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Recently, an intronic biallelic (AAGGG)n repeat expansion in RFC1 was shown to be a cause of CANVAS and adult-onset ataxia in multiple populations. As the prevalence of the RFC1 repeat expansion in Dutch cases was unknown, we retrospectively tested 9 putative CANVAS cases and two independent cohorts (A and B) of 395 and 222 adult-onset ataxia cases, respectively, using the previously published protocol and, for the first time optical genome mapping to determine the size of the expanded RFC1 repeat. We identified the biallelic (AAGGG)n repeat expansion in 5/9 (55%) putative CANVAS patients and in 10/617 (1.6%; cohorts A + B) adult-onset ataxia patients. In addition to the AAGGG repeat motif, we observed a putative GAAGG repeat motif in the repeat expansion with unknown significance in two adult-onset ataxia patients. All the expanded (AAGGG)n repeats identified were in the range of 800–1299 repeat units. The intronic biallelic RFC1 repeat expansion thus explains a number of the Dutch adult-onset ataxia cases that display the main clinical features of CANVAS, and particularly when ataxia is combined with neuropathy. The yield of screening for RFC1 expansions in unselected cohorts is relatively low. To increase the current diagnostic yield in ataxia patients, we suggest adding RFC1 screening to the genetic diagnostic workflow by using advanced techniques that attain long fragments.

Objective Current diagnostic criteria for bilateral vestibulopathy (BV) primarily involve measurements of vestibular reflexes. Perceptual self-motion thresholds however, are not routinely measured and their clinical value in this specific population is not yet fully determined. Objectives of this study were (1) to compare perceptual self-motion thresholds between BV patients and control subjects, and (2) to explore patterns of self-motion perception performance and vestibular function in BV patients. Methods Thirty-seven BV patients and 34 control subjects were included in this study. Perceptual self-motion thresholds were measured in both groups using a CAREN platform (Motek Medical BV, Amsterdam, The Netherlands). Vestibular function was evaluated (only in BV patients) by the caloric test, torsion swing test, video head impulse test of all semicircular canals, and cervical- and ocular vestibular-evoked myogenic potentials. Differences in thresholds between both groups were analyzed. Hierarchical cluster analysis was performed to visualize patterns between self-motion perception and vestibular function within the group of BV patients. Results Perceptual self-motion thresholds were significantly higher in BV patients compared to control subjects, regarding nearly all rotations and translations (depending on the age group) (p ≤ 0.001). Cluster analysis showed that within the group of BV patients, higher perceptual self-motion thresholds were generally associated with lower vestibular test results (significant for yaw rotation, caloric test, torsion swing test, and video head impulse test (p ≤ 0.001)). Conclusion Self-motion perception is significantly decreased in BV patients compared to control subjects regarding nearly all rotations and translations. Furthermore, decreased self-motion perception is generally associated with lower residual vestibular function in BV patients. Trial registration Trial registration number NL52768.068.15/METC

Background and purpose Research suggests comparable long-term psychosocial outcomes following mild traumatic brain injury (mTBI) and minor stroke, but no direct comparison has been made. This study aimed to directly compare psychosocial outcome over time in persons with mTBI and minor stroke. Methods In this multicenter, prospective longitudinal cohort study, community-dwelling persons with mTBI (n = 182) and minor stroke (n = 48) were assessed at 6 weeks, 3, 6 and 12 months post-injury. Outcome measures included anxiety and depression symptoms (Hospital Anxiety and Depression Scale—HADS), cognitive problems in daily life (Checklist for Cognitive and Emotional Consequences of Stroke—CLCE-24) and quality of life (EuroQol-5D-5L—EQ-5D-5L). Multilevel growth curve modeling, controlled for demographic variables, was used to determine outcomes over time between groups. Proportions of persons reporting persistent psychosocial symptoms at 6 months post-injury were compared using Pearson’s Chi-squared tests. Results Improvements in outcomes were observed in the first 6 months and effects stabilized to 12 months post-injury in both groups. Minor stroke cases reported significantly higher levels of HADS anxiety and a significantly reduced increase in EQ-5D-5L utility scores than mTBI cases, but differences were small in absolute numbers. No significant differences were observed between groups regarding HADS depression and CLCE-24 cognition scores. Proportions of persons reporting persistent psychosocial symptoms were equal between groups. Conclusions Psychosocial outcome is largely comparable following mTBI and minor stroke. Specific attention should be paid to anxiety symptoms and cognitive problems in daily life for which uniform aftercare seems appropriate.

Unilateral or bilateral vestibular hypofunction presents most commonly with symptoms of dizziness or postural imbalance and affects a large population. However, it is often missed because no quantitative testing of vestibular function is performed, or misdiagnosed due to a lack of standardization of vestibular testing. Therefore, this article reviews the current status of the most frequently used vestibular tests for canal and otolith function. This information can also be used to reach a consensus about the systematic diagnosis of vestibular hypofunction.

