Plectin plays a role in the migration and volume regulation of astrocytes: a potential biomarker of glioblastoma.

BACKGROUND: The expression of aquaporin 4 (AQP4) and intermediate filament (IF) proteins is altered in malignant glioblastoma (GBM), yet the expression of the major IF-based cytolinker, plectin (PLEC), and its contribution to GBM migration and invasiveness, are unknown. Here, we assessed the contribution of plectin in affecting the distribution of plasmalemmal AQP4 aggregates, migratory properties, and regulation of cell volume in astrocytes. METHODS: In human GBM, the expression of glial fibrillary acidic protein (GFAP), AQP4 and PLEC transcripts was analyzed using publicly available datasets, and the colocalization of PLEC with AQP4 and with GFAP was determined by immunohistochemistry. We performed experiments on wild-type and plectin-deficient primary and immortalized mouse astrocytes, human astrocytes and permanent cell lines (U-251 MG and T98G) derived from a human malignant GBM. The expression of plectin isoforms in mouse astrocytes was assessed by quantitative real-time PCR. Transfection, immunolabeling and confocal microscopy were used to assess plectin-induced alterations in the distribution of the cytoskeleton, the influence of plectin and its isoforms on the abundance and size of plasmalemmal AQP4 aggregates, and the presence of plectin at the plasma membrane. The release of plectin from cells was measured by ELISA. The migration and dynamics of cell volume regulation of immortalized astrocytes were assessed by the wound-healing assay and calcein labeling, respectively. RESULTS: A positive correlation was found between plectin and AQP4 at the level of gene expression and protein localization in tumorous brain samples. Deficiency of plectin led to a decrease in the abundance and size of plasmalemmal AQP4 aggregates and altered distribution and bundling of the cytoskeleton. Astrocytes predominantly expressed P1c, P1e, and P1g plectin isoforms. The predominant plectin isoform associated with plasmalemmal AQP4 aggregates was P1c, which also affected the mobility of astrocytes most prominently. In the absence of plectin, the collective migration of astrocytes was impaired and the dynamics of cytoplasmic volume changes in peripheral cell regions decreased. Plectin's abundance on the plasma membrane surface and its release from cells were increased in the GBM cell lines. CONCLUSIONS: Plectin affects cellular properties that contribute to the pathology of GBM. The observed increase in both cell surface and released plectin levels represents a potential biomarker and therapeutic target in the diagnostics and treatment of GBMs.

Direct Transpedicular C2 Fixation for the Surgical Management of Hangman's Fractures: A "Second Youth" for the Judet Approach.

PURPOSE: The optimal management of hangman's fractures is controversial and the standard of care has been neither established nor supported by strong evidence. The Judet approach has been introduced in 1970 as surgical option to treat selected cases of hangman's fractures, harboring the advantage to preserve motion of the craniovertebral junction and to restore the C2 vertebra anatomy by insertion of transpedicular screws through the fracture line. This paper reviews the literature on hangman's fractures surgically managed by Judet approach, and reports two new illustrative cases. METHODS: The PubMed database was searched for the review process. After initial screening of abstracts and papers, 13 manuscripts were included in the present review.Two cases of hangman's fractures, a Levine-Edwards type I and a type IIA, respectively, treated with direct transpedicular C2 screw fixation are reported. Surgical steps of the Judet approach are also described. RESULTS: Our literature review revealed that the technique described by Judet is gaining appeal only in recent years and there is no consensus on surgical indications.No surgery-related complications were observed in the two reported cases. Patients experienced a significant reduction of neck pain postoperatively. Motion of craniovertebral junction was preserved in both patients at 3-, 6-, and 12-month follow-ups. CONCLUSIONS: Direct transpedicular osteosynthesis of C2-pars interarticularis fracture has been already demonstrated as effective in type II and IIA hangman's fractures. The application of such technique in selected patients with atypical type I fractures should also be considered in order to achieve early mobilization and avoid external fixation.

