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IntroductionEstimating differences in neural health across different sites within the individual cochlea potentially enables clinical applications for subjects with a cochlear implant. The electrically evoked compound action potential (ECAP) is a measure of neural excitability that possibly provides an indication of a neural condition. There are many factors, however, that affect this measure and increase the uncertainty of its interpretation. To better characterize the ECAP response, its relationship with electrode positioning, impedances, and behavioral stimulation levels was explored.MethodsA total of 14 adult subjects implanted with an Advanced Bionics cochlear electrode array were prospectively followed up from surgery to 6 months postoperative. Insertion depth, distance to the modiolus, and distance to the medial wall were assessed for each electrode by postoperative CT analysis. ECAPs were measured intraoperatively and at three visits postoperatively on all 16 electrodes using the NRI feature of clinical programming software and characterized using multiple parameters. Impedances and behavioral stimulation levels were measured at every fitting session.ResultsPatterns in ECAPs and impedances were consistent over time, but high variability existed among subjects and between different positions in the cochlea. Electrodes located closer to the apex of the cochlea and closer to the modiolus generally showed higher neural excitation and higher impedances. Maximum loudness comfort levels were correlated strongly with the level of current needed to elicit a response of 100 μV ECAP.ConclusionMultiple factors contribute to the ECAP response in subjects with a cochlear implant. Further research might address whether the ECAP parameters used in this study will benefit clinical electrode fitting or the assessment of auditory neuron integrity.

Biomarker discovery, development, and validation are reliant on large-scale analyses of high-quality samples and data. Currently, significant quantities of data and samples have been generated by European studies on Alzheimer's disease (AD) and other neurodegenerative diseases (NDD), representing a valuable resource for developing biomarkers to support early detection of disease, treatment monitoring, and patient stratification. However, discovery of, access to, and sharing of data and samples from AD and NDD research are hindered both by silos that limit collaboration, and by the array of complex requirements for secure, legal, and ethical sharing. In this Perspective article, we examine key challenges currently hampering large-scale biomarker research, and outline how the European Platform for Neurodegenerative Diseases (EPND) plans to address them. The first such challenge is a fragmented landscape filled with technical barriers that make it difficult to discover and access high-quality samples and data in one location. A second challenge is related to the complex array of legal and ethical requirements that must be navigated by researchers when sharing data and samples, to ensure compliance with data protection regulations and research ethics. Another challenge is the lack of broad-scale collaboration and opportunities to facilitate partnerships between data and sample contributors and researchers, in addition to a lack of regulatory engagement early in the research process to enable validation of potential biomarkers. A further challenge facing projects is the need to remain sustainable beyond initial funding periods, ensuring data and samples are shared and reused, thereby driving further research and innovation. In addressing these challenges, EPND will enable an environment of faster and more disruptive research on diagnostics and disease-modifying therapies for Alzheimer's disease and other neurodegenerative diseases.

BackgroundPhenytoin is widely used as primary seizure prophylaxis in hematopoietic stem cell transplantation in patients undergoing myeloablative conditioning with busulfan. Because of the negative side effects of phenytoin, we abandoned phenytoin use in these patients. To assess the effect of this change, we performed a retrospective cohort study on all patients receiving busulfan.MethodsWe included 139 patients who underwent conditioning with busulfan for hematopoietic stem cell therapy. We registered the use of phenytoin, as well as the occurrence of seizures, until 7 days after busulfan administration. We compared seizure incidence between patients who received phenytoin and those who did not.ResultsOf the 43 patients who received phenytoin prophylaxis, four patients (9.3%) had a seizure during the conditioning regimen, of which two patients had cerebral non-Hodgkin lymphoma. Furthermore, all these 4 patients had very high levels of phenytoin (intoxication). Of the 96 patients that did not receive phenytoin prophylaxis, three patients (3.1%) had a seizure, and one of these patients had an undefined cerebral lesion. Phenytoin did not relate to seizure prevention in a logistic regression analysis.ConclusionWe conclude that phenytoin prophylaxis in patients treated with busulfan is obsolete and possibly harmful, as phenytoin intoxication can occur. We recommend discontinuing the use of phenytoin as primary seizure prophylaxis in these patients.

