BRD8 maintains glioblastoma by epigenetic reprogramming of the p53 network.

Inhibition of the tumour suppressive function of p53 (encoded by TP53) is paramount for cancer development in humans. However, p53 remains unmutated in the majority of cases of glioblastoma (GBM)-the most common and deadly adult brain malignancy1,2. Thus, how p53-mediated tumour suppression is countered in TP53 wild-type (TP53WT) GBM is unknown. Here we describe a GBM-specific epigenetic mechanism in which the chromatin regulator bromodomain-containing protein 8 (BRD8) maintains H2AZ occupancy at p53 target loci through the EP400 histone acetyltransferase complex. This mechanism causes a repressive chromatin state that prevents transactivation by p53 and sustains proliferation. Notably, targeting the bromodomain of BRD8 displaces H2AZ, enhances chromatin accessibility and engages p53 transactivation. This in turn enforces cell cycle arrest and tumour suppression in TP53WT GBM. In line with these findings, BRD8 is highly expressed with H2AZ in proliferating single cells of patient-derived GBM, and is inversely correlated with CDKN1A, a canonical p53 target that encodes p21 (refs. 3,4). This work identifies BRD8 as a selective epigenetic vulnerability for a malignancy for which treatment has not improved for decades. Moreover, targeting the bromodomain of BRD8 may be a promising therapeutic strategy for patients with TP53WT GBM.

Autologous cell immunotherapy (IGV-001) with IGF-1R antisense oligonucleotide in newly diagnosed glioblastoma patients.

Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM. The primary end point is progression-free survival, and key secondary end points include overall survival and safety.

Glioblastoma (GBM) is a fast-growing brain tumor that happens in about half of all gliomas. Surgery is the first treatment for patients with newly diagnosed GBM, followed by the usual radiation and chemotherapy pills named temozolomide. Temozolomide pills are then given as a long-term treatment. The outcome for the patient with newly diagnosed GBM remains poor. IGV-001 is specially made for each patient. The tumor cells are removed during surgery and mixed in the laboratory with a small DNA, IMV-001. This mix is the IGV-001 therapy that is designed to give antitumor immunity against GBM. IGV-001 is put into small biodiffusion chambers that are irradiated to stop the growth of any tumor cells in the chambers. In the phase IIb study, patients with newly diagnosed GBM are chosen and assigned to either the IGV-001 or the placebo group. A placebo does not contain any active ingredients. The small biodiffusion chambers containing either IGV-001 or placebo are surgically placed into the belly for 48 to 52 h and then removed. Patients then receive the usual radiation and chemotherapy treatment. Patients must be adults aged between 18 and 70 years. Patients also should be able to care for themselves overall, but may be unable to work or have lower ability to function. Patients with tumors on both sides of the brain are not eligible. The main point of this study is to see if IGV-001 helps patients live longer without making the illness worse compared with placebo. Clinical Trial Registration: NCT04485949 (ClinicalTrials.gov).

An Institutional Experience of Directional Deep Brain Stimulation and a Review of the Literature.

INTRODUCTION: Directional deep brain stimulation (dDBS) has been suggested to have a similar therapeutic effect when compared with the traditional omnidirectional DBS, but with an improved therapeutic window that yields optimized clinical effect owing to the ability to better direct, or "steer," electric current. We present our single-center, retrospective analysis of our experience in the use of dDBS in patients with movement disorders and provide a review of the literature. MATERIALS AND METHODS: We identified all patients with Parkinson disease (PD) and essential tremor (ET) who received a dDBS system between 2018 and 2022 and retrospectively examined characteristics of their longitudinal treatment. A total of 70 leads were identified across 42 patients (28 PD, 14 ET). RESULTS: Three types of systems were implemented (single-segment activation, 45.2% of patients; multiple independent current control, 50.0%; and local field potential sensing-enabled, 4.7%). The subthalamic nucleus or globus pallidus internus was targeted in PD, and the ventral intermediate nucleus of the thalamus in ET. Across the entire cohort (n = 70 leads), at initial programming, 54.2% of leads (n = 38) were programmed using directional stimulation. At the most recent reprogramming, 58.6% of leads (n = 41) implemented directionality. In patients with PD, the average decrease in levodopa-equivalent daily dose at six months after implantation was 35.4% ± 39.2%. Despite the ability to steer current to relieve stimulation-induced side effects, ten leads in six patients required surgical revision owing to electrode malposition. CONCLUSIONS: We show wide adaptability and implementation of directional stimulation, adding to the growing compendium of real-world uses of dDBS therapy. We used directionality to improve clinical response in both patients with PD and patients with ET and found that its programming flexibility was used at high rates long after implantation and initial programming. In patients with PD, dDBS led to a significant reduction in dopaminergic medication, suggesting sustained clinical improvement. Nonetheless, accurate surgical placement remains necessary to ensure optimal clinical outcomes.

