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Is inclusion of the occiput necessary in fusion for C1–2 instability in rheumatoid arthritis?

Is inclusion of the occiput necessary in fusion for C1–2 instability in rheumatoid arthritis?

J Neurosurg Spine 18:50–56, 2013

The atlantoaxial joint is the location most and earliest affected in patients with rheumatoid arthritis (RA). In longstanding disease, ligamentous and osseous destruction can progress and involve all cervical segments. If surgical intervention is necessary, some prefer, to be safe, undertaking fusion to the occiput, whereas others advocate 1-level fusion of C1–2. Sparing the occiput (Oc)–C1 segment would allow retention of a considerable amount of physiological range of motion and seems beneficial against subaxial overload. Previous clinical studies on this topic have provided only nonspecific data after short-term follow-up, rendering a segment-sparing approach questionable. The purpose of the present investigation was to assess long-term progression of inflammatory or degenerative destruction in the Oc–C1 segment after isolated C1–2 fusion for RA.

Methods. In a series of 113 consecutive patients with RA-related destruction restricted to the craniocervical junction, 14 individuals underwent Oc–C2 fusion and 99 underwent surgery exclusively at the C1–2 level. After a mean follow-up period of 9.4 years (range 4.9–14.7 years), 46 patients were available for clinical and radiographic examination, including CT imaging.

Results. None of the 46 patients needed additional surgery to extend the fusion to the occiput. Despite marked deterioration in the subaxial cervical spine, in general there were little or no changes in the atlantooccipital region. All but one patient presented with bony fusion of the fixed C1–2 level at follow-up.

Conclusions. The results of this investigation suggest that if the Oc–C1 joint is free of osseous destructions on conventional radiographs and free of abnormalities on MRI scans at the time of surgery (for transarticular fixation and fusion of C1–2), there is a very low risk for relevant destruction in the following 5–14 years. Thus, no prophylactic oligosegmental approach, but rather a segment-sparing monosegmental approach, is preferred, even in patients with high inflammatory levels.

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Spinal Glomus (Type II) Arteriovenous Malformations

Spinal Glomus (Type II) AVM

Neurosurgery 72:25–32, 2013

The natural history and treatment results for spinal glomus (type II) arteriovenous malformations (AVMs) remain relatively obscure.

OBJECTIVE: To calculate spinal glomus (type II) AVM hemorrhages rates and amalgamate results of intervention.

METHODS: We performed a pooled analysis via the PubMed database through May 2012, including studies with at least 3 cases. Data on individual patients were extracted and analyzed using a Cox proportional hazards regression model to obtain hazard ratios for hemorrhage risk factors.

RESULTS: The annual hemorrhage rate before treatment was 4% (95% confidence interval [confidence interval]: 3%-6%), increasing to 10% (95% CI: 7%-16%) for AVMs with previous hemorrhage. The hazard ratio for hemorrhage after hemorrhagic presentation was 2.25 (95% CI: 0.71-7.07), increasing to 13.0 within the first 10 years (95% CI: 1.44-118). The overall rates of complete obliteration were 78% (95% CI: 72%-83%) for surgery and 33% (95% CI: 24%-43%) for endovascular treatment. Long-term clinical worsening occurred in 12% of patients after surgical treatment (95% CI: 8%-16%) and in 13% after endovascular treatment (95% CI: 7%-21%). No hemorrhages occurred after complete obliteration. After partial surgical treatment, the annual hemorrhage rate was 3% (95% CI: 1%-6%); no hemorrhages were reported over 196 patient-years after partial endovascular treatment.

CONCLUSION: Spinal glomus (type II) AVMs with previous hemorrhage, particularly within 10 years, demonstrated a greater risk of hemorrhage. Complete obliteration and even partial endovascular treatment significantly decreased their hemorrhage rate.

KEY WORDS:

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Relationship of glioblastoma multiforme to the subventricular zone is associated with survival

Relationship of glioblastoma multiforme to the subventricular zone is associated with survival

Neuro-Oncology 15(1):91–96, 2013

The subventricular zone (SVZ) lines the lateral ventricles and represents the origin of neural and some cancer stem cells. Tumors contacting the SVZ may be more invasive with higher potential to recruit migratory progenitor cells.

Our specific aim was to determine whether SVZ involvement in glioblastoma multiforme (GBM) is associated with a higher recurrence rate and shorter overall survival.

