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Validation of a prognostic score for early mortality in severe head injury cases

Brain_trauma_CT

J Neurosurg 121:1314–1322, 2014

Traumatic brain injury (TBI) represents a large health and economic burden. Because of the inability of previous randomized controlled trials (RCTs) on TBI to demonstrate the expected benefit of reducing unfavorable outcomes, the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in TBI) and CRASH (Corticosteroid Randomisation After Significant Head Injury) studies provided new methods for performing prognostic studies of TBI. This study aimed to develop and externally validate a prognostic model for early death (within 48 hours). The secondary aim was to identify patients who were more likely to succumb to an early death to limit their inclusion in RCTs and to improve the efficiency of RCTs.

Methods. The derivation cohort was recruited at 1 center, Hospital 12 de Octubre, Madrid (1990–2003, 925 patients). The validation cohort was recruited in 2004–2006 from 7 study centers (374 patients). The eligible patients had suffered closed severe TBIs. The study outcome was early death (within 48 hours post-TBI). The predictors were selected using logistic regression modeling with bootstrapping techniques, and a penalized reduction was used. A risk score was developed based on the regression coefficients of the variables included in the final model.

Results. In the validation set, the final model showed a predictive ability of 50% (Nagelkerke R2), with an area under the receiver operating characteristic curve of 89% and an acceptable calibration (goodness-of-fit test, p = 0.32). The final model included 7 variables, and it was used to develop a risk score with a range from 0 to 20 points. Age provided 0, 1, 2, or 3 points depending on the age group; motor score provided 0 points, 2 (untestable), or 3 (no response); pupillary reactivity, 0, 2 (1 pupil reacted), or 6 (no pupil reacted); shock, 0 (no) or 2 (yes); subarachnoid hemorrhage, 0 or 1 (severe deposit); cisternal status, 0 or 3 (compressed/absent); and epidural hematoma, 0 (yes) or 2 (no). Based on the risk of early death estimated with the model, 4 risk of early death groups were established: low risk, sum score 0–3 (< 1% predicted mortality); moderate risk, sum score 4–8 (predicted mortality between 1% and 10%); high risk, sum score 9–12 (probability of early death between 10% and 50%); and very high risk, sum score 13–20 (early mortality probability > 50%). This score could be used for selecting patients for clinical studies. For example, if patients with very high risk scores were excluded from our study sample, the patients included (eligibility score < 13) would represent 80% of the original sample and only 23% of the patients who died early.

Conclusions. The combination of Glasgow Coma Scale score, CT scanning results, and secondary insult data into a prognostic score improved the prediction of early death and the classification of TBI patients.

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Ultrasonic Total Uncinectomy

Ultrasonic Total Uncinectomy

Operative Neurosurgery 10:535–541, 2014

In standard anterior cervical diskectomy, complete resection of the uncinate process is not commonly attempted because of the risk of injury to the vertebral artery. This may result in incomplete decompression of the nerve root when there is severe osseous foraminal stenosis.

OBJECTIVE: To demonstrate the feasibility of total uncinectomy with an ultrasonic bone dissector in patients with concomitant central and foraminal stenosis requiring anterior decompression and fusion.

METHODS: A case series of patients with cervical radiculopathy or myeloradiculopathy who underwent single-level or multilevel ultrasonic total uncinectomy (UTU) in combination with anterior cervical diskectomy and fusion is presented. The uncinate process was amputated along its base with an ultrasonic bone dissector and removed en bloc to expose the cervical root and the vertebral artery. Data gathered in accordance with routine practice were analyzed retrospectively.

RESULTS: Forty-four uncinate processes were resected in 38 patients. No UTU procedures were aborted because of technical difficulties, and no vertebral artery or nerve root injury occurred. Mean follow-up was 28 weeks (range, 14-37 weeks). Mean Neck Disability Index and Visual Analog Scale scores for neck and arm pain improved from 42%, 4.9%, and 6.8% to 23%, 2.6%, and 2.1%, respectively. Postoperative computed tomography and oblique radiographs revealed complete decompression of the neural foramen after UTU.

CONCLUSION: UTU is a safe and effective technique for complete decompression of cervical nerve roots when the coexistence of central and foraminal pathology dictates an anterior approach. The surgical technique is described in detail.

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Three-Dimensional Microsurgical Anatomy and the Safe Entry Zones of the Brainstem

Three-Dimensional Microsurgical Anatomy and the Safe Entry Zones of the Brainstem

Operative Neurosurgery 10:602–620, 2014

There have been no studies of the structure and safe surgical entry zones of the brainstem based on fiber dissection studies combined with 3-dimensional (3-D) photography.

