Nimodipine-associated standard dose reductions and neurologic outcomes after aneurysmal subarachnoid hemorrhage: the era of pharmacogenomics.

Nimodipine, an L-type cerebroselective calcium channel antagonist, is the only drug approved by the US Food and Drug Administration for the neuroprotection of patients with aneurysmal subarachnoid hemorrhage (aSAH). Four randomized, placebo-controlled trials of nimodipine demonstrated clinical improvement over placebo; however, these occurred before precision medicine with pharmacogenomics was readily available. The standard enteral dose of nimodipine recommended after aSAH is 60 mg every 4 h. However, up to 78% of patients with aSAH develop systemic arterial hypotension after taking the drug at the recommended dose, which could theoretically limit its neuroprotective role and worsen cerebral perfusion pressure and cerebral blood flow, particularly when concomitant vasospasm is present. We investigated the association between nimodipine dose changes and clinical outcomes in a consecutive series of 150 patients (mean age, 56 years; 70.7% women) with acute aSAH. We describe the pharmacogenomic relationship of nimodipine dose reduction with clinical outcomes. These results have major implications for future individualized dosing of nimodipine in the era of precision medicine.

Long-Term Safety and Efficacy of Pipeline Embolization Device in Anterior and Posterior Circulation Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND: Flow diversion using the pipeline embolization device (PED) has been a paradigm shift for anterior circulation (AC) aneurysms. However, only a few studies report the long-term (≥1 year) angiographic and clinical outcomes for posterior circulation (PC) aneurysms. This study aims to compare the long-term safety and efficacy of treatment of AC and PC aneurysms with PED. METHODS: The databases included Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane, and Scopus. Studies with at least 10 patients and 1-year follow-up were included. Twenty-four studies met our inclusion criteria. A random effect meta-analysis was performed to estimate the ischemic and hemorrhagic complications. A meta-analysis of proportions was performed to estimate the pooled rates of long-term complete aneurysmal occlusion, symptomatic stroke, aneurysmal rupture, and intracranial hemorrhage. RESULTS: There were 1952 aneurysms, of which 1547 (79.25%) were in the AC and 405 (20.75%) in the PC. The 1-year occlusion rate was 78% in AC compared to 73% in PC aneurysms (P < 0.01). The symptomatic infarct rate was 5% in AC compared to 13% in PC (P < 0.01). While the rupture rate was 1% in AC compared to 4% in PC (P = 0.01), the rate of intracranial hemorrhage was 2% for both (P = 0.99). CONCLUSIONS: The long-term occlusion rate after PED was higher in AC aneurysms, and the cumulative incidence of stroke and aneurysm rupture was higher in PC aneurysms.

Mesenchymal Stem Cell Therapy in Acute Intracerebral Hemorrhage: A Dose-Escalation Safety and Tolerability Trial.

BACKGROUND: We conducted a preliminary phase I, dose-escalating, safety, and tolerability trial in the population of patients with acute intracerebral hemorrhage (ICH) by using human allogeneic bone marrow-derived mesenchymal stem/stromal cells. METHODS: Eligibility criteria included nontraumatic supratentorial hematoma less than 60 mL and Glasgow Coma Scale score greater than 5. All patients were monitored in the neurosciences intensive care unit for safety and tolerability of mesenchymal stem/stromal cell infusion and adverse events. We also explored the use of cytokines as biomarkers to assess responsiveness to the cell therapy. We screened 140 patients, enrolling 9 who met eligibility criteria into three dose groups: 0.5 million cells/kg, 1 million cells/kg, and 2 million cells/kg. RESULTS: Intravenous administration of allogeneic bone marrow-derived mesenchymal stem/stromal cells to treat patients with acute ICH is feasible and safe. CONCLUSIONS: Future larger randomized, placebo-controlled ICH studies are necessary to validate this study and establish the effectiveness of this therapeutic approach in the treatment of patients with ICH.

