Clinical Implication of Time of Ischaemic Stroke Among Post-Stroke Survivors from Eastern India: A Circadian Perspective

Abstract

The circadian variation in stroke occurrence is a well-documented phenomenon. However, the circadian effect on stroke outcome, particularly on post-stroke cognition, has not yet been fully elucidated. We aim to evaluate the influence of diurnal variation of stroke onset upon post-stroke cognition and development of post-stroke depression. 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 outcomes among 24 acute phase cases with day-time or night-time stroke occurrence. Furthermore, the genetic susceptibility towards a higher number of cases in the morning was examined by genotyping CLOCK (rs1801260T/C, rs4580704G/C) and CRY2 (rs2292912C/G) genes variants in cases and 292 controls. In our study, the peak for highest incidence although observed during the early morning from 4 to 8 am, the nocturnal-onset stroke cases showed more severity (12.2 ± 5.67) at the time of admission irrespective of arterial territory involved. The night onset cases were also found to be more susceptible to develop language impairment and post-stroke depression in due course of time. Upon transcript analysis, circadian genes (BMAL1 and CRY1) were found to be downregulated in night-time cases than day-time ones during the acute phase of onset. In addition, those mRNA levels also showed a correlation with raw scores for language and depression. However, the difference in incidence frequency along a day did not reveal any genetic correlation. Therefore, we suggest night-time stroke to be positively associated with higher immediate severity and poor cognitive outcome than day-time injury and propose downregulation of circadian genes during the acute phase could be the underlying molecular mechanism for this.

Keywords: Circadian genes; Cognitive outcome; India; Stroke; Time of stroke.