Predictors of Skip Laminotomy for Placement of Paddle Leads for Spinal Cord Stimulation.

OBJECTIVES: Placement of a standard paddle lead for spinal cord stimulation (SCS) requires a laminotomy for positioning of the lead within the epidural space. During initial placement, an additional laminotomy or laminectomy, termed a "skip" laminotomy, may be necessary at a higher level to pass the lead to the appropriate midline position. Patient and radiographic factors that predict the need for a skip laminotomy have yet to be identified. MATERIALS AND METHODS: Participants who underwent SCS paddle placement at Albany Medical Center between 2016 and 2017 were identified. Operative reports were reviewed to identify the paddle type, level of initial laminotomy, target level, and skip laminotomy level. Preoperative thoracic magnetic resonance images (MRIs) were reviewed, and spinal canal diameter, interpedicular distance, and dorsal cerebral spinal fluid thickness were measured for each participant when available. RESULTS: A total of 106 participants underwent thoracic SCS placement. Of these, 97 had thoracic MRIs available for review. Thirty-eight participants required a skip laminotomy for placement of the paddle compared with 68 participants who did not. There was no significant difference in demographic features including age, sex, body mass index, and surgical history. Univariate analyses that suggested trends were selected for further analysis using binary logistic regression. Level of initial laminotomy (odds ratio [OR] = 1.51, p = 0.028), spinal canal diameter (OR = 0.71, p = 0.015), and dorsal cerebrospinal fluid thickness (OR = 0.61, p = 0.011) were correlated with skip laminotomy. Target level (OR = 1.27, p = 0.138) and time from trial (1.01, p = 0.117) suggested potential association. The multivariate regression was statistically significant, X2(10) = 28.02, p = 0.002. The model explained 38.3% of the variance (Nagelkerke R2) and predicted skip laminectomy correctly in 73.3% of cases. However, for the multivariate regression, only a decrease in spinal canal diameter (OR = 0.59, p = 0.041) was associated with a greater odds of skip laminotomy. CONCLUSIONS: This study aims to characterize the patient and radiographic factors that may predict the need to perform a skip laminotomy during the initial placement of SCS paddles. Here, we show that radiographic and anatomic variables, primarily spinal canal diameter, play an important role in predicting the need for a skip laminotomy. Furthermore, we suggest that target level for placement and level of initial laminotomy also may contribute. Further investigation of the predictive factors for performing a skip laminotomy would help optimize surgical planning and preoperative patient selection and counseling.

Revision and Replacement of Spinal Cord Stimulator Paddle Leads.

OBJECTIVES: Paddle leads for spinal cord stimulation (SCS) offer more efficient energy delivery and advantages in some patients. However, there is concern for how safely SCS paddles can be replaced once previously implanted because of scar tissue and the relative vulnerability of the thoracic cord. In this study, we share our experience on SCS paddle replacement. MATERIALS AND METHODS: Participants who underwent SCS replacement at Albany Medical Center between 2011 and 2020 were identified. The medical records were reviewed for demographic data and information regarding initial complications, reason for removal or revision, subsequent complications of replacement surgery and its timing, and whether the implant was ultimately removed. Percutaneous lead replacement cases performed over the same period were used as a comparison group. RESULTS: A total of 1265 patients were identified to have had an SCS-related procedure based on billing codes. Of these, 73 involved replacement of epidural leads (51 paddles, 22 percutaneous). Most paddles (48/51) were replaced at the time of removal. A total of 30 of the 51 paddle replacements required additional lamina removal. Re-operations that occurred more than one year after initial implant were significantly more likely to require additional bone removal (p < 0.001). Paddle re-operations lasted in general 1.7 ± 0.2 hours and had 35 ± 5 mL of blood loss, whereas percutaneous operations lasted 1.3 ± 0.2 hours and had 12.5 ± 2 mL of blood loss. Despite the invasive nature of paddle replacement, there was no difference in complications (p = 0.23) compared with that in percutaneous leads. CONCLUSIONS: This study characterizes the safety profile of SCS paddle replacement surgeries. Here, we demonstrate that the replacement of paddle leads at the time of removal, with additional lamina removal if needed because of scar, is associated with low rates of complications. This validates the feasibility and low-risk profile of replacing paddle leads when clinically indicated for experienced surgeons with specialization in SCS.