Hybrid Implants in Anterior Cervical Spine Surgery: The State of the Art and New Trends for Multilevel Degenerative Disc Disease.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) still represents the first surgical option in the treatment of cervical degenerative disc disease (DDD) but is still burdened by several complications secondary to the loss of mobility at the treated segment and adjacent segment diseases (ASDs). To overcome those complications, hybrid surgery (HS) incorporating ACDF and cervical disc arthroplasty (CDA) is increasingly performed for DDD. METHODS: We retrospectively reviewed the clinical, surgical, and outcome data of 85 consecutive patients (M/F, 41/44) harboring cervical disc herniation with or without osteophytes, with radiculopathy and with or without myelopathy, who underwent the anterior approach to a cervical discectomy on two or more levels with at least one disc prosthesis, along with a cage and plate or an O Profile screwed plate. RESULTS: All the patients improved regardless of the cervical construct used. No significant relationship between different kinds of prosthesis and their surgical level; the number of cages; and the site of the cages (screwed and/or plated) was found concerning immediate stability, dynamic prosthesis effectiveness, and clinical improvement in all the patients up to the maximum follow-up time. CONCLUSIONS: Although the optimal surgical technique for cervical DDD remains controversial, HS represents a safe and effective procedure in select patients with multilevel cervical DDD, as demonstrated by biomechanical and clinical studies and the present series.

Image-Guided Surgery in Complex Skull Base and Facial Fractures: Initial Experience on the Role of Intra-Operative Computer Tomography.

Surgery of fractures involving the skull base and the facial skeleton often presents challenges that should be addressed to prevent secondary brain injuries (i.e., cerebro-spinal fluid leak), preserve visual functioning, and guarantee a good esthetic result. Complex craniofacial reconstruction can be aided by navigation and pre-operative planning. In recent years, computerized planning of surgical reconstruction drastically increased the safety and efficacy of surgery, but the impact of intraoperative high quality image devices such as an intraoperative computed tomography (CT) scan has not been investigated yet. This case-control study reports the institutional preliminary experience of using intraoperative CT scans in the surgical management of complex cranio-facial fractures. The results in terms of accuracy of bony reconstruction and neurological or surgical complications have been analyzed in 12 consecutive patients treated with (6 cases) or without (6 cases) i-CT. Comparative analysis demonstrated a greater accuracy of reconstruction in patients treated with the assistance of i-CT. Intraoperative CT is a useful tool with a promising role in a multidisciplinary surgical approach to complex cranio-facial surgery.

Retro-odontoid Degenerative Pseudotumour Causing Spinal Cord Compression and Myelopathy: Current Evidence on the Role of Posterior C1-C2 Fixation in Treatment.

BACKGROUND: A retro-odontoid pseudotumour compressing the spinal cord and causing myelopathy is often associated with an inflammatory condition such as rheumatoid arthritis. A degenerative non-inflammatory retro-odontoid pseudotumour responsible for clinically relevant spinal cord compression is a rare condition described in small clinical series and is likely associated with craniovertebral junction hypermobility or instability-like conditions. For several years, direct removal of the lesion through an anterior or lateral approach has been advocated as the best surgical option. However, in the last decade the posterior approach to the craniovertebral junction, to perform C1-C2 fixation and C1 laminectomy without removal of the retro-odontoid tissue, has demonstrated its efficacy in reducing retro-odontoid pannus as well as in obtaining improvement of myelopathy. METHODS: In this paper we analyse the clinical and radiological outcomes of seven patients (five males and two females) treated with posterior C1-C2 fixation and C1 laminectomy for a degenerative non-inflammatory retro-odontoid pseudotumour responsible for spinal cord compression. C1 laminectomy provided immediate spinal cord decompression. We also review the relevant literature focusing on associated cervical degenerative conditions that may contribute to triggering or acceleration of atlantoaxial hypermobility or 'instability', causing formation of the retro-odontoid tissue. RESULTS: The mean follow-up period (of six followed-up patients) was 55.8 months (range 10-96 months). In all cases the Nurick score at the latest follow-up visit demonstrated clinical improvement; magnetic resonance imaging during follow-up demonstrated progressive reduction of the retro-odontoid pseudotumour in all but one patient, who died of surgery-unrelated disease in the early postoperative period. No vascular or neural damage secondary to C1-C2 fixation was observed. CONCLUSION: C1-C2 fixation associated with C1 laminectomy is an effective surgical option to treat myelopathy secondary to a degenerative retro-odontoid pseudotumour. In these cases, direct removal of intracanalar tissue compressing the spinal cord is not required, as C1-C2 fixation is sufficient to cause its disappearance.

