Improved outcomes for triple negative breast cancer brain metastases patients after stereotactic radiosurgery and new systemic approaches.

PURPOSE: Although ongoing studies are assessing the efficacy of new systemic therapies for patients with triple negative breast cancer (TNBC), the overwhelming majority have excluded patients with brain metastases (BM). Therefore, we aim to characterize systemic therapies and outcomes in a cohort of patients with TNBC and BM managed with stereotactic radiosurgery (SRS) and delineate predictors of increased survival. METHODS: We used our prospective patient registry to evaluate data from 2012 to 2023. We included patients who received SRS for TNBC-BM. A competing risk analysis was conducted to assess local and distant control. RESULTS: Forty-three patients with 262 tumors were included. The median overall survival (OS) was 16 months (95% CI 13-19 months). Predictors of increased OS after initial SRS include Breast GPA score > 1 (p < 0.001) and use of immunotherapy such as pembrolizumab (p = 0.011). The median time on immunotherapy was 8 months (IQR 4.4, 11.2). The median time to new CNS lesions after the first SRS treatment was 17 months (95% CI 12-22). The cumulative rate for development of new CNS metastases after initial SRS at 6 months, 1 year, and 2 years was 23%, 40%, and 70%, respectively. Thirty patients (70%) underwent multiple SRS treatments, with a median time of 5 months (95% CI 0.59-9.4 months) for the appearance of new CNS metastases after second SRS treatment. CONCLUSIONS: TNBC patients with BM can achieve longer survival than might have been previously anticipated with median survival now surpassing one year. The use of immunotherapy is associated with increased median OS of 23 months.

Widespread decline in Central European plant diversity across six decades.

Based on plant occurrence data covering all parts of Germany, we investigated changes in the distribution of 2136 plant species between 1960 and 2017. We analyzed 29 million occurrence records over an area of ~350,000 km2 on a 5 × 5 km grid using temporal and spatiotemporal models and accounting for sampling bias. Since the 1960s, more than 70% of investigated plant species showed declines in nationwide occurrence. Archaeophytes (species introduced before 1492) most strongly declined but also native plant species experienced severe declines. In contrast, neophytes (species introduced after 1492) increased in their nationwide occurrence but not homogeneously throughout the country. Our analysis suggests that the strongest declines in native species already happened in the 1960s-1980s, a time frame in which often few data exist. Increases in neophytic species were strongest in the 1990s and 2010s. Overall, the increase in neophytes did not compensate for the loss of other species, resulting in a decrease in mean grid cell species richness of -1.9% per decade. The decline in plant biodiversity is a widespread phenomenon occurring in different habitats and geographic regions. It is likely that this decline has major repercussions on ecosystem functioning and overall biodiversity, potentially with cascading effects across trophic levels. The approach used in this study is transferable to other large-scale trend analyses using heterogeneous occurrence data.

Endothelium-Independent Primitive Myxoid Vascularization Creates Invertebrate-Like Channels to Maintain Blood Supply in Optic Gliomas.

Optic gliomas are brain tumors characterized by slow growth, progressive loss of vision, and limited therapeutic options. Optic gliomas contain various amounts of myxoid matrix, which can represent most of the tumor mass. We sought to investigate biological function and protein structure of the myxoid matrix in optic gliomas to identify novel therapeutic targets. We reviewed histological features and clinical imaging properties, analyzed vasculature by immunohistochemistry and electron microscopy, and performed liquid chromatography-mass spectrometry on optic gliomas, which varied in the amount of myxoid matrix. We found that although subtypes of optic gliomas are indistinguishable on imaging, the microvascular network of pilomyxoid astrocytoma, a subtype of optic glioma with abundant myxoid matrix, is characterized by the presence of endothelium-free channels in the myxoid matrix. These tumors show normal perfusion by clinical imaging and lack histological evidence of hemorrhage organization or thrombosis. The myxoid matrix is composed predominantly of the proteoglycan versican and its linking protein, a vertebrate hyaluronan and proteoglycan link protein 1. We propose that pediatric optic gliomas can maintain blood supply without endothelial cells by using invertebrate-like channels, which we termed primitive myxoid vascularization. Enzymatic targeting of the proteoglycan versican/hyaluronan and proteoglycan link protein 1 rich myxoid matrix, which is in direct contact with circulating blood, can provide novel therapeutic avenues for optic gliomas of childhood.

