The lesion core extent modulates the impact of early perfusion mismatch imaging on outcome variability after thrombectomy in stroke.

Introduction: Despite profitable group effects on functional outcomes after mechanical thrombectomy (MT) in large vessel occlusion (LVO), many patients with successful reperfusion show a non-favorable long-term outcome, highlighting the necessity to identify potential biomarkers predicting outcome variability. In this regard, the role of perfusion mismatch imaging for outcome variability in the early time window within 6 h after symptom onset is a matter of debate. We attempted to investigate under which conditions early perfusion mismatch imaging accounts for variability in functional outcomes after mechanical thrombectomy. Patients and methods: In a retrospective single-center study, we examined 190 consecutive patients with LVO who were admitted to the Medical Center Lübeck within 6 h after symptom onset, all of whom underwent MT. Perfusion mismatch was quantified by applying the Alberta Stroke Program Early CT score (ASPECTS) on CT-measured cerebral blood flow (CBF-ASPECTS) and subtracting it from an ASPECTS application on cerebral blood volume (CBV-ASPECTS), i.e., ASPECTS mismatch. Using multivariate ordinal regression models, associations between ASPECTS mismatch and modified Rankin Scale (mRS) after 90 days were assessed. Furthermore, the interaction between ASPECTS mismatch and the core lesion volume was calculated to evaluate conditional associations. Results: ASPECTS mismatch did not correlate with functional outcomes when corrected for multiple influencing covariables. However, interactions between ASPECTS mismatch and CBV-ASPECTS [OR: 1.12 (1.06-1.18), p-value < 0.001], as well as NCCT-ASPECTS [OR: 1.15 (1.06-1.25), p-value < 0.001], did show a significant association with functional outcomes. Model comparisons revealed that, profoundly, in patients with large core lesion volumes (CBV-ASPECTS < 6 or NCCT-ASPECTS < 6), perfusion mismatch showed a negative correlation with the mRS. Discussion and conclusion: Perfusion mismatch imaging within the first 6 h of symptom onset provides valuable insights into the outcome variability of LVO stroke patients receiving thrombectomy but only in patients with large ischemic core lesions.

Preserved Corticospinal Tract Revealed by Acute Perfusion Imaging Relates to Better Outcome After Thrombectomy in Stroke.

BACKGROUND: The indication for mechanical thrombectomy (MT) in stroke patients with large vessel occlusion has been constantly expanded over the past years. Despite remarkable treatment effects at the group level in clinical trials, many patients remain severely disabled even after successful recanalization. A better understanding of this outcome variability will help to improve clinical decision-making on MT in the acute stage. Here, we test whether current outcome models can be refined by integrating information on the preservation of the corticospinal tract as a functionally crucial white matter tract derived from acute perfusion imaging. METHODS: We retrospectively analyzed 162 patients with stroke and large vessel occlusion of the anterior circulation who were admitted to the University Medical Center Lübeck between 2014 and 2020 and underwent MT. The ischemic core was defined as fully automatized based on the acute computed tomography perfusion with cerebral blood volume data using outlier detection and clustering algorithms. Normative whole-brain structural connectivity data were used to infer whether the corticospinal tract was affected by the ischemic core or preserved. Ordinal logistic regression models were used to correlate this information with the modified Rankin Scale after 90 days. RESULTS: The preservation of the corticospinal tract was associated with a reduced risk of a worse functional outcome in large vessel occlusion-stroke patients undergoing MT, with an odds ratio of 0.28 (95% CI, 0.15-0.53). This association was still significant after adjusting for multiple confounding covariables, such as age, lesion load, initial symptom severity, sex, stroke side, and recanalization status. CONCLUSIONS: A preinterventional computed tomography perfusion-based surrogate of corticospinal tract preservation or disconnectivity is strongly associated with functional outcomes after MT. If validated in independent samples this concept could serve as a novel tool to improve current outcome models to better understand intersubject variability after MT in large vessel occlusion stroke.

Sensitivity and specificity in signal detection with the reporting odds ratio and the information component.