MR imaging and clinical data from 91 patients with GBM treated at our institution were retrospectively reviewed. Tumors were classified as type I if the contrast- enhancing lesion contacted both the SVZ and cortex on pre-operative MRI, type II if only the SVZ was involved, type III if only cortex was involved, and type IV if the lesion did not contact either the SVZ or cortex. Progression-free survival (PFS) and overall survival were estimated based on Kaplan-Meier calculations.

When comparing type I tumors with types II-IV, only 39% of patients with type I tumors were free of recurrence and alive at 6 months, significantly fewer than for all other types combined (67%; P = .01). PFS at 6 months was also less, at only 47% among patients with SVZ-positive tumors, compared with 69% in the SVZ-negative group (P = .002). Patients with SVZ involvement also demonstrated a more rapid time to progression, compared with those not involving the SVZ (P = .003). Patients with GBM involving the SVZ have decreased overall survival and PFS, which may have prognostic and therapeutic implications.

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Spinal Robotics: Current Applications and Future Perspectives

Robotics Spinal Surgery

Neurosurgery 72:A12–A18, 2013

Even though robotic technology holds great potential for performing spinal surgery and advancing neurosurgical techniques, it is of utmost importance to establish its practicality and to demonstrate better clinical outcomes compared with traditional techniques, especially in the current cost-effective era. Several systems have proved to be safe and reliable in the execution of tasks on a routine basis, are commercially available, and are used for specific indications in spine surgery. However, workflow, usability, interdisciplinary setups, efficacy, and cost-effectiveness have to be proven prospectively.

This article includes a short description of robotic structures and workflow, followed by preliminary results of a randomized prospective study comparing conventional free-hand techniques with routine spine navigation and robotic-assisted procedures. Additionally, we present cases performed with a spinal robotic device, assessing not only the accuracy of the robotic-assisted procedure but also other factors (eg, minimal invasiveness, radiation dosage, and learning curves).

Currently, the use of robotics in spinal surgery greatly enhances the application of minimally invasive procedures by increasing accuracy and reducing radiation exposure for patients and surgeons compared with standard procedures. Second-generation hardware and software upgrades of existing devices will enhance workflow and intraoperative setup. As more studies are published in this field, robot-assisted therapies will gain wider acceptance in the near future.

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The Value of Scheduled Repeat Cranial Computed Tomography After Mild Head Injury

concusion_TBI

Neurosurgery 72:56–64, 2013

After an initial computed tomography (CT) scan revealing intracranial hemorrhage resulting from traumatic brain injury, a standard of care in many trauma centers is to schedule a repeat CT scan to rule out possible progression of bleed.

OBJECTIVE: To evaluate the utility of routine follow-up CT in changing the management of mild head injury patients despite clinical stability, although repeat imaging is indicated to assess a deteriorating patient.

METHODS: The trauma database at our institution was retrospectively reviewed and the literature was searched to identify patients after mild head injury with positive initial CT finding and scheduled repeat scan. Patients were divided into 2 groups for comparison. Group A included patients who had intervention based on neurological examination changes. Group B comprised patients requiring a change in management according to CT results exclusively. The meta-analysis of the present cohort and included articles was performed with a random-effects model.

RESULTS: Overall, 15 studies and 445 patients met our eligibility criteria, totaling 2693 patients. Intervention rates of groups A and B were 2.7% (95% confidence interval, 1.7-3.9; P = .003) and 0.6% (95% confidence interval, 0.3-1; P = .21), respectively. The statistical difference between both intervention rates was clinically significant with P , .001.

CONCLUSION: The available evidence indicates that it is unnecessary to schedule a repeat CT scan after mild head injury when patients are unchanged or improving neurologically. In the absence of supporting data, we question the value of routine follow-up imaging given the associated accumulative increase in cost and risks.

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Total Disc Replacement for Chronic Discogenic Low Back Pain: A Cochrane Review

TDR

 Spine 2013 ; 38 : 24 – 36

Study Design. Systematic literature review.

Objective. To assess the effect of total disc replacement for chronic low back pain due to lumbar degenerative disc disease compared with fusion or other treatment options.

Summary of Background Data. There is an increasing use in disc replacement devices for degenerative disc disease, but their effectiveness compared with other interventions such as fusion of the motion segment or conservative treatment remains unclear.

Methods. A comprehensive search in PubMedCentral, MEDLINE, EMBASE, BIOSIS, ClinicalTrials.gov, and FDA trials register was conducted. Randomized controlled trials comparing total disc replacement with any other intervention for degenerative disc disease were included. Risk of bias was assessed using the criteria of the Cochrane Back Review Group. Quality of evidence was graded according to the GRADE approach. Two review authors independently selected studies, assessed risk of bias, and extracted data. Results and upper bounds of confidence intervals were compared with predefined clinically relevant differences.

