampal and whole-brain MRI volumes were compared in adults aged between 55 and 83 years. Participants with BV (n = 16) were compared to controls individually matched on age, sex, and hearing status (n = 16). Otolith influence on hippocampal volume in preserved semicircular canal function was evaluated (n = 34). RESULTS: Whole-brain and targeted hippocampal approaches using volumetric and surface-based measures yielded no significant differences when comparing BV to controls. Binary support vector machines were unable to classify inner ear health status above chance level. Otolith parameters were not associated with hippocampal volume in preserved semicircular canal function. CONCLUSIONS: No significant differences in whole-brain or hippocampal volume were found when comparing BV participants with healthy controls. Saccular parameters in subjects with preserved semicircular canal function were not associated with hippocampal volume changes.

Evaluation of hearing levels and vestibular function and the impact on cognitive performance in (pre)-symptomatic patients with DFNA9: protocol for a prospective longitudinal study (Rosetta study).

INTRODUCTION: Untreated hearing loss is the largest potentially modifiable risk factor for dementia. Additionally, vestibular dysfunction has been put forward as a potential risk factor for accelerated cognitive decline. Patients with Deafness Autosomal Dominant 9 (DFNA9) present with progressive sensorineural hearing loss and bilateral vestibulopathy and show significantly worse results in cognitive performance compared with a cognitively healthy control group. This highlights the need for adequate treatment to prevent further cognitive decline. This study aims to determine how hearing and vestibular function evolve in (pre-)symptomatic carriers of the p.Pro51Ser mutation in the COCH gene and how this impacts their cognitive performance and health-related quality of life. METHODS AND ANALYSIS: A prospective, longitudinal evaluation of hearing, vestibular function and cognitive performance will be acquired at baseline, 1-year and 2-year follow-up. A total of 40 patients with DFNA9 will be included in the study. The study will be a single-centre study performed at the ORL department at the Antwerp University Hospital (UZA), Belgium. The control group will encompass cognitively healthy subjects, already recruited through the GECkO study. The primary outcome measure will be the Repeatable Battery for the Assessment of Neuropsychological Status adjusted for the Hearing-Impaired total score. Secondary outcome measures include Cortical Auditory-Evoked Potentials, vestibular assessments and health-related quality of life questionnaires. The expected outcomes will aid in the development of gene therapy by providing insight in the optimal time window for the application of gene therapy for the inner ear. ETHICS AND DISSEMINATION: The ethical committee of UZA approved the study protocol on 19 December 2022 (protocol number B3002022000170). All participants have to give written initial informed consent in accordance with the Declaration of Helsinki. Results will be disseminated to the public through conference presentations, lectures and peer-reviewed scientific publications.

Mutated Toll-like receptor 9 increases Alzheimer's disease risk by compromising innate immunity protection.

The development of Alzheimer's disease (AD) involves central and peripheral immune deregulation. Gene identification and studies of AD genetic variants of peripheral immune components may aid understanding of peripheral-central immune crosstalk and facilitate new opportunities for therapeutic intervention. In this study, we have identified in a Flanders-Belgian family a novel variant p.E317D in the Toll-like receptor 9 gene (TLR9), co-segregating with EOAD in an autosomal dominant manner. In human, TLR9 is an essential innate and adaptive immune component predominantly expressed in peripheral immune cells. The p.E317D variant caused 50% reduction in TLR9 activation in the NF-κB luciferase assay suggesting that p.E317D is a loss-of-function mutation. Cytokine profiling of human PBMCs upon TLR9 activation revealed a predominantly anti-inflammatory response in contrast to the inflammatory responses from TLR7/8 activation. The cytokines released upon TLR9 activation suppressed inflammation and promoted phagocytosis of Aß42 oligomers in human iPSC-derived microglia. Transcriptome analysis identified upregulation of AXL, RUBICON and associated signaling pathways, which may underline the effects of TLR9 signaling-induced cytokines in regulating the inflammatory status and phagocytic property of microglia. Our data suggest a protective role of TLR9 signaling in AD pathogenesis, and we propose that TLR9 loss-of-function may disrupt a peripheral-central immune crosstalk that promotes dampening of inflammation and clearance of toxic protein species, leading to the build-up of neuroinflammation and pathogenic protein aggregates in AD development.

