Ultrasound Ablation in Neurosurgery: Current Clinical Applications and Future Perspectives

Neurosurgery 87:1–10, 2020

The concept of focusing high-intensity ultrasound beams for the purpose of cerebral ablation has interested neurosurgeons for more than 70 yr. However, the need for a craniectomy or a cranial acoustic window hindered the clinical diffusion of this technique.

Recent technological advances, including the development of phased-array transducers and magnetic resonance imaging technology, have rekindled the interest in ultrasound for ablative brain surgery and have led to the development of the transcranial magnetic resonance-guided focused ultrasound (MRgFUS) thermal ablation procedure. In the last decade, this method has become increasingly popular, and its clinical applications are broadening.

Despite the demonstrated efficacy of MRgFUS, transcranial thermal ablation using ultrasound is limited in that it can target exclusively the central region of the brain where the multiple acoustic beams are most optimally focused. On the contrary, lesioning of the cortex, the superficial subcortical areas, and regions close to the skull base is not possible with the limited treatment envelope of current phased-array transducers.

Therefore, new ultrasound ablative techniques, which are not based on thermal mechanisms, have been developed and tested in experimental settings. This review describes the mechanisms by which these novel, nonthermal ablative techniques are based and also presents the current clinical applications of MRgFUS thermal ablation.

The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin

Acta Neurochirurgica (2020) 162: 1053–1066

Deep brain stimulation alleviates tremor of various origins. The dentato-rubro-thalamic tract (DRT) has been suspected as a common tremor-reducing structure. Statistical evidence has not been obtained. We here report the results of an uncontrolled case series of patients with refractory tremor who underwent deep brain stimulation under tractographic assistance.

Methods A total of 36 patients were enrolled (essential tremor (17), Parkinson’s tremor (8), multiple sclerosis (7), dystonic head tremor (3), tardive dystonia (1)) and received 62 DBS electrodes (26 bilateral; 10 unilateral). Preoperatively, diffusion tensor magnetic resonance imaging sequences were acquired together with high-resolution anatomical T1Wand T2W sequences. The DRTwas individually tracked and used as a direct thalamic or subthalamic target. Intraoperative tremor reduction was graded on a 4-point scale (0 = no tremor reduction to 3 = full tremor control) and recorded together with the current amplitude, respectively. Stimulation point coordinates were recorded and compared to DRT. The relation of the current amplitude needed to reduce tremor was expressed as TiCR (tremor improvement per current ratio).

Results Stimulation points of 241 were available for analysis. A total of 68 trajectories were tested (62 dB leads, 1.1 trajectories tested per implanted lead). Tremor improvement was significantly decreasing (p < 0.01) if the distance to both the border and the center of the DRT was increasing. On the initial trajectory, 56 leads (90.3%) were finally placed. Long-term outcomes were not part of this analysis.

Discussion Tremor of various origins was acutely alleviated at different points along the DRT fiber tract (above and below the MCP plane) despite different tremor diseases. DRT is potentially a common tremor-reducing structure. Individual targeting helps to reduce brain penetrating tracts. TiCR characterizes stimulation efficacy and might help to identify an optimal stimulation point.

Embolized cerebral arteriovenous malformations: a multivariate analysis of 101 excised specimens

J Neurosurg 132:1140–1146, 2020

Endovascular approaches have evolved from a technique practiced at very few centers to a widely available option in the management of arteriovenous malformations (AVMs) of the central nervous system. Embolization can be employed as definitive therapy or as an adjunct to surgical excision. A wide variety of embolic agents have been successfully developed and used in the clinical setting. In addition to facilitating vascular occlusion, embolic agents induce a number of reactive and destructive changes in vessel walls and the surrounding tissue. However, studies examining the pathological changes induced by different embolic agents and varying times of exposure are scarce. The goal of the present study was to compare embolic agents and time of exposure on the pathology in excised specimens.

METHODS The records of the Department of Pathology at the London Health Sciences Centre were searched for embolized AVMs for the 35-year period 1980–2015. All cases were reevaluated for clinical and technical variables and standardized histopathological findings. Cases were grouped by embolic agent, volume of agent used, and time to excision.

RESULTS A total of 101 specimens were identified. Embolic agents were invariably associated with a range of pathological findings, some of which may affect the integrity of vessel walls or the reestablishment of flow, thrombosis, acute and chronic inflammatory changes, angionecrosis, extravasation, and recanalization. The type of embolic agent did not predict differences in the incidence or severity of histopathological changes. Larger volumes of embolic agent were associated with a greater proportion of vessels containing embolic material. AVMs excised early (< 1 week postembolization) contained more acute vasculitis, while those excised later (≥ 1 week postembolization) were more likely to exhibit recanalization and foreign body giant cell infiltrates.

