Role of the Periaqueductal Gray in Autonomic and Electrocardiographic Alterations During Subarachnoid Hemorrhage With Intraventricular Extension: A Systematic Review

Background: Subarachnoid hemorrhage (SAH), particularly with intraventricular extension (Fisher grade IV), is frequently accompanied by electrocardiographic (ECG) abnormalities, which are often attributed to autonomic dysfunction. The periaqueductal gray (PAG), a midbrain structure involved in autonomic and nociceptive processing, may play a pivotal role in these cardiovascular manifestations. This systematic review aims to analyze ECG alterations in patients with SAH complicated by intraventricular hemorrhage (IVH) and examine the autonomic effects of PAG stimulation in both experimental and clinical studies. Methods: A systematic search of PubMed, Scopus, and Web of Science was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Eligible studies included adult or neonatal patients with SAH+IVH reporting ECG or autonomic outcomes, and human or animal studies assessing autonomic effects of PAG stimulation. Data extraction focused on ECG changes, heart rate variability (HRV), blood pressure, autonomic indices, stimulation parameters, and neuroanatomical correlations. Results: Of 59 initially identified studies, 22 met the inclusion criteria. Among these, 10 clinical studies described ECG abnormalities in Fisher IV SAH patients, including corrected QT interval (QTc) prolongation, ST-segment changes, and T-wave inversion. The remaining 12 studies, focusing on PAG stimulation, revealed its modulatory effects on HRV, heart rate, and blood pressure. Specifically, ventral PAG stimulation enhanced parasympathetic output, whereas stimulation of lateral regions was associated with sympathetic activation. Conclusions: The review highlights a possible pathophysiological link between intraventricular blood extension in SAH and ECG abnormalities, potentially mediated by PAG involvement. Experimental data reinforce the role of the PAG in autonomic regulation. Future studies should focus on neurocardiac monitoring strategies and targeted neuromodulation in patients with hemorrhagic brain injury.