Relationship between lumbar lordosis, pelvic parameters, PI-LL mismatch and outcome after short fusion surgery for lumbar degenerative disease. Literature review, rational and presentation of public study protocol: RELApSE study (registry for evaluation of lumbar artrodesis sagittal alignEment).

Background: Vertebral arthrodesis for degenerative pathology of the lumbar spine still remains burdened by clinical problems with significant negative results. The introduction of the sagittal balance assessment with the evaluation of the meaning of pelvic parameters and spinopelvic (PI-LL) mismatch offered new evaluation criteria for this widespread pathology, but there is a lack of consistent evidence on long-term outcome. Methods: The authors performed an extensive systematic review of literature, with the aim to identify all potentially relevant studies about the role and usefulness of the restoration or the assessment of Sagittal balance in lumbar degenerative disease. They present the study protocol RELApSE (NCT05448092 ID) and discuss the rationale through a comprehensive literature review. Results: From the 237 papers on this topic, a total of 176 articles were selected in this review. The analysis of these literature data shows sparse and variable evidence. There are no observations or guidelines about the value of lordosis restoration or PI-LL mismatch. Most of the works in the literature are retrospective, monocentric, based on small populations, and often address the topic evaluation partially. Conclusions: The RELApSE study is based on the possibility of comparing a heterogeneous population by pathology and different surgical technical options on some homogeneous clinical and anatomic-radiological measures aiming to understanding the value that global lumbar and segmental lordosis, distribution of lordosis, pelvic tilt, and PI-LL mismatch may have on clinical outcome in lumbar degenerative pathology and on the occurrence of adjacent segment disease.

Blood-tissue analysis of TP53 polymorphisms and survival of patients with glioma.

BACKGROUND: The role of single nucleotide polymorphisms (SNPs) in TP53 in the pathogenesis of glioma is still debated. The aim of our study was to investigate the role of several TP53 SNPs in the risk of glioma and their possible role as prognostic biomarkers of overall and progression-free survival. METHODS: We examined 12 SNPs in TP53 from peripheral blood and neoplastic tissue of patients with a diagnosis of glioma who underwent surgery from 2012 to 2015. Direct genomic sequencing of TP53 was performed to detect the presence of polymorphisms. We compared data with a matched cancer-free control group and the NCBI SNPs database. Overall and progression-free survival were analyzed in patients with glioblastoma subjected to gross total resection and concomitant radio-chemotherapy. RESULTS: No association was observed with glioma susceptibility and overall survival. Two new SNPs were detected: c.97-46 G>A (intron 3) and c.783-31 A>G (intron 7). The number of SNPs observed was higher (21.4%) in blood than in tumoral samples. We observed a significant reduction in progression-free survival in patients with at least one exonic SNP. CONCLUSIONS: We can hypothesize an involvement of TP53 SNPs in response mechanisms to adjuvant treatment that may affect progression-free survival. Moreover, our blood-tissue combined study revealed a significant difference in SNPs between blood and tumoral samples, probably due to glioma heterogeneity and genomic instability.

Double cystic brain metastasis in a patient with stable pancreatic intraductal papillary mucinous neoplasm.

BACKGROUND: Brain metastases in pancreatic cancer are a rare condition and are usually seen in case of pancreatic adenocarcinoma. Only few cases of brain metastasis in patients affected by Intraductal papillary mucinous neoplasm (IPMN) are actually reported. CASE DESCRIPTION: We report a patient diagnosed with double cystic brain lesions that the histological examination reveal to be consistent, with pancreatic metastasis. Our patient had an history shown of stable pancreatic IPMN which has never made the oncologist suspicious about neoplastic progression or degeneration into pancreatic carcinoma. Considering the rarity of these metastasis we did a literature review on the topic. CONCLUSIONS: Despite rare, pancreatic origin of a cystic brain metastasis should considered in differential diagnosis in both patient with IPMN or patient with unknown primitive tumor.

The Neurology-Stability-Epidural compression assessment: A new score to establish the need for surgery in spinal metastases.

OBJECTIVE: The aim of this study was to translate new evidence about management of spinal metastases in a practical and reliable score for surgeons, radiation oncologists and oncologists, able to establish the need for surgery regardless the available technology and settings. PATIENTS AND METHODS: Three main items were identified and graded: Neurological status (0-5 points), Stability of the spine according to the Spinal Instability Neoplastic Score (SINS) Score (0-5 points), and Epidural compression according to the Epidural Spinal Cord Compression (ESCC) scale (0-3 points). Patients were considered suitable for surgery with ASA score < 4 and ECOG score <3. A retrospective clinical validation of the NSE score was made on 145 patients that underwent surgical or non surgical treatment. RESULTS: Agreement between the undertaken treatment and the score (88.3% of patients), resulted in a strong association with improvement or preservation of clinical status (neurological functions and mechanical pain) (p < 0.001) at 3 and 6 months. In the non-agreement group no association was recorded at the 3 and 6 months follow-up (p 0.486 and 0.343 for neurological functions, 0.063 and 0.858 for mechanical pain). CONCLUSION: Functional outcomes of the study group showed that the proposed NSE score could represent a practical and reliable tool to establish the need for surgery. Agreement between the score and the performed treatments resulted in better clinical outcomes, when compared with patients without agreement. Further validation is needed with a larger number of patients and to assess reproducibility among surgeons, radiation oncologists, and oncologists.

