Training novice users to assess stroke aetiology in remote settings using transcranial ultrasound: pilot study.

INTRODUCTION: Emergency care delivery to patients in remote and rural areas is limited by diagnostic restrictions and long transport times to major centres of care. People with suspected acute stroke living long distances from a hospital are unlikely to receive time-critical reperfusion therapy for these reasons. Basic brain imaging assessing blood flow in the major intracranial arteries could facilitate such care in remote settings. A 3-hour training package for novice transcranial ultrasound users has been piloted on a small group of volunteers to investigate whether they could acquire transcranial ultrasound images and video clips to potentially allow remote interpretation and optimise pre-hospital management of acute stroke. METHODS: A pilot training project was set up in a university setting in Inverness, Scotland. Volunteer clinicians and students of nursing or medicine with no practical experience in transcranial ultrasound were recruited. Participants received three 1-hour training sessions combining theoretical aspects and hands-on practice on healthy volunteers provided by a qualified neurologist with more than 2 years of experience in transcranial ultrasound. Transcranial greyscale and colour-coded duplex sonography was performed to visualise midline structures and major intracranial vessels, and to measure blood flow velocity in the middle cerebral artery, followed by an unsupervised assessment. Qualitative analysis of the anonymised feedback from participants on the training experience and its potential application was also performed. RESULTS: A total of 11 volunteers were recruited in the current pilot study. The average time to complete transcranial ultrasound assessment was approximately 40 minutes. The brain midline and cerebral peduncles were correctly labelled by 64% (7/11) and 91% (10/11) of volunteers, respectively. Participants demonstrated a good performance in detecting major intracranial vessels. The correct labelling rate for the middle cerebral artery was 73% (8/11), and 64% (7/11) for the anterior and posterior cerebral arteries. There was agreement between the trainer and the participants on rating the quality of scans as assessed using a visual analogue scale. All participants gave positive feedback on the provided training and time allocated for each session. Generally, volunteers thought that operating the ultrasound machine and the probe simultaneously was difficult. It was also suggested that further follow-up training, with possible supervision, would be useful to retain the acquired skills. CONCLUSIONS: Transcranial ultrasound scans of a quality to allow expert interpretation can be acquired by inexperienced transcranial ultrasound operators after receiving a brief training. This could potentially be used by medical staff working in remote and rural areas to facilitate acute care for stroke patients, but further work with a larger sample is needed.

The use of transcranial ultrasound and clinical assessment to diagnose ischaemic stroke due to large vessel occlusion in remote and rural areas.

Rapid endovascular thrombectomy, which can only be delivered in specialist centres, is the most effective treatment for acute ischaemic stroke due to large vessel occlusion (LVO). Pre-hospital selection of these patients is challenging, especially in remote and rural areas due to long transport times and limited access to specialist clinicians and diagnostic facilities. We investigated whether combined transcranial ultrasound and clinical assessment ("TUCA" model) could accurately triage these patients and improve access to thrombectomy. We recruited consecutive patients within 72 hours of suspected stroke, and performed non-contrast transcranial colour-coded ultrasonography within 24 hours of brain computed tomography. We retrospectively collected clinical information, and used hospital discharge diagnosis as the "gold standard". We used binary regression for diagnosis of haemorrhagic stroke, and an ordinal regression model for acute ischaemic stroke with probable LVO, without LVO, transient ischaemic attacks (TIA) and stroke mimics. We calculated sensitivity, specificity, positive and negative predictive values and performed a sensitivity analysis. We recruited 107 patients with suspected stroke from July 2017 to December 2019 at two study sites: 13/107 (12%) with probable LVO, 50/107 (47%) with acute ischaemic stroke without LVO, 18/107 (17%) with haemorrhagic stroke, and 26/107 (24%) with stroke mimics or TIA. The model identified 55% of cases with probable LVO who would have correctly been selected for thrombectomy and 97% of cases who would not have required this treatment (sensitivity 55%, specificity 97%, positive and negative predictive values 75% and 93%, respectively). Diagnostic accuracy of the proposed model was superior to the clinical assessment alone. These data suggest that our model might be a useful tool to identify pre-hospital patients requiring mechanical thrombectomy, however a larger sample is required with the use of CT angiogram as a reference test.

Diagnostic value of transcranial ultrasonography for selecting subjects with large vessel occlusion: a systematic review.

