Lateropulsion in Right-Sided Stroke: Brain Anatomical Correlates of Severity and Duration.

BACKGROUND AND PURPOSE: Lateropulsion (LP) is a profound disorder of postural control that has a significant impact on neurorehabilitation. Knowledge of relevant brain areas could guide decisions on appropriate intervention methods. Although LP severity and duration are highly variable in individuals with LP, imaging studies on LP have not sufficiently considered these aspects. The aim of this study was to investigate the lesion location in individuals after stroke and the correlation with LP duration and severity. METHODS: A retrospective case-control study using voxel lesion symptom mapping (VLSM) in 74 individuals with right-sided brain lesion (49 with and 25 without LP) was performed to analyze the correlation between lesion location and LP severity. Duration was investigated in a subsample of 22 individuals with LP. LP was diagnosed by means of the Scale for Contraversive Pushing. RESULTS: Individuals with LP showed significantly larger lesion sizes compared with the individuals with no LP. VLSM analysis of LP severity did not reveal statistically significant results. VLSM analysis showed a statistically significant association with longer LP duration for the inferior frontal gyrus, the hippocampus, the inferior parietal gyrus, the supramarginal gyrus, the angular gyrus, the temporal cortex, the sagittal stratum, and the superior longitudinal fasciculus. DISCUSSION AND CONCLUSION: LP-relevant areas are located in the multisensory network. Areas of the frontoparietal network, which are related to spatial cognition, memory, and attention, were found to be relevant for duration and severity. The findings, especially those regarding duration involving the middle temporal cortex, could explain the better intervention outcomes for methods based more on implicit than on explicit knowledge of verticality.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A433 ).

Konzepte der Sturzrisikoabschätzung bei neurogeriatrischen Patienten.

Neurogeriatric patients are prone to falls. Particularly, patients with central neurological diseases (e. g., Parkinson's disease, cerebellar disorders) fall more often and more severe compared to patients with peripheral neurological disorders (e. g., peripheral neuropathy, bilateral vestibulopathy). Falls can lead to severe injuries with prolonged hospital treatment with subsequently impaired mobility, reduced quality of life and fear of falling. This article depicts general, clinical and mobility-based fall risk factors in neurogeriatric patients and gives an overview how to identify patients with a high risk of falling. Furthermore, a multimodal fall risk assessment is illustrated, which expands the diagnostic approach utilising clinical, instrument-based and mobile motion analysis.

Quantification of pathological gait parameter thresholds of idiopathic normal pressure hydrocephalus patients in clinical gait analysis.

The aim of the study was to distinguish the hypokinetic gait disorder in idiopathic normal pressure hydrocephalus (NPH) patients from the gait decline in the elderly population by quantifying pathological gait parameter thresholds utilizing a multiple condition gait assessment. 55 NPH patients and 55 age-matched healthy subjects underwent a standardized gait assessment with eight gait conditions. Spatiotemporal gait parameters were assessed through a pressure-sensitive carpet. Statistical analysis consisted of a binary logistic regression (BLR) model, logistic curve-fit evaluated by a Chi-square goodness-of-fit-test, receiver operating characteristic models with area under the curves (AUC), and inverse BLR. Most discriminative gait parameter thresholds were observed in pace, gait cycle, and support gait domains. The most distinct gait conditions were preferred walking speed and semantic dual task. During preferred walking speed, the most significant gait parameter thresholds were stride length ≤ 1.02 m (sensitivity 0.93/specificity 0.91/AUC 0.96), gait velocity ≤ 0.83 m/s (0.80/0.91/0.93), double support phase ≥ 27.0% (0.96/0.76/0.91), and stride length coefficient of variation ≥ 3.4% (0.93/0.72/0.90). In conclusion, the hypokinetic gait disorder in NPH can be quantitatively differentiated from gait patterns of the elderly population. In future studies, this approach may be useful to differentiate clinical entities with similar gait disorders utilizing instrumented gait analysis procedures.

Determinants of functioning and health-related quality of life after vestibular stroke.

