Emerging therapeutic targets for cerebral edema.

INTRODUCTION: Cerebral edema is a key contributor to death and disability in several forms of brain injury. Current treatment options are limited, reactive, and associated with significant morbidity. Targeted therapies are emerging based on a growing understanding of the molecular underpinnings of cerebral edema. AREAS COVERED: We review the pathophysiology and relationships between different cerebral edema subtypes to provide a foundation for emerging therapies. Mechanisms for promising molecular targets are discussed, with an emphasis on those advancing in clinical trials, including ion and water channels (AQP4, SUR1-TRPM4) and other proteins/lipids involved in edema signaling pathways (AVP, COX2, VEGF, and S1P). Research on novel treatment modalities for cerebral edema [including recombinant proteins and gene therapies] is presented and finally, insights on reducing secondary injury and improving clinical outcome are offered. EXPERT OPINION: Targeted molecular strategies to minimize or prevent cerebral edema are promising. Inhibition of SUR1-TRPM4 (glyburide/glibenclamide) and VEGF (bevacizumab) are currently closest to translation based on advances in clinical trials. However, the latter, tested in glioblastoma multiforme, has not demonstrated survival benefit. Research on recombinant proteins and gene therapies for cerebral edema is in its infancy, but early results are encouraging. These newer modalities may facilitate our understanding of the pathobiology underlying cerebral edema.

Subarachnoid hemorrhage rebleeding in the first 24 h is associated with external ventricular drain placement and higher grade on presentation: Cohort study.

BACKGROUND: Rebleeding after aneurysmal subarachnoid hemorrhage (aSAH) confers a poor prognosis; however, risk factors and differential outcomes associated with early rebleeding in the first 24 h after symptom presentation are incompletely understood. METHODS: A retrospective cohort study of all aSAH presenting to our institution between 2001 and 2016 was performed. Early rebleeding events were defined as clinical neurologic decline with radiographically confirmed acute intracranial hemorrhage within 24 h after symptom presentation. Univariate and multivariate logistic regression analyses were used to assess clinical associations, with a specific focus on baseline Glasgow Coma Score (GCS), World Federation of Neurosurgical Societies (WFNS), and modified Fisher scores. RESULTS: Of 471 aSAH cases, 33 (7%) experienced early rebleeding. Multivariate regression identified extraventricular drain (EVD) placement (OR = 2.16, P = 0.04) and WFNS 3-5 (OR = 2.69, P = 0.02) as significant predictors of early rebleeding. Good functional outcomes were observed in 8 patients with early rebleeding (24%), all of whom underwent aneurysm treatment. Higher SAH grade prior to rebleeding (WFNS 3-5) was significantly associated with increased odds of an unfavorable functional outcome (OR = 8.09, P < 0.01). Anticoagulation, aneurysm size and location were not significantly associated with either early rebleeding incidence or functional outcome. CONCLUSIONS: Early rebleeding in aSAH is associated with unfavorable functional outcomes. EVD placement and higher SAH grade on presentation appear to be significantly and independently associated with increased risk of rebleeding within first 24 h, as well as unfavorable long-term functional outcome; however, the clinical benefit of hyper-acute aneurysm treatment requires further investigation.

Parasagittal and parafalcine meningiomas: integral strategy for optimizing safety and retrospective review of a single surgeon series.

Background: Parafalcine and parasagittal meningiomas present unique challenges for resection. Although maximal safe resection is the primary goal of surgical management for these lesions, venous infarction and eloquent cortical structure damage occur in up to 14% of cases. Therefore, optimal preoperative planning and intraoperative technique is critical.Methods: We retrospectively reviewed a single surgeon's case series with resection of 58 parafalcine and parasagittal meningiomas. Operative strategy included not crossing the superior sagittal sinus (SSS) during craniotomy, not resecting the falx, use of motor evoked potentials (MEPs) to avoid damage to eloquent brain, and selective use of preoperative embolization.Results: Fifty-eight patients, 45 with parasagittal meningiomas and 13 with parafalcine meningiomas were evaluated. Median age 58.34 years and mean follow-up was 7.7 months. Gross total resection (GTR) was achieved in 51.7% of patients and near-gross total resection rate was 48.3%. Postoperative day one discharge rate was 62.1%. Complication rate was 8.6%, with new postoperative neurologic deficit rate of 5.2%. Tumor recurrence/growth documented on postoperative imaging rate was 3.4%.Conclusions: In our series of parasagittal and parafalcine meningioma resection, we report a 51.7% GTR rate associated with a low complication rate. Techniques to minimize perioperative morbidity include not crossing the SSS on craniotomy, avoiding falx resection, using MEPs, and selective preoperative embolization to optimize the chance of a maximal safe resection. We utilize a strategy of conservative initial tumor resection focused on maximizing the chances of a favorable neurologic outcome, followed as necessary by adjuvant therapies such as radiosurgery and salvage therapies such as laser interstitial thermal therapy, although longer follow-up comparable to that of series with more radical approaches is required to determine if long term outcomes are comparable.

