Intracerebral hemorrhage remains a significant cause of morbidity and mortality. Current surgical therapies aim to use a minimally invasive approach to remove as much of the clot as possible without causing undue disruption to surrounding neural structures. Transcranial MR-guided focused ultrasound (MRgFUS) surgery is an emerging technology that permits a highly concentrated focal point of ultrasound energy to be deposited to a target deep within the brain without an incision or craniotomy. With appropriate ultrasound parameters it has been shown that MRgFUS can effectively liquefy large-volume blood clots through the human calvaria. In this review the authors discuss the rationale for using MRgFUS to noninvasively liquefy intracerebral hemorrhage (ICH), thereby permitting minimally invasive aspiration of the liquefied clot via a small drainage tube. The mechanism of action of MRgFUS sonothrombolysis; current investigational work with in vitro, in vivo, and cadaveric models of ICH; and the potential clinical application of this disruptive technology for the treatment of ICH are discussed.
Stephen J. Monteith, Neal F. Kassell, Oded Goren and Sagi Harnof
Ricky Medel, Stephen J. Monteith, R. Webster Crowley and Aaron S. Dumont
Although initially described in the 19th century, cerebral venous sinus thrombosis (CVST) remains a diagnostic and therapeutic dilemma. It has an unpredictable course, and the propensity for hemorrhagic infarction produces significant consternation among clinicians when considering anticoagulation. It is the purpose of this review to analyze the evidence available on the management of CVST and to provide appropriate recommendations.
A thorough literature search was conducted through MEDLINE and PubMed, with additional sources identified through cross-referencing. A classification and level of evidence assignment is provided for recommendations based on the American Heart Association methodologies for guideline composition.
Of the publications identified, the majority were isolated case reports or small case series. Few prospective trials have been conducted. Existing data support the use of systemic anticoagulation as an initial therapy in all patients even in the presence of intracranial hemorrhage. Chemical and/or mechanical thrombectomy, in conjunction with systemic anticoagulation, is an alternative strategy in patients with progressive deterioration on heparin therapy or in those who are moribund on presentation. Mechanical thrombectomy is probably preferred in patients with preexisting intracranial hemorrhage.
Effective treatments exist for the management of CVST, and overall outcomes are more favorable than those for arterial stroke. Further research is necessary to determine the role of individual therapies; however, the rarity of the condition poses a significant limitation.
Stephen Monteith, John Snell, Mathew Eames, Neal F. Kassell, Edward Kelly and Ryder Gwinn
In appropriate candidates, the treatment of medication-refractory mesial temporal lobe epilepsy (MTLE) is primarily surgical. Traditional anterior temporal lobectomy yields seizure-free rates of 60%–70% and possibly higher. The field of magnetic resonance–guided focused ultrasound (MRgFUS) is an evolving field in neurosurgery. There is potential to treat MTLE with MRgFUS; however, it has appeared that the temporal lobe structures were beyond the existing treatment envelope of currently available clinical systems. The purpose of this study was to determine whether lesional temperatures can be achieved in the target tissue and to assess potential safety concerns.
Cadaveric skulls with tissue-mimicking gels were used as phantom targets. An ablative volume was then mapped out for a “virtual temporal lobectomy.” These data were then used to create a target volume on the InSightec ExAblate Neuro system. The target was the amygdala, uncus, anterior 20 mm of hippocampus, and adjacent parahippocampal gyrus. This volume was approximately 5cm3. Thermocouples were placed on critical skull base structures to monitor skull base heating.
Adequate focusing of the ultrasound energy was possible in the temporal lobe structures. Using clinically relevant ultrasound parameters (power 900 W, duration 10 sec, frequency 650 kHz), ablative temperatures were not achieved (maximum temperature 46.1°C). Increasing sonication duration to 30 sec demonstrated lesional temperatures in the mesial temporal lobe structures of interest (up to 60.5°C). Heating of the skull base of up to 24.7°C occurred with 30-sec sonications.
MRgFUS thermal ablation of the mesial temporal lobe structures relevant in temporal lobe epilepsy is feasible in a laboratory model. Longer sonications were required to achieve temperatures that would create permanent lesions in brain tissue. Heating of the skull base occurred with longer sonications. Blocking algorithms would be required to restrict ultrasound beams causing skull base heating. In the future, MRgFUS may present a minimally invasive, non-ionizing treatment of MTLE.