Cerebrospinal Fluid Fistula for the Craniofacial Surgeon: A Review and Management Paradigm.

Craniofacial surgeons perform operations that involve exposure of the dura. Typical procedures include cranial vault remodeling (CVR), fronto-orbital advancement (FOA), Le Fort III, monobloc, bipartition advancement, or distraction. Cerebrospinal fluid (CSF) fistulas remain one of the most common complications encountered, occurring in up to 30% of patients. Cerebrospinal fluid fistulas can be encountered intraoperatively, acutely, or in the late postoperative period. Traditional management has been well described in the neurosurgical literature. While several studies of complications exist, there is a relative lack of adequate information for craniofacial surgeons. The authors review current literature and provide 3 patients to illustrate our management paradigm.The authors review 30 years of experience at our institution and the pertinent literature. The mean rate of CSF fistula was 11.2%; rates were lowest for FOA/CVR, 5.5%. Patients with fistulas persisting after 2 days of conservative therapy or whom were symptomatic prompted placement of a lumbar subarachnoid catheter. Failure of the leak to resolve with CSF diversion prompted exploration and therapy which could include a patch, pericranial flap, and/or endonasal repair with septal flaps. Three patients are used to illustrate the paradigm, all of which have had no recurrence thus far.Cerebrospinal fluid fistula remains one of most common complications craniofacial surgeons encounter. Although neurosurgeons are often part of the clinical team, the craniofacial surgeon should be familiar with all aspects of treatment. Prompt diagnosis and appropriate knowledgeable management may avoid morbidity and mortality.

Noncarboplatin-induced Sensorineural Hearing Loss in a Patient With an Intracranial Nongerminomatous Germ Cell Tumor.

Treatment for intracranial germ cell tumors includes platinum-based chemotherapy and external beam radiation therapy, which are risk factors for hearing loss. In patients who experience significant sensorineural ototoxicity due to cochlear hair cell injury, dose reduction of chemotherapy may be necessary. This report describes an adolescent male, with excellent treatment response for an intracranial nongerminomatous germ cell tumor, who developed sensorineural hearing loss, which was central rather than cochlear in origin and unrelated to carboplatin. This patient highlights the need to carefully differentiate the type and etiology of sensorineural hearing loss in patients with brain tumors receiving ototoxic chemotherapy.

Open and endoscopic excision of calvarial dermoid and epidermoid cysts: a single center experience on 128 consecutive cases.

OBJECTIVE: Dermoid and epidermoid cysts rank among the most common pediatric tumors. We analyzed the outcomes of surgical excision of dermal and epidermal inclusion cysts in a large consecutive series of children. METHODS: We retrospectively reviewed 128 consecutive children who underwent calvarial inclusion cyst resection between 2000 and 2010 at NYU Langone Medical Center. Demographic information, neurological exam, lesion location, lesion diameter, type of treatment, extent of resection, time of follow-up, and recurrence were collected. RESULTS: The cohort includes 67 girls (52.3 %) and 61 boys (47.7 %). Age at diagnosis ranged from birth to 6.5 years (mean of 1.2 years) with surgical intervention between 1 month and 20 years of age (1.5 ± 2.1). Of the 128 patients, 107 underwent open resection. Surgical approach was determined by the senior surgeon. Location, postoperative cosmesis, and family preference were the determining factors. Endoscopic resection was favored with supraorbital and glabellar lesions (75 % endoscopic versus 25 % open) using a rigid scope via a single incision. Erosion of the outer table and involvement of the inner table was noted in 20 patients (15 %), 14 of which were reconstructed using a split thickness calvarial graft. These lesions were noted to be significantly larger than lesions where cranioplasty was not used (1.9 ± 2.81 cm versus 1.23 ± 0.98 cm, p = 0.022). Gross total resection was achieved in all cases. DISCUSSION: Complete removal and cure from dermoid and epidermoid inclusion cysts are possible. Complications are few. Endoscopic approaches are useful to improve cosmesis and limit tissue damage for lesions near the orbits.

"The Predictive role of Early Postoperative MRI after Endoscopic Third Ventriculostomy".