Results. We included 7 randomized controlled trials with a follow-up of 24 months. There is risk of bias in the included studies due to sponsoring and absence of any kind of blinding. One study compared disc replacement with rehabilitation and found a signifi cant advantage in favor of surgery, which, however, did not reach the predefi ned threshold. Six studies compared disc replacement with fusion and found that the mean improvement in visual analogue scale score of back pain was 5.2 mm higher (2 studies; 95% confidence interval 0.2–10.3) with a low quality of evidence. The improvement of Oswestry disability index score at 24 months in the disc replacement group was 4.3 points more than in the fusion group (5 studies; 95% confidence interval 1.85–6.68) with a low quality of evidence. Both upper bounds of the confidence intervals were below the predefined clinically relevant difference.

Conclusion. Although statistically significant, the differences in clinical improvement were not beyond generally accepted boundaries for clinical relevance. Prevention of adjacent level disease and/or facet joint degeneration was not properly assessed. Therefore, because we think that harm and complications may occur after some years, the spine surgery community should be prudent to adopt this technology on a large scale, despite the fact that total disc replacement seems to be effective in treating low back pain in selected patients, and in the short term is at least equivalent to fusion surgery.

Key words: s.

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Transphenoidal surgery in acromegalic patients: anatomical considerations and potential pitfalls

Transphenoidal surgery in acromegalic patients- anatomical considerations and potential pitfalls.1 Transphenoidal surgery in acromegalic patients- anatomical considerations and potential pitfalls

Acta Neurochir (2013) 155:125–130

Transphenoidal surgery is an effective treatment for acromegalic patients with growth hormone (GH) producing pituitary adenomas. Since acromegaly is a systemic disease which causes multiple bony alterations, we hypothesized that it could affect the sphenoid sinus anatomy. The aim of the study was to determine whether acromegalic patients have sphenoid sinus alterations with potential surgical impact.

Methods Fourty-six consecutive patients (23 acromegalics- GH group, 23 non-acromegalics-nGH group) undergoing transphenoidal surgery were included in this study. Preoperative volumetric CT scan of the head was used to assess the following anatomic characteristics: type of sphenoid sinus (sellar, pre-sellar, conchal); number of intrasphenoid septa; number of carotid-directed septa; intercarotid distance; depth of the sphenoid sinus; depth and size of the sella.

Results The sphenoid sinus was of the pre-sellar/conchal type in 26 % of the patients with acromegaly (n023) versus 9 % of the patients of the nGH group (n023). The number of intrasphenoid septations was significantly higher in the GH group than in the nGH group (P=.03). Interestingly, the intercarotid distance was smaller in GH patients than in nGH displaying a trend toward significance (P=.05). The sphenoid bone was deeper in the GH group as compared to the nGH group (P=.01) but the distance sphenoid sinus-sella was reduced (P<.01). Finally, the sella was not deeper, nor larger in acromegalic patients.

Conclusions The sphenoid sinus of acromegalic patients resulted in being deeper, characterized by more septa and by a reduced intercarotid distance. These alterations deserve special pre- and intraoperative care, being potentially responsible for surgical difficulties.

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ELTD1, a Potential New Biomarker for Gliomas

ELTD1, a Potential New Biomarker for Gliomas

Neurosurgery 72:77–91, 2013

Glioblastoma multiforme (GBM), a high-grade glioma, is characterized by being diffuse, invasive, and highly angiogenic and has a very poor prognosis. Identification of new biomarkers could help in the further diagnosis of GBM.

OBJECTIVE: To identify ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1) as a putative gliomaassociated marker via a bioinformatic method.

METHODS: We used advanced data mining and a novel bioinformatics method to predict ELTD1 as a potential novel biomarker that is associated with gliomas. Validation was done with immunohistochemistry, which was used to detect levels of ELTD1 in human high-grade gliomas and rat F98 glioma tumors. In vivo levels of ELTD1 in rat F98 gliomas were assessed using molecular magnetic resonance imaging.

RESULTS: ELTD1 was found to be significantly higher (P = .03) in high-grade gliomas (50 patients) compared with low-grade gliomas (21 patients) and compared well with traditional immunohistochemistry markers including vascular endothelial growth factor, glucose transporter 1, carbonic anhydrase IX, and hypoxia-inducible factor 1a. ELTD1 gene expression indicates an association with grade, survival across grade, and an increase in the mesenchymal subtype. Significantly high (P , .001) in vivo levels of ELTD1 were additionally found in F98 tumors compared with normal brain tissue.