PURPOSE: As measures of association between an adverse drug reaction (ADR) and exposure to a drug the reporting odds ratio (ROR) and the information component (IC) can be used. We sought to test the reliability of signal detection with these. METHODS: We simulated ADR counts as binomially distributed random numbers for different expected ADR frequencies and theoretical reporting odds ratios (RORs). We then calculated the empirical IC and the empirical ROR and their confidence intervals. The rate of signals that was detected despite a theoretical ROR of 1 represented the false positive rate, and represented the sensitivity if the ROR was >1. RESULTS: For expected case counts below 1 the false positive rate oscillates from 0.01 to 0.1 even though 0.025 were intended. Even beyond expected case counts of 5 oscillations can cover a range of 0.018 to 0.035. The first n oscillations with the largest amplitude are eliminated if a minimum case count of n is required. To detect an ROR of 2 with a sensitivity of 0.8, a minimum of 12 expected ADRs are required. In contrast, 2 expected ADRs suffice to detect an ROR of 4. CONCLUSION: Summaries of measures for disproportionality should include the expected number of cases in the group of interest if a signal was detected. If no signal was detected the sensitivity for the detection of a representative ROR or the minimum ROR that could be detected with probability 0.8 should be reported.

Combined optokinetic stimulation and cueing-assisted reading therapy to treat hemispatial neglect: A randomized controlled crossover trial.

BACKGROUND: Hemispatial neglect is a disabling cognitive disorder following stroke and effective therapies are required. OBJECTIVES: To evaluate the effects of combined optokinetic stimulation (OKS) and cueing-assisted reading therapy (READ) on the remission of hemispatial neglect following stroke. METHODS: Randomized, controlled, two-period, crossover trial conducted at a German neurorehabilitation center. Twenty participants with left neglect following right hemispheric stroke (mean age 66 years (SD 11), mean time since stroke 50 days (SD 33)) finished the trial (12 received OKSREAD first, 8 CONTROL first). The intervention consisted of 15 daily sessions of OKS (20 min) and text reading assisted by a therapist providing cues (20 min). The control treatment was a same-number, same-length neuropsychological treatment not targeting visuospatial attention. Primary outcomes were the change in performance of a customized neuropsychological test battery for neglect (0% worst - 100% best) and a test of neglect-related functional disability (Catherine Bergego Scale, 0 no impairment - 30 severest impairment), assessed before and after each treatment period. Secondary outcomes were performance in the 6 single tests composing the battery (e.g., omissions in text reading, center of cancellation in the Bells test, spatial bias of fixations when freely viewing photographs) and a clinical test of anosognosia. RESULTS: Overall performance in the neglect test battery improved slightly more after OKSREAD than after CONTROL (d=6%; p=0.002). The remission of neglect-related functional disability did not differ between treatments (d=-2; p=0.291). Ipsilesional fixation bias during free viewing was the only secondary outcome that was improved by OKSREAD as compared to CONTROL (d= -2.8°; p=0.005). CONCLUSION: At the applied intensity, the combined OKSREAD intervention slightly attenuated the ipsilesional attention bias in persons with neglect, but it did not improve neglect-related functional disability, anosognosia, or other neglect symptoms to a clinically meaningful degree. CLINICAL TRIAL REGISTRATION: URL: http://www. CLINICALTRIALS: gov. Unique identifier: NCT04273620.

Downbeat Nystagmus Is Abolished by Alcohol in Nonalcoholic Wernicke Encephalopathy.

Background and Objectives: Lesions of the cerebellar flocculus cause enduring downbeat nystagmus (DBN) with unrelenting oscillopsia. Unlike most patients with DBN, the flocculus is structurally spared in nonalcoholic Wernicke encephalopathy (nWE) with chronic DBN. The objective was to study the effects of alcohol in nWE. Methods: We recorded eye movements of a unique patient with nWE under controlled alcohol consumption who said his oscillopsia disappeared with a few drinks of alcohol. Results: His DBN was markedly diminished by alcohol (by 77.4%), although he remained alert with normal saccades. Discussion: This striking observation may be caused by the differential effect of alcohol on the perihypoglossal complex and the paramedian tract neurons, which control the level of activity in the flocculus, with opposite (inhibition and excitation, respectively) effects. The finding suggests new ideas about the treatment and pathophysiology of DBN with a structurally intact cerebellum.

