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Objectives To describe the prevalence and associated risk factors of new onset anisocoria (new pupil size difference of at least 1 mm) and its subtypes: new onset anisocoria accompanied by abnormal and normal pupil reactivities in patients with acute neurologic injuries. Design We tested the association of patients who experienced new onset anisocoria subtypes with degree of midline shift using linear regression. We further explored differences between quantitative pupil characteristics associated with first-time new onset anisocoria and nonnew onset anisocoria at preceding observations using mixed effects logistic regression, adjusting for possible confounders. Setting All quantitative pupil observations were collected at two neuro-ICUs by nursing staff as standard of care. Patients We conducted a retrospective two-center study of adult patients with intracranial pathology in the ICU with at least a 24-hour stay and three or more quantitative pupil measurements between 2016 and 2018. Measurements and main results We studied 221 patients (mean age 58, 41% women). Sixty-three percent experienced new onset anisocoria. New onset anisocoria accompanied by objective evidence of abnormal pupil reactivity occurring at any point during hospitalization was significantly associated with maximum midline shift (β = 2.27 per mm; p = 0.01). The occurrence of new onset anisocoria accompanied by objective evidence of normal pupil reactivity was inversely associated with death (odds ratio, 0.34; 95% CI, 0.16-0.71; p = 0.01) in adjusted analyses. Subclinical continuous pupil size difference distinguished first-time new onset anisocoria from nonnew onset anisocoria in up to four preceding pupil observations (or up to 8 hr prior). Minimum pupil reactivity between eyes also distinguished new onset anisocoria accompanied by objective evidence of abnormal pupil reactivity from new onset anisocoria accompanied by objective evidence of normal pupil reactivity prior to first-time new onset anisocoria occurrence. Conclusions New onset anisocoria occurs in over 60% of patients with neurologic emergencies. Pupil reactivity may be an important distinguishing characteristic of clinically relevant new onset anisocoria phenotypes. New onset anisocoria accompanied by objective evidence of abnormal pupil reactivity was associated with midline shift, and new onset anisocoria accompanied by objective evidence of normal pupil reactivity had an inverse relationship with death. Distinct quantitative pupil characteristics precede new onset anisocoria occurrence and may allow for earlier prediction of neurologic decline. Further work is needed to determine whether quantitative pupillometry sensitively/specifically predicts clinically relevant anisocoria, enabling possible earlier treatments.

Animal experiments recently demonstrated that replacing urinary loses with crystalloid diminishes the therapeutic effect of mannitol by reducing the increase in osmolality. We aimed to investigate whether this effect is similarly seen in in brain-injured patients by studying the association between total body fluid balance (TBB) and the osmolar response to mannitol.We performed a retrospective cohort study of adult patients with acute brain injury between 2015 and 2021 who received ≥ 2 doses of mannitol within 8 hours and no intercurrent concentrated saline solution. We analyzed the association between the change in TBB (∆Of 6,145 patients who received mannitol, 155 patients met inclusion criteria (mean age 60 ± 17 years, 48% male, 83% white). The mean total mannitol dose was 2 ± 0.5 g/kg and the mean change in plasma osmolality was 7.9 ± 7.1 mOsm/kg. Each 1 L increase in ∆In patients with acute brain injury, a positive TBB is associated with a diminished mannitol-induced increase in plasma osmolality. Future prospective studies are needed to confirm these findings and their influence on the therapeutic effect of mannitol.

Introduction: The FOUR (Full Outline of UnResponsiveness) score was developed as a more effective alternative to the Glasgow Coma Scale for prognostication of critically-ill neurology patients. Current research on the FOUR score in cardiac arrest is limited, but suggests that it may be useful. Given that whether or not a patient over-breathes the ventilator can often be confounded by the set respiratory rate, hypocarbia, and other factors, we evaluated the FOUR score with and without the respiratory component (FOUR-). Methods: We retrospectively studied 83 cardiac arrest patients treated at an urban hospital from 2011-2018 from the Multimodal outcome characterization in comatose cardiac arrest (MOCHA) registry. FOUR and FOUR- score within first 24 hours (day 1) and 72-96 hours (day 4) after arrest were evaluated for ability to predict in-hospital mortality and survival to discharge. Results: Day 1 FOUR score < 4 had 78% (67%-87%) sensitivity and 57% (29%-82%) specificity, while FOUR- score < 4 had 84% (73%-92%) sensitivity and 50% (23%-77%) specificity for predicting in-hospital mortality. Day 4 FOUR and FOUR- scores < 4 had higher specificities (both 94% [71%-100%]) but lower sensitivities (63% [45%-79%] and 69% [51%-83%], respectively) for mortality than day 1. With outcome changed to survival to discharge, day 1 FOUR score > 8 had 29% (8%-58%) sensitivity and 97% (90%-100%) specificity, while FOUR- > 8 had 21% (5%-51%) sensitivity and 100% (95%-100%) specificity. Day 4 FOUR and FOUR- scores > 8 had lower specificities (89% [73%-97%] and 91% [77%-98%], respectively), but higher sensitivities (53% [28%-77%]) and 47% [23%-72%], respectively) than day 1. There were no differences in mortality between FOUR and FOUR- < 4 on day 1 (p=0.89) or 4 (p=0.95), and no differences in survival between FOUR and FOUR- > 8 on day 1 (p=0.26) or 4 (p=0.85). Conclusions: Both the FOUR and FOUR- scores had high specificity for mortality and survival, which is important given that incorrectly predicting a bad outcome could lead to premature withdrawal of life support. The absence of a significant difference between the FOUR and FOUR- and the stronger prognostic ability of the FOUR- suggest that the respiratory component may not provide additional prognostic utility in cardiac arrest.

Purpose: Tractography is the most anatomically accurate method for delineating white matter tracts in the brain, yet few studies have examined multiple tracts using tractography in patients with schizophrenia (SCZ). We analyze 5 white matter connections important in the pathophysiology of SCZ: uncinate fasciculus, cingulum bundle (CB), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus, and arcuate fasciculus (AF). Additionally, we investigate the relationship between diffusion tensor imaging (DTI) markers and neuropsychological measures. Methods: High-resolution DTI data were acquired on a 3 Tesla scanner in 30 patients with early-course SCZ and 30 healthy controls (HC) from the Boston Center for Intervention Development and Applied Research study. After manually guided tracts delineation, fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD) were calculated and averaged along each tract. The association of DTI measures with the Scales for the Assessment of Negative and Positive Symptoms and neuropsychological measures was evaluated. Results: Compared to HC, patients exhibited reduced FA and increased trace and RD in the right AF, CB, and ILF. A discriminant analysis showed the possible use of FA of these tracts for better future group membership classifications. FA and RD of the right ILF and AF were associated with positive symptoms while FA and RD of the right CB were associated with memory performance and processing speed. Conclusion: We observed white matter alterations in the right CB, ILF, and AF, possibly caused by myelin disruptions. The structural abnormalities interact with cognitive performance, and are linked to clinical symptoms.