CONCLUSION: Results of this study strongly suggests that associative analysis was able to accurately identify ELTD1 as a putative glioma-associated biomarker. The detection of ELTD1 was also validated in both rodent and human gliomas and may serve as an additional biomarker for gliomas in preclinical and clinical diagnosis of gliomas.

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Analysis of lumbar plexopathies and nerve injury after lateral retroperitoneal transpsoas approach

Analysis of lumbar plexopathies and nerve injury after lateral retroperitoneal transpsoas approach

DOI: 10.3171/2012.11.SPINE12755

The minimally invasive lateral transpsoas approach has become an increasingly popular means of fusion. The most frequent complication is related to lumbar plexus nerve injuries; these can be diagnosed based on distribution of neurological deficit following the motor and/or sensory nerve injury. However, the literature has failed to provide a clinically relevant description of these complications. With accurate clinical diagnosis, spine practitioners can provide more precise prognostic and management recommendations to include observation, nerve blocks, neurodestructive procedures, medications, or surgical repair strategies. The purpose of this study was to standardize the clinical findings of lumbar plexopathies and nerve injuries associated with minimally invasive lateral retroperitoneal transpsoas lumbar fusion.

Methods. A thorough literature search of the MEDLINE database up to June 2012 was performed to identify studies that reported lumbar plexus and nerve injuries after the minimally invasive lateral retroperitoneal transpsoas approach. Included studies were assessed for described neurological deficits postoperatively. Studies that did attempt to describe nerve-related complications clinically were excluded. A clinically relevant assessment of lumbar plexus nerve injury was derived to standardize early diagnosis and outline prognostic implications.

Results. A total of 18 studies were selected with a total of 2310 patients; 304 patients were reported to have possible plexus-related complications. The incidence of documented nerve and/or root injury and abdominal paresis ranged from 0% to 3.4% and 4.2%, respectively. Motor weakness ranged from 0.7% to 33.6%. Sensory complications ranged from 0% to 75%. A lack of consistency in the descriptions of the lumbar plexopathies and/or nerve injuries as well as a lack of diagnostic paradigms was noted across studies reviewed. Sensory dermal zones were established and a standardized approach was proposed.

Conclusions. There is underreporting of postoperative lumbar plexus nerve injury and a lack of standardization of clinical findings of neural complications related to the minimally invasive lateral retroperitoneal transpsoas approach. The authors provide a diagnostic paradigm that allows for an efficient and accurate classification of postoperative lumbar plexopathies and nerve injuries.

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Endoscopic endonasal surgery for giant pituitary adenomas: advantages and limitations

Endoscopic endonasal surgery limitations

J Neurosurg / January 4, 2013. DOI: 10.3171/2012.11.JNS121190

Giant pituitary adenomas (> 4 cm in maximum diameter) represent a significant surgical challenge. Endoscopic endonasal surgery (EES) has recently been introduced as a treatment option for these tumors. The authors present the results of EES for giant adenomas and analyze the advantages and limitations of this technique.

Methods. The authors retrospectively reviewed the medical files and imaging studies of 54 patients with giant pituitary adenomas who underwent EES and studied the factors affecting surgical outcome.

Results. Preoperative visual impairment was present in 45 patients (83%) and partial or complete pituitary deficiency in 28 cases (52%), and 7 patients (13%) presented with apoplexy. Near-total resection (> 90%) was achieved in 36 patients (66.7%). Vision was improved or normalized in 36 cases (80%) and worsened in 2 cases due to apoplexy of residual tumor. Significant factors that limited the degree of resection were a multilobular configuration of the adenoma (p = 0.002) and extension to the middle fossa (p = 0.045). Cavernous sinus invasion, tumor size, and intraventricular or posterior fossa extension did not influence the surgical outcome. Complications included apoplexy of residual adenoma (3.7%), permanent diabetes insipidus (9.6%), new pituitary insufficiency (16.7%), and CSF leak (16.7%, which was reduced to 7.4% in recent years). Fourteen patients underwent radiation therapy after EES for residual mass or, in a later stage, for recurrence, and 10 with functional pituitary adenomas received medical treatment. During a mean follow-up of 37.9 months (range 1–114 months), 7 patients were reoperated on for tumor recurrence. Three patients were lost to follow-up.

