Implantable Neurostimulation for Headache Disorders: Effect on Healthcare Utilization and Expenditures.

OBJECTIVES: Chronic daily headache is a considerable source of morbidity for patients and also carries an enormous economic burden. Patients who fail standard medication regimens lack well-defined therapies, and neurostimulation is an emerging option for these patients. The purpose of this study was to analyze the cost utility of implantable neurostimulation for treatment of headache. METHODS: We utilized the Thompson Reuters Marketscan Data base to identify individuals diagnosed with headache disorders who underwent percutaneous neurostimulation. Healthcare expenditures for individuals who subsequently received permanent, surgically implanted neurostimulatory devices were compared to those who did not. Only individuals who sought implantable neurostimulation were included to account for headache severity. The cohorts were adjusted for comorbidity and prior headache-related expenses. Costs were modeled longitudinally using a generalized estimating equation. RESULTS: A total of 579 patients who underwent percutaneous trial of neurostimulation were included, of which 324 (55.96%) converted to permanent neurostimulation within one year. Unadjusted expenditures were greater for patients who underwent conversion to the permanent neurostimulation device, as expected. Costs grew at a lower rate for patients who converted to permanent device implantation. Cost neutrality for patients receiving the permanent device was reached in less than five years after the enrollment date. The mean cost of conversion to a permanent implantation was $18,607.53 (SD $26,441.34). CONCLUSIONS: Our study suggests that implantable neurostimulation reduces healthcare expenditures within a relatively short time period in patients with severe refractory headache.

A national survey of spinal cord stimulation trial-to-permanent conversion rates.

OBJECTIVES: Conversion rates from trial leads to permanent spinal cord stimulation (SCS) systems have recently come under scrutiny. Our goal was to examine the rate of conversion from trial lead to permanent system placement as well as identify factors associated with successful SCS conversion. MATERIALS AND METHODS: We designed a large retrospective analysis using the Thomson Reuters MarketScan database. We included all patients who underwent a percutaneous trial of neurostimulatory electrodes from the years 2000 to 2009 who were aged 18 and older. Patients were then tracked to see if they went on to receive a permanent SCS system. Patients were also analyzed in univariate and multivariate models to identify factors associated with successful conversion. RESULTS: A total of 21,672 unique instances of percutaneous trials were identified. Overall, 41.4% of those receiving trials went on to have a permanent SCS system installed within the subsequent three months. Factors associated with increased likelihood of successful conversion included having commercial insurance (43% vs. 37%, p < 0.0001), younger age (43% for those aged 35-44 vs. 39% for those aged 65 and older, p < 0.0001), and never having had a previous percutaneous trial attempt (44% for first-time trials vs. 27% for those on their second trial vs. 14% for those on their third or later trial, p < 0.0001). In multivariate analysis, we found significant variation in conversion rate by geographic area (patients in the North Central region vs. Northeast region: odds ratio 1.48, 95% confidence interval [1.31, 1.66]; p < 0.0001). CONCLUSIONS: In this study of a national cohort of patients, we identified specific factors associated with higher conversion rates, along with significant geographical variation. In general, there is a need for better patient selection by physicians who practice neuromodulation.

Clearance of amyloid-beta by circulating lipoprotein receptors.

Low-density lipoprotein receptor-related protein-1 (LRP) on brain capillaries clears amyloid beta-peptide (Abeta) from brain. Here, we show that soluble circulating LRP (sLRP) provides key endogenous peripheral 'sink' activity for Abeta in humans. Recombinant LRP cluster IV (LRP-IV) bound Abeta in plasma in mice and Alzheimer's disease-affected humans with compromised sLRP-mediated Abeta binding, and reduced Abeta-related pathology and dysfunction in a mouse model of Alzheimer disease, suggesting that LRP-IV can effectively replace native sLRP and clear Abeta.

Improved preventive care for asthma: a randomized trial of clinician prompting in pediatric offices.