Let's make size not matter: tumor control and toxicity outcomes of hypofractionated Gamma Knife radiosurgery for large brain metastases.

PURPOSE: Management of patients with large brain metastases poses a clinical challenge, with poor local control and high risk of adverse radiation events when treated with single-fraction stereotactic radiosurgery (SF-SRS). Hypofractionated SRS (HF-SRS) may be considered, but clinical data remains limited, particularly with Gamma Knife (GK) radiosurgery. We report our experience with GK to deliver mask-based HF-SRS to brain metastases greater than 10 cc in volume and present our control and toxicity outcomes. METHODS: Patients who received hypofractionated GK radiosurgery (HF-GKRS) for the treatment of brain metastases greater than 10 cc between January 2017 and June 2022 were retrospectively identified. Local failure (LF) and adverse radiation events of CTCAE grade 2 or higher (ARE) were identified. Clinical, treatment, and radiological information was collected to identify parameters associated with clinical outcomes. RESULTS: Ninety lesions (in 78 patients) greater than 10 cc were identified. The median gross tumor volume was 16.0 cc (range 10.1-56.0 cc). Prior surgical resection was performed on 49 lesions (54.4%). Six- and 12-month LF rates were 7.3% and 17.6%; comparable ARE rates were 1.9% and 6.5%. In multivariate analysis, tumor volume larger than 33.5 cc (p = 0.029) and radioresistant histology (p = 0.047) were associated with increased risk of LF (p = 0.018). Target volume was not associated with increased risk of ARE (p = 0.511). CONCLUSIONS: We present our institutional experience treating large brain metastases using mask-based HF-GKRS, representing one of the largest studies implementing this platform and technique. Our LF and ARE compare favorably with the literature, suggesting that target volumes less than 33.5 cc demonstrate excellent control rates with low ARE. Further investigation is needed to optimize treatment technique for larger tumors.

Postoperative stereotactic radiosurgery for intracranial solitary fibrous tumors: systematic review and pooled quantitative analysis.

BACKGROUND: Intracranial solitary fibrous tumors (SFTs), formerly hemangiopericytomas (HPCs), are rare, aggressive dural-based mesenchymal tumors. While adjuvant radiation therapy has been suggested to improve local tumor control (LTC), especially after subtotal resection, the role of postoperative stereotactic radiosurgery (SRS) and the optimal SRS dosing strategy remain poorly defined. METHODS: PubMed, EMBASE, and Web of Science were systematically searched according to PRISMA guidelines for studies describing postoperative SRS for intracranial SFTs. The search strategy was defined in the authors' PROSPERO protocol (CRD42023454258). RESULTS: 15 studies were included describing 293 patients harboring 476 intracranial residual or recurrent SFTs treated with postoperative SRS. At a mean follow-up of 21-77 months, LTC rate after SRS was 46.4-93% with a mean margin SRS dose of 13.5-21.7 Gy, mean maximum dose of 27-39.6 Gy, and mean isodose at the 42.5-77% line. In pooled analysis of individual tumor outcomes, 18.7% of SFTs demonstrated a complete SRS response, 31.7% had a partial response, 18.9% remained stable (overall LTC rate of 69.3%), and 30.7% progressed. When studies were stratified by margin dose, a mean margin dose > 15 Gy showed an improvement in LTC rate (74.7% versus 65.7%). CONCLUSIONS: SRS is a safe and effective treatment for intracranial SFTs. In the setting of measurable disease, our pooled data suggests a potential dose response of improving LTC with increasing SRS margin dose. Our improved understanding of the aggressive biology of SFTs and the tolerated adjuvant SRS parameters supports potentially earlier use of SRS in the postoperative treatment paradigm for intracranial SFTs.

