Neurosurgery Blog

J Neurosurg Spine 15:610–619, 2011. DOI: 10.3171/2011.7.SPINE1132
Iatrogenic injury of the V2 segment of the vertebral artery (VA) is a rare but serious complication and can be catastrophic. The purpose of this study was to characterize the relationship of the V2 segment of the VA to the surrounding anatomical structures and to highlight the potential site and mechanisms of injury that can occur during common neurosurgical procedures involving the subaxial cervical spine.
Methods. Ten adult cadaveric specimens (20 sides) were included in this study. Quantitative anatomical measurements between selected landmarks and the VA were obtained. In addition, lateral mass screws were placed bilaterally, from C-3 to C-7, reproducing either the Magerl technique or a modified technique. The safety angle, defined as the axial deviation from the screw trajectory needed to injure the VA, and the distance from the entry point to the VA were measured at each level for both techniques.
Results. The VA coursed closer to the midline at C3–4 and C4–5 (mean distance [SD] 14.9 ± 1.1 mm) than at C2–3 or C5–6. Within the intertransverse space it coursed closer to the uncinate processes of the vertebral bodies (1.8 ± 1.1 mm) than to the anterior tubercle of the transverse processes (3.4 ± 1.6 mm). The distance between the VA and the uncinate process was less at C3–6 (1.3 ± 0.7 mm) than at C2–3 (3.3 ± 0.8 mm). The VA coursed on average at a distance of 11.9 ± 1.7 mm from the anterior and 4.2 ± 2.6 mm from the posterior aspect of the intervertebral disc space. Lateral mass screw angles were 25° lateral and 39.1° cranial for the Magerl technique, and 36.6° lateral and 46.1° cranial for the modified technique. The safety angle was greater and screw length longer when using this modified technique.
Conclusions. The relation of the V2 segment of the VA to anterior procedures and lateral mass instrumentation at the subaxial cervical spine was reviewed in this study. A detailed anatomical knowledge of the V2 segment of the VA combined with careful preoperative imaging is mandatory for safe cervical spine surgery.

J Neurosurg 115:906–914, 2011. DOI: 10.3171/2011.6.JNS11131

Vestibular schwannomas are histopathologically benign tumors arising from the Schwann cell sheath surrounding the vestibular branch of cranial nerve VIII and are related to the NF2 gene and its product merlin.

Merlin acts as a tumor suppressor and as a mediator of contact inhibition. Thus, deficiencies in both NF2 genes lead to vestibular schwannoma development.

Recently, there have been major advances in our knowledge of the molecular biology of vestibular schwannomas as well as the development of novel therapies for its treatment.

In this article the authors comprehensively review the recent advances in the molecular biology and characterization of vestibular schwannomas as well as the development of modern treatments for vestibular schwannoma. For instance, merlin is involved with a number of receptors including the CD44 receptor, EGFR, and signaling pathways, such as the Ras/raf pathway and the canonical Wnt pathway. Recently, merlin was also shown to interact in the nucleus with E3 ubiquitin ligase CRL4DCAF1.

A greater understanding of the molecular mechanisms behind vestibular schwannoma tumorigenesis has begun to yield novel therapies. Some authors have shown that Avastin induces regression of progressive schwannomas by over 40% and improves hearing. An inhibitor of VEGF synthesis, PTC299, is currently in Phase II trials as a potential agent to treat vestibular schwannoma.

Furthermore, in vitro studies have shown that trastuzumab (an ERBB2 inhibitor) reduces vestibular schwannoma cell proliferation.

With further research it may be possible to significantly reduce morbidity and mortality rates by decreasing tumor burden, tumor volume, hearing loss, and cranial nerve deficits seen in vestibular schwannomas.

Neuro-Oncology DOI:10.1093/neuonc/nor169

Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients with primary CNS lymphoma. Because of the involvement of miRNA in carcinogenesis, miRNAs in CSF may serve as unique biomarkers for minimally invasive diagnosis of glioma.

The objective of this pilot study was to identify differentially expressed microRNAs in CSF samples from patients with glioma as potential novel glioma biomarkers.

With use of a candidate approach of miRNA quantification by reverse-transcriptase polymerase chain reaction (qRT-PCR), miRNAs with significant levels in CSF samples from patients with gliomas were identified. MiR-15b and miR-21 were differentially expressed in CSF samples from patients with gliomas, compared to control subjects with various neurologic disorders, including patients with primary CNS lymphoma and carcinomatous brain metastases. Receiver- operating characteristic analysis of miR-15b level revealed an area under the curve of 0.96 in discriminating patients with glioma from patients without glioma. Moreover, inclusion of miR-15b and miR-21 in combined expression analyses resulted in an increased diagnostic accuracy with 90% sensitivity and 100% specificity to distinguish patients with glioma from control subjects and patients with primary CNS lymphoma.