Conclusions. Endoscopic endonasal surgery provides effective initial management of giant pituitary adenomas with favorable results compared with traditional microscopic transsphenoidal and transcranial approaches.

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Patterns of Aneurysm Recurrence After Microsurgical Clip Obliteration

Patterns of Aneurysm Recurrence After Microsurgical Clip Obliteration

Neurosurgery 72:65–69, 2013

Microsurgical clip obliteration remains a time-honored and viable option for the treatment of select aneurysms with very low rates of recurrence.

OBJECTIVE: We studied previously clipped aneurysms that were found to have recurrences to better understand the patterns and configurations of these rare entities.

METHODS: A retrospective review was performed of 2 prospectively maintained databases of aneurysm treatments from 2 institutions spanning 14 years to identify patients with recurrence of previously clipped intracranial aneurysms.

RESULTS: Twenty-six aneurysm recurrences were identified. Three types of recurrence were identified: type I, proximal to the clip tines; type II, distal; and type III, lateral. The most common type of recurrence was that arising distal to the clip tines (46.1%), and the least frequently encountered recurrence was that arising proximal to the tines (19.2%). Laterally located recurrences were found in 34.6% of cases.

CONCLUSION: We describe 3 different patterns of aneurysm recurrence with respect to clip application: those occurring proximal, distal, or lateral to the clip tines.

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Dorsal location of the cochlear nerve on vestibular schwannoma: preoperative evaluation, frequency, and functional outcome

Dorsal location of the cochlear nerve on vestibular schwannoma

Neurosurg Rev (2013) 36:39–44

The cochlear nerve is most commonly located on the caudoventral portion of the capsule of vestibular schwannomas and rarely on the dorsal portion. In such a condition, total removal of the tumor without cochlear nerve dysfunction is extremely difficult.

The purpose of our study was to identify the frequency of this anatomical condition and the status of postoperative cochlear nerve function; we also discuss the preoperative radiological findings.

The study involved 114 patients with unilateral vestibular schwannomas operated on via a retrosigmoid (lateral suboccipital) approach. Locations of the cochlear nerve on the tumor capsule were ventral, dorsal, caudal, and rostral. Ventral and dorsal locations were further subdivided into rostral, middle, and caudal third of the tumor capsule. The postoperative cochlear nerve function and preoperative magnetic resonance (MR) findings were reviewed retrospectively.

In 56 patients that had useful preoperative hearing, useful hearing was retained in 50.0 % (28 of 56) of patients after surgery. The cochlear nerve was located on the dorsal portion of the tumor capsule in four patients (3.5 %), and useful hearing was preserved in only one of these patients (25 %) in whom the tumor had been partially resected.

This tumor-nerve anatomical relationship was identified in all tumors of <2 cm at preoperative MR cisternography. MR cisternography has the potential to identify the tumor–nerve anatomical relationship, especially in small-sized tumors that usually require therapeutic intervention that ensures hearing preservation. Hence, careful evaluation of the preoperative MR cisternography is important in deciding the therapeutic indications.

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Retrograde Leptomeningeal Venous Drainage and Venous Congestion With Dural Arteriovenous Fistula

The Use of Susceptibility-Weighted Imaging as an Indicator of Retrograde Leptomeningeal Venous Drainage and Venous Congestion With Dural Arteriovenous Fistula

Neurosurgery 72:47–55, 2013

Retrograde leptomeningeal venous drainage (RLVD) in dural arteriovenous fistulas (DAVFs) is associated with intracerebral hemorrhage and nonhemorrhagic neurological deficits or death. Angiographic evidence of RLVD is a definite indication for treatment, but less invasive methods of identifying RLVD are required.

OBJECTIVE: To evaluate the efficacy of susceptibility-weighted magnetic resonance imaging (SWI) in detecting RLVD in DAVFs.

METHODS: We retrospectively identified 17 DAVF patients who had angiographic evidence of RLVD and received treatment. Conventional angiography and SWI were assessed at pretreatment and posttreatment time points. The presence of RLVD on SWI was defined as cortical venous hyperintensity, and the presence of venous congestion on SWI venograms was defined as increased caliber of cortical or medullary veins.

RESULTS: Cortical venous hyperintensity was identified in pretreatment SWI of 15 patients. Cortical venous hyperintensity was absent in early posttreatment SWI, consistent with the absence of RLVD in posttreatment angiography, in all but one of these patients. In 2 patients, cortical venous hyperintensity was identified during follow-up, indicating the recurrence of RLVD. Cortical venous hyperintensity was not identified in the pretreatment SWI of 2 patients despite angiographic evidence of RLVD. Venous congestion was identified in pretreatment SWI venograms of 11 patients and had an appearance similar to that identified from angiography. Venous congestive signs improved over the follow-up period.