BackgroundTo date, the burden and severity of the full spectrum of bilateral vestibulopathy (BVP) symptoms has not yet been measured in a standardized manner. Since therapeutic interventions aiming to improve BVP symptoms are emerging, the need for a new standardized assessment tool that encompasses the specific aspects of BVP arises. Therefore, the aim of this study was to develop a multi-item Patient Reported Outcome Measure (PROM) that captures the clinically important symptoms of BVP and assesses its impact on daily life.MethodsThe development of the Bilateral Vestibulopathy Questionnaire (BVQ) consisted of two phases: (I) initial item generation and (II) face and content validity testing. Items were derived from a literature review and individual semi-structured interviews focusing on the full spectrum of reported BVP symptoms (I). Subsequently (IIa), individual patient interviews were conducted using “thinking aloud” and concurrent verbal probing techniques to assess the comprehensibility of the instructions, questions and response options, and the relevance, missing domains, or missing items. Interviews continued until saturation of input was reached. Finally, international experts with experience in the field of the physical, emotional, and cognitive symptoms of BVP participated in an online focus group to assess the relevance and comprehensiveness of the BVQ (IIb).ResultsThe BVQ consisted of two sections. The first section included 50 items scored on a six-point Likert scale arranged into seven constructs (i.e., imbalance, oscillopsia, other physical symptoms, cognitive symptoms, emotional symptoms, limitations and behavioral changes and social life). The second section consisted of four items, scored on a visual analog scale from 0 to 100, to inquire about limitations in daily life, perceived health and expectations regarding future recovery. Interviews with BVP patients [n= 8, 50% female, mean age 56 years (range 24–88 years)] and the expert meeting confirmed face and content validity of the developed BVQ.ConclusionThe BVQ, which was developed to assess the spectrum of BVP symptoms and its impact on daily life, proved to have good face and content validity. It can be used to characterize current self-reported symptoms and disability and to evaluate symptom burden before and after therapeutic interventions in future research and clinical practice.

Background: It is hypothesized that, for patients with hearing loss, surgically placing an implant/abutment combination whilst leaving the subcutaneous tissues intact will improve cosmetic and clinical results, increase quality of life (QoL) for the patient, and reduce medical costs. Here, incremental costs and consequences associated with soft tissue preservation surgery with a hydroxyapatite (HA)-coated abutment (test) were compared with the conventional approach, soft tissue reduction surgery with an all-titanium abutment (control). Methods: A cost-consequence analysis was performed based on data gathered over a period of 3 years in an open randomized (1:1) controlled trial (RCT) running in four European countries (The Netherlands, Spain, France, and Sweden). Subjects with conductive or mixed hearing loss or single-sided sensorineural deafness were included. Results: During the first year, in the Netherlands (NL), France (FR), and Spain (ES) a net cost saving was achieved in favor of the test intervention because of a lower cost associated with surgery time and adverse event treatments [NL €86 (CI -50.33; 219.20), FR €134 (CI -3.63; 261.30), ES €178 (CI 34.12; 97.48)]. In Sweden (SE), the HA-coated abutment was more expensive than the conventional abutment, which neutralized the cost savings and led to a negative cost (SE €-29 CI -160.27; 97.48) of the new treatment modality. After 3 years, the mean cost saving reduced to €17 (CI -191.80; 213.30) in the Netherlands, in Spain to €84.50 (CI -117.90; 289.50), and in France to €80 (CI -99.40; 248.50). The mean additional cost in Sweden increased to €-116 (CI -326.90; 68.10). The consequences in terms of the subjective audiological benefit and Health-related quality of life (HRQoL) were comparable between treatments. A trend was identified for favorable results in the test group for some consequences and statistical significance is achieved for the cosmetic outcome as assessed by the clinician. Conclusions: From this multinational cost-consequence analysis it can be discerned that health care systems can achieve a cost saving during the first year that regresses after 3 years, by implementing soft tissue preservation surgery with a HA-coated abutment in comparison to the conventional treatment. The cosmetic results are better. (sponsored by Cochlear Bone Anchored Solutions AB; Clinical and health economic evaluation with a new Baha® abutment design combined with a minimally invasive surgical technique, ClinicalTrials.gov NCT01796236).

