Long-term Outcomes After Staged-Volume Stereotactic Radiosurgery for Large Arteriovenous Malformations

Neurosurgery 71:632–644, 2012 DOI: 10.1227/NEU.0b013e31825fd247

Stereotactic radiosurgery is an effective treatment modality for small arteriovenous malformations (AVMs) of the brain. For larger AVMs, the treatment dose is often lowered to reduce potential complications, but this decreases the likelihood of cure. One strategy is to divide large AVMs into smaller anatomic volumes and treat each volume separately.

OBJECTIVE: To prospectively assess the long-term efficacy and complications associated with staged-volume radiosurgical treatment of large, symptomatic AVMs.

METHODS: Eighteen patients with AVMs larger than 15 mL underwent prospective staged-volume radiosurgery over a 13-year period. The median AVM volume was 22.9 mL (range, 15.7-50 mL). Separate anatomic volumes were irradiated at 3- to 9-month intervals (median volume, 10.9 mL; range, 5.3-13.4 mL; median marginal dose, 15 Gy; range, 15-17 Gy). The AVM was divided into 2 volumes in 10 patients, 3 volumes in 5 patients, and 4 volumes in 3 patients. Seven patients underwent retreatment for residual disease.

RESULTS: Actuarial rates of complete angiographic occlusion were 29% and 89% at 5 and 10 years. Five patients (27.8%) had a hemorrhage after radiosurgery. Kaplan-Meier analysis of cumulative hemorrhage rates after treatment were 12%, 18%, 31%, and 31% at 2, 3, 5, and 10 years, respectively. One patient died after a hemorrhage (5.6%).

CONCLUSION: Staged-volume radiosurgery for AVMs larger than 15 mL is a viable treatment strategy. The long-term occlusion rate is high, whereas the radiation-related complication rate is low. Hemorrhage during the lag period remains the greatest source of morbidity and mortality.

Diffusion tensor imaging in hydrocephalus—findings before and after shunt surgery

Acta Neurochir (2012) 154:1699–1706

To evaluate changes in diffusion tensor imaging (DTI)-derived parameters in patients with hydrocephalus (HC) before and several weeks after shunt surgery.

Methods Thirteen HC patients were examined with DTI before and after shunt surgery. In a combined region of interest and whole brain voxel-based analysis, different DTI parameters were compared with an age-matched control group.

Results Alteration of DTI parameters in HC patients and changes after shunt surgery are regionally different. HC patients show an increase in fractional anisotropy values based on increases in parallel diffusivity in the corticospinal tract. On the other hand, reduced fractional anisotropy values are found in the corpus callosum of HC patients. Following shunt surgery, all DTI parameters showed a trend towards normalization, yet differences to healthy control subjects remained.

Conclusion Our results show that DTI parameter changes are regionally dependent and need a careful interpretation of the underlying diffusivities to serve as a diagnostic or follow-up measure in patients with hydrocephalus.

Technical nuances of resection of giant (> 5 cm) vestibular schwannomas: pearls for success

Neurosurg Focus 33 (3):E15, 2012

Removal of vestibular schwannomas (VSs, or acoustic neuromas) remains one of the most challenging operations in neurosurgery. Giant or huge tumors (> 5 cm) heighten these challenges, and technical nuances play a special role in maximizing tumor resection while minimizing complications.

In this article, the senior author describes his technical experience with microsurgical excision of giant VSs. The accompanying video further illustrates these details.

 

The Contralateral Transcingulate Approach

Neurosurgery 71[ONS Suppl 1]:ons4–ons14, 2012

The contralateral transcingulate approach is a variation of the contralateral transcallosal approach for lesions located in the cingulate gyrus and deep white matter of the medial frontal lobe.

OBJECTIVE: To more thoroughly describe the contralateral transcingulate approach by reporting our operative technique and results.

METHODS: This approach positions the head with the midline horizontally, lesion on the upside, allowing gravity retraction of the dependent frontal lobe. Bifrontal craniotomy and splitting of the interhemispheric fissure create a crossing trajectory from the contralateral fissure to the ipsilateral cingulate gyrus that maximizes lateral exposure.

RESULTS: Eleven patients with vascular lesions were treated with the contralateral transcingulate approach (9 patients with cavernous malformations and 2 patients with arteriovenous malformations). Eight lesions were located on the left side, 5 in the cingulate gyrus, and 6 in the deep frontal lobe. The falx was cut in 5 patients to extend the crossing trajectory. All lesions were removed completely, with neurological morbidity in 1 patient caused by venous infarction.