CONCLUSIONS Embolic agents induce a predictable range and temporal progression of pathological changes in cerebral AVMs. The embolic agents studied are indistinguishable in terms of the range and frequency of pathological reactions induced. Greater volumes of embolic agent are associated with more abundant agent within the lesion, but the proportion of vessels and vascular cross-sectional areas containing agent is small. Several changes are significantly associated with time postembolization. Acute vasculitis is a more common finding in the 1st week, while recanalization and foreign body–type granulomatous inflammation are more common at 1 week and beyond.


Risk of First Hemorrhage of Brain Arteriovenous Malformations During Pregnancy

Neurosurgery 85:E806–E814, 2019

Recommendations on the management of brain arteriovenous malformations (bAVM) with respect to pregnancy are based upon conflicting literature.

OBJECTIVE: To systematically review the reported risk and annualized rate of first intracranial hemorrhage (ICH) from bAVM during pregnancy and puerperium.

METHODS: MEDLINE, EMBASE, and Scopus databases were searched for relevant articles in English published before April 2018. Studies providing a quantitative risk of ICH in bAVM during pregnancy were eligible.

RESULTS: From 7 initially eligible studies, 3 studies met the criteria for providing quanti- tative risk of first ICH bAVM during pregnancy. Data from 47 bAVM ICH during pregnancy across 4 cohorts were extracted for analysis. Due to differences in methodology and defini- tions of exposure period, it was not appropriate to combine the cases. The annualized risk of first ICH during pregnancy for these 4 cohorts was 3.0% (95% confidence interval [CI]: 1.7- 5.2%); 3.5% (95% CI: 2.4-4.5%); 8.6% (95% CI: 1.8-25%); and 30% (95% CI: 18-49%). Only the last result from the last cohort could be considered significantly increased in comparison with the nonpregnant period (relative rate 6.8, 95% CI: 3.6-13). The limited number of eligible studies and variability in results highlighted the need for enhanced rigor of future research.

CONCLUSION: There is no conclusive evidence of an increased risk of first hemorrhage during pregnancy from bAVM. Because advice to women with bAVM may influence the management of pregnancy or bAVM with significant consequences, we believe that a retrospective multicenter, case crossover study is urgently required.

Machine learning—aided personalized DTI tractographic planning for deep brain stimulation of the superolateral medial forebrain bundle using HAMLET

Acta Neurochirurgica (2019) 161:1559–1569

Growing interest exists for superolateral medial forebrain bundle (slMFB) deep brain stimulation (DBS) in psychiatric disorders. The surgical approach warrants tractographic rendition. Commercial stereotactic planning systems use deterministic tractography which suffers from inherent limitations, is dependent on manual interaction (ROI definition), and has to be regarded as subjective. We aimed to develop an objective but patient-specific tracking of the slMFB which at the same time allows the use of a commercial surgical planning system in the context of deep brain stimulation.

Methods The HAMLET (Hierarchical Harmonic Filters for Learning Tracts from Diffusion MRI) machine learning approach was introduced into the standardized workflow of slMFB DBS tractographic planning on the basis of patientspecific dMRI. Rendition of the slMFB with HAMLET serves as an objective comparison for the refinement of the deterministic tracking procedure. Our application focuses on the tractographic planning of DBS (N = 8) for major depression and OCD.

Results Previous results have shown that only fibers belonging to the ventral tegmental area to prefrontal/orbitofrontal axis should be targeted. With the proposed technique, the deterministic tracking approach, that serves as the surgical planning data, can be refined, over-sprouting fibers are eliminated, bundle thickness is reduced in the target region, and thereby probably a more accurate targeting is facilitated. The HAMLET-driven method is meant to achieve a more objective surgical fiber display of the slMFB with deterministic tractography.

Conclusions The approach allows overlying the results of patient-specific planning from two different approaches (manual deterministic and machine learningHAMLET). HAMLET shows the slMFB as a volume and thus serves as an objective tracking corridor. It helps to refine results from deterministic tracking in the surgical workspace without interfering with any part of the standard software solution. We have now included this workflow in our daily clinical experimental work on slMFB DBS for psychiatric indications.

Microsurgery for Spetzler-Ponce Class A and B arteriovenous malformations utilizing an outcome score adopted from Gamma Knife radiosurgery

J Neurosurg 127:1105–1116, 2017

The purpose of this study was to adapt and apply the extended definition of favorable outcome established for Gamma Knife radiosurgery (GKRS) to surgery for brain arteriovenous malformations (bAVMs). The aim was to derive both an error around the point estimate and a model incorporating angioarchitectural features in order to facilitate comparison among different treatments.