OBJECTIVE: To examine the 3-D internal architecture and relationships of the proposed safe entry zones into the midbrain, pons, and medulla.

METHODS: Fifteen formalin and alcohol-fixed human brainstems were dissected by using fiber dissection techniques, ·6 to ·40 magnification, and 3-D photography to define the anatomy and the safe entry zones. The entry zones evaluated were the perioculomotor, lateral mesencephalic sulcus, and supra- and infracollicular areas in the midbrain; the peritrigeminal zone, supra- and infrafacial approaches, acoustic area, and median sulcus above the facial colliculus in the pons; and the anterolateral, postolivary, and dorsal medullary sulci in the medulla.

RESULTS: The safest approach for lesions located below the surface is usually the shortest and most direct route. Previous studies have often focused on surface structures. In this study, the deeper structures that may be at risk in each of the proposed safe entry zones plus the borders of each entry zone were defined. This study includes an examination of the relationships of the cerebellar peduncles, long tracts, intra-axial segments of the cranial nerves, and important nuclei of the brainstem to the proposed safe entry zones.

CONCLUSION: Fiber dissection technique in combination with the 3-D photography is a useful addition to the goal of making entry into the brainstem more accurate and safe.

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Localizing hand motor area using resting-state fMRI: validated with direct cortical stimulation

resting

Acta Neurochir (2014) 156:2295–2302

Resting-state functional magnetic resonance imaging (R-fMRI) is a promising tool in clinical application, especially in presurgicalmapping for neurosurgery. This study aimed to investigate the sensitivity and specificity of R-fMRI in the localization of hand motor area in patients with brain tumors validated by direct cortical stimulation (DCS).We also compared this technique to task-based blood oxygenation level-dependent (BOLD) fMRI (T-fMRI).

Methods R-fMRI and T-fMRI were acquired from 17 patients with brain tumors. The cortex sites of the hand motor area were recorded by DCS. Site-by-site comparisons between R-fMRI/TfMRI andDCS were performed to calculate R-fMRI and T-fMRI sensitivity and specificity using DCS as a “gold standard”. RfMRI and T-fMRI performances were compared statistically

Results A total of 609 cortex sites were tested with DCS and compared with R-fMRI findings in 17 patients. For hand motor area localization, R-fMRI sensitivity and specificity were 90.91 and 89.41%, respectively. Given that two subjects could not comply with T-fMRI, 520 DCS sites were compared with T-fMRI findings in 15 patients. The sensitivity and specificity of T-fMRI were 78.57 and 84.76 %, respectively. In the 15 patients who successfully underwent both R-fMRI and T-fMRI, there was no statistical difference in sensitivity or specificity between the two methods (p=0.3198 and p= 0.1431, respectively)

Conclusions R-fMRI sensitivity and specificity are high for localizing hand motor area and even equivalent or slightly higher compared with T-fMRI. Given its convenience for patients, R-fMRI is a promising substitute for T-fMRI for pre-surgical mapping.

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A comparison of lumboperitoneal and ventriculoperitoneal shunting for idiopathic intracranial hypertension

IIH

Neurosurg Focus 37 (5):E4, 2014

Complications following lumboperitoneal (LP) shunting have been reported in 18% to 85% of cases. The need for multiple revision surgeries, development of iatrogenic Chiari malformation, and frequent wound complications have prompted many to abandon this procedure altogether for the treatment of idiopathic benign intracranial hypertension (pseudotumor cerebri), in favor of ventriculoperitoneal (VP) shunting. A direct comparison of the complication rates and health care charges between first-choice LP versus VP shunting is presented.

Methods. The Nationwide Inpatient Sample database was queried for all patients with the diagnosis of benign intracranial hypertension (International Classification of Diseases, Ninth Revision, code 348.2) from 2005 to 2009. These data were stratified by operative intervention, with demographic and hospitalization charge data generated for each.

Results. A weighted sample of 4480 patients was identified as having the diagnosis of idiopathic intracranial hypertension (IIH), with 2505 undergoing first-time VP shunt placement and 1754 undergoing initial LP shunt placement. Revision surgery occurred in 3.9% of admissions (n = 98) for VP shunts and in 7.0% of admissions (n = 123) for LP shunts (p < 0.0001). Ventriculoperitoneal shunts were placed at teaching institutions in 83.8% of cases, compared with only 77.3% of first-time LP shunts (p < 0.0001). Mean hospital length of stay (LOS) significantly differed between primary VP (3 days) and primary LP shunt procedures (4 days, p < 0.0001). The summed charges for the revisions of 92 VP shunts ($3,453,956) and those of the 6 VP shunt removals ($272,484) totaled $3,726,352 over 5 years for the study population. The summed charges for revision of 70 LP shunts ($2,229,430) and those of the 53 LP shunt removals ($3,125,569) totaled $5,408,679 over 5 years for the study population.

