Implantable Intracranial Pressure Sensor with Continuous Bluetooth Transmission via Mobile Application.

Hydrocephalus is a clinical disorder caused by excessive cerebrospinal fluid (CSF) buildup in the ventricles of the brain, often requiring permanent CSF diversion via an implanted shunt system. Such shunts are prone to failure over time; an ambulatory intracranial pressure (ICP) monitoring device may assist in the detection of shunt failure without an invasive diagnostic workup. Additionally, high resolution, noninvasive intracranial pressure monitoring will help in the study of diseases such as normal pressure hydrocephalus (NPH) and idiopathic intracranial hypertension (IIH). We propose an implantable, continuous, rechargeable ICP monitoring device that communicates via Bluetooth with mobile applications. The design requirements were met at the lower ICP ranges; the obtained error fell within the idealized ±2 mmHg margin when obtaining pressure values at or below 20 mmHg. The error was slightly above the specified range at higher ICPs (±10% from 20-100 mmHg). The system successfully simulates occlusions and disconnections of the proximal and distal catheters, valve failure, and simulation of A and B ICP waves. The mobile application accurately detects the ICP fluctuations that occur in these physiologic states. The presented macro-scale prototype is an ex-vivo model of an implantable, rechargeable ICP monitoring system that has the potential to measure clinically relevant ICPs and wirelessly provide accessible and continuous data to aid in the workup of shunt failure.

Response to Preoperative Dexamethasone Predicts Postoperative Neurological Improvement of Focal Neurological Deficits in Patients With Brain Metastases.

BACKGROUND: Steroids are used ubiquitously in the preoperative management of patients with brain tumor. The rate of improvement in focal deficits with steroids and the prognostic value of such a response are not known. OBJECTIVE: To determine the rate at which focal neurological deficits respond to preoperative corticosteroids in patients with brain metastases and whether such an improvement could predict long-term recovery of neurological function after surgery. METHODS: Patients with brain metastases and related deficits in language, visual field, or motor domains who received corticosteroids before surgery were identified. Characteristics between steroid responders and nonresponders were compared. RESULTS: Ninety six patients demonstrated a visual field (13 patients), language (19), or motor (64) deficit and received dexamethasone in the week before surgery (average cumulative dose 43 mg; average duration 2.7 days). 38.5% of patients' deficits improved with steroids before surgery, while 82.3% of patients improved by follow-up. Motor deficits were more likely to improve both preoperatively ( P = .014) and postoperatively ( P = .010). All 37 responders remained improved at follow-up whereas 42 of 59 (71%) of nonresponders ultimately improved ( P < .001). All other clinical characteristics, including dose and duration, were similar between groups. CONCLUSION: A response to steroids before surgery is highly predictive of long-term improvement postoperatively in brain metastasis patients with focal neurological deficits. Lack of a response portends a somewhat less favorable prognosis. Duration and intensity of therapy do not seem to affect the likelihood of response.

Defining the Clival Recess Surgical Corridor and Clival Classification System for Approach to Sellar Pathology.

BACKGROUND: Sellar masses within the pars intermedius, bordered anteriorly by normal pituitary gland/stalk, and/or with ectatic cavernous carotid anatomy are challenging and high risk when approached through the endonasal standard direct/anterior sellar approach. This approach portends itself to a higher risk of pituitary gland/stalk injury and subtotal resection with the aforementioned anatomic variants. OBJECTIVE: To describe the indirect clival recess corridor approach to sellar lesions. This corridor is a "silent" point of access to lesions in this region endoscopically. While skull base teams may have used this approach to some degree, it has not yet been described in the literature to our knowledge. METHODS: We defined the clival recess surgical corridor with skull base craniometric measurements and use a case example with aberrant anatomy to illustrate the approach. We cross-sectionally reviewed 42 patients with sellar and suprasellar masses. To describe the approach's anatomy, we devised and defined the terms dorsum sella plumb line, anatomic corridor, angle of osseous, and operative corridor. RESULTS: Created novel clival aeration grade informing surgical planning. Classified clival aeration as Grade 1 (100%-75% aeration), Grade 2 (75%-50% aeration), Grade 3 (50%-25% aeration), and Grade 4 (25%-0% aeration). This classification system determines extent of drilling of the clivus required to optimize the clival recess corridor approach and its limitations. CONCLUSION: The clival recess surgical corridor is effective for accessing pituitary lesions within the sella. Consider the indirect approach when a standard direct/anterior sellar approach has high risk for vascular injury and/or endocrinological dysfunction.