Background Most questionnaires currently used for assessing symptomatology of vestibular disorders are retrospective, inducing recall bias and lowering ecological validity. An app-based diary, administered multiple times in daily life, could increase the accuracy and ecological validity of symptom measurement. The objective of this study was to introduce a new experience sampling method (ESM) based vestibular diary app (DizzyQuest), evaluate response rates, and to provide examples of DizzyQuest outcome measures which can be used in future research. Methods Sixty-three patients diagnosed with a vestibular disorder were included. The DizzyQuest consisted of four questionnaires. The morning- and evening-questionnaires were administered once each day, the within-day-questionnaire 10 times a day using a semi-random time schedule, and the attack questionnaire could be completed after the occurrence of a vertigo or dizziness attack. Data were collected for 4 weeks. Response rates and loss-to-follow-up were determined. Reported symptoms in the within-day-questionnaire were compared within and between patients and subgroups of patients with different vestibular disorders. Results Fifty-one patients completed the study period. Average response rates were significantly higher than the desired response rate of > 50% (p Conclusion The DizzyQuest is able to capture vestibular symptoms within their psychosocial context in daily life, with little recall bias and high ecological validity. The DizzyQuest reached the desired response rates and showed different disease profiles between subgroups of patients with different vestibular disorders. This is the first time ESM was used to assess daily symptoms and quality of life in vestibular disorders, showing that it might be a useful tool in this population.

The impact of vibrotactile feedback of the gravity vector, provided by a “balance” belt worn around the waist, was evaluated in 39 patients with a severe bilateral vestibular loss, confirmed by extensive laboratory testing and suffering from a low quality of life, mainly due to imbalance. The mobility and balance score (MBS) of all patients prior to the use of the belt was equal or less than 5 out of a scale of 10. Thirty-one out of the 39 patients experienced the effect of the belt on their balance and mobility as positive in a preselection trial of 2 h in the hospital. The 31 positive responders then used the belt for 1 month in daily life. The average MBS increased significantly from 4.2 to 7.9 (paired T test, T = 9.82, p

Background/objective Different testing paradigms have been proposed to investigate perceptual self-motion thresholds. They can differ regarding the amount of possible motions that patients have to choose from. Objective of this study was to compare the two-option paradigm and twelve-option paradigm, to investigate whether reducing the choice options significantly influences the reported thresholds of self-motion perception of healthy subjects. Methods Thirty-three volunteers with no prior vestibular complaints were included and sequentially tested with both paradigms at a random sequence. Perceptual self-motion thresholds were measured using a hydraulic motion platform in the absence of external visual and auditory cues. The platform delivered twelve different movements: six translations and six rotations. Each subject had to report the correct type and direction of movements. Thresholds were determined by a double confirmation of the lowest threshold, in combination with a double rejection of the one-step lower stimulus. Perceptual self-motion thresholds of both paradigms were compared using the mixed model analysis. Results The twelve-option paradigm showed significantly higher reported thresholds for yaw rotations and translations left, right and down (p Conclusion Reported thresholds of self-motion perception of healthy subjects are influenced by the testing paradigm. The twelve-option paradigm showed significantly higher thresholds than the two-option paradigm. Results obtained with each testing paradigm should, therefore, be compared to paradigm-specific normative data.

Background The DizzyQuest, an app-based vestibular diary, provides the opportunity to capture the number and nature of vertigo attacks in daily life. To accomplish this, the DizzyQuest provides different strategies: event sampling using an attack questionnaire, and time sampling using an evening questionnaire. Objective of this study was to investigate whether the number and nature of reported vertigo attacks was comparable between the two questionnaires. Methods Fifty-seven patients, who reported vertigo attacks, used the DizzyQuest for on average 24 days. The number and nature (including symptoms, triggers and duration) of vertigo attacks were compared between the attack and the evening questionnaire. Results The attack questionnaire was used 192 times. In contrast, at least 749 new vertigo attacks were reported in 446 evening questionnaires. A vertigo attack was not always reported in both questionnaires during the same day. Vertigo attacks that were most likely captured by both questionnaires were not always reported the same in both questionnaires regarding triggers and duration. Conclusion Event sampling using an attack questionnaire has low recall bias and, therefore, reliably captures the nature of the attack, but induces a risk of under-sampling. Time sampling using an evening questionnaire suffers from recall bias, but seems more likely to capture less discrete vertigo attacks and it facilitates registration of the absence of vertigo attacks. Depending on the clinical or research question, the right strategy should be applied and participants should be clearly instructed about the definition of a vertigo attack.