Management of spinal infection: a review of the literature.

Spinal infection (SI) is defined as an infectious disease affecting the vertebral body, the intervertebral disc, and/or adjacent paraspinal tissue and represents 2-7% of all musculoskeletal infections. There are numerous factors, which may facilitate the development of SI including not only advanced patient age and comorbidities but also spinal surgery. Due to the low specificity of signs, the delay in diagnosis of SI remains an important issue and poor outcome is frequently seen. Diagnosis should always be supported by clinical, laboratory, and imaging findings, magnetic resonance imaging (MRI) remaining the most reliable method. Management of SI depends on the location of the infection (i.e., intraspinal, intervertebral, paraspinal), on the disease progression, and of course on the patient's general condition, considering age and comorbidities. Conservative treatment mostly is reasonable in early stages with no or minor neurologic deficits and in case of severe comorbidities, which limit surgical options. Nevertheless, solely medical treatment often fails. Therefore, in case of doubt, surgical treatment should be considered. The final result in conservative as well as in surgical treatment always is bony fusion. Furthermore, both options require a concomitant antimicrobial therapy, initially applied intravenously and administered orally thereafter. The optimal duration of antibiotic therapy remains controversial, but should never undercut 6 weeks. Due to a heterogeneous and often comorbid patient population and the wide variety of treatment options, no generally applicable guidelines for SI exist and management remains a challenge. Thus, future prospective randomized trials are necessary to substantiate treatment strategies.

Restoration of Thoracolumbar Spine Stability and Alignment in Elderly Patients Using Minimally Invasive Spine Surgery (MISS). A Safe and Feasible Option in Degenerative and Traumatic Spine Diseases.

Minimally invasive spine surgery (MISS), including percutaneous pedicle-screw fixation (PPSF), mini-open transforaminal lumbar interbody fusion (m-open TLIF), vertebroplasty, and stentoplasty, allows the preservation of neurological function and the restoration of spine stability, while reducing associated risks and complications. This study aimed to analyze the safety and efficacy of MISS in elderly patients suffering from degenerative or traumatic thoracolumbar diseases. Forty-five patients (28 females), with a mean age of 73 years (range 65-89), suffering from osteoporotic vertebral fractures (24), degenerative spondylolisthesis (15), and lumbar canal stenosis with instability and/or de novo scoliosis (6) were included.Twenty-one patients underwent PPSF and m-open TLIF. The remaining patients received PPSF without interbody fusion, and in six of these fenestrated screws were used for vertebral body cement augmentation.Functional evaluation was obtained with a visual analog scale (VAS) and the Oswestry Disability Index (ODI) pre- and postoperatively. Preoperative imaging included X-rays, computed tomography (CT), and magnetic resonance imaging (MRI). Patients were followed-up with X-rays, and a CT scan was also obtained at the last follow-up. Follow-up ranged from 6 to 59 months (mean 28 months). Follow-up CT scan documented intersomatic fusion in only 14 % of patients treated with m-open TLIF. Despite the high incidence of non-union, mean VAS and ODI scores showed a significant improvement, with a reduction of mean VAS from 9 to 4 and a reduction of mean ODI from 76.33 to 38.15 %. Only three patients developed postoperative complications. No patients showed neurological deficits.Minimally invasive spine surgery for degenerative and traumatic spinal diseases is a safe and effective treatment also in elderly patients.

Multilevel mini-open TLIFs and percutaneous pedicle screw fixation: description of a simple technical nuance used to increase intraoperative safety and improve workflow. Tips and tricks and review of the literature.

