Histopathological correlation of brain tumor recurrence vs. radiation effect post-radiosurgery as detected by MRI contrast clearance analysis: a validation study.

PURPOSE: The differentiation between adverse radiation effects (ARE) and tumor recurrence or progression (TRP) is a major decision-making point in the follow-up of patients with brain tumors. The advent of immunotherapy, targeted therapy and radiosurgery has made this distinction difficult to achieve in several clinical situations. Contrast clearance analysis (CCA) is a useful technique that can inform clinical decisions but has so far only been histologically validated in the context of high-grade gliomas. METHODS: This is a series of 7 patients, treated between 2018 and 2023, for various brain pathologies including brain metastasis, atypical meningioma, and high-grade glioma. MRI with contrast clearance analysis was used to inform clinical decisions and patients underwent surgical resection as indicated. The histopathology findings were compared with the CCA findings in all cases. RESULTS: All seven patients had been treated with gamma knife radiosurgery and were followed up with periodic MR imaging. All patients underwent CCA when the necessity to distinguish tumor recurrence from radiation necrosis arose, and subsequently underwent surgery as indicated. Concordance of CCA findings with histological findings was found in all cases (100%). CONCLUSIONS: Based on prior studies on GBM and the surgical findings in our series, delayed contrast extravasation MRI findings correlate well with histopathology across a wide spectrum of brain tumor pathologies. CCA can provide a quick diagnosis and have a direct impact on patients' treatment and outcomes.

Use of Novel Automated Active Irrigation With Drainage Versus Passive Drainage Alone for Chronic Subdural Hematoma-A Propensity Score-Matched Comparative Study With Volumetric Analysis.

BACKGROUND: Passive drainage post-surgical evacuation of symptomatic chronic subdural hematoma (cSDH) is currently standard of care. High rates of infection, drain occlusion, and recurrence are associated complications. OBJECTIVE: To explore the use of a novel double-lumen active automated irrigation and aspiration system, IRRAflow (IRRAS), for patients with cSDH and compared procedural and clinical outcomes against passive drainage alone with propensity score matching (PSM) and volumetric analysis. METHODS: A prospectively maintained database was retrospectively searched for consecutive patients presenting with cSDH. One-to-one PSM of covariates (including baseline comorbidities and presentation hematoma volume) in active and passive irrigation groups was performed to adjust for treatment selection bias. Rates of hematoma clearance, catheter-related occlusion, and infection; number of revisions; and length of hospital stay were recorded. RESULTS: This study included 55 patients: active continuous irrigation-drainage-21 (21 post-PSM) and passive drainage-34 (21 post-PSM). For PSM groups, a significantly higher rate of hematoma clearance was obtained in the active irrigation-drainage group (0.5 ± 0.4 vs 0.4 ± 0.5 mL/day) and in the passive drainage group; odds ratio (OR) = 1.291 (CI: 1.062-1.570, P = .002) and a significantly lower rate of catheter-related infections (OR = 0.051; CI: 0.004-0.697, P = .039). A nonsignificantly lower hematoma expansion rate at discharge was noted in the active irrigation-drainage group (4.8% vs 23.8%; OR = 0.127; P = .186). No statistical difference in all-cause in-hospital mortality or discharge Glasgow Coma Scale score was observed between groups. CONCLUSION: Active and automated continuous irrigation plus drainage after cSDH surgical evacuation resulted in faster hematoma clearance and led to favorable clinical outcomes and low complication and revision rates compared with passive irrigation.

Cerebral Proliferative Angiopathy Presenting as Subdural Hematoma: A Case Report and Systematic Literature Review.

Cerebral proliferative angiopathy (CPA) is a rare cerebrovascular pathology that presents with unique clinical features due to distinct histologic, angiographic, and pathophysiologic characteristics that separate it from classical arteriovenous malformation. The disorder is characterized by uncontrolled angiogenesis in which functional brain parenchyma is interspersed with abnormal vascular channels without a distinct nidus. Common presenting symptoms include headache, seizures, and stroke-like symptoms. Hemorrhagic presentations are rare in contrast to the typical presentations of classical arteriovenous malformation. Here, we report a young woman with a history of a suspected connective tissue disorder who presented to the emergency department with worsening headaches in a delayed fashion after experiencing minor head trauma and was found to have a left-sided subdural hematoma. Angiography confirmed a diagnosis of CPA after abnormal cortical vasculature was noted during the patient's craniotomy. A systematic review of CPA cases described in the literature was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with the findings discussed.

