Perivascular Space Burden and Cerebrospinal Fluid Biomarkers in US Veterans With Blast-Related Mild Traumatic Brain Injury.

Blast-related mild traumatic brain injury (mTBI) is recognized as the "signature injury" of the Iraq and Afghanistan wars. Sleep disruption, mTBI, and neuroinflammation have been individually linked to cerebral perivascular space (PVS) dilatation. Dilated PVSs are putative markers of impaired cerebrospinal fluid (CSF) and interstitial fluid exchange, which plays an important role in removing cerebral waste. The aim of this cross-sectional, retrospective study was to define associations between biomarkers of inflammation and MRI-visible PVS (MV-PVS) burden in Veterans after blast-related mTBI (blast-mTBI) and controls. The CSF and plasma inflammatory biomarker concentrations were compared between blast-mTBI and control groups and correlated with MV-PVS volume and number per white matter cm3. Multiple regression analyses were performed with inflammatory biomarkers as predictors and MV-PVS burden as the outcome. Correction for multiple comparisons was performed using the Banjamini-Hochberg method with a false discovery rate of 0.05. There were no group-wise differences in MV-PVS burden between Veterans with blast-mTBI and controls. Greater MV-PVS burden was significantly associated with higher concentrations of several proinflammatory biomarkers from CSF (i.e., eotaxin, MCP-1, IL-6, IL-8) and plasma (i.e., MCP-4, IL-13) in the blast-mTBI group only. After controlling for sleep time and symptoms of post-traumatic stress disorder, temporal MV-PVS burden remained significantly associated with higher CSF markers of inflammation in the blast-mTBI group only. These data support an association between central, rather than peripheral, neuroinflammation and MV-PVS burden in Veterans with blast-mTBI independent of sleep. Future studies should continue to explore the role of blast-mTBI related central inflammation in MV-PVS development, as well as investigate the impact of subclinical exposures on MV-PVS burden.

Characterizing utilization patterns and reoperation risk factors of interspinous process devices: analysis of a national claims database.

INTRODUCTION: Interspinous process devices (IPDs) were developed as minimally invasive alternatives to open decompression surgery for spinal stenosis. However, given high treatment failure and reoperation rates, there has been minimal adoption by spine surgeons. This study leveraged a national claims database to characterize national IPD usage patterns and postoperative outcomes after IPD implantation. METHOD: Using the PearlDiver database, we identified all patients who underwent 1- or 2-level IPD implantation between 2010 and 2018. Univariate and multivariable logistic regression was performed to identify predictors of the number of IPD levels implanted and reoperation up to 3 years after the index surgery. Right-censored Kaplan-Meier curves were plotted for duration of reoperation-free survival and compared with log-rank tests. RESULTS: Patients (n = 4865) received 1-level (n = 3246) or 2-level (n = 1619) IPDs. Patients who were older (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.01-1.03, P < .001), male (aOR 1.31, 95% CI 116-1.50, P < .001), and obese (aOR 1.19, 95% CI 1.05-1.36, P < .01) were significantly more likely to receive a 2-level IPD than to receive a 1-level IPD. The 3-year reoperation rate was 9.3% of patients when mortality was accounted for during the follow-up period. Older age decreased (aOR 0.97, 95% CI 0.97-0.99, P = .0039) likelihood of reoperation, whereas 1-level IPD (aOR 1.37, 95% CI 1.01-1.89, P = .048), Charlson Comorbidity Index (aOR 1.07, 95% CI 1.01-1.14, P = .018), and performing concomitant open decompression increased the likelihood of reoperation (aOR 1.68, 95% CI 1.35-2.09, P = .0014). CONCLUSION: Compared with 1-level IPDs, 2-level IPDs were implanted more frequently in older, male, and obese patients. The 3-year reoperation rate was 9.3%. Concomitant open decompression with IPD placement was identified as a significant risk factor for subsequent reoperation and warrants future investigation.

Surgical Resection of Focal Cortical Dysplasia in a Neonate with Novel TSC1 Mutation Leading to Resolution of Refractory Seizures: Case Report.