Conclusions. The presented results appear to call into question the selection of LP shunt placement as primary treatment for IIH, as this procedure is associated with a significantly greater likelihood of need for shunt revision, increased LOS, and greater overall charges to the health care system.

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The stereotactic approach for mapping epileptic networks

pb-red28

J Neurosurg 121:1239–1246, 2014

Stereoelectroencephalography (SEEG) is a methodology that permits accurate 3D in vivo electroclinical recordings of epileptiform activity. Among other general indications for invasive intracranial electroencephalography (EEG) monitoring, its advantages include access to deep cortical structures, its ability to localize the epileptogenic zone when subdural grids have failed to do so, and its utility in the context of possible multifocal seizure onsets with the need for bihemispheric explorations. In this context, the authors present a brief historical overview of the technique and report on their experience with 2 SEEG techniques (conventional Leksell frame-based stereotaxy and frameless stereotaxy under robotic guidance) for the purpose of invasively monitoring difficult-to-localize refractory focal epilepsy.

Methods. Over a period of 4 years, the authors prospectively identified 200 patients with refractory epilepsy who collectively underwent 2663 tailored SEEG electrode implantations for invasive intracranial EEG monitoring and extraoperative mapping. The first 122 patients underwent conventional Leksell frame-based SEEG electrode placement; the remaining 78 patients underwent frameless stereotaxy under robotic guidance, following acquisition of a stereotactic ROSA robotic device at the authors’ institution. Electrodes were placed according to a preimplantation hypothesis of the presumed epileptogenic zone, based on a standardized preoperative workup including video-EEG monitoring, MRI, PET, ictal SPECT, and neuropsychological assessment. Demographic features, seizure semiology, number and location of implanted SEEG electrodes, and location of the epileptogenic zone were recorded and analyzed for all patients. For patients undergoing subsequent craniotomy for resection, the type of resection and procedure-related complications were prospectively recorded. These results were analyzed and correlated with pathological diagnosis and postoperative seizure outcomes.

Results. The epileptogenic zone was confirmed by SEEG in 154 patients (77%), of which 134 (87%) underwent subsequent craniotomy for epileptogenic zone resection. Within this cohort, 90 patients had a minimum follow-up of at least 12 months; therein, 61 patients (67.8%) remained seizure free, with an average follow-up period of 2.4 years. The most common pathological diagnosis was focal cortical dysplasia Type I (55 patients, 61.1%). Per electrode, the surgical complications included wound infection (0.08%), hemorrhagic complications (0.08%), and a transient neurological deficit (0.04%) in a total of 5 patients (2.5%). One patient (0.5%) ultimately died due to intracerebral hematoma directly ensuing from SEEG electrode placement.

Conclusions. Based on these results, SEEG methodology is safe, reliable, and effective. It is associated with minimal morbidity and mortality, and serves as a practical, minimally invasive approach to extraoperative localization of the epileptogenic zone in patients with refractory epilepsy.

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Joint Indexes for the Craniovertebral Junction

New Indexes for the Craniovertebral Junction

Neurosurgery 10:621–630, 2014

Joint-distraction and intra-operative manipulation surgeries to correct basilar invagination (BI) and atlantoaxial dislocation (AAD) are becoming standard procedures. However, current data are unable to aid in the understanding of normal and abnormal morphology of the C1/C2 joints.

OBJECTIVE: To study various aspects of C1/C2 joint morphology to create normative and patient data on joint abnormalities that could provide the surgeon with objective data for surgical planning and approach.

METHODS: Seventy patients (age, 15-45 years) were compared with an equal number of age- and sex-matched control subjects (age, 21.9±8.2 years) with irreducible BI and AAD from a developmental origin (May 2010-July 2013). Joint anatomy was studied with the use of thin-slice computed tomography scans. The joint parameters studied included sagittal joint inclination, craniocervical tilt, coronal joint inclination, surface area, joint overlap index, and joint reciprocity. The severity of BI and the severity of AAD were compared.

RESULTS: Sagittal joint inclination and craniocervical tilt significantly correlated with both BI and AAD (P , .01). Coronal joint inclination correlated with BI (P = .2). The mean sagittal joint inclination value in control subjects was 87.15±5.65 and in patients with BI and AAD was 127.1±22.05. The mean craniocervical tilt value in controls was 60.2±9.2 and in patients with BI and AAD was 84.0±15.1. The mean coronal joint inclination value in control subjects was 110.3±4.23 and in patients with BI and AAD was 121.15±14.6.

CONCLUSION: This study has demonstrated for the first time the important role of joint orientation and its correlation with the severity of BI and AAD and has described new joint indexes.

