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Introduction: The TOAST (Trial of ORG 10172 in Acute Stroke Treatment) is the most commonly used ischemic stroke subtype classification system worldwide and a required field in the US National Get With The Guidelines-Stroke (GWTGStroke) registry. However, stroke diagnostics have advanced substantially since the TOAST classification was designed 30 years ago, potentially making it difficult to apply reliably. Methods: In this prospective diagnostic accuracy study, we analyzed consecutive ischemic stroke patients admitted to a Comprehensive Stroke Center between July-October 2021. Clinical practice TOAST classification diagnoses rendered by the stroke team in the electronic medical record (EMR) at discharge were retrieved from GWTG-Stroke registry and compared to a reference ("gold") standard diagnosis derived from agreement between two expert raters after review of the EMR and patient imaging. Results: Among 49 patients; age was 72.3 years (±12.1), 53% female, and presenting NIHSS median 3 (IQR 1-11). Work-up included: brain imaging in 100%; cardiac rhythm assessment in 100%; cervical/cerebral vessel imaging in 98%; TTE ± TEE in 92%; and TCD emboli evaluation in 51%. Reference standard diagnoses were: LAA-6%, SVD-14%, CE-39%, OTH-10%, UND-M (more than one cause)-20%, and UND-C (cryptogenic)-10%. GWTG-Stroke TOAST diagnoses agreed with reference standard diagnoses in 30/49 (61%). Among the 6 subtype diagnoses, specificity was generally high (84.8%-97.7%), but sensitivity suboptimal for LAA (33%), OTH (60%), UND-M (10%), and UND-C (20%). Positive predictive value was suboptimal for 5 of the 6 subtypes: LAA (13%), SVD (58%), OTH (75%), UND-M (50%), and UND-C (50%). Discussion: Clinical practice TOAST classification subtype diagnoses entered into the GWTG-Stroke registry were accurate in only 61% of patients, a performance rate that, if similarly present at other centers, would hamper the ability of the national registry to provide dependable insights into subtype-related care. Development of an updated ischemic stroke subtype classification system, with algorithmic logic embedded in electronic medical records, is desirable. [ABSTRACT FROM AUTHOR]

Damage to axons is a core feature of ischemic stroke and cerebrovascular disease. The burden of axonal injury is correlated with the acute clinical deficits, the underlying burden of ischemic brain injury, the prognosis of recovery, and may be a meaningful therapeutic target for brain repair. Neurofilament light chain (NfL) has been identified as a blood-based biomarker that reflects neuroaxonal damage resulting from stroke. However, the utility of NfL as a blood-based biomarker in stroke is confounded by studies examining different temporal windows and patient populations. We conducted a systematic review and meta-analysis to verify the utility of blood NfL as a diagnostic, prognostic, and monitoring stroke biomarker. Nineteen studies reporting serum/plasma NfL values for a total of 4,237 distinct patients with stroke were identified. Using available summary data from the 10 studies that employed a common immunoassay platform, we utilized random effects linear mixed modeling and weighted averages to create a phasic model of serum/plasma NfL values in distinct time periods of acute stroke. Weighted averages show that blood NfL levels vary significantly across three distinct temporal epochs of acute (0–7 days), subacute (9–90 days), and chronic (>90 days) stroke with a steep peak in the early subacute period between 14 and 21 days after stroke. Blood NfL values can function as a diagnostic biomarker in distinguishing acute ischemic stroke from transient ischemic attack as well as amongst other cerebrovascular subtypes. Release of NfL into the bloodstream after stroke follows a distinct temporal dynamic that lags several weeks behind stroke onset and reliably associates with a stroke diagnosis despite some variability based on stroke subtype and severity. Identification of these temporal dynamics and the contribution of co- existent cerebrovascular disease states can improve the value of NfL as a stroke biomarker. [ABSTRACT FROM AUTHOR]