METHODS A prospective microsurgical cohort was analyzed. This cohort included patients undergoing embolization who did not proceed to microsurgery and patients denied surgery because of perceived risk of treatment. Data on bAVM residual and recurrence during long-term follow-up as well as complications of surgery and preoperative embolization were analyzed. Patients with Spetzler-Ponce Class C bAVMs were excluded because of extreme selection bias. First, patients with a favorable outcome were identified for both Class A and Class B lesions. Patients were considered to have a favorable outcome if they were free of bAVM recurrence or residual at last follow-up, with no complication of surgery or preoperative embolization, and a modified Rankin Scale score of more than 1 at 12 months after treatment. Patients who were denied surgery because of perceived risk, but would otherwise have been candidates for surgery, were included as not having a favorable outcome. Second, the authors analyzed favorable outcome from microsurgery by means of regression analysis, using as predictors characteristics previously identified to be associated with complications. Third, they created a prediction model of favorable outcome for microsurgery dependent upon angioarchitectural variables derived from the regression analysis.

RESULTS From a cohort of 675 patients who were either treated or denied surgery because of perceived risk of surgery, 562 had Spetzler-Ponce Class A or B bAVMs and were included in the analysis. Logistic regression for favorable outcome found decreasing maximum diameter (continuous, OR 0.62, 95% CI 0.51–0.76), the absence of eloquent location (OR 0.23, 95% CI 0.12–0.43), and the absence of deep venous drainage (OR 0.19, 95% CI 0.10–0.36) to be significant predictors of favorable outcome. These variables are in agreement with previous analyses of microsurgery leading to complications, and the findings support the use of favorable outcome for microsurgery. The model developed for angioarchitectural features predicts a range of favorable outcome at 8 years following microsurgery for Class A bAVMs to be 88%–99%. The same model for Class B bAVMs predicts a range of favorable outcome of 62%–90%.

CONCLUSIONS Favorable outcome, derived from GKRS, can be successfully used for microsurgical cohort series to assist in treatment recommendations. A favorable outcome can be achieved by microsurgery in at least 90% of cases at 8 years following microsurgery for patients with bAVMs smaller than 2.5 cm in maximum diameter and, in the absence of either deep venous drainage or eloquent location, patients with Spetzler-Ponce Class A bAVMs of all diameters. For patients with Class B bAVMs, this rate of favorable outcome can only be approached for lesions with a maximum diameter just above 6 cm or smaller and without deep venous drainage or eloquent location.


Cystic Vestibular Schwannomas Respond Best to Radiosurgery

Neurosurgery 81:490–497, 2017

Vestibular schwannomas (VS) have a well-documented response to Gamma Knife R  (Elekta AB, Stockholm, Sweden) Stereotactic radiosurgery (SRS). However, there are limited data available regarding the volumetric response of cystic tumors.

OBJECTIVE: This report correlates the radiographic appearance of VS before radiosurgery with the delayed volumetric response.

METHODS: This study reviewed our SRS experience with 219 VS patients between 2003 and 2013. Patients were treatment naïve and had a significant extracanalicular tumor volume. Magnetic resonance imaging at the time of SRS identified 42 contrast-enhancing macrocystic tumors, 45 contrast-enhancing microcystic tumors, and 132 homogeneously enhancing tumors with no intratumoral cyst formation. The median follow-up was 49.1 months. The median tumor volume was 2.6 cm3 (0.70-16.1 cm3) and the median dose was 12.5 Gy (11-13 Gy).

RESULTS: The actuarial tumor control rate was 99.4% at 2 years and 96.4% at 5 years. A volumetric reduction of >20% occurred in 85.4% of macrocystic tumors, 76.1% of microcystic tumors, and 62.8% of homogeneously enhancing VS. The median volume decrease per year for macrocystic, microcystic, and homogenous tumors was 17.2%, 7.5%, and 7.9% per year respectively (P < .001). A 2:1 blinded volumetric case match showed a significant size reduction in macrocystic tumors compared to noncystic tumors (P = .007). Serviceable hearing was maintained in 61.5% of patients that had Gardner-Robertson grade I-II hearing before treatment. Surgical resection or repeat radiosurgery was performed in 8 patients (3.6%) who had sustained tumor progression.

CONCLUSION: SRS provided VS tumor control in >95% of patients, regardless of radiographic characteristics. Tumor volume regression was most evident in patients with cystic tumors.

Critical review of brain AVMsurgery, surgical results and natural history in 2017

Acta Neurochir (2017) 159:1457–1478

An understanding of the present standing of surgery, surgical results and the role in altering the future morbidity and mortality of untreated brain arteriovenous malformations (bAVMs) is appropriate considering the myriad alternative management pathways (including radiosurgery, embolization or some combination of treatments), varying risks and selection biases that have contributed to confusion regarding management. The purpose of this review is to clarify the link between the incidence of adverse outcomes that are reported from a management pathway of either surgery or no intervention with the projected risks of surgery or no intervention.

Methods A critical review of the literature was performed on the outcomes of surgery and non-intervention for bAVM. An analysis of the biases and how these may have influenced the outcomes was included to attempt to identify reasonable estimates of risks.

