Indication for a skull base approach in microvascular decompression for hemifacial spasm.

BACKGROUND: A thorough observation of the root exit zone (REZ) and secure transposition of the offending arteries is crucial for a successful microvascular decompression (MVD) for hemifacial spasm (HFS). Decompression procedures are not always feasible in a narrow operative field through a retrosigmoid approach. In such instances, extending the craniectomy laterally is useful in accomplishing the procedure safely. This study aims to introduce the benefits of a skull base approach in MVD for HFS. METHODS: The skull base approach was performed in twenty-eight patients among 335 consecutive MVDs for HFS. The site of the neurovascular compression (NVC), the size of the flocculus, and the location of the sigmoid sinus are measured factors in the imaging studies. The indication for a skull base approach is evaluated and verified retrospectively in comparison with the conventional retrosigmoid approach. Operative outcomes and long-term results were analyzed retrospectively. RESULTS: The extended retrosigmoid approach was used for 27 patients and the retrolabyrinthine presigmoid approach was used in one patient. The measurement value including the site of NVC, the size of the flocculus, and the location of the sigmoid sinus represents well the indication of the skull base approach, which is significantly different from the conventional retrosigmoid approach. The skull base approach is useful for patients with medially located NVC, a large flocculus, or repeat MVD cases. The long-term result demonstrated favorable outcomes in patients with the skull base approach applied. CONCLUSIONS: Preoperative evaluation for lateral expansion of the craniectomy contributes to a safe and secure MVD.

Recurrent Glioblastoma Treated with Recombinant Poliovirus.

BACKGROUND: The prognosis of patients with recurrent World Health Organization (WHO) grade IV malignant glioma is dismal, and there is currently no effective therapy. We conducted a dose-finding and toxicity study in this population of patients, evaluating convection-enhanced, intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera (PVSRIPO). PVSRIPO recognizes the poliovirus receptor CD155, which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor microenvironment. METHODS: We enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV malignant glioma, confirmed on histopathological testing, with measurable disease (contrast-enhancing tumor of ≥1 cm and ≤5.5 cm in the greatest dimension). The study evaluated seven doses, ranging between 107 and 1010 50% tissue-culture infectious doses (TCID50), first in a dose-escalation phase and then in a dose-expansion phase. RESULTS: From May 2012 through May 2017, a total of 61 patients were enrolled and received a dose of PVSRIPO. Dose level -1 (5.0×107 TCID50) was identified as the phase 2 dose. One dose-limiting toxic effect was observed; a patient in whom dose level 5 (1010 TCID50) was administered had a grade 4 intracranial hemorrhage immediately after the catheter was removed. To mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use, dose level 5 was deescalated to reach the phase 2 dose. In the dose-expansion phase, 19% of the patients had a PVSRIPO-related adverse event of grade 3 or higher. Overall survival among the patients who received PVSRIPO reached a plateau of 21% (95% confidence interval, 11 to 33) at 24 months that was sustained at 36 months. CONCLUSIONS: Intratumoral infusion of PVSRIPO in patients with recurrent WHO grade IV malignant glioma confirmed the absence of neurovirulent potential. The survival rate among patients who received PVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls. (Funded by the Brain Tumor Research Charity and others; ClinicalTrials.gov number, NCT01491893 .).

Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients.

After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers including glioblastoma, the factors dictating DC vaccine efficacy remain poorly understood. Here we show that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumour-antigen-specific DCs. To assess the effect of vaccine site pre-conditioning in humans, we randomized patients with glioblastoma to pre-conditioning with either mature DCs or Td unilaterally before bilateral vaccination with DCs pulsed with Cytomegalovirus phosphoprotein 65 (pp65) RNA. We and other laboratories have shown that pp65 is expressed in more than 90% of glioblastoma specimens but not in surrounding normal brain, providing an unparalleled opportunity to subvert this viral protein as a tumour-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumour growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve anti-tumour immunotherapy.

Neurosurgical management of petrous bone lesions: classification system and selection of surgical approaches.