CONCLUSION: Although similar to the contralateral transcallosal approach, the contralateral transcingulate approach accesses lesions outside the ventricle and has a steeper crossing trajectory. This approach requires no disruption of brain tissue with lesions on the cingulate surface and only a small incision in cingulate gyrus with lesions in the deep frontal lobe. The ipsilateral pericallosal and callosomarginal arteries provide dependable landmarks for transcingulate dissection. The contralateral transcingulate approach offers an alternative medial approach to lesions near language and motor areas and avoids lateral transcortical approaches, awake speech mapping, and risk to eloquent cortex in the dominant hemisphere.

Natural history of DAVFs without cortical venous drainage

J Neurosurg 117:539–545, 2012

The goal of this study was to determine the clinical course of Borden-Shucart Type I cranial dural arteriovenous fistulas (DAVFs) and to calculate the annual rate of conversion of these lesions to more aggressive fistulas that have cortical venous drainage (CVD).

Methods. A retrospective chart review was conducted of all patients harboring DAVFs who were seen at the authors’ institution between 1997 and 2009. Twenty-three patients with Type I DAVFs who had available clinical follow-up were identified. Angiographic and clinical data from these patients were reviewed. Neurological outcome and status of presenting symptoms were assessed during long-term follow-up.

Results. Of the 23 patients, 13 underwent endovascular treatment for intolerable tinnitus or ophthalmological symptoms, and 10 did not undergo treatment. Three untreated patients died of unrelated causes. In those who were treated, complete DAVF obliteration was achieved in 4 patients, and palliative reduction in DAVF flow was achieved in 9 patients. Of the 19 patients without radiographic cure, no patient developed intracranial hemorrhage or nonhemorrhagic neurological deficits (NHNDs), and no patient died of DAVF-related causes over a mean follow-up of 5.6 years. One patient experienced a spontaneous, asymptomatic obliteration of a partially treated DAVF in late follow-up, and 2 patients experienced a symptomatic conversion of their DAVF to a higher-grade fistula with CVD in late follow-up. The annual rate of conversion to a higher-grade DAVF based on Kaplan-Meier cumulative event-free survival analysis was 1.0%. The annual rate of intracranial hemorrhage, NHND, and DAVF-related death was 0.0%.

Conclusions. A small number of Type I DAVFs will convert to more aggressive DAVFs with CVD over time. This conversion to a higher-grade DAVF is typically heralded by a change in patient symptoms. Follow-up vascular imaging is important, particularly in the setting of recurrent or new symptoms.

Assessment of a Quick Reference Table Algorithm for Determining Initial Postoperative Pressure Settings of Programmable Pressure Valves in Patients With Idiopathic Normal Pressure Hydrocephalus: SINPHONI Subanalysis

Neurosurgery 71:722–728, 2012 

Management of overdrainage complications in shunted patients with idiopathic normal pressure hydrocephalus (INPH) remains a difficult task despite the use of programmable pressure valves.

OBJECTIVE: To assess the usefulness of a quick reference table (QRT) algorithm for achieving a suitable initial programmable pressure valve setting in INPH patients who participated in the Study for INPH on Neurological Improvement (SINPHONI).

METHODS: One hundred registered patients diagnosed with probable INPH were treated with ventriculoperitoneal shunts using Codman-Hakim programmable valves (CHPVs). In this series, the initial CHPV setting was decided prospectively according to the QRT algorithm. Shunt effectiveness, complications, and the number of CHPV readjustments during follow-up periods were investigated.

RESULTS: Eighty patients were considered better than shunt responders (more than 1 point improvement in modified Rankin Scale at any follow-up period). Readjustments of CHPVs within 3 months after treatment with ventriculoperitoneal shunt were performed 56 times in 44 cases (44%, 0.56 times/patient). Low-pressure headache occurred in 9 patients, all of whom improved by readjustment alone. Nontraumatic subdural fluid collections and chronic subdural hematomas occurred in 15 cases (15%); however, most of the cases were subclinical and improved after CHPV readjustments alone. Burr hole irrigation was necessary in only 1 case.

CONCLUSION: Use of the QRT algorithm was associated with a decrease in postoperative CHPV readjustments and serious overdrainage complications during the followup period. The QRT algorithm is an easy, safe, and effective method for determining the initial CHPV pressure setting in INPH patients.