A Method of Intraoperative Registration Verification to Prevent Accuracy Errors in Robot-Assisted Stereotactic Electroencephalography Electrode Placement.

BACKGROUND: Robotic-assisted stereotactic electroencephalography (sEEG) electrode placement is increasingly common at specialized epilepsy centers. High accuracy and low complication rates are essential to realizing the benefits of sEEG surgery. The aim of this study was to describe for the first time in the literature a method for a stereotactic registration checkpoint to verify intraoperative accuracy during robotic-assisted sEEG and to report our institutional experience with this technique. METHODS: All cases performed with this technique since the adoption of robotic-assisted sEEG at our institution were retrospectively reviewed. RESULTS: In 4 of 111 consecutive sEEG operations, use of the checkpoint detected an intraoperative registration error, which was addressed before completion of sEEG electrode placement. CONCLUSIONS: The use of a registration checkpoint in robotic-assisted sEEG surgery is a simple technique that can prevent electrode misplacement and improve the safety profile of this procedure.

Stealth Autoguide for robotic-assisted laser ablation for lesional epilepsy: illustrative case.

BACKGROUND: Laser interstitial thermal therapy has been used in tumor and epilepsy surgery to maximize clinical treatment impact while minimizing morbidity. This intervention places a premium on accuracy. With the advent of robotics, neurosurgery is entering a new age of improved accuracy. Here, the authors described the use of robotic-assisted laser placement for the treatment of epileptiform lesions. OBSERVATIONS: The authors presented a case of a 21-year-old woman with medically intractable epilepsy, localized to left mesial temporal sclerosis and left temporal encephalocele by way of stereotactic electroencephalography, who presented for consideration of surgical intervention. When presented with resection versus laser ablation, the patient opted for laser ablation. The patient received robotic-assisted stereotactic laser ablation (RASLA) using a Stealth Autoguide. The patient was seizure free (10 weeks) after surgical ablation. LESSONS: RASLA is an effective way to treat epilepsy. Here, the authors reported the first RASLA procedure with a Stealth Autoguide to treat epilepsy. The procedure can be performed effectively and efficiently for multiple epileptic foci without the need for bulkier robotic options or head frames that may interfere with the use of magnetic resonance imaging for heat mapping.

Rare Case of Pediatric Disseminated Choroid Plexus Papilloma: Literature Review and Call for Reclassification.

INTRODUCTION: Choroid plexus tumors are rare neuroectodermal tumors that arise from the choroid plexus. Choroid plexus papillomas (CPPs) represent the lowest grade of these types of tumors and have a WHO grade I designation. Despite their typical low grade, some CPPs can exhibit aggressive behaviors including parenchymal invasion and dissemination throughout the neuro-axis. Due to their association with the choroid plexus, patients with CPP commonly present with signs and symptoms of hydrocephalus and increased intracranial pressure. CASE PRESENTATION: A 2-year-old male presented in extremis with acute hydrocephalus and seizure. He was found to have a large left intraventricular mass with innumerable intraparenchymal and extra-axial cysts throughout his neuro-axis. A literature review revealed five similar disseminated CPP cases with innumerable lesions. This is the youngest reported patient with disseminated CPP and the first with multiple compressive lesions. Following cranial resection and thoracic decompression, the patient's lesions have remained stable (2 years of follow-up). A literature search of the PubMed/Medline databases was performed using the search terms ["disseminated choroid plexus papilloma" OR "choroid plexus papilloma" OR "metastatic choroid plexus papilloma"] up to March 2021. Articles were then screened for similar patient radiographic presentation and histological diagnosis. To mitigate publication bias, referenced articles were utilized to identify other case reports and case series. DISCUSSION/CONCLUSION: We describe a rare case of a lateral ventricle CPP with widespread leptomeningeal dissemination causing acute obstructive hydrocephalus and compressive myelopathy requiring cerebrospinal fluid diversion and intracranial resection followed by thoracic spine decompression. This case report serves to broaden knowledge of disseminated CPP and to encourage complete neuro-axis imaging for choroid plexus tumors. Additionally, we propose a naming paradigm refinement that includes radiographic characteristics.