ObjectiveThis study aimed to investigate (1) the patterns of vestibular impairment in bilateral vestibulopathy (BVP) and subsequently, the implications regarding patient eligibility for vestibular implantation, and (2) whether this pattern and severity of vestibular impairment is etiology dependent.MethodsA total of one hundred and seventy-three subjects from three tertiary referral centers in Europe were diagnosed with BVP according to the Bárány Society diagnostic criteria. The subjects underwent vestibular testing such as the caloric test, torsion swing test, video Head Impulse Test (vHIT) in horizontal and vertical planes, and cervical and/or ocular vestibular evoked myogenic potentials (c- and oVEMPs). The etiologies were split into idiopathic, genetic, ototoxicity, infectious, Menière's Disease, (head)trauma, auto-immune, neurodegenerative, congenital, and mixed etiology.ResultsThe caloric test and horizontal vHIT more often indicated horizontal semicircular canal impairment than the torsion swing test. The vHIT results showed significantly higher gains for both anterior canals compared with the horizontal and posterior canals (p < 0.001). The rates of bilaterally absent oVEMP responses were higher compared to the bilaterally absent cVEMP responses (p = 0.010). A total of fifty-four percent of the patients diagnosed with BVP without missing data met all three Bárány Society diagnostic test criteria, whereas 76% of the patients were eligible for implantation according to the vestibular implantation criteria. Regarding etiology, only horizontal vHIT results were significantly lower for trauma, neurodegenerative, and genetic disorders, whereas the horizontal vHIT results were significantly higher for Menière's Disease, infectious and idiopathic BVP. The exploration with hierarchical cluster analysis showed no significant association between etiology and patterns of vestibular impairment.ConclusionThis study showed that caloric testing and vHIT seem to be more sensitive for measuring vestibular impairment, whereas the torsion swing test is more suited for measuring residual vestibular function. In addition, no striking patterns of vestibular impairment in relation to etiology were found. Nevertheless, it was demonstrated that although the implantation criteria are stricter compared with the Bárány Society diagnostic criteria, still, 76% of patients with BVP were eligible for implantation based on the vestibular test criteria. It is advised to carefully examine every patient for their overall pattern of vestibular impairment in order to make well-informed and personalized therapeutic decisions.

Objective: To assess the prevalence of each symptom listed in the acronym DISCOHAT (worsening of symptoms in Darkness and/or uneven ground, Imbalance, Supermarket effect, Cognitive complaints, Oscillopsia, Head movements worsen symptoms, Autonomic complaints, and Tiredness) in patients with bilateral vestibulopathy (BVP), compared to patients with unilateral vestibulopathy (UVP).Methods: A descriptive case-control study was performed on BVP and UVP patients who were evaluated for their vestibular symptoms by two of the authors (RvdB, MCG) at a tertiary referral center, between 2017 and 2020. During history taking, the presence of each DISCOHAT symptom was checked and included in the electronic health record. Presence of a symptom was categorized into: “present,” “not present,” and “missing.”Results: Sixty-six BVP patients and 144 UVP patients were included in this study. Prevalence of single DISCOHAT symptoms varied from 52 to 92% in BVP patients and 18–75% in UVP patients. Patients with BVP reported “worsening of symptoms in darkness,” “imbalance,” “oscillopsia,” and “worsening of symptoms with fast head movements” significantly more than UVP patients (p ≤ 0.004).Conclusion: The DISCOHAT acronym is able to capture a wide spectrum of symptoms related to vestibulopathy, while it is easy and quickly to use in clinic. Application of this acronym might facilitate a more thorough and uniform assessment of bilateral vestibulopathy, within and between vestibular clinics worldwide.

Objective: This study aimed to identify differences in vestibulo-ocular reflex gain (VOR gain) and saccadic response in the suppression head impulse paradigm (SHIMP) between predictable and less predictable head movements, in a group of healthy subjects. It was hypothesized that higher prediction could lead to a lower VOR gain, a shorter saccadic latency, and higher grouping of saccades.Methods: Sixty-two healthy subjects were tested using the video head impulse test and SHIMPs in four conditions: active and passive head movements for both inward and outward directions. VOR gain, latency of the first saccade, and the level of saccade grouping (PR-score) were compared among conditions. Inward and active head movements were considered to be more predictable than outward and passive head movements.Results: After validation, results of 57 tested subjects were analyzed. Mean VOR gain was significantly lower for inward passive compared with outward passive head impulses (p < 0.001), and it was higher for active compared with passive head impulses (both inward and outward) (p ≤ 0.024). Mean latency of the first saccade was significantly shorter for inward active compared with inward passive (p ≤ 0.001) and for inward passive compared with outward passive head impulses (p = 0.012). Mean PR-score was only significantly higher in active outward than in active inward head impulses (p = 0.004).Conclusion: For SHIMP, a higher predictability in head movements lowered gain only in passive impulses and shortened latencies of compensatory saccades overall. For active impulses, gain calculation was affected by short-latency compensatory saccades, hindering reliable comparison with gains of passive impulses. Predictability did not substantially influence grouping of compensatory saccades.