Background: Stroke accounts for 5-10% of all presentations with acute vertigo and dizziness. The objective of the current study was to examine determinants of long-term functioning and health-related quality of life (HRQoL) in a patient cohort with vestibular stroke. Methods: Thirty-six patients (mean age: 66.1 years, 39% female) with an MRI-proven vestibular stroke were followed prospectively (mean time: 30.2 months) in the context of the EMVERT (EMergency VERTigo) cohort study at the Ludwig-Maximilians Universität, Munich. The following scores were obtained once in the acute stage (<24 h of symptom onset) and once during long-term follow-up (preferably >1 year after stroke): European Quality of Life Scale-five dimensions-five levels questionnaire (EQ-5D-5L) and Visual Analog Scale (EQ-VAS) for HRQoL, Dizziness Handicap Inventory (DHI) for symptom severity, and modified Rankin Scale (mRS) for general functioning and disability. Anxiety state and trait were evaluated by STAI-S/STAI-T, and depression was evaluated by the Patient Health Questionnaire-9 (PHQ-9). Voxel-based lesion mapping was applied in normalized MRIs to analyze stroke volume and localization. Multiple linear regression models were calculated to determine predictors of functional outcome (DHI, EQ-VAS at follow-up). Results: Mean DHI scores improved significantly from 45.0 in the acute stage to 18.1 at follow-up (p < 0.001), and mean mRS improved from 2.1 to 1.1 (p < 0.001). Mean HRQoL (EQ-5D-5L index/EQ-VAS) changed from 0.69/58.8 to 0.83/65.2 (p = 0.01/p = 0.11). Multiple linear regression models identified higher scores of STAI-T and DHI at the time of acute vestibular stroke and larger stroke volume as significant predictors for higher DHI at follow-up assessment. The effect of STAI-T was additionally enhanced in women. There was a significant effect of patient age on EQ-VAS, but not DHI during follow-up. Conclusion: The average functional outcome of strokes with the chief complaint of vertigo and dizziness is favorable. The most relevant predictors for individual outcomes are the personal anxiety trait (especially in combination with the female sex), the initial symptom intensity, and lesion volume. These factors should be considered for therapeutic decisions both in the acute stage of stroke and during subsequent rehabilitation.

[Options for the symptomatic treatment of chronic neurological gait disorders]. / Symptomatische Behandlungsoptionen chronischer, neurologischer Gangstörungen.

Gait and mobility impairments are common and relevant in patients with chronic neurological disorders. It reduces the health-related quality of life and induces falls with morbidity. Symptomatic treatment options are therefore necessary in order to improve the health status of patients with neurological disorders.By means of a selective literature research focusing on studies with specific gait-related outcome measures. We discuss the differential treatment options for (1) hypokinetic gait disorders (Parkinson´s disease, Normal pressure hydrocephalus, vascular encephalopathy), (2) gait unsteadiness with ataxia (sensory and cerebellar ataxia), and (3) gait with spasticity and paresis (due to multiple sclerosis). Therapeutical options for the symptomatic treatment of gait disorders comprise non-pharmacological and pharmacological approaches. Both address the functional domains of "locomotion", "postural control", "modulation" and "adaptability" of gait.Pharmacological options are orientated to pathophysiology of the underlying diseases. Supportive physiotherapeutic interventions offer broader and unspecific options for treatment. Clinical conditions that specifically disturb the execution of locomotion or gait can also be addressed by the provision of physical therapy or supportive devices.Effective options for the symptomatic treatment of patients with neurological gait disorders are available. Applications of options addressing the pathophysiology of the underlying disease, a functional domain-based exercise and physiotherapy program, and the provision of walking aides for specific symptoms that further worsen gait performance can be recommended.

The gait disorder in primary orthostatic tremor.