We describe a neonate presenting on first day of life with refractory seizures secondary to a single, large area of focal cortical dysplasia (FCD) who underwent surgical resection at age 3 weeks leading to resolution of seizure activity and dramatic improvement in developmental trajectory. Surgical intervention for epilepsy is infrequently offered for neonates, often reserved only for those with catastrophic presentations. This case demonstrates that surgical intervention can be safe and efficacious in neonates for pharmaco-resistant seizures associated with a focal lesion. Rapid whole exome sequencing in this case yielded a germline novel de novo TSC1 mutation, leading to a genetic diagnosis of tuberous sclerosis complex (TSC). Our patient demonstrates an atypical neonatal presentation of TSC. Limited data is available for those with isolated FCD in TSC; this is the first reported case in a neonate.

Bone morphogenetic protein and cancer in spinal fusion: a propensity score-matched analysis.

OBJECTIVE: Bone morphogenetic protein (BMP) has been increasingly used in spinal surgery to promote arthrodesis. Because BMP stimulates cellular proliferation, its association with tumorigenesis is a concern. Previous research has generated conflicting conclusions on the risk of cancer in patients receiving BMP. The authors aimed to compare the incidence of solid organ and hematopoietic malignancies in patients undergoing spinal arthrodesis with or without BMP. METHODS: The PearlDiver Mariner Patient Claims Database was queried for patients undergoing thoracolumbar fusion between 2015 and 2021. Patients with preexisting malignancy were excluded. Data were analyzed for incidence of solid organ malignancy and hematopoietic malignancy diagnosed after spinal surgery. Propensity score matching using age, sex, tobacco usage, and year of surgery was performed between patients who did and those who did not receive BMP. RESULTS: Among patients without prior solid organ malignancy, BMP was used in 22,139 patients and not used in 306,249. In the propensity score-matched group, 3.1% of the BMP group developed solid organ malignancy following surgery compared with 3.5% in the non-BMP group. The relative risk (RR) of developing solid organ malignancy after BMP exposure was 0.89 (95% CI 0.81-0.98, p = 0.02). Among patients without prior hematopoietic malignancy, BMP was used in 23,505 patients and not used in 328,796 patients. In the propensity score-matched group, 0.4% of the BMP group developed hematopoietic malignancy compared with 0.6% of the non-BMP group. The RR of developing hematopoietic malignancy after BMP exposure was 0.71 (95% CI 0.55-0.93, p = 0.015). CONCLUSIONS: BMP use in thoracolumbar fusion was not associated with an increased risk of new malignancy, which further supports emerging data on the lack of an association between BMP use and increased malignancy.

Stereotactic electroencephalography in epilepsy patients for mapping of neural circuits related to emotional and psychiatric behaviors: a systematic review.

OBJECTIVE: Stereotactic electroencephalography (sEEG) is an increasingly utilized method for identifying electrophysiological processes underlying sensorimotor, cognitive, and emotional behaviors. In this review, the authors outline current research using sEEG to investigate the neural activity underlying emotional and psychiatric behaviors. Understanding the current structure of intracranial research using sEEG will inform future studies of psychiatric disease and therapeutics for effective neuromodulation. METHODS: The authors conducted a comprehensive systematic review of studies according to PRISMA guidelines to investigate behaviors related to psychiatric conditions in patients with epilepsy undergoing monitoring with sEEG. Articles indexed on PubMed between 2010 and 2022 were included if they studied emotions or affective behaviors or met the National Institute of Mental Health Research Domain Criteria positive and negative valence domains. Data extracted from articles included study sample size, paradigms and behavioral tasks employed, cortical and subcortical targets, EEG analysis methods, and identified electrophysiological activity underlying the studied behavior. The Newcastle-Ottawa Scale was used to assess bias risk. RESULTS: Thirty-two primary articles met inclusion criteria. Study populations ranged from 3 to 39 patients. The most common structures investigated were the amygdala, insula, orbitofrontal cortex (OFC), hippocampus, and anterior cingulate cortex (ACC). Paradigms, stimuli, and behavioral tasks widely varied. Time-frequency analyses were the most common, followed by connectivity analyses. Multiple oscillations encoded a variety of behaviors related to emotional and psychiatric conditions. High gamma activity was observed in the amygdala and anterior insula in response to aversive audiovisual stimuli and in the OFC in response to reward processing. ACC beta band power increases and hippocampal-amygdala beta coherence variations were predictive of worsening mood states. Insular and amygdalar theta oscillations encoded social pain and fear learning, respectively. Most studies performed passing recordings, allowing for the decoding of affective states and depression symptoms, while other studies utilized direct stimulation, such as in the OFC to improve mood symptoms. CONCLUSIONS: Stereotactic EEG in epilepsy has identified multiple corticolimbic structures with specific oscillatory and synchronization activity underlying a diverse range of behaviors related to emotions and affective conditions. Given the heterogeneity of psychiatric conditions, sEEG provides an opportunity to study these neural correlates to develop personalized effective neuromodulatory treatments. Future studies should focus on optimizing paradigms and tasks to investigate a broad range of behavioral phenotypes that overlap across psychiatric conditions.

