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The benefits of hypothermia for the treatment of subarachnoid hemorrhage (SAH) remain controversial. In 1999, we initiated brain hypothermia treatment (BHT) in the hyperacute phase to mitigate the evolution of early brain injury in patients with World Federation of Neurological Surgeons (WFNS) grade V SAH. In June 2014, we introduced endovascular cooling to maintain normothermia for seven days following the initial BHT period. Immediately after the decision to treat the sources of bleeding, cooling was initiated, with a target temperature of 33-34°C. Bleeding sources were extirpated primarily by clipping with decompressive craniectomy. Patients were rewarmed at a rate of ≤1°C/day after ≥48 hours of surface cooling. After being rewarmed to 36°C, temperatures were controlled with antipyretic (chronologically divided into groups A-C with 47, 46, and 46 patients, respectively) or endovascular (group D, 38 patients) cooling. Overall, 177 patients (median age, 62 [52-68] years; 94 [53.1%] women; onset-to-arrival time, 36 minutes [28-50]) were included. The median Glasgow Coma Scale (GCS) score upon admission was 4 (3-6). Median core body temperature was 36 (35.3-36.6)°C on arrival, 34.6 (34.0-35.3)°C on entering the operating room, 33.8 (33.4-34.3)°C upon starting the microsurgical or interventional radiology procedure, and 33.7 (33.3-34.2)°C upon admission to the intensive care unit. There were no significant differences in age, sex, GCS score, pupillary findings, location of bleeding sources, or treatment methods. There were 69 (39.0%) overall favorable outcomes (modified Rankin Scale score of 0-3) at 6 months and 11 (23.4%), 18 (39.1%), 17 (37.0%), and 23 (60.5%) in groups A-D, respectively (p = 0.0065). The outcomes of patients with WFNS grade V SAH improved over time. Herein, we report our experience using BHT for severe SAH through a narrative review.

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The incidence of aging-related neurodegenerative disorders and neurocritical care diseases is increasing worldwide. Microglia, the main inflammatory cells in the brain, could be potential viable therapeutic targets for treating neurological diseases. Interestingly, mitochondrial functions, including energy metabolism, mitophagy and transfer, fission and fusion, and mitochondrial DNA expression, also change in activated microglia. Notably, mitochondria play an active and important role in the pathophysiology of neurodegenerative disorders and neurocritical care diseases. This review briefly summarizes the current knowledge on mitochondrial dysfunction in microglia in neurodegenerative disorders and neurocritical care diseases and comprehensively discusses the prospects of the application of neurological injury prevention and treatment targets by mitochondria.

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Paradoxical herniation is a dreadful neurosurgical complication often underdiagnosed, which typically becomes evident over the course of weeks to months after the initial intervention. Here we present a unique case with manifestations in the post-operative period. A patient initially referred to neurosurgery for a meningioma underwent an uneventful surgical excision, followed by the transient placement of a lumbar drain for 48 hours. On the first post-operative day, the patient exhibited progressively altered neurological status, with corresponding imaging revealing a transfalcine herniation, necessitating emergent decompressive craniectomy. Despite the medical and surgical interventions, there were continuous signs of neurological and imaging worsening, with increase in herniation, which led to the diagnosis suspicion of a paradoxical brain herniation. Consequently, a rapid reversal of neurological deficits was observed after applying maneuvers to augment the intracranial pressure, followed by cranioplasty. This case illustrates the utmost importance of clinical suspicion for the uncommon complications of neurointerventions.

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Hypoxic-ischemic encephalopathy is the most common cause of neonatal seizures. Continuous electroencephalographic monitoring is recommended given high rates of subclinical seizures. Prompt diagnosis and treatment of seizures may improve neurodevelopmental outcomes. International League Against Epilepsy guidelines indicate that (1) phenobarbital remains the first-line treatment of neonatal seizures and (2) early discontinuation of antiseizure medications following resolution of acute provoked seizures, and prior to discharge home, is recommended. Long-term follow-up of these infants is necessary to screen for postneonatal epilepsy and support neurodevelopment.