Evaluation of Cognitive Functioning Before and After Cochlear Implantation in Adults Aged 55 Years and Older at Risk for Mild Cognitive Impairment.

Importance: Given the rapidly rising dementia incidence, management of modifiable risk factors, such as hearing loss, is vital. Multiple studies have demonstrated an improvement of cognitive functioning in older adults with severe hearing loss after cochlear implantation; however, few of these studies, to the authors' knowledge, specifically analyzed participants achieving poor cognitive results preoperatively. Objective: To evaluate the cognitive functioning of older adults with severe hearing loss at risk for mild cognitive impairment (MCI) before and after cochlear implantation. Design, Setting, and Participants: This prospective, longitudinal cohort study performed at a single center reports data obtained over a 6-year period (April 2015 to September 2021) of an ongoing prospective, longitudinal cohort study on cochlear implant outcomes in older adults. A consecutive sample of older adults with severe hearing loss eligible for cochlear implantation was included. All participants obtained a Repeatable Battery for the Assessment of Neuropsychological Status for hearing-impaired patients (RBANS-H) total score indicative of MCI preoperatively. Participants were assessed before cochlear implant activation and 12 months after cochlear implant activation. Intervention: The intervention consisted of cochlear implantation. Main Outcome and Measure: The primary outcome measure was cognition, measured by the RBANS-H. Results: A total of 21 older adult cochlear implant candidates were included in the analysis (mean [SD] age, 72 [9] years; 13 [62%] men). Cochlear implantation was associated with an improvement of overall cognitive functioning 12 months after activation (median [IQR] percentile, 5 [2-8] vs 12 [7-19]; difference, 7 [95% CI, 2-12]). Eight participants (38%) surpassed the MCI cutoff (16th percentile) postoperatively, while the overall median cognitive score remained under this cutoff. In addition, participants' speech recognition in noise improved, with a lower score indicating improvement (mean [SD] score, +17.16 [5.45] vs +5.67 [6.3]; difference, -11.49 [95% CI, -14.26 to -8.72]), after cochlear implant activation. Improvement of speech recognition in noise was positively associated with improvement in cognitive functioning (rs, -0.48 [95% CI, -0.69 to -0.19]). Years of education, sex, RBANS-H version, and symptoms of depression and anxiety were not related to the evolution in RBANS-H scores. Conclusions and Relevance: In this prospective, longitudinal cohort study, cognitive functioning and speech perception in noise showed a clinically meaningful improvement 12 months after cochlear implant activation in older adults with severe hearing loss at risk for MCI, suggesting that cochlear implantation is not contraindicated in cochlear implant candidates with cognitive decline and should be considered after multidisciplinary evaluation.

Accelerated Cognitive Decline Associated With Hearing Loss and Bilateral Vestibulopathy: Insights From a Prospective Cross-Sectional Study Using the Repeatable Battery for the Assessment of Neuropsychological Status Adjusted for the Hearing Impaired in the DFNA9 Population.

