Clinical Research Directory

The Effect of Transcutaneous Vagal Nerve Stimulation (tVNS) on Cerebral Vasospasm Secondary to Aneurysmal Subarachnoid Hemorrhage

The significance of developing a safe and effective therapy for aneurysmal subarachnoid hemorrhage (aSAH) patients suffering cerebral vasospasm (CVS) cannot be overstated. Vasospasm - a clamping down of normal arteries in the days following rupture - remains incredibly challenging to treat.1,2 Current drugs and minimally invasive surgical therapies are helpful, yet woefully insufficient. Symptomatic cerebral vasospasm afflicts about 30% of aneurysmal subarachnoid hemorrhage patients and nearly half will go on to suffer a stroke, despite aggressive medical care.1-3 The autonomic nervous system is a balance between sympathetic (fight or flight) and parasympathetic (rest and digest) influence with sympathetic overactivity and inflammation shown to play an important role in the development and severity of cerebral vasospasm.4,5,17-20 Prior studies of autonomic nervous system neuromodulation highlight its promise as a promising potential avenue to improve morbidity and mortality from CVS in aSAH.6-15 Despite progress, continued high levels of CVS morbidity and mortality stress the urgent need for exploration of neuromodulation therapy. In this proposal, the study team will modulate the autonomic nervous system function in aSAH patients using transcutaneous vagal nerve stimulation (tVNS). tVNS involves placement of a stimulation electrode on the external ear to non-invasively stimulate a branch of the vagal nerve and increase parasympathetic influence. This device has FDA approval for epilepsy and cluster headache. The study hypothesis is that neuromodulation of the autonomic nervous system with tVNS (increasing parasympathetic influence) reduces sympathetic overactivity and inflammation in aSAH resulting in decreased morbidity of CVS.

The Effect of Sympathetic Modulation on Cerebral Vasospasm Secondary to Aneurysmal Subarachnoid Hemorrhage

The purpose of the study is to see that in addition to existing therapy, how well an additional procedure named spinal cord stimulation might reduce blood vessel spasm from aneurysm rupture.

Mechanisms of Brain-Heart Injury of Post-Intracranial Hemorrhage

Intracranial hemorrhage is a condition characterized by high mortality rates and suboptimal functional outcomes. It precipitates both direct brain injury and subsequent secondary injuries, including delayed cerebral ischemia, brain edema, and hydrocephalus. Complications such as cardiac injury may also arise, categorizing them within the cerebrocardiac syndrome (CCS). The clinical spectrum of CCS encompasses acute myocardial injury, acute coronary syndrome, left ventricular systolic and diastolic dysfunction, cardiac arrhythmias, and sudden cardiac death, all of which are associated with increased mortality and deterioration in patient status. The precise pathophysiological mechanisms underlying both cerebral and cardiac injuries remain enigmatic, and the implications for diagnosis and therapeutic strategies are yet to be fully explored. In this study, we propose to enroll patients with intracranial hemorrhage who will undergo conventional treatment and comprehensive multidisciplinary evaluations. Our observational research is grounded in a multimodal omics and imaging approach, aimed at investigating both local and systemic injuries subsequent to intracranial hemorrhage. This comprehensive strategy is intended to facilitate precise diagnosis, risk stratification, and clinical decision-making, while also shedding light on the pathophysiological mechanisms involved. The primary objectives of this research are to address the following key questions: * \[Question 1\] What are the pathophysiological mechanisms underlying cardiac injury in patients with intracranial hemorrhage? * \[Question 2\] What are the pathophysiological mechanisms responsible for early and delayed brain injuries following intracranial hemorrhage?\"

Prevention of Vasospasm in SAH Through CSF Treatment

The pathophysiological mechanisms of aneurysmal subarachnoid haemorrhage (aSAH) involve early brain injury (EBI) and delayed cerebral ischemia (DCI). Several mechanisms contribute to EBI pathogenesis, including cell death, inflammatory response, oxidative stress, excitotoxicity, microcirculatory dysfunction, microthrombosis and cortical spreading depolarization. All are suggested to be linked due to common pathogenic pathways and direct interaction. Despite advances in research of diagnostics and treatment strategies, brain injury remains the major cause of death and disability in SAH patients. There is no sufficient treatment of SAH and its devastating consequences known so far. Developing and improving diagnostic methods to monitor SAH patients and to evaluate efficacy of treatment strategies are essential in SAH research. These include neuroimaging, biomarkers, and other parameters such as invasive multimodal neuromonitoring and intraoperative electrophysiological monitoring. Cerebral vasospasm (CV) - mostly responsible for DCI - can be depicted on angiograms. Altogether, tremendous efforts have been taken to conquer the occurrence and sustainability of CV. The mortality of patients suffering aSAH rises up to 50% if the patients' condition is critical (Hunt\&Hess (HH) Grade 5, WFNS Grade 5, modified Fisher Grade 4). Reports of beneficial outcome in patients with pre-existing CSF shunting have been published. The hypothesis of early CSF reapplication to the bloodstream, in order to prevent CV seems to be positively approved by the mentioned reports. Nevertheless, no data could be found on the mechanisms of action in this phenomenon. To confirm the presence of interaction of the mechanisms of EBI and evaluate the application of cerebrospinal fluid (CSF), a pilot clinical trial was planned. Due to the lack of validated animal models for aSAH it is necessary to perform the trial first-in-human. A pilot (proof of concept) trial - is done through inclusion of 10 patients with severe aSAH (≥HH4). According to clinical guidelines, these patients receive external ventricular drainages in order to drain CSF and lower intracranial pressure. An interim analysis of data will be performed after inclusion and treatment of 5 patients. Blood-/CSF-sampling for further analysis will be collected before, during and after treatment according to the study protocol.