The clock out of sync: Insights into circadian disruption in wake-up vs non-wake-up stroke

BACKGROUND: Wake-up stroke (WUS), an ischemic stroke occurring during sleep, accounts for 15-25% of acute ischemic strokes (AIS) cases and poses unique therapeutic challenges due to an unknown onset time. Circadian rhythms, regulated by the suprachiasmatic nucleus (SCN), influence various cardiovascular and metabolic processes, and disruptions of these rhythms have been implicated in stroke pathogenesis. OBJECTIVES: This study explored whether WUS patients exhibit distinct circadian abnormalities compared with non-WUS patients, focusing on markers such as melatonin, cortisol, circadian clock gene expression, blood pressure (BP), and heart rate (HR). MATERIAL AND METHODS: This exploratory, cross-sectional study included 28 participants (WUS: 8; non-WUS; 9, controls: 11). Blood samples were collected every 6 h over 24-h period, with melatonin and cortisol levels assessed via ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and chemiluminescence, respectively. Circadian gene expression (CLOCK, CRY1, CRY2, PER1, PER2, and BMAL1) was analyzed using quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). Blood pressure and HR were recorded at 2-h intervals, and circadian rhythmicity was determined using MetaCycle analysis. RESULTS: The results revealed significant circadian rhythms in melatonin and cortisol in the non-WUS and control groups, with WUS patients showing a complete loss of melatonin rhythm and a 3-h phase delay in cortisol. Blood pressure and HR circadian variations were absent in both stroke groups, and none of the 6 clock genes exhibited rhythmicity in either the WUS or non-WUS group. CONCLUSIONS: This study highlights the potential role of disrupted circadian rhythms in WUS pathogenesis, providing insights into targeted interventions such as light therapy. Future studies with larger cohorts are essential to confirm these findings and assess their clinical implications for stroke prevention and recovery.