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.

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.

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.

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.

Teleneurosonology: a novel application of transcranial and carotid ultrasound.

BACKGROUND: To demonstrate the technical feasibility of interfacing transcranial Doppler (TCD) and carotid "duplex" ultrasonography (CUS) peripherals with telemedicine end points to provide real-time spectral waveform and duplex imaging data for remote review and interpretation. METHODS: We performed remote TCD and CUS examinations on a healthy, volunteer employee from our institution without known cerebrovascular disease. The telemedicine end point was stationed in our institution's hospital where the neurosonology examinations took place and the control station was in a dedicated telemedicine room in a separate building. The examinations were performed by a postgraduate level neurohospitalist trainee (M.N.R.) and interpreted by an attending vascular neurologist, both with experience in the performance and interpretation of TCD and CUS. RESULTS: Spectral waveform and duplex ultrasound data were successfully transmitted from TCD and CUS instruments through a telemedicine end point to a remote reviewer at a control station. Image quality was preserved in all cases, and technical failures were not encountered. CONCLUSIONS: This proof-of-concept study demonstrates the technical feasibility of interfacing TCD and CUS peripherals with a telemedicine end point to provide real-time spectral waveform and duplex imaging data for remote review and interpretation. Medical diagnostic and telemedicine devices should be equipped with interfaces that allow simple transmission of high-quality audio and video information from the medical devices to the telemedicine technology. Further study is encouraged to determine the clinical impact of teleneurosonology.

Refractory and super-refractory status epilepticus--an update.

Status epilepticus is a medical emergency with a high mortality. Early recognition and initiation of treatment leads to a better response and may improve outcomes. Refractory status epilepticus is defined as recurrent seizure activity despite two appropriately selected and dosed antiepileptic drugs including a benzodiazepine. The term "super-refractory status epilepticus" was introduced during the London-Innsbruck Colloquium on status epilepticus in 2011 and refers to status epilepticus that continues or recurs 24 h or more after the initiation of treatment with anesthetic antiepileptic drugs. This includes cases in which seizure control is attained after induction of anesthesia but recurs on weaning the patient off the anesthetic agent. This article reviews the approach to refractory status epilepticus and super-refractory status epilepticus, including management as well as common pathophysiological causes of these entities.

Safety and efficacy of repeated doses of 14.6 or 23.4 % hypertonic saline for refractory intracranial hypertension.

BACKGROUND: The efficacy of administering single bolus doses of 14.6 or 23.4 % hypertonic saline (HTS) to treat refractory intracranial hypertension has been demonstrated in the literature and has emerged as an important therapeutic option in treating these patients. However, many institutions lack experience with this therapy and there are few published studies evaluating the safety of repeated bolus dosing of HTS. METHODS: A retrospective review of patients admitted between January 2008 and July 2012 was conducted to evaluate the use of repeated dosing of HTS in patients with refractory intracranial hypertension. The primary objective was to evaluate the safety of repeated dosing of HTS assessed by documented adverse effects such as central pontine myelinolysis (CPM) and severe fluctuations in serum sodium concentrations. Secondary objectives were to evaluate the efficacy of repeated dosing HTS in reducing intracranial pressure (ICP) and to compare the dose-response relationship of 14.6 and 23.4 % doses. RESULTS: Fifty-five patients were included for evaluation, each receiving an average of 8.9 (range 2-61) doses of HTS. A statistically significant increase in mean serum sodium concentration occurred with the administration of HTS (p < 0.0001). No cases of CPM were identified. The use of HTS was found to be effective based on decreases in ICP after administration (p < 0.0001, mean ICP reduction: 10.1 mmHg, range 3-23.6 mmHg). The efficacy of 23.4 % saline in decreasing ICP was not found to be significantly different than 14.6 % saline (p = 0.23). CONCLUSIONS: Repeat bolus dosing of 14.6 or 23.4 % HTS appears to be relatively safe and effective for treating refractory intracranial hypertension assuming there is frequent electrolyte monitoring and concomitant fluid management.

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.

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.

Intracranial hemorrhage following neuroendovascular procedures with abciximab is associated with high mortality: a multicenter series.

BACKGROUND: Abciximab is being used as an adjunct to neuroendovascular procedures both to prevent and treat ischemic sequelae. Experience with abciximab in this setting is limited; major bleeding complications, including fatal intracranial hemorrhage (ICH), are of particular concern. We report our multicenter experience with ICH following the administration of abciximab during neuroendovascular procedures. METHODS: We identified neuroendovascular procedures (including cerebral angiograms, aneurysm coiling procedures, angioplasty/vascular stenting procedures, and emergent revascularization procedures) that used abciximab at Mayo Clinic Hospitals in Rochester, Jacksonville, and Phoenix between November 2000 and April 2009. Cases of periprocedural ICH were identified and pertinent demographic, historical, procedural, radiographic, and laboratory data were collected. Clinical outcome was measured either at death or discharge by the Glasgow Outcome Scale (GOS). RESULTS: Abciximab was used in 51 neuroendovascular procedures; 9 cases of ICH were identified. Procedures performed and indications for abciximab use varied. Route of abciximab administration included IV bolus only (n = 4), IA bolus followed by IV infusion (n = 3), IV bolus followed by IV infusion (n = 1), and IV infusion without preceding bolus (n = 1). All but 1 of the patients received concomitant periprocedural antiplatelet, anticoagulant, or thrombolytic agents. Eight of the 9 cases of ICH were detected within 7 h of abciximab administration. ICH pattern varied. Four patients died following ICH. CONCLUSIONS: Adjunctive use of abciximab to prevent or treat ischemic sequelae during neuroendovascular procedures is associated with a high risk of ICH (18%). We report 9 cases of ICH associated with abciximab administration during neuroendovascular procedures with 44% mortality.

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.

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.

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.

Spontaneous intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (sICH) is defined as bleeding within the brain parenchyma, and occurs twice as commonly as subarachnoid hemorrhage, but is equally as deadly. Risk factors for sICH include hypertension, advanced age, leukoaraiosis, prior ICH, renal failure, use of anticoagulant drugs, and cerebral amyloid angiopathy. When a patient is clinically suspected of having sICH, head computed tomography scan is the standard diagnostic tool. However, newer magnetic resonance neuroimaging techniques may aid in determining the underlying pathology and aid in prognosis. Supportive care and blood pressure management are important in the care of patients with sICH. Ongoing research is aimed at determining a safe blood pressure goal that may also prevent expansion of hemorrhage. Hemostatic medications and neuroprotectants have thus far not shown clinical improvement. Although several neurosurgical trials have failed to demonstrate benefit for surgical evacuation of sICH, multiple research trials are ongoing investigating acute blood pressure control, deep or basal ganglionic hemorrhage evacuation via minimally invasive approach (MISTIE; http://mistietrial.com/default.aspx), lobar ICH evacuation (STICH; II http://research.ncl.ac.uk/stich/), and intraventricular thrombolysis with tissue plasminogen activator (tPA) (CLEAR III; http://biosgroup-johnshopkinsmedicine.health.officelive.com/default.aspx).