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Immune cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) are both common adverse effects of chimeric antigen receptor (CAR) T-cell therapy. Blinatumomab is a commonly used CAR T-cell treatment in patients with B-cell acute lymphoblastic leukemia (B-ALL). Our patient presented with an extensive past medical history, including refractory B-ALL, and developed CRS and ICANS following treatment with blinatumomab CAR-T cell therapy. Early clinical detection of ICANS, monitoring using immune effector cell encephalopathy scores, following the appropriate protocol for ICANS grade, and adding anakinra (IL-1 receptor antagonist) were crucial steps in managing his condition. The approach to managing and monitoring this patient was unique in that we added anakinra to the standard treatment regimen. With this report, we emphasize the need for further research regarding CAR T-cell therapeutic regimens and how to decrease the morbidity and mortality of its adverse effects.

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OBJECTIVE: Targeting single monitoring modalities such as intracranial pressure (ICP) or cerebral perfusion pressure alone has shown to be insufficient in improving outcome after traumatic brain injury (TBI). Multimodality monitoring (MMM) allows for a more complete description of brain function and for individualized management. Transcranial Doppler (TCD) represents the gold standard for continuous cerebral blood flow velocity assessment, but requires high levels skill and time. In TBI, the practical aspects of conducting extended TCD monitoring sessions have yet to be evaluated. METHODS: Patients with acute moderate-to-severe TBI admitted to the neurocritical care unit between March 2022 and December 2023 receiving invasive ICP measurements were evaluated for inclusion. Exclusion criteria included trauma incompatible with TCD monitoring and if MMM was unwarranted. Daily MMM sessions (in addition to regular monitoring) were performed using TCD (Delica EMS 9D System or the DWL Doppler Box) for ≤5 d. Quantitative and qualitative feasibility, safety, and quality metrics were assessed. RESULTS: Of 74 patients, 36 (75% male; mean age, 44 ± 17 y) were included. Common reasons for exclusion were skull fractures (n = 12) and decompressive craniectomy (n = 9). We acquired 88 recordings (mean, 275 ± 88 min). Overall monitoring times increased, and set-up times decreased. Physiologic variables (including ICP/brain temperature) did not change with TCD application. A single adverse event (dislodging of a microdialysis catheter) occurred. CONCLUSION: Implementing extended TCD monitoring in MMM protocols is feasible and safe. Considering these results, inclusion of long-term TCD as part of the MMM is strongly encouraged to allow for in-depth description and direct evaluation of hemodynamic changes after TBI.

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BACKGROUND: Volatile anesthetics have shown neuroprotective effects in preclinical studies, but clinical data on their use after aneurysmal subarachnoid hemorrhage (aSAH) are limited. This study aimed to analyze whether the use of volatile anesthetics for neurocritical care sedation affects the incidence of delayed cerebral ischemia (DCI), cerebral vasospasm (CVS), DCI-related infarction, or functional outcome. METHODS: Data were retrospectively collected for ventilated aSAH patients (2016-2022), who received sedation for at least 180 hours. For comparative analysis, patients were assigned to a control and a study group according to the sedation used (intravenous vs. volatile sedation). Logistic regression analysis was performed to identify independent predictors of DCI, CVS, DCI-related infarction, and functional outcome. RESULTS: Ninety-nine patients with a median age of 58 years (interquartile range: 52-65 years) were included. Forty-seven patients (47%) received intravenous sedation, while 52 patients (53%) received (additional) volatile sedation with isoflurane (n = 30, 58%) or sevoflurane (n = 22, 42%) for a median duration of 169 hours (range: 5-298 hours). There were no significant differences between the 2 groups regarding the occurrence of DCI, angiographic CVS, DCI-related infarction, or functional outcome. In a multivariable logistic regression analysis, the use of volatile anesthetics had no impact on the incidence of DCI-related infarction or the patients' functional outcome. CONCLUSIONS: Volatile sedation in aSAH patients is not associated with the incidence of DCI, CVS, DCI-related infarction, or functional outcome. Although we could not demonstrate neuroprotective effects of volatile anesthetics, our results suggest that volatile sedation after aSAH has no negative effect on the patient's outcome.