BACKGROUND: Surgery of petrous bone lesions (PBLs) is challenging for neurosurgeons. Selection of the surgical approach is an important key for success. In this study, the authors present an anatomical classification for PBLs that has been used by our group for over the past 26 years. The objective of this study is to investigate the benefits and applicability of this classification. METHODS: Between 1994 and 2019, 117 patients treated for PBLs were retrospectively reviewed. Using the V3 and arcuate eminence as reference points, the petrous bone is segmented into 3 parts: petrous apex, rhomboid, and posterior. The pathological diagnoses, selection of the operative approach, and the extent of resection (EOR) were analyzed and correlated using this classification. RESULTS: This series included 22 facial nerve schwannomas (18.8%), 22 cholesterol granulomas (18.8%), 39 chordomas/chondrosarcomas (33.3%), 6 trigeminal schwannomas (5.1%), 13 epidermoids/dermoids (11.1%), and 15 other pathologies (12.8%). PBLs were most often involved with the petrous apex and rhomboid areas (46.2%). The extradural subtemporal approach (ESTA) was most frequently used (57.3%). Gross total resection was achieved in 58.4%. Symptomatic improvement occurred in 92 patients (78.6%). Our results demonstrated a correlation between this classification with each type of pathology (p < .001), selection of surgical approaches (p < 0.001), and EOR (p = 0.008). Chordoma/chondrosarcoma, redo operations, and lesions located medially were less likely to have total resection. Temporary complications occurred in 8 cases (6.8%), persistent morbidity in 5 cases (4.3%), and mortality in 1 case. CONCLUSION: In this study, we proposed a simple classification of PBLs. Using landmarks on the superior petrosal surface, the petrous bone is divided into 3 parts, apex, rhomboid, and posterior. Our results demonstrated that chordoma/chondrosarcoma, redo operations, and lesions involving the tip of the petrous apex or far medial locations were more difficult to achieve total resection. This classification could help surgeons understand surgical anatomy framework, predict possible structures at risk, and select the most appropriate approach for each patient.

How I do it: total resection of a giant sphenoclinoidal meningioma with normalization of near blind vision.

BACKGROUND: Resection of giant sphenoclinoidal meningiomas (SCLM) remains difficult. We discuss a patient presenting with right eye near blindness who underwent total removal of a giant SCLM, resulting in normal vision and no recurrence. METHOD: Utilizing frontotemporal craniotomy, devascularization, debulking, and detachment was achieved. Microdissection of tumor off the optic nerve and carotid perforators was accomplished, resulting in total resection, visual normalization, and no deficits using efficient face-to-face microscope set-up, 2-surgeon 4-hand technique, and double bipolar-suction arrangement. CONCLUSION: Frontotemporal craniotomy was adequate. Preservation of the optic nerve and carotid artery is key. Meticulous microsurgical techniques and refined instruments are important for success.

Petrous bone lesions: surgical implementation and outcomes of extradural subtemporal approach.

BACKGROUND: Petrous bone lesions (PBLs) are rare with few reports in the neurosurgical literature. In this study, the authors describe our current technique of extradural subtemporal approach (ESTA). The objective of this study was to evaluate the role and efficacy of ESTA for treatment of the PBLs. To our knowledge, this is the largest reported clinical series of using an ESTA-treated PBLs in which the clinical outcomes were evaluated. METHODS: Between 1994 and 2019, 67 patients with PBLs treated by ESTA were retrospectively reviewed. Extent of resection, neurological outcomes, recurrence rate, and surgical complications were evaluated and compared with previous studies. The indications, advantages, limitations, and outcomes of ESTA were analyzed according to pathology. RESULTS: This series included 7 facial nerve schwannomas (10.4%), 16 cholesterol granulomas (23.9%), 16 chordomas (23.9%), 6 chondrosarcomas (9%), 5 trigeminal schwannomas (7.5%), 9 epidermoids/dermoids (13.4%), and 8 other pathologies (11.9%). The most common location of PBLs operated with ESTA was at the petrous apex and rhomboid areas (68.7%). Gross total resection was achieved in 35 (55.6%). Symptomatic improvement occurred in 56 patients (83.6%). Complications occurred in 7 (10.4%) of cases including one mortality. Nine patients (17%) had recurrence within the mean follow-up 71 months. Compared to previous literature, our results demonstrated comparable outcomes but with higher rates of hearing and facial nerve preservation as well as minimal morbidity. From our results, ESTA is an effective therapeutic option for lesions located at the rhomboid and petrous apex, particularly when patients presented with intact facial and hearing function. CONCLUSION: Our series demonstrated that ESTA provided satisfactory outcomes with excellent benefits of hearing and facial function preservation for patients with petrous bone lesions. ESTA should be considered as a safe and effective therapeutic option for selected patients with PBLs.

Eosinophilic globules in a classic ependymoma: evidence of a possible secretory role.