Surgical site infection in thoracic and lumbar fractures: incidence and risk factors in 11,401 patients from a nationwide administrative database.

BACKGROUND CONTEXT: The rate of surgical site infection (SSI) following elective spine surgery ranges from 0.5%‒10%. Published reports suggest a higher SSI rate in non-elective spine surgery such as spine trauma; however, there is a paucity of large database studies examining this issue. PURPOSE: The objective of this study was to investigate the incidence and risk factors of SSI in patients undergoing spine surgery for thoracic and lumbar fractures in a large population database. STUDY DESIGN/SETTING: This is a retrospective study utilizing the PearlDiver Patient Claims Database. PATIENT SAMPLE: Patients undergoing spine surgery for thoracic and lumbar fractures between 2015-2020 were identified in the PearlDiver Patient Claims Database using ICD-10 codes. Patients were excluded who had another surgery either 14 days before or 21 days after the index spine surgery, or pathologic fracture. OUTCOME MEASURES: Rate of surgical site infection. METHODS: Clinical data collected from the PearlDiver database based on ICD-10 codes included gender, age, diabetes, smoking status, obesity, Elixhauser Comorbidity Index (ECI), Charlson Comorbidity Index (CCI), and SSI. Univariate analysis was used to assess the association of potential risk factors and SSI. Multivariable analysis was used to identify independent risk factors of SSI. The authors have no conflicts of interest or funding sources to declare. RESULTS: A total of 11,401 patients undergoing spine surgery for thoracic and lumbar fractures met inclusion criteria, and 1,065 patients were excluded. 860 patients developed SSI (7.5%). Risk factors significantly associated with SSI in univariate analysis included diabetes (OR 1.50; 95% CI, 1.30‒1.73; p<.001), obesity (OR 1.66; 95% CI, 1.44‒1.92; p<.001), increased age (p<.001), ECI (p<.001), and CCI (p<.001). On multivariable analysis, obesity and ECI were independently associated with SSI (p<.001 and p<.001, respectively). CONCLUSIONS: Non-elective surgery for thoracic and lumbar fractures is associated with a 7.5% risk of SSI. Obesity and ECI are independent predictors of SSI in this population. Limitations include the reliance on accurate insurance coding which may not fully capture all SSI, and in particular superficial SSI. These findings provide a broad overview of the risk of SSI in this population at a national level and may also help counsel patients regarding risk.

Treating Chronic Pain with Deep Brain Stimulation.

PURPOSE OF REVIEW: Deep brain stimulation (DBS) for chronic pain has been controversial. Despite the discouraging outcomes from multicenter clinical trial in the twentieth century, there is sustained interest in optimizing its use to improve patient outcomes. Here we provide a concise overview of DBS for chronic pain as a reference for clinicians. RECENT FINDINGS: Recently published data lends tentative support for DBS as a means of treating chronic pain. Still, high level-of-evidence data remain elusive. There are a handful of ongoing and prospective clinical trials exploring DBS for pain in the context of closed-loop neuromodulation, invasive electroencephalography monitoring, stimulation parameters, and novel intracranial targets. DBS is a potentially viable method of treating chronic pain. Procedure success is dependent on a number of factors including proper patient and intracranial target selection. Outcomes for ongoing and future clinical trials will help clinicians refine DBS use for this clinical indication.