Spinal cord stimulation programming: a crash course.

The aim of this comprehensive review is to provide an instructional guide for providers regarding the parameters and programming of spinal cord stimulation (SCS) devices. Knowing these fundamentals will aid in providing superior pain relief to patients. SCS has four programmable parameters: contact (electrode) selection, amplitude, pulse width, and frequency. Each parameter needs to be accounted for when assessing which program works for which patient. Traditional open-loop systems allow for different "programs," or combinations of these four parameters, to be pre-set by the provider and medical device representative. These allow for flexibility in the type of stimulation delivered to the patient depending on activity. Patients are also given control over programs and changing the amplitudes of these programs. However, some open-loop systems place the burden of toggling between programs to manage pain control on patients, though this tends to be less in subparesthesia programs. Newer closed-loop systems make it possible for stimulation settings to automatically adjust in response to accelerometry and evoked compound action potential feedback, and therefore have the potential to streamline the patient experience. This article provides practitioners with the basic knowledge of SCS parameters and programming systems. Understanding their use is essential to providing optimal pain relief to patients.

Craniofacial Peripheral Nerve Stimulation: Analysis of a Single Institution Series.

OBJECTIVE: Objective real-world experience with peripheral nerve stimulation (PNS) is limited. Furthermore, the lack of robust outcome metrics, long-term follow-up and data comparing responders and nonresponders limit the refinement of selection criteria to better identify patients likely to benefit from PNS. MATERIALS AND METHODS: We retrospectively analyzed 22 patients with craniofacial pain treated with PNS, and responders were classified as having ≥50% postoperative improvement in the numeric rating scale (NRS). In a subset of patients (n = 11), detailed prospective outcomes metrics were obtained preoperatively and postoperatively, including NRS, Beck Depression Index (BDI), Pain Catastrophizing Scale (PCS), and McGill Pain Questionnaire (MPQ). RESULTS: About 59.1% (13 of 22) of subjects were classified as responders at a mean follow-up of 37.5 ± 5.27 months. Diagnoses included migraine (n = 6), occipital neuralgia (n = 9), trigeminal neuropathic pain (TNP; n = 6), and central poststroke pain (n = 1). Within the TNP subgroup, responders were more likely to have undergone two or more trigeminal neuralgia procedures prior to PNS (p < 0.05). In the 11 patients with comprehensive preoperative and postoperative outcome data, we noted significant improvement in NRS (p = 0.0005), BDI (p = 0.04), PCS (p = 0.01), as well as components of PCS (helplessness and magnification, p = 0.02) and MPQ (affective, p = 0.02). CONCLUSIONS: The present study adds to the PNS literature by providing long-term data and multiple outcome metrics in a subset of patients. We suggest that BDI, PCS, and MPQ may provide more insight into meaningful response over time. Evaluating functional and quality of life outcomes in patients with craniofacial pain may be more informative than assessing benefit solely based on pain intensity and responder rates.

Progesterone-only contraception is associated with a shorter progression-free survival in premenopausal women with WHO Grade I meningioma.

The hormonally active nature of intracranial meningioma has prompted research examining the risk of tumorigenesis in patients using hormonal contraception. Studies exploring estrogen-only and estrogen/progesterone combination contraceptives have failed to demonstrate a consistent increased risk of meningioma. By contrast, the few trials examining progesterone-only contraceptives have shown higher odds ratios for risk of meningioma. With progesterone-only contraception on the rise, the risk of tumor recurrence with these specific medications warrants closer study. We sought to determine whether progesterone-only contraception increases recurrence rate and decreases progression-free survival in pre-menopausal women with surgically resected WHO Grade I meningioma. Comparative analysis of 67 pre-menopausal women taking hormone-based contraceptives (progesterone-only medication, n = 21; estrogen-only or estrogen/progesterone combination medication, n = 46) who underwent surgical resection of WHO Grade I intracranial meningioma was performed. Differences in demographics, degree of resection, adjuvant therapy and time to recurrence were compared between the two groups. Compared to patients taking combination or estrogen-only contraception, those taking progesterone-only contraception demonstrated a greater recurrence rate (33.3 vs. 19.6%) with a reduced time to recurrence (18 vs. 32 months, p = 0.038) despite a significantly shorter follow-up (p = 0.014). There were no significant demographic or treatment related differences. The results from this study suggest that exogenous progesterone-only medications may represent a specific contraceptive subgroup that should be avoided in patients with meningioma.