Removing Craniofacial Titanium Screws: Technical Note.

Craniotomy, cranioplasty, and craniofacial procedures may involve reoperation for additional treatment of the primary pathological condition or treatment of complications, requiring removal of previously placed hardware. During removal of the titanium hardware, there is a risk of losing, dropping, or misplacing the titanium screws because of their small size. There are also instances of difficulty disengaging the screw from the screwdriver. We describe the use of a plastic specimen cup in retrieving titanium screws after detaching them from the screwdriver by screwing the screw into the cup, thus rapidly and safely securing and storing screws for collection/discarding or possible reuse. When the empty screwdriver is used to retrieve and unscrew the titanium screw from the cranial flap or the skull bone, a plastic specimen cup should be placed adjacent to the site of screw removal. Once the screw is removed, while it is still fastened to the screwdriver, it is immediately re-screwed and secured onto the base of the plastic specimen cup, which is then placed into a second plastic specimen cup. This method prevents misplacement or dropping of the screw that may otherwise occur when manipulating the screw on or off the screwdriver and avoids perforating the surgeon's glove during handling. We describe the adjunctive use of a plastic specimen cup when removing cranial screws and hardware to rapidly and safely detach the screw and prevent the misplacement, dropping, or loss of screws intraoperatively that results in additional operative time and personnel assistance.

Therapeutic Targeting of the Notch Pathway in Glioblastoma Multiforme.

BACKGROUND: Glioblastoma (GBM) is the most common and deadly form of brain tumor. After standard treatment of resection, radiotherapy, and chemotherapy, the 5-year survival is <5%. In recent years, research has uncovered several potential targets within the Notch signaling pathway, which may lead to improved patient outcomes. METHODS: A literature search was performed for articles containing the terms "Glioblastoma" and "Receptors, Notch" between 2003 and July 2015. Of the 62 articles retrieved, 46 met our criteria and were included in our review. Nine articles were identified from other sources and were subsequently included, leaving 55 articles reviewed. RESULTS: Of the 55 articles reviewed, 47 used established human GBM cell lines. Seventeen articles used human GBM surgical samples. Forty-five of 48 articles that assessed Notch activity showed increased expression in GBM cell lines. Targeting the Notch pathway was carried out through Notch knockdown and overexpression and targeting δ-like ligand, Jagged, γ-secretase, ADAM10, ADAM17, and Mastermindlike protein 1. Arsenic trioxide, microRNAs, and several other compounds were shown to have an effect on the Notch pathway in GBM. Notch activity in GBM was also shown to be associated with hypoxia and certain cancer-related molecular pathways such as PI3K/AKT/mTOR and ERK/MAPK. Most articles concluded that Notch activity amplifies malignant characteristics in GBM and targeting this pathway can bring about amelioration of these effects. CONCLUSIONS: Recent literature suggests targeting the Notch pathway has great potential for future therapies for GBM.

Role of bevacizumab for treatment-refractory meningiomas: A systematic analysis and literature review.