A number of neoplasms of the central nervous system can demonstrate diffuse eosinophilic globules, known to be secretory products of the corresponding cell type, but they have not been a salient feature in descriptions of classic ependymoma. Here, we present a case of a posterior fossa ependymoma demonstrating glassy PAS-positive, diastase-resistant, eosinophilic globules with light microscopic and ultrastructural features resembling Reissner fiber, the secretory product of the subcommissural organ. While there has been a single published description of an ependymoma with intra- and extracellular granulofibrillary material suggested to be evidence of secretory differentiation, ours is the first case to demonstrate diffuse eosinophilic globules in an ependymoma. The extent of globules allowed full study by electron microscopy to provide new insight into the secretory material and the surrounding structures. Our findings suggest that neoplastic ependymal cells can recapitulate the secretory capacity of the subcommissural organ.

History of awake mapping and speech and language localization: from modules to networks.

Lesion-symptom correlations shaped the early understanding of cortical localization. The classic Broca-Wernicke model of cortical speech and language organization underwent a paradigm shift in large part due to advances in brain mapping techniques. This initially started by demonstrating that the cortex was excitable. Later, advancements in neuroanesthesia led to awake surgery for epilepsy focus and tumor resection, providing neurosurgeons with a means of studying cortical and subcortical pathways to understand neural architecture and obtain maximal resection while avoiding so-called critical structures. The aim of this historical review is to highlight the essential role of direct electrical stimulation and cortical-subcortical mapping and the advancements it has made to our understanding of speech and language cortical organization. Specifically, using cortical and subcortical mapping, neurosurgeons shifted from a localist view in which the brain is composed of rigid functional modules to one of dynamic and integrative large-scale networks consisting of interconnected cortical subregions.

Microsurgical resection of vestibular schwannomas: complication avoidance.

Vestibular schwannoma (VS) surgery requires appropriate patient selection, meticulous microsurgical technique and optimal post-operative care. Focused radiation is an effective alternative for the treatment of smaller VSs. For VS surgery to remain a reasonable option, surgery must be performed with a limited number of complications. Complication rates for VS surgery have increased over the last decade. This is likely due to (1) decreased surgical volume and as a result decreased microsurgical experience, (2) larger tumors undergoing surgery while smaller tumors are reserved for radiation, and (3) surgery for previously radiated tumors resulting in more difficult anatomic dissection. Appropriate management of complications is paramount. Herein, we discuss complications related to VS microsurgery and methods of avoidance. Specifically, we discuss the most frequently encountered complications, intraoperative monitoring and finally, methods of addressing these complications. With meticulous microsurgical technique, careful intraoperative monitoring and vigilant perioperative care one will ensure optimal patient outcomes.

Middle infratemporal fossa less invasive approach for radical resection of parapharyngeal tumors: surgical microanatomy and clinical application.

Surgery of the infratemporal fossa (ITF) and parapharyngeal area presents a formidable challenge to the surgeon due to its anatomical complexity and limited access. Conventional surgical approaches to these regions were often too invasive and necessitate sacrifice of normal function and anatomy. To describe a less invasive transcranial extradural approach to ITF parapharyngeal lesions and to determine its advantages, 17 patients with ITF parapharyngeal neoplasms who underwent tumor resection via this approach were enrolled in the study. All lesions located in the ITF precarotid parapharyngeal space were resected through a small operative corridor between the trigeminal nerve third branch (V3) and the temporomandibular joint (TMJ). Surgical outcomes and postoperative complications were evaluated. Pathological diagnosis included schwannoma in eight cases, paraganglioma in two cases, gangliocytoma in two cases, carcinosarcoma in one case, giant cell tumor in one case, pleomorphic adenoma in one case, chondroblastoma in one case, and juvenile angiofibroma in one case. Gross total resection was achieved in 12 cases, near-total and subtotal resection were in 3 and 2 cases, respectively. The most common postoperative complication was dysphagia. Surgical exposure can be customized from minimal (drilling of retrotrigeminal area) to maximal (full skeletonization of V3, removal of all structures lying lateral to the petrous segment of internal carotid artery) according to tumor size and location. Since the space between the V3 and TMJ is the main corridor of this approach, the key maneuver is the anterior translocation of V3 to obtain an acceptable surgical field.

Surgical management of vestibular schwannomas after failed radiation treatment.