Cerebral perfusion may be altered in sepsis patients. However, there are conflicting findings on cerebral autoregulation (CA) in healthy participants undergoing the experimental endotoxemia protocol, a proxy for systemic inflammation in sepsis. In the current study, a newly developed near-infrared spectroscopy (NIRS)-based CA index is investigated in an endotoxemia study population, together with an index of focal cerebral oxygenation.Methods: Continuous-wave NIRS data were obtained from 11 healthy participants receiving a continuous infusion of bacterial endotoxin for 3 h (ClinicalTrials.gov NCT02922673) under extensive physiological monitoring. Oxygenated–deoxygenated hemoglobin phase differences in the (very)low frequency (VLF/LF) bands and the Tissue Saturation Index (TSI) were calculated at baseline, during systemic inflammation, and at the end of the experiment 7 h after the initiation of endotoxin administration.Results: The median (inter-quartile range) LF phase difference was 16.2° (3.0–52.6°) at baseline and decreased to 3.9° (2.0–8.8°) at systemic inflammation (p = 0.03). The LF phase difference increased from systemic inflammation to 27.6° (12.7–67.5°) at the end of the experiment (p = 0.005). No significant changes in VLF phase difference were observed. The TSI (mean ± SD) increased from 63.7 ± 3.4% at baseline to 66.5 ± 2.8% during systemic inflammation (p = 0.03) and remained higher at the end of the experiment (67.1 ± 4.2%, p = 0.04). Further analysis did not reveal a major influence of changes in several covariates such as blood pressure, heart rate, PaCO2, and temperature, although some degree of interaction could not be excluded.Discussion: A reversible decrease in NIRS-derived cerebral autoregulation phase difference was seen after endotoxin infusion, with a small, sustained increase in TSI. These findings suggest that endotoxin administration in healthy participants reversibly impairs CA, accompanied by sustained microvascular vasodilation.

Patients with bilateral vestibulopathy (BVP) present with unsteadiness during standing and walking, limiting their activities of daily life and, more importantly, resulting in an increased risk of falling. In BVP patients, falls are considered as one of the major complications, with patients having a 31-fold increased risk of falling compared to healthy subjects. Thus, highlighting objective measures that can easily and accurately assess the risk of falling in BVP patients is an important step in reducing the incidence of falls and the accompanying burdens. Therefore, this study investigated the interrelations between demographic characteristics, vestibular function, questionnaires on self-perceived handicap and balance confidence, clinical balance measures, gait variables, and fall status in 27 BVP patients. Based on the history of falls in the preceding 12 months, the patients were subdivided in a “faller” or “non-faller” group. Results on the different outcome measures were compared between the “faller” and “non-faller” subgroups using Pearson's chi-square test in the case of categorical data; for continuous data, Mann–WhitneyUtest was used. Performances on the clinical balance measures were comparable between fallers and non-fallers, indicating that, independent from fall status, the BVP patients present with an increased risk of falling. However, fallers tended to report a worse self-perceived handicap and confidence during performing activities of daily life. Spatiotemporal parameters of gait did not differ between fallers and non-fallers during walking at slow, preferred, or fast walking speed. These results may thus imply that, when aiming to distinguish fallers from non-fallers, the BVP patients' beliefs concerning their capabilities may be more important than the moderately or severely affected physical performance within a clinical setting. Outcome measures addressing the self-efficacy and fear of falling in BVP patients should therefore be incorporated in future research to investigate whether these are indeed able to distinguish fallers form non-fallers. Additionally, information regarding physical activity could provide valuable insights on the contextual information influencing behavior and falls in BVP.