Report of four cases and review of the literature
Peter A. Heppner, Stephen J. Monteith and Andrew J. J. Law
✓ The purpose of this article is to raise awareness of spontaneous spinal hematomas that develop after administration of low-molecular-weight heparin therapy. The authors describe four patients in whom these hematomas developed without precipitating events while receiving a treatment dose of enoxaparin (Clexane) (∼1 mg/kg). Spontaneous spinal hematomas (not related to trauma, surgery, or lumbar puncture) are a rare clinical entity. Several causes have been identified, including acquired and congenital clotting abnormalities and underlying vascular lesions. Aspirin, warfarin, tissue plasminogen activator, and heparin have all been implicated in causing spinal hematomas. Concerns regarding the use of low-molecular-weight heparin agents in neuraxis anesthesia have been well documented. Their possible contribution to nontraumatic spinal hematomas has been less well described. The authors believe that low-molecular-weight heparin agents present a small but significant risk of spinal hematoma. This should be considered when prescribing therapy because such a complication may be catastrophic.
Stephen J. Monteith, Robert M. Starke, John A. Jane Jr. and Edward H. Oldfield
Subnormal postoperative serum cortisol levels indicate successful surgery and predict long-term remission of Cushing disease. Given the short serum half-lives of adrenocorticotropic hormone (ACTH) and cortisol, it is unclear why the decline in cortisol postoperatively is delayed for 18–36 hours. Furthermore, the relevance of the rate of cortisol drop immediately after surgery has not been investigated.
Patient data were analyzed from a prospectively accrued database. After surgery, cortisol replacement was withheld and serum cortisol measurements were obtained every 6 hours until values of 1.0–2.0 μg/dl or less were reached. The authors selected patients in whom serum cortisol dropped to 2 μg/dl or less after surgery (101 patients). Tumor resection was categorized as follows: 1) complete resection using the histological pseudocapsule as a surgical capsule, 2) complete piecemeal resection), 3) known incomplete resection, and 4) total hypophysectomy.
The median time to reach a cortisol level of less than or equal to 2.0 μg/dl was 9.9, 19.4, 25.3, and 29.5 hours with hypophysectomy, pseudocapsule, incomplete resection, and piecemeal techniques, respectively. Pseudocapsule resection produced a faster decline in cortisol than piecemeal techniques (p = 0.0001), but not as rapid a decline as hypophysectomy (p = 0.033).
Complete resection by other techniques is associated with delayed cortisol decline compared with pseudocapsule surgery, which may represent the product of residual tumor cells and therefore may explain the higher rate of recurrent disease associated with piecemeal techniques. The prompt drop in cortisol after hypophysectomy compared with patients with pseudocapsule surgery suggests that the corticotrophs of the normal gland can secrete ACTH for 10–36 hours after surgery despite prolonged and severe hypercortisolism.
Oded Goren, Stephen J. Monteith, Moshe Hadani, Mati Bakon and Sagi Harnof
This paper reviews the current intraoperative imaging tools that are available to assist neurosurgeons in the treatment of intracerebral hemorrhage (ICH). This review shares the authors' experience with each modality and discusses the advantages, potential limitations, and disadvantages of each.
Surgery for ICH is directed at blood clot removal, reduction of intracranial pressure, and minimization of secondary damage associated with hematoma breakdown products. For effective occlusion and safe obliteration of vascular anomalies associated with ICH, vascular neurosurgeons today require a thorough understanding of the various intraoperative imaging modalities available for obtaining real-time information. Use of one or more of these modalities may improve the surgeon's confidence during the procedure, the patient's safety during surgery, and surgical outcome.
The modern techniques discussed include 1) indocyanine green–based video angiography, which provides real-time information based on high-quality images showing the residual filling of vascular pathological entities and the patency of blood vessels of any size in the surgical field; and 2) intraoperative angiography, which remains the gold standard intraoperative diagnostic test in the surgical management of cerebral aneurysms and arteriovenous malformations. Hybrid procedures, providing multimodality image-guided surgeries and combining endovascular with microsurgical strategies within the same surgical session, have become feasible and safe. Microdoppler is a safe, noninvasive, and reliable technique for evaluation of hemodynamics of vessels in the surgical field, with the advantage of ease of use. Intraoperative MRI provides an effective navigation tool for cavernoma surgery, in addition to assessing the extent of resection during the procedure. Intraoperative CT scanning has the advantage of very high sensitivity to acute bleeding, thereby assisting in the confirmation of the extent of hematoma evacuation and the extent of vascular anomaly resection. Intraoperative ultrasound aids navigation and evacuation assessment during intracerebral hematoma evacuation surgeries. It supports the concept of minimally invasive surgery and has undergone extensive development in recent years, with the quality of ultrasound imaging having improved considerably.
Image-guided therapy, combined with modern intraoperative imaging modalities, has changed the fundamentals of conventional vascular neurosurgery by presenting real-time visualization of both normal tissue and pathological entities. These imaging techniques are important adjuncts to the surgeon's standard surgical armamentarium. Familiarity with these imaging modalities may help the surgeon complete procedures with improved safety, efficiency, and clinical outcome.