BACKGROUND: DeaFNess Autosomal dominant 9 (DFNA9) is a hereditary disorder known to affect both hearing and vestibular function in its carriers. Its phenotype is characterized by progressive sensorineural hearing loss (SNHL) and vestibular dysfunction evolving towards bilateral vestibulopathy (BV) by the 3rd to 5th life decade. Recent studies have identified the impact of hearing loss and vestibular dysfunction on cognitive functioning. OBJECTIVE: The main objective of this study was to investigate how the cognitive functioning of carriers of the p.Pro51Ser variant in the COCH gene is affected by the disease and compare these results with a matched healthy control group. STUDY DESIGN: Forty-six carriers of the pathogenic p.Pro51Ser variant in the COCH gene were included in this study, of which 38 met the Bárány Society criteria and were thus diagnosed with BV. All subjects were between the age of 22 and 72 years old. Each control was individually matched based on age, gender, and education level. A cognitive, vestibular, and hearing assessment was performed in all subjects. All participants completed the Repeatable Battery for the Assessment of Neuropsychological Status, adjusted for the Hearing Impaired (RBANS-H), a cognitive test battery that includes subtests probing Immediate and Delayed Memory, Visuospatial/Constructional, Language, and Attention. RESULTS: Overall, the DFNA9 patients demonstrated significantly lower scores on the Immediate Memory subscale and lower Total Scale scores than their healthy matched controls. The total sample was divided into two groups: age <55 years old and age ≥55 years old. The DFNA9 group aged ≥55 years old obtained significantly lower scores on the Attention subscale and lower Total Scale scores than their matched controls. Cognition of DFNA9 patients aged <55 years old no longer differed significantly from their matched controls. CONCLUSION: This cross-sectional study found that DFNA9 patients demonstrated cognitive deficits in comparison with their healthy matched controls. The DFNA9 group aged ≥ 55 years old obtained significantly lower scores on the Total Scale and Attention subscale. This finding; however, was not observed for the age group younger than 55 years old. Further research is needed on the individual trajectory of SNHL and vestibular function, and how hearing rehabilitation affects cognitive functioning.

The involvement of palliative care with neurology - a comparison of UK, Switzerland and Italy.

OBJECTIVES: To ascertain the involvement of palliative care with neurology services in the care of people with amyotrophic lateral sclerosis (ALS) in the United Kingdom, Italy and Switzerland, in particular the collaboration with and referral from neurology, the involvement in multidisciplinary team care and in the respiratory support of ALS patients. METHODS: In 2019, two online surveys were undertaken of palliative care specialists, using specialist groups of the European Academy of Neurology, European Association of Palliative Care and the Association of Palliative Medicine for Great Britain and Ireland. RESULTS: The respondents were specialist palliative care professionals, predominantly senior doctors, involved in the care of people with ALS. As the numbers of respondents from many countries were in single figures the analysis was restricted to the United Kingdom, Italy and Switzerland. The time of involvement varied, with early involvement commonest in the UK. Barriers to referral included neurologists not referring and financial issues, particularly in Switzerland. The reluctance of patients and families to see palliative care services was reported as less than 20% in all countries. Respondents were often involved in the care of people receiving noninvasive ventilation (NIV), in all countries. and with tracheostomy ventilation (TV), particularly in Italy. CONCLUSIONS: Palliative care services are often involved in the care of people with ALS, but the extent and timing of involvement varies. The use of clinical guidelines and education on palliative care for neurology services may encourage collaboration, for the benefit of people with ALS and their families.

Effectiveness and safety of safinamide in routine clinical practice in a Belgian Parkinson's disease population: an open-label, levodopa add-on study.

BACKGROUND: Safinamide is a recent multimodal antiparkinsonian drug that inhibits monoamine oxidase B and modulates the glutamatergic system with positive effects on motor and nonmotor symptoms of Parkinson's disease (PD). This post-hoc analysis of the European SYNAPSES study provides first-time data on the use of safinamide in routine clinical practice in Belgium. OBJECTIVE: To describe the efficacy and safety of safinamide in Belgian PD patients in real-life conditions. METHODS: Post-hoc analysis of the Belgian cohort from the European SYNAPSES trial, which was an observational, multicenter, retrospective-prospective cohort study. Patients were followed up to 12 months. Analyses were performed in the overall population and according to different criteria such as the age limit (> 75 years), presence or absence of relevant comorbidities, presence or absence of psychiatric conditions such as depression and anxiety, patients on levodopa monotherapy or levodopa in combination with other treatments, patients on rasagiline before inclusion or not. RESULTS: Of the 172 patients included, 29.2% were > 75 years, 58.9% had relevant comorbidities and 32.7% had psychiatric conditions. Almost all the patients reported motor (98.8%) or non-motor (86.3%) symptoms. During the study, 36.3% of patients reported drug-related reactions. The adverse drug reactions were those already described in the patients' information leaflet. The majority were mild or moderate and completely resolved and no differences were detected between the subgroups of patients. Almost 35% of the patients demonstrated a clinically significant improvement in the UPDRS and 50% of the patients with wearing-off at baseline, did not report wearing-off anymore after one year of treatment. Patients under levodopa monotherapy compared to patients receiving levodopa combined with other antiparkinsonian treatments benefit more from safinamide treatment. Patients switched from rasagiline to safinamide seemed also to benefit more from safinamide treatment. CONCLUSION: The study confirms the excellent safety and efficacy profile of safinamide, particularly in more vulnerable groups of patients such as the elderly and patients with significant comorbidities or psychiatric conditions such as depression or anxiety.