HSP90 inhibitors in the context of heat shock and the unfolded protein response: effects on a primary canine pulmonary adenocarcinoma cell line.

BACKGROUND: Agents targeting HSP90 and GRP94 are seldom tested in stressed contexts such as heat shock (HS) or the unfolded protein response (UPR). Tumor stress often activates HSPs and the UPR as pro-survival mechanisms. This begs the question of stress effects on chemotherapeutic efficacy, particularly with drugs targeting chaperones such as HSP90 or GRP94. We tested the utility of several HSP90 inhibitors, including PU-H71 (targeting GRP94), on a primary canine lung cancer line under HS/UPR stress compared to control conditions. METHODS: We cultured canine bronchoalveolar adenocarcinoma cells that showed high endogenous HSP90 and GRP94 expression; these levels substantially increased upon HS or UPR induction. We treated cells with HSP90 inhibitors 17-DMAG, 17-AAG or PU-H71 under standard conditions, HS or UPR. Cell viability/survival was assayed. Antibody arrays measured intracellular signalling and apoptosis profiles. RESULTS: HS and UPR had varying effects on cells treated with different HSP90 inhibitors; in particular, HS and UPR promoted resistance to inhibitors in short-term assays, but combinations of UPR stress and PU-H571 showed potent cytotoxic activity in longer-term assays. Array data indicated altered signalling pathways, with apoptotic and pro-survival implications. UPR induction + dual targeting of HSP90 and GRP94 swayed the balance toward apoptosis. CONCLUSION: Cellular stresses, endemic to tumors, or interventionally inducible, can deflect or enhance chemo-efficacy, particularly with chaperone-targeting drugs. Stress is likely not held accountable when testing new pharmacologics or assessing currently-used drugs. A better understanding of stress impacts on drug activities should be critical in improving therapeutic targeting and in discerning mechanisms of drug resistance.

An assessment of the long-term impacts of the coronavirus disease 2019 pandemic on academic neurosurgery.

OBJECTIVE: The goal of this study was to survey residents, fellows, and residency program leadership to assess the long-term impacts of the coronavirus disease 2019 (COVID-19) on residency training by using a structured survey methodology. METHODS: A survey was distributed to US neurosurgical residents and fellows (n = 2085) as well as program directors (PDs) and chairs (n = 216) in early 2022. Bivariate analysis was performed to identify factors associated with a decreased likelihood of pursuing a career in academic neurosurgery because of the pandemic, a perception that surgical skills preparation was negatively impacted, personal financial concerns, and a preference for remote education. Significant differences in the bivariate analysis underwent further multivariate logistic regression analysis to evaluate for predictors of these outcomes. RESULTS: An analysis of complete surveys from 264 residents and fellows (12.7%) and 38 PDs and chairs (17.6%) was performed. Over half of the residents and fellows (50.8%) believed that their surgical skills preparation was negatively impacted by the pandemic, and a notable proportion believed that they were less likely to go into academics because of the pandemic's impact on their professional (20.8%) and personal (28.8%) life. Those less likely to pursue academics were more likely to report that work-life balance did not improve (p = 0.049), personal financial concerns increased (p = 0.01), and comradery among residents (p = 0.002) and with faculty (p = 0.001) did not improve. Residents who indicated they were less likely to go into academics were also more likely to have been redeployed (p = 0.038). A large majority of PDs and chairs indicated that the pandemic resulted in financial setbacks for their departments (71.1%) and institutions (84.2%), with 52.6% reporting reduced faculty compensation. Financial setbacks at the institutional level were associated with a worsened opinion of hospital leadership (p = 0.019) and reports of a reduced quality of care for non-COVID-19 patients (p = 0.005) but not from faculty member losses (p = 0.515). A plurality of trainees (45.5%) reported a preference for a remote format for educational conferences compared to 37.1% who disagreed. CONCLUSIONS: This study provides a cross-section of the pandemic's impact on academic neurosurgery, highlighting the importance of continued efforts to assess and address the long-term consequences of the COVID-19 pandemic for US academic neurosurgery.