Patients with idiopathic trigeminal neuralgia have a sharper-than-normal trigeminal-pontine angle and trigeminal nerve atrophy

Acta Neurochir (2012) 154:1627–1633

Trigeminal neuralgia (TN) is primarily diagnosed by symptoms and patient history. Magnetic resonance (MR) imaging can be helpful in visualizing the neurovascular compression of the trigeminal nerve in TN patients, but the current parameters used as diagnostic markers for TN are less than optimal. The aim of this study is to assess whether the angle between the trigeminal nerve and the pons (the trigeminal-pontine angle) on the affected side of patients with idiopathic TN differs from that of the unaffected side and that found in controls without TN.

Methods A case-control study of 30 clinically diagnosed idiopathic TN patients aged 30 to 79 years and 30 age- and sexmatched controls was conducted.We compared the trigeminalpontine angle and trigeminal nerve atrophy via fast-imaging employing steady-state acquisition (FIESTA) MR imaging.

Results A sharp trigeminal-pontine angle was observed in 25 patients (25/30) on the affected side. As such, the mean angle of the trigeminal nerve on the affected side (40.17) was significantly smaller than that on the unaffected side (48.91, p=0.001) and that in the control group (52.02, p<0.001).

Conclusions A sharp trigeminal-pontine angle on the affected side was found in idiopathic TN patients by FIESTA imaging. This suggests that a sharp trigeminal-pontine angle increases the chance of neurovascular compression on the medial side of the trigeminal nerve.

The Impact of Standing Regional Cervical Sagittal Alignment on Outcomes in Posterior Cervical Fusion Surgery

Neurosurgery 71:662–669, 2012

Positive spinal regional and global sagittal malalignment has been repeatedly shown to correlate with pain and disability in thoracolumbar fusion.

OBJECTIVE: To evaluate the relationship between regional cervical sagittal alignment and postoperative outcomes for patients receiving multilevel cervical posterior fusion.

METHODS: From 2006 to 2010, 113 patients received multilevel posterior cervical fusion for cervical stenosis, myelopathy, and kyphosis. Radiographic measurements made at intermediate follow-up included the following: (1) C1-C2 lordosis, (2) C2-C7 lordosis, (3) C2-C7 sagittal vertical axis (C2-C7 SVA; distance between C2 plumb line and C7), (4) center of gravity of head SVA (CGH-C7 SVA), and (5) C1-C7 SVA. Health-related quality-of-life measures included neck disability index (NDI), visual analog pain scale, and SF-36 physical component scores. Pearson product-moment correlation coefficients were calculated between pairs of radiographic measures and health-related quality-oflife scores.

RESULTS: Both C2-C7 SVA and CGH-C7 SVA negatively correlated with SF-36 physical component scores (r = -0.43, P <.001 and r = -0.36, P = .005, respectively). C2-C7 SVA positively correlated with NDI scores (r = 0.20, P = .036). C2-C7 SVA positively correlated with C1-C2 lordosis (r = 0.33, P = .001). For significant correlations between C2-C7 SVA and NDI scores, regression models predicted a threshold C2-C7 SVA value of approximately 40 mm, beyond which correlations were most significant.

CONCLUSION: Our findings demonstrate that, similar to the thoracolumbar spine, the severity of disability increases with positive sagittal malalignment following surgical reconstruction.

A randomized study of urgent computed tomography–based hematoma puncture and aspiration in the emergency department and subsequent evacuation using craniectomy versus craniectomy only

J Neurosurg 117:566–573, 2012

When treating patients with a spontaneous supratentorial massive (≥ 70 ml) intracerebral hemorrhage (ICH), the results of surgery are gloomy. A worsening pupil response has been observed in patients preoperatively, despite blood pressure control and diuretic administration. Because open surgery needs time for decompression to occur, the authors conducted a prospective randomized study to determine whether patients who have suffered a massive ICH can benefit from a more urgently performed decompressive procedure.