In conclusion, the results of this pilot study demonstrate that miR-15b and miR-21 are markers for gliomas, which can be assessed in the CSF by means of qRT-PCR. Accordingly, miRNAs in the CSF have the potential to serve as novel biomarkers for the detection of gliomas.

Neurosurgery 69:349–356, 2011 DOI: 10.1227/NEU.0b013e31821661c3

The risk of aneurysm rupture appears to be related to multiple factors such as topology, morphology, size, perianeurysmal environment, and blood flow hemodynamics.

OBJECTIVE: To evaluate aneurysm morphology and to quantitatively compare the volumetric parameters between ruptured and unruptured aneurysms from our clinical database at the UCLA Medical Center.

METHODS: Novel algorithms that automatically compute aneurysm geometry were tested on the basis of voxel data obtained from angiographic images, and measurements of aneurysm morphology were automatically recorded. We studied a total of 50 aneurysms (25 ruptured and 25 unruptured) with sizes ranging from 3 to 26 mm. To compare the geometric characteristics between ruptured and unruptured groups, we examined measurements, including volume and surface area, and the ratios of these measurements to the minimal bounding sphere around each aneurysm.

RESULTS: More than 65% of ruptured aneurysms had a ratio of aneurysm volume to bounding sphere volume (AVSV) of > 0.5. More than 70% of ruptured aneurysms had a ratio of aneurysm surface to bounding sphere surface (AASA) of < 1. A trend differentiating ruptured and unruptured aneurysms was observed in AVSV (P = .07) and AASA (P = .04). Classification and regression trees analysis showed 68% correct classification with rupture for AVSV and 70% for AASA.

CONCLUSION: By comparing aneurysm geometry with the bounding sphere, we found a trend associating the ratios of aneurysm volume and surface area with rupture. These geometric parameters may be useful for understanding the influence of morphology on the risk of aneurysm rupture.

J Neurosurg 115:387–397, 2011.DOI: 10.3171/2011.3.JNS101413

The conceptual division of intracranial arteries into segments provides a better understanding of their courses and a useful working vocabulary. Segmental anatomy of cerebral arteries is commonly cited by a numerical nomenclature, but an analogous nomenclature for cerebellar arteries has not been described. In this report, the microsurgical anatomy of the cerebellar arteries is reviewed, and a numbering system for cerebellar arteries is proposed.

Methods. Cerebellar arteries were designated by the first letter of the artery’s name in lowercase letters, distinguishing them from cerebral arteries with the same first letter of the artery’s name. Segmental anatomy was numbered in ascending order from proximal to distal segments.

Results. The superior cerebellar artery was divided into 4 segments: s1, anterior pontomesencephalic segment; s2, lateral pontomesencephalic segment; s3, cerebellomesencephalic segment; and s4, cortical segment. The anterior inferior cerebellar artery was divided into 4 segments: a1, anterior pontine segment; a2, lateral pontine segment; a3, flocculopeduncular segment; and a4, cortical segment. The posterior inferior cerebellar artery was divided into 5 segments: p1, anterior medullary segment; p2, lateral medullary segment; p3, tonsillomedullary segment; p4, telovelotonsillar segment; and p5, cortical segment.

Conclusions. The proposed nomenclature for segmental anatomy of cerebellar artery complements established nomenclature for segmental anatomy of cerebral arteries. This nomenclature is simple, easy to learn, and practical. The nomenclature localizes distal cerebellar artery aneurysms and also localizes an anastomosis or describes a graft’s connections to donor and recipient arteries. These applications of the proposed nomenclature with cerebellar arteries mimic the applications of the established nomenclature with cerebral arteries.

Eur Spine J (2011) 20:422–428. DOI 10.1007/s00586-010-1587-3

There are discrepancy between MR findings and clinical presentations. The compressed cervical cord in patients of the spondylotic myelopathy may be normal on conventional MRI when it is at the earlier stage or even if patients had severe symptoms. Therefore, it is necessary to take a developed MR technique—diffusion tensor imaging (DTI)—to detect the intramedullary lesions.

Prospective MR and DTI were performed in 53 patients with cervical compressive myelopathy and twenty healthy volunteers. DTI was performed along six non-collinear directions with single-shot spin echo echo-planar imaging (EPI) sequence. Intramedullary apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in four segments (C2/3, C3/4, C4/5, C5/6) for volunteers, in lesions (or the compressed cord) and normal cord for patients. DTI original images were processed to produce color DTI maps.