Background: Meningiomas are the most prevalent primary tumor of the central nervous system (CNS), and although the majority of these neoplasms are classified as benign, nearly one fourth of the lesions display an aggressive profile characterized by pleomorphic histology, high recurrence rates, and overall resistance to standard treatment. Despite the ubiquitous nature of these tumors, no adjuvant therapeutic regimen has been identified which effectively controls disease recurrence and progression after surgery and radiation, leading to a dismal prognosis in this patient population. The primary focus of this research study is, hence, to assess the recently emerging use of bevacizumab, an anti-angiogenic agent, in the treatment of meningiomas. This systematic literature review analyzes the efficacy and safety of therapeutic bevacizumab for treatment-refractory meningiomas. Methods: A systematic PubMed search was conducted according to PRISMA guidelines to identify all relevant reports investigating the anti-angiogenic agent bevacizumab in the treatment of intracranial meningiomas. The reported parameters from pertinent retrospective reviews, prospective studies, and case studies were volumetric reduction, radiographic response, clinical stability, overall survival (OS), and progression free survival (PFS) measured at 6 and 12 months postinitiation of treatment. Complications were cataloged based on the range and severity of the therapy-related toxicities. Results: A total of 11 articles, 5 retrospective series, 2 prospective trials, and 4 case reports, reporting on a total of 92 patients, were included in this review. The use of bevacizumab therapy for intracranial meningiomas demonstrated median overall PFS of 16.8 months (range: 6.5-22 months) and PFS-6 of 73% (range: 44%-93%). Conclusions: Therapeutic bevacizumab, either alone or with combination chemotherapies, for select patient populations with recurrent or progressive meningiomas, offers a treatment option that confers improved overall progression-free survival. To assess OS parameters, larger randomized controlled trials assessing the use of anti-angiogenic agents for recurrent/progressive meningiomas are warranted.

Neuroendovascular Fellowship Training: Self-Assessment of a Program Accredited by the Committee on Advanced Subspecialty Training.

The University at Buffalo's neuroendovascular fellowship is one of the longest running fellowship programs in North America. The burgeoning neurointerventional workforce and the rapid growth in the neurointerventional space on the heels of groundbreaking clinical trials prompted us to assess the fellowship's academic impact and its graduates' perceptions and productivity. An anonymized web-based survey was sent to all former neuroendovascular fellows with specific questions pertaining to current practice, research and funding, and perceptions about the fellowship's impact on their skills, competitiveness, and compensation. Additionally, the h-index was calculated to assess the academic productivity of each graduated fellow. Among 50 former fellows, 42 (84%) completed the survey. The fellows came from various countries, ethnic backgrounds, and specialties including neurosurgery (n = 39, 93%), neurology (n = 2, 5%), and neuroradiology (n = 1, 2%). Twenty (48%) respondents were currently chairs or directors of their practice. Most (n = 30, 71%) spent at least 10% of their time on research activities, with 27 (64%) receiving research funding. The median h-index of all 50 former fellows was 14. The biggest gains from the fellowship were reported to be improvement in endovascular skills (median = 10 on a scale of 0-10 [highest]) and increase in competitiveness for jobs in vascular neurosurgery (median = 10), followed by increase in academic productivity (median = 8), and knowledge of vascular disease (median = 8). In an era with open calls for moratoriums on endovascular fellowships, concerns over market saturation, and pleas to improve training, fellowship programs perhaps merit a more objective assessment. The effectiveness of a fellowship program may best be measured by the academic impact and leadership roles of former fellows.

Neurosarcoidosis presenting as an incidental solitary cranial ring-enhancing lesion.

Isolated neurosarcoidosis without prior systemic symptoms is extremely rare, occurring in approximately 2% of patients with neurosarcoidosis. Due to its rarity, mistakes in diagnosis and treatment occur commonly. We present a case of a 47-year-old female who was found to have an incidentally discovered solitary intracranial lesion that mimicked a high-grade neoplasm, but was later confirmed to be neurosarcoidosis. Incidental solitary neurosarcoid granulomas are difficult to diagnose due to its nonspecific clinical and imaging presentations. Early diagnosis by biopsy in these rare incidental cases remains paramount for adequate treatment.

Increased Expression of Epileptiform Spike/Wave Discharges One Year after Mild, Moderate, or Severe Fluid Percussion Brain Injury in Rats.