Methods. Overall, 36 eligible patients admitted 6 or fewer hours post-ictus were enrolled in the study. In Group A, 12 patients underwent CT-based hematoma puncture and partial aspiration in the emergency department (ED) and subsequent evacuation via a craniectomy; in Group B, 24 patients underwent hematoma evacuation via a craniectomy only. Pupil responses were categorized into 5 grades (Grade 0, bilaterally fixed; Grade 1, unilaterally fixed with the fixed pupil > 7 mm; Grade 2, unilaterally fixed with the fixed pupil ≤ 7 mm; Grade 3, a unilaterally sluggish response; and Grade 4, a bilaterally brisk response). Grades were obtained on admission, at surgical decompression (defined as the point at which liquid hematoma began to flow out in Group A and at dural opening in Group B), and at completion of craniectomy. The Barthel Scale was used to assess survivors’ functional outcome at 12 months. Comparisons were made between Groups A and B. Logistic regression analysis was used to evaluate the positive likelihood ratio of all variables for survival and function (Barthel Scale score of ≥ 35 at 12 months).

Results. Decompressive surgery was undertaken approximately 60 minutes earlier in Group A than B. A worsening pupil reflex before decompression was observed in no Group A patient and in 9 Group B patients. At the time of decompression pupil response was better in Group A than B (p < 0.05). Although only approximately one-third of the hematoma volume documented on initial CT scanning had been drained before the craniectomy in Group A, when partial aspiration was followed by craniectomy, better pupil-response results were obtained in Group A at the completion of craniectomy, and survival rate and 12-month Barthel Scale score were better as well (p < 0.05). Logistic regression analysis revealed that one variable, a minimum pupil grade of 3 at the time of decompression, had the highest predictive value for survival at 12 months (8.0, 95% CI 2.0–32.0), and a pupil grade of 4 at the same time was the most valuable predictor of a Barthel Scale score of 35 or greater at 12 months (15.0, 95% CI 1.9–120.9).

Conclusions. Patients with massive spontaneous supratentorial ICHs may benefit from more urgent surgical decompression. The results of logistic regression analysis implied that, to improve long-term functional outcome, decompression should be performed in patients before herniation occurs. Due to the fact that most of these patients have signs of herniation when presenting to the ED and because conventional surgical decompression requires time to take effect, this combination of surgical treatment provides a feasible and effective surgical option.

Surgical Management of Giant Posterior Communicating Artery Aneurysms

Neurosurgery 71[ONS Suppl 1]:ons43–ons51, 2012

Giant posterior communicating artery (PCoA) aneurysms (> 25 mm) are rare lesions associated with a poor prognosis and high rates of morbidity and mortality.

OBJECTIVE: To review the clinical results of giant PCoA aneurysms surgically treated at our institution, focusing on operative nuances.

METHODS: All cases of giant PCoA aneurysms treated surgically at our institution were identified from a prospectively maintained patient database. Patient demographic factors, medical comorbidities, rupture status, neurological presentation, clinical outcomes, and surgical records were critically reviewed.

RESULTS: From 1989 to 2010, 11 patients (10 women) underwent surgical clipping of giant PCoA aneurysms. Presenting signs and symptoms included cranial nerve palsies, diminished mental status, headache, visual changes, and seizures. Five aneurysms were ruptured on admission. All aneurysms were clipped primarily except 1, which was treated by parent artery sacrifice and extracranial-to-intracranial bypass after intraoperative aneurysm rupture. Perioperative morbidity and mortality rates were 36% (4 of 11) and 18.3% (2 of 11), respectively. Excellent or good clinical outcomes, defined as modified Rankin Scale scores ≤ 2, were achieved in 86% (5 of 6) of patients available for long-term clinical follow-up (mean, 12.5 ± 13.6 months).

CONCLUSION: Giant PCoA aneurysms are rare vascular lesions that may present with a variety of neurological signs and symptoms. These lesions can be successfully managed surgically with satisfactory morbidity and mortality rates. To the best of our knowledge, this is the largest surgical series of giant PCoA aneurysms published to date.

Surgery for vestibular schwannomas: a systematic review of complications by approach

Neurosurg Focus 33 (3):E14, 2012

Various studies report outcomes of vestibular schwannoma (VS) surgery, but few studies have compared outcomes across the various approaches. The authors conducted a systematic review of the available data on VS surgery, comparing the different approaches and their associated complications.

Methods. MEDLINE searches were conducted to collect studies that reported information on patients undergoing VS surgery. The authors set inclusion criteria for such studies, including the availability of follow-up data for at least 3 months, inclusion of preoperative and postoperative audiometric data, intraoperative monitoring, and reporting of results using established and standardized metrics. Data were collected on hearing loss, facial nerve dysfunction, persistent postoperative headache, CSF leak, operative mortality, residual tumor, tumor recurrence, cranial nerve (CN) dysfunction involving nerves other than CN VII or VIII, and other neurological complications. The authors reviewed data from 35 studies pertaining to 5064 patients who had undergone VS surgery.

