Validating Existing Scales for Identification of Acute Stroke in an Inpatient Setting.

Background and Purpose: A significant proportion of strokes occur while patients are hospitalized for other reasons. Numerous stroke scales have been developed and validated for use in pre-hospital and emergency department settings, and there is growing interest to adapt these scales for use in the inpatient setting. We aimed to validate existing stroke scales for inpatient stroke codes. Methods: We retrospectively reviewed charts from inpatient stroke code activations at an urban academic medical center from January 2016 through December 2018. Receiver operating characteristic analysis was performed for each specified stroke scale including NIHSS, FAST, BE-FAST, 2CAN, FABS, TeleStroke Mimic, and LAMS. We also used logistic regression to identify independent predictors of stroke and to derive a novel scale. Results: Of the 958 stroke code activations reviewed, 151 (15.8%) had a final diagnosis of ischemic or hemorrhagic stroke. The area under the curve (AUC) of existing scales varied from .465 (FABS score) to .563 (2CAN score). Four risk factors independently predicted stroke: (1) recent cardiovascular procedure, (2) platelet count less than 50 × 109 per liter, (3) gaze deviation, and (4) presence of unilateral leg weakness. Combining these 4 factors into a new score yielded an AUC of .653 (95% confidence interval [CI] .604-.702). Conclusion: This study suggests that currently available stroke scales may not be sufficient to differentiate strokes from mimics in the inpatient setting. Our data suggest that novel approaches may be required to help with diagnosis in this unique population.

Distinct conformers of transmissible misfolded SOD1 distinguish human SOD1-FALS from other forms of familial and sporadic ALS.

Evidence of misfolded wild-type superoxide dismutase 1 (SOD1) has been detected in spinal cords of sporadic ALS (sALS) patients, suggesting an etiological relationship to SOD1-associated familial ALS (fALS). Given that there are currently a number of promising therapies under development that target SOD1, it is of critical importance to better understand the role of misfolded SOD1 in sALS. We previously demonstrated the permissiveness of the G85R-SOD1:YFP mouse model for MND induction following injection with tissue homogenates from paralyzed transgenic mice expressing SOD1 mutations. This prompted us to examine whether WT SOD1 can self-propagate misfolding of the G85R-SOD1:YFP protein akin to what has been observed with mutant SOD1. Using the G85R-SOD1:YFP mice, we demonstrate that misfolded conformers of recombinant WT SOD1, produced in vitro, induce MND with a distinct inclusion pathology. Furthermore, the distinct pathology remains upon successive passages in the G85R-SOD1:YFP mice, strongly supporting the notion for conformation-dependent templated propagation and SOD1 strains. To determine the presence of a similar misfolded WT SOD1 conformer in sALS tissue, we screened homogenates from patients diagnosed with sALS, fALS, and non-ALS disease in an organotypic spinal cord slice culture assay. Slice cultures from G85R-SOD1:YFP mice exposed to spinal homogenates from patients diagnosed with ALS caused by the A4V mutation in SOD1 developed robust inclusion pathology, whereas spinal homogenates from more than 30 sALS cases and various controls failed. These findings suggest that mutant SOD1 has prion-like attributes that do not extend to SOD1 in sALS tissues.