Gaze-contingent display technology can help to reduce the ipsilesional attention bias in hemispatial neglect following stroke.

BACKGROUND: Hemispatial neglect results from unilateral brain damage and represents a disabling unawareness for objects in the hemispace opposite the brain lesion (contralesional). The patients' attentional bias for ipsilesional hemispace represents a hallmark of neglect, which results from an imbalanced attentional priority map in the brain. The aim of this study was to investigate whether gaze-contingent display (GCD) technology, reducing the visual salience of objects in ipsilesional hemispace, is able to rebalance this map and increase awareness and exploration of objects in the neglected contralesional hemispace. METHODS: Using remote eye-tracking, we recorded gaze positions in 19 patients with left hemispatial neglect following right-hemisphere stroke and 22 healthy control subjects, while they were watching static naturalistic scenes. There were two task conditions, free viewing (FV) or goal-directed visual search (VS), and four modification conditions including the unmodified original picture, a purely static modification and two differently strong modifications with an additional gaze-contingent mask (GC-LOW, GC-HIGH), that continuously reduced color saturation and contrast of objects in the right hemispace. RESULTS: The patients' median gaze position (Center of Fixation) in the original pictures was markedly deviated to the right in both tasks (FV: 6.8° ± 0.8; VS: 5.5° ± 0.7), reflecting the neglect-typical ipsilesional attention bias. GC modification significantly reduced this bias in FV (GC-HIGH: d = - 3.2 ± 0.4°; p < 0.001). Furthermore, in FV and VS, GC modification increased the likelihood to start visual exploration in the (neglected) left hemifield by about 20%. This alleviation of the ipsilesional fixation bias was not associated with an improvement in detecting left-side targets, in contrast, the GC mask even decreased and slowed the detection of right-side targets. Subjectively, patients found the intervention pleasant and most of the patients did not notice any modification. CONCLUSIONS: GCD technology can be used to positively influence visual exploration patterns in patients with hemispatial neglect. Despite an alleviation of the neglect-related ipsilesional fixation bias, a concomitant functional benefit (improved detection of contralesional targets) was not achieved. Future studies may investigate individualized GCD-based modifications as augmented reality applications during the activities of daily living.

Bilateral lesion of the cerebellar fastigial nucleus: Effects on smooth pursuit acceleration and non-reflexive visually-guided saccades.

Background: "Central dizziness" due to acute bilateral midline cerebellar disease sparing the posterior vermis has specific oculomotor signs. The oculomotor region of the cerebellar fastigial nucleus (FOR) crucially controls the accuracy of horizontal visually-guided saccades and smooth pursuit eye movements. Bilateral FOR lesions elicit bilateral saccade hypermetria with preserved pursuit. It is unknown whether the initial acceleration of smooth pursuit is impaired in patients with bilateral FOR lesions. Objective: We studied the effect of a cerebellar lesion affecting the deep cerebellar nuclei on the initial horizontal pursuit acceleration and investigated whether saccade dysmetria also affects other types of volitional saccades, i.e., memory-guided saccades and anti-saccades, which are not performed in immediate response to the visual target. Methods: We recorded eye movements during a sinusoidal and step-ramp target motion paradigm as well as visually-guided saccades, memory-guided saccades, and anti-saccades in one patient with a circumscribed cerebellar hemorrhage and 18 healthy control subjects using a video-based eye tracker. Results: The lesion comprised the FOR bilaterally but spared the posterior vermis. The initial pursuit acceleration was low but not significantly different from the healthy control subjects and sinusoidal pursuit was normal. Bilateral saccade hypermetria was not only seen with visually-guided saccades but also with anti-saccades and memory-guided saccades. The final eye position remained accurate. Conclusion: We provide new insights into the contribution of the bilateral deep cerebellar nuclei on the initial acceleration of human smooth pursuit in midline cerebellar lesions. In line with experimental bilateral FOR lesion data in non-human primates, the initial pursuit acceleration in our patient was not significantly reduced, in contrast to the effects of unilateral experimental FOR lesions. Working memory and neural representation of target locations seem to remain unimpaired. Our data argue against an impaired common command feeding the circuits controlling saccadic and pursuit eye movements and support the hypothesis of independent influences on the neural processes generating both types of eye movements in the deep cerebellar nuclei.