Artificial intelligence and machine learning in aneurysmal subarachnoid hemorrhage: Future promises, perils, and practicalities.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke with thirty-day mortality as high as 40%. Given the expansion of Machine Learning (ML) and Artificial intelligence (AI) methods in health care, SAH patients desperately need an integrated AI system that detects, segments, and supports clinical decisions based on presentation and severity. OBJECTIVES: This review aims to synthesize the current state of the art of AI and ML tools for the management of SAH patients alongside providing an up-to-date account of future horizons in patient care. METHODS: We performed a systematic review through various databases such as Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, Cochrane Database of Systematic Reviews, and Embase. RESULTS: A total of 507 articles were identified. Following extensive revision, only 21 articles were relevant. Two studies reported improved mortality prediction using Glasgow Coma Scale and biomarkers such as Neutrophil to Lymphocyte Ratio and glucose. One study reported that ffANN is equal to the SAHIT and VASOGRADE scores. One study reported that metabolic biomarkers Ornithine, Symmetric Dimethylarginine, and Dimethylguanidine Valeric acid were associated with poor outcomes. Nine studies reported improved prediction of complications and reduction in latency until intervention using clinical scores and imaging. Four studies reported accurate prediction of aneurysmal rupture based on size, shape, and CNN. One study reported AI-assisted Robotic Transcranial Doppler as a substitute for clinicians. CONCLUSION: AI/ML technologies possess tremendous potential in accelerating SAH systems-of-care. Keeping abreast of developments is vital in advancing timely interventions for critical diseases.

TeleNeuroICU: Expanding the Reach of Subspecialty Neurocritical Care.

Telemedicine is a rapidly growing field of medicine due to a combination of high-speed global telecommunication systems and accessibility of small, fast mobile computing platforms with bidirectional audiovisual camera capabilities. Teleneurology is a subset of telemedicine. TeleNeuroICU, one form of teleneurology, is the practice of virtually consulting on patients in the ICU setting with neurological and neurosurgical conditions. Given the current and future shortage of neurologists and neurointensivists, there is a high demand for TeleNeuroICU services around the globe and this is expected to increase in the future. This review summarizes the state of the art around the TeleNeuroICU practice for practitioners in the field, emerging research in this area, and new technologies and integrations that enhance the value of TeleNeuroICU to health care systems.

Colistin neurotoxicity mimicking Guillain-Barré syndrome in a patient with cystic fibrosis: case report and review.

Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy, which is characterized by areflexia and ascending paresthesia which can progress to a respiratory failure. Certain conditions, such as vasculitis and heavy metal and drug toxicity, may have misleadingly similar clinical presentation to GBS. We describe a case of a patient with cystic fibrosis and intravenous colistin-induced neurotoxicity mimicking GBS. The patient had used inhaled colistin on five occasions with no adverse effects, however, developed symptoms on the second day of intravenous treatment. Overlapping findings between immune-mediated polyneuropathy and drug-induced neurotoxicity include limb paresthesia and decreased reflexes. Perioral tingling, however, is a common presentation of colistin-induced neurotoxicity, and therefore, is an important differentiating factor. Early diagnosis prevents further neurologic decline, extensive unnecessary workup and potentially harmful incorrect management.

Intracerebral Hemorrhage: A Common yet Disproportionately Deadly Stroke Subtype.

Spontaneous intracerebral hemorrhage (ICH) is a medical emergency and is disproportionately associated with higher mortality and long-term disability compared with ischemic stroke. The phrase "time is brain" was derived for patients with large vessel occlusion ischemic stroke in which approximately 1.9 million neurons are lost every minute. Similarly, this statement holds true for ICH patients due to a high volume of neurons that are damaged at initial onset and during hematoma expansion. Most cases of spontaneous ICH pathophysiologically stem from chronic hypertension and rupture of small perforating vessels off of larger cerebral arteries supplying deep brain structures, with cerebral amyloid angiopathy being another cause for lobar hemorrhages in older patients. Optimal ICH medical management strategies include timely diagnosis, aggressive blood pressure control, correction of underlying coagulopathy defects if present, treatment of cerebral edema, and continuous assessment for possible surgical intervention. Current strategies in the surgical management of ICH include newly developed minimally invasive techniques for hematoma evacuation, with the goal of mitigating injury to fiber tracts while accessing the clot. We review evidence-based medical and surgical management of spontaneous ICH with the overall goal of reducing neurologic injury and optimizing functional outcome.