INTRODUCTION: A number of pre-hospital clinical assessment tools have been developed to triage subjects with acute stroke due to large vessel occlusion (LVO) to a specialised endovascular centre, but their false negative rates remain high leading to inappropriate and costly emergency transfers. Transcranial ultrasonography may represent a valuable pre-hospital tool for selecting patients with LVO who could benefit from rapid transfer to a dedicated centre. METHODS: Diagnostic accuracy of transcranial ultrasonography in acute stroke was subjected to systematic review. Medline, Embase, PubMed, Scopus, and The Cochrane Library were searched. Published articles reporting diagnostic accuracy of transcranial ultrasonography in comparison to a reference imaging method were selected. Studies reporting estimates of diagnostic accuracy were included in the meta-analysis. RESULTS: Twenty-seven published articles were selected for the systematic review. Transcranial Doppler findings, such as absent or diminished blood flow signal in a major cerebral artery and asymmetry index ≥ 21% were shown to be suggestive of LVO. It demonstrated sensitivity ranging from 68 to 100% and specificity of 78-99% for detecting acute steno-occlusive lesions. Area under the receiver operating characteristics curve was 0.91. Transcranial ultrasonography can also detect haemorrhagic foci, however, its application is largely restricted by lesion location. CONCLUSIONS: Transcranial ultrasonography might potentially be used for the selection of subjects with acute LVO, to help streamline patient care and allow direct transfer to specialised endovascular centres. It can also assist in detecting haemorrhagic lesions in some cases, however, its applicability here is largely restricted. Additional research should optimize the scanning technique. Further work is required to demonstrate whether this diagnostic approach, possibly combined with clinical assessment, could be used at the pre-hospital stage to justify direct transfer to a regional thrombectomy centre in suitable cases.

Diagnostic accuracy of clinical tools for assessment of acute stroke: a systematic review.

INTRODUCTION: Recanalisation therapy in acute ischaemic stroke is highly time-sensitive, and requires early identification of eligible patients to ensure better outcomes. Thus, a number of clinical assessment tools have been developed and this review examines their diagnostic capabilities. METHODS: Diagnostic performance of currently available clinical tools for identification of acute ischaemic and haemorrhagic strokes and stroke mimicking conditions was reviewed. A systematic search of the literature published in 2015-2018 was conducted using PubMed, EMBASE, Scopus and The Cochrane Library. Prehospital and in-hospital studies with a minimum sample size of 300 patients reporting diagnostic accuracy were selected. RESULTS: Twenty-five articles were included. Cortical signs (gaze deviation, aphasia and neglect) were shown to be significant indicators of large vessel occlusion (LVO). Sensitivity values for selecting subjects with LVO ranged from 23 to 99% whereas specificity was 24 to 97%. Clinical tools, such as FAST-ED, NIHSS, and RACE incorporating cortical signs as well as motor dysfunction demonstrated the best diagnostic accuracy. Tools for identification of stroke mimics showed sensitivity varying from 44 to 91%, and specificity of 27 to 98% with the best diagnostic performance demonstrated by FABS (90% sensitivity, 91% specificity). Hypertension and younger age predicted intracerebral haemorrhage whereas history of atrial fibrillation and diabetes were associated with ischaemia. There was a variation in approach used to establish the definitive diagnosis. Blinding of the index test assessment was not specified in about 50% of included studies. CONCLUSIONS: A wide range of clinical assessment tools for selecting subjects with acute stroke has been developed in recent years. Assessment of both cortical and motor function using RACE, FAST-ED and NIHSS showed the best diagnostic accuracy values for selecting subjects with LVO. There were limited data on clinical tools that can be used to differentiate between acute ischaemia and haemorrhage. Diagnostic accuracy appeared to be modest for distinguishing between acute stroke and stroke mimics with optimal diagnostic performance demonstrated by the FABS tool. Further prehospital research is required to improve the diagnostic utility of clinical assessments with possible application of a two-step clinical assessment or involvement of simple brain imaging, such as transcranial ultrasonography.

Expression of DJ-1 in Neurodegenerative Disorders.

In 2003, autosomal recessive loss-of-function mutations were identified in PARK7 gene that caused early-onset Parkinson's disease (PD). The PARK7 gene encodes a conserved protein termed DJ-1. DJ-1 is a ubiquitous protein, and within the brain, it is present in the nucleus and cytoplasm of both neuronal and glial cells. DJ-1 is a multifunctional protein, and numerous studies have ascribed various roles, including antioxidative properties, chaperone function, protease activities, mitochondrial functions and regulation of transcription to the protein. The DJ-1 protein undergoes oxidation and post-translational modifications that are important for its function. Not only is DJ-1 linked to familial PD, but it is also associated with the pathogenic mechanisms of sporadic PD and other neurodegenerative disorders where oxidative stress is implicated. In this chapter we provide an overview on the expression of DJ-1 mRNA and protein in different neurodegenerative disorders and discuss some of its main functions together with DJ-1's potential for neuroprotection.