Mechanism of Action and Biology of Flow Diverters in the Treatment of Intracranial Aneurysms.

Flow diverters have drastically changed the landscape of intracranial aneurysm treatment and are now considered first-line therapy for select lesions. Their mechanism of action relies on intrinsic alteration in hemodynamic parameters, both at the parent artery and within the aneurysm sac. Moreover, the device struts act as a nidus for endothelial cell growth across the aneurysm neck ultimately leading to aneurysm exclusion from the circulation. In silico computational analyses and investigations in preclinical animal models have provided valuable insights into the underlying biological basis for flow diverter therapy. Here, we review the present understanding pertaining to flow diverter biology and mechanisms of action, focusing on stent design, induction of intra-aneurysmal thrombosis, endothelialization, and alterations in hemodynamics.

Sphenoorbital meningioma: a unique skull base tumor. Surgical technique and results.

OBJECTIVE: Sphenoorbital meningioma (SOM) is a unique skull base tumor, characterized by infiltrative involvement and hyperostosis primarily of the lesser wing of sphenoid bone, with frequent involvement of the orbital compartment. SOM often manifests with proptosis and visual impairment. Surgical technique and outcome are highly variable among studies reported in the literature. The authors present a single-surgeon experience with SOM. METHODS: A retrospective review of a prospectively maintained institutional database was performed. A blinded imaging review by 2 study team members was completed to confirm SOM, after which chart review was carried out to capture demographics and outcomes. All statistical testing was completed using JMP Pro version 14.1.0, with significance defined as p < 0.05. RESULTS: Forty-seven patients who underwent surgery between 2000 and 2017 were included. The median age at surgery was 47 years (range 36-70 years), 81% of patients were female, and the median follow-up was 43 months (range 0-175 months). All operations were performed via a frontotemporal craniotomy, orbitooptic osteotomy, and anterior clinoidectomy, with extensive resection of all involved bone and soft tissue. Preoperatively, proptosis was noted in 44 patients, 98% of whom improved. Twenty-eight patients (60%) had visual deficits before surgery, 21 (75%) of whom improved during follow-up. Visual field defect other than a central scotoma was the only prognostic factor for improvement in vision on multivariate analysis (p = 0.0062). Nine patients (19%) had recurrence or progression during follow-up. CONCLUSIONS: SOM is a unique skull base tumor that needs careful planning to optimize outcome. Aggressive removal of involved bone and periorbita is crucial, and proptosis and visual field defect other than a central scotoma can improve after surgery.

Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Mesial Temporal Epilepsy: A Case Series Analysis of Outcomes and Complications at 2-Year Follow-Up.

BACKGROUND: Laser interstitial thermal therapy (LITT) presents an important new minimally invasive tool in the management of drug-resistant mesial temporal epilepsy (MTE). However, because of its relative novelty, not much is known about long-term seizure freedom rates. The objective of this study was to evaluate the postsurgical seizure outcome following LITT after a minimum follow-up period of 2 years. METHODS: Medical records of all patients who underwent LITT for MTE from 2013 to 2018 at our comprehensive epilepsy center under a single surgeon were retrospectively reviewed. Data related to demographics, presurgical evaluations, and seizure outcome were compared between seizure-free (SF) and non-seizure-free (NSF) patients. RESULTS: In all, 26 patients were identified with at least 2 years of follow-up. Mean age was 43.8 years ± 11.6 years, and 46.2% were female. After a mean follow-up time of 42.9 months (range, 24.3-58.8 months), 61.5% (16/26) were free of disabling seizures, and 26.9% (7/26) had only rare disabling seizures. Whereas seizure-freedom rates between patients with and without mesial temporal sclerosis (MTS) were not statistically different (68% vs. 43%, P = 0.23), NSF patients without MTS had a shorter median time to first seizure than did NSF patients with MTS (0.55 month vs. 10 months, log-rank test P = 0.007). Postoperative complications occurred in 2 patients (7.7%), consisting of 1 permanent and 1 transient homonymous hemianopia. CONCLUSIONS: LITT appears to be a safe and effective initial surgical option for treatment-resistant MTE. Among patients who have seizures after treatment, those without MTS appear to have seizures earlier than those with MTS.