Technical challenges to anterior temporal lobectomy after laser interstitial thermal therapy for mesial temporal lobe epilepsy: technical note.

Mesial temporal sclerosis (MTS) is a frequent cause of medically refractory epilepsy, for which laser interstitial thermal therapy (LITT) is an effective treatment. However, experience with the technical considerations posed by additional surgery after an initial LITT procedure is lacking. The authors present the case of a 12-year-old female with medically refractory temporal lobe epilepsy and left MTS who underwent LITT at a separate institution prior to referral. This patient had no change in early postoperative seizure control (Engel class IVB) and then her seizures worsened despite ongoing medical treatment (Engel class IVC). Post-LITT MRI revealed sparing of the mesial hippocampus head, a poor prognostic factor. The authors describe the technical details illustrated by this case of secondary, stereotactic electroencephalography-guided mesial temporal resection following LITT. The case was managed with anterior temporal lobectomy including the resection of residual hippocampus and amygdala.

Optimal timing of radiotherapy following brain metastases surgery.

Background: There is growing evidence supporting the need for a short time delay before starting radiotherapy (RT) treatment postsurgery for most optimal responses. The timing of RT initiation and effects on outcomes have been evaluated in a variety of malignancies, but the relationship remains to be well established for brain metastasis. Methods: Retrospective study of 176 patients (aged 18-89 years) with brain metastases at a single institution (March 2009 to August 2018) who received RT following surgical resection. Time interval (≤22 and >22 days) from surgical resection to initiation of RT and any potential impact on patient outcomes were assessed. Results: Patients who underwent RT >22 days after surgical resection had a decreased risk for all-cause mortality of 47.2% (95% CI: 8.60, 69.5%). Additionally, waiting >40 days for RT after surgical resection more than doubled the risk of tumor progression; adjusted hazard ratio 2.02 (95% CI: 1.12, 3.64). Conclusions: Findings indicate that a short interval delay (>22 days) following surgical resection is required before RT initiation for optimal treatment effects in brain metastasis. Our timing of RT postsurgical resection data adds definition to current heterogeneity in RT timing, which is especially important for standardized clinical trial design and patient outcomes.

Neurological emergency from rare spinal metalloma: Case report and literature review.

Metallosis is a rare and poorly understood long-term complication of instrumented surgery that can result in an inflammatory pseudotumor termed metalloma. We describe a particularly unique case and compare it to 6 analogous cases identified by PubMed and/or Medline search through July 2020. A 79-year-old male with multiple prior spinal lumbar fusion procedures presented with progressive weakness and pain. Imaging revealed a large mass surrounding the right-sided paraspinal rod with extension into the spinal canal, neural foramina, extraforaminal spaces, psoas muscle, marrow spaces, and right sided pedicles. The case presented is a unique example of a unilateral metalloma with mixed-metal instrumentation that created a progressive neurologic deficit without infection, pseudoarthrosis, or hardware failure. This case highlights the lack of understanding regarding the pathophysiology of metallosis and metalloma in spinal instrumentation. We highlight the imaging findings of metalloma to encourage early identification for removal and decompression.