Platforms for Personalized Polytherapeutics Discovery in COVID-19.

The COVID-19 pandemic entered its third and most intense to date wave of infections in November 2020. This perspective article describes how combination therapies (polytherapeutics) are a needed focus for helping battle the severity of complications from SARS-CoV-2 infection. It outlines the types of systems that are needed for fast and efficient combinatorial assessment of therapeutic candidates. Proposed are micro-physiological systems using human iPSC as a format for tissue-specific modeling of infection, the use of gene-humanized zebrafish and C. elegans for combinatorial drug screens due to the animals being addressable in liquid multi-well formats, and the use of engineered pseudo-typing systems to safely model infection in the transgenic animals and engineered tissue systems.

Robotics in Simulated COVID-19 Patient Room for Health Care Worker Effector Tasks: Preliminary, Feasibility Experiments.

The coronavirus disease 2019 (COVID-19) pandemic has strained health care systems and personal protective equipment (PPE) supplies globally. We hypothesized that a collaborative robot system could perform health care worker effector tasks inside a simulated intensive care unit (ICU) patient room, which could theoretically reduce both PPE use and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures. We planned a prospective proof-of-concept feasibility and design pilot study to test 5 discrete medical tasks in a simulated ICU room of a COVID-19 patient using a collaborative robot: push a button on intravenous pole machine when alert occurs for downstream occlusion, adjust ventilator knob, push button on ICU monitor to silence false alerts, increase oxygen flow on wall-mounted flow meter to allow the patient to walk to the bathroom and back (dial-up and dial-down oxygen flow), and push wall-mounted nurse call button. Feasibility was defined as task completion robotically. A training period of 45 minutes to 1 hour was needed to program the system de novo for each task. In less than 30 days, the team completed 5 simple effector task experiments robotically. Selected collaborative robotic effector tasks appear feasible in a simulated ICU room of the COVID-19 patient. Theoretically, this robotic approach could reduce PPE use and staff SARS-CoV-2 exposure. It requires future validation and health care worker learning similar to other ICU device training.

Minimally invasive surgery and transsulcal parafascicular approach in the evacuation of intracerebral haemorrhage.

Intracerebral haemorrhage (ICH) describes haemorrhage into the brain parenchyma that may result in a decline of the patient's neurological function. ICH is a common cause of morbidity and mortality worldwide. Aggressive surgical treatment for ICH has remained controversial as clinical trials have failed to demonstrate substantial improvement in patient outcome and mortality. Recently, promising mechanical and pharmacological minimally invasive surgery (MIS) techniques for the treatment of ICH have been described. MIS was designed with the objective of reducing morbidity due to complications of surgical manipulation. Mechanical MIS includes the use of tubular retractors and small diameter instruments for ICH removal. Pharmacological methods consist of catheter placement inside the haematoma cavity for the passive drainage of the haematoma over the course of several days. One of the most favourable approaches for MIS is the use of natural corridors for reaching the lesion, such as the transsulcal parafascicular approach. This approach provides an anatomical dissection of the subjacent white matter tracts, causing the least amount of damage while evacuating the haematoma. A detailed description of the currently known MIS techniques and devices is presented in this review. Special attention is given to the transsulcal parafascicular approach, which has particular benefits to provide a less traumatic MIS with promising overall patient outcome.