Results In the absence of treatment, the cumulative risk of future hemorrhage is approximately 16% and 29% at 10 and 20 years after diagnosis of bAVM without hemorrhage and 35% and 45% at 10 and 20 years when presenting with hemorrhage (annualized, this risk would be approximately 1.8% for unruptured bAVMs and 4.7% for 8 years for bAVMs presenting with hemorrhage followed by the unruptured bAVM rate). The cumulative outcome of these hemorrhages depends upon whether the patient remains untreated and is allowed to have a further hemorrhage or is treated at this time. Overall, approximately 42% will develop a new permanent neurological deficit or death from a hemorrhagic event. The presence of an associated proximal intracranial aneurysm (APIA) and restriction of venous outflow may increase the risk for subsequent hemorrhage. Other risks for increased risk of hemorrhage (age, pregnancy, female) were examined, and their purported association with hemorrhage is difficult to support. Both the Spetzler-Martin grading system (and its compaction into the Spetzler-Ponce tiers) and Lawton-Young supplementary grading system are excellent in predicting the risk of surgery. The 8-year risk of unfavorable outcome from surgery (complication leading to a permanent new neurological deficit with a modified Rankin Scale score of greater than one, residual bAVM or recurrence) is dependent on bAVM size, the presence of deep venous drainage (DVD) and location in critical brain (eloquent location). For patients with bAVMs who have neither a DVD nor eloquent location, the 8-year risk for an unfavorable outcome increases with size (increasing from 1 cm to 6 cm) from 1% to 9%. For patients with bAVMwho have either a DVD or eloquent location (but not both), the 8- year risk for an unfavorable outcome increases with the size (increasing from 1 cm to 6 cm) from 4% to 35%. For patients with bAVM who have both a DVD and eloquent location, the 8-year risk for unfavorable outcome increases with size (increasing from 1 cm to 3 cm) from 12% to 38%.

Conclusion Patients with a Spetzler-Ponce A bAVM expecting a good quality of life for the next 8 years are likely to do better with surgery in expert centers than remaining untreated. Ongoing research is urgently required on the outcome of management pathways for bAVM.

Clinical Experience and Results of Microsurgical Resection of Arteriovenous Malformation in the Presence of Space-Occupying Intracerebral Hematoma

Neurosurgery 81:75–86, 2017

Management of ruptured arteriovenous malformations (AVMs) with a mass-producing intracerebral hematoma (ICH) represents a surgical dilemma.

OBJECTIVE: To evaluate the clinical outcome and obliteration rates of microsurgical resection of AVM when performed concomitantly with evacuation of an associated spaceoccupying ICH.

METHODS: Data of patients with AVMwere collected prospectively. Cases were identified in which an AVM was resected and an associated space-occupying ICH was evacuated at the same time, and divided into “group 1,” in which the surgery was performed acutely within 48 h of presentation (secondary to elevated intracranial pressure); and “group 2,” in which selected patients were operated upon in the presence of a liquefying ICH in the “subacute”stage. Clinical outcomes were assessed using themodified Rankin Scale, with a score of 0 to 2 considered a good outcome. Obliteration rateswere assessed using postoperative angiography.

RESULTS: From 2001 to 2015, 131 patients underwent microsurgical resection of an AVM, of which 65 cases were included. In “group 1” (n = 21; Spetzler-Ponce class A = 13, class B = 5, and class C = 3), 11 of 21 (52%) had a good outcome and in 18 of 19 (95%) of those who had a postoperative angiogramthe AVMswere completely obliterated. In “group 2”(n=44; Spetzler-Ponce class A=33, class B=9, and class C=2), 31 of 44 (93%) had a good outcome and 42 of 44 (95%) were obliterated with a single procedure. For supratentorial AVMs, the ICH cavity was utilized to provide an operative trajectory to a deep AVM in 11 cases, and in 26 cases the ICH cavity was deep to the AVM and hence facilitated the deep dissection of the nidus.

CONCLUSION: In selected patients the presence of a liquefying ICH cavity may facilitate the resection of AVMs when performed in the subacute stage resulting in a good neurological outcome and high obliteration rate.

Transdural arterial recruitment to brain arteriovenous malformation

J Neurosurg 127:51–58, 2017

The occurrence of transdural arterial recruitment (TDAR) in association with brain arteriovenous malformation (bAVM) is uncommon, and the reason for TDAR is not understood. The aim of this cohort study was to examine patient and bAVM characteristics associated with TDAR and the implications of TDAR on management.

METHODS A prospective surgical database of bAVMs was examined. Cases previously treated elsewhere or incompletely examined by digital subtraction angiography (DSA) assessment were excluded. Three studies of this cohort were performed, as follows: characteristics associated with TDAR, the relationship between TDAR and neurological deficits unassociated with hemorrhage (NDUH), and the impact of TDAR on outcome from surgery. Regression models were performed.