Objectives The aim of this study was to explore expectations of patients with bilateral vestibulopathy regarding vestibular implant treatment. This could advance the definition of recommendations for future core outcome sets of vestibular implantation and help to determine on which characteristics of bilateral vestibulopathy future vestibular implant research should focus. Methods Semi-structured interviews were conducted with 50 patients diagnosed with bilateral vestibulopathy at Maastricht UMC + . Interviews followed a semi-structured interview guide and were recorded and transcribed. Transcripts were analyzed thematically by two independent researchers. A consensus meeting took place to produce a joint interpretation for greater dimensionality and to confirm key themes. Results Overall, patient expectations centralized around three key themes: (physical) symptom reduction, functions and activities, and quality of life. These themes appeared to be interrelated. Patient expectations focused on the activity walking (in a straight line), reducing the symptom oscillopsia and being able to live the life they had before bilateral vestibulopathy developed. In general, patients indicated to be satisfied with small improvements. Conclusion This study demonstrated that patient expectations regarding a vestibular implant focus on three key themes: symptom reduction, functions and activities, and quality of life. These themes closely match the functional improvements shown in recent vestibular implantation research. The results of this study provide a clear guideline from the patient perspective on which characteristics of bilateral vestibulopathy, future vestibular implant research should focus. Trial registration NL52768.068.15/METC

ObjectiveTo optimize the current diagnostic and treatment procedures for patients with bilateral vestibulopathy (BV), this study aimed to determine the complete spectrum of symptoms associated with BV.MethodA prospective mixed-method study design was used. Qualitative data were collected by performing semi-structured interviews about symptoms, context, and behavior. The interviews were recorded and transcribed until no new information was obtained. Transcriptions were analyzed in consensus by two independent researchers. In comparison to the qualitative results, quantitative data were collected using the Dizziness Handicap Inventory (DHI), Hospital Anxiety and Depression Scale (HADS) and a health-related quality of life questionnaire (EQ-5D-5L).ResultsEighteen interviews were transcribed. Reported symptoms were divided into fourteen physical symptoms, four cognitive symptoms, and six emotions. Symptoms increased in many situations, such as darkness (100%), uneven ground (61%), cycling (94%) or driving a car (56%). These symptoms associated with BV often resulted in behavioral changes: activities were performed more slowly, with greater attention, or were avoided. The DHI showed a mean score of severe handicap (54.67). The HADS questionnaire showed on average normal results (anxiety = 7.67, depression = 6.22). The EQ-5D-5L demonstrated a mean index value of 0.680, which is lower compared to the Dutch age-adjusted reference 0.839 (60–70 years).ConclusionBV frequently leads to physical, cognitive, and emotional complaints, which often results in a diminished quality of life. Importantly, this wide range of symptoms is currently underrated in literature and should be taken into consideration during the development of candidacy criteria and/or outcome measures for therapeutic interventions such as the vestibular implant.

Contains fulltext : 182353.pdf (Publisher’s version ) (Open Access) Seizures after intracerebral hemorrhage are repeatedly seen. Whether the development of seizures after intracerebral hemorrhage affects survival in the long term is unknown. This study aims to determine the relation between seizures (i.e., with and without anti-epileptic therapy) and long-term mortality risk in a large patient population with intracerebral hemorrhage. We retrospectively included patients with a non-traumatic ICH in all three hospitals in the South Limburg region in the Netherlands between January 1st 2004 and December 31st 2009, and we assessed all-cause mortality until March 14th 2016. Patient who did not survive the first seven days after intracerebral hemorrhage were excluded from analyses. We used Cox multivariate analyses to determine independent predictors of mortality. Of 1214 patients, 783 hemorrhagic stroke patients fulfilled the inclusion criteria, amongst whom 37 (4.7%) patients developed early seizures (within 7 days after hemorrhage) and 77 (9.8%) developed late seizures (more than 7 days after hemorrhage). Seizure development was not significantly related to mortality risk after correction for conventional vascular risk factors and hemorrhage severity. However, we found a small but independent relation between the use of anti-epileptic drugs and a lower long-term mortality (HR = 0.32, 95% CI 0.11-0.91). In our large population, seizures and epilepsy did not relate independently to an increased mortality risk after hemorrhage.