On the quest for hidden ovarian teratomas in therapy-refractory anti-NMDA receptor encephalitis: a case report.

BACKGROUND: Anti-NMDA-receptor (anti-NMDAR) encephalitis is often associated with ovarian teratoma (OT). The best management of anti-NMDAR encephalitis patients with normal imaging studies (pelvic ultrasound/MRI) but clinically high risk of OT (e.g., female, adult, black) is unclear. We report on the surprising diagnostic quest in a young black woman with anti-NMDAR encephalitis, in whom invasive procedures could finally disclose two OTs that were hidden from the initial non-invasive diagnostics. CASE REPORT: The patient presented with a one-week history of psychotic symptoms, developing oro-facial dyskinesia, seizures and coma, eventually requiring mechanical ventilation. NMDA-receptor antibodies were positive in serum and cerebrospinal fluid. Pelvic MRI and transabdominal ultrasound were normal. Exploratory laparoscopy was also unremarkable at first, but due to a suspicious echogenic mass (15 mm) in the right ovary on perioperative transvaginal ultrasound, an ovarian incision was performed which led to the detection of a first OT and its removal via ovarian-preserving cystectomy. Following a severe therapy-refractory clinical course despite aggressive immunotherapy and tumor removal, 6 months later bilateral oophorectomy was performed as ultima ratio, disclosing a second micro-OT (6 mm) in the left ovary. Unfortunately, the patient has not improved clinically yet. CONCLUSIONS: In therapy-refractory anti-NMDAR encephalitis with high risk of OT, small and bilateral OTs hidden from primary non-invasive diagnostics should be considered, which may trigger further invasive diagnostic procedures.

A Simple Gain-Based Evaluation of the Video Head Impulse Test Reliably Detects Normal Vestibulo-Ocular Reflex Indicative of Stroke in Patients With Acute Vestibular Syndrome.

Objective: The head impulse test (HIT) assesses the vestibulo-ocular reflex (VOR) and is used to differentiate vestibular neuritis (abnormal VOR) from stroke (normal VOR) in patients presenting with an acute vestibular syndrome (AVS). The video-oculography-based HIT (vHIT) quantifies VOR function and provides information imperceptible for the clinician during clinical bedside HIT. However, the vHIT-like an electrocardiogram-requires experienced interpretation, which is especially difficult in the emergency setting. This calls for a simple, reliable and rater-independent way of analysis. Methods: We retrospectively collected 171 vHITs performed in patients presenting with AVS to our emergency department. Three neuro-otological experts comprehensively assessed the vHITs including interpretability (artifacts), VOR gain (eye/head velocity ratio), velocity profile (abrupt decline) and corrective saccades (overt/covert). Their consensus rating (abnormal/peripheral vs. normal/central) was compared to a simple algorithm that automatically classified the vHITs based on a single VOR gain cutoff (0.7). Results: Inter-rater agreement between experts was high (Fleiss' kappa = 0.74). Five (2.9 %) vHITs were "uninterpretable" according to experts' consensus, 80 (46.8 %) were rated "normal" and 86 (50.3 %) "abnormal". The algorithm had substantial agreement with the experts' consensus (Cohen's kappa = 0.75). Importantly, it correctly classified all of the normal/central vHITs denoted by the experts (100% specificity) and at the same time it had sufficient sensitivity (75.6%) in detecting abnormal/peripheral vHITs. Conclusion: A simple, automated, gain-based evaluation of the vHIT reliably detects normal/central VOR and may be a feasible and effective tool to screen AVS patients for potentially underlying stroke in the emergency setting.

Effects of post-interventional antiplatelet therapy on angiographic vasospasm, delayed cerebral ischemia, and clinical outcome after aneurysmal subarachnoid hemorrhage: a single-center experience.