OBJECTIVE: To uncover possible impairments of walking and dynamic postural stability in patients with primary orthostatic tremor (OT). METHODS: Spatiotemporal gait characteristics were quantified in 18 patients with primary OT (mean age 70.5 ± 5.9 years, 10 females) and 18 age-matched healthy controls. One-third of patients reported disease-related fall events. Walking performance was assessed on a pressure-sensitive carpet under seven conditions: walking at preferred, slow, and maximal speed, with head reclination or eyes closed, and while performing a cognitive or motor dual-task paradigm. RESULTS: Patients exhibited a significant gait impairment characterized by a broadened base of support (p = 0.018) with increased spatiotemporal gait variability (p = 0.010). Walking speed was moderately reduced (p = 0.026) with shortened stride length (p = 0.001) and increased periods of double support (p = 0.001). Gait dysfunction became more pronounced during slow walking (p < 0.001); this was not present during fast walking. Walking with eyes closed aggravated gait disability as did walking during cognitive dual task (p < 0.001). CONCLUSION: OT is associated with a specific gait disorder with a staggering wide-based walking pattern indicative of a sensory and/or a cerebellar ataxic gait. The aggravation of gait instability during visual withdrawal and the normalization of walking with faster speeds further suggest a proprioceptive or vestibulo-cerebellar deficit as the primary source of gait disturbance in OT. In addition, the gait decline during cognitive dual task may imply cognitive processing deficits. In the end, OT is presumably a complex network disorder resulting in a specific spino-cerebello-frontocortical gait disorder that goes beyond mere tremor networks.

A Prospective Analysis of Lesion-Symptom Relationships in Acute Vestibular and Ocular Motor Stroke.

Background: Diagnosing stroke as a cause of acute vertigo, dizziness, or double vision remains a challenge, because symptom characteristics can be variable. The purpose of this study was to prospectively investigate lesion-symptom relationships in patients with acute vestibular or ocular motor stroke. Methods: Three hundred and fifty one patients with acute and isolated vestibular or ocular motor symptoms of unclear etiology were enrolled in the EMVERT lesion trial. Symptom quality was assessed by the chief complaint (vertigo, dizziness, double vision), symptom intensity by the visual analog scale, functional impairment by EQ-5D-5L, and symptom duration by daily rating. Acute vestibular and ocular motor signs were registered by videooculography. A standardized MRI (DWI-/FLAIR-/T2-/T2*-/3D-T1-weighted sequences) was recorded within 7 days of symptom onset. MRIs with DWI lesions were further processed for voxel-based lesion-symptom mapping (VLSM). Results: In 47 patients, MRI depicted an acute unilateral stroke (13.4%). The chief complaints were dizziness (42.5%), vertigo (40.4%) and double vision (17.0%). Lesions in patients with vertigo or dizziness showed a large overlap in the cerebellar hemisphere. VLSM indicated that strokes in the medial cerebellar layers 7b, 8, 9 were associated with vertigo, strokes in the lateral cerebellar layer 8, crus 1, 2 with dizziness, and pontomesencephalic strokes with double vision. Symptom intensity and duration varied largely between patients. Higher symptom intensity and longer duration were associated with medial cerebellar lesions. Hemispheric lesions of the cortex were rare and presented with milder symptoms of shorter duration. Conclusions: Prospective evaluation of patients with acute vestibular or ocular motor stroke revealed that symptom quality, intensity and duration were not suited to differentiating peripheral from central etiologies. Lesions in the lateral cerebellum, thalamus, or cortex presented with unspecific, mild and transient symptoms prone to being misdiagnosed.

Modern machine-learning can support diagnostic differentiation of central and peripheral acute vestibular disorders.

