OBJECTIVE: To validate our previously developed 16 plasma-protein biomarker panel to differentiate between transient ischaemic attack (TIA) and non-cerebrovascular emergency department (ED) patients.
...METHOD: Two consecutive cohorts of ED patients prospectively enrolled at two urban medical centers into the second phase of SpecTRA study (training, cohort 2A, n = 575; test, cohort 2B, n = 528). Plasma samples were analyzed using liquid chromatography/multiple reaction monitoring-mass spectrometry. Logistic regression models which fit cohort 2A were validated on cohort 2B.
RESULTS: Three of the panel proteins failed quality control and were removed from the panel. During validation, panel models did not outperform a simple motor/speech (M/S) deficit variable. Post-hoc analyses suggested the measured behaviour of L-selectin and coagulation factor V contributed to poor model performance. Removal of these proteins increased the external performance of a model containing the panel and the M/S variable.
CONCLUSIONS: Univariate analyses suggest insulin-like growth factor-binding protein 3 and serum paraoxonase/lactonase 3 are reliable and reproducible biomarkers for TIA status. Logistic regression models indicated L-selectin, apolipoprotein B-100, coagulation factor IX, and thrombospondin-1 to be significant multivariate predictors of TIA. We discuss multivariate feature subset analyses as an exploratory technique to better understand a panel's full predictive potential.
Objective: To derive a plasma biomarker protein panel from a list of 141 candidate proteins which can differentiate transient ischaemic attack (TIA)/minor stroke from non-cerebrovascular (mimic) ...conditions in emergency department (ED) settings.
Design: Prospective clinical study (#NCT03050099) with up to three timed blood draws no more than 36 h following symptom onset. Plasma samples analysed by multiple reaction monitoring-mass spectrometry (MRM-MS).
Participants: Totally 545 participants suspected of TIA enrolled in the EDs of two urban medical centres.
Outcomes: 90-day, neurologist-adjudicated diagnosis of TIA informed by clinical and radiological investigations.
Results: The final protein panel consists of 16 proteins whose patterns show differential abundance between TIA and mimic patients. Nine of the proteins were significant univariate predictors of TIA odds ratio (95% confidence interval): L-selectin 0.726 (0.596-0.883); Insulin-like growth factor-binding protein 3 0.727 (0.594-0.889); Coagulation factor X 0.740 (0.603-0.908); Serum paraoxonase/lactonase 3 0.763 (0.630-0.924); Thrombospondin-1 1.313 (1.081-1.595); Hyaluronan-binding protein 2 0.776 (0.637-0.945); Heparin cofactor 2 0.775 (0.634-0.947); Apolipoprotein B-100 1.249 (1.037-1.503); and von Willebrand factor 1.256 (1.034-1.527). The scientific plausibility of the panel proteins is discussed.
Conclusions: Our panel has the potential to assist ED physicians in distinguishing TIA from mimic patients.
Background The relationship between duration of transient neurological events and presence of diffusion-weighted lesions by symptom type is unclear. Methods and Results This was a substudy of SpecTRA ...(Spectrometry for Transient Ischemic Attack Rapid Assessment), a multicenter prospective cohort of patients with minor ischemic cerebrovascular events or stroke mimics at academic emergency departments in Canada. For this study we included patients with resolved symptoms and determined the presence of diffusion-weighted imaging (DWI) lesion on magnetic resonance imaging within 7 days. Using logistic regression, we evaluated the association between symptom duration and DWI lesion, assessing for interaction with symptom type (focal only versus nonfocal/mixed), and adjusting for age, sex, education, comorbidities, and systolic blood pressure. Of 658 patients included, a DWI lesion was present in 232 (35.1%). There was a significant interaction between symptom duration and symptom type. For those with focal-only symptoms, there was a continuous increase in DWI probability up to 24 hours in duration (ranging from ≈40% to 80% probability). In stratified analyses, the increase in probability of DWI lesion with increased duration of focal symptoms was seen in women but not men. For those with nonfocal or mixed symptoms, predicted probability of DWI lesion was ≈35% and was greater in men, but did not increase with longer duration. Conclusions Increased duration of neurological deficits is associated with greater probability of DWI lesion in those with focal symptoms only. For individuals with nonfocal or mixed symptoms, about one-third had DWI lesions, but the probability did not increase with duration. These results may be important to improve risk stratification of transient neurological events.
Elevated blood pressure (BP) at emergency department (ED) presentation and advancing age have been associated with risk of ischemic stroke; however, the relationship between BP, age, and transient ...ischemic attack/minor stroke (TIA/MS) is not clear.
A multi-site, prospective, observational study of 1084 ED patients screened for suspected TIA/MS (symptom onset < 24 h, NIHSS< 4) between December 2013 and April 2016. Systolic and diastolic BP measurements (SBP, DBP) were taken at ED presentation. Final diagnosis was consensus adjudication by stroke neurologists; patients were diagnosed as either TIA/MS or stroke-mimic (non-cerebrovascular conditions). Conditional inference trees were used to define age cut-points for predicting binary diagnosis (TIA/MS or stroke-mimic). Logistic regression models were used to estimate the effect of BP, age, sex, and the age-BP interaction on predicting TIA/MS diagnosis.
Over a 28-month period, 768 (71%) patients were diagnosed with TIA/MS: these patients were older (mean 71.6 years) and more likely to be male (58%) than stroke-mimics (61.4 years, 41%; each p < 0.001). TIA/MS patients had higher SBP than stroke-mimics (p < 0.001). DBP did not differ between the two groups (p = 0.191). SBP was predictive of TIA/MS diagnosis in younger patients, after accounting for age and sex; an increase of 10 mmHg systolic increased the odds of TIA/MS 18% (odds ratio OR 1.18, 95% CI 1.00-1.39) in patients < 60 years, and 23% (OR 1.23, 95% CI 11.12-1.35) in those 60-79 years, while not affecting the odds of TIA/MS in patients ≥80 years (OR 0.99, 95% CI 0.89-1.07).
Raised SBP in patients younger than 80 with suspected TIA/MS may be a useful clinical indicator upon initial presentation to help increase clinicians' suspicion of TIA/MS.
ClinicalTrials.gov NCT03050099 (10-Feb-2017) and NCT03070067 (3-Mar-2017). Retrospectively registered.
A series of recent reports have identified cases of a quadriplegic myopathy characterized by myofiber necrosis and loss of myosin filaments associated with the use of nondepolarizing muscle blocking ...agents and glucocorticoids. We report electrophysiological findings in 7 intensive care unit patients who developed evidence of an acute myopathy in association with the use of nondepolarizing muscle blocking agents. Several important features were identified: (i) a neuromuscular transmission deficit was observed in 3 patients up to 7 days following withdrawal of vecuronium; (ii) motor M potentials were of low amplitude, there was mild abnormal spontaneous activity on needle electromyography, and sensory conduction was relatively preserved; (iii) not all patients received glucocorticoids or were asthmatic; (iv) 2 patients given vecuronium had very high creatine kinase levels and developed acute renal failure associated with myoglobinuria; and (v) rises in motor M potentials accompanied clinical recovery. This complication of intensive care may be severe, but is reversible and possibly avoidable. Our findings implicate nondepolarizing muscle blocking agents in the development of the myopathy. Electrophysiological studies provide important prognostic guidance.
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