Polysomnographic Predictors of Sleep, Motor, and Cognitive Dysfunction Progression in Parkinson's Disease.

PURPOSE OF REVIEW: Sleep disturbances are an important nonmotor feature of Parkinson's disease (PD) that can cause polysomnographic (PSG) alterations. These alterations are already present in early PD and may be associated with a specific disease course. This systematic review describes the role of PSG variables as predictors of sleep dysfunction, motor and cognitive dysfunction progression in PD. RECENT FINDINGS: Nineteen longitudinal cohort studies were included. Their main findings were that (1) REM sleep behavioral events, REM sleep without atonia (RSWA), and electroencephalography (EEG) changes (mainly microsleep instability) are predictors of the development of REM sleep behavior disorder (RBD); (2) RBD, RSWA, and lower slow-wave sleep energy predict motor progression; (3) RBD, EEG slowing, and sleep spindles changes are predictors of cognitive deterioration; and (4) OSA is associated with severe motor and cognitive symptoms at baseline, with inconsistent findings on the effect of continuous positive airway pressure (CPAP) therapy for these symptoms. The results of our systematic review support a role of the video-PSG in disease progression prediction in PD and its usefulness as a biomarker. However, future studies are needed to investigate whether treatment of these PSG abnormalities and sleep disturbances may have a neuroprotective effect on disease progression.

Apathy in Parkinson's Disease: Defining the Park Apathy Subtype.

Apathy is a neurobehavioural symptom affecting Parkinson's disease patients of all disease stages. Apathy seems to be associated with a specific underlying non-motor disease subtype and reflects dysfunction of separate neural networks with distinct neurotransmitter systems. Due to the complicated neuropsychiatric aetiology of apathy, clinical assessment of this invalidating non-motor symptom remains challenging. We aim to summarize the current findings on apathy in Parkinson's disease and highlight knowledge gaps. We will discuss the prevalence rates across the different disease stages and suggest screening tools for clinically relevant apathetic symptoms. We will approach the fundamental knowledge on the neural networks implicated in apathy in a practical manner and formulate recommendations on patient-tailored treatment. We will discuss the Park apathy phenotype in detail, shedding light on different clinical manifestations and implications for prognosis. With this review, we strive to distil the vast available theoretical knowledge into a clinical and patient-oriented perspective.

Associations of Bilateral Vestibulopathy With Cognition in Older Adults Matched With Healthy Controls for Hearing Status.