Advances in Technical Aspects of Deep Brain Stimulation Surgery.

BACKGROUND: Deep brain stimulation has become an established technology for the treatment of patients with a wide variety of conditions, including movement disorders, psychiatric disorders, epilepsy, and pain. Surgery for implantation of DBS devices has enhanced our understanding of human physiology, which in turn has led to advances in DBS technology. Our group has previously published on these advances, proposed future developments, and examined evolving indications for DBS. SUMMARY: The crucial roles of structural MR imaging pre-, intra-, and post-DBS procedure in target visualization and confirmation of targeting are described, with discussion of new MR sequences and higher field strength MRI enabling direct visualization of brain targets. The incorporation of functional and connectivity imaging in procedural workup and their contribution to anatomical modelling is reviewed. Various tools for targeting and implanting electrodes, including frame-based, frameless, and robot-assisted, are surveyed, and their pros and cons are described. Updates on brain atlases and various software used for planning target coordinates and trajectories are presented. The pros and cons of asleep versus awake surgery are discussed. The role and value of microelectrode recording and local field potentials are described, as well as the role of intraoperative stimulation. Technical aspects of novel electrode designs and implantable pulse generators are presented and compared.

Microsurgical resection of gliomas of the cingulate gyrus: a systematic review and meta-analysis.

Cingulate gyrus gliomas are rare among adult, hemispheric diffuse gliomas. Surgical reports are scarce. We performed a systematic review of the literature and meta-analysis, with the aim of focusing on the extent of resection (EOR), WHO grade, and morbidity and mortality, after microsurgical resection of gliomas of the cingulate gyrus. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we reviewed articles published between January 1996 and December 2022 and referenced in PubMed or Embase. Inclusion criteria were peer-reviewed clinical studies of microsurgical series reporting resection of gliomas of the cingulate gyrus. Primary outcome was EOR, classified as gross total (GTR) versus subtotal (STR) resection. Five studies reporting 295 patients were included. Overall GTR was 79.4% (range 64.1-94.7; I2= 88.13; p heterogeneity and p < 0.001), while STR was done in 20.6% (range 5.3-35.9; I2= 88.13; p heterogeneity < 0.001 and p= 0.008). The most common WHO grade was II, with an overall rate of 42.7% (24-61.5; I2= 90.9; p heterogeneity, p< 0.001). Postoperative SMA syndrome was seen in 18.6% of patients (10.4-26.8; I2= 70.8; p heterogeneity= 0.008, p< 0.001), postoperative motor deficit in 11% (3.9-18; I2= 18; p heterogeneity= 0.003, p= 0.002). This review found that while a GTR was achieved in a high number of patients with a cingulate glioma, nearly half of such patients have a postoperative deficit. This finding calls for a cautious approach in recommending and doing surgery for patients with cingulate gliomas and for consideration of new surgical and management approaches.

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.

Contemporary surgical management of skull base chordomas-Anatomical reflections on a single center experience retrospective case series.

Chordoma, a rare, locally aggressive tumor can affect the central skull base, usually centered at the midline. Complete surgical resection remains mainstay of therapy in case of primary as well as recurrent tumors. Owing to their secluded location, surgical resection of skull base chordomas remains a challenge, even though the recent advancement of endoscopic endonasal approaches has had a significant positive impact on the management of these patients. Endoscopic endonasal approaches have been shown to significantly reduce surgical morbidity when compared to traditional open approaches; however, the classical endoscopic transclival midline approach fails to sufficiently expose parts of many skull base chordomas. More recent refinements of the technique, such as the interdural pituitary transposition and posterior clinoidectomy, the transpterygoid plate approach and the transcondylar far medial approach enable the surgeon the increase the resection rate in these patients. This retrospective case series focuses on anatomical aspects in the surgical management of patients with skull base chordomas. We outline the surgical anatomy of contemporary endoscopic approaches to the skull base based intraoperative illustrations as well as pre- and postoperative 3D reconstructed CT and MR images if our patients. This article should help the clinical choose the most appropriate approach and be aware of relevant anatomy as well as potential shortcomings of a given approach.

