BackgroundAneurysmal subarachnoid hemorrhage (SAH) is a catastrophic disease with devastating consequences, including a high mortality rate and severe disabilities among survivors. Inflammation is induced following SAH, but the exact role and phenotype of innate immune cells remain poorly characterized. We investigated the inflammatory components of the early brain injury in an animal model and in SAH patients.MethodSAH was induced through injection of blood in the subarachnoid space of C57Bl/6 J wild-type mice. Prospective blood collections were obtained at 12 h, days 1, 2, and 7 to evaluate the systemic inflammatory consequences of SAH by flow cytometry and enzyme-linked immunosorbent-assay (ELISA). Brains were collected, enzymatically digested, or fixed to characterize infiltrating inflammatory cells and neuronal death using flow cytometry and immunofluorescence. Phenotypic evaluation was performed at day 7 using the holding time and footprint tests. We then compared the identified inflammatory proteins to the profiles obtained from the plasma of 13 human SAH patients.ResultsFollowing SAH, systemic IL-6 levels increased rapidly, whereas IL-10 levels were reduced. Neutrophils were increased both in the brain and in the blood reflecting local and peripheral inflammation following SAH. More intracerebral pro-inflammatory monocytes were found at early time points. Astrocyte and microglia activation were also increased, and mice had severe motor deficits, which were associated with an increase in the percentage of caspase-3-positive apoptotic neurons. Similarly, we found that IL-6 levels in patients were rapidly increased following SAH. ICAM-1, bFGF, IL-7, IL-12p40, and MCP-4 variations over time were different between SAH patients with good versus bad outcomes. Moreover, high levels of Flt-1 and VEGF at admission were associated with worse outcomes.ConclusionSAH induces an early intracerebral infiltration and peripheral activation of innate immune cells. Furthermore, microglia and astrocytic activation are present at later time points. Our human and mouse data illustrate that SAH is a systemic inflammatory disease and that immune cells represent potential therapeutic targets to help this population of patients in need of new treatments.

Deep brain stimulation (DBS) represents an important treatment modality for movement disorders and other circuitopathies. Despite their miniaturization and increasing sophistication, DBS systems share a common set of components of which the implantable pulse generator (IPG) is the core power supply and programmable element. Here we provide an overview of key hardware and software specifications of commercially available IPG systems such as rechargeability, MRI compatibility, electrode configuration, pulse delivery, IPG case architecture, and local field potential sensing. We present evidence-based approaches to mitigate hardware complications, of which infection represents the most important factor. Strategies correlating positively with decreased complications include antibiotic impregnation and co-administration and other surgical considerations during IPG implantation such as the use of tack-up sutures and smaller profile devices.Strategies aimed at maximizing battery longevity include patient-related elements such as reliability of IPG recharging or consistency of nightly device shutoff, and device-specific such as parameter delivery, choice of lead configuration, implantation location, and careful selection of electrode materials to minimize impedance mismatch. Finally, experimental DBS systems such as ultrasound, magnetoelectric nanoparticles, and near-infrared that use extracorporeal powered neuromodulation strategies are described as potential future directions for minimally invasive treatment.

Background: Tumor-associated macrophages (TAMs) are principal immune cells in glioma microenvironment which support tumor growth and proliferation. Our aim in this study was to assess the relationship between CD204-expressed TAMs and O 6 -methylguanine-DNA methyltransferase (MGMT)-promoter methylation in World Health Organization (WHO) grade 4 astrocytomas, and its impact on patient's clinical outcome. Methods:The expression of CD204 + TAMs was quantitively assessed on 45 samples of WHO grade 4 astrocytomas using immunohistochemistry. MGMT-promoter methylation was tested by methylation techniques. The relationship between TAMs, MGMT-promoter methylation, and recurrence-free interval (RFI) was statistically analyzed.Results: There were 10 cases (22.2%) with isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytoma and 35 cases (77.8%) with IDHwildtype glioblastoma. MGMT-promotor was methylated in 18 cases (40%), unmethylated in 15 cases (33%), and the remaining 12 cases showed no MGMT status because of nucleic acid degradations. The expression of CD204 + TAMs was high in 32 cases (71.7%) and low in 13 cases (28.8%). The relationship between IDH1 mutation and CD204 + TAM expression was insignificant (P = 0.93). However, the significant difference was found between MGMT methylation and CD204 + TAMs expression (P = 0.01), in which CD204 + TAMs were diffusely expressed in MGMT-methylated cases. There was no significant difference in RFI between CD204 + TAMs expression, MGMTpromoter methylation and treatment modalities.Conclusions: Grade 4 astrocytomas with diffusely expressed CD204 + TAMs are usually associated with MGMT-promoter methylation. Although this association is unclear, CD204 + TAMs may neutralize the effect of MGMT-DNA protein to loss its function, which contributes to tumor progression. This relationship had no significant impact on the patient's clinical outcome after different treatment modalities.

Study DesignRetrospective case series.PurposeTo evaluate the clinical and radiological efficacy of anterolateral kyphoplasty for cervical spinal metastasis.Overview of LiteratureAlthough the spine is the third most common site of tumor metastasis, the cervical spine is the least commonly affected (incidence, 10%–15%). Surgical decompression is highly challenging because of the proximity of neural and vascular elements. Kyphoplasty for cervical spine metastasis has been described in small case reports with promising results.MethodsRetrospective analysis of a prospective collected single-center spine metastasis database was done for cervical kyphoplasty cases. Data pertaining to age, sex, primary tumor diagnosis, modified Tokuhashi score, Spinal Instability Neoplastic Score (SINS), preoperative Visual Analog Scale (VAS) score, and analgesic medication were extracted. Postoperative data included VAS score at postoperative day 1, duration of hospitalization, self-reported functional outcome, and VAS score at the last follow-up.ResultsEleven patients (mean age, 62.5 years) with cervical spine metastases were treated with 15-level kyphoplasty. Mean Tokuhashi score was 8.1, and mean SINS was 7.85. Mean preoperative pain score was 7.1, and 82% of patients used opioid analgesics. Mean total bleeding volume was 100 mL. Mean complication-free length of stay was 2.6 days with a decrease in postoperative pain (VAS score=2.8, p <0.05). There was a 56% decrease in opioid dosage and the number of consumed analgesics (1.09, p =0.004). Eighty-two percent of the patients reported excellent improvement at the last follow-up self-assessment.ConclusionsTo our knowledge, this case series represents the largest series of vertebral augmentation using balloon kyphoplasty for cervical spinal metastasis. This technique is associated with low postoperative complications as well as significant decrease in pain, use of opioids, and length of hospital stay. The main indications for vertebral kyphoplasty are lytic lesions of the cervical spine, painful lesions refractory to medical treatment, SINS score of 6–10, and absence of posterior wall defect.