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BACKGROUND: Interventions to reduce intracranial pressure (ICP) in patients with traumatic brain injury (TBI) are multimodal but variable, including sedation-dosing strategies. This article quantifies the different sedation intensities administered in patients with moderate to severe TBI (msTBI) using the therapy intensity level (TIL) across different intensive care units (ICUs), including the use of additional ICP-lowering therapies. METHODS: Within the prospective Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, we performed a retrospective analysis of adult patients with msTBI admitted to an ICU for a least 5 days from seven US level 1 trauma centers who received invasive ICP monitoring and intravenous sedation. Sedation intensity was classified prospectively as one of three ordinal levels as part of the validated TIL score, which were collected at least once a day. RESULTS: A total of 127 patients met inclusion criteria (mean age 41.6 ± 17.7 years; 20% female). The median Injury Severity Score was 27 (interquartile range 17-33), with a median admission Glasgow Coma Score of 3 (interquartile range 3-7); 104 patients had severe TBI (82%), and 23 patients had moderate TBI (18%). The sedation intensity score was highest on the first ICU day (2.69 ± 1.78), independent of patient severity. Time to reaching each sedation intensity level varied by site. Sedation level I was reached within 24 h for all sites, but sedation levels II and III were reached variably between days 1 and 3. Sedation level III was never reached by two of seven sites. The total TIL score was highest on the first ICU day, with a modest decrease for each subsequent ICU day, but there was high site-specific practice-pattern variation. CONCLUSIONS: Intensity of sedation and other therapies for elevated ICP for patients with msTBI demonstrate large practice-pattern variation across level 1 trauma centers within the TRACK-TBI cohort study, independent of patient severity. Optimizing sedation strategies using patient-specific physiologic and pathoanatomic information may optimize patient outcomes.

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How to cite this article: Salhotra R. Transient Cerebral Circulation Arrest in SAH. Indian J Crit Care Med 2024;28(6):620-621.

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The placement of an external ventricular drain (EVD) is a critical neurosurgical procedure used to relieve intracranial pressure in patients with conditions such as hydrocephalus, traumatic brain injury, and intracranial hemorrhage. Traditional methods rely heavily on anatomical landmarks and the surgeon's experience, which can lead to variability in outcomes and increased risk of complications. Neuronavigation, while available, is infrequently used due to the size, cost, and set-up times associated with these devices. This report explores the use of a headset-based augmented reality (AR) system for guidance during the EVD placement procedure. We describe an AR system that overlays a 3D model of the patient's cranial anatomy, derived from preoperative imaging, onto the patient's head. This system is a head-mounted display and utilizes a rapid fiducial-less registration to provide the surgeon with visualization of 3D anatomy, and targeted trajectories. The system was used with a 32-year-old patient undergoing EVD placement prior to a cranioplasty. Due to the atypical cranial anatomy and due to prior procedures and midline shift, this relatively high-risk catheter placement was an ideal circumstance for the use of AR guidance during the EVD placement. This report described an early use of AR for EVD placement and represents a substantial advancement in neurosurgical practice, offering enhanced precision, efficiency, and safety. Further large-scale studies are warranted to validate these findings and explore the broader applicability of AR in other neurosurgical procedures.

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Background: The protocols and therapeutic guidance established for treating traumatic brain injury (TBI) in neurointensive care focus on managing cerebral blood flow (CBF) and brain tissue oxygenation based on pressure signals. The decision support process relies on assumed relationships between cerebral perfusion pressure (CPP) and blood flow, pressure-flow relationships (PFRs), and shares this framework of assumptions with mathematical intracranial hemodynamics models. These foundational assumptions are difficult to verify, and their violation can impact clinical decision-making and model validity. Methods: A hypothesis- and model-driven method for verifying and understanding the foundational intracranial hemodynamic PFRs is developed and applied to a novel multi-modality monitoring dataset. Results: Model analysis of joint observations of CPP and CBF validates the standard PFR when autoregulatory processes are impaired as well as unmodelable cases dominated by autoregulation. However, it also identifies a dynamical regime -or behavior pattern-where the PFR assumptions are wrong in a precise, data-inferable way due to negative CPP-CBF coordination over long timescales. This regime is of both clinical and research interest: its dynamics are modelable under modified assumptions while its causal direction and mechanistic pathway remain unclear. Conclusion: Motivated by the understanding of mathematical physiology, the validity of the standard PFR can be assessed a) directly by analyzing pressure reactivity and mean flow indices (PRx and Mx) or b) indirectly through the relationship between CBF and other clinical observables. This approach could potentially help to personalize TBI care by considering intracranial pressure and CPP in relation to other data, particularly CBF. The analysis suggests a threshold using clinical indices of autoregulation jointly generalizes independently set indicators to assess CA functionality. These results support the use of increasingly data-rich environments to develop more robust hybrid physiological-machine learning models.