We describe a technical variation used to enhance intraoperative safety and efficiency in multilevel percutaneous pedicle screw fixation (PPSFs) and mini-open transforaminal lumbar interbody fusion (m-TLIFs). A review of the literature on percutaneous screw insertion techniques and related pitfalls is presented. PPSFs and m-TLIFs are increasingly used techniques in multilevel lumbar degenerative disease. Facetectomy and TLIF are usually performed before inserting ipsilateral pedicle screws. Such techniques can cause unintended violation of the pedicle and injure the dura or neural structures, particularly in multilevel cases. A literature review revealed a lack of intraoperative and fluoroscopic images detailing the technique for multilevel PPSF and m-TLIF(s) performed through tubular, expandable retractors. Thirteen patients with two- to four-level disease underwent multilevel PPSF and m-TLIF (one to four levels). The Kirschner Cage Screw (KCS) technique, consisting of early insertion of K-wires in all pedicles followed by facetectomy and m-TLIF(s) and, finally, screw insertion, was used in order to minimize the risk of dural/neural injuries. Neither CSF (cerebrospinal fluid) leaks nor nerve root injuries nor technique-related complications were encountered with a follow-up ranging from 7 to 38 months (mean 23.6). In conclusion, the KCS technique allows safe identification of the pedicles without opening the canal during m-TLIF(s). Moreover, by visualizing the K-wires inside the retractor, the surgeon can check the pedicle position during facetectomy, and screws can be introduced with a minimal risk of neural or dural injuries. We believe that the proposed technique increases the safety and ease of the procedure, particularly in multilevel cases.

Odontoid process and clival regeneration with Chiari malformation worsening after transoral decompression: an unexpected and previously unreported cause of "accordion phenomenon".

PURPOSE: Transoral odontoidectomy followed by occipito-cervical fixation is a widely used approach to relieve ventral compressions at the craniovertebral junction (CVJ). Despite the large amount of literature on this approach and its complications, no previous reports of odontoid process and clival regeneration following transoral odontoidectomy are present in the English literature. METHODS: We report the case of odontoid process and clival regeneration following transoral odontoidectomy. RESULTS: A 7-year-old boy presented with symptoms of brainstem and upper cervical spinal cord compression due to a complex malformation at the CVJ including a basilar invagination with Chiari malformation. A successful transoral microsurgical endoscopic-assisted odontoidectomy extended to the clivus was performed along with occipito cervical instrumentation and fusion. Clinical and radiological resolution of the CVJ compression was evident up to 2 years post-op, when the child had a relapse of some of the presenting symptoms and the follow-up CT and MRI scans showed a quite complete regrowth of the odontoid process, clival partial regeneration and recurrence of preoperative Chiari malformation. CONCLUSIONS: Besides the need of an accurate complete resection of the periosteum, which apparently was incompletely performed in our case, our experience suggests the need of resection of the odontoid down to the dentocentral synchondrosis and an accurate lateral removal of the bone surrounding the anterior tubercle of the Clivus is advised when an anterior CVJ decompression is required in children presenting a still evident synchondrosis at neuroradiological investigation.

Bilateral tubular minimally invasive surgery for low-dysplastic lumbosacral lytic spondylolisthesis (LDLLS): analysis of a series focusing on postoperative sagittal balance and review of the literature.

PURPOSE: To report our early experience with minimally invasive surgery (MIS) in low-dysplastic lumbosacral lytic spondylolisthesis (LDLLS), and to analyze the impact of surgery on postoperative spino-pelvic and sacro-pelvic parameters. METHODS: Eight patients (mean age 47.6 years) underwent MIS for LDLLS involving in all but one the L5-S1 level. VAS and ODI were used for clinical assessment. Imaging included pre-operative X-rays, CT and MRI scans. Post-operatively, all patients underwent X-rays and CT-scans. Pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS) values as well as lumbar lordosis (LL) have been derived from pre- and post-operative standard X-rays. RESULTS: Mean follow-up is 30.12 months (range 15-42). No complications related to the surgical procedure were observed. Patients reported a satisfactory clinical outcome, as demonstrated by variation in mean VAS (from 9.1 to 3.6) and ODI (from 70.50 to 28.25 %) scores. Comparison between pre- and post-operative sacro-pelvic parameters documented moderate changes, with reduction of PT and increase of SS in all but one patient. Overall sagittal balance of the spine has been evaluated using the sagittal vertical axis (SVA), obtained from post-operative X-rays. Mean value of SVA demonstrated a good sagittal balance of the spine. CONCLUSION: This series demonstrates that MIS is feasible and effective for LDLLS, as witnesses by the satisfactory clinical results maintained at medium-term follow-up. We submit that TLIF is a valid option but an adequately sized and positioned interbody cage is a key factor to allow satisfactory restoration of segmental lordosis.