Introduction: Superior canal dehiscence syndrome (SCDS) is a condition characterized by a defect in the bone overlying the superior semicircular canal, creating a third mobile window into the inner ear. Patients can experience disabling symptoms and opt for surgical management. Limited data are available on the impact of SCDS on health-related quality of life (HRQoL) and disease-specific HRQoL more specifically. Objective: To perform a prospective analysis on generic HRQoL in SCDS patients compared to healthy age-matched controls. Methods: A prospective study was performed on patients diagnosed with SCDS and who did not undergo reconstructive surgery yet. Patients were recruited between November 2017 and January 2020 and asked to complete the Health Utility Index (HUI) Mark 2 (HUI2)/Mark 3 (HUI3) questionnaire. For the control group, age-matched participants without otovestibular pathology or other chronic pathology were recruited. The multi-attribute utility function (MAUF) score was calculated for the HUI2 and HUI3. Results of both groups were compared using the Mann-Whitney U test. Results: A total of 20 patients completed the questionnaire. Age ranged from 37 to 79 years with a mean age of 56 years (45% males and 55% females). The control group consisted of 20 participants with a mean age of 56.4 years and ranged from 37 to 82 years (35% males and 65% females). For the case group, median HUI2 MAUF score was 0.75 and median HUI3 MAUF score was 0.65. For the control group, the median scores were 0.88 and 0.86 respectively. There was a statistically significant difference for both HUI2 (p = 0.024) and HUI3 (p = 0.011). SCDS patients had a worse generic HRQoL than age-matched healthy controls. One patient with unilateral SCDS had a negative HUI3 MAUF score (−0.07), indicating a health-state worse than death. Conclusion: SCDS patients have significantly lower health utility values than an age-matched control group. This confirms the negative impact of SCDS on generic HRQoL, even when using an instrument that is not designed to be disease-specific but to assess health state in general. These data can be useful to compare impact on HRQoL among diseases.

Background: Previous studies have demonstrated spatial cognitive deficits in patients with bilateral vestibulopathy (BVP). However, BVP patients frequently present with a concomitant sensorineural hearing loss, which is a well-established risk factor of cognitive impairment and incident dementia. Nonetheless, previous research on spatial cognitive deficits in BVP patients have not taken hearing status into account. Objective: This study aims to compare spatial cognition of BVP patients with healthy controls, with analyses adjusting for hearing status. Methods: Spatial cognition was assessed in 64 BVP patients and 46 healthy controls (HC) by use of the Virtual Morris Water Task (VMWT). All statistical analyses were adjusted for hearing (dys)function, sex, age, education, and computer use. Results: Overall, patients with BVP performed worse on all outcome measures of the VMWT. However, these differences between BVP patients and healthy controls were not statistically significant. Nonetheless, a statistically significant link between sensorineural hearing loss and spatial cognition was observed. The worse the hearing, the longer subjects took to reach the hidden platform in the VMWT. Furthermore, the worse the hearing, the less time was spent by the subjects in the correct platform quadrant during the probe trial of the VMWT. Conclusion: In this study, no difference was found regarding spatial cognition between BVP patients and healthy controls. However, a statistically significant link was observed between sensorineural hearing loss and spatial cognition.

Cerebral small vessel disease (cSVD) plays an important role in dementia and is a major cause for vascular cognitive impairment (VCI). Recent studies hypothesized that capillary dysfunction including reduction of capillary patency, rather than a flow-limiting pathology is crucial in cSVD. As cSVD is considered a systemic microvascular disease, we examined sublingual microvascular blood flow and capillary density in patients with VCI and controls. Fifteen patients with VCI due to cSVD and 15 controls underwent intravital microscopy of the sublingual microvessels. Microvascular blood flow and capillary density in high and low flow areas were determined for each participant. Flow-density coupling was examined by determining the ratio of density changes to flow changes, and the ratio of feed vessel red blood cell (RBC) velocity to capillary RBC velocity. These were compared between VCI and controls. In healthy controls, capillary density increased proportionally with feed vessel blood flow increase. In patients with VCI, no increase of capillary density was observed. Moreover, increase of feed vessel RBC velocity led to significant increase of capillary RBC velocity in VCI, whereas in controls, the capillary RBC increased only slightly. Flow-density coupling differed significantly between VCI and controls, also after correcting for age and hypertension. Our findings suggest uncoupling of microvascular blood flow and capillary density in patients with VCI. This uncoupling may impair oxygen and nutrients exchange when blood flow increases in response to increased metabolic demand, ultimately leading to tissue damage.

