Patients experiencing ICH during the evening and particularly at night had higher discharge disability compared to those with symptom onset in the morning or midday, underscoring the potential for chronobiologically informed prevention and treatment strategies.
Key Findings
Results
ICH incidence follows a bimodal daily pattern with peak occurrences around 8:30 AM and 5:00 PM and a minimum at approximately midnight.
Data were drawn from the prospective stroke inpatient quality assurance registry of Hesse, Germany, covering 2015 to 2023.
5665 patients were included in the final analysis after exclusions.
Patients were grouped into four time windows: morning (5:00 AM–10:59 AM), midday (11:00 AM–4:59 PM), evening (5:00 PM–10:59 PM), and night (11:00 PM–4:59 AM).
The bimodal pattern confirms daily patterns previously observed in ICH onset, with peak onset during daytime.
Results
Evening and nighttime ICH onset was associated with worse functional outcomes at hospital discharge compared to morning or midday onset.
The primary outcome was global disability at discharge, analyzed using ordinal logistic regression.
Evening and particularly nighttime onset patients had higher discharge disability scores.
Analyses incorporated both inverse probability weighting (IPW) and propensity score matching (PSM) to account for confounding based on baseline characteristics.
The association between time of onset and functional outcome remained significant after adjustment.
Results
Unadjusted analyses showed daily variations in in-hospital mortality and complications, but these differences were no longer statistically significant after propensity score matching or inverse probability weighting.
Secondary outcomes included mortality and complications during hospitalization.
Daily variation in mortality and in-hospital complications was observed in unadjusted analyses.
After adjustment by PSM or IPW, these differences lost statistical significance.
This suggests that baseline characteristic differences between time-of-onset groups may explain mortality and complication variation, but not the functional outcome differences.
Methods
The study design used a large prospective registry with rigorous adjustment methods to evaluate time-of-day effects on ICH outcomes.
Consecutive ICH patient data were obtained from the prospective stroke inpatient quality assurance registry of Hesse, Germany.
The study period spanned 2015 to 2023.
Both inverse probability weighting (IPW) and propensity score matching (PSM) were employed to control for baseline confounders.
5665 patients underwent final analysis after exclusions.
Discussion
The authors conclude that chronobiologically informed prevention and treatment strategies for ICH merit further investigation.
The findings underscore 'the potential for chronobiologically informed prevention and treatment strategies.'
The authors call for 'further research into time-dependent pathophysiology and care delivery.'
The study links circadian biology to ICH outcomes, suggesting that time-of-day may influence both biological susceptibility and potentially care processes.
The persistence of functional outcome differences after adjustment implies that factors beyond baseline patient characteristics—potentially including circadian physiology or care delivery patterns—may play a role.
What This Means
This research suggests that the time of day when a brain bleed (intracerebral hemorrhage, or ICH) begins may influence how well patients recover. Using data from nearly 5,700 patients admitted to hospitals in Hesse, Germany between 2015 and 2023, the researchers found that brain bleeds were most common around 8:30 in the morning and again around 5:00 in the evening, with the fewest occurring around midnight. Patients whose brain bleeds started in the evening or at night tended to have worse disability when they left the hospital compared to those whose bleeds started in the morning or midday—even after accounting for differences in patient health and other background factors.
While initial analyses also suggested that death rates and in-hospital complications varied by time of day, these differences disappeared once the researchers statistically accounted for differences between patient groups. The worse functional outcomes for evening and nighttime onset patients, however, remained even after these adjustments, suggesting something specific about the timing—rather than just who gets sick at night—may be contributing to poorer recovery.
This research suggests that the body's internal clock (circadian biology) could play a role in both when brain bleeds occur and how severe their consequences are. This opens the door to further study of whether treatments or preventive strategies timed to account for these daily rhythms could improve patient outcomes. The findings also raise questions about whether nighttime hospital care delivery differs in ways that might affect recovery, warranting investigation into staffing, monitoring, and treatment protocols across different hours of the day.
Lieschke F, Lo E, Mandeville E, Foerch C, Klerman E, Saver J, et al.. (2026). Association of Time of Day With Functional Outcome in Intracerebral Hemorrhage.. European journal of neurology. https://doi.org/10.1111/ene.70762