Value of Broad Range 16S Ribosomal RNA Gene PCR / Sequencing (Br-PCR) of CSF in the Diagnosis of Bacterial Meningitis.

Bacterial meningitis is a life-threatening condition that requires quick and definitive diagnosis. Bacterial cultures from cerebrospinal fluid (CSF) return with a negative result as treatment with antimicrobials are sometimes started before sampling of CSF can be obtained which makes isolating the causative bacteria challenging. The value of Broad Range 16S Ribosomal RNA Gene Polymerase Chain Reaction / Sequencing of CSF (Br-PCR) can address this problem by amplifying and identifying any bacterial DNA present in a clinical sample. A 65-year-old female presented with rapid onset of high fevers, headache, chills and right hip pain. She had blood cultures drawn, unremarkable CSF analysis in the emergency department, and was discharged home. Ten hours later, she developed vomiting and altered mental status, returned to hospital and started on antimicrobials for gram negative bacteremia and emergently intubated with repeat lumbar puncture showed evidence of bacterial meningitis with pleocytosis and elevated opening pressures. Empiric antimicrobial therapy was started. All subsequent CSF microbiological stains, cultures, and molecular analyses were negative. The blood cultures grew Haemophilus influenzae and H. influenzae meningitis was presumed to be the cause. Therefore, Br-PCR on CSF was sent which detected Haemophilus species DNA. She received a 3-week course of ceftriaxone. After rehabilitation, she returned home without any significant neurological deficits. No relapse of meningitis at 4 months was noted. The application for Br-PCR in the setting of suspected bacterial meningitis with negative stains and cultures could improve a diagnostic algorithm for bacterial meningitis.

Can Baseline Computed Tomography Scans Be Used to Identify Patients at High Risk of Vision Loss due to Terson Syndrome?

PURPOSE: To determine if routinely performed computed tomographic (CT) scanning in patients with aneurysmal subarachnoid hemorrhages (aSAHs) is sufficient to identify patients at high risk of vision loss due to Terson syndrome (TS). METHODS: Consecutive patients with a diagnosis of aSAH admitted to the neurologic intensive care unit of a regional referral hospital over a 3-year period were prospectively evaluated. Head CT scans performed in the emergency department were assessed for the presence of a "crescent sign" (evidence of significant subinternal limiting membrane hemorrhage). Dilated funduscopic examinations were performed by an ophthalmologist, masked to the results of the CT scan, to identify retinal and vitreous hemorrhages consistent with TS. Retinal hemorrhages were categorized according to size-those smaller than 2 mm in diameter were deemed low risk (lrTS) for vision loss and those larger than 2 mm in diameter were deemed high risk (hrTS) for vision loss. RESULTS: One hundred seventeen patients with aSAH were enrolled in the study. The overall incidence of TS was 24.9% (29 of 117 patients; 12 were bilateral). Compared to patients without TS, those with TS had a higher Fisher Hemorrhage Grade and a lower mean (±standard deviation) GCS score (8.66 ± 4.97 vs 12.09 ± 1.10; P < 0.001). The CT crescent sign was positive in 7 patients (6.0%), 6 (5.1%; 2 were bilateral) of whom were found to have hrTS. Of the 110 patients without a CT crescent sign, 88 (75.1%) patients did not have TS, 21 had lrTS, and 1 patient had hrTS in one eye. The CT crescent sign was highly sensitive (85.7%) and specific (99.1%) for diagnosing hrTS. CONCLUSION: The CT crescent sign is a highly sensitive and specific marker for hrTS. CT scanning may replace routine ophthalmologic examinations to identify patients at risk of vision loss due to aSAH.