Frame-Based and Mask-Based Stereotactic Radiosurgery: The Patient Experience, Compared.

INTRODUCTION: Noninvasive frameless modalities have become increasingly utilized for stereotactic radiosurgery (SRS) for benign and malignant pathologies. There is minimal comparison in the literature of frame-based (FB) and mask-based (MB) SRS. With the dual capabilities of the Elekta Gamma Knife® Icon™, we sought to compare patient perceptions of FB and MB SRS with respect to comfort and pain and to examine effects of lesion type on the patient experience of SRS. METHODS: Over a 1-year period, patients who underwent single fraction, fractionated or hypofractionated FB or MB Gamma Knife SRS at our institution were given an 8-question survey about their experience with the procedure immediately after treatment was completed. Descriptive statistics were applied. RESULTS: A total of 117 patients completed the survey with 65 FB and 52 MB SRS treatments. Mean pain for FB SRS (5.64 ± 2.55) was significantly greater than mean pain for MB SRS (0.92 ± 2.24; t114 = 10.46, p < 0.001). Patient comfort during the procedure was also higher for those having MB SRS (p < 0.001). Mixed results were obtained when investigating if benign versus malignant diagnosis affected patient experience of SRS. For the purposes of this study, malignant diagnoses were almost entirely metastatic lesions. Diagnosis played no role on pain levels when all patients were analyzed together. The treatment technique had no effect on patient comfort in patients with benign diagnoses, while patients with malignant diagnoses treated with MB SRS were more likely to be comfortable (p < 0.001). Among patient's receiving FB treatments, diagnosis played no role on patient comfort. When only MB treatments were analyzed, patients were more likely to be comfortable if they had a malignant lesion (p < 0.01). CONCLUSIONS: Patients treated with MB SRS experience the procedure as more comfortable and less painful compared to those treated using a FB modality. Overall, this difference was not affected by a benign versus a malignant diagnosis and the treatment type is more indicative of the patient experience during SRS. A more homogenous sample between modalities and diagnoses and further follow-up with the patient's input on their experience would be beneficial.

Diffusion Tensor Imaging Color-Coded Maps: An Alternative to Tractography.

INTRODUCTION: White matter tracts can be observed using tractograms generated from diffusion tensor imaging (DTI). However, the dependence of these white matter tract images on subjective variables, including how seed points are placed and the preferred level of fractional anisotropy, introduces interobserver inconsistency and potential lack of reliability. We propose that color-coded maps (CCM) generated from DTI can be a preferred method for the visualization of important white matter tracts, circumventing bias in preoperative brain tumor resection planning. METHODS: DTI was acquired retrospectively in 25 patients with brain tumors. Lesions included 15 tumors of glial origin, 9 metastatic tumors, 2 meningiomas, and 1 cavernous angioma. Tractograms of the pyramidal tract and/or optic radiations, based on tumor location, were created by marking seed regions of interest using known anatomical locations. We compared the degree of tract involvement and white matter alteration between CCMs and tractograms. Neurological outcomes were obtained from chart reviews. RESULTS: The pyramidal tract was evaluated in 20/25 patients, the visual tracts were evaluated in 10/25, and both tracts were evaluated in 5/25. In 19/25 studies, the same patterns of white matter alternations were found between the CCMs and tractograms. In the 6 patients where patterns differed, 2 tractograms were not useful in determining pattern alteration; in the remaining 4/6, no practical difference was seen in comparing the studies. Two patients were lost to follow-up. Thirteen patients were neurologically improved or remained intact after intervention. In these, 10 of the 13 patients showed tumor-induced white matter tract displacement on CCM. Twelve patients had no improvement of their preoperative deficit. In 9 of these 12 patients, CCM showed white matter disruption. CONCLUSION: CCMs provide a convenient, practical, and objective method of visualizing white matter tracts, obviating the need for potentially subjective and time-consuming tractography. CCMs are at least as reliable as tractograms in predicting neurological outcomes after neurosurgical intervention.

Impact of combined use of intraoperative MRI and awake microsurgical resection on patients with gliomas: a systematic review and meta-analysis.