RESULTS Of 769 patients with complete DSA who had no previous treatment, 51 (6.6%) were found to have TDAR. The presence of TDAR was associated with increasing age (p < 0.01; OR 1.05; 95% CI 1.02–1.07); presentation with NDUH (p < 0.01; OR 2.71; 95% CI 1.29–5.71); increasing size of the bAVM (p < 0.01; OR 1.57; 95% CI 1.29–1.91); and combined supply from both anterior and posterior circulations (p = 0.02; OR 2.37; 95% CI 1.17–4.78). Further analysis of TDAR cases comparing those with and without NDUH found an association of larger size (6.6 cm [2.9 SD] compared with 4.7 cm [1.8 SD]; p < 0.01) and combined supply from both anterior and posterior circulations (relative risk 2.5; 95% CI 1.0–6.2; p = 0.04) to be associated with an NDUH presentation. For the 632 patients undergoing surgery there was an increased risk of complications (where this produced a new permanent neurological deficit at 12 months represented by a modified Rankin Scale score of > 1) with the following variables: size; location in eloquent brain; deep venous drainage; increasing age; and no presentation with hemorrhage. The presence of TDAR was not associated with an increased risk of complications from surgery.

CONCLUSIONS The authors found that TDAR occurs in older patients with larger bAVMs, and that TDAR is also more likely to be associated with bAVMs presenting with NDUH. The likely explanation for the presence of TDAR is a secondary recruitment arising as a consequence of shear stress, rather than a primary vascular supply present from the earliest development of the bAVM.

The Risk of Seizure After Surgery for Unruptured Intracranial Aneurysms

Incidence of growth and rupture of unruptured intracranial aneurysms followed by serial MRA

Neurosurgery 79:222–230, 2016

We aimed to identify a group of patients with a low risk of seizure after surgery for unruptured intracranial aneurysms (UIA).

OBJECTIVE: To determine the risk of seizure after discharge from surgery for UIA.

METHODS: A consecutive prospectively collected cohort database was interrogated for all surgical UIA cases. There were 726 cases of UIA (excluding cases proximal to the superior cerebellar artery on the vertebrobasilar system) identified and analyzed. Cox proportional hazards regression models and Kaplan-Meier life table analyses were generated assessing risk factors.

RESULTS: Preoperative seizure history and complication of aneurysm repair were the only risk factors found to be significant. The risk of first seizure after discharge from hospital following surgery for patients with neither preoperative seizure, treated middle cerebral artery aneurysm, nor postoperative complications (leading to a modified Rankin Scale score .1) was ,0.1% and 1.1% at 12 months and 7 years, respectively. The risk for those with preoperative seizures was 17.3% and 66% at 12 months and 7 years, respectively. The risk for seizures with either complications (leading to a modified Rankin Scale score .1) from surgery or treated middle cerebral artery aneurysm was 1.4% and 6.8% at 12 months and 7 years, respectively. These differences in the 3 Kaplan-Meier curves were significant (log-rank P , .001).

CONCLUSION: The risk of seizures after discharge from hospital following surgery for UIA is very low when there is no preexisting history of seizures. If this result can be supported by other series, guidelines that restrict returning to driving because of the risk of postoperative seizures should be reconsidered.

Factors Associated With Proximal Intracranial Aneurysms to Brain Arteriovenous Malformations

Factors Associated With Proximal Intracranial Aneurysms to Brain Arteriovenous Malformations

Neurosurgery 78:787–792, 2016

The risk of hemorrhage from a brain arteriovenous malformation (bAVM) is increased when an associated proximal intracranial aneurysm (APIA) is present. Identifying factors that are associated with APIA may influence the prediction of hemorrhage in patients with bAVM.

OBJECTIVE: To identify patient- and bAVM-specific factors associated with APIA.

METHODS: We analyzed a prospective database of bAVMs for factors associated with the presence of APIA. Factors analyzed included age, sex, bAVM size, aneurysm size, circulation contributing to the bAVM, location of the aneurysm, deep venous drainage, and Spetzler-Ponce categories. Multiple logistic regression was performed to identify an association with APIA.

RESULTS: Of 753 cases of bAVM with complete angiographic surveillance, 67 (9%) were found to have APIA. Older age (continuous variable; odds ratio, 1.04; 95% confidence interval, 1.02-1.05) and posterior circulation supply to the bAVM (odds ratio, 2.29; 95% confidence interval, 1.32-3.99) were factors associated with increased detection of APIA. The association of posterior circulation–supplied bAVM was not due to infratentorial bAVM location because 72% of posterior circulation APIAs were supplying supratentorial bAVM.

CONCLUSION: APIAs appear to develop with time, as evident from the increased age for those with APIAs. Furthermore, they were more likely present in bAVMs supplied by the posterior circulation. This may be due to a difference in hemodynamic stress.