Results. The analyses for hearing loss and facial nerve dysfunction were stratified into the following tumor categories: intracanalicular (IC), size (extrameatal diameter) < 1.5 cm, size 1.5–3.0 cm, and size > 3.0 cm. The middle cranial fossa approach was found to be superior to the retrosigmoid approach for hearing preservation in patients with tumors < 1.5 cm (hearing loss in 43.6% vs 64.3%, p < 0.001). All other size categories showed no significant difference between middle cranial fossa and retrosigmoid approaches with respect to hearing loss. The retrosigmoid approach was associated with significantly less facial nerve dysfunction in patients with IC tumors than the middle cranial fossa method was; however, neither differed significantly from the translabyrinthine corridor (4%, 16.7%, 0%, respectively, p < 0.001). The middle cranial fossa approach differed significantly from the translabyrinthine approach for patients with tumors < 1.5 cm, whereas neither differed from the retrosigmoid approach (3.3%, 11.5%, and 7.2%, respectively, p = 0.001). The retrosigmoid approach involved less facial nerve dysfunction than the middle cranial fossa or translabyrinthine approaches for tumors 1.5–3.0 cm (6.1%, 17.3%, and 15.8%, respectively; p < 0.001). The retrosigmoid approach was also superior to the translabyrinthine approach for tumors > 3.0 cm (30.2% vs 42.5%, respectively, p < 0.001). Postoperative headache was significantly more likely after the retrosigmoid approach than after the translabyrinthine approach, but neither differed significantly from the middle cranial fossa approach (17.3%, 0%, and 8%, respectively; p < 0.001). The incidence of CSF leak was significantly greater after the retrosigmoid approach than after either the middle cranial fossa or translabyrinthine approaches (10.3%, 5.3%, 7.1%; p = 0.001). The incidences of residual tumor, mortality, major non-CN complications, residual tumor, tumor recurrence, and dysfunction of other cranial nerves were not significantly different across the approaches.

Conclusions. The middle cranial fossa approach seems safest for hearing preservation in patients with smaller tumors. Based on the data, the retrosigmoid approach seems to be the most versatile corridor for facial nerve preservation for most tumor sizes, but it is associated with a higher risk of postoperative pain and CSF fistula. The translabyrinthine approach is associated with complete hearing loss but may be useful for patients with large tumors and poor preoperative hearing.

The use of intraoperative near-infrared indocyanine green videoangiography in the microscopic resection of hemangioblastomas

Acta Neurochir (2012) 154:1407–1412 

The authors assessed the usefulness of intraoperative near-infrared indocyanine green videoangiography (ICG-VA) in the microscopic resection of hemangioblastomas.

Methods From January 2009 to February 2012, nine consecutive patients (seven men, two women) who underwent surgery for hemangioblastomas using intraoperative ICGVA were included in this study. Surgery was performed on four cystic cerebellar lesions with mural nodules, two solid tumors (one in the cerebellar hemisphere and one in the medulla oblongata), one spinal tumor and multiple tumors in two patients with von Hippel-Lindau disease. Of the nine patients, three were treated for recurrent tumor. The ICGinduced fluorescence images of hemangioblastomas with variable presentation were evaluated.

Results All tumors could be completely removed en bloc. Blood flow in the tumor and tumor-related vessels at the brain surface were clearly detected by ICG-VA in all cases, except one recurrent tumor where postoperative adhesive scar tissue obstructed ICG-induced fluorescence resulting in poor delineation of the blood flow patterns and tumor margins. ICG-VAwas also helpful for detecting the multiple small mural nodules within the cyst or the tumors buried under thin gliotic neural tissue despite reduced fluorescence.

Conclusion Intraoperative ICG-VA is a safe and easy modality for confirming the vascular flow patterns in hemangioblastomas. In addition, ICG-VA provided useful information for intracystic small lesions or lesions concealed under thin brain tissue in order to accomplish total resection of these tumors.

Hemorrhage From Arteriovenous Malformations During Pregnancy

Neurosurgery 71:349–356, 2012 DOI: 10.1227/NEU.0b013e318256c34b

Previous hemorrhage, deep venous drainage, and deep location are established risk factors for arteriovenous malformation (AVM) hemorrhage. Although pregnancy is an assumed risk factor, there is a relative paucity of data to support this neurosurgical tenet.