Background: Intracranial carotid artery calcification (ICAC) on computed tomography (CT) is a marker of atherosclerosis and an independent predictor of vascular events including stroke. While vitamin K antagonists (VKAs) are used to prevent embolic stroke, they have been shown to increase levels of both coronary and extracoronary artery calcification. This has not been studied for (intracranial) carotid arteries. The aim of this study is to investigate the association between VKA use and degree of ICAC. We tested our hypothesis in a cohort of patients with nontraumatic intracerebral hemorrhage (ICH) of which a substantial part used VKAs. Materials and Methods: We retrospectively semiquantified ICAC on brain unenhanced CT of consecutive adult patients with nontraumatic ICH. Assessment was performed blinded to clinical characteristics and status of VKA use. We used a 5-point visual scale and dichotomized degree of ICAC in low and high degree. Patient demographics, VKA use, duration of VKA treatment, as well as known risk factors for intracranial calcification were collected. Univariable and multivariable logistic regression analyses were performed to investigate the association between ICAC and VKA use. Results: Three hundred and seventy-six nontraumatic ICH patients were included of whom 77 were using VKAs (20.5%) with a median treatment duration of 35 months. Any degree of ICAC was detected in 289 patients (76.9%). Univariable analysis showed that a high degree of ICAC was significantly associated with older age [odds ratio (OR), 1.06, 95% confidence interval (CI), 1.03-1.08], hypertension (OR, 2.14; 95% CI, 1.27-3.62), diabetes mellitus (OR, 2.38; 95% CI, 1.27-4.49), and the use of VKAs (OR, 1.84; 95% CI, 1.06-3.20). In multivariable regression analysis, only older age was significantly associated with a higher degree of ICAC (OR, 1.05; 95% CI, 1.02-1.08), while VKA use was not (OR, 1.22; 95% CI, 0.67-2.24). Conclusions: Our findings do not support VKA use as an independent risk factor for higher ICAC degree in patients with ICH. We could not confirm the concerns about VKA use and intracranial carotid vascular calcification. We suggest further research in other cohorts with VKA users such as patients with ischemic stroke and atrial fibrillation.

Objective: Clinical vestibular testing mainly consists of testing reflexes, but does not routinely include testing for perceptual symptoms. The objective of this study was to investigate a new and faster test for vestibular perception, and to compare its results with previous studies.Methods: Fifty-five healthy subjects with no prior vestibular complaints were included and divided into three age groups. Vestibular perceptual thresholds were measured using a hydraulic platform in the dark. The platform delivered 12 different movements: six translations (forward, backward, right, left, up, and down) and six rotations/tilt (yaw left, yaw right, pitch forward, pitch backward, roll left, and roll right). The subject had to report the correct type and direction of movements. Thresholds were determined by a double confirmation of the lowest threshold. General trends in thresholds like relative interrelationship and the influence of age were analyzed and compared with values reported previously.Results: Mean thresholds of age groups ranged between 0.092 and 0.221 m/s(2) for translations, and between 0.188 and 2.255 degrees/s(2) for rotations. The absolute values differed from previous reports, but the relative interrelationship of thresholds between type and direction of motion remained. An association between age and vestibular thresholds was found, similar to previous reports.Conclusion: This new and faster test for vestibular perception showed comparable patterns in perceptual thresholds when compared to more research oriented, lengthy tests. This might pave the way for establishing vestibular perception testing protocols useful for the clinic.