OBJECTIVE: To determine whether clinician prompting regarding a child's symptom severity and guideline recommendations at the time of an office visit improves the delivery of preventive asthma care. DESIGN: Randomized controlled trial. SETTING: Two inner-city pediatric practices in Rochester, NY. PARTICIPANTS: Two hundred twenty-six children with persistent asthma (aged 2-12 years) presenting to the clinics for well-child care, asthma care, or non-asthma-related illness care. Intervention We assigned children randomly to a clinician-prompting group (single-page prompt including the child's symptoms and guideline recommendations given to the clinician at the time of the visit) or a standard-care group (no prompt given). Interviewers called parents after the visit to inquire about preventive measures taken, and medical charts were reviewed. MAIN OUTCOME MEASURES: Any preventive action related to asthma taken at the visit. RESULTS: Children in the clinician-prompting group were more likely to have had any preventive measures taken at the visit compared with children in the standard-care group (87% vs 69%). Specifically, visits for children in the clinician-prompting group were more likely to include delivery of an action plan (50% vs 24%), discussions regarding asthma (87% vs 76%), and recommendations for an asthma follow-up visit (54% vs 37%). In a regression model, children in the clinician-prompting group had 3-fold greater odds of receiving any preventive action compared with the standard-care group. CONCLUSION: Clinician prompting regarding asthma severity and care guidelines at the time of an office visit significantly improved the delivery of preventive asthma care.

Impact of advancing age on post-operative complications of deep brain stimulation surgery for essential tremor.

Essential tremor (ET) was the original indication for deep brain stimulation (DBS), with USA Food and Drug Administration approval since 1997. Despite the efficacy of DBS, it is associated with surgical complications that cause sub-optimal clinical outcomes. Given that ET is a progressive disease with increase in symptom severity with increasing age, this study evaluated the impact of increasing age on short-term complications following DBS surgery for ET. The Thomson-Reuters MarketScan database was utilized (New York, NY, USA). Patients selected were over age 18 and underwent DBS for ET between the years 2000 and 2009. Multivariable logistic regression analysis was used to calculate complication odds ratios (OR) for a 5 year increase in age, after controlling for other covariates. Six hundred sixty-one patients were included in the analysis. The mean (standard deviation) age was 61.9 (14.3) years, with 17% of individuals aged ⩾75 years. Overall 56.9% of patients were male, and 44.6% had a Charlson Comorbidity Score of ⩾1. Additionally, 7.1% of patients experienced at least one complication within 90 days, including wound infections (3.0%), pneumonia (2.4%), hemorrhage or hematoma (1.5%), or pulmonary embolism (0.6%). Increasing age was not significantly associated with the overall 90 day complication rates (OR 0.89; 95% confidence interval [CI] 0.77-1.02; p=0.102). The risk of the two most common procedure-related complications, hemorrhage and infection, did not significantly increase with age (hemorrhage: OR 1.02; 95%CI 0.77-1.37; p=0.873; and infection: OR 0.88; 95%CI 0.72-1.07; p=0.203). Our findings suggest that age should not be a primary exclusion factor for determining candidacy for DBS and also suggest a possible expansion of the traditional therapeutic window since post-operative complications remained relatively stable.

Delayed sub-aponeurotic fluid collections in infancy: Three cases and a review of the literature.

BACKGROUND: Sub-aponeurotic fluid collections (SFCs) in the neonatal period are poorly described in the literature. We describe the occurrence, possible etiologies and treatment of sub-aponeurotic fluid collections following the neonatal period. CASE DESCRIPTION: We present 3 cases of previously healthy children who developed soft, fluctuant, extracranial masses several weeks after birth. All 3 children were seen by a pediatric neurosurgeon after parents noticed scalp masses between 5 and 9 weeks of age. All 3 children were found to be otherwise healthy. Two of the children were born via C-section and 1 child was born vaginally. The vaginal delivery was described as difficult and utilized vacuum assist. Scalp electrodes were placed in all 3 children for intensive monitoring during labor. These children received plain skull x-rays to assess for abnormalities, and 2 of the children underwent a non-contrast brain CT scan to better characterize the fluid collection. Plain x-rays and CT scans showed no abnormalities of the skull or ventricles. In both patients who underwent a CT scan, a soft tissue prominence was noted with a Hounsfield unit similar to water. All cases resolved between 5 and 9 weeks after initial presentation, with no long-term sequelae. CONCLUSION: SFCs presenting after the neonatal period are usually associated with benign soft tissue swellings. Use of fetal scalp electrodes has been shown to cause cerebrospinal fluid (CSF) leakage in the neonatal period and may result in delayed SFC. This condition is benign, and the recommended course of treatment is conservative management.