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Minimally invasive lateral fusion for adjacent disease

Minimally invasive lateral interbody fusion for the treatment of rostral adjacent-segment lumbar degenerative stenosis without supplemental pedicle screw fixation

J Neurosurg Spine 21:861–866, 2014

Adjacent-segment degeneration and stenosis are common in patients who have undergone previous lumbar fusion. Treatment typically involves a revision posterior approach, which requires management of postoperative scar tissue and previously implanted instrumentation. A minimally invasive lateral approach allows the surgeon to potentially reduce the risk of these hazards. The technique relies on indirect decompression to treat central and foraminal stenosis and placement of a graft with a large surface area to promote robust fusion and stability in concert with the surrounding tensioned ligaments. The goal in this study was to determine if lateral interbody fusion without supplemental pedicle screws is effective in treating adjacent-segment disease.

Methods. For a 30-month study period at two institutions, the authors obtained all cases of lumbar fusion with new back and leg pain due to adjacent-segment stenosis and spondylosis failing conservative measures. All patients had undergone minimally invasive lateral interbody fusion from the side of greater leg pain without supplemental pedicle screw fixation. Patients were excluded from the study if they had undergone surgery for a nondegenerative etiology such as infection or trauma. They were also excluded if the intervention involved supplemental posterior instrumented fusion with transpedicular screws. Postoperative metrics included numeric pain scale (NPS) scores for leg and back pain. All patients underwent dynamic radiographs and CT scanning to assess stability and fusion after surgery.

Results. During the 30-month study period, 21 patients (43% female) were successfully treated using minimally invasive lateral interbody fusion without the need for subsequent posterior transpedicular fixation. The mean patient age was 61 years (range 37–87 years). Four patients had two adjacent levels fused, while the remainder had single-level surgery. All patients underwent surgery without conversion to a traditional open technique, and recombinant human bone morphogenetic protein–2 was used in the interbody space in all cases. The mean follow-up was 23.6 months. The mean operative time was 86 minutes, and the mean blood loss was 93 ml. There were no major intraoperative complications, but one patient underwent subsequent direct decompression in a delayed fashion. The leg pain NPS score improved from a mean of 6.3 to 1.9 (p < 0.01), and the back pain NPS score improved from a mean of 7.5 to 2.9 (p < 0.01). Intervertebral settling averaged 1.7 mm. All patients had bridging bone on CT scanning at the last follow-up, indicating solid bony fusion.

Conclusions. Adjacent-segment stenosis and spondylosis can be treated with a number of different operative techniques. Lateral interbody fusion provides an attractive alternative with reduced blood loss and complications, as there is no need to re-explore a previous laminectomy site. In this limited series a minimally invasive lateral approach provided high fusion rates when performed with osteobiological adjuvants.

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Subdural motor cortex stimulation

Subdural motor cortex stimulation

Acta Neurochir (2014) 156:2289–2294

Motor cortex stimulation (MCS) is considered to be an effective treatment in some types of chronic refractory neuropathic pain. The aim of this study is to evaluate and confirm the feasibility, efficacy and security of our surgical technique for subdural motor cortex stimulation (SDMCS) on 18 consecutive cases with follow-up of at least 3 years.

Methods Our population consists of 18 consecutive patients (12male) between 2000 and 2010,with a mean age of 63 years (11–91). The mean follow-up was 86 months (20–140 months). We identified the central sulcus by using classical anatomic landmarks and neuronavigation (BrainLab system; BrainLAB, Inc., Redwood City, CA). An elongated craniotomy (3 cm in length, 1 cm in width)was performed followed by linear opening of the dura mater. An eight-polar plate electrode (Specify Lead, 3998;Medtronic,Minneapolis,MN) was then slipped smoothly through this linear opening. In patients with interhemispheric electrodes (patients 2 and 17), we performed a parasagittal craniotomy of 4 cm length and 2 cm width.

Results At last follow-up assessment, 14 patients had a favourable outcome (77.7 %): 10 patients with excellent relief of pain (>80 %), 1 with good relief of pain (60–80 %) and 3 with satisfactory relief of pain (50–60 %). Four patients showed bad results (<50 %). We did not observe any late complications specific to SD MCS.

Conclusion We report an efficacy at least as good as ED MCS, with no complications specific to SD MCS, even with prolonged follow-up. The data are insufficient to actually prove a lower energy use in SD MCS.

Keywords Neuropathic pain , Neurostimulation , Motor cortex stimulation, Subdural

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The 1-piece transbasal approach

The 1-piece transbasal approach

J Neurosurg 121:1446–1452, 2014

The transbasal approach (TBA) is an anterior skull base approach, which provides access to the anterior skull base, sellar-suprasellar region, and clivus. The TBA typically involves a bifrontal craniotomy with orbital bar and/or nasal bone osteotomies performed in 2 separate steps. The authors explored the feasibility of routinely performing this approach in 1 piece with a quantitative cadaveric anatomical study, and present an operative case example of their approach.