Importance: Recent literature suggests there may be a significant effect of the vestibular system on cognition and visuospatial processing. Given the increasing prevalence of dementia and individuals at risk for it, exploring possible modifiable risk factors, including vestibular dysfunction, is vital. Objectives: To explore the association of bilateral vestibulopathy (BV) with cognitive function in older adults, taking hearing status into account, and to explore multiple vestibular characteristics and their potential associations with cognition in patients with BV. Design, Setting, and Participants: This cross-sectional study assessed older adults (age 55-84 years) with diagnosed BV from a single center using baseline measurements from the Gehoor, Evenwicht en Cognitie (GECKO) study, an ongoing prospective longitudinal cohort study. Each participant was individually matched with a healthy control based on age, sex, and hearing performance. Data were analyzed in January 2022. Main Outcomes and Measures: The primary outcome measure was cognition, measured by the Repeatable Battery for the Assessment of Neuropsychological Status for Hearing-Impaired Individuals (RBANS-H). Results: A total of 68 patients were assessed, including 34 patients with BV (mean [SD] age, 63.3 [6.0] years; 18 [53%] men) matched with 34 control individuals without BV. Overall, participants with BV had a clinically meaningful lower score on the RBANS-H total scale compared with those without BV (mean [SD] score, 98.62 [12.70] vs 105.91 [11.03]). This decline was most pronounced in the subdomains of immediate memory (mean [SD] score, 107.74 [10.66] vs 112.26 [10.66]), visuospatial cognition (mean [SD] score, 90.06 [13.34] vs 100.47 [13.91]), and attention (mean [SD] score, 94.79 [16.39] vs 102.06 [12.97]). There were no differences in language or delayed memory subdomains. Within the BV population, 1 vestibular parameter (the Performance-Oriented Mobility Assessment, in particular the balance subscale) was associated with lower cognitive scores (r32 = 0.51; 95% CI, 0.20 to 0.72; η2 = 0.26). Other vestibular parameters, including measurements of the peripheral vestibular end organ and questionnaires, showed no association. Conclusions and Relevance: These findings suggest there was an association between vestibular loss and cognitive impairment. Further research on the causal mechanisms underlying this association and the possible impact of vestibular rehabilitation on cognition is needed.

Concordance of cerebrospinal fluid real-time quaking-induced conversion across the European Creutzfeldt-Jakob Disease Surveillance Network.

BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) has a high degree of sensitivity and specificity for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) and this has led to its being included in revised European CJD Surveillance Network diagnostic criteria for sCJD. As CSF RT-QuIC becomes more widely established, it is crucial that the analytical performance of individual laboratories is consistent. The aim of this ring-trial was to ascertain the degree of concordance between European countries undertaking CSF RT-QuIC. METHODS: Ten identical CSF samples, seven from probable or neuropathologically confirmed sCJD and three from non-CJD cases, were sent to 13 laboratories from 11 countries for RT-QuIC analysis. A range of instrumentation and different recombinant prion protein substrates were used. Each laboratory analysed the CSF samples blinded to the diagnosis and reported the results as positive or negative. RESULTS: All 13 laboratories correctly identified five of the seven sCJD cases and the remaining two sCJD cases were identified by 92% of laboratories. Of the two sCJD cases that were not identified by all laboratories, one had a disease duration >26 months with a negative 14-3-3, whilst the remaining case had a 4-month disease duration and a positive 14-3-3. A single false positive CSF RT-QuIC result was observed in this study. CONCLUSIONS: This study shows that CSF RT-QuIC demonstrates an excellent concordance between centres, even when using a variety of instrumentation, recombinant prion protein substrates and CSF volumes. The adoption of CSF RT-QuIC by all CJD surveillance centres is recommended.

Impaired bed mobility in prediagnostic and de novo Parkinson's disease.

BACKGROUND: Wearable technology research suggests that nocturnal movements are disturbed in early Parkinson's disease (PD). In this study, we investigate if patients also already experience impaired bed mobility before PD diagnosis. Furthermore, we explore its association with motor and nonmotor features and its value for phenoconversion and disease progression prediction. METHODS: PPMI data were downloaded for de novo PD subjects, subjects at-risk for developing a synucleinopathy (with isolated REM sleep behavior disorder, hyposmia or a pathogenic genetic variant) and controls. Impaired bed mobility was assessed with the MDS-UPDRS part 2 item 9. A frequency analysis was performed. Multivariable logistic regression analyses were used to investigate the association with other PD variables. Cox proportional-hazards models were used to test if difficulties with turning in bed could predict phenoconversion. Linear mixed models were used to evaluate if difficulties with turning in bed could predict disease progression. RESULTS: Of the at-risk subjects, 9.2-12.5% experienced difficulties with turning in bed vs. 25.0% of de novo PD subjects and 2.5% of controls. Impaired turning ability was associated with MDS-UPDRS motorscore (axial signs in the at-risk group, bradykinesia in the de novo PD group) and SCOPA-AUT score (gastrointestinal symptoms). In addition, difficulties with turning in bed were a significant predictor for phenoconversion in the at-risk group and for development of motor complications in the de novo PD group. CONCLUSION: Our findings suggest that difficulties with turning in bed can be helpful as clinical symptom for a prodromal PD screening and for motor complication prediction in early PD.