Activated protein C analog with reduced anticoagulant activity improves functional recovery and reduces bleeding risk following controlled cortical impact.

The anticoagulant activated protein C (APC) protects neurons and vascular cells from injury through its direct cytoprotective effects that are independent of its anticoagulant action. Wild-type recombinant murine APC (wt-APC) exerts significant neuroprotection in mice if administered early after traumatic brain injury (TBI). Here, we compared efficacy and safety of a late therapy for TBI with wt-APC and 3K3A-APC, an APC analog with approximately 80% reduced anticoagulant activity but normal cytoprotective activity, using a controlled cortical impact model of TBI. Mice received 0.8 mg/kg intraperitoneally of recombinant murine 3K3A-APC, wt-APC or saline at 6, 12, 24 and 48 h after injury. 3K3A-APC (n=15) relative to wt-APC (n=15) improved motor and sensorimotor recovery within the first three days post-trauma as demonstrated by rotarod (p<0.05) and beam balance test (p<0.05), respectively. Both, wt-APC and 3K3A-APC reduced the lesion volume seven days after injury by 36% (n=8; p<0.01) and 56% (n=8; p<0.01), respectively, compared to saline (n=8). Three days post-TBI, the hemoglobin levels in the injured brain were increased by approximately 3-fold after wt-APC treatment compared to saline indicating an increased risk for intracerebral bleeding. In contrast, comparable levels of brain hemoglobin in 3K3A-APC-treated and saline-treated mice suggested that 3K3A-APC treatment did not increase risk for bleeding after TBI. Thus, compared to wt-APC, 3K3A-APC is more efficacious and safer therapy for TBI with no risk for intracerebral hemorrhage.

Activated protein C is neuroprotective and mediates new blood vessel formation and neurogenesis after controlled cortical impact.

OBJECTIVE: Activated protein C (APC) is neuroprotective in stroke models and promotes postischemic neovascularization and neurogenesis. We used a controlled cortical impact (CCI) in mice to determine the effects of APC on neuroprotection and angiogenesis and neurogenesis after traumatic brain injury (TBI). METHODS: Mice were given (1) single-dose APC (0.8 mg/kg intraperitoneally) 15 minutes after injury, (2) multidose APC (0.8 mg/kg intraperitoneally) 15 minutes and 6 to 48 hours after injury, or (3) vehicle. We then assessed the effects of APC on posttraumatic motor function with the rotarod and wire grip and beam balance tasks, and we determined the lesion volumes and studied the formation of new blood vessels and markers of neurogenesis. RESULTS: Mice treated with single-dose or multidose APC, compared with vehicle, showed significantly improved motor function on all tests. In the single-dose and multidose APC treatment groups, at 7 days after treatment, lesion volume was significantly decreased by 30% and 50%, respectively. Multidose APC, but not single-dose APC, increased new blood vessel formation as shown by CD105(+)/Ki-67(+) double immunostaining by nearly 2-fold at 7 days. Multidose APC also promoted posttraumatic proliferation of neuroblasts in the subventricular zone (SVZ) and their migration from the SVZ to the perilesional area. CONCLUSION: Activated protein C improves functional outcome and is neuroprotective after TBI. It also promotes angiogenesis and survival and migration of neuroblasts from the SVZ to the perilesional area, but the exact role of these brain repair mechanisms remains to be determined. The present findings suggest that APC therapy may hold a significant therapeutic potential for TBI.