OBJECTIVE: To elucidate the hemorrhage rate of AVMs during pregnancy.

METHODS: We reviewed the records of 54 women with an angiographic diagnosis of an AVM at our institution. Annual hemorrhage rates were calculated as the ratio of the number of bleeds to total number of patient-years of follow-up. Patient-years of followup were tallied assuming lesion presence from birth until AVM obliteration. The Cox proportional hazards model for hemorrhage with pregnancy as the time-dependent variable was used to calculate the hazard ratio.

RESULTS: Five hemorrhages in 4 patients occurred over 62 pregnancies, yielding a hemorrhage rate of 8.1% per pregnancy or 10.8% per year. Over the remaining 2461.3 patient-years of follow-up, only 28 hemorrhages occurred, yielding an annual hemorrhage rate of 1.1%. The hazard ratio for hemorrhage during pregnancy was 7.91 (P = 2.23 x 10-4), increasing to 18.12 (P = 7.31 x 10-5) when limiting the analysis to patient follow-up up to age 40.

CONCLUSION: Because of the increased risk of hemorrhage from AVMs during pregnancy, we recommend intervention in women who desire to bear children, particularly if the AVM has bled. If the AVM is discovered during pregnancy, we recommend early intervention if it has ruptured; if it is unruptured, we recommend comprehensive counseling, weighing risks of intervention against continuation of pregnancy without intervention.

 

High-Definition Fiber Tractography of the Human Brain: Neuroanatomical Validation and Neurosurgical Applications

Neurosurgery 71:430–453, 2012

High-definition fiber tracking (HDFT) is a novel combination of processing, reconstruction, and tractography methods that can track white matter fibers from cortex, through complex fiber crossings, to cortical and subcortical targets with subvoxel resolution.

OBJECTIVE: To perform neuroanatomical validation of HDFT and to investigate its neurosurgical applications.

METHODS: Six neurologically healthy adults and 36 patients with brain lesions were studied. Diffusion spectrum imaging data were reconstructed with a Generalized Q-Ball Imaging approach. Fiber dissection studies were performed in 20 human brains, and selected dissection results were compared with tractography.

RESULTS: HDFT provides accurate replication of known neuroanatomical features such as the gyral and sulcal folding patterns, the characteristic shape of the claustrum, the segmentation of the thalamic nuclei, the decussation of the superior cerebellar peduncle, the multiple fiber crossing at the centrum semiovale, the complex angulation of the optic radiations, the terminal arborization of the arcuate tract, and the cortical segmentation of the dorsal Broca area. From a clinical perspective, we show that HDFT provides accurate structural connectivity studies in patients with intracerebral lesions, allowing qualitative and quantitative white matter damage assessment, aiding in understanding lesional patterns of white matter structural injury, and facilitating innovative neurosurgical applications. High-grade gliomas produce significant disruption of fibers, and low-grade gliomas cause fiber displacement. Cavernomas cause both displacement and disruption of fibers.

CONCLUSION: Our HDFT approach provides an accurate reconstruction of white matter fiber tracts with unprecedented detail in both the normal and pathological human brain. Further studies to validate the clinical findings are needed.

Cancer Immunoediting in Malignant Glioma

Neurosurgery 71:201–223, 2012

Significant work from many laboratories over the last decade in the study of cancer immunology has resulted in the development of the cancer immunoediting hypothesis. This contemporary framework of the naturally arising immune system–tumor interaction is thought to comprise 3 phases: elimination, wherein immunity subserves an extrinsic tumor suppressor function and destroys nascent tumor cells; equilibrium, wherein tumor cells are constrained in a period of latency under immune control; and escape, wherein tumor cells outpace immunity and progress clinically.

In this review, we address in detail the relevance of the cancer immunoediting concept to neurosurgeons and neuro-oncologists treating and studying malignant glioma by exploring the de novo immune response to these tumors, how these tumors may persist in vivo, the mechanisms by which these cells may escape/attenuate immunity, and ultimately how this concept may influence our immunotherapeutic approaches.