Fiber tracts of the dorsal language stream in the human brain

Fiber tracts of the dorsal language stream in the human brain

J Neurosurg 124:1396–1405, 2016

The aim of this study was to examine the arcuate (AF) and superior longitudinal fasciculi (SLF), which together form the dorsal language stream, using fiber dissection and diffusion imaging techniques in the human brain.

Methods Twenty-five formalin-fixed brains (50 hemispheres) and 3 adult cadaveric heads, prepared according to the Klingler method, were examined by the fiber dissection technique. The authors’ findings were supported with MR tractography provided by the Human Connectome Project, WU-Minn Consortium. The frequencies of gyral distributions were calculated in segments of the AF and SLF in the cadaveric specimens.

Results The AF has ventral and dorsal segments, and the SLF has 3 segments: SLF I (dorsal pathway), II (middle pathway), and III (ventral pathway). The AF ventral segment connects the middle (88%; all percentages represent the area of the named structure that is connected to the tract) and posterior (100%) parts of the superior temporal gyri and the middle part (92%) of the middle temporal gyrus to the posterior part of the inferior frontal gyrus (96% in pars opercularis, 40% in pars triangularis) and the ventral premotor cortex (84%) by passing deep to the lower part of the supramarginal gyrus (100%). The AF dorsal segment connects the posterior part of the middle (100%) and inferior temporal gyri (76%) to the posterior part of the inferior frontal gyrus (96% in pars opercularis), ventral premotor cortex (72%), and posterior part of the middle frontal gyrus (56%) by passing deep to the lower part of the angular gyrus (100%).

Conclusions This study depicts the distinct subdivision of the AF and SLF, based on cadaveric fiber dissection and diffusion imaging techniques, to clarify the complicated language processing pathways.

Complication-Effectiveness Analysis for Unruptured Intracranial Aneurysm Surgery

Aneurysm surgery

Neurosurgery 78:648–659, 2016

The aim of intervention for unruptured intracranial aneurysms (UIAs) is safe, effective treatment.

OBJECTIVE: To analyze a prospective database for variables influencing the risk of surgery to produce a risk model adjusting this risk for effectively treated aneurysms.

METHODS: First, we identified variables to create a model from multiple logistic regression for complications of surgery leading to a 12-month modified Rankin Scale score .1. Second, we established the long-term cumulative incidence of freedom from retreatment or rupture (treated aneurysm) from Kaplan-Meier analysis. Third, we combined these analyses to establish a model of risk of surgery per effective treatment.

RESULTS: One thousand twelve patients with 1440 UIA underwent 1080 craniotomies. We found that 10.1% (95% confidence interval [CI], 8.4-12.0) of craniotomies resulted in a complication leading to a modified Rankin Scale score .1 at 12 months. Logistic regression found age (odds ratio, 1.04; 95% CI, 1.02-1.06), size (odds ratio, 1.12; 95% CI, 1.09-1.15), and posterior circulation location (odds ratio, 2.95; 95% CI, 1.82-4.78) to be significant. Cumulative 10-year risk of retreatment or rupture was 3.0% (95% CI, 1.3-7.0). The complication-effectiveness model was derived by dividing the complication risk by the 10-year cumulative freedom from retreatment or rupture proportion. Risk per effective treatment ranged from 1% for a 5-mm anterior circulation UIA in a 20-year-old patient to 70% for a giant posterior circulation UIA in a 70-year-old patient.

CONCLUSION: Complication-effectiveness analyses increase the information available with regard to outcome for the management of UIAs.

Adenosine-induced transient asystole during intracranial aneurysm surgery

Adenosine-induced transient asystole

Acta Neurochir (2015) 157:1879–1886

Several flow-arrest techniques have been introduced for the treatment of complex aneurysms that cannot be treated with conventional clipping or endovascular coil embolization. Adenosine-induced transient asystole is an alternative method of flow arrest. However, given the limited number of studies that have reported on this topic, there is no consensus regarding the dose, regimen, efficacy, and potential risks of adenosine.

Method A total of 22 aneurysms in 22 different patients that underwent adenosine-induced transient asystole during aneurismal neck clipping within the past 4 years were retrospectively reviewed. Adenosine was administrated intravenously in a test-incremental manner (starting with 6–12 mg and then giving additional doses as needed) in 11 patients and in an estimated manner (pre-calculated as 0.3–0.4 mg/kg) in 11 patients.

Results Overall, the study consisted of 18 unruptured saccular aneurysms, three ruptured saccular aneurysms, and a ruptured pseudoaneurysm. Adenosine-induced transient asystole was used in cases of temporary clipping inability, wide necked aneurysm, deep-seated aneurysm, or a thin aneurysm wall. The number of administrations, dose (mg/kg in ideal body weight) and duration of asystole were 1–4 (mean, 2.3) times, 0.08–1.27 (mean, 0.36) mg/kg and 0–30 (mean 13) seconds in the test-incremental manner and 1–2 (mean, 1.09) times, 0.24–0.42 (mean, 0.34) mg/kg and 13–41 (mean, 24) seconds in the estimated manner, respectively. There was a linear relationship between the dose and the duration of asystole. Twenty out of 22 aneurysms were clipped successfully with adenosine-induced transient asystole. However, in the other two cases, additional suction decompression was required for the final clipping. Adenosine-related cardiologic complications occurred in two cases of self-limited atrial fibrillation during restoration of the cardiac rhythm.