Microsurgical resection of primary brain tumors located within or near eloquent areas is challenging. Primary aim is to preserve neurological function, while maximizing the extent of resection (EOR), to optimize long-term neurooncological outcomes and quality of life. Here, we review the combined integration of awake craniotomy and intraoperative MRI (IoMRI) for primary brain tumors, due to their multiple challenges. A systematic review of the literature was performed, in accordance with the Prisma guidelines. Were included 13 series and a total number of 527 patients, who underwent 541 surgeries. We paid particular attention to operative time, rate of intraoperative seizures, rate of initial complete resection at the time of first IoMRI, the final complete gross total resection (GTR, complete radiological resection rates), and the immediate and definitive postoperative neurological complications. The mean duration of surgery was 6.3 h (median 7.05, range 3.8-7.9). The intraoperative seizure rate was 3.7% (range 1.4-6; I^2 = 0%, P heterogeneity = 0.569, standard error = 0.012, p = 0.002). The intraoperative complete resection rate at the time of first IoMRI was 35.2% (range 25.7-44.7; I^2 = 66.73%, P heterogeneity = 0.004, standard error = 0.048, p < 0.001). The rate of patients who underwent supplementary resection after one or several IoMRI was 46% (range 39.8-52.2; I^2 = 8.49%, P heterogeneity = 0.364, standard error = 0.032, p < 0.001). The GTR rate at discharge was 56.3% (range 47.5-65.1; I^2 = 60.19%, P heterogeneity = 0.01, standard error = 0.045, p < 0.001). The rate of immediate postoperative complications was 27.4% (range 15.2-39.6; I^2 = 92.62%, P heterogeneity < 0.001, standard error = 0.062, p < 0.001). The rate of permanent postoperative complications was 4.1% (range 1.3-6.9; I^2 = 38.52%, P heterogeneity = 0.123, standard error = 0.014, p = 0.004). Combined use of awake craniotomy and IoMRI can help in maximizing brain tumor resection in selected patients. The technical obstacles to doing so are not severe and can be managed by experienced neurosurgery and anesthesiology teams. The benefits of bringing these technologies to bear on patients with brain tumors in or near language areas are obvious. The lack of equipoise on this topic by experienced practitioners will make it difficult to do a prospective, randomized, clinical trial. In the opinion of the authors, such a trial would be unnecessary and would deprive some patients of the benefits of the best available methods for their tumor resections.

The Proud History of Psychosurgery in the USA.

To understand the development and growth of psychosurgery, the context of psychiatric care in the mid-twentieth-century USA must be considered-for example, overpopulation and understaffing of public institutions, and typical use of psychotherapy, which was generally useless in treating the symptomatology of severe mental illness. Therefore, the introduction of prefrontal lobotomy (and, later, transorbital lobotomy) by Drs. Walter Freeman and James Watts, who modified the technique of leukotomy developed by Nobel Prize laureate Dr. Egas Moniz, was considered revolutionary and quickly gained widespread acceptance by medical community. No other alternative treatment at the time demonstrated comparable efficacy. At its peak, psychosurgery was sometimes applied inappropriately, but records from multiple institutions across the USA demonstrate that these were exceptional cases, whereas, as a rule, selection of surgical candidates was based on very strict criteria, indicating the high professionalism and humanity of medical staff. Although psychosurgery has declined heavily since the 1950s, it is not obsolete and is currently considered a valuable treatment option, realized through various open, stereotactic, or radiosurgical procedures.

Subtotal Resection Followed by Adjuvant Radiosurgery for Large Vestibular Schwannomas: Outcomes with Regard to the Timing and Regimen of Irradiation.