Long-term therapy with temozolomide is a feasible option for newly diagnosed glioblastoma: a single-institution experience with as many as 101 temozolomide cycles.

OBJECT: The objective of this study was to report the authors' experience with the long-term administration of temozolomide (TMZ; > 6 cycles, up to 101) in patients with newly diagnosed glioblastoma and to analyze its feasibility and safety as well as its impact on survival. The authors also compared data obtained from the group of patients undergoing long-term TMZ treatment with data from patients treated with a standard TMZ protocol. METHODS: A retrospective analysis was conducted of 37 patients who underwent operations for glioblastoma between 2004 and 2012. Volumetric analysis of postoperative Gd-enhanced MR images, obtained within 48 hours, confirmed tumor gross-total resection (GTR) in all but 2 patients. All patients received the first cycle of TMZ at a dosage of 150 mg/m(2) starting on the second or third postsurgical day. Afterward, patients received concomitant radiochemotherapy according to the Stupp protocol. With regard to adjuvant TMZ therapy, the 19 patients in Group A, aged 30-72 years (mean 56.1 years), received 150 mg/m(2) for 5 days every 28 days for more than 6 cycles (range 7-101 cycles). The 18 patients in Group B, aged 46-82 years (mean 64.8 years), received the same dose, but for no more than 6 cycles. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was analyzed for both groups and correlated with overall survival (OS) and progression-free survival (PFS). The impact of age, sex, Karnofsky Performance Scale score, and Ki 67 staining were also considered. RESULTS: All patients but 1 in Group A survived at least 18 months (range 18-101 months), and patients in Group B survived no more than 17 months (range 2-17 months). The long-term survivors (Group A), defined as patients who survived at least 12 months after diagnosis, were 51.3% of the total (19/37). Kaplan-Meier curve analysis showed that patients treated with more than 6 TMZ cycles had OS and PFS that was significantly longer than patients receiving standard treatment (median OS 28 months vs 8 months, respectively; p = 0.0001; median PFS 20 months vs 4 months, respectively; p = 0.0002). By univariate and multivariate Cox proportional hazard regression analysis, MGMT methylation status and number of TMZ cycles appeared to be survival prognostic factors in patients with glioblastoma. After controlling for MGMT status, highly significant differences related to OS and PFS between patients with standard and long-term TMZ treatment were still detected. Furthermore, in Group A and B, the statistical correlation of MGMT status to the number of TMZ cycles showed a significant difference only in Group A patients, suggesting that MGMT promoter methylation was predictive of response for long-term TMZ treatment. Prolonged therapy did not confer hematological toxicity or opportunistic infections in either patient group. CONCLUSIONS: This study describes the longest experience so far reported with TMZ in patients with newly diagnosed glioblastomas, with as many as 101 cycles, who were treated using GTR. Statistically significant data confirm that median survival correlates with MGMT promoter methylation status as well as with the number of TMZ cycles administered. Long-term TMZ therapy appears feasible and safe.

5-ALA fluorescence-assisted surgery in pediatric brain tumors: report of three cases and review of the literature.

5-aminolevulinic acid (5-ALA) has been used for the last 5 years to increase the extent of resection in adult brain tumors, mostly glioblastomas, but it is not approved yet as standard adjuvant treatment in the pediatric population. We report three different cases of pediatric brain tumors (two glioblastomas and one medulloblastoma) recently operated using 5-ALA fluorescence guidance, highlighting how useful it is in pediatric high-grade glioma (but not in medulloblastoma) also and confirming the lack of 5-ALA-related side effects. The first glioma was a recurrent GBM, whilst the second was a primary tumor. In all children, 5-ALA was administrated after discussing its use, including pros and cons, with the parents. 5-ALA fluorescence was a very useful tool to better identify tumor tissue and achieve gross-total tumor resection in GBMs, as confirmed by postoperative magnetic resonance imaging (MRI). In the medulloblastoma case no useful 5-ALA fluorescence was identified. No hematological or dermatological complications nor other side effects related to use of 5-ALA were observed. We submit that 5-ALA fluorescence guided surgery can be safe and useful in pediatric high-grade glioma, although its use in children still remains an off-label indication and requires validation through larger studies.