Platelet activation has been postulated to be involved in the pathogenesis of delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to investigate potentially beneficial effects of antiplatelet therapy (APT) on angiographic CVS, DCI-related infarction and functional outcome in endovascularly treated aSAH patients. Retrospective single-center analysis of aSAH patients treated by endovascular aneurysm obliteration. Based on the post-interventional medical regime, patients were assigned to either an APT group or a control group not receiving APT. A subgroup analysis separately investigated those APT patients with aspirin monotherapy (MAPT) and those receiving dual treatment (aspirin plus clopidogrel, DAPT). Clinical and radiological characteristics were compared between groups. Possible predictors for angiographic CVS, DCI-related infarction, and an unfavorable functional outcome (modified Rankin scale ≥ 3) were analyzed. Of 160 patients, 85 (53%) had received APT (n = 29 MAPT, n = 56 DAPT). APT was independently associated with a lower incidence of an unfavorable functional outcome (OR 0.40 [0.19-0.87], P = 0.021) after 3 months. APT did not reduce the incidence of angiographic CVS or DCI-related infarction. The pattern of angiographic CVS or DCI-related infarction as well as the rate of intracranial hemorrhage did not differ between groups. However, the lesion volume of DCI-related infarctions was significantly reduced in the DAPT subgroup (P = 0.011). Post-interventional APT in endovascularly treated aSAH patients is associated with better functional outcome at 3 months. The beneficial effect of APT might be mediated by reduction of the size of DCI-related infarctions.

Usability of the head impulse test in routine clinical practice in the emergency department to differentiate vestibular neuritis from stroke.

BACKGROUND AND PURPOSE: The bedside head impulse test (bHIT) is used to differentiate vestibular neuritis (VN) from posterior circulation stroke (PCS) in patients presenting with acute vestibular syndrome (AVS). If assessed by neuro-otological experts, diagnostic accuracy is high. We report on its diagnostic accuracy when applied by nonexperts during routine clinical practice in the emergency department (ED), its impact on patient management, and the potential diagnostic yield of the video-oculography-supported head impulse test (vHIT). METHODS: Medical chart review of 38 AVS patients presenting to our university medical center's ED, assessed by neurology residents. We collected bHIT results (abnormal/peripheral or normal/central) and whether patients were admitted to the stroke unit or general neurological ward. Final diagnosis (VN, n = 24; PCS, n = 14) was determined by clinical course, magnetic resonance imaging, and vHIT. RESULTS: The bHIT's accuracy was only 58%. Its sensitivity for VN was high (88%), but due to many false-abnormal bHITs in PCS (36%), the specificity was low (64%). The vHIT yielded excellent specificity (100%) and moderate sensitivity (67%). The decision on the patient's further care was almost arbitrary and independent from the bHIT: 58% of VN and 57% of PCS patients were admitted to the stroke unit. CONCLUSIONS: The bHIT, applied by nonexperts during routine practice in the ED, has low accuracy, is too often mistaken as abnormal/peripheral, and is not consistently used for patients' in-hospital triage. As false-abnormal bHITs can lead to misdiagnosis/mistreatment of stroke patients, we recommend that bHIT applied by nonexperts should be reassessed by a neuro-otological expert or preferably quantitative vHIT in the ED.

Routine use of perfusion computed tomography for the detection of delayed cerebral ischemia in unconscious patients after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) is difficult to diagnose in unconscious patients, but it is essential for the prognosis. We analyzed the diagnostic value of routinely performed perfusion computed tomography (rPCT) to detect DCI-related hypoperfusion in this subgroup of patients. METHODS: Retrospective analysis of unconscious aSAH patients who underwent rPCT according to a predefined protocol. We exclusively analyzed PCT examinations in patients who were clinically and functionally asymptomatic with regard to transcranial Doppler ultrasound (TCD) and invasive neuromonitoring at the time of the PCT examination. The perfusion maps were quantitatively evaluated to detect DCI-related hypoperfusion. Possible clinical risk factors for the occurrence of DCI-related hypoperfusion in rPCT imaging were analyzed by multivariate analyses. RESULTS: One hundred thirty-six rPCTs were performed in 55 patients. New onset of DCI-related hypoperfusion was observed in 18% of rPCTs. The positive predictive value of rPCT to detect angiographic CVS was 0.80. Between examination days 6 and 10, the rate of DCI-related hypoperfusion was increased significantly (p < 0.05). After rPCT imaging with proof of DCI-related hypoperfusion, short-term follow-up showed secondary cerebral infarction (SCI) in 38%, compared with 5% for patients with normal perfusion on rPCT. The parameters "high risk phase (examination days 6-10)" and "new onset of DCI-related SCI" were significantly associated with the occurrence of DCI-related hypoperfusion in rPCT. CONCLUSIONS: In unconscious and asymptomatic aSAH patients, rPCT identifies DCI-related hypoperfusion in a relevant number of examinations. However, despite timely endovascular rescue therapy, a significant proportion of secondary infarction still occurs in this subgroup.