OBJECTIVE: Endoscopic third ventriculostomy (ETV) is a treatment option for obstructive hydrocephalus; reported success rates vary. We investigated immediate postoperative magnetic resonance imaging (MRI) to evaluate the role of imaging parameters associated with outcomes. METHODS: Retrospective chart review was performed patients undergoing initial ETV between 2005 -2019. Patients with pre- and postoperative MRI with follow-up >one year were included. The following were noted: changes in subarachnoid CSF, third ventricle diameter (TV), bowing of the TV floor, and postoperative flow void. Kaplan-Meier survival methods were used to assess ETV success, Univariable and multivariable Cox proportional-hazards models were fitted to assess factors contributing to ETV success. RESULTS: Fifty-eight subjects were included. Nineteen (32.8%) experienced failure within one year, individually, no single imaging parameter predicted success. However, all cases with failure had no identifiable flow void. Any postoperative radiological change was not consistently associated with decreased odds of failure. Obstructive hydrocephalus treated with ETV demonstrated significantly better ETV success than patients treated for non-obstructive hydrocephalus Inter-observer reliability was moderate for two of the radiological variables and substantial for one of the radiological variables. CONCLUSIONS: Individually none of the qualitative radiologic parameters measured in our study predicted ETV success. Absence of a flow void predicted ETV failure, but additional studies are needed to determine its true negative predictive value. Inability to clarify which specific parameter predicts success, reflects the limited role of immediate postoperative imaging in influencing clinical management.

Auditory brainstem implantation: surgical experience and audiometric outcomes in the pediatric population.

OBJECTIVE: Pediatric data regarding treatment via an auditory brainstem implant (ABI) remains sparse. The authors aimed to describe their experience at their institution and to delineate associated demographic data, audiometric outcomes, and surgical parameters. METHODS: An IRB-approved, retrospective chart review was conducted among the authors' pediatric patients who had undergone auditory brainstem implantation between 2012 and 2021. Demographic information including sex, age, race, coexisting syndrome(s), history of cochlear implant placement, average duration of implant use, and follow-up outcomes were collected. Surgical parameters collected included approach, intraoperative findings, number of electrodes activated, and complications. RESULTS: A total of 19 pediatric patients had an ABI placed at the authors' institution, with a mean age at surgery of 4.7 years (range 1.5-17.8 years). A total of 17 patients (89.5%) had bilateral cochlear nerve aplasia/dysplasia, 1 (5.3%) had unilateral cochlear nerve aplasia/dysplasia, and 1 (5.3%) had a hypoplastic cochlea with ossification. A total of 11 patients (57.9%) had a history of cochlear implants that were ineffective and required removal. The mean length of implant use was 5.31 years (0.25-10 years). Two patients (10.5%) experienced CSF-related complications requiring further surgical intervention. The most recent audiometric outcomes demonstrated that 15 patients (78.9%) showed improvement in their hearing ability: 5 with sound/speech awareness, 5 able to discriminate among speech and environmental sounds, and 5 able to understand common phrases/conversation without lip reading. Nine patients (47.4%) are in a school for the deaf and 7 (36.8%) are in a mainstream school with support. CONCLUSIONS: The authors' surgical experience with a multidisciplinary team demonstrates that the retrosigmoid approach for ABI placement in children with inner ear pathologies and severe sensorineural hearing loss is a safe and effective treatment modality. Audiometric outcome data showed that nearly 79% of these patients had an improvement in their environmental and speech awareness. Further multicenter collaborations are necessary to improve these outcomes and potentially standardize/enhance electrode placement.

Association between structural rib autograft and the rate of arthrodesis in children undergoing occiput-C2 instrumentation and fusion.