Adult idiopatic occlusion of Monro foramina: intraoperative endoscopic reinterpretation of radiological data and review of the literature.

Adult idiopathic occlusion of the foramen of Monro (AIOFM) is a rare condition, with only few cases described in the modern literature. We propose that AIOFM may result from unilateral or bilateral occlusion of Monro foramina, as well as from progression of a monolateral hydrocephalus. Different surgical strategies may be required for effective treatment according to the type of occlusion. To date, only 12 cases of AIOFM have been reported in the literature. We report the cases of two patients, aged 20 and 47 years respectively, who presented with intracranial hypertension secondary to bilateral ventricular dilatation due to obstruction at the level of the foramen of Monro. Both patients were successfully treated with endoscopic fenestration of the primarily obstructed foramen of Monro and, in one patient, fenestration of the septum. We propose that septum pellucidum displacement could play a role in the occlusion of the second foramen of Monro. AIOFM can, therefore, result also from unilateral stenosis of Monro. The difference in AIOFM (i.e. unilateral vs bilateral) will be useful in guiding the most suitable surgical approach in this rare condition.

Zero-P: a new zero-profile cage-plate device for single and multilevel ACDF. A single institution series with four years maximum follow-up and review of the literature on zero-profile devices.

PURPOSE: To analyze the prospectively collected data in a series of patients treated with single- or multilevel ACDF with a stand-alone, zero-profile device, focusing on clinico-radiological outcome, complications and technical hints, and to review the literature on such new devices. METHODS: Eighty-five patients harboring symptomatic DDD underwent ACDF with the Zero-P cage-plate: 29 at 1-level and 56 at 2-4 levels (total 162 devices). In the multilevel group, 9 patients received a combination of Zero-P and stand-alone cages (hybrid implants). This study focuses on 32 patients with follow-up ranging from 20 to 48 months. NDI, SF-36 and arm pain VAS scores were registered preoperatively and at follow-up visits. Dysphagia was assessed using the Bazaz score. Imaging included X-rays, CT and MRI, also to assess the presence of vertebral body fractures in multilevel cases. Paired Student t test was used for statistical analysis. RESULTS: SF-36 and NDI showed a statistically significant improvement (p < 0.01) and mean arm pain VAS score decreased from 79 to 41. X-rays and CT demonstrated, respectively, a 94.5 % and a 92 % fusion rate. Three patients complained of moderate and two of mild transient dysphagia (15.5 %). No device-related complications occurred and no fractures, secondary to four screws insertion in one vertebral body (i.e., swiss cheese effect), were detected in multilevel cases. In patients with extensive anterior osteophytes only a "focal spondylectomy" was required. CONCLUSION: The Zero-P device is safe and efficient, even in multilevel cases. Dysphagia is minimal, extensive anterior osteophytectomy is unnecessary and technical hints may ease the surgical workflow. This is the largest series, with the longest follow-up, reported.

Disappearance of degenerative, non-inflammatory, retro-odontoid pseudotumor following posterior C1-C2 fixation: case series and review of the literature.