CONCLUSION: The presence of SWI hyperintensity within the venous structure could be a useful indicator of RLVD in DAVF patients. Thus, SWI offers a noninvasive alternative to angiography for the identification of RLVD in pretreated and posttreated DAVF patients.

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Clinical outcomes of tuberculum sellae meningiomas focusing on reversibility of postoperative visual function

Tuberculum Sellae Meningiomas

Acta Neurochir (2013) 155:25–31

Tuberculum sellae meningiomas present a special challenge because of their proximity to major arteries, visual pathways, and the hypothalamus. The aim of this study was to determine the prognostic determinants of clinical and visual outcomes of these tumors, focusing on the functional reversibility of an unserviceable eye after surgery.

Methods We retrospectively reviewed 86 patients on the basis of clinical and radiological factors that appeared to affect outcome. The visual acuity and visual fields were analyzed according to the visual impairment score (VIS). Unserviceable visual acuity included no perception of light (NPL), hand movement (HM), and counting fingers (CF). Ophthalmological functioning was tested in the preoperative period, the postoperative short-term period (≤2 weeks after surgery), and the postoperative long-term period (>6 months after surgery). Our own clinical outcome criteria including tumor control, visual improvement, and complications were used for evaluation.

Results Seventy-four of 86 patients (86 %) underwent total removal of the tumor. In three of these cases (3.4 %), recurrence developed. Thirty patients were classified into the “Excellent” group, 21 into the “Good” group, 20 into the “Fair” group, and 15 into the “Poor” group. In multivariate analysis, adhesion to optic nerve was an independent and significant predictor of clinical outcome. Favorable visual outcomes in both short- and long-term postoperative periods were achieved in 80.8%of cases. Preoperative and short-term visual outcomes were closely related to long-term visual outcome. Six of eight patients with preoperative CF status showed reversibility to a serviceable status after surgery. However, there was no conversion to serviceable status from NPL or HM.

Conclusions For patients with unilateral unserviceable visual function, maintenance of serviceable visual function on the opposite side might be more important. Of the patients with unserviceable visual function, careful surgery might be able to improve the visual function in CF eyes.

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Targeted therapy with bevacizumab and erlotinib tailored to the molecular profile of patients with recurrent glioblastoma

Targeted therapy with bevacizumab and erlotinib tailored to the molecular profile of patients with recurrent glioblastoma

Acta Neurochir (2013) 155:33–40

Advances in comprehension of molecular biology of glioblastoma (GBM) have led to the development of targeted therapies. The aim of the present study was to evaluate the efficacy and safety of a targeted therapeutic approach in which administration of bevacizumab and erlotinib was tailored on the molecular profile of recurrent GBM.

Methods We prospectively enrolled ten adult patients suffering from recurrent GBM who had undergone surgical resection and standard chemo-radiotherapy. Tumor tissue was assessed for the expression of EGFRvIII and MGMT promoter methylation by RT-PCR, and for PTEN and VEGF expression by immunohistochemistry. Normal PTEN status was required for inclusion. Patients with VEGF overexpressing tumors (10/10) were treated with bevacizumab (10 mg/kg iv every 2 weeks in 6-weekcycles); patients whose tumor expressed EGFRvIII (4/ 10) added erlotinib (150 mg/day orally; 300 mg/day if on enzyme-inducing antiepileptic drugs). Therapy was continued until disease progression or unacceptable toxicity. Primary endpoints of the study were response rate (RR), 6-month progression-free survival (PFS-6), and safety profile.

Results The RR and PFS-6 were 100 % (4/4) and 50 % (3/6) in patients treated with bevacizumab+erlotinib (n=4) and bevacizumab (n=6), respectively. In the whole cohort (n= 10), RR and PFS-6 were both 70 % (7/10); median PFS and overall survival (OS) were 8.0 (3.0–31.0) and 9.5 (5.0–31.0) months, respectively. No grade 3/4 adverse events were observed; three patients treated with bevacizumab+erlotinib displayed grade 1/2 rash not requiring dose reduction; one patient treated with bevacizumab developed intratumoral hemorrhage requiring treatment discontinuation.

Conclusion To our knowledge, this is the first study on recurrent GBM in which administration of bevacizumab and erlotinib was tailored on the molecular profile of the patient’s tumor. Although we treated a limited number of patients, we obtained significantly higher RR and PFS-6 than those reported in a previous trial lacking molecular tumor analysis.