Venous Sinus Stenting: Safety and Health Care Resource Evaluation for Optimal Recovery in an Evolving Health Care Environment.

BACKGROUND: Increasing evidence supports the effectiveness of venous sinus stenting (VSS) with favorable outcomes, safety, and expenses compared with shunting for idiopathic intracranial hypertension. Yet, no evidence is available regarding optimal postoperative recovery, which has increasing importance with the burdens on health care imposed by the coronavirus disease 2019 pandemic. We examined adverse events and costs after VSS and propose an optimal recovery pathway to maximize patient safety and reduce stress on health care resources. METHODS: A retrospective review was undertaken of elective VSS operations performed from May 2008 to August 2021 at a single institution. Primary data included hospital length of stay, intensive care unit (ICU) length of stay, adverse events, need for ICU interventions, and hospital costs. RESULTS: Fifty-three patients (98.1% female) met the inclusion criteria. Of these patients, 51 (96.2%) were discharged on postoperative day (POD) 1 and 2 patients were discharged on POD 2. Both patients discharged on POD 2 remained because of groin hematomas from femoral artery access. There were no major complications or care that required an ICU. Eight patients (15.1%) were lateralized to other ICUs or remained in a postanesthesia care unit because the neurosciences ICU was above capacity. Total estimated cost for initial recovery day in a neurosciences ICU room was $2361 versus $882 for a neurosurgery/neurology ward room. In our cohort, ward convalescence would save an estimated $79,866 for bed placement alone and increase ICU bed availability. CONCLUSIONS: Our findings reaffirm the safety of VSS. These patients should recover on a neurosurgery/neurology ward, which would save health care costs and increase ICU bed availability.

Assessment of Pediatric Pseudotumor Cerebri Clinical Characteristics and Outcomes.

Pseudotumor cerebri also known as idiopathic intracranial hypertension is a relatively uncommon disorder of unknown pathophysiology. Although pseudotumor cerebri occurs in both children and adults, the pseudotumor cerebri literature is heavily dominated by adult studies. The aim of this study is to retrospectively describe the clinical presentation, imaging, treatment, and outcomes of a large pediatric pseudotumor cerebri population over a 23-year period. We also discuss secondary pseudotumor cerebri (44%) as well as the increasingly recognized patient subgroups without headache (13.3%) and without papilledema (7.3%). Female sex, obesity, and initial symptoms were consistent with the literature; however radiographic findings were surprisingly low in this cohort. Headache outcomes at 1 week, 1 month, and 3 months following initial lumbar puncture/treatment and visual function outcomes are reported.

Low Levels of Vitamin D Promote Memory B Cells in Lupus.

Background: Vitamin D deficiency is a known risk factor for Systemic Lupus Erythematosus (SLE), yet clinical trials have not demonstrated efficacy and few studies have utilized lupus models to understand the mechanism underlying this relationship. The Act1-/- mouse is a spontaneous model of lupus and Sjögren's syndrome, characterized by increased Th17 cells and peripheral B cell expansion. Vitamin D3 has anti-inflammatory properties, reduces Th17 cells and impairs B cell differentiation/activation. Therefore, we assessed how varying amounts of vitamin D3 affected lupus-like disease in the Act1-/- mouse. Methods: Act1-/- mice were fed either low/restricted (0 IU/kg), normal (2 IU/kg), or high/supplemented (10 IU/kg) vitamin D3 chow for 9 weeks, after which lupus-like features were analyzed. Results: While we found no differences in Th17 cells between vitamin D3 groups, vitamin D3 restriction specifically promoted memory B cell development, accompanied by elevated levels of serum IgM, IgG1, IgG3, and anti-dsDNA IgG. A similar significant negative association between serum vitamin D and memory B cells was confirmed in a cohort of SLE patients. Conclusion: Low levels of vitamin D3 are associated with elevated levels of memory B cells in an animal model of lupus and well-controlled SLE patients.

