ABSTRACT
Background: Acute dizziness, vertigo, and imbalance are frequent and difficult to interpret symptoms in the emergency department (ED). Primary care hospitals often lack the expertise to identify stroke or TIA as underlying causes. A telemedical approach based on telestroke networks may offer adequate diagnostics and treatment. Aim: The aim of this study is to evaluate the accuracy of a novel ED algorithm in differentiating between peripheral and central vestibular causes. Methods: Within the Telemedical Project for Integrative Stroke Care (TEMPiS), a telemedical application including a videooculography (VOG) system was introduced in 2018 in 19 primary care spoke hospitals. An ED triage algorithm was established for all patients with acute dizziness, vertigo, or imbalance of unknown cause (ADVIUC) as a leading complaint. In three predefined months, all ADVIUC cases were prospectively registered and discharge letters analyzed. Accuracy of the ED triage algorithm in differentiation between central and peripheral vestibular cases was analyzed by comparison of ED diagnoses to final discharge diagnoses. The rate of missed strokes was calculated in relation to all cases with a suitable brain imaging. Acceptance of teleconsultants and physicians in spoke hospitals was assessed by surveys. Results: A total number of 388 ADVIUC cases were collected, with a median of 12 cases per months and hospital (IQR 8-14.5). The most frequent hospital discharge diagnoses are vestibular neuritis (22%), stroke/TIA (18%), benign paroxysmal positioning vertigo (18%), and dizziness due to internal medicine causes (15%). Detection of a central vestibular cause by the ED triage algorithm has a high sensitivity (98.6%), albeit poor specificity (45.9%). One stroke out of 32 verified by brain scan was missed (3.1%). User satisfaction, helpfulness of the project, improvement of care, personal competence, and satisfaction about handling of the VOG systems were rated consistently positive. Discussion: The concept shows good acceptance for a telemedical and network-based approach to manage ADVIUC cases in the ED of primary care hospitals. Identification of stroke cases is accurate, while specificity needs further improvement. The concept could be a major step toward a broadly available state of the art diagnostics and therapy for patients with ADVIUC in primary care hospitals.
ABSTRACT
BACKGROUND: Acute dizziness, vertigo and imbalance are common symptoms in emergency departments. Stroke needs to be distinguished from vestibular diseases. A battery of three clinical bedside tests (HINTS: Head Impulse Test, Nystagmus, Test of Skew) has been shown to detect stroke as underlying cause with high reliability, but implementation is challenging in primary care hospitals. Aim of this study is to prove the feasibility of a telemedical HINTS examination via a remotely controlled videooculography (VOG) system. METHODS: The existing video system of our telestroke network TEMPiS (Telemedic Project for Integrative Stroke Care) was expanded through a VOG system. This feature enables the remote teleneurologist to assess a telemedical HINTS examination based on inspection of eye movements and quantitative video head impulse test (vHIT) evaluation. ED doctors in 11 spoke hospitals were trained in performing vHIT, nystagmus detection and alternating cover test. Patients with first time acute dizziness, vertigo or imbalance, whether ongoing or resolved, presented to the teleneurologist were included in the analysis, as long as no focal neurological deficit according to the standard teleneurological examination or obvious internal medicine cause was present and a fully trained team was available. Primary outcome was defined as the feasibility of the telemedical HINTS examination. RESULTS: From 01.06.2019 to 31.03.2020, 81 consecutive patients were included. In 72 (88.9%) cases the telemedical HINTS examination was performed. The complete telemedical HINTS examination was feasible in 46 cases (63.9%), nystagmus detection in all cases (100%) and alternating covert test in 70 cases (97.2%). The vHIT was recorded and interpretable in 47 cases (65.3%). Results of the examination with the VOG system yielded clear results in 21 cases (45.7%) with 14 central and 7 peripheral lesions. The main reason for incomplete examination was the insufficient generation of head impulses. CONCLUSION: In our analysis the telemedical HINTS examination within a telestroke network was feasible in two thirds of the patients. This offers the opportunity to improve specific diagnostics and therapy for patients with acute dizziness and vertigo even in primary care hospitals. Improved training for spoke hospital staff is needed to further increase the feasibility of vHIT.
ABSTRACT
The interaction between the stromal cell-derived factor-1 alpha (SDF-1α, CXCL12) and its chemokine receptor CXCR4 has been reported to regulate stem cell migration, mobilization and homing. The CXCR4 antagonist plerixafor is highly efficient in mobilizing hematopoietic progenitor cells (HPCs). However, the precise regulatory mechanisms governing the CXCR4/SDF-1α axis between the bone marrow niche and HPCs remain unclear. In this study, we quantify the impact of plerixafor on the interaction between human bone marrow derived mesenchymal stromal cells (MSCs) and human CD34+ HPCs. An assessment of SDF-1α levels in the supernatant of MSC cultures revealed that exposure to plerixafor led to a transient increase but had no long-term effect. In Transwell experiments, we observed that the addition of SDF-1α significantly stimulated HPC migration; this stimulation was almost completely antagonized by the addition of plerixafor, confirming the direct impact of the CXCR4/SDF-1α interaction on the migration capacity of HPCs. We also developed a new microstructural niche model to determine the chemotactic sensitivity of HPCs. Time-lapse microscopy demonstrated that HPCs migrated actively along an SDF-1α gradient within the microchannels and the quantitative assessment of the required minimum gradient initiating this chemotaxis revealed a surprisingly high sensitivity of HPCs. These data demonstrate the fine-tuned balance of the CXCR4/SDF-1α axis and the synergistic effects of plerixafor on HPCs and MSCs, which most likely represent the key mechanisms for the consecutive mobilization of HPCs from the bone marrow niche into the circulating blood.