Methods. Seven latex-injected cadaveric heads underwent a 1-piece TBA, followed by additional bone removal typical for a traditional 2-piece approach. Six surgical angles relative to the pituitary stalk, as well as the surface area of the orbital roof osteotomy, were measured before and after additional bone removal. The vertical angle from the frontonasal suture to the foramen cecum was measured in all specimens. In addition to an anatomical study, the authors have used this technique in the operating room, and present an illustrative case of resection of an anterior skull base meningioma.

Results. Morphometric results were as follows: the vertical angle from the frontonasal suture to the foramen cecum ranged from 17.4° to 29.7° (mean 23.8° ± 4.8°) superiorly. Of the 6 surgical angle measures, only the middle horizontal angle was increased in the 2-piece versus the 1-piece approach (mean 43.4° ± 4.6° vs 43.0° ± 4.3°, respectively; p = 0.049), with a mean increase of 0.4°. The surface area of the orbital osteotomy was increased in the 2-piece versus the 1-piece approach (mean 2467 mm2 ± 360 mm2 vs 2045 mm2 ± 352 mm2, respectively; p < 0.001). The patient in the illustrative clinical case had a good outcome, both clinically and cosmetically.

Conclusions. The 1-piece TBA provides an alternative to the traditional 2-piece approach. It allows easier reconstruction, potentially decreased operative time, and improved cosmesis. While more of the orbital roof can be removed with the 2-piece approach, this additional bone removal offers only a small increase in 1 of 6 surgical angles that were measured.

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Endoscope-Assisted Retrosigmoid Intradural Suprameatal Approach for Surgical Treatment of Trigeminal Schwannomas

Endoscope-Assisted Retrosigmoid Intradural Suprameatal Approach

Operative Neurosurgery 10:565–575, 2014

Trigeminal schwannomas are the most common intracranial nonvestibular schwannomas, and the dumbbell-shaped subtype is the most challenging.

OBJECTIVE: To evaluate the efficiency and safety of the endoscope-assisted retrosigmoid intradural suprameatal approach (EA-RISA) for dumbbell trigeminal schwannomas and to compare EA-RISA with classic RISA.

METHODS: A retrospective study of all patients with trigeminal schwannomas was performed with a focus on dumbbell tumors. Tumors were classified according to a modified Samii classification. Extent of tumor removal, outcome, and morbidity rates in the 2 subgroups were compared.

RESULTS: Twenty patients were enrolled: 8 had dumbbell-shaped tumors (type C1), 8 had middle fossa tumors (A1-3), 3 had extracranial extension (D2), and 1 had posterior fossa tumor. Gross total resection was achieved in 15 and near-total resection in 5 patients. In 4 patients with dumbbell tumors, the classic RISA (Samii approach) was used; EA-RISA was used in the other 4 patients. The extent of petrous apex drilling was determined individually on the basis of the anatomic variability of suprameatal tubercle and degree of tumor-induced petrous apex erosion; in 2 patients, only minimal drilling was needed. The endoscope was applied after microsurgical tumor removal and in 3 of 4 patients revealed a significant unrecognized tumor remnant in the anterolateral and superolateral aspects of the Meckel cave. Thus, the EA-RISA technique allowed gross total resection of the tumor.

CONCLUSION: The EA-RISA enlarges the exposure obtained with the classic RISA. Its judicious use can help achieve safe and radical removal of dumbbell-shaped trigeminal schwannomas (C1 type).

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Localizing hand motor area using resting-state fMRI

Localizing hand motor area using resting-state fMRI

Acta Neurochir (2014) 156:2295–2302

Resting-state functional magnetic resonance imaging (R-fMRI) is a promising tool in clinical application, especially in presurgicalmapping for neurosurgery. This study aimed to investigate the sensitivity and specificity of R-fMRI in the localization of hand motor area in patients with brain tumors validated by direct cortical stimulation (DCS).We also compared this technique to task-based blood oxygenation level-dependent (BOLD) fMRI (T-fMRI).

