Precision medicine of aneurysmal subarachnoid hemorrhage, vasospasm and delayed cerebral ischemia

Abstract

Introduction Precision medicine is an emerging paradigm aimed at providing individualized prevention and treatment of diseases through understanding and leveraging patient-to-patient variation. Aneurysmal subarachnoid hemorrhage (aSAH) carries tremendous morbidity and mortality with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) proving devastating and unpredictable. The paucity of effective treatment or prevention measures for these conditions could potentially be improved through implementation of precision medicine. Areas covered This review presents the basic pathophysiology of CV and DCI, current treatment guidelines, and evidence for the use of precision medicine in the prediction and prevention of poor outcomes following aSAH. An extensive PubMed literature search was performed using keywords cerebral vasospasm or delayed cerebral ischemia and either biomarkers, precision medicine, metabolomics, proteomics, or genomics. Over 200 peer-reviewed articles were reviewed. The studies presented focus on biomarkers identified as predictive markers or therapeutic targets following aSAH. Expert Commentary The array of novel biomarkers reviewed here, ranging from genotypes to metabolites, has been found to correlate with CV, DCI, and neurologic outcomes after aSAH. Though their practical use in the clinical management of aSAH is not well established, using these biomarkers as predictive tools or therapeutic targets demonstrates the potential of precision medicine in the treatment of aSAH.

An RCVS Spectrum Disorder? New Daily Persistent Headache Starting as a Single Thunderclap Headache (3 New Cases)

“…A fascinating seasonal predilection is becoming apparent in various NDPH subtypes and is again possibly demonstrated with this thunderclap headache subform, with the fall clock change time period through winter solstice being predominant . Is this a neuroinflammatory issue as it has been noted there is a circadian variation to multiple cytokines including interleukin (IL)‐6, IL‐1β, interferon (IFN)‐γ, and tumor necrosis factor (TNF)‐α? Interestingly, TNF‐α and IL‐6 have been linked to subarachnoid hemorrhage‐induced vasospasm . Are there specific CNS‐based vasoactive compounds more readily released during this time period?…”

“…10 Interestingly, TNF-α and IL-6 have been linked to subarachnoid hemorrhage-induced vasospasm. 11 Are there specific CNS-based vasoactive compounds more readily released during this time period? Finally, what is the possible role of the hypothalamic-pituitary axis in this condition?…”

Serum soluble lectin‐like oxidized low‐density lipoprotein receptor‐1 as a biomarker of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

“…Aneurysmal subarachnoid hemorrhage (aSAH) is one of the commonest cerebrovascular diseases and is characterized by a high mortality (Etminan & Macdonald, ; Grimm, ; Serrone, Maekawa, Tjahjadi, & Hernesniemi, ). After aSAH, cerebral vasospasm can induce the decreased cerebral blood flow, subsequently resulting in delayed cerebral ischemia (DCI), and finally leading to severe neurological deficit and even death (Burrell et al, ; Francoeur & Mayer, ; Geraghty & Testai, ). The accumulating evidence shows microvasculature, coagulation and fibrinolytic systems, cortical spreading depressions, and the immune system might participate in pathophysiological process of DCI (Bacigaluppi et al, ; Carr, Zuckerman, & Mocco, ; Foreman, ).…”

Utility of cerebrospinal fluid lactate in aneurysmal subarachnoid hemorrhage

“…Biomarkers predictive of vasospasm and patient outcome represent an important area of research in aSAH. [ 2 ] Cerebral microdialysis as a technique allows continuous measurements of the brain extracellular milieu. Since its conception by Ungerstedt and Pycock in the 1970s, the procedure has undergone significant refinement and there is a growing body of literature regarding its use in patients with trauma and aSAH.…”