Machine Learning in Spinal Cord Stimulation for Chronic Pain.

Spinal cord stimulation (SCS) is an effective treatment for chronic neuropathic pain. The success of SCS is dependent on candidate selection, response to trialing, and programming optimization. Owing to the subjective nature of these variables, machine learning (ML) offers a powerful tool to augment these processes. Here we explore what work has been done using data analytics and applications of ML in SCS. In addition, we discuss aspects of SCS which have narrowly been influenced by ML and propose the need for further exploration. ML has demonstrated a potential to complement SCS to an extent ranging from assistance with candidate selection to replacing invasive and costly aspects of the surgery. The clinical application of ML in SCS shows promise for improving patient outcomes, reducing costs of treatment, limiting invasiveness, and resulting in a better quality of life for the patient.

A Modified Technique for Interventional MRI-Guided Deep Brain Stimulation Using the ClearPoint System.

BACKGROUND: Deep brain stimulation (DBS) is increasingly performed using imaging-based techniques, which are rapidly evolving to minimize invasiveness and use limited resources efficiently. OBJECTIVE: To describe a modified surgical technique for interventional MRI-guided stereotactic procedures using ClearPoint. METHODS: A total of 160 consecutive DBS cases for Parkinson disease (48%), essential tremor (44%), dual essential tremor/Parkinson disease (3%), and dystonia (5%) were studied. Technique modifications included (1) preplanning the target/trajectory, (2) adoption of a smaller incision and new stereotactic frame, (3) changing the sequence of surgical steps, aiming to final target PRIOR to drilling, (4) reducing burr hole size, (5) minimizing dural opening, and (6) anchoring leads with a bio cement/plate combination in lieu of commercial devices. Demographic data, radial error, number of passes, and case time were prospectively collected while complications and clinical outcomes were retrospectively assessed. RESULTS: One hundred and forty seven DBS patients had 262 total leads placed. Average radial error was 0.41 mm bilaterally. Seventy nine leads had error <0.2 mm; 6 leads had error >1 mm. Pin-to-stylet insertion time, pin-to-frame removal time, and pin-to-room departure time were 2 hours 1 minute, 2 hours 48 minutes, and 3 hours 16 minutes, respectively, and were significantly shorter than those obtained with the original ClearPoint technique for our first 150 DBS cases ( P < .0001). Complications included infection with hardware removal (2.5%) and superficial hemorrhage without permanent neurological sequelae (1.9%). CONCLUSION: The modified ClearPoint technique maintains accuracy while reducing invasiveness and MRI time. This workflow can be expanded to other applications, including laser interstitial thermal therapy and gene delivery.

Drainage, Irrigation, and Fibrinolytic Therapy (DRIFT) for Adult Intraventricular Hemorrhage Associated with Primary Hypertensive Hemorrhages Using IRRAflow Self-Irrigating Catheter: A Report of Three Cases and Prior Historical Controls.

BACKGROUND: Spontaneous primary intracerebral hemorrhage (ICH) accounts for 10%-15% of strokes and is accompanied by ventricular involvement in 10%-30% of cases. Intraventricular hemorrhage (IVH) is a poor prognostic factor and the current treatment paradigm of external ventricular drainage requires frequent flushing and replacement. Given the documented high rate of failure standard EVD catheters, we sought to determine if the use of the IRRAflow system with the addition of alteplase would be beneficial in this patient population for the treatment of IVH associated with primary hypertensive ganglionic hemorrhages. METHODS: Three patients with ganglionic hemorrhages and IVH underwent treatment with the IRRAflow system at our institution from December 2022 to January 2023. A retrospective review was then performed of patients with primary hypertensive ganglionic hemorrhages and EVD placement at our institution from January 2021 to present day. RESULTS: Three patients underwent treatment with the IRRAflow system and continuous lavage of Tissue Plasminogen Activator (tPA). The IVH was efficiently cleared in all cases and the drains were removed within 8 days in all cases. No patients required replacement of the drain and there were no hemorrhagic complications noted. In our retrospective review, 28 patients were identified who underwent placement of a standard EVD for the treatment of primary hypertensive ganglionic hemorrhages. When patients who had early withdrawal of care were excluded, the average length of EVD treatment was 11.3 days and the EVD replacement rate was 24%. CONCLUSIONS: We demonstrate here that the use of the IRRAflow system for the treatment of primary hypertensive hemorrhages with IVH results in rapid clearance of the IVH without safety concerns. Compared to historical controls there was a decrease in EVD duration, EVD replacement and, ICU LOS.