Increasing numbers of patients with vestibular schwannoma (VS) have been treated with focused-beam stereotactic radiation treatment (SRT) including Gamma knife, CyberKnife, X-knife, Novalis, or proton beam therapy. The purpose of this study was to document the incidence of tumor regrowth or symptoms that worsened or first developed following SRT and to discuss surgical strategies for patients who have failed SRT for VS. A consecutive series of 39 patients with SRT failed VS were surgically treated. Clinical symptoms, tumor regrowth at follow-up, intraoperative findings, and surgical outcome were evaluated. There were 15 males and 24 females with a mean age of 51.8 years. Thirty-six patients (92.3%) demonstrated steady tumor growth after SRT. Two (5.1%) patients with slight increase of the mass underwent surgical resection because of development of unbearable facial pain. Symptoms that worsened or newly developed following SRT in this series were deafness (41%), dizziness (35.9%), facial numbness (25.6%), tinnitus (20.5%), facial nerve palsy (7.7%), and facial pain (7.7%). Intraoperative findings demonstrated fibrous changes of the tumor mass, cyst formation, and brownish-yellow or purple discoloration of the tumor capsule. Severe adhesions between the tumor capsule and cranial nerves, vessels, and the brainstem were observed in 69.2%. Additionally, the facial nerve was more fragile and irritable in all cases. Gross total resection (GTR) was achieved in 33.3% of patients, near-total resection (NTR) in 35.9%, and subtotal resection (STR) in 30.8% of patients. New facial nerve palsy was seen in seven patients (19.4%) postoperatively. Our findings suggest that patients with VS who fail SRT with either tumor progression or worsening of clinical symptoms will have an increased rate of adhesions to the neurovascular structures and may have radiation-influenced neuromalacia. Salvage surgery of radiation-failed tumors is more difficult and will have a higher risk of postoperative complications. Radical total resection may not be feasible, and conservative modality of subtotal resection needs to be considered to avoid new neurologic deficits.

TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal.

Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (≥15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.

Central Nervous System Cancers, Version 1.2015.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Central Nervous System (CNS) Cancers provide interdisciplinary recommendations for managing adult CNS cancers. Primary and metastatic brain tumors are a heterogeneous group of neoplasms with varied outcomes and management strategies. These NCCN Guidelines Insights summarize the NCCN CNS Cancers Panel's discussion and highlight notable changes in the 2015 update. This article outlines the data and provides insight into panel decisions regarding adjuvant radiation and chemotherapy treatment options for high-risk newly diagnosed low-grade gliomas and glioblastomas. Additionally, it describes the panel's assessment of new data and the ongoing debate regarding the use of alternating electric field therapy for high-grade gliomas.

Oncolytic polio virotherapy of cancer.

Recently, the century-old idea of targeting cancer with viruses (oncolytic viruses) has come of age, and promise has been documented in early stage and several late-stage clinical trials in a variety of cancers. Although originally prized for their direct tumor cytotoxicity (oncolytic virotherapy), recently, the proinflammatory and immunogenic effects of viral tumor infection (oncolytic immunotherapy) have come into focus. Indeed, a capacity for eliciting broad, sustained antineoplastic effects stemming from combined direct viral cytotoxicity, innate antiviral activation, stromal proinflammatory stimulation, and recruitment of adaptive immune effector responses is the greatest asset of oncolytic viruses. However, it also is the source for enormous mechanistic complexity that must be considered for successful clinical translation. Because of fundamentally different relationships with their hosts (malignant or not), diverse replication strategies, and distinct modes of tumor cytotoxicity/killing, oncolytic viruses should not be referred to collectively. These agents must be evaluated based on their individual merits. In this review, the authors highlight key mechanistic principles of cancer treatment with the polio:rhinovirus chimera PVSRIPO and their implications for oncolytic immunotherapy in the clinic.

Central nervous system cancers, version 2.2014. Featured updates to the NCCN Guidelines.

The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases.

Malignant brainstem gliomas in adults: clinicopathological characteristics and prognostic factors.

Adult malignant brainstem gliomas (BSGs) are poorly characterized due to their relative rarity. We have examined histopathologically confirmed cases of adult malignant BSGs to better characterize the patient and tumor features and outcomes, including the natural history, presentation, imaging, molecular characteristics, prognostic factors, and appropriate treatments. A total of 34 patients were identified, consisting of 22 anaplastic astrocytomas (AAs) and 12 glioblastomas (GBMs). The overall median survival for all patients was 25.8 months, with patients having GBMs experiencing significantly worse survival (12.1 vs. 77.0 months, p = 0.0011). The majority of tumors revealed immunoreactivity for EGFR (93.3 %) and MGMT (64.7 %). Most tumors also exhibited chromosomal abnormalities affecting the loci of epidermal growth factor receptor (92.9 %), MET (100 %), PTEN (61.5 %), and 9p21 (80 %). AAs more commonly appeared diffusely enhancing (50.0 vs. 27.3 %) or diffusely nonenhancing (25.0 vs. 0.0 %), while GBMs were more likely to exhibit focal enhancement (54.6 vs. 10.0 %). Multivariate analysis revealed confirmed histopathology for GBM to significantly affect survival (HR 4.80; 95 % CI 1.86-12.4; p = 0.0012). In conclusion, adult malignant BSGs have an overall poor prognosis, with GBM tumors faring significantly worse than AAs. As AAs and GBMs have differing imaging characteristics, tissue diagnosis may be necessary to accurately determine patient prognosis and identify molecular characteristics which may aid in the treatment of these aggressive tumors.