OBJECTIVE: The purpose of this study was to identify factors associated with fusion success among pediatric patients undergoing occiput-C2 rigid instrumentation and fusion. METHODS: The Pediatric Spine Study Group registry was queried to identify patients ≤ 21 years of age who underwent occiput-C2 posterior spinal rigid instrumentation and fusion and had a 2-year minimum clinical and radiographic (postoperative lateral cervical radiograph or CT scan) follow-up. Fusion failure was defined clinically if a patient underwent hardware revision surgery > 30 days after the index procedure or radiographically by the presence of hardware failure or screw haloing on the most recent follow-up imaging study. Univariate comparisons and multivariable logistic regression analyses were subsequently performed. RESULTS: Seventy-six patients met inclusion criteria. The median age at surgery was 9 years (range 1.5-17.2 years), and 51% of the cohort was male. Overall, 75% of patients had syndromic (n = 41) or congenital (n = 15) etiologies, with the most frequent diagnoses of Down syndrome (28%), Chiari malformation (13%), and Klippel-Feil syndrome (12%). Data were available to determine if there was a fusion failure in 97% (74/76) of patients. Overall, 38% (28/74) of patients had fusion failure (95% CI 27%-50%). Univariate analysis demonstrated that use of a rigid cervical collar postoperatively (p = 0.04) and structural rib autograft (p = 0.02) were associated with successful fusion. Multivariable logistic regression analysis determined that patients who had rib autograft used in surgery had a 73% decrease in the odds of fusion failure (OR 0.27, 95% CI 0.09-0.82; p = 0.02). Age, etiology including Down syndrome, instrumentation type, unilateral instrumentation, use of recombinant human bone morphogenetic protein, and other variables did not influence the risk for fusion failure. CONCLUSIONS: In this multicenter, multidisciplinary, international registry of children undergoing occiput-C2 instrumentation and fusion, fusion failure was seen in 38% of patients, a higher rate than previously reported in the literature. The authors' data suggest that postoperative immobilization in a rigid cervical collar may be beneficial, and the use of structural rib autograft should be considered, as rib autograft was associated with a 75% higher chance of successful fusion.

Impact of Rare and Multiple Concurrent Gene Fusions on Diagnostic DNA Methylation Classifier in Brain Tumors.

DNA methylation is an essential molecular assay for central nervous system (CNS) tumor diagnostics. While some fusions define specific brain tumors, others occur across many different diagnoses. We performed a retrospective analysis of 219 primary CNS tumors with whole genome DNA methylation and RNA next-generation sequencing. DNA methylation profiling results were compared with RNAseq detected gene fusions. We detected 105 rare fusions involving 31 driver genes, including 23 fusions previously not implicated in brain tumors. In addition, we identified 6 multi-fusion tumors. Rare fusions and multi-fusion events can impact the diagnostic accuracy of DNA methylation by decreasing confidence in the result, such as BRAF, RAF, or FGFR1 fusions, or result in a complete mismatch, such as NTRK, EWSR1, FGFR, and ALK fusions. IMPLICATIONS: DNA methylation signatures need to be interpreted in the context of pathology and discordant results warrant testing for novel and rare gene fusions.

Developing consensus for the management of pediatric cervical spine disorders and stabilization: a modified Delphi study.

OBJECTIVE: Cervical spine disorders in children are relatively uncommon; therefore, paradigms for surgical and nonsurgical clinical management are not well established. The purpose of this study was to bring together an international, multidisciplinary group of pediatric cervical spine experts to build consensus via a modified Delphi approach regarding the clinical management of children with cervical spine disorders and those undergoing cervical spine stabilization surgery. METHODS: A modified Delphi method was used to identify consensus statements for the management of children with cervical spine disorders requiring stabilization. A survey of current practices, supplemented by a literature review, was electronically distributed to 17 neurosurgeons and orthopedic surgeons experienced with the clinical management of pediatric cervical spine disorders. Subsequently, 52 summary statements were formulated and distributed to the group. Statements that reached near consensus or that were of particular interest were then discussed during an in-person meeting to attain further consensus. Consensus was defined as ≥ 80% agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree). RESULTS: Forty-five consensus-driven statements were identified, with all participants willing to incorporate them into their practice. For children with cervical spine disorders and/or stabilization, consensus statements were divided into the following categories: A) preoperative planning (12 statements); B) radiographic thresholds of instability (4); C) intraoperative/perioperative management (15); D) postoperative care (11); and E) nonoperative management (3). Several important statements reaching consensus included the following recommendations: 1) to obtain pre-positioning baseline signals with intraoperative neuromonitoring; 2) to use rigid instrumentation when technically feasible; 3) to provide postoperative external immobilization for 6-12 weeks with a rigid cervical collar rather than halo vest immobilization; and 4) to continue clinical postoperative follow-up at least until anatomical cervical spine maturity was reached. In addition, preoperative radiographic thresholds for instability that reached consensus included the following: 1) translational motion ≥ 5 mm at C1-2 (excluding patients with Down syndrome) or ≥ 4 mm in the subaxial spine; 2) dynamic angulation in the subaxial spine ≥ 10°; and 3) abnormal motion and T2 signal change on MRI seen at the same level. CONCLUSIONS: In this study, the authors have demonstrated that a multidisciplinary, international group of pediatric cervical spine experts was able to reach consensus on 45 statements regarding the management of pediatric cervical spine disorders and stabilization. Further study is required to determine if implementation of these practices can lead to reduced complications and improved outcomes for children.