Conclusions In our experience, adenosine-induced transient asystole was safe and helpful for satisfactory clipping of a complicated aneurysm. An estimated dose injection of adenosine was more convenient than the test-incremental method and did not result in serious cardiologic problems.

Three-Dimensional Topographic Fiber Tract Anatomy of the Cerebrum

Three-Dimensional Topographic Fiber Tract Anatomy of the Cerebrum

Neurosurgery 11:274–305, 2015

The fiber tracts of the cerebrum may be a more important determinant of resection limits than the cortex. Better knowledge of the 3-dimensional (3-D) anatomic organization of the fiber pathways is important in planning safe and accurate surgery for lesions within the cerebrum.

OBJECTIVE: To examine the topographic anatomy of fiber tracts and subcortical gray matter of the human cerebrum and their relationships with consistent cortical, ventricular, and nuclear landmarks.

METHODS: Twenty-five formalin-fixed human brains and 4 whole cadaveric heads were examined by fiber dissection technique and ·6 to ·40 magnification. The fiber tracts and central core structures, including the insula and basal ganglia, were examined and their relationships captured in 3-D photography. The depth between the surface of the cortical gyri and selected fiber tracts was measured.

RESULTS: The topographic relationships of the important association, projection, and commissural fasciculi within the cerebrum and superficial cortical landmarks were identified. Important landmarks with consistent relationships to the fiber tracts were the cortical gyri and sulci, limiting sulci of the insula, nuclear masses in the central core, and lateral ventricles. The fiber tracts were also organized in a consistent pattern in relation to each other. The anatomic findings are briefly compared with functional data from clinicoradiological analysis and intraoperative stimulation of fiber tracts.

CONCLUSION: An understanding of the 3-D anatomic organization of the fiber tracts of the brain is essential in planning safe and accurate cerebral surgery.

Flow-Diverter Devices for Intracranial Aneurysms

Flow-Diverter Devices for Intracranial Aneurysms

Neurosurgery 73:193–200, 2013

Although the introduction of flow-diverter devices (FDDs) has aroused great enthusiasm, the level of evidence supporting their use has not been systematically evaluated.

OBJECTIVE: To report a systematic review of medical literature up to May 2012 on FDDs to assess the morbidity, case fatality rate, and efficacy of FDDs for intracranial aneurysms.

METHODS: The literature was searched by using MEDLINE, Embase, and all Evidence- Based Medicine in the OVID database. Eligibility criteria were studies including at least 10 patients, reporting duration of follow-up and number of patients lost to follow-up, and documenting the rate of aneurysm occlusion and death and neurological complications. The endpoints were angiographic success, early and late mortality, and neurological morbidity.

RESULTS: Fifteen studies were analyzed consisting of 897 patients with 1018 aneurysms. The mean value of methodological quality score was 14.4 using the STROBE score. The early mortality rate was 2.8% (95% confidence interval [CI]: 1.7-3.8; I2 = 93.4%) and the late mortality rate was 1.3% (95% CI: 0.2-2.3; I2 = 36.9%). The early neurological morbidity rate was 7.3% (95% CI: 5.7-9; I2 = 91.8%) and the late morbidity rate was 2.6% (95% CI: 1.1-4; I2 = 81.3%). The Egger test for early and late morbidity and aneurysm occlusion was ,0.001.

CONCLUSION: With the available data from the studies, both heterogeneity and publication biases imply that the current clinical use of FDDs is not supported by highquality evidence. In the absence of reliable evidence, the use of FDDs in patients eligible for more conventional treatments should be restricted to controlled clinical trials.

Intraoperative Seizures During Awake Craniotomy: Incidence and Consequences: Analysis of 477 Patients

Awake cranio

Neurosurgery 73:135–140, 2013

Awake craniotomy (AC) for removal of intra-axial brain tumors is a well-established procedure. However, the occurrence and consequences of intraoperative seizures during AC have not been well characterized.

OBJECTIVE: To analyze the incidence, risk factors, and consequences of seizures during AC.

METHODS: The database of AC at Tel Aviv Medical Center between 2003 to 2011 was reviewed. Occurrences of intraoperative seizures were analyzed with respect to medical history, medications, tumor characteristics, and postoperative outcome.