Deep Brain Stimulation for Pain in the Modern Era: A Systematic Review.

BACKGROUND: Deep brain stimulation (DBS) has been considered for patients with intractable pain syndromes since the 1950s. Although there is substantial experience reported in the literature, the indications are contested, especially in the United States where it remains off-label. Historically, the sensory-discriminative pain pathways were targeted. More recently, modulation of the affective sphere of pain has emerged as a plausible alternative. OBJECTIVE: To systematically review the literature from studies that used contemporary DBS technology. Our aim is to summarize the current evidence of this therapy. METHODS: A systematic search was conducted in the MEDLINE, EMBASE, and Cochrane libraries through July 2017 to review all studies using the current DBS technology primarily for pain treatment. Study characteristics including patient demographics, surgical technique, outcomes, and complications were collected. RESULTS: Twenty-two articles were included in this review. In total, 228 patients were implanted with a definitive DBS system for pain. The most common targets used were periaqueductal/periventricular gray matter region, ventral posterior lateral/posterior medial thalamus, or both. Poststroke pain, phantom limb pain, and brachial plexus injury were the most common specific indications for DBS. Outcomes varied between studies and across chronic pain diagnoses. Two different groups of investigators targeting the affective sphere of pain have demonstrated improvements in quality of life measures without significant reductions in pain scores. CONCLUSION: DBS outcomes for chronic pain are heterogeneous thus far. Future studies may focus on specific pain diagnosis rather than multiple syndromes and consider randomized placebo-controlled designs. DBS targeting the affective sphere of pain seems promising and deserves further investigation.

Immunological effects of vitamin D and their relations to autoimmunity.

Vitamin D deficiency is an established risk factor for many autoimmune diseases and the anti-inflammatory properties of vitamin D underscore its potential therapeutic value for these diseases. However, results of vitamin D3 supplementation clinical trials have been varied. To understand the clinical heterogeneity, we reviewed the pre-clinical data on vitamin D activity in four common autoimmune diseases: multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD), in which patients are commonly maintained on oral vitamin D3 supplementation. In contrast, many pre-clinical studies utilize other methods of manipulation (i.e. genetic, injection). Given the many actions of vitamin D3 and data supporting a vitamin D-independent role of the Vitamin D receptor (VDR), a more detailed mechanistic understanding of vitamin D3 activity is needed to properly translate pre-clinical findings into the clinic. Therefore, we assessed studies based on route of vitamin D3 administration, and identified where discrepancies in results exist and where more research is needed to establish the benefit of vitamin D supplementation.

Relationships Between Vitamin D, Gut Microbiome, and Systemic Autoimmunity.

There is increasing recognition of the role the microbiome plays in states of health and disease. Microbiome studies in systemic autoimmune diseases demonstrate unique microbial patterns in Inflammatory Bowel Disease, Rheumatoid Arthritis, and Systemic Lupus Erythematosus to a lesser extent, whereas there is no single bug or pattern that characterizes Multiple Sclerosis. Autoimmune diseases tend to share a predisposition for vitamin D deficiency, which alters the microbiome and integrity of the gut epithelial barrier. In this review, we summarize the influence of intestinal bacteria on the immune system, explore the microbial patterns that have emerged from studies on autoimmune diseases, and discuss how vitamin D deficiency may contribute to autoimmunity via its effects on the intestinal barrier function, microbiome composition, and/or direct effects on immune responses.

Act1 is a negative regulator in T and B cells via direct inhibition of STAT3.

