Brain temperature regulation in poor-grade subarachnoid hemorrhage patients – A multimodal neuromonitoring study

Elevated body temperature (Tcore) is associated with poor outcome after subarachnoid hemorrhage (SAH). Brain temperature (Tbrain) is usually higher than Tcore. However, the implication of this difference (Tdelta) remains unclear. We aimed to study factors associated with higher Tdelta and its association with outcome. We included 46 SAH patients undergoing multimodal neuromonitoring, for a total of 7879 h of averaged data of Tcore, Tbrain, cerebral blood flow, cerebral perfusion pressure, intracranial pressure and cerebral metabolism (CMD). Three-months good functional outcome was defined as modified Rankin Scale ≤2. Tbrain was tightly correlated with Tcore (r = 0.948, p < 0.01), and was higher in 73.7% of neuromonitoring time (Tdelta +0.18°C, IQR −0.01 – 0.37°C). A higher Tdelta was associated with better metabolic state, indicated by lower CMD-glutamate ( p = 0.003) and CMD-lactate ( p < 0.001), and lower risk of mitochondrial dysfunction (MD) (OR = 0.2, p < 0.001). During MD, Tdelta was significantly lower (0°C, IQR −0.2 – 0.1; p < 0.001). A higher Tdelta was associated with improved outcome (OR = 7.7, p = 0.002). Our study suggests that Tbrain is associated with brain metabolic activity and exceeds Tcore when mitochondrial function is preserved. Further studies are needed to understand how Tdelta may serve as a surrogate marker for brain function and predict clinical course and outcome after SAH

What Should a Clinician Do When Spreading Depolarizations are Observed in a Patient?

Abstract: The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in the September of 2018 devoted a section to address the question, “What should a clinician do when spreading depolarizations are observed in a patient?” Discussants represented a wide range of expertise, including neurologists, neurointensivists, neuroradiologists, neurosurgeons, and pre-clinical neuroscientists, to provide both clinical and basic pathophysiology perspectives. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was formally collated, reviewed, and incorporated into the final document which was subsequently approved by all authors

Multimodal neuromonitoring in patients with hemorrhagic stroke

Unter hämorrhagischen Schlaganfall, der mit hoher Morbidität und Mortalität assoziiert ist, werden die spontane Subarachnoidalblutung (SAB) und intracerebrale Blutung (ICB) subsumiert. Patienten mit Sedoanalgesie und mechanischer Beatmung können neurologisch nicht adäquat monitorisiert werden. Das multimodale Neuromonitoring ermöglicht über invasive Mikrokatheter eine kontinuierliche Messung des Hirnsauerstoffpartialdrucks (PbtO2), intrakraniellen Drucks (ICP), Metabolismus (durch die zerebrale Mikrodialyse) sowie Elektrokortikographie (EcoG). Die frühzeitige Erkennung und somit Vermeiden von sekundärer Hirnschädigung ist ein wichtiger Aspekt der neurologischen Intensivmedizin. Diese PhD Arbeit beschäftigte sich mit drei Themenbereichen: I.) der Untersuchung von physiolgischen Effekten von Diclofenac als antipyretische Therapie: Ein signifikanter Abfall von PbtO2 unter kritische Werte wurde nach Gabe von Diclofenac-Infusion (75mg) beobachtet, was mit schlechtem Outcome assoziiert war. II.) der Pathophysiologie des hämorrhagischen Schlaganfalls: Hier wurde gezeigt, dass eine Erhöhung des zerebralem extrazellulären Kaliums mit schlechtem Outcome und zerebraler metabolischer Dysfunktion nach SAB assoziiert ist. Weiters wurde mittels EcoG ein elekrophysiologisches Phänomen (Cortical Spreading Depolarisationen, CSDs) in vivo nach ICB untersucht. Es wurden Clusters von CSDs mit erhöhten zerebralen Matrix Metalloproteinasen (MMP)-9 als Marker für eine Bluthirnschrankenstörung während der Ödemprogression in einer Kasuistik beschrieben. III.) der Prognoseeinschätzung in der akuten Phase des hämorrhagischen Schlaganfalls mittels zerebraler Mikrodialyse: Hier wurde gezeigt, dass TAU-Protein im Mikrodialysat von SAB Patienten erhöht ist und eine extrazelluläre Erhöhung von TAU-Protein mit schlechtem funktionellen und neuropsychologischen Outcome assoziiert ist. Zusammenfassend ermöglicht das multimodale Neuromonitoring inklusive Elektrokortikographie ein online Monitoring von zerebralen physiologischen Veränderungen am Patientenbett, sowie eine Erweiterung des pathophysiologischen Verständnisses des hämorrhagischen Schlaganfalls.Hemorrhagic stroke subsumes spontaneous subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH), which are both associated with high morbidity and mortality. The aim of neurointensive care is to avoid secondary brain injury by timely detection of detrimental cascades after brain injury. In patients necessitating deep sedoanalgesia and ventilatory support, invasive multimodal neuromonitoring techniques allow early detection of these detrimental processes to optimize therapeutic counter strategies. This PhD Thesis consists of three major aims: I.) To investigate brain physiologic data of SAH patients following antipyretic therapy: Parenteral diclofenac infusion after aSAH was associated with cerebral perfusion pressure decrease and brain tissue oxygen tension (PbtO2) below critical threshold levels, which was associated with poor outcome in our study. II.) To analyze pathophysiologic processes after hemorrhagic stroke using advanced multimodal neuromonitoring techniques: Higher brain extracellular potassium levels were significantly associated with metabolic energy failure, poor 3-month outcome and may serve as a surrogate marker for brain tissue injury in poor-grade SAH patients. III.) To quantify proteins from brain extracellular fluid of SAH patients and correlate them with outcome: CMD-total-tau levels were positively correlated with brain extracellular metabolic distress and poor functional outcome (modified Rankin Scale 4) and neuropsychologic outcome 12 months after aSAH even after adjusting for disease severity and age. Therefore, CMD-total tau might be an important biomarker for predicting long-term outcome in patients with severe aSAH. In conclusion, multimodal neuromonitoring enables online monitoring of therapeutic measures at the bedside as well as improved understanding of pathophysiologic processes of hemorrhagic stroke.Alois SchiefeckerEnth. u.a. 6 Veröff. d. Verf. aus den Jahren 2013 - 2014Innsbruck, Med. Univ., Diss., 2015OeBB(VLID)76747