BACKGROUND: Diagnostic classification of central vs. peripheral etiologies in acute vestibular disorders remains a challenge in the emergency setting. Novel machine-learning methods may help to support diagnostic decisions. In the current study, we tested the performance of standard and machine-learning approaches in the classification of consecutive patients with acute central or peripheral vestibular disorders. METHODS: 40 Patients with vestibular stroke (19 with and 21 without acute vestibular syndrome (AVS), defined by the presence of spontaneous nystagmus) and 68 patients with peripheral AVS due to vestibular neuritis were recruited in the emergency department, in the context of the prospective EMVERT trial (EMergency VERTigo). All patients received a standardized neuro-otological examination including videooculography and posturography in the acute symptomatic stage and an MRI within 7 days after symptom onset. Diagnostic performance of state-of-the-art scores, such as HINTS (Head Impulse, gaze-evoked Nystagmus, Test of Skew) and ABCD2 (Age, Blood, Clinical features, Duration, Diabetes), for the differentiation of vestibular stroke vs. peripheral AVS was compared to various machine-learning approaches: (i) linear logistic regression (LR), (ii) non-linear random forest (RF), (iii) artificial neural network, and (iv) geometric deep learning (Single/MultiGMC). A prospective classification was simulated by ten-fold cross-validation. We analyzed whether machine-estimated feature importances correlate with clinical experience. RESULTS: Machine-learning methods (e.g., MultiGMC) outperform univariate scores, such as HINTS or ABCD2, for differentiation of all vestibular strokes vs. peripheral AVS (MultiGMC area-under-the-curve (AUC): 0.96 vs. HINTS/ABCD2 AUC: 0.71/0.58). HINTS performed similarly to MultiGMC for vestibular stroke with AVS (AUC: 0.86), but more poorly for vestibular stroke without AVS (AUC: 0.54). Machine-learning models learn to put different weights on particular features, each of which is relevant from a clinical viewpoint. Established non-linear machine-learning methods like RF and linear methods like LR are less powerful classification models (AUC: 0.89 vs. 0.62). CONCLUSIONS: Established clinical scores (such as HINTS) provide a valuable baseline assessment for stroke detection in acute vestibular syndromes. In addition, machine-learning methods may have the potential to increase sensitivity and selectivity in the establishment of a correct diagnosis.

Key gait findings for diagnosing three syndromic categories of dynamic instability in patients with balance disorders.

With the emergence of affordable, clinical-orientated gait analysis techniques, clinicians may benefit from a general understanding of quantitative gait analysis procedures and their clinical applications. This article provides an overview of the potential of a quantitative gait analysis for decision support in three clinically relevant scenarios of early stage gait disorders: scenario I: gait ataxia and unsteadiness; scenario II: hypokinesia and slow gait; scenario III: apparently normal gait with a specific fall tendency in complex mobility situations. In a first part, we justify the advantages of standardized data collection and analysis procedures including data normalization and dimensionality reduction techniques that facilitate clinical interpretability of instrument-based gait profiles. We then outline typical patterns of pathological gait and their modulation during different walking conditions (variation of speed, sensory perturbation, and dual tasking) and highlight key aspects that are particularly helpful to support and guide clinical decision-making.

Clinical and automated gait analysis in patients with vestibular, cerebellar, and functional gait disorders: perspectives and limitations.

This article outlines recent developments in the clinical and automated assessment of neurological gait disorders. With a primary focus on vestibular, cerebellar, and functional gait disorders, we discuss how instrumented gait examination may assist clinical decision making in these disorders with respect to the initial differential diagnosis and prognosis as well as the objective monitoring of disease progression and therapeutic interventions. We delineate strategies for data handling and analysis of quantitative gait examinations that can facilitate the clinical characterization and interpretation of walking impairments. These strategies include data normalization and dimensionality reduction procedures. We further emphasize the value of a comprehensive, standardized gait assessment protocol. Accordingly, the examination of walking conditions that challenge patients with respect to their biomechanical, sensory, or cognitive resources are particularly helpful to disclose and characterize the causes underlying their gait impairment. Finally, we provide a perspective on the emerging implementation of pattern recognition approaches within the framework of clinical management of gait disorders and discuss their potential to assist clinical decision making with respect to the differential diagnosis and the prognosis of fall risk in individual patients.

Non-invasive vagus nerve stimulation significantly improves quality of life in patients with persistent postural-perceptual dizziness.

Persistent postural-perceptual dizziness (PPPD) is one of the most common causes of chronic vestibular disorders, with a substantial portion of the affected patients showing no significant improvement to standard therapies (i.e., pharmacotherapy, behavioral psychotherapy). Patients with PPPD have been shown to have a significant comorbidity with anxiety disorders and depression. Further, these patients show an activation of the autonomic nervous system resulting in symptoms such as nausea, increase of heart rate, and sweating. Based on the comorbidities and the activation of the autonomic nervous system, we addressed the question whether non-invasive vagus nerve stimulation (nVNS) might be a treatment option for these patients. In this prospective study we, therefore, applied nVNS to patients with treatment-refractory (to the standard therapy) PPPD. The stimulation protocol was similar to previous studies in patients with cluster headache and consisted of stimulations during exacerbations or acute attacks of vertigo, but also with regular stimulations in the morning and evening as prophylactic treatment. Results showed that non-invasive vagus nerve stimulation significantly improved quality of life, as measured by the EQ-5D-3L (p = 0.04), and depression, as measured by the HADS-D (p = 0.002), in the nVNS group, but not in the age- and sex-matched group with standard of care (SOC) treatment. Moreover, in the pooled analysis (additional 4 weeks of stimulation also in the SOC-group), less severe vertigo attacks/exacerbations (p = 0.04), a decrease in total postural sway path as measured by posturography (p = 0.02), as well as tendentious less anxiety (p = 0.08), occurred after stimulation. These data imply that short term nVNS is a safe and promising treatment option in patients with otherwise refractory PPPD.

Protocol for a prospective interventional trial to develop a diagnostic index test for stroke as a cause of vertigo, dizziness and imbalance in the emergency room (EMVERT study).

INTRODUCTION: Identifying stroke as a cause of acute vertigo, dizziness and imbalance in the emergency room is still a clinical challenge. Many patients are admitted to stroke units, but only a minority will have strokes. This imposes a heavy financial burden on the healthcare system. The aim of this study is to develop a diagnostic index test to identify patients with a high risk of having a stroke as the cause of acute vertigo and imbalance. METHODS AND ANALYSIS: Patients with acute onset of vertigo, dizziness, postural imbalance or double vision within the last 24 hours lasting for at least 10 min are eligible to be included in the study. Patients with clinically proven peripheral or central aetiology will be excluded. In the emergency room, all enrolled patients will undergo standardised neuro-ophthalmological/physiological testing (including video-oculography, mobile posturography, measurement of subjective visual vertical) (EMVERT block 1). Within 10 days, standardised MRI will be performed as a reference test to identify stroke (EMVERT block 2). Data from EMVERT block 2 will be compared with results from block 1 in order to devise a diagnostic index test with a high specificity and sensitivity to predict the risk of stroke in the emergency room. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the University of Munich and will be conducted according to the Guideline for Good Clinical Practice, the Federal Data Protecting Act and the Helsinki Declaration of the World Medical Association in its recent version. Study results are expected to be published in international peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: German Clinical Trial Register: DRKS00008992; Universal trial number: U1111-1172-8719); pre-results.

Gait ataxia in humans: vestibular and cerebellar control of dynamic stability.

During human locomotion, vestibular feedback control is fundamental for maintaining dynamic stability and adapting the gait pattern to external circumstances. Within the supraspinal locomotor network, the cerebellum represents the key site for the integration of vestibular feedback information. The cerebellum is further important for the fine-tuning and coordination of limb movements during walking. The aim of this review article is to highlight the shared structural and functional sensorimotor principles in vestibular and cerebellar locomotion control. Vestibular feedback for the maintenance of dynamic stability is integrated into the locomotor pattern via midline, caudal cerebellar structures (vermis, flocculonodular lobe). Hemispheric regions of the cerebellum facilitate feed-forward control of multi-joint coordination and higher locomotor functions. Characteristic features of the gait disorder in patients with vestibular deficits or cerebellar ataxia are increased levels of spatiotemporal gait variability in the fore-aft and the medio-lateral gait dimension. In the fore-aft dimension, pathologic increases of gait fluctuations critically depend on the locomotion speed and predominantly manifest during slow walking velocities. This feature is associated with an increased risk of falls in both patients with vestibular hypofunction as well as patients with cerebellar ataxia. Pharmacological approaches for the treatment of vestibular or cerebellar gait ataxia are currently not available. However, new promising options are currently tested in randomized, controlled trials (fampridine/FACEG; acetyl-DL-leucine/ALCAT).