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Factors affecting peritumoral brain edema in meningioma: special histological subtypes with prominently extensive edema

Peritumoral edema in meningioma

J Neurooncol (2013) 111:49–57

Various degrees of peritumoral brain edema (PTBE) are observed in patients with intracranial meningiomas. Factors affecting the occurrence of PTBE in intracranial meningioma were investigated.

PTBE was investigated retrospectively for 110 patients with primary intracranial meningiomas. Predictive factors related to PTBE were analyzed, for example patient age, sex, magnetic resonance imaging features (contrast enhancement, tumor shape, tumor location, tumor volume), angiographical features (tumor stain, pial–cortical arterial supply, venous obstruction), and histopathological features (histological subtypes, mindbomb homolog 1 labeling index (MIB1-LI)). Histological subtypes were classified into World Health Organization (WHO) grade I common type (meningothelial, transitional, fibrous), grade I uncommon type, and grade II and III types. The extent of PTBE was assessed by calculation of the edema index (EI).

PTBE was present in 53 cases (48 %). Male sex, heterogeneous enhancement, superficial location, tumor volume (≥10 cm3), remarkable tumor stain, pial supply, venous obstruction, malignant pathology, and MIB1-LI ≥4 % were correlated with PTBE in univariate analysis. Pial supply and remarkable tumor stain were correlated with PTBE in multivariate analysis. WHO grade I uncommon type had obviously higher EI than WHO grade I common type, and WHO grade II and III types (P<0.001). Seven cases with prominently high EI (EI ≥10) were all WHO grade I uncommon type, including angiomatous, microcystic, secretory, and lymphoplasmacyte-rich meningioma. Prominently extensive PTBE might indicate the presence of WHO grade I uncommon type meningioma.

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Microsurgical Management of Jugular Foramen Schwannomas

Primary Jugular Foramen Meningioma- Imaging Appearance and Differentiating Features1

Neurosurgery 72:42–46, 2013

Jugular foramen schwannomas are uncommon and surgically challenging lesions.

OBJECTIVE: To determine the importance of surgical technique on morbidity and recurrence of jugular foramen schwannomas.

METHODS: A retrospective review and case-control analysis of a single-senior-surgeon series of 81 patients with surgically treated jugular foramen schwannomas was performed, focusing on operative technique. Patients undergoing an aggressive, total tumor resection (series 1) were compared with those undergoing more conservative resection focusing on preserving the pars nervosa (series 2).

RESULTS: There was a statistically significant (P = .04) decrease in permanent deficits of the cranial nerve 9/10 complex with a conservative technique. Recurrence was seen in 3 patients (5.7%) in series 1 and in 3 patients (10.7%) in series 2 (P = .36). Recurrence was treated with reoperation in 1 patient, radiation in 1 patient, and observation in the others.

CONCLUSION: Although radical gross total resection is desirable, it is not optimal for cranial nerve preservation in patients with jugular foramen schwannomas. A more conservative approach resulted in a statistically significant decrease in lower cranial nerve deficits. There was a nonstatistically significant trend toward increasing recurrence, which may be treated with multiple modality therapy in the modern era.

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Lateral Extracavitary vs Costotransversectomy Approaches to the Thoracic Spine

Lateral Extracavitary vs Costotransversectomy Approaches to the Thoracic Spine- Reflections on Lessons Learned Lateral Extracavitary vs Costotransversectomy Approaches to the Thoracic Spine- Reflections on Lessons Learned_2

Neurosurgery 71:1096–1102, 2012

The lateral extracavitary approach (LECA) and costotransversectomy (CTE) are 2 dorsolateral approaches that avoid entrance into the pleural cavity and facilitate ventral decompression. The indications and outcomes of each of these approaches have not been fully defined in the literature.

OBJECTIVE: To assess the techniques, indications, and complications associated with the LECA and CTE approaches to the thoracic spine.

METHODS: A retrospective analysis was performed on all patients who underwent LECA and CTE between 2000 and 2009 at our institution.

RESULTS: A total of 54 patient charts were reviewed (19 LECA, 35 CTE). Indications for operation included disk herniation, trauma, tumor, osteomyelitis, and scoliosis/kyphosis. Osteomyelitis was treated significantly more often with LECA (47%) than with CTE (9%; P = .002). Mean blood loss was 2134 mL and 1556 mL (P = .3) in LECA and CTE, respectively, and hospital stay was 17.2 days for LECA and 9.8 days for CTE (P = .07). Thirteen LECA patients (68%) and 19 CTE patients (54%; P = 1.0) had preoperative or postoperative complications.