Preoperative multimodal motor mapping: a comparison of magnetoencephalography imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation

J Neurosurg 117:354–362, 2012

Direct cortical stimulation (DCS) is the gold-standard technique for motor mapping during craniotomy. However, preoperative noninvasive motor mapping is becoming increasingly accurate. Two such noninvasive modalities are navigated transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) imaging. While MEG imaging has already been extensively validated as an accurate modality of noninvasive motor mapping, TMS is less well studied. In this study, the authors compared the accuracy of TMS to both DCS and MEG imaging.

Methods. Patients with tumors in proximity to primary motor cortex underwent preoperative TMS and MEG imaging for motor mapping. The patients subsequently underwent motor mapping via intraoperative DCS. The loci of maximal response were recorded from each modality and compared. Motor strength was assessed at 3 months postoperatively.

Results. Transcranial magnetic stimulation and MEG imaging were performed on 24 patients. Intraoperative DCS yielded 8 positive motor sites in 5 patients. The median distance ± SEM between TMS and DCS motor sites was 2.13 ± 0.29 mm, and between TMS and MEG imaging motor sites was 4.71 ± 1.08 mm. In no patients did DCS motor mapping reveal a motor site that was unrecognized by TMS. Three of 24 patients developed new, early neurological deficit in the form of upper-extremity paresis. At the 3-month follow-up evaluation, 2 of these patients were significantly improved, experiencing difficulty only with fine motor tasks; the remaining patient had improvement to 4/5 strength. There were no deaths over the course of the study.

Conclusions. Maps of the motor system generated with TMS correlate well with those generated by both MEG imaging and DCS. Negative TMS mapping also correlates with negative DCS mapping. Navigated TMS is an accurate modality for noninvasively generating preoperative motor maps.

 

Obesity and Brain Addiction Circuitry: Implications for Deep Brain Stimulation

Neurosurgery 71:224–238, 2012 DOI: 10.1227/NEU.0b013e31825972ab

Obesity is a growing health problem worldwide and is responsible for a significant proportion of health expenditures in developed nations. It is also notoriously difficult to treat. Prior attempts at pharmacological or neurological modulation, including deep brain stimulation, have primarily targeted homeostatic mechanisms of weight control centered in the hypothalamus. To date, these attempts have had limited success. Multiple lines of independent data suggest that dysregulated reward circuitry in the brain underlies behaviors leading to obesity.

Here, we review the existing data and related neurocircuitry, as well as the scope of obesity and currently available treatments. Finally, we suggest a neuromodulation strategy geared toward regulating these dysfunctional circuits, primarily by alteration of frontolimbic circuits.

Safety and efficacy of Gliadel wafers for newly diagnosed and recurrent glioblastoma

Acta Neurochir (2012) 154:1371–1378

Combining Gliadel wafers and radiochemotherapy with TMZ may carry the risk of increased adverse events (AE). We analyzed the efficacy and safety in patients with glioblastoma who underwent multimodal treatment with implantation of Gliadel wafers.

Methods One hundred sixty-five consecutive patients with newly diagnosed (77 patients) or recurrent (88 patients) glioblastoma were studied. Forty-seven patients underwent surgery + Gliadel. The impact of age (≥65 vs. <65), resection extent (gross total vs. partial), use of Gliadel and adjuvant treatment (TMZ vs. other schemes/no adjuvant therapy) on overall survival (OS, for patients with newly diagnosed glioblastoma) and on recurrence-survival (for patients with recurrent glioblastoma) was analyzed with Cox regression. The impact of age, history (newly diagnosed vs. recurrent glioblastoma), number of Gliadel wafers implanted (0 vs. <8 vs. 8), resection extent (gross-total vs. partial) and adjuvant treatment (TMZ vs. other schemes/no adjuvant therapy) on the occurrence of AE and on the occurrence of implantation site-related AE (ISAE) was analyzed with the logistic regression model. Significance was set at p<0.05.

Results Multivariate analysis showed the only factor associated with longer survival, both for newly diagnosed and for recurrent GBM, was resection extent. Both patients with a higher number of wafers implanted and patients with recurrent tumors were significantly at risk for AE and ISAE. Patients with eight Gliadel wafers implanted had a 3-fold increased risk of AE and a 5.6-fold increased risk of ISAE, and patients with recurrent tumor had a 2.8-fold increased risk of AE and a 9.3-fold increased risk of ISAE.

Conclusions Adding Gliadel to standard treatment did not significantly improve the outcome. The toxicity after Gliadel use was significantly higher, both for patients with newly diagnosed and patients with recurrent glioblastoma.