Resting-State Functional Connectivity in the Dorsal Attention Network Relates to Behavioral Performance in Spatial Attention Tasks and May Show Task-Related Adaptation.

Between-subject variability in cognitive performance has been related to inter-individual differences in functional brain networks. Targeting the dorsal attention network (DAN) we questioned (i) whether resting-state functional connectivity (FC) within the DAN can predict individual performance in spatial attention tasks and (ii) whether there is short-term adaptation of DAN-FC in response to task engagement. Twenty-seven participants first underwent resting-state fMRI (PRE run), they subsequently performed different tasks of spatial attention [including visual search (VS)] and immediately afterwards received another rs-fMRI (POST run). Intra- and inter-hemispheric FC between core hubs of the DAN, bilateral intraparietal sulcus (IPS) and frontal eye field (FEF), was analyzed and compared between PRE and POST. Furthermore, we investigated rs-fMRI-behavior correlations between the DAN-FC in PRE/POST and task performance parameters. The absolute DAN-FC did not change from PRE to POST. However, different significant rs-fMRI-behavior correlations were revealed for intra-/inter-hemispheric connections in the PRE and POST run. The stronger the FC between left FEF and IPS before task engagement, the better was the learning effect (improvement of reaction times) in VS (r = 0.521, p = 0.024). And the faster the VS (mean RT), the stronger was the FC between right FEF and IPS after task engagement (r = -0.502, p = 0.032). To conclude, DAN-FC relates to the individual performance in spatial attention tasks supporting the view of functional brain networks as priors for cognitive ability. Despite a high inter- and intra-individual stability of DAN-FC, the change of FC-behavior correlations after task performance possibly indicates task-related adaptation of the DAN, underlining that behavioral experiences may shape intrinsic brain activity. However, spontaneous state fluctuations of the DAN-FC over time cannot be fully ruled out as an alternative explanation.

What guides decision-making on intravenous thrombolysis in acute vestibular syndrome and suspected ischemic stroke in the posterior circulation?

Intravenous thrombolysis (IVT) is rarely performed in dizzy patients with acute vestibular syndrome (AVS) or acute imbalance (AIS) even if posterior circulation stroke (PCS) is suspected. Decision-making may be affected by uncertainties in discriminating central from peripheral vestibulopathy or concerns of IVT-related harm, particularly intracerebral hemorrhage (ICH), but related studies are missing. Using an in-house register of dizzy patients coming to the emergency room, we identified 29 AVS/AIS patients who presented within 4.5 h after onset, revealed clinical signs indicative of PCS (central oculomotor signs, mild focal abnormalities), and had non-contrast computed tomography (NCCT). Patients treated with IVT (n = 15) were compared to NoIVT patients (n = 14) with regard to clinical and imaging (including perfusion computed tomography, CTP) parameters, occurrence of ICH and short-term clinical outcome (NIHSS improvement; ability to walk independently). IVT and NoIVT patients did not differ in baseline characteristics, central oculomotor signs, or clinical outcome. IVT patients more often exhibited disabling vestibular symptoms (severe dizziness/vertigo, inability to stand unsupported) and focal abnormalities than NoIVT patients. There was no ICH in either group. CTP was performed in 0% of NoIVT versus 80% of IVT patients, seven of twelve revealing posterior circulation hypoperfusion. Comparison of initial hypoperfusion (CTP) and final stroke (NCCT) revealed IVT-related benefit (smaller lesion) in three of seven IVT patients. In AVS/AIS patients with suspected PCS, disabling vestibular symptoms, focal neurological deficits, and hypoperfusion on CTP seem to direct decision-making pro IVT. In our small cohort, there were no significant IVT-related clinical benefits, no IVT-related ICHs, and salvage of brain tissue in some patients.