RESULTS: Of the 549 ACs performed during the index period, 477 with complete records were identified. Sixty patients (12.6%) experienced intraoperative seizures. The AC procedure failed in 11 patients (2.3%) due to seizures. Patients with intraoperative seizures were significantly younger than nonseizing patients (45 6 14 years vs 52 6 16 years, P = .003), had a higher incidence of frontal lobe involvement (86% vs % 57%, P , .0001), and had higher prevalence of a history of seizures (P = .008). Short-term motor deterioration developed postoperatively in a higher percentage of patients with intraoperative seizures (20% vs 10.1%, P = .02) with a longer hospitalization period (4.0 6 3.0 days vs 3.0 6 3.0 days, P = .045).

CONCLUSION: Although in most cases intraoperative seizures will not result in AC failure, the surgical team should be prepared to treat them promptly to avoid intractable seizures. Intraoperative seizures are more common in younger patients with a tumor in the frontal lobe and those with a history of seizures. Moreover, they are associated with a higher incidence of transient postoperative motor deterioration and protracted length of hospital stay.

The failure of preoperative ethylene-vinyl alcohol copolymer embolization to improve outcomes in arteriovenous malformation management: case series


J Neurosurg 118:969–977, 2013

Ethylene-vinyl alcohol copolymer embolization is increasingly used preoperatively in the resection of brain arteriovenous malformations (AVMs). However, the case for embolization improving the outcome of resection has not been evaluated. In this paper the authors set out to compare outcomes after surgery for brain AVMs in 2 consecutive periods of practice. In the first period, selective embolization was used without the use of ethylene-vinyl alcohol copolymer. In the second period, selective embolization with ethylene-vinyl alcohol copolymer was performed.

Methods. A consecutive case series (prospectively collected data) was retrospectively analyzed. Adverse outcomes were considered to be an outcome modified Rankin Scale score greater than 2 due to embolization or surgery.

Results. A total of 538 surgical cases were included. The percentages of adverse outcomes were as follows: 0.34% for Spetzler-Martin AVMs less than Grade III (1 of 297 cases); 5.23% (95% CI 2.64%–9.78%) for Grade III AVMs (9 of 172 cases); and 17% (95% CI 10%–28%) for AVMs greater than Grade III (12 of 69 cases). There was no improvement in outcomes from the first period to the second period. The adverse outcome for Grade III brain AVMs in the first period was 5.2% (7 of 135 cases) and in the second period (after ethylene-vinyl alcohol copolymer was introduced) it was 5.4% (2 of 37 cases). For AVMs greater than Grade III, the adverse outcome was 12% (6 of 49 cases) in the first period and 30% (6 of 20 cases) in the second period.

Conclusions. Outcomes for brain AVM surgery were not improved by ethylene-vinyl alcohol copolymer embolization. Preoperative embolization of high-grade AVMs with an ethylene-vinyl alcohol copolymer did not prevent those hemorrhagic complications which embolization is hypothesized to prevent based on theoretical speculations but not demonstrated in practice.

Failed awake craniotomy: a retrospective analysis in 424 patients undergoing craniotomy for brain tumor

Awake cranio

J Neurosurg 118:243–249, 2013

Awake craniotomy for removal of intraaxial tumors within or adjacent to eloquent brain regions is a well-established procedure. However, awake craniotomy failures have not been well characterized. In the present study, the authors aimed to analyze and assess the incidence and causes for failed awake craniotomy.

Methods. The database of awake craniotomies performed at Tel Aviv Medical Center between 2003 and 2010 was reviewed. Awake craniotomy was considered a failure if conversion to general anesthesia was required, or if adequate mapping or monitoring could not have been achieved.

Results. Of 488 patients undergoing awake craniotomy, 424 were identified as having complete medical, operative, and anesthesiology records. The awake craniotomies performed in 27 (6.4%) of these 424 patients were considered failures. The main causes of failure were lack of intraoperative communication with the patient (n = 18 [4.2%]) and/or intraoperative seizures (n = 9 [2.1%]). Preoperative mixed dysphasia (p < 0.001) and treatment with phenytoin (p = 0.0019) were related to failure due to lack of communication. History of seizures (p = 0.03) and treatment with multiple antiepileptic drugs (p = 0.0012) were found to be related to failure due to intraoperative seizures. Compared with the successful awake craniotomy group, a significantly lower rate of gross-total resection was achieved (83% vs 54%, p = 0.008), there was a higher incidence of short-term speech deterioration postoperatively (6.1% vs 23.5%, p = 0.0017) as well as at 3 months postoperatively (2.3% vs 15.4%, p = 0.0002), and the hospitalization period was longer (4.9 ± 6.2 days vs 8.0 ± 10.1 days, p < 0.001). Significantly more major complications occurred in the failure group (4 [14.8%] of 27) than in the successful group (16 [4%] of 397) (p = 0.037).

Conclusions. Failures of awake craniotomy were associated with a lower incidence of gross-total resection and increased postoperative morbidity. The majority of awake craniotomy failures were preventable by adequate patient selection and avoiding side effects of drugs administered during surgery.