Inpatient mortality and healthcare resource utilization of nontraumatic intracerebral hemorrhage complications in the US.

OBJECTIVE: Nontraumatic, primary intracerebral hemorrhage (ICH) accounts for 2 million strokes worldwide annually and has a 1-year survival rate of 50%. Recent studies examining functional outcomes from ICH evacuation have been performed, but limited work has been done quantifying the incidence of subsequent complications and their healthcare economic impact. The purpose of this study was to quantify the incidence and healthcare resource utilization (HCRU) for major complications that can arise from ICH. METHODS: The IBM MarketScan Research databases were used to retrospectively identify patients with ICH from 2010 to 2015. Complications examined included cerebral edema, hydrocephalus, venous thromboembolic events (VTEs), pneumonia, urinary tract infections (UTIs), and seizures. For each complication, inpatient mortality and HCRU were assessed. RESULTS: Of 25,322 adult patients included, 10,619 (42%) developed complications during the initial admission of ICH: 22% had cerebral edema, 11% hydrocephalus, 10% pneumonia, 6% UTIs, 5% seizures, and 5% VTEs. The inpatient mortality rates at 7 and 30 days for each complication of ICH ranked from highest to lowest were hydrocephalus (24% and 32%), cerebral edema (15% and 20%), pneumonia (8% and 18%), seizure (7% and 13%), VTE (4% and 11%), and UTI (4% and 8%). Hydrocephalus had the highest total cost (median $92,776, IQR $39,308-$180,716) at 7 days post-ICH diagnosis and the highest cumulative total cost (median $170,839, IQR $91,462-$330,673) at 1 year post-ICH diagnosis. CONCLUSIONS: This study characterizes one of the largest cohorts of patients with nontraumatic ICH in the US. More than 42% of the patients with ICH developed complications during initial admission, which resulted in high inpatient mortality and considerable HCRU.

Evaluation of neurapheresis therapy in vitro: a novel approach for the treatment of leptomeningeal metastases.

BACKGROUND: Leptomeningeal metastases (LM), late-stage cancer when malignant cells migrate to the subarachnoid space (SAS), have an extremely poor prognosis. Current treatment regimens fall short in effectively reducing SAS tumor burden. Neurapheresis therapy is a novel approach employing filtration and enhanced circulation of the cerebrospinal fluid (CSF). Here, we examine the in vitro use of neurapheresis therapy as a novel, adjunctive treatment option for LM by filtering cells and augmenting the distribution of drugs that may have the potential to enhance the current clinical approach. METHODS: Clinically relevant concentrations of VX2 carcinoma cells were suspended in artificial CSF. The neurapheresis system's ability to clear VX2 carcinoma cells was tested with and without the chemotherapeutic presence (methotrexate [MTX]). The VX2 cell concentration following each filtration cycle and the number of cycles required to reach the limit of detection were calculated. The ability of neurapheresis therapy to circulate, distribute, and maintain therapeutic levels of MTX was assessed using a cranial-spinal model of the SAS. The distribution of a 6 mg dose was monitored for 48 h. An MTX-specific ELISA measured drug concentration at ventricular, cervical, and lumbar sites in the model over time. RESULTS: In vitro filtration of VX2 cancer cells with neurapheresis therapy alone resulted in a 2.3-log reduction in cancer cell concentration in 7.5 h and a 2.4-log reduction in live-cancer cell concentration in 7.5 h when used with MTX. Cranial-spinal model experiments demonstrated the ability of neurapheresis therapy to enhance the circulation of MTX in CSF along the neuraxis. CONCLUSION: Neurapheresis has the potential to act as an adjunct therapy for LM patients and significantly improve the standard of care.

In vitro and numerical simulation of blood removal from cerebrospinal fluid: comparison of lumbar drain to Neurapheresis therapy.

