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.

Prognostic model for nephrotoxicity among HIV-positive Zambian adults receiving tenofovir disoproxil fumarate-based antiretroviral therapy.

Persons living with HIV (PLWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) risk suffering TDF-associated nephrotoxicity (TDFAN). TDFAN can result in short- and long-term morbidity, including permanent loss of kidney function, chronic kidney disease (CKD), and end-stage kidney disease (ESKD) requiring dialysis. Currently, there is no model to predict this risk or discern which patients to initiate TDF-based therapy. Consequently, some patients suffer TDFAN within the first few months of initiating therapy before switching to another suitable antiretroviral or a lower dose of TDF. In a prospective observational cohort study of adult Zambian PLWH, we modelled the risk for TDFAN before initiating therapy to identify individuals at high risk for experiencing AKI after initiating TDF-based therapy. We enrolled 205 HIV-positive, ART-naïve adults initiating TDF-based therapy followed for a median of 3.4 months for TDFAN at the Adult Infectious Disease Research Centre (AIDC) in Lusaka, Zambia. We defined TDFAN as meeting any of these acute kidney disease (AKD) criteria: 1) An episode of estimated glomerular filtration rate (eGFR)< 60ml/ min/1.73m2 within 3 months, 2) reduced eGFR by> 35% within 3 months or 3) increased serum creatinine by> 50% within 3 months. A total of 45 participants (22%) developed acute kidney disease (AKD) after TDF-based therapy. The development of AKD within the first 3 months of commencing TDF-based therapy was associated with an increase in baseline serum creatinine, age, baseline eGFR and female sex. We concluded that baseline characteristics and baseline renal function biomarkers predicted the risk for AKD within the first 3-months of TDF-based therapy.

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.

Endotheliitis, endothelin, and endothelin receptor blockers in COVID-19.

We summarize the role of endothelin as a potent vasoconstrictor, pro-inflammatory, pro-oxidative agent in the pathophysiologic effects and end-organ dysfunction of coronavirus disease 2019 (COVID-19). Endotheliitis is an under-recognized pathophysiologic process that causes various types of dysfunction in end organs, including heart, lung, kidney, and brain. Endothelin receptor blockers, such as bosentan and sitaxentan, can pave a path ahead in the realm of COVID-19 therapies. These agents have a potential role against COVID-19 and should be studied in research trials to determine their efficacy in treatment of this severe disease.

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.

Three-tier stratification for CNS COVID-19 to help decide which patients should undergo lumbar puncture with CSF analysis: a case report and literature review.

The COVID-19 pandemic continues to overwhelm global healthcare systems. While the disease primarily causes pulmonary complications, reports of central nervous system (CNS) involvement have recently emerged ranging from encephalopathy to stroke. This raises a practical dilemma for clinicians as to when to pursue neuroimaging and lumbar tap with cerebrospinal fluid (CSF) analysis in COVID-19 patients with neurological symptoms. We present a case of an encephalopathic patient infected with SARS-CoV-2 with no pulmonary symptoms. We propose a three-tier risk stratification for CNS COVID-19 aiming to help clinicians to decide which patients should undergo CSF analysis. The neurological examination remains an integral component of screening and evaluating patients for COVID-19 considering the range of emerging CNS complications.

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.

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.

Prevalence of Previously Undiagnosed Abdominal Aortic Aneurysms in Patients with Intracranial Aneurysms: From the Brain and Aortic Aneurysms Study (BAAS).

BACKGROUND: A relationship between intracranial and abdominal aortic aneurysms (AAA) has been appreciated through genome-wide association studies suggesting a shared pathophysiology. However, the actual prevalence of AAA in patients presenting with ruptured intracranial aneurysms is not known. Our aim was to estimate the prevalence of previously undiagnosed AAA in patients presenting with aneurysmal subarachnoid hemorrhage (aSAH) to see if it may be high enough to justify formally testing the utility of screening. METHODS: A prospective, observational inception cohort study of 81 consecutive patients presenting to Mayo Clinic Florida with aSAH was performed from August 14, 2011 to February 10, 2014. These individuals were then screened using an abdominal ultrasound technique for an AAA. Our primary end point was detection of AAA. Our secondary end points were 30-day good-to-fair functional status (modified Rankin scale < 4) and all-cause mortality. RESULTS: We detected an AAA in 10 patients (rate: 12%; 95% CI 6-22%) with aSAH. The mean diameter of these AAA was 3.4 ± 1.0 cm. Among these 10 patients, there was one death within the first month of aSAH hospitalization. There were no significant differences in demographic or clinical characteristics based on AAA detection status. Mean follow-up time was 4.7 years. The rate of good-to-fair functional status at 30-days was 79%. All-cause mortality during follow-up at 1-year was higher for patients with AAA (36%; 95% CI 0-61%) compared to patients without AAA (7%; 95% CI 1-14%) (log-rank p = 0.045). CONCLUSIONS: The co-prevalence of AAA in patients presenting with ruptured brain aneurysms may be sufficiently high such that screening for AAA among likely survivors of aSAH might be appropriate. Larger studies would be needed to establish a net clinical benefit from screening AAA and then treating newly identified large AAAs in this morbid population.

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.