Building consensus for the medical management of children with moderate and severe acute spinal cord injury: a modified Delphi study.

OBJECTIVE: The focus of this modified Delphi study was to investigate and build consensus regarding the medical management of children with moderate and severe acute spinal cord injury (SCI) during their initial inpatient hospitalization. This impetus for the study was based on the AANS/CNS guidelines for pediatric SCI published in 2013, which indicated that there was no consensus provided in the literature describing the medical management of pediatric patients with SCIs. METHODS: An international, multidisciplinary group of 19 physicians, including pediatric neurosurgeons, orthopedic surgeons, and intensivists, were asked to participate. The authors chose to include both complete and incomplete injuries with traumatic as well as iatrogenic etiologies (e.g., spinal deformity surgery, spinal traction, intradural spinal surgery, etc.) due to the overall low incidence of pediatric SCI, potentially similar pathophysiology, and scarce literature exploring whether different etiologies of SCI should be managed differently. An initial survey of current practices was administered, and based on the responses, a follow-up survey of potential consensus statements was distributed. Consensus was defined as ≥ 80% of participants reaching agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree). A final meeting was held virtually to generate final consensus statements. RESULTS: Following the final Delphi round, 35 statements reached consensus after modification and consolidation of previous statements. Statements were categorized into the following eight sections: inpatient care unit, spinal immobilization, pharmacological management, cardiopulmonary management, venous thromboembolism prophylaxis, genitourinary management, gastrointestinal/nutritional management, and pressure ulcer prophylaxis. All participants stated that they would be willing or somewhat willing to change their practices based on consensus guidelines. CONCLUSIONS: General management strategies were similar for both iatrogenic (e.g., spinal deformity, traction, etc.) and traumatic SCIs. Steroids were recommended only for injury after intradural surgery, not after acute traumatic or iatrogenic extradural surgery. Consensus was reached that mean arterial pressure ranges are preferred for blood pressure targets following SCI, with goals between 80 and 90 mm Hg for children at least 6 years of age. Further multicenter study of steroid use following acute neuromonitoring changes was recommended.

Clinical utility of whole-genome DNA methylation profiling as a primary molecular diagnostic assay for central nervous system tumors-A prospective study and guidelines for clinical testing.

Background: Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis. Methods: We performed a prospective study using DNA methylation analysis as a primary diagnostic method for 1921 brain tumors. All tumors received a pathology diagnosis and profiling by whole genome DNA methylation, followed by next-generation DNA and RNA sequencing. Results were stratified by concordance between DNA methylation and histopathology, establishing diagnostic utility. Results: Of the 1602 cases with a World Health Organization histologic diagnosis, DNA methylation identified a diagnostic mismatch in 225 cases (14%), 78 cases (5%) did not classify with any class, and in an additional 110 (7%) cases DNA methylation confirmed the diagnosis and provided prognostic information. Of 319 cases carrying 195 different descriptive histologic diagnoses, DNA methylation provided a definitive diagnosis in 273 (86%) cases, separated them into 55 methylation classes, and changed the grading in 58 (18%) cases. Conclusions: DNA methylation analysis is a robust method to diagnose primary CNS tumors, improving diagnostic accuracy, decreasing diagnostic errors and inconclusive diagnoses, and providing prognostic subclassification. This study provides a framework for inclusion of DNA methylation profiling as a primary molecular diagnostic test into professional guidelines for CNS tumors. The benefits include increased diagnostic accuracy, improved patient management, and refinements in clinical trial design.

Epilepsy control following intracranial monitoring without resection in young children.