BACKGROUND: Blood removal from cerebrospinal fluid (CSF) in post-subarachnoid hemorrhage patients may reduce the risk of related secondary brain injury. We formulated a computational fluid dynamics (CFD) model to investigate the impact of a dual-lumen catheter-based CSF filtration system, called Neurapheresis™ therapy, on blood removal from CSF compared to lumbar drain. METHODS: A subject-specific multiphase CFD model of CSF system-wide solute transport was constructed based on MRI measurements. The Neurapheresis catheter geometry was added to the model within the spinal subarachnoid space (SAS). Neurapheresis flow aspiration and return rate was 2.0 and 1.8 mL/min, versus 0.2 mL/min drainage for lumbar drain. Blood was modeled as a bulk fluid phase within CSF with a 10% initial tracer concentration and identical viscosity and density as CSF. Subject-specific oscillatory CSF flow was applied at the model inlet. The dura and spinal cord geometry were considered to be stationary. Spatial-temporal tracer concentration was quantified based on time-average steady-streaming velocities throughout the domain under Neurapheresis therapy and lumbar drain. To help verify CFD results, an optically clear in vitro CSF model was constructed with fluorescein used as a blood surrogate. Quantitative comparison of numerical and in vitro results was performed by linear regression of spatial-temporal tracer concentration over 24-h. RESULTS: After 24-h, tracer concentration was reduced to 4.9% under Neurapheresis therapy compared to 6.5% under lumbar drain. Tracer clearance was most rapid between the catheter aspiration and return ports. Neurapheresis therapy was found to have a greater impact on steady-streaming compared to lumbar drain. Steady-streaming in the cranial SAS was ~ 50× smaller than in the spinal SAS for both cases. CFD results were strongly correlated with the in vitro spatial-temporal tracer concentration under Neurapheresis therapy (R2 = 0.89 with + 2.13% and - 1.93% tracer concentration confidence interval). CONCLUSION: A subject-specific CFD model of CSF system-wide solute transport was used to investigate the impact of Neurapheresis therapy on tracer removal from CSF compared to lumbar drain over a 24-h period. Neurapheresis therapy was found to substantially increase tracer clearance compared to lumbar drain. The multiphase CFD results were verified by in vitro fluorescein tracer experiments.

Impact of Neurapheresis System on Intrathecal Cerebrospinal Fluid Dynamics: A Computational Fluid Dynamics Study.

It has been hypothesized that early and rapid filtration of blood from cerebrospinal fluid (CSF) in postsubarachnoid hemorrhage patients may reduce hospital stay and related adverse events. In this study, we formulated a subject-specific computational fluid dynamics (CFD) model to parametrically investigate the impact of a novel dual-lumen catheter-based CSF filtration system, the Neurapheresis™ system (Minnetronix Neuro, Inc., St. Paul, MN), on intrathecal CSF dynamics. The operating principle of this system is to remove CSF from one location along the spine (aspiration port), externally filter the CSF routing the retentate to a waste bag, and return permeate (uncontaminated CSF) to another location along the spine (return port). The CFD model allowed parametric simulation of how the Neurapheresis system impacts intrathecal CSF velocities and steady-steady streaming under various Neurapheresis flow settings ranging from 0.5 to 2.0 ml/min and with a constant retentate removal rate of 0.2 ml/min simulation of the Neurapheresis system were compared to a lumbar drain simulation with a typical CSF removal rate setting of 0.2 ml/min. Results showed that the Neurapheresis system at a maximum flow of 2.0 ml/min increased average steady streaming CSF velocity 2× in comparison to lumbar drain (0.190 ± 0.133 versus 0.093 ± 0.107 mm/s, respectively). This affect was localized to the region within the Neurapheresis flow loop. The mean velocities introduced by the flow loop were relatively small in comparison to normal cardiac-induced CSF velocities.

Novel Treatment of Cryptococcal Meningitis via Neurapheresis Therapy.

Cryptococcal meningitis (CM) has emerged as the most common life-threatening fungal meningitis worldwide. Current management involves a sequential, longitudinal regimen of antifungals; despite a significant improvement in survival compared with uniform mortality without treatment, this drug paradigm has not led to a consistent cure. Neurapheresis therapy, extracorporeal filtration of yeasts from cerebrospinal fluid (CSF) in infected hosts, is presented here as a novel, one-time therapy for CM. In vitro filtration of CSF through this platform yielded a 5-log reduction in concentration of the yeast and a 1-log reduction in its polysaccharide antigen over 24 hours. Additionally, an analogous closed-loop system achieved 97% clearance of yeasts from the subarachnoid space in a rabbit model over 4-6 hours. This is the first publication demonstrating the direct ability to rapidly clear, both in vitro and in vivo, the otherwise slowly removed fungal pathogen that directly contributes to the morbidity and mortality seen in CM.