Introduction: Carotid artery dissection (CAD) and atherosclerotic carotid artery occlusion (ACAO) are major causes of a tandem occlusion in patients with intracranial large vessel occlusion (LVO). Presence of tandem occlusions may hamper intracranial access and potentially increases the risk of procedural complications of endovascular treatment (EVT). Our aim was to assess neurological, functional and technical outcome and complications of EVT for intracranial LVO in patients with CAD in comparison to patients with ACAO and to patients without CAD or ACAO.Methods: We analyzed data of the MR CLEAN trial intervention arm and MR CLEAN Registry, acquired in 16 Dutch EVT-centers. Primary outcome was the change in stroke severity by comparing the National Institute of Health Stroke Scale (NIHSS) score at 24-48 h after treatment vs. baseline. Secondary outcomes included reperfusion rate and symptomatic intracranial hemorrhage (sICH). We compared outcomes and complications between patients with CAD vs. patients with ACAO and patients without CAD or ACAO.Results: In total, we identified 74 (4.7%) patients with CAD, 92 (5.9%) patients with ACAO and 1398 (89.4%) patients without CAD or ACAO. Neurological improvement at short-term after EVT in patients with CAD was significantly better compared to ACAO (raw mean -5 vs. mean -1 NIHSS point; p = 0.03) and did not differ compared to patients without CAD or ACAO (-4 NIHSS points; p = 0.62). Rates of successful reperfusion in patients with CAD (47%) was comparable to patients with ACAO (47%; p = 1.00), but was less often achieved compared to patients without CAD or ACAO (58%; p = 0.08). Occurrence of sICH did not differ significantly between CAD patients (5%) and ACAO (11%; p = 0.33) or without CAD/ACAO (6%; p = 1.00).Conclusion: EVT in patients with intracranial LVO due to CAD results in neurological improvement comparable to patients without tandem occlusions. Therefore, carotid artery dissection by itself should not be a contraindication for endovascular treatment in stroke patients with intracranial large vessel occlusion. Although more challenging endovascular procedures are to be suspected in both patients with CAD or ACAO, accurate distinction between CAD and ACAO might influence clinical decision making as better clinical outcome can be expected in patients with CAD.

INTRODUCTION: Multiple sclerosis (MS) has been associated with both a poor vitamin D status and hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis. Since nuclear receptor ligands may regulate each other, we explored the association of vitamin D3 supplements with circadian cortisol levels in a double-blind and placebo-controlled supplementation study. METHODS: Female patients with relapsing-remitting MS received vitamin D3 supplements (4000 IU/day; n=22) or placebo (n=19) during 16 weeks. Salivary cortisol levels, repeatedly measured during the day, and serum 25(OH)D levels were assessed before (T0) and after (T1) this treatment period. RESULTS: Median 25(OH)D levels at T1 were 139.9 nmol/L (interquartile range 123.5 – 161.2) and 74.5 nmol/L (58.6 – 88.1) in the vitamin D3 and placebo group, respectively (p

Objective: To determine the influence of daily use of spectacles to correct a refractive error, on the vestibulo-ocular reflex (VOR) gain measured with the video head impulse test (vHIT). Study design: This prospective study enrolled subjects between 18 and 80 years old with and without a refractive error. Subjects were classified into three groups: (1) contact lenses, (2) spectacles, and (3) control group without visual impairment. Exclusion criteria comprised ophthalmic pathology, history of vestibular disorders, and alternated use of spectacles and contact lenses in daily life. Corrective spectacles were removed seconds before testing. One examiner performed all vHIT's under standardized circumstances using the EyeSeeCam system. This system calculated the horizontal VOR gain for rightward and leftward head rotations separately. Results: No statistically significant difference was found in VOR gain between the control group (n = 16), spectacles group (n = 48), and contact lenses group (n = 15) (p = 0.111). Both the spectacles group and contact lenses group showed no statistically significant correlation between VOR gain and amount of refractive error, for rightwards (p = 0.071) and leftwards (p = 0.716) head rotations. There was no statistical significant difference in VOR gain between testing monocularly or binocularly (p = 0.132) and between testing with or without wearing contact lenses (p = 0.800). Conclusion: In this study, VOR gain was not influenced by wearing corrective spectacles or contact lenses on a daily basis. Based on this study, no corrective measures are necessary when performing the vHIT on subjects with a refractive error, regardless of the way of correction.