Review of the Treatments for Central Neuropathic Pain.

Central neuropathic pain (CNP) affects millions worldwide, with an estimated prevalence of around 10% globally. Although there are a wide variety of treatment options available, due to the complex and multidimensional nature in which CNP arises and presents symptomatically, many patients still experience painful symptoms. Pharmaceutical, surgical, non-invasive, cognitive and combination treatment options offer a generalized starting point for alleviating symptoms; however, a more customized approach may provide greater benefit. Here, we comment on the current treatment options that exist for CNP and further suggest the need for additional research regarding the use of biomarkers to help individualize treatment options for patients.

Does Pre-existing Anticoagulation or Antiplatelet Therapy Increase the Risk of Traumatic Subarachnoid Hemorrhage Progression?

BACKGROUND: Isolated traumatic subarachnoid hemorrhage (tSAH) is a common finding in mild traumatic brain injury that often results in transfer to a tertiary center. Patients prescribed blood-thinning medications (BTs) are believed to be at higher risk of clinical or radiographic worsening. OBJECTIVE: To compare the rates of radiographic progression and need for neurosurgical intervention in patients with tSAH who are on anticoagulation (AC) and antiplatelet (AP) therapies with those who are not. METHODS: Analysis using a retrospective cohort design identified patients older than 18 years with isolated tSAH and a Glasgow Coma Scale of 15 on admission. Clinical information including use of BTs, administration of reversal agents, radiographic progression, and need for neurosurgical intervention was collected. Patients on BTs were divided into AP, AC, and AP/AC groups based on drug type. RESULTS: Three hundred eighty-four patients were included with 203 in the non-BT group and 181 in the BT group. Overall, 2.1% had worsening scans, and none required operative intervention. There was no difference in radiographic worsening between the non-BT and BT groups (2.4% vs 1.6%; P = 1.00). Crosswise comparison revealed no difference between the non-BT group and each BT subtype (AP, AP/AC, or AC). The non-BT group was more likely to have radiographic improvement than the BT group (45.8% vs 30.9%; P = .002). CONCLUSION: Neurologically intact patients on BTs with isolated tSAH are not at increased risk of radiographic progression or neurosurgical intervention. The presence of BTs should not influence management decisions for increased surveillance.

A safety review of approved intrathecal analgesics for chronic pain management.

Introduction: Intrathecal (IT) drug therapy is an effective treatment option for patients with chronic pain of malignant or nonmalignant origin, with an established safety profile and fewer adverse effects compared to oral or parenteral pain medications. Morphine (a µ-opioid receptor agonist) and ziconotide (a non-opioid calcium channel antagonist) are the only IT agents approved by the U.S. Food and Drug Administration for the treatment of chronic pain. Although both are considered first-line IT therapies, each drug has unique properties and considerations.Areas Covered: This review will evaluate the pivotal trials that established the use of morphine and ziconotide as first-line IT therapy for patients with chronic pain, as well as safety and efficacy data generated from various retrospective and prospective studies.Expert Opinion: Morphine and ziconotide are effective IT therapies for patients with chronic malignant or nonmalignant pain that is refractory to other interventions. IT ziconotide is recommended as a first-line therapy due to its efficacy and avoidance of many adverse effects commonly associated with opioids. The use of IT morphine is also considered first-line; however, the risks of respiratory depression, withdrawal with drug discontinuation or pump malfunction, and the development of tolerance require careful patient selection and management.

Comparative Analysis of Unruptured Cerebral Aneurysm Treatment Outcomes and Complications with the Classic versus Flex Pipeline Embolization Devices and Phenom versus Marksman Microcatheter Delivery System: The Role of Microcatheter Choice on Complication Rate.