Methods R-fMRI and T-fMRI were acquired from 17 patients with brain tumors. The cortex sites of the hand motor area were recorded by DCS. Site-by-site comparisons between R-fMRI/TfMRI andDCS were performed to calculate R-fMRI and T-fMRI sensitivity and specificity using DCS as a “gold standard”. RfMRI and T-fMRI performances were compared statistically

Results A total of 609 cortex sites were tested with DCS and compared with R-fMRI findings in 17 patients. For hand motor area localization, R-fMRI sensitivity and specificity were 90.91 and 89.41%, respectively. Given that two subjects could not comply with T-fMRI, 520 DCS sites were compared with T-fMRI findings in 15 patients. The sensitivity and specificity of T-fMRI were 78.57 and 84.76 %, respectively. In the 15 patients who successfully underwent both R-fMRI and T-fMRI, there was no statistical difference in sensitivity or specificity between the two methods (p=0.3198 and p= 0.1431, respectively)

Conclusions R-fMRI sensitivity and specificity are high for localizing hand motor area and even equivalent or slightly higher compared with T-fMRI. Given its convenience for patients, R-fMRI is a promising substitute for T-fMRI for pre surgical mapping.

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Flow-Diverting Stents for Intracranial Bifurcation Aneurysm Treatment

Flowdiverter

Neurosurgery 75:623–631, 2014

Although initially considered safe when covering bifurcation sites, flow-diverting stents may provoke thrombosis of side branches that are covered during aneurysm treatment.

OBJECTIVE: To understand the occurrence and clinical expression of side-branch remodeling in distal intracranial arterial sites after flow diverter deployment by means of correlation of imaging and clinical data.

METHODS: We analyzed our prospectively collected data on a series of patients treated with flow diverters for intracranial aneurysms at bifurcation sites. From February 2011 to May 2013, 32 patients with 37 aneurysms (anterior communicating artery, 9 [24.3%]; anterior cerebral artery, 5 [13.5%]; middle cerebral artery, 19 (51.4%); terminal internal carotid artery, 4 [10.8%]) were treated. We divided aneurysms into 2 groups based on the side branches covered by the stent during treatment. Group A consisted of cases with side branches that supplied brain territories also receiving a direct collateral supply. Group B consisted of cases in which side branches supplied territories without direct collateral supply. The 2 groups were compared statistically.

RESULTS: Total exclusion occurred in 97.3% of aneurysms at follow-up. Initial modified Rankin Scale (mRS) score was 0 to 1 for 29 patients (90.6%) and 2 for 3 patients (9.4%). New permanent neurological deficit was reported in 3 patients (9.4%). At the 6-month follow-up, the mRS score was 0 to 1 for 31 patients (96.8%) and 3 for 1 patient (3.2%). Although 78.5% of side branches in group A underwent narrowing or occlusion after 6 months, no new stroke was found on magnetic resonance imaging.

CONCLUSION: Symptomatic modifications of side branches after flow diverter treatment depend on the extent and type of collateral supply.

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The role of cancer stem cells in glioblastoma

The role of cancer stem cells in glioblastoma

Neurosurg Focus 37 (6):E6, 2014

Recurrence in glioblastoma is nearly universal, and its prognosis remains dismal despite significant advances in treatment over the past decade. Glioblastoma demonstrates considerable intratumoral phenotypic and molecular heterogeneity and contains a population of cancer stem cells that contributes to tumor propagation, maintenance, and treatment resistance. Cancer stem cells are functionally defined by their ability to self-renew and to differentiate, and they constitute the diverse hierarchy of cells composing a tumor. When xenografted into an appropriate host, they are capable of tumorigenesis.

Given the critical role of cancer stem cells in the pathogenesis of glioblastoma, research into their molecular and phenotypic characteristics is a therapeutic priority.

In this review, the authors discuss the evolution of the cancer stem cell model of tumorigenesis and describe the specific role of cancer stem cells in the pathogenesis of glioblastoma and their molecular and microenvironmental characteristics. They also discuss recent clinical investigations into targeted therapies against cancer stem cells in the treatment of glioblastoma.

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Widening of the basilar bifurcation angle: association with presence of intracranial aneurysm, age, and female sex

Basilar art. bif.

J Neurosurg 121:1401–1410, 2014

Arterial bifurcations represent preferred locations for aneurysm formation, especially when they are associated with variations in divider geometry. The authors hypothesized a link between basilar apex aneurysms and basilar bifurcation (a) and vertebrobasilar junction (VBJ) angles.

Methods. The a and VBJ angles were measured in 3D MR and rotational angiographic volumes using a coplanar 3-point technique. Angle a was compared between age-matched cohorts in 45 patients with basilar artery (BA) aneurysms, 65 patients with aneurysms in other locations (non-BA), and 103 nonaneurysmal controls. Additional analysis was performed in 273 nonaneurysmal controls. Computational fluid dynamics (CFD) simulations were performed on parametric BA models with increasing angles.