In the volunteers’ group, cervical cord exhibited blue on the color DTI map. FA values between four segments had a significant difference (P<0.01), with the highest FA value (0.85 ±  0.03) at C2/3 level. However, ADC value between them had no significant difference (P> 0.05). For patients, only 24 cases showed hyperintense on T2-weighted image, while 39 cases shown patchy green signal on color DTI maps. ADC and FA values between lesions or the compressed cord and normal spinal cord of patients had a significant difference (both P< 0.01). FA value at C2/3 cord is the highest of other segments and it gradually decreases towards the caudal direction. Using single-shot spin echo EPI sequence and six non-collinear diffusion directions with b  value of 400 s mm-2 ,

DTI can clearly show the intramedullary microstructure and more lesions than conventional MRI.

J Neurooncol (2011) 102:71–80.DOI 10.1007/s11060-010-0284-8

Diagnosis of a glioblastoma (GBM) is triggered by the onset of symptoms and is based on cerebral imaging and histological examination. Serum-based biomarkers may support detection of GBM. Here, we explored serum protein concentrations of GBM patients and used data mining to explore profiles of biomarkers and determine whether these are associated with the clinical status of the patients.

Gene and protein expression data for astrocytoma and GBM were used to identify secreted proteins differently expressed in tumors and in normal brain tissues. Tumor expression and serum concentrations of 14 candidate proteins were analyzed for 23 GBM patients and nine healthy subjects. Datamining methods involving all 14 proteins were used as an initial evaluation step to find clinically informative profiles.

Data mining identified a serum protein profile formed by BMP2, HSP70, and CXCL10 that enabled correct assignment to the GBM group with specificity and sensitivity of 89 and 96%, respectively (p< 0.0001, Fischer’s exact test). Survival for more than 15 months after tumor resection was associated with a profile formed by TSP1, HSP70, and IGFBP3, enabling correct assignment in all cases (p< 0.0001, Fischer’s exact test). No correlation was found with tumor size or age of the patient.

This study shows that robust serum profiles for GBM may be identified by data mining on the basis of a relatively small study cohort. Profiles of more than one biomarker enable more specific assignment to the GBM and survival group than those based on single proteins, confirming earlier attempts to correlate  single markers with cancer. These conceptual findings will be a basis for validation in a larger sample size.

Neurosurgery 68:491–495, 2011 DOI: 10.1227/NEU.0b013e3181ffa21c

Cerebrospinal fluid (CSF) diversionary methods are fraught with complications (eg, infection, obstruction, and CSF malabsorption at the distal site).

INTRODUCTION: The authors investigated the sternum, specifically the manubrium, as a potential CSF receptacle for patients with hydrocephalus.

METHODS: Five fresh adult human cadavers had the manubrium cannulated in a suprasternal location. Tap water was infused via a metal trocar for approximately 60 minutes. Additionally, morphometric examination of the manubrium from 40 adult human skeletons was performed. Next, 4 anesthetized rhesus monkeys underwent cannulation of the manubrium: 2 were infused with 50 mL of saline over approximately 1 hour, and 2 were infused by gravity drip of saline over 24 hours. Finally, 2 adult pigs underwent long-term ventriculosternal tube placement with analysis for function and potential development of osteomyelitis.

RESULTS: Thirty liters of water were injected into all cadaveric specimens without overflow or noticeable edema. No fluid accumulation was identified. The manubrium had a mean length, width, and thickness of 5.1 cm, 5.0 cm, and 1 cm, respectively. The animals that underwent infusion of 50 mL of saline and the animals that underwent gravity drip tolerated the procedure without vital sign changes or evidence of saline leakage into the pleural cavity. The 2 pigs did not show any vital sign changes, and, 2 weeks post procedure, they had no findings of osteomyelitis.

CONCLUSION: Based on our studies, the manubrium of the sternum appears to be an ideal location for the placement of the distal end of a CSF diversionary shunt when other anatomic receptacles are not an option. In vivo human studies are now required to verify our findings.

J Neurosurg 114:359–366, 2011.DOI: 10.3171/2009.10.JNS091135

Vestibular schwannomas (VSs) are benign tumors arising from the sheath of cranial nerve VIII. The pathogenesis underlying most familial and sporadic VSs has been linked to a mutation in a single gene, the neurofibromin 2 (NF2) gene located on chromosome 22, band q11–13.1.