OBJECTIVE: The second-generation pipeline embolization device (PED), flex, has improved opening and resheathing ability compared to the first-generation classic PED device. A previously reported single-institutional study suggests that the PED flex devices are associated with lower rates of complications. However, there was limited discussion regarding the complication rate with respect to microcatheter choice for PED delivery and deployment. The present study aims to evaluate outcomes of aneurysm treatment with PED flex versus classic along with the Phenom microcatheter versus Marksman microcatheter. METHODS: A retrospective, IRB-approved database of all patients who received a PED classic or PED flex device between January 2012 and July 2018 was analyzed. Microcatheter choice, patient demographics, medical comorbidities, aneurysm characteristics, treatment information, and outcome data were analyzed using univariate analyses. RESULTS: A total of 75 PED procedures were analyzed. There was no significant difference in major complications between the PED classic and PED flex. However, those treated using the Marksman microcatheter were more likely to have a major complication (periprocedural hemorrhage or ischemic event; 16.6% vs. 0%, p = 0.0248) than those treated with the Phenom microcatheter. Within the PED flex cohort, all major complications were associated with the Marksman microcatheter (p = 0.0289). CONCLUSIONS: The present study does not replicate significantly fewer complications with PED flex but demonstrates a significant reduction in complications with the Phenom microcatheter. Ultimately, this suggests multiple factors are involved in achieving positive outcomes and low complication rates in PED treated unruptured cerebral aneurysms.

Intraosseous Cannulation of a Calvarial Diploic Vein for Embolization of a Symptomatic Dural Arteriovenous Fistula: A Technical Case Report.

BACKGROUND AND IMPORTANCE: Dural arteriovenous fistulas (DAVFs) may present unique challenges for treatment depending on the anatomy and pattern of venous drainage. If endovascular techniques are to be employed, the DAVF must be amenable to transvenous or transarterial therapy. When access of peripheral vasculature does not provide a straightforward path, less conventional options may be available. This case highlights a novel, technically simple, and effective approach for the treatment of a subset of DAVFs, with venous drainage through calvarial diploic veins, that would make endovascular treatment otherwise challenging or impossible. CLINICAL PRESENTATION: We present a case of a 66-yr-old female patient who was diagnosed with a symptomatic DAVF located along the sphenoid ridge with a large intraosseous channel containing the draining vein of the fistula. This lesion was successfully treated with transcranial endovascular embolization via direct intraosseous cannulation of the calvarial diploic vein. This novel approach obviated the need for a full-thickness craniotomy, afforded only minimal bone loss, and preserved the integrity of the dura. A 3-mo follow-up angiogram confirmed complete cure of the DAVF with no residual arteriovenous shunt. At 20 mo postembolization, the patient was symptom free, with no reported neurologic deficits. Complete diagnostic work-up, treatment planning in a multidisciplinary environment, and a novel approach for endovascular embolization utilizing a hybrid operating suite played key roles in the successful implementation of this technique. CONCLUSION: This is the first report of direct intraosseous cannulation of a calvarial diploic vein for successful transcranial endovascular embolization of a symptomatic DAVF.

Frailty as a Predictor of Neurosurgical Outcomes in Brain Tumor Patients.

BACKGROUND: Preoperative risk assessment is important, but inexact because physiologic reserves are difficult to measure. When assessing quality of life for patients with brain tumors, having a better predictor of postsurgical outcome would be beneficial in counseling these patients. Frailty is thought to estimate physiologic reserves, and it has been found to predict postoperative complications, length of stay, and discharge to a skilled nursing facility or assisted living facility in patients undergoing various types of surgery. Frailty as an adjunct to preoperative assessment of neurosurgical patients has never been evaluated. This study aimed to determine whether frailty predicts neurosurgical complications in patients with brain tumors and enhances current perioperative risk models. METHODS: Frailty was preoperatively assessed in 260 patients undergoing surgery for brain tumor resection using a validated scale that assessed weakness, weight loss, exhaustion, low physical activity, and slowed walking speed. Patients were classified as nonfrail (score of 0-1), moderately frail (score of 2-3), or frail (score of 4-5). Moderately frail and frail patients were combined for analysis. RESULTS: Preoperative frailty was associated with an increased risk for discharge to a location other than home (10.36; 95% confidence interval, 3.6-30.1), postoperative complications (2.09; 95% confidence interval, 1.09-3.98), and a longer length of stay (1.66; 95% confidence interval, 1.24-2.21). CONCLUSIONS: Frailty independently predicts discharge disposition, postoperative complications, and length of stay in patients undergoing surgery for brain tumor resection. Preoperative assessment of frailty can help neurosurgeons and patients make more informed decisions about pursing surgical treatment.