OBJECTIVE: To evaluate the results of combined management of large vestibular schwannomas (VS) with initial subtotal resection (STR) followed by adjuvant stereotactic radiosurgery (SRS), with a particular emphasis on the timing and regimen of irradiation. METHODS: Seventeen patients underwent STR of a VS followed by SRS, whereas five others were observed after STR. Early SRS (<6 months after surgery) and late SRS (>6 months after surgery) were done in 8 and 9 patients, respectively. Single- and multisession SRS treatments were administered in 10 and 7 patients, respectively. The mean follow-up durations after surgery and SRS were 40 and 28 months, respectively. RESULTS: The rates of radiological and oncological tumor control after SRS were 82% and 100%, respectively. The tumor volume at the last follow-up and its relative changes after SRS did not differ significantly on the basis of the irradiation timing (early versus late) or on the basis of the irradiation regimen (single-session versus multisession). In no patient who was observed after STR of a VS was tumor regrowth noted during a mean follow-up period of 49 months. At 12 months after surgery, motor function of the ipsilateral facial nerve corresponded to House-Brackmann grades I, II, III, and IV in 16 patients (73%), 3 patients (14%), 1 patient (5%), and 2 patients (9%), respectively. Facial nerve function at the last follow-up did not differ significantly on the basis of the irradiation timing (early versus late) or on the basis of the irradiation regimen (single-session versus multisession). CONCLUSION: The combination of initial STR followed by adjuvant SRS is an effective treatment strategy for patients with a large VS. Although the optimal timing and regimen of postoperative irradiation of the residual lesion should be defined further, our preliminary data suggest that either early or late SRS after surgery may provide good tumor control and optimal functional results.

Tumor control and survival in patients with ten or more brain metastases treated with stereotactic radiosurgery: a retrospective analysis.

INTRODUCTION: To assess tumor control and survival in patients treated with stereotactic radiosurgery (SRS) for 10 or more metastatic brain tumors. METHODS: Patients were retrospectively identified. Clinical records were reviewed for follow-up data, and post-treatment MRI studies were used to assess tumor control. For tumor control studies, patients were separated based on synchronous or metachronous treatment, and control was assessed at 3-month intervals. The Kaplan-Meier method was employed to create survival curves, and regression analyses were employed to study the effects of several variables. RESULTS: Fifty-five patients were treated for an average of 17 total metastases. Forty patients received synchronous treatment, while 15 received metachronous treatment. Univariate analysis revealed an association between larger brain volumes irradiated with 12 Gy and decreased overall survival (p = 0.0406); however, significance was lost on multivariate analysis. Among patients who received synchronous treatment, the median percentage of tumors controlled was 100%, 91%, and 82% at 3, 6, and 9 months, respectively. Among patients who received metachronous treatment, the median percentage of tumors controlled after each SRS encounter was 100% at all three time points. CONCLUSIONS: SRS can be used to treat patients with 10 or more total brain metastases with an expectation of tumor control and overall survival that is equivalent to that reported for patients with four or fewer tumors. Development of new metastases leading to repeat SRS is not associated with worsened tumor control or survival. Survival may be adversely affected in patients having a higher volume of normal brain irradiated.

Major complications from radiotherapy following treatment for atypical meningiomas.

OBJECTIVEComplications from radiotherapy (RT), in a primary or adjuvant setting, have overall been described as uncommon, with few detailed descriptions of major complications. The authors present two cases involving significant complications and their management in their review of patients undergoing RT for treatment of atypical meningioma.METHODSThe authors conducted a retrospective review of all patients with pathologically confirmed atypical meningioma (WHO grade II) treated with primary or adjuvant RT from February 2011 through February 2019. They identified two patients with long-term, grade 3 toxicity. The cases of these patients are described in detail.RESULTSTwo patients had major complications associated with postoperative RT. Patients 1 and 2 both were treated with postoperative RT for pathologically confirmed atypical meningioma. Patient 1 experienced worsening behavioral changes, cognitive decline, and hydrocephalus following treatment. This required cerebrospinal fluid diversion. Patient 2 developed radiation necrosis with mass effect and cognitive decline. Neither patient returned to his/her initial post-RT status after steroid therapy, and each remained in need of supportive care. Both patients remained free of tumor progression at 52 and 38 months following treatment.CONCLUSIONSThe postoperative management of patients with atypical meningioma continues to be defined, with questions remaining regarding timing of RT, dose, target delineation, and fractionation. Both of the patients in this study received fractionated RT, which included a greater volume of normal brain than more focal treatment options such as would be required by stereotactic radiosurgery (SRS). Further research is needed to compare SRS and fractionated RT for the management of patients with grade II meningiomas. The more focused nature of SRS may make this a preferred option in certain cases of focal recurrence.

Combined Brain Mapping and Compact Intraoperative MRI for Brain Tumor Resection.