Results. Angle a was significantly wider in patients with BA aneurysms (146.7° ± 20.5°) than in those with non-BA aneurysms (111.7° ± 18°) and in controls (103° ± 20.6°) (p < 0.0001), whereas no difference was observed for the VBJ angle. A wider angle a correlated with BA aneurysm neck width but not dome size, which is consistent with CFD results showing a widening of the impingement zone at the bifurcation apex. BA bifurcations hosting even small aneurysms (< 5 mm) had a significantly larger a angle compared with matched controls (p < 0.0001). In nonaneurysmal controls, a increased with age (p < 0.0001), with a threshold effect above 35 years of age and a steeper dependence in females (p = 0.002) than males (p = 0.04).

Conclusions. The a angle widens with age during adulthood, especially in females. This angular widening is associated with basilar bifurcation aneurysms and may predispose individuals to aneurysm initiation by diffusing the flow impingement zone away from the protective medial band region of the flow divider.

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A Novel Protocol of Continuous Navigation Guidance for Endoscopic Third Ventriculostomy

A Novel Protocol of Continuous Navigation Guidance for Endoscopic Third Ventriculostomy

Operative Neurosurgery 10:514–524, 2014

Although considered a standard neurosurgical procedure, endoscopic third ventriculostomy (ETV) is associated with a relatively high complication rate that is predominantly related to malpositioning of the trajectory.

OBJECTIVE: To develop an advanced navigation protocol for ETV, assess its possible benefits over commonly used ETV trajectories, and apply this protocol during surgery.

METHODS: After development of our advanced protocol, the imaging data of 59 patients who underwent ETV without navigation guidance was transferred to our navigation software. An individualized endoscope trajectory was created according to our protocol in all cases. This trajectory was compared with 2 standard trajectories, especially with regard to the distance to relevant neuronal structures: a trajectory manually measured on preoperative radiological images, as performed in all 59 cases, and a trajectory resulting from a commonly used fixed coronal burr hole. Subsequently, we applied the protocol in 15 ETVs to assess the feasibility and procedural complications.

RESULTS: Our individualized trajectory resulted in a significantly greater distance to the margins of the foramen of Monro, and the burr hole was located more posteriorly from the coronal suture in comparison with the standard trajectories. The advanced ETV technique was feasible in all 15 procedures, and no major complications occurred in any procedure. In 1 patient, a fornix contusion without clinical correlation was observed.

CONCLUSION: Our data indicate that the proposed navigation protocol for ETV optimizes the distance of the endoscope to important neuronal structures. Continuous endoscope and puncture device guidance may further add to the safety of this procedure.

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Modulation of the Cerebello-Thalamo-Cortical Network in Thalamic Deep Brain Stimulation for Tremor

Modulation of the Cerebello-Thalamo-Cortical Network in Thalamic Deep Brain Stimulation for Tremor- A Diffusion Tensor Imaging Study

Neurosurgery 75:657–670, 2014

Deep brain stimulation alleviates tremor of various origins. Several regions like the ventralis intermediate nucleus of thalamus, the caudal zona incerta, and the posterior subthalamic region are generally targeted. Previous work with fiber tractography has shown the involvement of the cerebello-thalamo-cortical network in tremor control.

OBJECTIVE: To report the results of a prospective trial in a group of patients with tremor who underwent post hoc tractographic analysis after treatment with traditional thalamic deep brain stimulation.

METHODS: A total of 11 patients (aged 64 6 17 years, 6 male) were enrolled (essential tremor [6], Parkinson tremor [3], and myoclonic tremor in myoclonus dystonia [2]). Patients received 1 (3 patients), 2 (7 patients), or 3 (1 patient) quadripolar electrodes. A 32-direction diffusion tensor magnetic resonance imaging sequence was acquired preoperatively. Tractography was processed postoperatively for evaluation and the dentato-rubro-thalamic tract (DRT) was individually tracked. Electrode positions were determined with helical computed tomography. Electric fields (EFs) were simulated according to individual stimulation parameters in a standardized atlas brain space (ICBMMNI 152).

RESULTS: Tremor was reduced in all patients (69.4% mean) on the global (bilateral) tremor score. Effective contacts were located inside or in proximity to the DRT. In moderate tremor reduction (2 patients), the EFs were centered on its anterior border. In good and excellent tremor reduction (9 patients), EFs focused on its center.

CONCLUSION: Deep brain stimulation of the cerebello-thalamo-cortical network reduces tremor. The DRT connects 3 traditional target regions for deep brain stimulation in tremor disease. Tractography techniques can be used to directly visualize the DRT and, therefore, optimize target definition in individual patients.

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Spinal CSF leakage and chronic subdural hematoma

Spinal cerebrospinal fluid leak as the cause of chronic subdural hematomas in nongeriatric patients

J Neurosurg 121:1380–1387, 2014

The etiology of chronic subdural hematoma (CSDH) in nongeriatric patients (≤ 60 years old) often remains unclear. The primary objective of this study was to identify spinal CSF leaks in young patients, after formulating the hypothesis that spinal CSF leaks are causally related to CSDH.

