Targeting Autoregulation-Guided Cerebral Perfusion Pressure after Traumatic Brain Injury (COGiTATE): A Feasibility Randomized Controlled Clinical Trial.

Managing traumatic brain injury (TBI) patients with a cerebral perfusion pressure (CPP) near to the cerebral autoregulation (CA)-guided "optimal" CPP (CPPopt) value is associated with improved outcome and might be useful to individualize care, but has never been prospectively evaluated. This study evaluated the feasibility and safety of CA-guided CPP management in TBI patients requiring intracranial pressure monitoring and therapy (TBIicp patients). The CPPopt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) parallel two-arm feasibility trial took place in four tertiary centers. TBIicp patients were randomized to either the Brain Trauma Foundation (BTF) guideline CPP target range (control group) or to the individualized CA-guided CPP targets (intervention group). CPP targets were guided by six times daily software-based alerts for up to 5 days. The primary feasibility end-point was the percentage of time with CPP concordant (±5 mm Hg) with the set CPP targets. The main secondary safety end-point was an increase in therapeutic intensity level (TIL) between the control and intervention group. Twenty-eight patients were randomized to the control and 32 patients to the intervention group. CPP in the intervention group was in the target range for 46.5% (interquartile range, 41.2-58) of the monitored time, significantly higher than the feasibility target specified in the published protocol (36%; p < 0.001). There were no significant differences between groups for TIL or for other safety end-points. Conclusively, targeting an individual and dynamic CA-guided CPP is feasible and safe in TBIicp patients. This encourages a prospective trial powered for clinical outcomes.

Severely Disturbed Sleep in Patients With Acute Ischemic Stroke on Stroke Units: A Pilot Study.

Introduction: Previous studies revealed a high prevalence of sleep-wake disturbances in subacute and chronic stroke. We analyzed sleep quantity and quality in patients with hyperacute ischemic stroke on stroke units. Methods: We categorized sleep stages as N1, N2, N3, and REM according to the 2017 criteria of the American Academy of Sleep Medicine in 23 continuous, overnight EEG registrations from 18 patients, starting within 48 h since the onset of cortical ischemic stroke. Associations between presence and duration of sleep stages, and secondary deterioration or functional outcome were analyzed. Results: Physiological sleep cycles were seen in none of the patients. Otherwise, sleep stages alternated chaotically, both during day- and during nighttime, with a sleep efficiency of 30% and 10.5 ± 4.4 (mean ± SD) awakenings per hour of sleep. We cannot differentiate between stroke related and external factors. Only few interruptions could be related to planned nightly wake up calls, but turbulence on stroke units may have played a role. Six patients (seven nights) did not reach deep sleep (N3), 10 patients (13 nights) did not reach REM sleep. If reached, the mean durations of deep and REM sleep were short, with 37 (standard deviation (SD) 25) and 18 (SD15) minutes, respectively. Patients with secondary deterioration more often lacked deep sleep (N3) than patients without secondary deterioration [4 (57%) vs. 2 (25%)], but without statistical significance (p = 0.12). Conclusion: We show that sleep is severely disturbed in patients with acute ischemic stroke admitted to stroke units. Larger studies are needed to clarify associations between deprivation of deep sleep and secondary deterioration.

Contralesional Brain Activity in Acute Ischemic Stroke.

BACKGROUND: The noninjured, contralateral hemisphere is increasingly acknowledged in the process of recovery from acute ischemic stroke. We estimated the value of conventional electroencephalography (EEG) recordings for identifying contralateral hemisphere involvement in relation to functional recovery. METHODS: We analyzed 2-min epochs from 21 electrode EEG registrations of 18 patients with acute hemispheric ischemic stroke and compared with 18 age-matched controls. Outcome was dichotomized as good (modified Rankin Scale [mRS] 0-2) or poor (mRS 3-5 or death) at 3 months. Effects of the infarct on the ipsi-and contralateral hemispheres were analyzed by the delta/alpha ratio (DAR) and 2 measures of functional connectivity (magnitude squared coherence [MSC] and weighted phase lag index [WPLI]). RESULTS: DAR was higher in patients than in controls, both in the ipsilateral and in the contralateral hemisphere (median 4.5 ± 6.7 ipsilateral and 2.4 ± 2.0 contralateral vs. 0.5 ± 0.5 in the control group, p < 0.001), indicating robust EEG changes in both lesioned and non-lesioned hemisphere. MSC and WPLI in the alpha and beta frequency bands were lower in patients than in controls in both hemispheres, indicating clear disturbances of functional connectivity (p < 0.05). In the poor outcome group, contralateral MSC and WPLI were lower than in the good outcome group, although these differences did not reach statistical significance. CONCLUSIONS: Short conventional EEG measurements show robust changes of brain activity and functional connectivity in both ipsilateral and contralateral hemispheres of patients with acute ischemic stroke. Changes of remote functional connectivity tend to interact with functional recovery. Future studies should estimate predictive values for individual patients and interactions with plasticity enhancing treatments.