Effects of perceptible and imperceptible galvanic vestibular stimulation on the postural control of patients with bilateral vestibulopathy.

Galvanic vestibular stimulation (GVS) has increasingly been used to stimulate the vestibular system in health and disease. While perceptible supra-threshold GVS destabilizes postural control in healthy control (HC) subjects, imperceptible 'noisy' GVS (nGVS) is reported to improve postural control in patients with bilateral vestibulopathy (BV) and therapeutic devices using nGVS are currently under development. We questioned (1) whether perceptible GVS destabilizes postural control of BV patients, expecting any effect to be smaller than in healthy subjects due to the patients' vestibulopathy, and (2) whether imperceptible nGVS improves postural control in comparison to an active sham stimulus in context-dependent conditions, hypothesizing that it fades off once postural control becomes more challenging with respect to its sensory (standing on foam) or cognitive (dual task) complexity. We tested postural responses of 30 BV patients to bimastoidal perceptible (lowGVS, highGVS) or imperceptible (nGVS, sham, noGVS) GVS in comparison to 24 age-matched HC. Perceptible GVS intensities were applied according to the participants' individual motion perception thresholds. Postural sway speed (PSS) was analyzed in a 4-factorial experimental design with the factors group (BV, HC), vision (eyes open/closed), condition (baseline, proprioception, cognition) and stimulation (noGVS, sham, nGVS, lowGVS, highGVS). With eyes open (EO), there were no group-related PSS differences in the baseline and cognition condition in response to either stimulations. With EO on foam and with eye closed (EC) in all conditions, patients showed larger PSS than HC, irrespective of the stimulation type. PSS differed with GVS intensities within each group but not between the groups. PSS under nGVS on EC was only smaller in patients when compared to perceptible GVS, but it was not different from noGVS or sham stimulation. Moreover, this nGVS effect was only found in the baseline but not in the more challenging dual task and foam condition. Almost half of the patients showed higher individual thresholds of motion perception of GVS compared to HC. Interestingly, this high-threshold subgroup showed significantly larger PSS with EC as compared to HC and the low-threshold patient subgroup, although both patient subgroups did not differ in vestibular parameters. We conclude, first, that perceptible GVS is able to destabilize BV patients similarly to HC subjects, suggesting sufficient vestibular afferent processing of GVS during vestibulo-spinal postural control. Second, the effect of the hitherto observed improved postural control by nGVS appears to be small during more demanding postural control conditions (foam, cognitive distraction) that are closer to the patients' everyday life, when active sham stimuli are used as control stimuli. These findings underline the meaning of active control conditions when the efficacy of nGVS is tested, e.g. in portable GVS devices in the attempt to improve postural control in BV patients. However, differential GVS effects on vestibulo-perceptional and vestibulo-spinal thresholds should be taken into account. Finally, our data suggest that individual motion perception thresholds for GVS could potentially serve as a predictor of postural control safety and falling risk in BV.

Risk of acute brain lesions in dizzy patients presenting to the emergency room: who needs imaging and who does not?