Methods. All consecutive patients 60 years of age or younger who underwent operations for CSDH between September 2009 and April 2011 at Bern University Hospital were included in this prospective cohort study. The patient workup included an extended search for a spinal CSF leak using a systematic algorithm: MRI of the spinal axis with or without intrathecal contrast application, myelography/fluoroscopy, and postmyelography CT. Spinal pathologies were classified according to direct proof of CSF outflow from the intrathecal to the extrathecal space, presence of extrathecal fluid accumulation, presence of spinal meningeal cysts, or no pathological findings. The primary outcome was proof of a CSF leak.

Results. Twenty-seven patients, with a mean age of 49.6 ± 9.2 years, underwent operations for CSDH. Hematomas were unilateral in 20 patients and bilateral in 7 patients. In 7 (25.9%) of 27 patients, spinal CSF leakage was proven, in 9 patients (33.3%) spinal meningeal cysts in the cervicothoracic region were found, and 3 patients (11.1%) had spinal cysts in the sacral region. The remaining 8 patients (29.6%) showed no pathological findings.

Conclusions. The direct proof of spinal CSF leakage in 25.9% of patients suggests that spinal CSF leaks may be a frequent cause of nongeriatric CSDH.

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Predicting the “usefulness” of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors

5-ALA in pedidatric brain tumors

Acta Neurochir (2014) 156:2315–2324

Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children.

Methods Information on patient characteristics, MRI characteristics of tumors, histology, fluorescence qualities, and outcomes were requested. Surgeons were further asked to indicate whether fluorescence was “useful”, i.e., leading to changes in surgical strategy or identification of residual tumor. Recursive partitioning analysis (RPA) was used for defining cohorts with high or low likelihoods for useful fluorescence.

Results Data on 78 patients <18 years of age were submitted by 20 centers. Fluorescence was found useful in 12 of 14 glioblastomas (85 %), four of five anaplastic astrocytomas (60 %), and eight of ten ependymomas grades II and III (80 %). Fluorescence was found inconsistently useful in PNETs (three of seven; 43 %), gangliogliomas (two of five; 40 %), medulloblastomas (two of eight, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23.1 %).

Conclusions Our survey demonstrates 5-ALA as being used in pediatric brain tumors. 5-ALA may be especially useful for contrast-enhancing supratentorial tumors. These data indicate controlled studies to be necessary and also provide a basis for planning such a study.

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Radical resection of nongerminomatous pineal region tumors via the occipital transtentorial approach based on arachnoidal consideration

Occipital transtentorial

Acta Neurochir (2014) 156:2253–2262

The role of radical resection for nongerminomatous pineal region tumors is still controversial. The purpose of this study was to present the surgical results in a large series and evaluate the feasibility of radical surgical strategy.

Methods We retrospectively reviewed the records of 143 patients with nongerminomatous pineal region tumors surgically treated via an occipital transtentorial approach between 2000 and 2011. The tumor was small (<2 cm) in 14.7 % of patients, medium (2–4 cm) in 52.4 %, and large (>4 cm) in 32.9 %.

Results Gross total tumor removal was achieved in 91.6 % of patients, subtotal in 7.0 %, and partial in 1.4 %. Histological diagnosis was nongerminomatous germ cell tumor in 41.3 %, pineal parenchymal tumor in 14.7 %, glial tumors in 28.7 %, and miscellaneous in 15.4 %. The overall complication and mortality rate was 18.2 % and 0.7 %, respectively. Permanent morbidity occurred in 5.6 % of patients, including hemianopsia in 3.5 % and Parinaud syndrome in 2.1 %. Hydrocephalus was resolved in 82.1 % without surgery for the CSF diversion. Sixty-eight patients with malignant tumors underwent radiotherapy; 35 also received adjuvant chemotherapy. One hundred thirty patients were successfully followed up with a mean duration of 43 months. Finally, 86.9 % of the patients achieved a favorable functional outcome (mRS≤ 2), 3.1 % had an mRS score of 3, 1.5 % had an mRS score of 4, and 8.5 % had died (mRS=6).

Conclusions Radical surgery was recommended as the optimal treatment for nongerminomatous pineal region tumors. Favorable results could be achieved by experienced neurosurgeons. Hydrocephalus could be cured by radical tumor removal in the majority of cases. The occipital transtentorial approach was indicated for most pineal region tumors, but surgeon’s preference and experience should also be considered. New understanding of the arachnoid membranes of this region may be helpful for tumor resection.

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