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Health disparities continue to plague racial and ethnic underserved patients in the United States. Disparities extend to the most critically ill patients, including those experiencing neurologic injury and patients at the end of life. Achieving health equity in palliative care in the neurointensive care unit requires clinicians to acknowledge and address structural racism and the social determinants of health. This article highlights racial and ethnic disparities in neurocritical care and palliative care and offers recommendations for an anti-racist approach to palliative care in the neurointensive care unit for clinicians.

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Spontaneous intracerebral hemorrhage (ICH) is the most devastating type of stroke, and it is associated with high morbidity and mortality. Patients with a spontaneous ICH are routinely admitted to an intensive care unit (ICU). However, an ICU is a valuable and limited resource, and not all patients may require this level of care. The authors conducted a systematic review and meta-analysis evaluating the safety and outcome of admission to a step-down level of care or stroke unit (SU) compared to intensive care in adult patients with low-risk spontaneous ICH. PubMed, Embase, and the Cochrane Library were searched for randomized clinical trials and observational cohort studies. The Mantel-Haenszel method or inverse variance, as applicable, was applied to calculate an overall effect estimate for each outcome by combining the specific risk ratio (RR) or standardized mean difference. Risk of bias was analyzed using the Newcastle-Ottawa Scale. The protocol was registered in PROSPERO (CRD42023481915). The primary outcome examined was in-hospital mortality. Secondary outcomes were unfavorable short-term outcome, length of hospital stay, and (re)admission to the ICU. Five retrospective cohort studies involving 1347 patients were included in the qualitative analysis. Two of the studies had severity-matched groups. The definition of low-risk ICH was heterogeneous among the studies. Admission to an SU was associated with a similar rate of mortality compared to admission to an ICU (1.4% vs. 0.6%; RR 1.66; 95% confidence interval [CI] 0.24-11.41; P = 0.61), a similar rate of unfavorable short-term outcome (14.6% vs. 19.2%; RR 0.77; 95% CI 0.43-1.36; P = 0.36), and a significantly shorter mean length of stay (standardized mean difference - 0.87 days; 95% CI - 1.15 to - 0.60; P < 0.01). Risk of bias was low to moderate for each outcome. The available literature suggests that a select subgroup of patients with ICH may be safely admitted to the SU without affecting short-term outcome, potentially saving in-hospital resources and reducing length of stay. Further studies are needed to identify specific and reliable characteristics of this subgroup of patients.

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The term "urban-rural divide" encompasses several dimensions and has remained an important concern for any country. The economic disparity; lack of infrastructure; dearth of medical specialists; limited opportunities to education, training, and health care; lower level of sanitation; and isolating effect of geographical location deepens this gap, especially in low-income and middle-income countries (LMICs). This article gives an overview of the rural-urban differences in terms of facilities related to neurocritical care (NCC) in LMICs. Issues related to common clinical conditions such as stroke, traumatic brain injury, myasthenia gravis, epilepsy, tubercular meningitis, and tracheostomy are also discussed. To facilitate delivery of NCC in resource-limited settings, proposed strategies include strengthening preventive measures, focusing on basics, having a multidisciplinary approach, promoting training and education, and conducting cost-effective research and collaborative efforts. The rural areas of LMICs bear the maximum impact because of their limited access to preventive health services, high incidence of acquired brain injury, inability to have timely management of neurological emergencies, and scarcity of specialist services in a resource-deprived health center. An increase in the health budget allocation for rural areas, NCC education and training of the workforce, and provision of telemedicine services for rapid diagnosis, management, and neurorehabilitation are some of the steps that can be quite helpful.

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OBJECTIVE: In intensive care, delirium is frequent, prolongs the stay, increases health care costs, and worsens patient outcome. Several substances and medications as well as stress can impact the risk of delirium; however, assessment of previous exposure to psychotropic agents and stress by self-reports or third-party information is not always reliable. Hair analysis can be used to objectively assess medication and substance use (including chronic alcohol consumption), and allows for the determination of stress-related long-term changes in steroid hormones and endocannabinoids. METHODS: Consecutive adult patients with acute brain injury admitted to the neurocritical care unit were included. Delirium was diagnosed using the Confusion Assessment Method for the Intensive Care Unit. Liquid chromatography coupled with tandem mass spectrometry was used to investigate psychoactive substances and medications, ethyl glucuronide, steroid hormones, and endocannabinoids in hair samples. Univariable and multivariable analyses were used to reveal any associations with the occurrence of delirium. RESULTS: Of 50 consecutive patients, 21 (42%) were diagnosed with delirium. Detection of antipsychotics or antidepressants in hair was more frequent in patients with delirium (antidepressants: 43% vs. 14%, p = 0.040; antipsychotics: 29% vs. 0%, p = 0.021). These patients also displayed higher ethyl glucuronide levels (p = 0.049). Anandamide (AEA) concentrations were higher in patients with delirium (p = 0.005), whereas oleoylethanolamide (p = 0.045) and palmitoylethanolamide (PEA) (p = 0.017) concentrations were lower in patients with delirium. Backward stepwise logistic regression analysis revealed antidepressants and AEA/PEA to be independent relevant predictors of delirium. CONCLUSIONS: Hair analysis provides crucial and otherwise unattainable information regarding chronic stress and the use of psychotropic substances and medications. Undisclosed antidepressant/antipsychotic use or intense chronic alcohol consumption is susceptible to treatment (continuation of medication or provision of low-dose benzodiazepines in case of alcohol). Chronic stress can be evaluated using stress markers and endocannabinoids in hair, potentially allowing for personalized delirium risk stratification and preventive measures.

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Neonatal neurocritical care (NNCC) has emerged as an important specialty to address neurological conditions affecting newborns including a wide spectrum of brain injuries and developmental impairment. Despite the discipline's growth, variability in NNCC service delivery, patient care, and clinical training poses significant challenges and potentially adversely impacts patient outcomes. Variations in neuroprotective strategies, postnatal care, and training methodologies highlight the urgent need for a unified approach to optimize both short- and long-term neurodevelopmental outcomes for these vulnerable population. This paper presents strategic blueprints for establishing standardized NNCC clinical care and training programs focusing on collaborative effort across medical and allied health professions. By addressing these inconsistencies, the paper proposes that standardizing NNCC practices can significantly enhance the quality of care, streamline healthcare resource utilization, and improve neurodevelopmental outcome, thus paving the way for a new era of neonatal neurological care.

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Hypoxic ischemic encephalopathy (HIE) remains a leading cause of neonatal mortality and lifelong disability across the world. While therapeutic hypothermia (HT) is beneficial, it is only partially protective and adjuvant treatments that further improve outcomes are urgently needed. In high-income countries where HT is standard care, novel treatments are tested in conjunction with HT. Mesenchymal stromal cells (MSC) represent a paradigm shift in brain protection, uniquely adapting to the host cellular microenvironment. MSC have low immunogenicity and potent paracrine effects stimulating the host tissue repair and regeneration and reducing inflammation and apoptosis. Preclinical studies in perinatal brain injury suggest that MSC are beneficial after hypoxia-ischemia (HI) and most preclinical studies of MSC with HT show protection. Preclinical and early phase clinical trials have shown that allogenic administration of MSC to neonates with perinatal stroke and HIE is safe and feasible but further safety and efficacy studies of HT with MSC in these populations are needed. Combination therapies that target all stages of the evolution of injury after HI (eg HT, melatonin and MSC) show promise for improving outcomes in HIE.

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For a subset of patients with severe acute brain injury (SABI) undergoing invasive mechanical ventilation, the primary barrier to successful extubation is depressed mental status. Amantadine is a neurostimulant that has been demonstrated to increase arousal and improve functional outcomes in patients with SABI. In this case series, we describe 5 patients with SABI and invasive mechanical ventilation who received amantadine as an agent to improve mental status to allow extubation. The primary barrier to extubation for all patients was depressed mental status. Median age was 77 (range 32 to 82). Primary diagnoses were ischemic stroke (n = 1), subdural hemorrhage (n = 2), intracerebral hemorrhage (n = 1), and traumatic brain injury (n = 1). Median Glasgow Coma Score was 7T prior to administration of amantadine and 10T on the day after amantadine was initiated, with improvements in eye-opening and motor response. Four patients displayed improvement in arousal and attention and were successfully extubated 1 to 4 days after initiation of amantadine (median 2 days). The fifth patient only displayed marginal improvement in mental status after starting amantadine, but was ultimately able to be extubated 7 days later. Amantadine may improve the likelihood of or reduce the time to successful extubation in patients with SABI.

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BACKGROUND: In the general intensive care unit (ICU) women receive invasive mechanical ventilation (IMV) less frequently than men. We investigated whether sex differences in the use of IMV also exist in the neurocritical care unit (NCCU), where patients are intubated not only due to respiratory failure but also due to neurological impairment. METHODS: This retrospective single-centre study included adults admitted to the NCCU of the University Hospital Zurich between January 2018 and August 2021 with neurological or neurosurgical main diagnosis. We collected data on demographics, intubation, re-intubation, tracheotomy, and duration of IMV or other forms of respiratory support from the Swiss ICU registry or the medical records. A descriptive statistics was performed. Baseline and outcome characteristics were compared by sex in the whole population and in subgroup analysis. RESULTS: Overall, 963 patients were included. No differences between sexes in the use and duration of IMV, frequency of emergency or planned intubations, tracheostomy were found. The duration of oxygen support was longer in women (men 2 [2, 4] vs. women 3 [1, 6] days, p = 0.018), who were more often admitted due to subarachnoid hemorrhage (SAH). No difference could be found after correction for age, diagnosis of admission and severity of disease. CONCLUSION: In this NCCU population and differently from the general ICU population, we found no difference by sex in the frequency and duration of IMV, intubation, reintubation, tracheotomy and non-invasive ventilation support. These results suggest that the differences in provision of care by sex reported in the general ICU population may be diagnosis-dependent. The difference in duration of oxygen supplementation observed in our population can be explained by the higher prevalence of SAH in women, where we aim for higher oxygenation targets due to the specific risk of vasospasm.

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Multimodal monitoring (MMM) in the intensive care unit (ICU) has become increasingly sophisticated with the integration of neurophysical principles. However, the challenge remains to select and interpret the most appropriate combination of neuromonitoring modalities to optimize patient outcomes. This manuscript reviewed current neuromonitoring tools, focusing on intracranial pressure, cerebral electrical activity, metabolism, and invasive and noninvasive autoregulation monitoring. In addition, the integration of advanced machine learning and data science tools within the ICU were discussed. Invasive monitoring includes analysis of intracranial pressure waveforms, jugular venous oximetry, monitoring of brain tissue oxygenation, thermal diffusion flowmetry, electrocorticography, depth electroencephalography, and cerebral microdialysis. Noninvasive measures include transcranial Doppler, tympanic membrane displacement, near-infrared spectroscopy, optic nerve sheath diameter, positron emission tomography, and systemic hemodynamic monitoring including heart rate variability analysis. The neurophysical basis and clinical relevance of each method within the ICU setting were examined. Machine learning algorithms have shown promise by helping to analyze and interpret data in real time from continuous MMM tools, helping clinicians make more accurate and timely decisions. These algorithms can integrate diverse data streams to generate predictive models for patient outcomes and optimize treatment strategies. MMM, grounded in neurophysics, offers a more nuanced understanding of cerebral physiology and disease in the ICU. Although each modality has its strengths and limitations, its integrated use, especially in combination with machine learning algorithms, can offer invaluable information for individualized patient care.