Hearing preservation surgery for vestibular schwannomas via the retrosigmoid transmeatal approach: surgical tips.

Maximum tumor extirpation with preservation of the facial and cochlear nerve function is the goal of surgery for vestibular schwannoma. To preserve cochlear nerve function, the surgeon must employ a detailed knowledge of microanatomy, precise microsurgical techniques, and persistence. This paper describes the "pearls" of surgical techniques based on the anatomical study inside the mastoid from the view of the retrosigmoid transmeatal approach. A total of 592 consecutive patients underwent surgical removal of unilateral vestibular schwannoma (VS) between January 1994 and December 2009. The hearing preservation rate was 53.7 % for large vestibular schwannomas (>20 mm in diameter) and 74.1 % for tumors of all sizes. The key procedures for hearing preservation surgery are as follows: bloodless microdissection, sufficient coring-debulking, capsular elevation to locate the facial and cochlear nerves both electrophysiologically and by visual observation, sharp dissection of the facial and cochlear nerves, and avoidance of heat and mechanical injury to the nerves, the internal auditory artery, and the brain stem. Besides these techniques, appropriate instruments are essential to preserve hearing. The function of the facial and cochlear nerves should be the foremost concern. Meticulous techniques and the knowledge of microsurgical anatomy lead to hearing preservation with maximum tumor removal.

Cognitive outcomes following aneurysmal subarachnoid hemorrhage: Rehabilitation strategies.

Despite decreases in mortality rate, the treatment of cognitive deficits following aneurysmal subarachnoid hemorrhage (aSAH) remains a serious challenge for clinicians and survivors alike. Deficits in executive function, language, and memory prevent more than half of survivors from returning to their previous level of work and put a tremendous amount of stress on the individual and their family. New therapies are needed for survivors of aSAH in order to improve cognitive outcomes and quality of life. The aim of this review is to discuss the prevalence and contributing factors of cognitive deficits following aSAH, as well as areas for therapeutic intervention. Due to the limited research on cognitive rehabilitative strategies for aSAH, a literature search of traumatic brain injury (TBI) was used to explore therapies with the potential to improve cognitive outcomes in aSAH. Across cognitive domains, existing rehabilitative and pharmacotherapeutic strategies for TBI show promise to be useful for survivors of aSAH. However, further study of these therapies in addition to consistent assessment of cognitive deficits are required to determine their efficacy in survivors of aSAH.

Antithrombotic Therapy in Cerebral Cavernous Malformations: A Systematic Review, Meta-Analysis, and Network Meta-Analysis.

BACKGROUND: Cerebral cavernous malformations are complex vascular anomalies in the central nervous system associated with a risk of intracranial hemorrhage. Traditional guidelines have been cautious about the use of antithrombotic therapy in this patient group, citing concerns about potential bleeding risk. However, recent research posits that antithrombotic therapy may actually be beneficial. This study aims to clarify the association between antithrombotic therapy, including antiplatelet and anticoagulant medications, and the risk of intracranial hemorrhage in patients with cerebral cavernous malformations. METHODS AND RESULTS: A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus databases, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Nine single-center, nonrandomized cohort studies involving 2709 patients were included. Outcomes were analyzed using random-effects model, and a network meta-analysis was conducted for further insight. Of the 2709 patients studied, 388 were on antithrombotic therapy. Patients on antithrombotic therapy had a lower risk of presenting with intracranial hemorrhage (odds ratio [OR], 0.56 [95% CI, 0.45-0.7]; P<0.0001). In addition, the use of antithrombotic therapy was associated with lower risk of intracranial hemorrhage from a cerebral cavernous malformation on follow-up (OR, 0.21 [95% CI, 0.13-0.35]; P<0.0001). A network meta-analysis revealed a nonsignificant OR of 0.73 (95% CI, 0.23-2.56) when antiplatelet therapy was compared with anticoagulant therapy. CONCLUSIONS: Our study explores the potential benefits of antithrombotic therapy in cerebral cavernous malformations. Although the analysis suggests a possible role for antithrombotic agents, it is critical to note that the evidence remains preliminary. Fundamental biases in study design, such as ascertainment and assignment bias, limit the weight of our conclusions. Therefore, our findings should be considered hypothesis-generating and not definitive for clinical practice change.