Immunotherapeutic Approaches for Glioblastoma Treatment.

Glioblastoma remains a challenging disease to treat, despite well-established standard-of-care treatments, with a median survival consistently of less than 2 years. In this review, we delineate the unique disease-specific challenges for immunotherapies, both brain-related and non-brain-related, which will need to be adequately overcome for the development of effective treatments. We also review current immunotherapy treatments, with a focus on clinical applications, and propose future directions for the field of GBM immunotherapy.

Regression of Multiple Meningiomas after Discontinuation of Chronic Hormone Therapy: A Case Report.

Introduction Meningiomas are more common in females and frequently express progesterone and estrogen receptors. Recent studies have revealed a high incidence of meningiomas in situations in which estrogen/progesterone levels are increased such as pregnancy, gender reassignment therapy, and fertility treatment. While the relationship remains unclear and controversial, these findings suggest exposure to high levels of endogenous or exogenous hormones may increase the risk of developing a meningioma. Patients and Methods A 40-year-old female with a history of endometriosis treated with chronic progesterone therapy presented with a visual deficit and was found to have multiple meningiomas, which regressed after cessation of exogenous progesterone. Conclusion A history of chronic hormone therapy should be included when evaluating patients diagnosed with meningiomas, particularly at a younger age and with multiple meningiomas. Cessation of exogenous progesterone resulting in regression of meningiomas suggests a direct action of progesterone on growth. Future studies are warranted to better elucidate this relationship.

Standardizing postoperative care for pediatric intradural Chiari decompressions to decrease length of stay.

OBJECTIVE: Amid national and local budget crises, cutting costs while maintaining quality care is a top priority. Chiari malformation is a relatively common pediatric neurosurgical pathology, and postoperative care varies widely. The postoperative course can be complicated by pain and nausea, which can extend the hospital stay. In this study, the authors aimed to examine whether instituting a standardized postoperative care protocol would decrease overall patient hospital length of stay (LOS) as well as cost to families and the hospital system. METHODS: A retrospective study of pediatric patients who underwent an intradural Chiari decompression with expansile duraplasty at a single institution from January 2016 to September 2019 was performed. A standardized postoperative care protocol was instituted on May 17, 2018. Pre- and postprotocol groups were primarily analyzed for demographics, LOS, and the estimated financial expense of the hospital stay. Secondary analysis included readmissions, opioid consumption, and follow-up. RESULTS: The analysis included 132 pediatric patients who underwent an intradural Chiari decompression with expansile duraplasty. The preprotocol group included 97 patients and the postprotocol group included 35 patients. Patient age ranged from 0.5 to 26 years (mean 9.5 years). The mean LOS preprotocol was 55.48 hours (range 25.90-127.77 hours), and the mean postprotocol LOS was 46.39 hours (range 27.58-77.38 hours). The comparison between means showed a statistically significant decrease following protocol initiation (95% CI 1.87-16.31 hours, p = 0.014). In the preprotocol group, 21 of 97 patients (22%) were discharged the first day after surgery compared with 14 of 35 patients (40%) in the postprotocol group (p = 0.045). The estimated cost of one night on the pediatric neurosurgical intermediate ward was approximately $4500, which gives overall cost estimates for 100 theoretical cases of $927,800 for the preprotocol group and $732,900 for the postprotocol group. CONCLUSIONS: By instituting a Chiari protocol, postoperative LOS was significantly decreased, which resulted in decreased healthcare costs while maintaining high-quality and safe care.

Safety assessment of intraparenchymal central nervous system biopsies: Single institution healthcare value review.