Stereotactic radiosurgery after embolization for AVMs

J Neurosurg 117:265–275, 2012

In this paper the authors’ goal was to define the long-term benefits and risks of stereotactic radiosurgery (SRS) for patients with arteriovenous malformations (AVMs) who underwent prior embolization.

Methods. Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 120 patients underwent embolization followed by SRS. In this series, 64 patients (53%) had at least one prior hemorrhage. The median number of embolizations varied from 1 to 5. The median target volume was 6.6 cm3 (range 0.2–26.3 cm3). The median margin dose was 18 Gy (range 13.5–25 Gy).

Results. After embolization, 25 patients (21%) developed symptomatic neurological deficits. The overall rates of total obliteration documented by either angiography or MRI were 35%, 53%, 55%, and 59% at 3, 4, 5, and 10 years, respectively. Factors associated with a higher rate of AVM obliteration were smaller target volume, smaller maximum diameter, higher margin dose, timing of embolization during the most recent 10-year period (1997–2006), and lower Pollock-Flickinger score. Nine patients (8%) had a hemorrhage during the latency period, and 7 patients died of hemorrhage. The actuarial rates of AVM hemorrhage after SRS were 0.8%, 3.5%, 5.4%, 7.7%, and 7.7% at 1, 2, 3, 5, and 10 years, respectively. The overall annual hemorrhage rate was 2.7%. Factors associated with a higher risk of hemorrhage after SRS were a larger target volume and a larger number of prior hemorrhages. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 3 patients (2.5%) after SRS, and 1 patient had delayed cyst formation 210 months after SRS. No patient died of AREs. A larger 12-Gy volume was associated with higher risk of symptomatic AREs. Using a case-control matched approach, the authors found that patients who underwent embolization prior to SRS had a lower rate of total obliteration (p = 0.028) than patients who had not undergone embolization.

Conclusions. In this 20-year experience, the authors found that prior embolization reduced the rate of total obliteration after SRS, and that the risks of hemorrhage during the latency period were not affected by prior embolization. For patients who underwent embolization to volumes smaller than 8 cm3, success was significantly improved. A margin dose of 18 Gy or more also improved success. In the future, the role of embolization after SRS should be explored.

Long-term visual outcome after microsurgical removal of occipital lobe cavernomas

J Neurosurg 117:295–301, 2012

Cavernomas in the occipital lobe are relatively rare. Because of the proximity to the visual cortex and incoming subcortical tracts, microsurgical removal of occipital cavernomas may be associated with a risk of visual field defects. The goal of the study was to analyze long-term outcome after operative treatment of occipital cavernomas with special emphasis on visual outcome.

Methods. Of the 390 consecutive patients with cavernomas who were treated at Helsinki University Central Hospital between 1980 and 2011, 19 (5%) had occipital cavernomas. Sixteen patients (4%) were surgically treated and are included in this study. The median age was 39 years (range 3–59 years). Seven patients (56%) suffered from hemorrhage preoperatively, 5 (31%) presented with visual field deficits, 11 (69%) suffered from seizures, and 4 (25%) had multiple cavernomas. Surgery was indicated for progressive neurological deterioration. The median follow-up after surgery was 5.25 years (range 0.5–14 years).

Results. All patients underwent thorough neuroophthalmological assessment to determine visual outcome after surgery. Visual fields were classified as normal, mild homonymous visual field loss (not disturbing the patient, driving allowed), moderate homonymous visual field loss (disturbing the patient, driving prohibited), and severe visual field loss (total homonymous hemianopia or total homonymous quadrantanopia). At the last follow-up, 4 patients (25%) had normal visual fields, 6 (38%) had a mild visual field deficit, 1 (6%) complained of moderate visual field impairment, and 5 (31%) had severe homonymous visual field loss. Cavernomas seated deeper than 2 cm from the pial surface carried a 4.4-fold risk of postoperative visual field deficit relative to superficial ones (p = 0.034). Six (55%) of the 11 patients presenting with seizures were seizure-free postoperatively. Eleven (69%) of 16 patients had no disability during the long-term follow-up.

Conclusions. Surgical removal of occipital cavernomas may carry a significant risk of postoperative visual field deficit, and the risk is even higher for deeper lesions. Seizure outcome after removal of these cavernomas appeared to be worse than that after removal in other supratentorial locations. This should be taken into account during preoperative planning.