Background and Purpose— Effective stroke prevention depends on accurate stroke risk prediction. We determined the discriminative ability of NfL (neurofilament light chain) levels for distinguishing between adults with diabetes mellitus who develop incident stroke and those who remain stroke free during a 7-year follow-up period. Methods— We performed a case-control study of participants selected from the previously completed ACCORD trial (Action to Control Cardiovascular Risk in Diabetes). Cases were all ACCORD subjects who were stroke free at enrollment and developed incident stroke during follow-up (n=113). Control subjects (n=250) were randomly selected ACCORD subjects who had no stroke events either before or after randomization. NfL was measured in baseline samples using Single Molecule Array technology (Quanterix). Results— Baseline NfL levels were higher in stroke subjects, compared to controls, after adjusting for age, race, blood pressure, weight, and the Framingham Stroke Risk Score. Relative to the subjects in the lowest quintile of NfL levels, the hazard ratios of incident stroke for subjects in the second to fifth quintiles were 3.91 (1.45–10.53), 4.05 (1.52–10.79), 5.63 (2.16–14.66), and 9.75 (3.84–27.71), respectively, after adjusting for race and Framingham Stroke Risk Score. Incorporating NfL levels into a predictive score that already included race and Framingham Stroke Risk Score increased the score’s C statistic from 0.71 (95% CI, 0.66–0.77) to 0.78 (95% CI, 0.73–0.83), P <0.001. Older age, nonwhite race, higher systolic blood pressure, glomerular filtration rate <60, and higher hemoglobin A1C were independent predictors of serum NfL in this cohort but diastolic blood pressure, durations of hypertension or diabetes mellitus, and lipid levels were not. In total, cardiovascular disease risk factors explained 19.2% of the variability in baseline NfL levels. Conclusions— Serum NfL levels predict incident stroke and add considerably to the discriminatory power of the Framingham Stroke Risk Score in a cohort of middle-aged and older adults with diabetes mellitus.

Functionally impaired patients diagnosed predominantly with mild TBI exhibit high rates of insomnia and short sleep, which may impede TBI recovery. Monitoring sleep after head injury may identify patients with poor prognoses and allow for early intervention to improve functional outcomes.

Head injury patients not meeting the American Congress of Rehabilitation Medicine (ACRM)'s criteria for mild traumatic brain injury (mTBI), referred to hereafter as HIBRID (Head Injury BRain Injury Debatable), are often excluded from studies. The prognostic importance of HIBRID is unclear. We investigated the differences in functional and symptomatic recovery at 1 month post-injury among TBI patients classified as: HIBRID, ACRM+ cranial computed tomography (CT)-, and cranial CT+; and trauma and healthy controls. Subjects were enrolled in an ongoing prospective cohort (Head Injury Serum Markers for Assessing Response to Trauma; HeadSMART). Outcomes measured at 1 month post-injury include: incomplete functional recovery (Glasgow Outcome Scale Extended <8); moderate/severe post-concussive symptoms (PCS), defined according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision definition; and moderate/severe depressive symptoms (Patient Health Questionnaire 9 ≥ 10). Between April 2014 and May 2016, 500 TBI and 100 control subjects were enrolled and 376 TBI and 78 control subjects completed outcome assessment. The HIBRID group, constituting 23.9% of study population, had a lower incidence of incomplete functional recovery (36.7% [33 of 90]) than ACRM+, CT- (60.7% [125 of 206]; p < 0.01) and CT+ (78.8% [63 of 80]; p < 0.01) groups. However, the incidence of delayed functional recovery within the HIBRID group was higher than in trauma (9.3% [5 of 54]; p < 0.01) and healthy controls (0% [0 of 24]; p < 0.01). Compared to trauma/healthy controls, the HIBRID group had a higher incidence of moderate/severe depressive symptoms and a similar incidence of moderate/severe PCS. Subjects in the HIBRID group are at high risk for adverse outcomes following head injury and warrant further investigation.

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