CONCLUSION: LECA was used more often to treat complex pathologies such as osteomyelitis and trended toward significance for more frequent use in extensive procedures involving 1- or 2-level corpectomies. As can be expected, CTE was associated with slightly less blood loss and a shorter hospital stay compared with the more extensive LECA operation. Adverse outcomes occurred with similar frequency for CTE and LECA.

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Frontal cortico-subcortical functional anatomy

Subcortical surgical anatomy of the lateral frontal region

J Neurosurg 117:1053–1069, 2012

Recent neuroimaging and surgical results support the crucial role of white matter in mediating motor and higher-level processing within the frontal lobe, while suggesting the limited compensatory capacity after damage to subcortical structures. Consequently, an accurate knowledge of the anatomofunctional organization of the pathways running within this region is mandatory for planning safe and effective surgical approaches to different diseases. The aim of this dissection study was to improve the neurosurgeon’s awareness of the subcortical anatomofunctional architecture for a lateral approach to the frontal region, to optimize both resection and postoperative outcome.

Methods. Ten human hemispheres (5 left, 5 right) were dissected according to the Klingler technique. Proceeding lateromedially, the main association and projection tracts as well as the deeper basal structures were identified. The authors describe the anatomy and the relationships among the exposed structures in both a systematic and topographical surgical perspective. Structural results were also correlated to the functional responses obtained during resections of infiltrative frontal tumors guided by direct cortico-subcortical electrostimulation with patients in the awake condition.

Results. The eloquent boundaries crucial for a safe frontal lobectomy or an extensive lesionectomy are as follows: 1) the motor cortex; 2) the pyramidal tract and premotor fibers in the posterior and posteromedial part of the surgical field; 3) the inferior frontooccipital fascicle and the superior longitudinal fascicle posterolaterally; and 4) underneath the inferior frontal gyrus, the head of the caudate nucleus, and the tip of the frontal horn of the lateral ventricle in the depth.

Conclusions. Optimization of results following brain surgery, especially within the frontal lobe, requires a perfect knowledge of functional anatomy, not only at the cortical level but also with regard to subcortical white matter connectivity.

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Awake mapping for resection of cavernous angioma and surrounding gliosis in the left dominant hemisphere

Awake mapping for resection of cavernous angioma and surrounding gliosis in the left dominant hemisphere

J Neurosurg 117:1076–1081, 2012

Maximal resection of symptomatic cavernous angioma (CA), including its surrounding gliosis if possible, has been recommended to minimize the risk of seizures or (re)bleeding. However, despite recent neurosurgical advances, such extensive CA removal is still a challenge in eloquent areas. The authors report a consecutive series of patients who underwent awake surgery for CA within the left dominant hemisphere in which intraoperative cortical– subcortical electrical stimulation was used.

Methods. Nine patients harboring a CA that was revealed by seizures in 6 cases and bleeding in 3 cases underwent resection. All CAs were located in the left dominant hemisphere: 3 temporal, 2 insular, 2 parietal, and 2 in the parietotemporal region. Awake mapping was performed in all cases by using intraoperative cortical–subcortical electrical stimulation and ultrasonography (except in 1 insular CA in which a neuronavigation system was used).

Results. Total removal of the CA was achieved in all patients, with identification and preservation of language and sensory-motor structures. In addition, the pericavernomatous gliosis was removed in 7 cases, according to the functional boundaries provided by intraoperative subcortical stimulation. In 2 cases, subcortical mapping revealed eloquent areas within the surrounding gliosis, which was voluntarily avoided. There was no postsurgical permanent deficit, no rebleeding, and no epilepsy in 7 cases (2 patients had rare seizures in the 1st year or two after surgery, and then complete arrest), with a mean follow-up of 28.5 months (range 3–64 months).

Conclusions. These results suggest that intraoperative cortical–subcortical stimulation in awake patients represents a valuable adjunct to image-guided surgery with the aim of selecting the safer surgical approach for CAs involving eloquent areas. Moreover, such online mapping can be helpful when removing the pericavernomatous gliosis while preserving functional structures, which can persist within the hemosiderin rim. Thus, the authors propose that awake surgery be routinely considered, both to optimize the resection and to improve the quality of life through seizure control and avoidance of (re)bleeding for CAs located in the left dominant hemisphere.

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