In this study, we describe increased expression of cortical epileptiform spike/wave discharges (SWD) in rats one year after mild, moderate, or severe fluid percussion traumatic brain injury (fpTBI). Groups of rats consisted of animals that had received mild, moderate, or severe fpTBI, or sham operation one year earlier than electrocorticography (ECoG) recordings. In addition, we included a group of age-matched naïve animals. ECoG was recorded from awake animals using epidural electrodes implanted on the injured hemisphere (right), sham-operated hemisphere (right), or right hemisphere in naïve animals. The SWDs were detected automatically using Fast Fourier Transformation and a novel algorithm for comparing changes in spectral power to control (nonepileptical) ECoG. The fpTBI resulted in increased expression of SWDs one year after injury compared with sham-operated or naïve animals. The number of SWD-containing ECoG epochs recorded in a 1 h recording session were: naïve 12.9 ± 10.3, n = 8, sham 23.6 ± 8.2, n = 10, mild TBI 78.9 ± 23.9, n = 10, moderate TBI 61.3 ± 32.5, n = 12, severe TBI 72.5 ± 28.3, n = 11 (mean ± standard error of the mean). Increased expression of SWDs was not related to injury severity. SWDs were observed to a lesser extent even in sham-operated and naïve animals. The data indicate that fpTBI exacerbates expression of SWDs in the rat and that this increase may be observed at least one year after injury. As others have discussed, the spontaneous occurrence of these epileptiform events in rodents limits the use of this model for investigations of acquired epilepsy, at least of the nonconvulsive type, after TBI.

Revisiting the Relationship Between Ethnicity and Outcome in Glioblastoma Patients.

BACKGROUND: Relationships between various ethnicities and glioma subtype have recently been established. As a tertiary referral center for Latin America and the Caribbean, our institution treats a diverse glioblastoma (GBM) population. We sought to clarify the role of ethnicity on patient prognosis in GBM and also compared these findings to a group consisting of elderly patients. We included 'elderly' as a group because the subgroups for ethnicities within them were too small. It allowed us to put in scope the effects of ethnicities on the overall survival.  Material and Methods: After Institutional Review Board approval, 235 patients with GBM were retrospectively identified. A total of 140 patients were separated into four groups: White adults (n = 47), Hispanic adults (n = 27), elderly (n = 58), and Black adults (n = 6). Overall survival (OS) was our primary endpoint. RESULTS: Overall survival in the White adult group was 24.3 months, compared to 13.0 months in the Hispanic adult group, 20.2 months in the Black group, and 13.8 months in the elderly group (p = 0.01). In the Hispanic group, hypertension (37.9%, p = 0.01) and diabetes (24.1%, p = 0.009) were significantly more prevalent compared to the White adult cohort. No difference in insurance status or postoperative complications was found between subgroups. CONCLUSION: Based on our analysis, Hispanic adults may have a decreased survival compared to White adults. However, the incidence of hypertension and diabetes was markedly higher in our Hispanic adult cohort; thus, estimating the risk of ethnicity and comorbidities on patient prognosis may be difficult. A prospective study correlating the genome and subgroup prognosis may help elucidate the role of ethnicity in GBM patients.

The role of brachytherapy in the treatment of glioblastoma multiforme.

Brachytherapy (BT) for glioblastoma multiforme (GBM) involves the use of radioactive isotopes to deliver ionizing radiation directly into the tumor bed. Its application as a means to prolong survival in GBM patients over the past few decades has come with variable success. The objective of this review is to describe the utility of BT in GBM, and to report the outcomes and adverse events associated with its use in different multimodal treatment approaches. A search of the literature was conducted using the PubMed database. The most recent search was performed in September 2015. Thirty-two series involving 1571 patients were included in our review. The longest median overall survival (MOS) following BT for newly diagnosed GBM reached 28.5 months. Overall, 1-, 2-, and 3-year survival rates were 46-89 %, 20-57 %, and 14-27 %. For recurrent GBM, the longest reported MOS after BT was 15.9 months. One-, 2- and 3-year survival rates for recurrent GBM were 10-66 %, 3-23 %, and 9-15 %. Adverse events were reported in 27 % of patients. Reoperation for radiation necrosis occurred in 4 and 27 % of patients following low- and high-dose rate BT, respectively. BT is a feasible option for extending survival in carefully selected GBM patients. As patient outcomes and overall survival improve with more aggressive radiotherapy, so does the risk of radiation-related complications. The most effective use of BT is likely as a part of multimodal treatment with other novel therapies.

Investigating the therapeutic role and molecular biology of curcumin as a treatment for glioblastoma.