Renal Cell Carcinoma with Primary Presentation via Metastasis to the Trigeminal Ganglion.

BACKGROUND: Renal cell carcinoma (RCC) accounts for ∼8% of all brain metastatic disease; however, spread to the cranial nerves and their ganglia is uncommon. To the best of our knowledge, we report the first case of RCC metastatic to Meckel's cave, which was diagnosed secondary to new trigeminal sensory loss. METHODS: A 45-year-old man had presented with acute-onset right V3 numbness. Magnetic resonance imaging demonstrated contrast enhancement of the ipsilateral V3, extending from its root at the Gasserian ganglion to the foramen ovale. RESULTS: He elected for observation, and his symptoms resolved over several weeks. At the scheduled, routine 3-month follow-up examination, he reported symptomatic relapse with new concomitant hyperesthetic/neuropathic pain. Magnetic resonance imaging demonstrated interval enlargement of the enhancing lesion in an atypical pattern, potentially consistent with trigeminal schwannoma versus meningioma, and operative resection was recommended. CONCLUSION: We have reported a case of RCC presenting with numbness via metastatic spread to Meckel's cave. Although uncommon, metastasis is an important diagnostic consideration for enhancing cranial nerve lesions. Our case has demonstrated that, although a history of malignancy, multiple lesions, or systemic/constitutional symptoms are typical, rare cases can demonstrate isolated central nervous system findings. Thus, short-term radiographic surveillance is indicated if the diagnosis of an intracranial or cranial nerve mass lesion is equivocal.

Management of Foramen Magnum Meningioma During Pregnancy: Literature Review and Case Report.

BACKGROUND: Foramen magnum meningiomas are very rare and challenging lesions. Their presentation in women during pregnancy tremendously complicates the course of gestation. Conservative management is always the first option, but in cases of a deteriorating clinical picture, there are currently no clear guidelines on best management. CASE DESCRIPTION: A woman presents in the 30th week of pregnancy with pain and progressive numbness in right posterior aspect of neck and right arm. Foramen magnum meningioma was diagnosed and successful surgical resection was performed with intraoperative fetal hearth monitoring and three fourths prone position of the patient. CONCLUSIONS: We believe a three fourths prone position of a pregnant patient is safe and adequate for the far-lateral exposure of craniocervical lesions. Rapid growing of tumor can be precipitated by steroids management during pregnancy.

Percutaneous Drainage of Chronic Destructive Lumbar Osteomyelitis Abscess Via the Use of Bilateral Transpedicular Trocar Access.

BACKGROUND: Pyogenic spondylodiskitis is an infection of intervertebral disks and spinal vertebral bodies. Various minimally invasive approaches to the infected disk spaces/abscesses have been described for management of early stages of the infection. Patients with chronic occurrence present with extensive infection, neurologic deficits, and bone destruction. Such patients commonly have substantial medical comorbidities. Despite the increased risks of complications, they often are treated with open surgical approaches without minimally invasive options. We describe a bilateral transpedicular approach to vertebral body abscess in a chronically infected patient with intraoperative contiguous irrigation. CASE DESCRIPTION: We present 2 cases, a 58-year-old man and a 61-year-old man, both with a diagnosis of vertebral osteomyelitis. Images of lumbar spine showed epidural abscess and adjacent vertebral body destruction. Because of their poor clinical condition and chronicity of disease, these patients underwent percutaneous bilateral transpedicular approach. CONCLUSION: Patients in poor health and with chronic vertebral osteomyelitis may benefit from minimally invasive percutaneous transpedicular drainage and irrigation of the abscess, representing a minimally invasive and effective treatment alternative for these patients.