Anti-neutrophil cytoplasmic antibody associated central nervous system vasculitis with brain and spinal cord subarachnoid hemorrhage: A rare case report and review of the literature.

This case report describes a 48-year old female who presented with altered mental status, lower extremity weakness, low back pain and a recent history of subjective fevers and night sweats found to have posterior parieto-occipital and spinal subarachnoid hemorrhage on imaging. Further work-up revealed vasculitic changes in the intracranial vasculature and the external carotid artery on angiography. She also demonstrated positivity for perinuclear anti-neutrophil cytoplasmic (p-ANCA) antibodies overall consistent with ANCA associated central nervous system vasculitis (AAV). The present case describes a rare and new presentation of AAV that caused both a cerebral and spinal subarachnoid hemorrhage. There has been no documentation of spinal subarachnoid hemorrhage associated with primary or secondary vasculitis in the literature. Ultimately, this case demonstrates the important finding that AAV can have spinal cord manifestations and cervical vasculature involvement along with the more classic intra-cranial vasculitis findings.

Shunt Nephritis: An Increasingly Unfamiliar Diagnosis.

BACKGROUND: Shunt nephritis is a rare, reversible immune-complex mediated complication of cerebrospinal fluid (CSF) shunt infection that can progress to end-stage renal disease and even death if diagnosis is delayed. CASE DESCRIPTION: The present case report details the manifestation and clinical course of shunt nephritis in a 50-year-old patient who presented with symptoms of nephrotic syndrome 30 years after ventriculojugular shunt placement. Diagnosis was delayed due to initial negative CSF and blood cultures, but a later CSF culture was positive for Propionibacterium acnes. After treatment with intravenous antibiotics and complete removal of shunt with subsequent replacement with a new ventriculoperitoneal shunt, the nephritic symptoms resolved, but the patient continued to have reduced kidney function consistent with stage IIIa chronic kidney disease. CONCLUSION: This case emphasizes the clinical importance of having a high index of suspicion in patients with a ventricular shunt who present with symptoms consistent with nephritis, even in the setting of negative cultures and delayed presentation.

Glioblastoma multiforme-derived extracellular vesicles drive normal astrocytes towards a tumour-enhancing phenotype.

Glioblastoma multiforme (GBM) is a devastating tumour with abysmal prognoses. We desperately need novel approaches to understand GBM biology and therapeutic vulnerabilities. Extracellular vesicles (EVs) are membrane-enclosed nanospheres released locally and systemically by all cells, including tumours, with tremendous potential for intercellular communication. Tumour EVs manipulate their local environments as well as distal targets; EVs may be a mechanism for tumourigenesis in the recurrent GBM setting. We hypothesized that GBM EVs drive molecular changes in normal human astrocytes (NHAs), yielding phenotypically tumour-promoting, or even tumourigenic, entities. We incubated NHAs with GBM EVs and examined the astrocytes for changes in cell migration, cytokine release and tumour cell growth promotion via the conditioned media. We measured alterations in intracellular signalling and transformation capacity (astrocyte growth in soft agar). GBM EV-treated NHAs displayed increased migratory capacity, along with enhanced cytokine production which promoted tumour cell growth. GBM EV-treated NHAs developed tumour-like signalling patterns and exhibited colony formation in soft agar, reminiscent of tumour cells themselves. GBM EVs modify the local environment to benefit the tumour itself, co-opting neighbouring astrocytes to promote tumour growth, and perhaps even driving astrocytes to a tumourigenic phenotype. Such biological activities could have profound impacts in the recurrent GBM setting.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.