The purpose of this study was to evaluate whether it is possible to restore the high-frequency angular vestibulo-ocular reflex (aVOR) in patients suffering from a severe bilateral vestibulopathy (BV) and implanted with a vestibular implant prototype. Three patients (S1-3) participated in the study. They received a prototype vestibular implant with one to three electrode branches implanted in the proximity of the ampullary branches of the vestibular nerve. Five electrodes were available for electrical stimulation: one implanted in proximity of the left posterior ampullary nerve in S1, one in the left lateral and another one in the superior ampullary nerves in S2, and one in the right lateral and another one in the superior ampullary nerves in S3. The high-frequency aVOR was assessed using the video head impulse test (EyeSeeCam; EyeSeeTec, Munich, Germany), while motion-modulated electrical stimulation was delivered via one of the implanted vestibular electrodes at a time. aVOR gains were compared to control measurements obtained in the same patients when the device was not activated. In three out of the five tested electrodes the aVOR gain increased monotonically with increased stimulation strength when head impulses were delivered in the plane of the implanted canal. In these cases, gains ranging from 0.4 to values above 1 were measured. A "reversed" aVOR could also be generated when inversed stimulation paradigms were used. In most cases, the gain for excitatory head impulses was superior to that recorded for inhibitory head impulses, consistent with unilateral vestibular stimulation. Improvements of aVOR gain were generally accompanied by a concomitant decrease of corrective saccades, providing additional evidence of an effective aVOR. High inter-electrode and inter-subject variability were observed. These results, together with previous research, demonstrate that it is possible to restore the aVOR in a broad frequency range using motion-modulated electrical stimulation of the vestibular afferents. This provides additional encouraging evidence of the possibility of achieving a useful rehabilitation alternative for patients with BV in the near future.

Objective The purpose of this exploratory study was to investigate whether a quantitative image analysis of the labyrinth in conventional MRI scans using a radiomics approach showed differences between patients with Meniere’s disease and the control group. Materials and methods In this retrospective study, MRI scans of the affected labyrinths of 24 patients with Meniere’s disease were compared to the MRI scans of labyrinths of 29 patients with an idiopathic asymmetrical sensorineural hearing loss. The 1,5T and 3T MRI scans had been previously made in a clinical setting between 2008 and 2015. 3D Slicer 4.4 was used to extract several substructures of the labyrinth. A quantitative analysis of the normalized radiomic image features was performed in Mathematica 10. The image features of the two groups were statistically compared. Results For numerous image features, there was a statistically significant difference (p-value

Objective: To evaluate the different etiologies and clinical subtypes of bilateral vestibular hypofunction (BVH) and the value of diagnostic tools in the diagnostic process of BVH. Materials and methods: A retrospective case review was performed on 154 patients diagnosed with BVH in a tertiary referral center, between 2013 and 2015. Inclusion criteria comprised 1) imbalance and/or oscillopsia during locomotion, and 2) summated slow phase velocity of nystagmus of less than 20 degrees per second during bithermal caloric tests. Results: The definite etiology of BVH was determined in 47% of the cases and the probable etiology in 22%. In 31%, the etiology of BVH remained idiopathic. BVH resulted from more than 20 different etiologies. In the idiopathic group, the percentage of migraine was significantly higher compared to the non-idiopathic group (50% versus 11%, p

Biobanks are important resources for biomarker discovery and assay development. Biomarkers for Alzheimer's and Parkinson's disease (BIOMARKAPD) is a European multicenter study, funded by the EU Joint Programme-Neurodegenerative Disease Research, which aims to improve the clinical use of body fluid markers for the diagnosis and prognosis of Alzheimer's disease (AD) and Parkinson's disease (PD). The objective was to standardize the assessment of existing assays and to validate novel fluid biomarkers for AD and PD. To support the validation of novel biomarkers and assays, a central and a virtual biobank for body fluids and associated data from subjects with neurodegenerative diseases have been established. In the central biobank, cerebrospinal fluid (CSF) and blood samples were collected according to the BIOMARKAPD standardized pre-analytical procedures and stored at Integrated BioBank of Luxembourg. The virtual biobank provides an overview of available CSF, plasma, serum, and DNA samples at each site. Currently, at the central biobank of BIOMARKAPD samples are available from over 400 subjects with normal cognition, mild cognitive impairment (MCI), AD, frontotemporal dementia (FTD), vascular dementia, multiple system atrophy, progressive supranuclear palsy, PD, PD with dementia, and dementia with Lewy bodies. The virtual biobank contains information on over 8,600 subjects with varying diagnoses from 21 local biobanks. A website has been launched to enable sample requests from the central biobank and virtual biobank. © 2015 Reijs, Teunissen, Goncharenko, Betsou, Blennow, Baldeiras, Brosseron, Cavedo, Fladby, Froelich, Gabryelewicz, Gurvit, Kapaki, Koson, Kulic, Lehmann, Lewczuk, Lleó, Maetzler, de Mendonça, Miller, Molinuevo, Mollenhauer, Parnetti, Rot, Schneider, Simonsen, Tagliavini, Tsolaki, Verbeek, Verhey, Zboch, Winblad, Scheltens, Zetterberg and Visser.