Although Act1 (adaptor for IL-17 receptors) is necessary for IL-17-mediated inflammatory responses, Act1- (but not Il17ra-, Il17rc-, or Il17rb-) deficient mice develop spontaneous SLE- and Sjögren's-like diseases. Here, we show that Act1 functions as a negative regulator in T and B cells via direct inhibition of STAT3. Mass spectrometry analysis detected an Act1-STAT3 complex, deficiency of Act1 (but not Il17ra-, Il17rc-, or Il17rb) results in hyper IL-23- and IL-21-induced STAT3 activation in T and B cells, respectively. IL-23R deletion or blockade of IL-21 ameliorates SLE- and Sjögren's-like diseases in Act1-/- mice. Act1 deficiency results in hyperactivated follicular Th17 cells with elevated IL-21 expression, which promotes T-B cell interaction for B cell expansion and antibody production. Moreover, anti-IL-21 ameliorates the SLE- and Sjögren's-like diseases in Act1-deficient mice. Thus, IL-21 blocking antibody might be an effective therapy for treating SLE- and Sjögren's-like syndrome in patients containing Act1 mutation.

Prediction of depression and anxiety via patient-assessed tremor severity, not physician-reported motor symptom severity, in patients with Parkinson's disease or essential tremor who have undergone deep brain stimulation.

OBJECTIVEDeep brain stimulation (DBS) is an effective therapy for movement disorders such as idiopathic Parkinson's disease (PD) and essential tremor (ET). However, some patients who demonstrate benefit on objective motor function tests do not experience postoperative improvement in depression or anxiety, 2 important components of quality of life (QOL). Thus, to examine other possible explanations for the lack of a post-DBS correlation between improved objective motor function and decreased depression or anxiety, the authors investigated whether patient perceptions of motor symptom severity might contribute to disease-associated depression and anxiety.METHODSThe authors performed a retrospective chart review of PD and ET patients who had undergone DBS at the Cleveland Clinic in the period from 2009 to 2013. Patient demographics, diagnosis (PD, ET), motor symptom severity, and QOL measures (Primary Care Evaluation of Mental Disorders 9-item Patient Health Questionnaire [PHQ-9] for depression, Generalized Anxiety Disorder 7-item Scale [GAD-7], and patient-assessed tremor scores) were collected at 4 time points: preoperatively, postoperatively, 1-year follow-up, and 2-year follow-up. Multivariable prediction models with solutions for fixed effects were constructed to assess the correlation of predictor variables with PHQ-9 and GAD-7 scores. Predictor variables included age, sex, visit time, diagnosis (PD vs ET), patient-assessed tremor, physician-reported tremor, Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score, and patient-assessed tremor over time.RESULTSSeventy PD patients and 17 ET patients were included in this analysis. Mean postoperative and 1-year follow-up UPDRS-III and physician-reported tremor scores were significantly decreased compared with preoperative scores (p < 0.0001). Two-year follow-up physician-reported tremor was also significantly decreased from preoperative scores (p < 0.0001). Only a diagnosis of PD (p = 0.0047) and the patient-assessed tremor rating (p < 0.0001) were significantly predictive of depression. A greater time since surgery, in general, significantly decreased anxiety scores (p < 0.0001) except when a worsening of patient-assessed tremor was reported over the same time period (p < 0.0013).CONCLUSIONSPatient-assessed tremor severity alone was predictive of depression in PD and ET following DBS. This finding suggests that a patient's perception of illness plays a greater role in depression than objective physical disability regardless of the time since surgical intervention. In addition, while anxiety may be attenuated by DBS, patient-assessed return of tremor over time can increase anxiety, highlighting the importance of long-term follow-up for behavioral health features in chronic neurological disorders. Together, these data suggest that the patient experience of motor symptoms plays a role in depression and anxiety-a finding that warrants consideration when evaluating, treating, and following movement disorder patients who are candidates for DBS.

Pediatric-Onset Multiple Sclerosis: A Single Center Study.

Pediatric-onset multiple sclerosis (POMS), once thought to be rare, is now being diagnosed in increasing numbers in children. Despite improvements to diagnostic criteria, the diagnosis and management of POMS remains challenging. The aim of this study is to retrospectively describe a growing POMS patient population seen at a single center over a 13 year period. Epidemiologic, clinical, neuroimaging, laboratory features and therapeutic management and outcome data were collected and analyzed. These data support associations between MS and environmental triggers such as obesity and vitamin D deficiency. Presenting symptoms, magnetic resonance imaging and laboratory findings were consistent with the existing literature; however, the prevalence of cortical lesions and abnormal saccadic pursuit is higher than other reports. Data also demonstrate a shift in practice from first- to second-line therapies over the observed period.