PURPOSE: Retro-odontoid pseudotumor, not related to inflammatory or traumatic conditions, is an uncommon pathology. Atlanto-axial instability has been advocated to explain the pathophysiology of retro-odontoid pseudotumor's formation and growth. Despite pseudotumor direct removal through transoral or lateral approach represented the main surgical strategy for a long time, in the last decade several authors highlighted the possibility to treat retro-odontoid pseudotumor by occipito-cervical or C1-C2 fixation without removal of the intracanalar tissue. The goal of this study is to analyze the data collected in a series of patients suffering from cervical myelopathy due to non-inflammatory, degenerative retro-odontoid pannus and treated by posterior C1-C2 fixation. The relevant literature is also reviewed. METHODS: Five patients, not suffering from inflammatory diseases, were treated between 2009 and 2012. Abnormalities of cranio-cervical junction and/or lower cervical spondylotic degeneration were observed in all patients. No evidence of atlanto-axial instability was demonstrated. Clinical and radiological evaluation included pre- and post-operative Nurick score as well as pre- and post-operative X-rays, CT and MRI. In one case, CT scan highlighted an eggshell calcification of the pannus. All patients underwent either a C1-C2 fixation (C1 lateral mass and C2 isthmus-pedicle screws) or occipito-cervical fixation (2 patients) in cases of C0-C1 fusion. RESULTS: Follow-up ranges from 22 to 45 months (mean 32) in four patients. One patient died of surgery-unrelated disease. Nurick score changes suggest a clinical improvement in four cases. Neuro-radiological evaluation shows a progressive but incomplete reduction of thickness of retro-odontoid pseudotumor in one patient, and its disappearance in the other three cases. A second-stage transoral or posterior lateral approach was not required. CONCLUSION: Although the etiopathogenesis of non-inflammatory, i.e., degenerative, retro-odontoid pseudotumor is still controversial, our series (the second largest on degenerative retro-odontoid pannus in the literature) confirms that a posterior approach may be sufficient and transoral surgery is not required.

Bilateral tubular minimally invasive approach for decompression, reduction and fixation in lumbosacral lythic spondylolisthesis.

This video demonstrates the minimally invasive surgical technique used in a 56-year-old woman suffering from L-5 spondylolysis and grade 2 L5-S1 spondylolisthesis. The first author used expandable tubular retractors bilaterally to perform neural decompression, mini-open TLIF, spondylolysthesis reduction and L5-S1 pedicle screw fixation. L-5 cement augmentation was performed through cannulated and fenestrated screws to enhance resistance to screw pull-out secondary to reduction maneuvers. Sequential surgical steps related to microsurgery, spondylolysthesis reduction and instrumentation are shown and commented. We submit that in cases of lythic spondylolisthesis a bilateral traversing and exiting nerve roots decompression is a safer option prior to performing the deformity reduction and fixation; the proposed minimally invasive technique may help in reducing surgical morbidity and improving postoperative recovery. The video can be found here: http://youtu.be/G4Qdg-A-Y3M.

Role of i-CT, i-US, and Neuromonitoring in Surgical Management of Brain Cavernous Malformations and Arteriovenous Malformations: A Case Series.

OBJECTIVE: We retrospectively reviewed the institutional experience in patients who underwent microsurgical resection of cavernous malformations (CMs) or arteriovenous malformations (AVMs) using a multimodal intraoperative protocol including neuronavigation, intraoperative ultrasound (i-US), computed tomography (i-CT), and neuromonitoring. METHODS: Twenty-four patients (14 male), with a mean age of 47.5 years (range 27-73), have been included: 20 of them suffered from CMs and 4 suffered from AVMs. Neuromonitoring was used in 18 cases, when lesions were located in eloquent areas; 2 patients underwent awake craniotomy. First, an i-CT scan with and without contrast was acquired after patient positioning. Navigated B-mode ultrasound acquisition was carried out after dural opening to identify the lesion (CMs or AVMs nidus). Following identification and resection of vascular lesions, postcontrast i-CT (or CT-angio) was performed to detect and localize any small or calcified remnant (in cases of CMs) or residual vessels feeding the nidus (in cases of AVMs). RESULTS: In 5 cases of CMs and in 1 case of AVM, i-CT identified small residual lesions. In these cases, new i-CT images were uploaded into the navigation system and used for further resection. i-US was useful before starting transsulcal or transcortical approach to identify the lesions and guide the trajectory of the approach. However, several artifacts were observed during subsequent steps of dissection, making image interpretation difficult. CONCLUSIONS: The combination of different intraoperative real-time imaging modalities (i-CT and i-US), coupled with neuromonitoring, in the surgical management of vascular lesions, particularly if located in eloquent areas, has a positive impact on clinical outcome.