Pharmacogenomics of Cytochrome P450 of Nimodipine Metabolism After Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is a type of stroke that is life threatening with high rates of mortality, and many survivors are left with permanent neurologic deficits. Nimodipine is the treatment of choice for aSAH with the goal of reduction of delayed cerebral ischemia. It is the only evidence-based medication that has been shown to have improved outcomes for delayed cerebral ischemia; therefore, it is important for neuroscience nurses to be knowledgeable of the pharmacology and pharmacogenomics properties of this medication, including cytochrome P450 (CYP450) enzymes. METHODS AND RESULTS: This article reviews the CYP450 enzyme system including a review of the pharmacotherapy and pharmacogenomics of nimodipine for patients with aSAH illustrated with case study of a patient with abnormal drug metabolism. CONCLUSION: CYP450 enzymes can be inhibited or induced by multiple medications resulting in clinically significant differences in drug metabolism. Food and Drug Administration-approved medication nimodipine is the only medication shown to improve outcomes in patients with aSAH. Hence, it is important to have awareness of potential drug-to-drug interactions and pharmacogenomics of nimodipine when caring for critically ill patients with aSAH.

Evaluation of Hospital-wide Readmission Risk Calculator to Predict 30-Day Readmission in Neurocritical Care Patients.

BACKGROUND AND PURPOSE: Thirty-day hospital readmissions have been shown to be a measure of quality and result in higher mortality and increased costs. Readmissions are a target for hospitals and payers; thus, several centers have developed predictive readmission scores to identify high-risk patients. The purpose of this study was to evaluate the current hospital-wide readmission risk calculator and the ability of this tool to predict 30-day readmissions in the neurocritical care population. METHODS: A retrospective chart review was performed that included 340 consecutive patients admitted to our neuroscience critical care unit. Data including readmission scores, reason for admission, length of stay, and whether they were readmitted were recorded. RESULTS: After removing patients without readmission scores or who died at the end of the original admission, the records of N = 279 patients were analyzed. Patients were more likely to be readmitted if they were initially emergently hospitalized or if there was a history of malignancy. Readmitted patients had a longer original hospital length of stay. Furthermore, 65.8% of the patients who were given a "low risk" for readmission were readmitted within 30 days. CONCLUSIONS: This small set of data in a specific patient population found that the current risk prediction score was inaccurate in predicting readmission in the neuroscience intensive care unit population. Further evaluation is needed of a larger patient population to generalize these results for all neuroscience intensive care unit patients. To design an accurate readmission risk tool, centers should create unique readmission scores based on less heterogeneous patient populations.

The Incidence of Catheter Tract Hemorrhage and Catheter Placement Accuracy in the CLEAR III Trial.

BACKGROUND: Incidence of catheter tract hemorrhage (CTH) after initial ventriculostomy placement ranges from 10 to 34%. We investigated CTH incidence in the Clot Lysis: Evaluation of Accelerated Resolution of Intraventricular Hemorrhage Phase III trial. METHODS: Prospective observational analysis of 1000 computer tomography (CT) scans from all 500 patients enrolled in the trial. All catheters were evaluated on first CT post-placement and on last CT prior to randomization for placement location and CTH size, location, and severity. Clinical variables were assessed for association with CTH with multivariable logistic regression. RESULTS: Of 563 catheters, CTH was detected in 14 and 21% of patients on first and last CT (median 3.7 and 43.4 h after catheter placement, respectively). All, but one were asymptomatic. Majority of CTH (86%) occurred within 24 h after placement, were located within 1 cm of the skull, and had at least one diameter > 5 mm. Most catheters (71%) terminated in the third or lateral ventricle ipsilateral to insertion site. Factors significantly associated with CTH were pre-admission use of antiplatelet drugs, accuracy of catheter placement, non-operating room catheter placement, Asian race, and intraventricular hemorrhage expansion. CONCLUSIONS: CTH incidence on initial catheter placement and during stabilization was relatively low, despite emergent placement in a high-risk population. Catheter placement accuracy was similar or better than convenience samples from the published literature. Decreasing risk of CTH may be achieved with attention to catheter placement accuracy and placement in the operating room. Antiplatelet agent use was an independent risk factor for CTH.