OBJECTIVES: Despite the aggressive standard of care for patients with glioblastoma multiforme, survival rates typically do not exceed 2 years. Therefore, current research is focusing on discovering new therapeutics or rediscovering older medications that may increase the overall survival of patients with glioblastoma. Curcumin, a component of the Indian natural spice, turmeric, also known for its antioxidant and anti-inflammatory properties, has been found to be an effective inhibitor of proliferation and inducer of apoptosis in many cancers. The goal of this study was to investigate the expanded utility of curcumin as an antiglioma agent. METHODS: Using the PubMed MeSH database, we conducted a systematic review of the literature to include pertinent studies on the growth inhibitory effects of curcumin on glioblastoma cell lines based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 19 in vitro and five in vivo studies were analyzed. All of the studies indicated that curcumin decreased glioblastoma cell viability through various pathways (i.e. decrease in prosurvival proteins such as nuclear factor κB, activator protein 1, and phosphoinositide 3 kinase, and upregulation of apoptotic pathways like p21, p53, and executor caspase 3). Curcumin treatment also increased animal survival compared with control groups. CONCLUSIONS: Curcumin inhibits proliferation and induces apoptosis in certain subpopulations of glioblastoma tumors, and its ability to target multiple signaling pathways involved in cell death makes it an attractive therapeutic agent. As such, it should be considered as a potent anticancer treatment. Further experiments are warranted to elucidate the use of a bioavailable form of curcumin in clinical trials.

Glioblastoma multiforme of the optic chiasm: A rare case of common pathology.

BACKGROUND: Malignant optic and chiasmatic gliomas are extremely rare, and are classified pathologically as anaplastic astrocytoma or glioblastoma multiforme (GBM). Approximately 40 cases of optic GBM in adults have been reported in the literature, and only five of them were described to originate from the optic chiasm. CASE DESCRIPTION: An 82-year-old male patient with a past medical history of diabetes mellitus type 2, melanoma, and bladder cancer presented with gradual vision loss of the left eye in a period of 1 month. After neuro-ophthalmological examination, the decision of thither magnetic resonance imaging (MRI) studies was made. It showed a contrast enhancing mass in the region of the optic chiasm. In this case, imaging study was not enough to establish an accurate diagnosis and a left pterional craniotomy for biopsy and resection of the optic chiasmal mass was performed. After histological evaluation of the mass tissue, the diagnosis of GBM was made. Taking into account the patient's poor condition and unfavorable prognosis he was moved to inpatient hospice. The patient deceased within 2 months after surgery. CONCLUSION: Chiasmal GBM is an extremely rare condition where a biopsy is necessary for accurate diagnosis and optimal treatment. Differential diagnosis for such lesions can be very difficult and include demyelinating optic neuritis and non-demyelinating inflammatory optic neuropathy (e.g., sarcoid), vascular lesions (e.g., cavernoma), compressive lesions of the optic apparatus, metastatic malignancy, and primary tumors of the anterior optic pathway. The role of chemotherapy and radiotherapy including novel stereotaxic radiosurgery methods is still unclear and will need to be evaluated.

The role of 5-aminolevulinic acid in brain tumor surgery: a systematic review.

Recently, 5-aminolevulinic acid (5-ALA) has been utilized as an adjuvant to the surgical resection of primary brain tumors and metastases. We conducted a systematic review of the literature to further understand the role of 5-ALA in neurosurgery. Our goal was to identify the utility of 5-ALA during resection by evaluating its sensitivity and specificity for different tumor types, as well as the extent of tumor resection achieved while using 5-ALA. A search of the literature was conducted using the PubMed database for the period January 1990 through May 2014. Surgical series in which 5-ALA was used for brain neoplasm resections were evaluated for tumor histology, sensitivity, specificity, extent of resection, complications, and outcomes. Twenty-two series, involving 1163 patients, were included in our review. 5-ALA sensitivity was highest in high-grade gliomas (85 %) and meningiomas (81 %). 5-ALA specificity was high in meningiomas (100 %), as well as metastases (84 %) and high-grade gliomas (82 %). Gross total resection (GTR) was achieved using 5-ALA in 66.2 % of all gliomas and 69.6 % of meningiomas, regardless of histological subtype. 5-ALA may be a useful tool in increasing the extent of resection and achieving GTR in intracranial tumors. The resection of tumors for which 5-ALA has high sensitivity and specificity, such as high-grade gliomas, may lead to an increase in extent of resection when compared to operations using only standard white light. Further evidence for the use of 5-ALA in meningiomas and certain subtypes of metastases may be needed to qualify its efficacy.