Clinical Use of Cerebral Microdialysis in Patients with Aneurysmal Subarachnoid Hemorrhage—State of the Art

ObjectiveTo review the published literature on the clinical application of cerebral microdialysis (CMD) in aneurysmal subarachnoid hemorrhage (SAH) patients and to summarize the evidence relating cerebral metabolism to pathophysiology, secondary brain injury, and outcome.MethodsStudy selection: Two reviewers identified all manuscripts reporting on the clinical use of CMD in aneurysmal SAH patients from MEDLINE. All identified studies were grouped according to their focus on brain metabolic changes during the early and subacute phase after SAH, their association with mechanisms of secondary brain injury and outcome.ResultsThe review demonstrated: (1) limited literature is available in the very early phase before the aneurysm is secured. (2) Brain metabolic changes related to early and delayed secondary injury mechanisms may be used in addition to other neuromonitoring parameters in the critical care management of SAH patients. (3) CMD markers of ischemia may detect delayed cerebral ischemia early (up to 16 h before onset), underlining the importance of trend analysis. (4) Various CMD-derived parameters may be associated with patient outcome at 3–12 months, including CMD-lactate-to-pyruvate-ratio, CMD-glucose, and CMD-glutamate.ConclusionThe clinical use of CMD is an emerging area in the literature of aneurysmal SAH patients. Larger prospective multi-center studies on interventions based on CMD findings are needed

Migraine and aura triggered by normobaric hypoxia

Background For future experimental studies or the development of targeted pharmaceutical agents, a deeper insight into the pathophysiology of migraine is of utmost interest. Reliable methods to trigger migraine attacks including aura are desirable to study this complex disease in vivo. Methods To investigate hypoxia as a trigger for migraine and aura, we exposed volunteers diagnosed with migraine, with (n = 16) and without aura (n = 14), to hypoxia utilizing a hypoxic chamber adjusted to a FiO2 of 12.6%. The occurrence of headache, migraine, aura, and accompanying symptoms were registered and vital signs were collected for 6 hours under hypoxia and 2 hours of follow-up. A binary logistic regression analysis examined the probability of triggering headaches, migraines, aura, photo- and phonophobia. Findings Of 30 participants, 24 (80.0%) developed headaches and 19 (63.3%) migraine, five (16.7%) reported aura. Two patients that developed aura never experienced aura symptoms before in their life. The increase of mean heart frequency was higher in patients developing headaches or migraine. Mean SpO2 during hypoxia was 83.39%. Conclusion Hypoxia was able to trigger migraine attacks and aura independently of any pharmacological agent

What Should a Clinician Do When Spreading Depolarizations are Observed in a Patient?

Abstract: The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in the September of 2018 devoted a section to address the question, “What should a clinician do when spreading depolarizations are observed in a patient?” Discussants represented a wide range of expertise, including neurologists, neurointensivists, neuroradiologists, neurosurgeons, and pre-clinical neuroscientists, to provide both clinical and basic pathophysiology perspectives. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was formally collated, reviewed, and incorporated into the final document which was subsequently approved by all authors

Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches