Artificial Intelligence and Machine Learning Applications in Critically Ill Brain Injured Patients.

The utilization of Artificial Intelligence (AI) and Machine Learning (ML) is paving the way for significant strides in patient diagnosis, treatment, and prognostication in neurocritical care. These technologies offer the potential to unravel complex patterns within vast datasets ranging from vast clinical data and EEG (electroencephalogram) readings to advanced cerebral imaging facilitating a more nuanced understanding of patient conditions. Despite their promise, the implementation of AI and ML faces substantial hurdles. Historical biases within training data, the challenge of interpreting multifaceted data streams, and the "black box" nature of ML algorithms present barriers to widespread clinical adoption. Moreover, ethical considerations around data privacy and the need for transparent, explainable models remain paramount to ensure trust and efficacy in clinical decision-making.This article reflects on the emergence of AI and ML as integral tools in neurocritical care, discussing their roles from the perspective of both their scientific promise and the associated challenges. We underscore the importance of extensive validation in diverse clinical settings to ensure the generalizability of ML models, particularly considering their potential to inform critical medical decisions such as withdrawal of life-sustaining therapies. Advancement in computational capabilities is essential for implementing ML in clinical settings, allowing for real-time analysis and decision support at the point of care. As AI and ML are poised to become commonplace in clinical practice, it is incumbent upon health care professionals to understand and oversee these technologies, ensuring they adhere to the highest safety standards and contribute to the realization of personalized medicine. This engagement will be pivotal in integrating AI and ML into patient care, optimizing outcomes in neurocritical care through informed and data-driven decision-making.

Multimodal and autoregulation monitoring in the neurointensive care unit.

Given the complexity of cerebral pathology in patients with acute brain injury, various neuromonitoring strategies have been developed to better appreciate physiologic relationships and potentially harmful derangements. There is ample evidence that bundling several neuromonitoring devices, termed "multimodal monitoring," is more beneficial compared to monitoring individual parameters as each may capture different and complementary aspects of cerebral physiology to provide a comprehensive picture that can help guide management. Furthermore, each modality has specific strengths and limitations that depend largely on spatiotemporal characteristics and complexity of the signal acquired. In this review we focus on the common clinical neuromonitoring techniques including intracranial pressure, brain tissue oxygenation, transcranial doppler and near-infrared spectroscopy with a focus on how each modality can also provide useful information about cerebral autoregulation capacity. Finally, we discuss the current evidence in using these modalities to support clinical decision making as well as potential insights into the future of advanced cerebral homeostatic assessments including neurovascular coupling.

The Clinical Impact of Recent Methamphetamine Exposure in Aneurysmal Subarachnoid Patients.

Background: Methamphetamines (MA) are a frequently used drug class with potent sympathomimetic properties that can affect cerebral vasculature. Conflicting reports in literature exist about the effect of exposure to MA on vasospasm risk and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to characterize the impact of recent MA use on the timing, severity and features of vasospasm in aneurysmal subarachnoid as well as neurological outcomes. Methods: We retrospectively screened 441 consecutive patients admitted to a tertiary care hospital with a diagnosis of SAH who underwent at least one cerebral digital subtraction angiogram (DSA). Patients were excluded if no urinary toxicology screen was performed within 24 hours of admission, if there was a diagnosis of non-aneurysmal SAH, or if ictus was greater than 72 hours from hospital admission. Vasospasm characteristics were collected from DSA and transcranial doppler (TCD) studies and demographic as well as clinical outcome data was abstracted from the chart. Results: 129 patients were included and 24 tested positive for MA. Among the 312 excluded patients, 281 did not have a urinary toxicology screen and 31 had a non-aneurysmal pattern of SAH or ictus occurring greater than 72 hours from hospital admission. No significant differences were found in respect to patient age, sex, or admission Hunt and Hess Score or Modified Fisher Scale based on MA use. There was no difference in the severity of vasospasm or time to peak severity using either TCD or DSA criteria on multivariate analysis. Aneurysms were more likely to be in the anterior circulation for both groups, however the MA cohort experienced less vasospasm involving the anterior circulation and more isolated posterior circulation vasospasm. There was no difference in delayed cerebral ischemia (DCI) incidence, length of ICU stay, need for ventriculoperitoneal shunt placement, functional outcome at discharge or hospital mortality. Interpretation: Recent MA use was not associated with worse vasospasm severity, time to vasospasm, or DCI in aSAH patients. Further investigations about localized MA effects in the posterior circulation and impact on long-term functional outcomes are warranted.

A multicenter retrospective study evaluating the impact of desmopressin on hematoma expansion in patients with antiplatelet-associated intracranial hemorrhage.

INTRODUCTION: Antiplatelet medications interfere with hemostasis which can contribute to increased risk of hematoma expansion and potentially worse outcomes in patients presenting with intracranial hemorrhages (ICH). Current Neurocritical Care Society guidelines recommend desmopressin (DDAVP) in patients with antiplatelet-associated ICH with evidence limited by small cohorts. MATERIALS AND METHODS: Patients were included in our multi-center, retrospective study if they had computed tomographic (CT) scan confirmed ICH and were taking antiplatelet medications. Patients were excluded if hospital length of stay was <24 h, administered DDAVP dose was <0.3 µg/kg, no follow-up head CT scan was performed within the first 24 h after baseline, major neurosurgical intervention was performed in between CT scans, or the injury was an acute on chronic ICH. The primary outcome was incidence of hematoma expansion (defined as >20 % increase from baseline). Secondary outcomes were incidence of thrombotic complications within 7 days, largest absolute decrease in serum sodium within the first 24 h, and patient disposition. RESULTS: Among the 209 patients included in the study, 118 patients received DDAVP while 91 did not. The frequency of hematoma expansion was similar between patients who received DDAVP and those who did not (16.1 % vs 17.6 %; P = 0.78). No difference in secondary outcomes was observed between the two groups. CONCLUSIONS: These findings in conjunction with recently published literature may suggest minimal benefit or harm with DDAVP treatment. However, further study could elucidate any potential impact on long-term function outcomes.

Geometric and Morphologic Features of Ruptured Intracranial Aneurysms Associated with Methamphetamine Use.

BACKGROUND: Methamphetamine (MA) use is associated with poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). MA exerts both hemodynamic and inflammatory effects, but whether these manifest with altered intracranial aneurysm (IA) remodeling is unknown. The objective of this study was to compare IA geometric and morphologic features in patients with and without MA detected on urine toxicology (Utox) at presentation. METHODS: We retrospectively reviewed 160 consecutive patients with SAH and Utox at time of admission. Geometric-morphologic IA characteristics were assessed by blinded neuroradiologists. Studied features were maximum sac diameter, location, size, ellipsoid volume, aspect ratio, size ratio, volume: neck ratio, dome: neck ratio, bottleneck factor, morphology (saccular, fusiform/dissecting, blister, mycotic), and presence of bleb, vasculopathy, or additional unruptured IA. RESULTS: Of 139/160 patients with aSAH, 23/139 (16.5%) were Utox MA+. There was no difference in aneurysm subtype frequency, presence of bleb, vasculopathy, or presence of an additional (unruptured) aneurysm with a trend toward posterior circulation location and higher Hunt and Hess grade (P = 0.09 for both) in the MA+ group. Maximum IA sac diameter, ellipsoid volume, dome-neck ratio, and size ratio were similar between groups. Only the aspect ratio (AR) differed between groups (MA+ = 2.20 vs. MA- = 1.74, P = 0.02). The AR remained a significant predictor of Utox MA+ in a multiple logistic regression analysis (odds ratio 1.87, 95% confidence interval 1.06-3.39). CONCLUSIONS: Active use of methamphetamine is independently associated with larger AR in patients with ruptured IA. This may indicate hazardous remodeling due to hemodynamic and/or inflammatory changes.

Combined Use of X-ray Angiography and Intraprocedural MRI Enables Tissue-based Decision Making Regarding Revascularization during Acute Ischemic Stroke Intervention.

Background For patients with acute ischemic stroke undergoing endovascular mechanical thrombectomy with x-ray angiography, the use of adjuncts to maintain vessel patency, such as stents or antiplatelet medications, can increase risk of periprocedural complications. Criteria for using these adjuncts are not well defined. Purpose To evaluate use of MRI to guide critical decision making by using a combined biplane x-ray neuroangiography 3.0-T MRI suite during acute ischemic stroke intervention. Materials and Methods This retrospective observational study evaluated consecutive patients undergoing endovascular intervention for acute ischemic stroke between July 2019 and May 2020 who underwent either angiography with MRI or angiography alone. Cerebral tissue viability was assessed by using MRI as the reference standard. For statistical analysis, Fisher exact test and Student t test were used to compare groups. Results Of 47 patients undergoing acute stroke intervention, 12 patients (median age, 69 years; interquartile range, 60-77 years; nine men) underwent x-ray angiography with MRI whereas the remaining 35 patients (median age, 80 years; interquartile range, 68-86 years; 22 men) underwent angiography alone. MRI results influenced clinical decision making in one of three ways: whether or not to perform initial or additional mechanical thrombectomy, whether or not to place an intracranial stent, and administration of antithrombotic or blood pressure medications. In this initial experience, decision making during endovascular acute stroke intervention in the combined angiography-MRI suite was better informed at MRI, such that therapy was guided in real time by the viability of the at-risk cerebral tissue. Conclusion Integrating intraprocedural 3.0-T MRI into acute ischemic stroke treatment was feasible and guided decisions of whether or not to continue thrombectomy, to place stents, or to administer antithrombotic medication or provide blood pressure medications. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lev and Leslie-Mazwi in this issue.

Early Do-Not-Resuscitate Orders and Outcome After Intracerebral Hemorrhage.

BACKGROUND: Do-not-resuscitate (DNR) orders are commonly used after intracerebral hemorrhage (ICH) and have been shown to be a predictor of mortality independent of disease severity. We determined the frequency of early DNR orders in ICH patients and whether a previously reported association with increased mortality still exists. METHODS: We performed a retrospective analysis of patients discharged from non-federal California hospitals with a primary diagnosis of ICH from January 2013 through December 2014. Characteristics included hospital ICH volume and type and whether DNR order was placed within 24 h of admission (early DNR order). The risk of in-hospital mortality was evaluated both on the individual and hospital level using multivariable analyses. A case mix-adjusted hospital DNR index was calculated for each hospital by comparing the actual number of DNR cases with the expected number of DNR cases from a multivariate model. RESULTS: A total of 9,958 patients were treated in 180 hospitals. Early DNR orders were placed in 20.1% of patients and 54.2% of these patients died during their hospitalization compared to 16.0% of patients without an early DNR order. For every 10% increase in a hospital's utilization of early DNR orders, there was a corresponding 26% increase in the likelihood of in-hospital mortality. Patients treated in hospitals within the highest quartile of adjusted DNR use had a higher relative risk of death compared to the lowest quartile (RR 3.9 vs 5.2) though the trend across quartiles was not statistically significant. CONCLUSIONS: The use of early DNR orders for ICH continues to be a strong predictor of in-hospital mortality. However, patients treated at hospitals with an overall high or low use of early DNR had similar relative risks of death whether or not there was an early DNR order, suggesting that such orders may not be a proxy for less aggressive care as seen previously.

Minimally invasive surgery for intracerebral hemorrhage.

PURPOSE OF REVIEW: Spontaneous intracerebral hemorrhage (ICH) is common, associated with a high degree of mortality and long-term functional impairment, and remains without effective proven treatments. Surgical hematoma evacuation can reduce mass effect and decrease cytotoxic effects from blood product breakdown. However, results from large clinical trials that have examined the role of open craniotomy have not demonstrated a significant outcome benefit over medical management. We review the data on minimally invasive surgery (MIS) that is emerging as a treatment modality for spontaneous ICH. RECENT FINDINGS: The use of MIS for supratentorial ICH has increased significantly in recent years and appears to be associated with decreased mortality and improved functional outcome compared with medical management. The role of MIS for posterior fossa ICH is ill-defined. Currently available MIS devices allow for stereotactic aspiration and thrombolysis, endoport-mediated evacuation, and endoscopic aspiration. Clinical series demonstrate that MIS can facilitate significant hematoma volume reduction and may be associated with less morbidity than conventional open surgical approaches. SUMMARY: MIS is an appealing treatment modality for supratentorial ICH and with careful patient selection and technologic advances has the potential to improve neurologic outcomes and reduce mortality. Early and extensive hematoma evacuation are important therapeutic targets and current studies are underway that have the potential to change the management for ICH patients.

Morphological changes of intracranial pressure quantifies vasodilatory effect of verapamil to treat cerebral vasospasm.

INTRODUCTION: After aneurysmal subarachnoid hemorrhage (SAH), both proximal and distal cerebral vasospasm can contribute to the development of delayed cerebral ischemia. Intra-arterial (IA) vasodilators are a mainstay of treatment for distal arterial vasospasm, but no methods of assessing the efficacy of interventions in real time have been established. OBJECTIVE: To introduce a new method for continuous intraprocedural assessment of endovascular treatment for cerebral vasospasm. METHODS: The premise of our approach was that distal cerebral arterial changes induce a consistent pattern in the morphological changes of intracranial pressure (ICP) pulse. This premise was demonstrated using a published algorithm in previous papers. In this study, we applied the algorithm to calculate the likelihood of cerebral vasodilation (VDI) and cerebral vasoconstriction (VCI) from intraprocedural ICP signals that are synchronized with injection of the IA vasodilator, verapamil. Cerebral blood flow velocities (CBFVs) on bilateral cerebral arteries were studied before and after IA therapy. RESULTS: 192 recordings of patients with SAH were reviewed, and 27 recordings had high-quality ICP waveforms. The VCI was significantly lower after the first verapamil injection (0.47±0.017) than VCI at baseline (0.49±0.020, p<0.001). A larger dose of injected verapamil resulted in a larger and longer VDI increase. CBFV of the middle cerebral artery increases across the days before the injection of verapamil and decreases after IA therapy. CONCLUSION: This study provides preliminary validation of an algorithm for continuous assessment of distal cerebral arterial changes in response to IA vasodilator infusion in patients with vasospasm and aneurysmal SAH.

Acquired Hemicerebral Atrophy Secondary to Chronic Internal Carotid Steno-Occlusive Disease: A Case Series.

Cerebral atrophy is a common finding in elderly patients; however, cerebrovascular disease causing progressive focal cerebral atrophy and dysfunction is unusual. In this report, we present 3 cases of hemicerebral atrophy due to ipsilateral internal carotid artery (ICA) stenosis or occlusion mimicking neurodegenerative conditions. Patient 1 had a frontal dysexecutive syndrome potentially consistent with a diagnosis of behavioral variant frontotemporal dementia; however, neuroimaging revealed a chronically occluded left ICA and a pattern of atrophy restricted to the left middle cerebral artery territory, suggestive of a vascular etiology. Patient 2 presented with progressively worsening seizures and right-sided weakness consistent with left hemispheric dysfunction, with radiographic evidence of left hemicerebral atrophy. Angiography revealed a chronic dissection of the left ICA leading to left cerebral hypoperfusion. Patient 3 had asymmetric parkinsonism, alien limb, and cognitive impairment consistent with a diagnosis of corticobasal syndrome. His imaging, however, revealed atrophy and encephalomalacia within the anterior circulation watershed territories with chronic, severe stenosis of the left ICA suggestive of a chronic hypoperfused state. In this case series, we report 3 examples of hemicerebral atrophy secondary to chronic ipsilateral ICA vascular disease with diverse progressive clinical symptoms mimicking primary neurodegenerative conditions. This case series highlights the importance of considering chronic hypoperfusion and large-vessel severe stenosis or occlusion in patients with cognitive impairment and evidence of asymmetric brain atrophy. In addition to symptomatic treatment, the management of vascular risk factors including treatment with antiplatelet agents, statins, and revascularization procedures can be considered.

Management of Blood Pressure During and After Recanalization Therapy for Acute Ischemic Stroke.

Ischemic stroke is a common neurologic condition and can lead to significant long term disability and death. Observational studies have demonstrated worse outcomes in patients presenting with the extremes of blood pressure as well as with hemodynamic variability. Despite these associations, optimal hemodynamic management in the immediate period of ischemic stroke remains an unresolved issue, particularly in the modern era of revascularization therapies. While guidelines exist for BP thresholds during and after thrombolytic therapy, there is substantially less data to guide management during mechanical thrombectomy. Ideal blood pressure targets after attempted recanalization depend both on the degree of reperfusion achieved as well as the extent of infarction present. Following complete reperfusion, lower blood pressure targets may be warranted to prevent reperfusion injury and promote penumbra recovery however prospective clinical trials addressing this issue are warranted.

Overview of Neurovascular Physiology.

PURPOSE OF REVIEW: Neurophysiology is a complex network of cellular, electrical, and vascular systems which function to maximize neuronal functioning and brain performance. The brain exists in a closed system made up of parenchyma, cerebrospinal fluid, and blood with any increase in volume leading to a corresponding decrease in one of the components. Once these compensatory mechanisms are exhausted, there is a precipitous increase in the intracranial pressure leading to decreases in cerebral perfusion and resulting ischemia. The cerebral vasculature has significant control over the total volume of blood and regional flow throughout the brain via autoregulation. Through this process, blood flow is tightly regulated to prevent fluctuations and is coupled precisely with metabolic demand. Moreover, oxygen delivery and aerobic respiration are essential for proper brain functioning and can become deranged in various disease states leading to cellular injury and death. RECENT FINDINGS: Ongoing trials have provided evidence that in addition to targeted therapy for intracranial pressure monitoring, optimizing brain tissue oxygenation and cerebral autoregulation may lead to improved clinical outcomes. An understanding of neurophysiology is not only essential for treating patients suffering from intracranial injury but also for the development of novel monitoring and therapeutic techniques.

Pleocytosis is not fully responsible for low CSF glucose in meningitis.

OBJECTIVE: The mechanism of hypoglycorrhachia-low CSF glucose-in meningitis remains unknown. We sought to evaluate the relative contribution of CSF inflammation vs microorganisms (bacteria and fungi) in lowering CSF glucose levels. METHODS: We retrospectively categorized CSF profiles into microbial and aseptic meningitis and analyzed CSF leukocyte count, glucose, and protein concentrations. We assessed the relationship between these markers using multivariate and stratified linear regression analysis for initial and repeated CSF sampling. We also calculated the receiver operating characteristics of CSF glucose and CSF-to-serum glucose ratios to presumptively diagnose microbial meningitis. RESULTS: We found that increasing levels of CSF inflammation were associated with decreased CSF glucose levels in the microbial but not aseptic category. Moreover, elevated CSF protein levels correlated more strongly than the leukocyte count with low CSF glucose levels on initial (R2 = 36%, p < 0.001) and repeated CSF sampling (R2 = 46%, p < 0.001). Hypoglycorrhachia (<40 mg/dL) was observed in 50.1% of microbial cases, but only 9.6% of aseptic cases, most of which were neurosarcoidosis. Absolute CSF glucose and CSF-to-serum glucose ratios had similar low sensitivity and moderate-to-high specificity in diagnosing microbial meningitis at thresholds commonly used. CONCLUSIONS: The main driver of hypoglycorrhachia appears to be a combination of microbial meningitis with moderate to high degrees of CSF inflammation and proteins, suggesting that the presence of microorganisms capable of catabolizing glucose is a determinant of hypoglycorrhachia in meningitis. A major notable exception is neurosarcoidosis. Low CSF glucose and CSF-to-serum glucose ratios are useful markers for the diagnosis of microbial meningitis.

Before-After Study of an Electronic Order Set for Reversal of Vitamin K Antagonist-Associated Intracerebral Hemorrhage.

BACKGROUND: Vitamin K antagonist (VKA)-associated intracerebral hemorrhages (ICHs) are more likely to expand and are associated with higher mortality than primary ICH. Prompt reversal of anticoagulant effect with prothrombin complex concentrate (PCC) may promote hemostasis and decrease hematoma expansion. The aim of this study was to evaluate the impact of an electronic order set designed to standardize and facilitate more timely reversal of coagulopathy in VKA-associated ICH. METHODS: We identified all adults who received PCC for VKA-associated ICH from June 2012 to June 2015 at University of California San Francisco Medical Center, which included a period before and after an electronic order set became available in 2014. We abstracted baseline demographics and clinical data from electronic health records. The primary outcome was time from radiographic identification of ICH to administration of PCC. RESULTS: Thirty-one patients received PCC for VKA-associated ICH, including 17 patients before and 14 patients after the order set became available. Baseline demographics and clinical features were similar. Order set use was associated with a significant decrease in the time from identification of ICH on imaging to the administration of PCC (median 83 vs 45 minutes; P = .02), more accurate dosing (29.4% vs 92.9%; P < .01), and a shorter time from the PCC order to follow-up international normalized ratio (INR) testing (median 164 vs 85 minutes, P = .001). CONCLUSION: An electronic order set for administering PCC for VKA-associated ICH was associated with significantly faster time to PCC administration and increased dosing accuracy.

Confirmed case of levamisole-associated multifocal inflammatory leukoencephalopathy in a cocaine user.

Levamisole is a common adulterant in cocaine and has previously been associated with a variety of serious complications including multifocal inflammatory leukoencephalopathy (MIL). There have been several reports of MIL in patients taking cocaine and, though suspected, the presence of levamisole was not confirmed. We present a case of a 63-year-old woman presenting with stupor and spastic quadraparesis found to have urine positive for cocaine and levamisole. An MRI brain revealed innumerable FLAIR hyperintensities with restricted diffusion and incomplete ring-enhancement. This is the first case to confirm the presence of levamisole in a patient with MIL associated with cocaine use.

Meiotic errors activate checkpoints that improve gamete quality without triggering apoptosis in male germ cells.

BACKGROUND: Meiotic checkpoints ensure the production of gametes with the correct complement and integrity of DNA; in metazoans, these pathways sense errors and transduce signals to trigger apoptosis to eliminate damaged germ cells. The extent to which checkpoints monitor and safeguard the genome differs between sexes and may contribute to the high frequency of human female meiotic errors. In the C. elegans female germline, DNA damage, chromosome asynapsis, and/or unrepaired meiotic double-strand breaks (DSBs) activate checkpoints that induce apoptosis; conversely, male germ cells do not undergo apoptosis. RESULTS: Here we show that the recombination checkpoint is in fact activated in male germ cells despite the lack of apoptosis. The 9-1-1 complex and the phosphatidylinositol 3-kinase-related protein kinase ATR, sensors of DNA damage, are recruited to chromatin in the presence of unrepaired meiotic DSBs in both female and male germlines. Furthermore, the checkpoint kinase CHK-1 is phosphorylated and the p53 ortholog CEP-1 induces expression of BH3-only proapoptotic proteins in germlines of both sexes under activating conditions. The core cell death machinery is expressed in female and male germlines; however, CED-3 caspase is not activated in the male germline. Although apoptosis is not triggered, checkpoint activation in males has functional consequences for gamete quality, because there is reduced viability of progeny sired by males with a checkpoint-activating defect in the absence of checkpoint function. CONCLUSIONS: We propose that the recombination checkpoint functions in male germ cells to promote repair of meiotic recombination intermediates, thereby improving the fidelity of chromosome transmission in the absence of apoptosis.