BACKGROUND: Surgery on patients with lesions in the dominant hemisphere for language is best done with awake language mapping. Intraoperative MRI (iMRI) has also been proposed as an ideal method for tumor resection control in patients with primary brain tumors. OBJECTIVES: This study examines the feasibility of low-field iMRI during awake craniotomy and tumor resection. METHODS: 36 patients underwent awake resection with a compact iMRI for guidance. Outcomes were grouped using an A-D classification. Outcome A was defined as gross total resection (GTR) without iMRI, B as GTR achieved secondary to iMRI findings, C as resection stopped due to mapping but prior to iMRI, and, finally, D as resection stopped after iMRI had showed residual tumor but subsequent mapping limited further resection. RESULTS: Diagnoses included primary brain tumors in all but 2 patients: 1 had mesial temporal sclerosis and 1 cysticercosis. Overall, outcomes A and D were the most common with 12 patients each, outcome C was the least common occurring in only 3 patients, and outcome B occurred in 9 patients. Hence, in 12 patients, iMRI led to increased tumor resection while in another 12 brain mapping limited the extent of resection. CONCLUSIONS: Combined awake language and motor mapping and iMRI guidance is feasible for resection of brain lesions. A compact iMRI has unique advantages for this approach.

Intraoperative MRI for resection of intracranial meningiomas.

OBJECTIVE: To examine whether intraoperative MRI can enhance safety and extent of resection of complex intracranial meningiomas, given its positive role in the resection of malignant brain tumors and pituitary tumors. METHODS: Over a ten-year period, 70 operations were performed on 66 patients with intracranial meningiomas using the compact, mobile PoleStar N20 iMRI navigation system. A retrospective review was conducted examining patient demographics, surgical characteristics, and outcomes. RESULTS: 36 meningiomas were above the skull base and 30 were of the skull base. Four (5.7%) operations were done for recurrent meningiomas. 63 patients (95.5%) had WHO grade I and 3 patients (4.5%) had WHO grade III meningiomas. 9 (12.8%) patients required additional tumor resection based on iMRI findings, and in 4 patients (6%) iMRI imaging allowed for avoidance of additional dissection near critical neurovascular structures. CONCLUSIONS: Up to 15.7% of patients had surgery positively affected by intraoperative imaging either improving the resection or avoiding unnecessary additional dissection which could potentially harm critical neurologic structures. As iMRI becomes more widely available it may be valuable to use in an appropriate subset of patients with intracranial meningiomas.

Acute generalized exanthematous pustulosis secondary to levetiracetam and valproic acid use.

Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption characterized by the appearance of diffuse, sterile pustules on an erythematous and edematous base. Most cases are attributed to drug reactions, with antibiotics being the most common offending agents. Only a handful of case reports have described AGEP in the setting of antiepileptic use. Here, we report a case of AGEP secondary to dual antiepileptic therapy with levetiracetam and valproic acid in a 73-year-old female. The patient presented to the emergency department with the characteristic AGEP rash, fever, and leukocytosis. Upon discontinuation of the two medications and conservative management, the patient's symptoms quickly abated, and she was discharged from the hospital several days later.

Compact Intraoperative MRI: Stereotactic Accuracy and Future Directions.

BACKGROUND: Intraoperative imaging must supply data that can be used for accurate stereotactic navigation. This information should be at least as accurate as that acquired from diagnostic imagers. OBJECTIVES: The aim of this study was to compare the stereotactic accuracy of an updated compact intraoperative MRI (iMRI) device based on a 0.15-T magnet to standard surgical navigation on a 1.5-T diagnostic scan MRI and to navigation with an earlier model of the same system. METHODS: The accuracy of each system was assessed using a water-filled phantom model of the brain. Data collected with the new system were compared to those obtained in a previous study assessing the older system. The accuracy of the new iMRI was measured against standard surgical navigation on a 1.5-T MRI using T1-weighted (W) images. RESULTS: The mean error with the iMRI using T1W images was lower than that based on images from the 1.5-T scan (1.24 vs. 2.43 mm). T2W images from the newer iMRI yielded a lower navigation error than those acquired with the prior model (1.28 vs. 3.15 mm). CONCLUSIONS: Improvements in magnet design can yield progressive increases in accuracy, validating the concept of compact, low-field iMRI. Avoiding the need for registration between image and surgical space increases navigation accuracy.