Cortical Auditory Evoked Potentials in Cognitive Impairment and Their Relevance to Hearing Loss: A Systematic Review Highlighting the Evidence Gap.

Background: Alzheimer's disease (AD) is the most prevalent cause of dementia which affects a growing number of people worldwide. Early identification of people at risk to develop AD should be prioritized. Hearing loss is considered an independent potentially modifiable risk factor for accelerated cognitive decline and dementia in older adults. The main outcome of interest of this review is the alteration of Cortical Auditory Evoked Potential (CAEP) morphology in an AD or mild cognitive impairment (MCI) population with and without hearing loss. Methods: Two investigators independently and systematically searched publications regarding auditory processing on a cortical level in people with cognitive impairment (MCI or AD) with and without hearing loss. Only articles which mentioned at least one auditory elicited event-related potential (ERP) component and that were written in English or Dutch were included. Animal studies were excluded. No restrictions were imposed regarding publication date. The reference list of potential sources were screened for additional articles. Results: This systematic review found no eligible articles that met all inclusion criteria. Therefore, no results were included, resulting in an empty systematic review. Conclusion: In general, dysfunction - being either from cognitive or auditory origin - reduces CAEP amplitudes and prolongs latencies. Therefore, CAEPs may be a prognostic indicator in the early stages of cognitive decline. However, it remains unclear which CAEP component alteration is due to cognitive impairment, and which is due to hearing loss (or even both). In addition, vestibular dysfunction - associated with hearing loss, cognitive impairment and AD - may also alter CAEP responses. Further CAEP studies are warranted, integrating cognitive, hearing, and vestibular evaluations.

Neuromyelitis Optica Spectrum Disorders in Africa: A Systematic Review.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica (NMO) is a CNS inflammatory disease that predominantly affects the optic nerves and the spinal cord. It is more frequent in Asian and African populations than in European ones. Data on epidemiology, clinical presentation, additional investigations, and treatment in the African continent are scarce. We aim to (1) collect and analyze published data on neuromyelitis optica spectrum disorder (NMOSD), (2) indicate challenges in the diagnosis and management, and (3) discuss opportunities for future research, education, and policy making, specifically on the African continent. METHODS: A systematic review was performed in January 2021 with the search terms "Neuromyelitis optica and Africa," "Devic Disease and Africa," and "NMOSD and Africa." We included all study types except case reports, correspondence, or conference abstracts on NMO or NMOSD. Extracted data included study design, country, study period, demographic and clinical characteristics, results of paraclinical investigations, and outcome. Data analysis was performed with descriptive statistics. RESULTS: We retrieved a total of 79 records, of which 19 were included. Ten of 54 African countries reported a total of 410 cases. Almost half of them were from North African countries. The mean age at diagnosis was 33 years (range 7-88 years), and 75% were female. Transverse myelitis followed by optic neuritis were the most frequent symptoms at the time of presentation. One hundred nineteen patients experienced at least 1 previous relapse, and 106 had a relapsing course after diagnosis. Relapses were treated with IV methylprednisolone. Azathioprine and steroids were used most often as maintenance treatments. Outcomes were rarely described. DISCUSSION: The majority of studies on NMOSD from the African continent are retrospective, and most countries do not report any data. Our systemic review shows that data derived from patients living in Africa correspond well to what has been previously published in meta-analyses on patients of African ancestry with NMOSD who live outside of Africa, except for a younger age at onset and a lower proportion of females. We advocate for systematic data collection to adequately capture and monitor the burden of NMOSD, for expansion of research efforts and facilities to perform fundamental and clinical research, and for improved access to health care including diagnostics, treatments, and rehabilitation services for people affected by NMOSD in the African continent.