Jason P. Sheehan, Britney Popp, Stephen Monteith, Sushila Toulmin, Jennifer Tomlinson, Jessica Martin, Christopher P. Cifarelli, Dae-Hee Lee and Deric M. Park
Intratumoral hypoxia is believed to be exhibited in high-grade gliomas. Trans sodium crocetinate (TSC) has been shown to increase oxygen diffusion to hypoxic tissues. In this research, the authors use oxygen-sensitive PET studies to evaluate the extent of hypoxia in vivo in a glioblastoma model and the effect of TSC on the baseline oxygenation of the tumor.
The C6 glioma cells were stereotactically implanted in the right frontal region of rat brains. Formation of intracranial tumors was confirmed on MR imaging. Animals were injected with Copper(II) diacetyl-di(N4-methylthiosemicarbazone) (Cu-ATSM) and then either TSC or saline (6 rats each). Positron emission tomography imaging was performed, and relative uptake values were computed to determine oxygenation within the tumor and normal brain parenchyma. Additionally, TSC or saline was infused into the animals, and carbonic anhydrase 9 (CA9) and hypoxia-inducing factor–1α (HIF-1α) protein expression were measured 1 day afterward.
On PET imaging, all glioblastoma tumors demonstrated a statistically significant decrease in uptake of Cu-ATSM compared with the contralateral cerebral hemisphere (p = 0.000002). The mean relative uptake value of the tumor was 3900 (range 2203–6836), and that of the contralateral brain tissue was 1017 (range 488–2304).
The mean relative hypoxic tumor volume for the saline group and TSC group (6 rats each) was 1.01 ± 0.063 and 0.69 ± 0.062, respectively (mean ± SEM, p = 0.002). Infusion of TSC resulted in a 31% decrease in hypoxic volume. Immunoblot analysis revealed expression of HIF-1α and CA9 in all tumor specimens.
Some glioblastomas exhibit hypoxia that is demonstrable on oxygen-specific PET imaging. It appears that TSC lessens intratumoral hypoxia on functional imaging. Further studies should explore relative hypoxia in glioblastoma and the potential therapeutic gains that can be achieved by lessening hypoxia during delivery of adjuvant treatment.
Stephen Monteith, Jason Sheehan, Ricky Medel, Max Wintermark, Matthew Eames, John Snell, Neal F. Kassell and W. Jeff Elias
Magnetic resonance–guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.
Stephen J. Monteith, Asterios Tsimpas, Aaron S. Dumont, Stavropoula Tjoumakaris, L. Fernando Gonzalez, Robert H. Rosenwasser and Pascal Jabbour
Despite advances in surgical and endovascular techniques, fusiform aneurysms remain a therapeutic challenge. Introduction of flow-diverting stents has revolutionized the treatment of aneurysms with wide necks and of complex morphology. The authors report their experience with the endovascular treatment of fusiform aneurysms using the Pipeline Embolization Device.
A retrospective review of 146 patients with cerebral aneurysms treated with the Pipeline Embolization Device between June 2011 and January 2013 was performed. Twenty-four patients were identified as having fusiform aneurysms. Twenty-four aneurysms in these 24 patients were treated. The mean patient age was 59 years. There were 9 men and 15 women. Angiographic and clinical data (including the modified Rankin Scale [mRS] score) were recorded at the time of treatment and at follow-up. The aneurysms were located in the internal carotid artery in 8 patients (33.3%), middle cerebral artery in 8 patients (33.3%), anterior cerebral artery in 1 patient (4%), and vertebrobasilar circulation in 7 patients (29%). The aneurysms were smaller than 10 mm in 3 patients, 10–25 mm in 16 patients, and larger than 25 mm in 5 patients. The mean largest dimension diameter was 18 mm.
Stent deployment was successful in all cases. The minor procedural morbidity was 4% (1 case). Morbidity and mortality related to aneurysm treatment were 4.2% and 4.2%, respectively. The mean mRS scores preoperatively and at clinical follow-up (median 6.0 months, mean 6.9 months) were 0.71 and 1.2, respectively (91.7% presented with an mRS score of 2 or better, and 79.2% had an mRS score of 2 or better at the 6.0-month follow-up). At clinical follow-up, 82.6% of patients were stable or had improved, 13.0% worsened, and 4.2% had died. Twenty-two (91.7%) of 24 patients had follow-up angiography available (mean follow-up time 6.3 months); 59% had excellent angiographic results (> 95% or complete occlusion), 31.8% had complete aneurysm occlusion, 27.3% had greater than 95% aneurysm occlusion, 18.2% had a moderate decrease in size (50%–95%), 4.5% had a minimal decrease in size (< 50%), 13.6% had not changed, and 4.5% had an increase in size.
This series demonstrates that endovascular treatment of fusiform cerebral aneurysms with flow diversion was a safe and effective treatment. Procedural complications were low. Long-term morbidity and mortality rates were acceptable given the complex nature of these lesions.