Introduction Nonfocal transient neurological attacks (TNAs) are associated with an increased risk of future dementia, but it is unclear whether TNAs are also associated with concurrent cognitive impairment. We hypothesized that recent TNAs are related to worse cognitive functioning. We tested our hypothesis in patients with heart failure, as these patients are at risk of cerebral hypoperfusion, which might play a role in the etiology of TNAs. Methods We performed neuropsychological testing in all patients with heart failure enrolled in the Heart Brain Connection study. We assessed global cognition, attention-psychomotor speed, executive functioning, memory and language. All patients were interviewed with a standardized questionnaire on the occurrence of TNAs in the preceding 6 months. We studied associations between TNAs and cognitive functioning with linear and logistic regression analyses, adjusted for age, sex and education. We performed additional analyses in patients without previous stroke or TIA and in patients without brain infarction on MRI. Results Thirty-seven (23%) of 158 patients (mean age 70 years, 67% men) experienced one or more TNAs. Patients with a recent TNA were more likely to be impaired on ≥ 1 cognitive domains than patients without TNAs [41% vs. 18%, adjusted odds ratio 4.6, 95% confidence interval (CI) 1.8–11.8]. Patients with TNAs performed worse than patients without TNAs on global cognition (mean difference in z scores − 0.36, 95% CI − 0.54 to − 0.18), and on the cognitive domains attention-psychomotor speed (mean difference − 0.40, 95% CI − 0.66 to − 0.14), memory (mean difference − 0.57, 95% CI − 0.98 to − 0.15) and language (mean difference − 0.47, 95% CI − 0.79 to − 0.16). These associations were independent of cardiac output and volume of white matter hyperintensities. Subgroup analyses in patients without previous stroke or TIA or brain infarction on MRI (n = 78) yielded comparable results, with the exception of the cognitive domain language, which was no longer different between patients with and without TNAs. Conclusion Among patients with heart failure, TNAs are associated with cognitive impairment, which warrants the need for more clinical awareness of this problem. Electronic supplementary material The online version of this article (10.1007/s00415-019-09376-z) contains supplementary material, which is available to authorized users.

Introduction Bilateral vestibulopathy (BVP) can affect visual acuity in dynamic conditions, like walking. This can be assessed by testing Dynamic Visual Acuity (DVA) on a treadmill at different walking speeds. Apart from BVP, age itself might influence DVA and the ability to complete the test. The objective of this study was to investigate whether DVA tested while walking, and the drop-out rate (the inability to complete all walking speeds of the test) are significantly influenced by age in BVP-patients and healthy subjects. Methods Forty-four BVP-patients (20 male, mean age 59 years) and 63 healthy subjects (27 male, mean age 46 years) performed the DVA test on a treadmill at 0 (static condition), 2, 4 and 6 km/h (dynamic conditions). The dynamic visual acuity loss was calculated as the difference between visual acuity in the static condition and visual acuity in each walking condition. The dependency of the drop-out rate and dynamic visual acuity loss on BVP and age was investigated at all walking speeds, as well as the dependency of dynamic visual acuity loss on speed. Results Age and BVP significantly increased the drop-out rate (p ≤ 0.038). A significantly higher dynamic visual acuity loss was found at all speeds in BVP-patients compared to healthy subjects (p p ≤ 0.036). Conclusion DVA tested while walking on a treadmill, is one of the few “close to reality” functional outcome measures of vestibular function in the vertical plane. It is able to demonstrate significant loss of DVA in bilateral vestibulopathy patients. However, since bilateral vestibulopathy and age significantly increase the drop-out rate at faster walking speeds, it is recommended to use age-matched controls. Furthermore, it could be considered to use an individual “preferred” walking speed and to limit maximum walking speed in older subjects when testing DVA on a treadmill.

Enlarged Virchow-Robin spaces (EVRS) are considered to be a sign of cerebral small vessel disease. Hypertension is an important risk factor for cerebral small vessel disease, whereas ambulatory blood pressure (BP) is the strongest predictor of hypertension-related brain damage. However, the association between ambulatory BP levels and EVRS has never been investigated. The aim of this study was to determine the association between ambulatory BP levels and EVRS. In 143 first-ever lacunar stroke patients, we performed 24-h ambulatory BP monitoring after the acute stroke phase. On brain MRI we counted EVRS in the basal ganglia and the centrum semiovale. We graded the number of EVRS at each level into a three-category severity scale. We assessed the association between BP levels and EVRS by ordinal regression analysis. After adjusting for age, sex, extensive white matter lesions, and asymptomatic lacunar infarcts, higher day systolic (OR 1.21; 95 % CI 1.00-1.46 per 10 mmHg), day diastolic (1.18; 95 % CI 1.02-1.37 per 5 mmHg) and 24-h diastolic (OR 1.18; 95 % CI 1.01-1.37 per 5 mmHg) ambulatory BP levels were associated with EVRS at the basal ganglia level. No relation was found between ambulatory BP levels and EVRS in the centrum semiovale. Higher day ambulatory BP levels are associated with EVRS in the basal ganglia. This association was independent of the presence of extensive white matter lesions and asymptomatic lacunar infarcts. Our results imply that basal ganglia EVRS should be regarded as a separate manifestation of BP-related brain damage.