The study objective was to evaluate a single institution experience with adult stereotactic intracranial biopsies and review any projected cost savings as a result of bypassing intensive care unit (ICU) admission and limited routine head computed tomography (CT). The authors retrospectively reviewed all stereotactic intracranial biopsies performed at a single institution between February 2012 and March 2019. Primary data collection included ICU length of stay (LOS), hospital LOS, ICU interventions, need for reoperation, and CT use. Secondarily, location of lesion, postoperative hematoma, neurological deficit, pathology, and preoperative coagulopathy data were collected. There were 97 biopsy cases (63% male). Average age, ICU LOS, and total hospital stay were 58.9 years (range; 21-92 years), 2.3 days (range; 0-40 days), and 8.8 days (range 1-115 days), respectively. Seventy-five (75 of 97) patients received a postoperative head CT. No patients required medical or surgical intervention for complications related to biopsy. Eight patients required transfer from the ward to the ICU (none directly related to biopsy). Nine patients transferred directly to the ward postoperatively (none required transfer to ICU). Of the patients who did not receive CT or went directly to the ward, none had extended LOS or required transfer to ICU for neurosurgical concerns. Eliminating routine head CT and ICU admission translates to approximately $584,971 in direct cost savings in 89 cases without a postoperative ICU requirement. These practice changes would save patients' significant hospitalization costs, decrease healthcare expenditures, and allow for more appropriate hospital resource use.

Cerebrospinal Fluid Hypovolemia: A Case Report of a Red Herring.

Mild intracranial hypotension can lead to classically recognizable symptoms such as positional headaches, nausea, vomiting, and occasionally blurred vision. Less commonly, severe cerebrospinal fluid (CSF) hypovolemia can lead to a life-threatening condition that mimics intracranial hypertension, including transtentorial herniation and subsequent rapid neurologic decline. In this report we present a unique case of severe intracranial hypotension from a thoracic tumor resection that led to symptoms initially mistaken for intracranial hypertension, however ultimately correctly diagnosed as severe CSF hypovolemia that improved with dural repair. Additionally, we describe a rare angiography finding associated with CSF hypovolemia, kinking of the basilar artery. Here we report a 47-year-old female with neurofibromatosis Type 2 found to have a T3 intradural extramedullary tumor. She initially presented with urinary incontinence and gait/balance difficulty. She underwent thoracic laminectomies at T3 and T4 for the excision of the lesion. She was discharged on postoperative day 4. On postoperative day 9, she was noted to have nausea, vomiting, and decreased consciousness. Head computed tomography (CT) demonstrated acute downward herniation. She was transferred to our institution from a community facility obtunded and was intubated for airway protection. She was placed in the Trendelenburg position with immediate improvement, and declined every time her head was raised. Angiogram showed significant kinking of her basilar artery. A CT myelogram revealed a CSF leak from her recent thoracic surgery. She underwent exploration of her thoracic wound, and a ventral durotomy was repaired. Following this, she began to tolerate the head of bed elevations and recovered back to her neurologic baseline. A postoperative head CT angiography obtained before discharge showed improvement of her basilar kink. Mild intracranial hypotension is a common finding in patients who undergo procedures that enter the CSF space. Severe intracranial hypotension can easily be missed diagnosed as the signs on the exam are similar to patients with signs of intracranial hypertension. It is of paramount importance that the clinician recognizes brain sag, as the treatment algorithms are vastly different from that of intracranial hypertension leading to transtentorial herniation.

Immune modulatory nanoparticle therapeutics for intracerebral glioma.

Background: Previously we showed therapeutic efficacy of unprotected miR-124 in preclinical murine models of glioblastoma, including in heterogeneous genetically engineered murine models by exploiting the immune system and thereby negating the need for direct tumor delivery. Although these data were promising, to implement clinical trials, we required a scalable formulation that afforded protection against circulatory RNases. Methods: We devised lipid nanoparticles that encapsulate and protect the miRs from degradation and provide enhanced delivery into the immune cell compartment and tested in vivo antitumor effects. Results: Treatment with nanoparticle-encapsulated miR-124, LUNAR-301, demonstrated a median survival exceeding 70 days, with an associated reversal of tumor-mediated immunosuppression and induction of immune memory. In both canine and murine models, the safety profile of LUNAR-301 was favorable. Conclusions: For the first time, we show that nanoparticles can direct a therapeutic response by targeting intracellular immune pathways. Although shown in the context of gliomas, this therapeutic approach would be applicable to other malignancies.

Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype.

Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages. Glioblastoma patients had an elevated number of monocytes relative to healthy donors. Among CD11b+ cells, microglia and MDSCs constituted a higher percentage of GAMs than did macrophages. GAM profiling using flow cytometry studies revealed a continuum between the M1- and M2-like phenotype. Contrary to current dogma, GAMs exhibited distinct immunological functions, with the former aligned close to nonpolarized M0 macrophages.

PD-L1 expression and prognostic impact in glioblastoma.

BACKGROUND: Therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule-4 (CTLA-4) and PD-1/PD-L1 has demonstrated tumor regression in clinical trials, and phase 2 trials are ongoing in glioblastoma (GBM). Previous reports have suggested that responses are more frequent in patients with tumors that express PD-L1; however, this has been disputed. At issue is the validation of PD-L1 biomarker assays and prognostic impact. METHODS: Using immunohistochemical analysis, we measured the incidence of PD-L1 expression in 94 patients with GBM. We categorized our results according to the total number of PD-L1-expressing cells within the GBMs and then validated this finding in ex vivo GBM flow cytometry with further analysis of the T cell populations. We then evaluated the association between PD-L1 expression and median survival time using the protein expression datasets and mRNA from The Cancer Genome Atlas. RESULTS: The median percentage of PD-L1-expressing cells in GBM by cell surface staining is 2.77% (range: 0%-86.6%; n = 92), which is similar to the percentage found by ex vivo flow cytometry. The majority of GBM patients (61%) had tumors with at least 1% or more PD-L1-positive cells, and 38% had at least 5% or greater PD-L1 expression. PD-L1 is commonly expressed on the GBM-infiltrating T cells. Expression of both PD-L1 and PD-1 are negative prognosticators for GBM outcome. CONCLUSIONS: The incidence of PD-L1 expression in GBM patients is frequent but is confined to a minority subpopulation, similar to other malignancies that have been profiled for PD-L1 expression. Higher expression of PD-L1 is correlated with worse outcome.

Angiogenic cytokines are antibody targets during graft-versus-leukemia reactions.

PURPOSE: The graft-versus-leukemia (GVL) reaction is an important example of immune-mediated tumor destruction. A coordinated humoral and cellular response accomplishes leukemia cell killing, but the specific targets remain largely uncharacterized. To learn more about the antigens that elicit antibodies during GVL reactions, we analyzed patients with advanced myelodysplasia (MDS) and acute myelogenous leukemia (AML) who received an autologous, granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor cell vaccine early after allogeneic hematopoietic stem cell transplantation (HSCT). EXPERIMENTAL DESIGN: A combination of tumor-derived cDNA expression library screening, protein microarrays, and antigen-specific ELISAs were used to characterize sera obtained longitudinally from 15 patients with AML/MDS who were vaccinated early after allogeneic HSCT. RESULTS: A broad, therapy-induced antibody response was uncovered, which primarily targeted intracellular proteins that function in growth, transcription/translation, metabolism, and homeostasis. Unexpectedly, antibodies were also elicited against eight secreted angiogenic cytokines that play critical roles in leukemogenesis. Antibodies to the angiogenic cytokines were evident early after therapy, and in some patients manifested a diversification in reactivity over time. Patients that developed antibodies to multiple angiogenic cytokines showed prolonged remission and survival. CONCLUSIONS: These results reveal a potent humoral response during GVL reactions induced with vaccination early after allogeneic HSCT and raise the possibility that antibodies, in conjunction with natural killer cells and T lymphocytes, may contribute to immune-mediated control of myeloid leukemias.