PURPOSE: Intracranial monitoring (IM) is a key diagnostic procedure for select patients with treatment-resistant epilepsy (TRE). Seizure focus resection may improve seizure control in both lesional and nonlesional TRE. IM itself is not considered to have therapeutic potential. We describe a cohort of patients with improved seizure control following IM without resective surgery. METHODS: Over 12.5 years, 161 children underwent 496 surgeries including intracranial monitoring. We retrospectively reviewed the patients' charts, operative reports, and radiologic scans, under an institutional review board-approved protocol. KEY FINDINGS: Seventeen patients underwent only IM, without additional resective surgery, and seven had a dramatic improvement in their epilepsy; six of the seven patients are seizure-free (Engel class I), and one rarely has seizures (Engel class II). All seven patients had frequent seizures that led to IM: either daily (five patients) or 1-2 per week (two patients). The mean age (± standard deviation, SD) at seizure onset was 1.6 ± 1.3 years (range 0.5-4 years). Etiologies were tuberous sclerosis (3 patients), trauma (1 patient), and unknown (3 patients). Mean age at surgery (± SD) was 4.1 ± 2 years (range 1-7 years), and duration of epilepsy 2.5 ± 1.1 years (range 0.5-4 years). Duration of IM was 11.7 ± 5.6 days (5-19 days). Six patients had bilateral and one unilateral invasive electrodes. At last follow-up, four patients required fewer antiepileptic drugs (AEDs), one had the same medication but a higher dose, and two patients were taking additional AEDs. Follow-up was 30.6 ± 9.5 months (range 19-41 months). SIGNIFICANCE: Although uncommon, patients with TRE may improve after IM alone. The explanation for this observation remains unclear; however, perioperative medications including steroids, direct cortical manipulation, or other factors may influence the epileptogenic network.

Cervical ependymoma resection.

Intradural intramedullary cervical spinal cord tumors pose a significant challenge for the neurosurgeon to resect with minimal morbidity. We present the case of a 12-year-old male with a cervical ependymoma and demonstrate our resection technique. The video can be found here: http://youtu.be/5DHlnxdggU0 .

Perioperative team communication through a mobile app for improving coordination and education in neurosurgery cases.

OBJECTIVE: Miscommunication and poor coordination among surgical teams are known causes of preventable medical harms and operating room inefficiencies and inhibit surgical training. Technology may help overcome these challenges. This study used the personal experience of one of the authors as a former Air Force F-15 pilot to design a combat aviation pre- and postoperative communication workflow in the neurosurgery department and tested its effect on safety, efficiency, and education. The authors hypothesized that the adoption of this workflow through a tailored technological platform will increase compliance and improve the chances of sustainability. METHODS: Data were prospectively collected from neurosurgery cases before (January-May 2020) and after (June-October 2020) implementation of this workflow. Briefing and debriefing were executed using a custom mobile platform and were defined as nonmandatory for all participants. All faculty and residents who operated at NYU Langone Medical Center (Tisch campus) during the intervention period were enrolled on the platform. Primary outcomes were morbidity and mortality per the department's criteria, and intraoperative last-minute requests as reported by operating room staff in a double-blinded fashion. Secondary outcomes were user responses on the subjective questionnaires. RESULTS: Data were collected from 637 and 893 cases during the preintervention and intervention periods, respectively. The average briefing rates for residents and surgeons were 71% and 81%, respectively, and the average debriefing rates for residents and surgeons were 67% and 88%. There was no significant difference in preoperative risk score between the preintervention and intervention patient populations (p = 0.24). The rate of intraoperative last-minute requests significantly decreased from 16.6% (35/211) to 10.5% (35/334, p = 0.048). There was no significant change in morbidity and mortality between the preintervention and intervention periods. On subjective questionnaires there was a statistically significant improvement in safety, efficiency, and educational aspects of the cases during the intervention period. CONCLUSIONS: Implementation of aviation-like structured team communication practices in the neurosurgery department through a technological platform improved education and communication between surgical teams and led to a reduction in last-minute surgical requests that could impact costs.

Clinical, Pathological, and Molecular Characteristics of Diffuse Spinal Cord Gliomas.

Diffuse spinal cord gliomas (SCGs) are rare tumors associated with a high morbidity and mortality that affect both pediatric and adult populations. In this retrospective study, we sought to characterize the clinical, pathological, and molecular features of diffuse SCG in 22 patients with histological and molecular analyses. The median age of our cohort was 23.64 years (range 1-82) and the overall median survival was 397 days. K27M mutation was significantly more prevalent in males compared to females. Gross total resection and chemotherapy were associated with improved survival, compared to biopsy and no chemotherapy. While there was no association between tumor grade, K27M status (p = 0.366) or radiation (p = 0.772), and survival, males showed a trend toward shorter survival. K27M mutant tumors showed increased chromosomal instability and a distinct DNA methylation signature.