The usefulness of brain imaging studies in dizzy patients presenting to the emergency department (ED) is controversial. We aimed to assess the 'real-world' probability of ischemic stroke and other acute brain lesions (ABLs) in these patients to create an algorithm that helps decision-making on whether which and when brain imaging is needed. By reviewing medical records, we identified 610 patients presenting with dizziness, vertigo or imbalance to our university hospital's ED and receiving neurological workup. We collected timing/triggers of symptoms, ABCD2 score, focal neurological abnormalities, HINTS (head impulse, nystagmus, test-of-skew) and other central oculomotor signs. ABLs were extracted from CT/MRI reports. Uni-/multivariate logistic regression analyses investigated associations between clinical parameters and ABLs. Finally, the likelihood of ABLs was assessed for different clinically defined subgroups ('dizziness syndromes'). Early CT (day 1) was performed in 539 (88%) and delayed MR imaging (median: day 4) in 299 (49%) patients. ABLs (89% ischemic stroke) were revealed in 75 (24%) of 318 patients with adequate imaging (MRI or lesion-positive CT). The risk for ABLs increased with the presence of central oculomotor signs (odds ratio 2.8, 95% confidence interval 1.5-5.2) or focal abnormalities (OR 3.3, 95% CI 1.8-6.2). The likelihood of ABLs differed between dizziness syndromes, e.g., HINTS-negative acute vestibular syndrome: 0%, acute imbalance syndrome with ABCD2-score ≥ 4: 50%. We propose a clinical pathway, according to which patients with HINTS-negative acute vestibular syndrome should not receive brain imaging, whereas imaging is suggested in dizzy patients with acute imbalance, central oculomotor signs or focal abnormalities.

Unbalancing the Attentional Priority Map via Gaze-Contingent Displays Induces Neglect-Like Visual Exploration.

Selective spatial attention is a crucial cognitive process that guides us to the behaviorally relevant objects in a complex visual world by using exploratory eye movements. The spatial location of objects, their (bottom-up) saliency and (top-down) relevance is assumed to be encoded in one "attentional priority map" in the brain, using different egocentric (eye-, head- and trunk-centered) spatial reference frames. In patients with hemispatial neglect, this map is supposed to be imbalanced, leading to a spatially biased exploration of the visual environment. As a proof of concept, we altered the visual saliency (and thereby attentional priority) of objects in a naturalistic scene along a left-right spatial gradient and investigated whether this can induce a bias in the exploratory eye movements of healthy humans (n = 28; all right-handed; mean age: 23 years, range 19-48). We developed a computerized mask, using high-end "gaze-contingent display (GCD)" technology, that immediately and continuously reduced the saliency of objects on the left-"left" with respect to the head (body-centered) and the current position on the retina (eye-centered). In both experimental conditions, task-free viewing and goal-driven visual search, this modification induced a mild but significant bias in visual exploration similar to hemispatial neglect. Accordingly, global eye movement parameters changed (reduced number and increased duration of fixations) and the spatial distribution of fixations indicated an attentional bias towards the right (rightward shift of first orienting, fixations favoring the scene's outmost right over left). Our results support the concept of an attentional priority map in the brain as an interface between perception and behavior and as one pathophysiological ground of hemispatial neglect.

Effects of galvanic vestibular stimulation on resting state brain activity in patients with bilateral vestibulopathy.

We examined the effect of galvanic vestibular stimulation (GVS) on resting state brain activity using fMRI (rs-fMRI) in patients with bilateral vestibulopathy. Based on our previous findings, we hypothesized that GVS, which excites the vestibular nerve fibers, (a) increases functional connectivity in temporoparietal regions processing vestibular signals, and (b) alleviates abnormal visual-vestibular interaction. Rs-fMRI of 26 patients and 26 age-matched healthy control subjects was compared before and after GVS. The stimulation elicited a motion percept in all participants. Using different analyses (degree centrality, DC; fractional amplitude of low frequency fluctuations [fALFF] and seed-based functional connectivity, FC), group comparisons revealed smaller rs-fMRI in the right Rolandic operculum of patients. After GVS, rs-fMRI increased in the right Rolandic operculum in both groups and in the patients' cerebellar Crus 1 which was related to vestibular hypofunction. GVS elicited a fALFF increase in the visual cortex of patients that was inversely correlated with the patients' rating of perceived dizziness. After GVS, FC between parietoinsular cortex and higher visual areas increased in healthy controls but not in patients. In conclusion, short-term GVS is able to modulate rs-fMRI in healthy controls and BV patients. GVS elicits an increase of the reduced rs-fMRI in the patients' right Rolandic operculum, which may be an important contribution to restore the disturbed visual-vestibular interaction. The GVS-induced changes in the cerebellum and the visual cortex were associated with lower dizziness-related handicaps in patients, possibly reflecting beneficial neural plasticity that might subserve visual-vestibular compensation of deficient self-motion perception.