In this review, the authors summarized what is known about the epidemiology of NF2 mutations and patients with VSs. The authors also discuss the function of the NF2 gene product, merlin, and describe the known and hypothetical effects of genetic mutations that lead to merlin dysfunction on a broad variety of cellular and histological end points.

A better understanding of the molecular pathobiology of VSs may lead to novel therapeutics to augment current modalities of treatment while minimizing morbidity.

Neurosurgery 68:291–301, 2011 DOI: 10.1227/NEU.0b013e3182011262

Traumatic injuries of the craniovertebral junction (CVJ) area are common and frequently the outcome of motor vehicle accidents, falls, and diving accidents.

To define and characterize CVJ traumatic injuries, some international classifications are currently in use, and they are thought and focused on junction bone fracture. However, recent data point out a major important role of the CVJ ligaments and membranes in traumatic injuries with a secondary function of the osseous structures.

Emphasizing the correct role of the ligaments and membranes is extremely important for determining appropriate medical or surgical planning for patients and also to design new CVJ injury classifications.

We reviewed every recent major publication on the ligaments and membranes of the CVJ area. We divided the information into sections concerning anatomy, embryology, biomechanics, trauma, and CVJ bone fractures.

A role of the ligaments and membranes in the traumatic injuries of the CVJ area has often been recognized; but only recently, with the increase in the knowledge of the anatomic and biomechanical junction area, supported by neuroradiological tools (magnetic resonance imaging) and a more detailed traumatic injuries assessment, has the role of the ligaments and membranes been highlighted.

Ligaments and membranes have a pivotal role in each junctional ability and are the key to orienting any medical or surgical indications in this unique area of the spine.

Neurosurgery 68:280–290, 2011 DOI: 10.1227/NEU.0b013e3181ff9cbb

Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue.

OBJECTIVE: To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents.

METHODS: Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity.

RESULTS: Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence.

CONCLUSION: The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of any organ and with a rapidity that allows real-time analysis.

SPINE Volume 36, Number 1, pp E27–E32

Study Design. Biomechanical study using human cadaveric lumbar spines.

Objective. To evaluate effects of total disc replacement (TDR) on spine biomechanics at the treated and adjacent levels.

Summary of Background Data. Previous studies on spine biomechanics after TDR were focused on facet forces and range of motion and report contradictory results. Characterization of contact pressure, peak contact pressure, force, and peak force before and after TDR may lead to a better understanding of facet joint function and may aid in prediction of long-term outcomes after TDR.

Methods. Seven fresh-frozen human cadaveric lumbar spines were potted at T12 and L5 and installed in a 6 degrees of freedom displacement- controlled testing system. Displacements of 15° flexion/ extension, 10° right/left bending, and 10° right/left axial rotation were applied. Contact pressure, peak contact pressure, force, peak force, and contact area for each facet joint were recorded at L2–L3 and L3–L4 both before and after TDR at L3–L4. The data were analyzed with analysis of variance and t tests.

Results. Axial rotation had the most impact on contact pressure, peak contact pressure, force, peak force, and contact area in intact spines. During lateral bending and axial rotation, TDR resulted in a significant increase in facet forces at the level of treatment and a decrease in contact pressure, peak contact pressure, and peak force at the level superior to the TDR. With flexion/extension, there was a decrease in peak contact pressure and peak contact force at the superior level.

Conclusion. Our study demonstrates that rotation is the most demanding motion for the spine. We also found an increase in facet forces at the treated level after TDR. We are the first to show a decrease in several biomechanical parameters after TDR at the adjacent superior level. In general, our findings suggest there is an increase in loading of the facet joints at the level of disc implantation and an overall unloading effect at the level above.

Neurosurgery 67:1703–1708, 2010 DOI: 10.1227/NEU.0b013e3181fb801b

Peritumoral brain edema (PTBE) may be crucial in the clinical outcome of meningioma patients. The underlying pathogenetic key mechanism has so far not been determined. Sex, age, tumor size, location, involvement of other structures, or the histological appearance was not found to sufficiently explain PTBE formation in meningiomas.

OBJECTIVE: As PTBE formation is widely accepted to be vasogenic, we investigated the role of vascular endothelial growth factor (VEGF) and pial supplying vessels in a series of World Health Organization (WHO) grade I meningiomas.

METHODS: A total of 79 patients with WHO grade I meningiomas were immunohistochemically studied for VEGF and MIB-1. Pre- and postoperative magnetic resonance imaging including 3-dimensional reconstruction of 1.3-mm thick layers, with calculation of tumor and edema volume, was performed. Intraoperatively, the vascular supply and arachnoidal state were noted by the neurosurgeon.