Intrathecal baclofen therapy: complication avoidance and management.

PURPOSE: Intrathecal baclofen (ITB) therapy is an accepted treatment modality for spasticity and dystonia. Several complications related to ITB have been described, including mechanical malfunctions, infections, cerebrospinal fluid fistula, and baclofen withdrawal or overdose. In this study, we present our institutional experience with ITB therapy, emphasizing complication avoidance and lessons learned. METHODS: The charts of 87 patients treated with ITB therapy were retrospectively reviewed. The primary surgical technique, complication type and timing, method of treatment, and outcome were analyzed. RESULTS: Thirteen out of 76 (17.1%) patients primarily treated at our department had 25 complications. The first complication occurred 17.5-30.9 months (mean 24.2±6.7) after the pump implantation. Additional four patients with pumps placed elsewhere had six complications and were subsequently treated by our group. The main complications were: catheter fracture (11), subcutaneous fluid collection (5), lumbar wound/CSF infection (3), lumbar catheter or connector protrusion (3), pump malfunction (3), distal catheter migration outside the thecal sac (2), and baclofen withdrawal (1). Of the patients in the NYULMC group, six were treated by a single surgical procedure, six underwent multiple surgical procedures, and one was managed conservatively. In retrospect, changing the surgical technique, or adding an abdominal binder may have prevented 17 complications (54.8%). There were two deaths that were unrelated to the ITB therapy. CONCLUSION: ITB therapy is associated with complications, many of which require additional surgery. Some of these complications are avoidable by adhering to a strict surgical technique and a proper criterion for patient selection.

Idiopathic bilateral stenosis of the foramina of Monro treated using endoscopic foraminoplasty and septostomy.

Hydrocephalus caused by stenosis of the foramen of Monro is rare. The authors describe a 28-year-old female patient with bilateral foraminal stenosis treated using endoscopic septostomy and unilateral foraminal balloon plasty (foraminoplasty). The patient's hydrocephalus and symptoms resolved postoperatively. Endoscopic strategies may be employed as first-line therapy in this condition.

Running out of time to smell the roseroots: Reviewing threats and trade in wild Rhodiola rosea L.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola rosea L. has a circumpolar distribution and is used in ethnomedicines of Arctic peoples, as well as in national systems of traditional medicine. Since the late 20th century, global demand for R. rosea has increased steadily, in part due to clinical research supporting new uses in modern phytotherapy. Global supply has been largely obtained from wild populations, which face threats from poorly regulated and destructive exploitation of the rootstocks on an industrial scale. AIM OF THE STUDY: To evaluate (i) the conservation status, harvesting and trade levels of R. rosea, in order to determine whether international trade should be monitored, (ii) the current state of experimental and commercial farming and whether cultivation may play a role to take pressure off wild stocks, and (iii) evidence of substitution of other Rhodiola species for R. rosea as an indicator of overexploitation and rarity. MATERIALS AND METHODS: We reviewed published studies on R. rosea biology and ecology, as well as information on impacts of wild harvest, on management measures at the national and regional levels, and on the current level of cultivation from across the geographic range of this species. Production and trade data were assessed and analysed from published reports and trade databases, consultations with R. rosea farmers, processors of extracts, and trade experts, but also from government and news reports of illegal harvesting and smuggling. RESULTS AND CONCLUSIONS: Our assessment of historical and current data from multiple disciplines shows that future monitoring and protection of R. rosea populations is of time-sensitive importance to the fields of ethnobotany, ethnopharmacology, phytochemistry and phytomedicine. We found that the global demand for R. rosea ingredients and products has been increasing in the 21st century, while wild populations in the main commercial harvesting areas continue to decrease, with conservation issues and reduced supply in some cases. The level of illegal harvesting in protected areas and cross border smuggling is increasing annually coupled with increasing incidences of adulteration and substitution of R. rosea with other wild Rhodiola species, potentially negatively impacting the conservation status of their wild populations, but also an indicator of scarcity of the genuine article. The current data suggests that the historical primary reliance on sourcing from wild populations of R. rosea should transition towards increased sourcing of R. rosea from farms that are implementing conservation oriented sustainable agricultural methods, and that sustainable wild collection standards must be implemented for sourcing from wild populations.