Utility of Montreal Cognitive Assessment in Differentiating Dementia With Lewy Bodies From Alzheimer's Dementia.

Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the 2 most common neurodegenerative dementias. Identification of patients with DLB is necessary to guide appropriate clinical management and medication trials. Patients with DLB are reported to perform poorly on tasks of visuospatial and executive function, compared to patients with AD who perform poorly on memory tasks. Using the Montreal Cognitive Assessment, we found that patients with DLB (n = 73) had statistically significant lower performance in clock drawing (visuospatial and executive function) and higher performance in delayed recall (memory) subscores compared to patients with AD (n = 57). This score pattern should raise suspicion for a DLB diagnosis at initial evaluation of patients with dementia.

Subsequent Pulse Generator Replacement Surgery Does Not Increase the Infection Rate in Patients With Deep Brain Stimulator Systems: A Review of 1537 Unique Implants at a Single Center.

INTRODUCTION: Deep brain stimulation (DBS) is a well-recognized treatment for patients with movement disorders and other neurological diseases. The implantable pulse generator (IPG) is a fundamental component of the DBS system. Although IPG implantation and replacement surgeries are comparatively minor procedures relative to the brain lead insertion, patients often require multiple IPG replacements during their lifetime with each operation carrying a small but possibly cumulative risk of complications. To better educate our patients and improve surgical outcomes, we reviewed our series of patients at our institution. METHODS: Using electronic health record data, we retrospectively reviewed all initial and subsequent IPG surgeries from patients who underwent at least one IPG surgery between the years of 2010 and 2015 at the Cleveland Clinic main campus. We calculated infection rates for initial IPG implantation surgeries and the infection rate for subsequent replacements. Fisher's exact tests were used to evaluate the chance of an infection between the initial implantation and replacement. Fisher's exact tests and simple logistic regression analyses were used to determine the predictive ability of selected demographic and clinical variables RESULTS: Our final sample included 697 patients and 1537 surgeries. For all patients, the infection rate at the first surgery was 2.01%; at the second surgery, it was 0.44%; and at the third surgery, it was 1.83%. When considering only patients that underwent at least three replacement surgeries (n = 114) the infection rate did not change in a significant manner with subsequent interventions compared to the first replacement. No other variable of interest was a significant predictor of infection. CONCLUSION: We did not find increasing rates of infection with subsequent IPG replacement procedures.

Effects of neuromyelitis optica-IgG at the blood-brain barrier in vitro.

OBJECTIVE: To address the hypothesis that physiologic interactions between astrocytes and endothelial cells (EC) at the blood-brain barrier (BBB) are afflicted by pathogenic inflammatory signaling when astrocytes are exposed to aquaporin-4 (AQP4) antibodies present in the immunoglobulin G (IgG) fraction of serum from patients with neuromyelitis optica (NMO), referred to as NMO-IgG. METHODS: We established static and flow-based in vitro BBB models incorporating co-cultures of conditionally immortalized human brain microvascular endothelial cells and human astrocyte cell lines with or without AQP4 expression. RESULTS: In astrocyte-EC co-cultures, exposure of astrocytes to NMO-IgG decreased barrier function, induced CCL2 and CXCL8 expression by EC, and promoted leukocyte migration under flow, contingent on astrocyte expression of AQP4. NMO-IgG selectively induced interleukin (IL)-6 production by AQP4-positive astrocytes. When EC were exposed to IL-6, we observed decreased barrier function, increased CCL2 and CXCL8 expression, and enhanced leukocyte transmigration under flow. These effects were reversed after application of IL-6 neutralizing antibody. CONCLUSIONS: Our results indicate that NMO-IgG induces IL-6 production by AQP4-positive astrocytes and that IL-6 signaling to EC decreases barrier function, increases chemokine production, and enhances leukocyte transmigration under flow.