Monitoring Cortical Spreading Depolarization: Advancements and Applications in Neurocritical Care: A Scoping Review

Cortical spreading depolarization (CSD) describes a slow, sustained depolarization within the cerebral gray matter that renders neurons unable to fire action potentials, resulting in widespread neuronal depression. CSD has been observed in stroke, subarachnoid hemorrhage, epilepsy, traumatic brain injury, and migraines and is a potential indicator of imminent neuronal death. Therefore, the identification, monitoring, and treatment of CSD are crucial in both neurointensive care and neurosurgical settings. Such measures are paramount for optimizing outcomes among patients with neurological injuries. However, this slow-spreading depolarization at high amplitudes presents challenges to identifying and monitoring CSD in clinical settings. We aim to identify various current and potential techniques for monitoring CSD in neurocritical care and neurosurgical settings, alongside exploring available treatment modalities. We also analyze current limitations in the detection of CSD, including the identification of potential biomarkers. A brief comprehensive scoping review of available literature utilizing search engines such as PubMed and Google Scholar was conducted using key search terms such as "cortical spreading depression", "CSD", "spreading depolarization", and "CSD monitoring". Eligibility for this review was restricted to full-text, English, peer-reviewed literature articles. There were no restrictions on publication dates. Around 450 articles discussing CSD were reviewed and ultimately 65 articles were included in the analysis. Electrocorticography (ECoG), an invasive modality that involves placing electrodes on the brain tissue directly, remains the primary modality to detect CSD, both in the neurosciences intensive care unit (NSICU) and during neurosurgical procedures. However, there are other potential modalities for detection such as Electroencephalogram (EEG), pressure reactivity index (PRx), magnetoencephalography (MEG), MRI/fMRI, and laser speckle imaging (LSI). These methods have been tested in animal models and/or in clinical practice but each has drawbacks that render these modalities not readily available or nonfunctional as independent detection methods in the NSICU. Nevertheless, a multimodal monitoring approach utilizing a combination of monitoring modalities such as ECoG in conjunction with tools that measure cerebral vascular response such as cerebral perfusion pressure, cerebral blood flow, and PRx could provide timely measurements of CSD. There are potential biomarkers being studied for early detection of CSD which include adenosine, GFAP, lactate, IL-6, or TNF-alpha. Some treatment modalities that have been studied that inhibit or halt CSD include: topiramate, valproate, propranolol, amitriptyline, methysergide, Propofol, and glutamate receptor inhibitors. Although several methods have been studied, invasive ECoG remains the gold standard for CSD detection. There are currently no reliable non-invasive modalities for CSD detection. Nevertheless, a multimodal approach that utilizes ECoG in conjunction with different methods of monitoring, could prove a useful tool in NSICU as well as neurosurgical procedures. Further research is needed to not only determine the utility and application of other monitoring methods in the clinical setting but also explore non-invasive monitoring methods.