Acute stroke care : strategies for improving diagnostics

Stroke is one of the leading causes of death and disability, with a high incidence of over 11 million cases annually worldwide. Costs of treatment and rehabilitation, loss of work, and the hardships resulting from stroke are a major burden both at the individual and at the societal level. Importantly, stroke therapies need to be initiated early for them to be effective. Thrombolytic therapy and mechanical thrombectomy are early treatment options of ischemic stroke. In hemorrhagic stroke, optimization of hemodynamic and hemostatic parameters is central, and surgery is considered in a subset of patients. Efficient treatment of stroke requires early and precise recognition of stroke at all stages of the treatment chain. This includes identification of patients with suspected acute stroke by emergency medical dispatchers and emergency medical services staff, and precise admission diagnostics by the receiving on-call stroke team. Success requires grasping the complexity of stroke symptoms that depend on the brain areas affected, and the plethora of medical conditions that can mimic stroke. The Helsinki Ultra-acute Stroke Biomarker Study includes a cohort of 1015 patients transported to hospital due to suspected acute stroke, as candidates for revascularization therapies. Based on this cohort, this thesis work has explored new avenues to improve early stroke diagnostics in all stages of the treatment chain. In a detailed investigation into the identification of stroke by emergency medical dispatchers, we analyzed emergency phone calls with missed stroke identification. We also combined data on dispatch and EMS and hospital records to identify causes for missing stroke during emergency calls. Most importantly, we found that a patient’s fall at onset and patient confusion were strongly associated with missed identification. Regarding the Face Arm Speech Test (FAST), the most likely symptom to be misidentified was acute speech disturbance. Using prehospital blood sampling of stroke patients, and ultrasensitive measurement, we investigated the early dynamics of the plasma biomarkers glial fibrillary acidic protein (GFAP) and total tau. Utilizing serial sampling, we demonstrate for the first time that monitoring the early release rate of GFAP can improve the diagnostic performance of this biomarker for early differentiation between ischemic and hemorrhagic stroke. In our analysis of early GFAP levels, we were able to differentiate with high accuracy two-thirds of all patients with acute cerebral ischemia from those with hemorrhagic stroke, supporting further investigation of this biomarker as a promising point-of-care tool for prehospital stroke diagnostics. We performed a detailed review of the admission diagnostics of our cohort of 1015 patients to explore causes and predictors of admission misdiagnosis. We then investigated the consequences of misdiagnosis on outcomes. We demonstrate in this large cohort that the highly optimized and rapid admission evaluation in our hospital district (door-to-needle times below 20 minutes) did not compromise the accuracy and safety of admission evaluation. In addition, we discovered targets for improving future diagnostics. Finally, our detailed neuropathological investigation of a case of cerebral amyloid angiopathy (CAA) -related hemorrhage after stroke thrombolysis provided unique tissue-level evidence for this common vasculopathy as a notable risk factor for intracranial hemorrhagic complications in the setting of stroke. These findings support research to improve the diagnostics of CAA, and the prediction of hemorrhagic complications associated with stroke thrombolysis. In conclusion, these proposed targets and strategies will aid in the future improvement and development of this highly important field of diagnostics. Our proof-of-concept discoveries on early GFAP kinetics help guide further study into this diagnostic approach just as highly sensitive point-of-care GFAP measurement instruments are becoming available. Finally, our results support the safety of worldwide efforts to optimize emergency department door-to- needle times when care is taken to ensure sufficient expertise is in place, highlighting the role of the on-call vascular neurologist as a central diagnostic asset.