Disappearing large calcified thoracic disc herniation in a patient with thalassaemia.

Regression of herniated disc fragments with subsequent improvement in clinical symptoms has been reported in the lumbar and cervical spine. Such regressions in the thoracic spine are extremely rare. We report a case of a 38-year-old patient with thalassaemia who had regression of a large calcified herniated thoracic disc causing cord compression, with subsequent herniation of a second calcified disc at a different level and discuss the possible aetiopathogenesis. This is the first such case reported in the thalassaemia population.

Primary spinal cord glioblastoma multiforme treated with temozolomide.

Since virtually no trials have evaluated the effectiveness of temozolomide (TMZ) in the treatment of spinal cord (SC) glioblastoma multiforme (GBM), we conducted a systematic review to evaluate its efficacy. Primary SC GBM is rare. Its management remains unclear, even though treatment guidelines have been established since 2005 for its cranial counterpart. We performed a medical subject heading search with the terms "glioblastoma" and "primary spinal cord neoplasms, intramedullary". We stratified the papers into two groups according to the use of TMZ, and analyzed survival rates using the Kaplan­Meier method with a two-sided log-rank scale. The TMZ subgroup contained nine articles and a total of 19 patients with primary SC GBM who were treated with adjuvant TMZ. The non-TMZ group consisted of 19 articles including 45 patients who underwent other treatment modalities. The TMZ subgroup had an overall survival of 16 months, compared to the non-TMZ group with a median overall survival of 10 months. The difference between these two groups was not statistically significant (p = 0.57). While this review did not demonstrate a statistically significant difference in long term survival between patients with SC GBM treated with TMZ versus those not treated with TMZ, a slightly longer survival time was seen in the TMZ group. The small number of patients is likely a contributing factor to the lack of statistical significance. Our analysis highlights the need for a multi-institutional, prospective, controlled study to evaluate the use of TMZ in the treatment of SC GBM.

Deep brain stimulation complicated by bilateral large cystic cavitation around the leads in a patient with Parkinson's disease.

Deep brain stimulation (DBS) is an approved and effective therapy for patients suffering from advanced Parkinson's disease (PD). Several clinical trials have indicated significant motor function improvement in patients undergoing subthalamic nucleus stimulation. This therapy is, rarely, associated with complications, mostly related to infections, seizures or stimulation-induced side effects. We report a case of a 71-year-old man with a 10-year history of PD who underwent bilateral placement of subthalamic nucleus DBS. As a complication, the patient showed subjective postoperative cognitive decline, and subsequent MRI showed peri-lead oedema, which progressed to large cystic cavitation around the leads without indication of infection. The patient received steroid therapy and the cavitations regressed without surgical intervention.

The role of awake craniotomy in reducing intraoperative visual field deficits during tumor surgery.

OBJECTIVE: Homonymous hemianopia due to damage to the optic radiations or visual cortex is a possible consequence of tumor resection involving the temporal or occipital lobes. The purpose of this review is to present and analyze a series of studies regarding the use of awake craniotomy (AC) to decrease visual field deficits following neurosurgery. MATERIALS AND METHODS: A literature search was performed using the Medline and PubMed databases from 1970 and 2014 that compared various uses of AC other than intraoperative motor/somatosensory/language mapping with a focus on visual field mapping. RESULTS: For the 17 patients analyzed in this study, 14 surgeries resulted in quadrantanopia, 1 in hemianopia, and 2 without visual deficits. Overall, patient satisfaction with AC was high, and AC was a means to reduce surgery-related complications and cost related with the procedure. CONCLUSION: AC is a safe and tolerable procedure that can be used effectively to map optic radiations and the visual cortices in order to preserve visual function during resection of tumors infiltrating the temporal and occipital lobes. In the majority of cases, a homonymous hemianopia was prevented and patients were left with a quadrantanopia that did not interfere with daily function.