Clinical Implication of Time of Stroke among Post Stroke Survivors from Eastern India: A Circadian Perspective

Introduction: The circadian variation in stroke occurrence is a well-documented phenomenon. However, the circadian effect on stroke outcome, particularly on post-stroke cognition, is not yet been fully elucidated. Aims and objective: We aim to evaluate the influence of diurnal variation of stroke onset upon post-stroke cognition and development of post-stroke depression. Materials and Methods: Based on 4-hourly time period of stroke occurrence, 249 recruited cohorts were categorized into 6 groups. Several clinical and cognitive parameters were compared among the groups. Then, the mRNA expression of core clock genes in Peripheral Blood Mononuclear Cells were quantified and correlated with post stroke outcome among 24 acute phase cases with day-time or night-time stroke occurrence. Furthermore, the genetic susceptibility towards higher number of cases in morning were examined by genotyping CLOCK (rs1801260T/C, rs4580704G/C) and CRY2 (rs2292912C/G) genes variants in cases and 292 controls. Results and conclusion: Among the six subgroups, the subgroup-1 represents the nocturnal-onset stroke cases; they were identified to have higher NIHSS score at the time of admission than other subgroups. In the same cohort, more number of diabetic individuals with higher fasting blood sugar level was also observed. After 6 months, those with nocturnal-onset stroke had higher prevalence of language impairment and depression score. A significant decrease in mRNA level of BMAL1 and CRY1 genes correlated with raw score for language and depression; data in nocturnal onset cases further established our observation. However, the higher incidence of stroke in day time did not reveal any genetic correlation. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Department of Science & Technology, Govt. of India (DST/CSRI-PDF/2021/12) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All procedures performed in studies involving human participants were in accordance with the ethical standards of the National Neurosciences Centre Calcutta, Kolkata, India and Nil Ratan Sircar Medical College & Hospital, Kolkata, India. The Ethics Committees (Institutional Ethics Committee, Nil Ratan Sircar Medical College & Hospital and Institutional Ethics Committee, National Neurosciences Centre Calcutta) of above-mentioned Institutes approved the study protocol. Informed consent was taken as per guidelines of the Indian Council of Medical Research, National Ethical guidelines for Biomedical and Health research involving human participants, India. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data will be available on request