RESULTS: VEGF was found to be exclusively confined to meningioma tumor cells. We identified 4 different patterns. VEGF and supplying pial vessels were found in 14 meningioma patients, pial vascular supply only in 3, VEGF expression only in 46, and neither VEGF expression nor supplying pial vessels in 16. Only the occurrence of both pial vascular supply and tumor VEGF expression was found to be correlated with PTBE formation (P , .002).

CONCLUSION: Our data suggest that VEGF may be crucial in angiogenesis and therefore indirectly in PTBE formation in World Health Organization grade I meningiomas

J Neurosurg Pediatrics 6:000–000, 2010. (DOI: 10.3171/2010.9.PEDS10267)

Surgery for medically intractable epilepsy secondary to unihemispheric pathology has evolved from more aggressive hemispherectomy to less aggressive variations of hemispherotomy. The authors propose a novel minimally invasive endoscopic hemispherotomy that should give results comparable to conventional open craniotomy and microsurgery.

Methods. Endoscopic transventricular hemispherotomy was performed in 5 silicon-injected cadaveric heads in the authors’ minimally invasive neurosurgery laboratory. The lateral ventricle was accessed endoscopically through a frontal and occipital bur hole. White matter disconnections were performed to unroof the temporal horn and to disconnect the frontobasal region, corpus callosum, and fornix.

Results. Using an endoscopic transventricular approach, all white matter disconnections were successfully performed in all 5 cadavers.

Conclusions. The authors have demonstrated the feasibility of endoscopic transventricular hemispherotomy in a cadaveric model. The technique is simple and could be useful in a subgroup of patients with parenchymal volume loss and ventriculomegaly.

Neurosurgery 67[ONS Suppl 2]:ons321–ons324, 2010 DOI: 10.1227/NEU.0b013e3181f74548.

Neuroendoscopy is increasingly used as an adjunctive tool in intracranial aneurysm surgery.

OBJECTIVE: To assess the versatility of a prototype continuously variable-view rigid endoscope in visualizing the anterior cerebral artery complex.

METHODS: In 5 formaldehyde-fixed, arterially injected specimens, a standard frontolateral approach was used on both sides. After meticulous microsurgical dissection using this approach, the prototype of a multivariable rigid endoscope (EndoCAMeleon; Karl Storz GmbH & Co, Tuttlingen, Germany) was inserted. It is a rigid endoscope that is capable of changing its angle of view while remaining stationary and shape invariant. We inspected the anterior cerebral artery complex, using and testing the capabilities of the device.

RESULTS: The continuously variable viewing mechanism enables the surgeon to adjust the field of view continuously and to optimize the visualization of the neurovascular structures. Because of the rigid tip combined with the continuously variable viewing mechanism, the need to move the endoscope within the surgical field was minimal. The field of view changes, but the tip itself hardly moves. The EndoCAMeleon was able to enhance both the visibility of the anterior cerebral artery complex and the accessibility of the A1 and A2 arterial walls to a range of approximately 270 degrees.

CONCLUSION: The EndoCAMeleon enhances the visibility of the anterior cerebral artery complex and facilitates endoscope-assisted inspection, planning of clip application, and clip control.

J Neurosurg 113:1135–1143, 2010.(DOI: 10.3171/2010.3.JNS091832)

The aim of this study was to evaluate, using diffusion tensor tractography, the white matter fibers crossing the hippocampus and the amygdala, and to perform a volumetric analysis and an anatomical study of the connections of these 2 structures. As a second step, the authors studied the white matter tracts crossing a virtual volume of resection corresponding to a selective amygdalo-hippocampectomy.

Methods. Twenty healthy right-handed individuals underwent 3-T MR imaging. Volumetric regions of interest were manually created to delineate the amygdala, the hippocampus, and the volume of resection. White matter fiber tracts were parcellated using the fiber assignment for continuous tracking tractography algorithm. All fibers were registered with the anatomical volumes.

Results. In all participants, the authors identified fibers following the hippocampus toward the fornix, the splenium of the corpus callosum, and the dorsal hippocampal commissure. With respect to the fibers crossing the amygdala, the authors identified the stria terminalis and the uncinate fasciculus. The virtual resection disrupted part of the fornix, fibers connecting the 2 hippocampi, and fibers joining the orbitofrontal cortex. The approach created a theoretical frontotemporal disconnection and also interrupted fibers joining the temporal pole and the occipital area.

Conclusions. This diffusion tensor tractography study allowed for good visualization of some of the connections of the amygdala and hippocampus. The authors observed that the virtual selective amygdalohippocampectomy disconnected a large number of fibers connecting frontal, temporal, and occipital areas