Hybrid implants in anterior cervical decompressive surgery for degenerative disease.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) still represent the mainstream surgical approach in the treatment of degenerative cervical Degenerative Disc Disease (DDD), being a loss of mobility at the treated segment and adjacent segment diseases well-known complications. To overcome those complications, hybrid surgery (HS) incorporating ACDF and cervical disk arthroplasty is increasingly performed for DDD. METHODS: We retrospectively reviewed the clinical, surgical, and outcome data of 62 consecutive patients (male/female, 29/37) harboring cervical disk herniation with or without osteophytes, with radiculopathy with or without myelopathy, who underwent a cervical discectomy on two or more levels with the anterior approach with at least one disk prosthesis along with cage and plate or O Profile screwed plate. RESULTS: All the patients improved regardless of the cervical construct used. No significant relationship between different kind of prostheses as well as their surgical level, the number and the site of the cages (screwed and/or plated) was found out concerning immediate stability, dynamic prosthesis effectiveness, and clinical improvement in all the patients up to the maximum follow-up. CONCLUSIONS: Although the optimal surgical technique for cervical DDD remains controversial, HS represents a safe and effective procedure in selected patients with multilevel cervical DDD, as demonstrated by biomechanical and clinical studies and the present series. Some technical aspects should be considered when dealing with this procedure, like the drilling of the endplate, and some radiological findings have to be detected because potentially predictive of future misplacement.

FLAIRectomy in Supramarginal Resection of Glioblastoma Correlates With Clinical Outcome and Survival Analysis: A Prospective, Single Institution, Case Series.

BACKGROUND: Extent of tumor resection (EOTR) in glioblastoma surgery plays an important role in improving survival. OBJECTIVE: To analyze the efficacy, safety and reliability of fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) images used to guide glioblastoma resection (FLAIRectomy) and to volumetrically measure postoperative EOTR, which was correlated with clinical outcome and survival. METHODS: A total of 68 glioblastoma patients (29 males, mean age 65.8) were prospectively enrolled. Hyperintense areas on FLAIR images, surrounding gadolinium-enhancing tissue on T1-weighted MR images, were screened for signal changes suggesting tumor infiltration and evaluated for supramaximal resection. The surgical protocol included 5-aminolevulinic acid (5-ALA) fluorescence, neuromonitoring, and intraoperative imaging tools. 5-ALA fluorescence intensity was analyzed and matched with the different sites on navigated MR, both on postcontrast T1-weighted and FLAIR images. Volumetric evaluation of EOTR on T1-weighted and FLAIR sequences was compared. RESULTS: FLAIR MR volumetric evaluation documented larger tumor volume than that assessed on contrast-enhancing T1 MR (72.6 vs 54.9 cc); residual tumor was seen in 43 patients; postcontrast T1 MR volumetric analysis showed complete resection in 64 cases. O6-methylguanine-DNA methyltransferase promoter was methylated in 8/68 (11.7%) cases; wild type Isocytrate Dehydrogenase-1 (IDH-1) was found in 66/68 patients. Progression free survival and overall survival (PFS and OS) were 17.43 and 25.11 mo, respectively. Multiple regression analysis showed a significant correlation between EOTR based on FLAIR, PFS (R2 = 0.46), and OS (R2 = 0.68). CONCLUSION: EOTR based on FLAIR and 5-ALA fluorescence is feasible. Safety of resection relies on the use of neuromonitoring and intraoperative multimodal imaging tools. FLAIR-based EOTR appears to be a stronger survival predictor compared to gadolinium-enhancing, T1-based resection.

Review of current microsurgical management of insular gliomas.

The insular lobe is a functionally complex structure, harbouring peculiar anatomical and vascular features and specific neuronal connectivity with surrounding cerebral structures. It is situated in the depth of the Sylvian fissure and can be affected by either low-grade or high-grade gliomas. Because of its complexity, surgery of insular tumours has been traditionally regarded as hazardous. Nonetheless, currently improved diagnostic, neurophysiological and surgical tools allow the neurosurgeon to perform surgery of insular gliomas in a safer way, thus bringing forward the pioneering work performed by neurosurgeons in the past two decades.The aim of this paper is to provide the reader with an updated review of the anatomy, the clinical picture, diagnosis and surgical management of insular gliomas.