Exploring the anatomy of negative motor areas (NMAs): Findings in awake surgery.

Positive motor responses have been used in neurosurgery for the identification of motor structures. With the term "negative motor responses" (NMRs) a complete inhibition of movement without loss of muscle tone or consciousness is meant. Papers already exist in the literature regarding cortical areas in which such NMRs are evoked, the so-called "negative motor areas" (NMAs), but their location and functional meaning are still poorly understood. This paper discusses the anatomy of the NMAs of the human brain, in light of our brain mapping experience. 21 patients underwent awake surgery and direct electrical stimulation (DES) was performed using bipolar electrodes. Excision was interrupted when functional responses were intraoperatively identified through DES. The labeled mapping sites were recorded by photography prior to and following tumor resection. Results depicting a probabilistic map of negative motor network anatomy were retrospectively analyzed. Our findings strongly support the fact that the precentral gyrus, classical site of the of the Primary Motor Areas, is also strongly involved in generating NMRs. The distribution of NMAs was noted not to be as rigid as previously described, ranging in different brain areas with a somatotopic arrangement. Presented anatomical results are consistent with the literature, but the exact functional meaning of NMAs and their subcortical connectivity is still far from being completely understood.

Management of Extramedullary Intradural Spinal Tumors: The Impact of Clinical Status, Intraoperative Neurophysiological Monitoring and Surgical Approach on Outcomes in a 12-Year Double-Center Experience.

Objective: Intradural Extramedullary (IDEM) tumors are usually treated with surgical excision. The aim of this study was to investigate the impact on clinical outcomes of pre-surgical clinical conditions, intraoperative neurophysiological monitoring (IONM), surgical access to the spinal canal, histology, degree of resection and intra/postoperative complications. Methods: This is a retrospective observational study analyzing data of patients suffering from IDEM tumors who underwent surgical treatment over a 12 year period in a double-center experience. Data were extracted from a prospectively maintained database and included: sex, age at diagnosis, clinical status according to the modified McCormick Scale (Grades I-V) at admission, discharge, and follow-up, tumor histology, type of surgical access to the spinal canal (bilateral laminectomy vs. monolateral laminectomy vs. laminoplasty), degree of surgical removal, use and type of IONM, occurrence and type of intraoperative complications, use of Ultrasonic Aspirator (CUSA), radiological follow-up. Results: A total number of 249 patients was included with a mean follow-up of 48.3 months. Gross total resection was achieved in 210 patients (84.3%) mostly in Schwannomas (45.2%) and Meningiomas (40.4%). IONM was performed in 162 procedures (65%) and D-wave was recorded in 64.2% of all cervical and thoracic locations (99 patients). The linear regression diagram for McCormick grades before and after surgery (follow-up) showed a correlation between preoperative and postoperative clinical status. A statistically significant correlation was found between absence of worsening of clinical condition at follow-up and use of IONM at follow-up (p = 0.01) but not at discharge. No associations were found between the choice of surgical approach and the extent of resection (p = 0.79), the presence of recurrence or residual tumor (p = 0.14) or CSF leakage (p = 0.25). The extent of resection was not associated with the use of IONM (p = 0.91) or CUSA (p = 0.19). Conclusion: A reliable prediction of clinical improvement could be made based on pre-operative clinical status. The use of IONM resulted in better clinical outcomes at follow-up (not at discharge), but no associations were found with the extent of resection. The use of minimally invasive approaches such as monolateral laminectomy showed to be effective and not associated with worse outcomes or increased complications.

Natural history of de novo high grade glioma: first description of growth parabola.

Etiopathogenesis and physiopathology of gliomas are largely unknown. Recently, many authors have proved a strict correlation between the velocity of diametric expansion (VDE) on the magnetic resonance imaging (MRI) and the biological behavior of these tumors, especially in low grade gliomas (LGGs). Unfortunately, natural history of High Grade Gliomas (HGGs) has not been well clarified because of its fast progression, late diagnoses and early surgical intervention. We describe, for the first time to our knowledge, the case of asymptomatic patient with an incidentally discovered de novo HGG with a total of 17 months of follow-up. A male patient was referred to our consultation for routinely follow-up after meningioma resection 5 years before. He underwent MRI every year without any neuroradiological alterations. A new MRI image presented a non-enhancing lesion in the right temporal lobe with 3.55 cm of mean tumor diameter (MTD) and 35.6 mm/year of VDE. After two months interval, the lesion had 3.97 cm of MTD and 27.8 mm/year of VDE. Although we have strongly suggested surgical resection, patient have delayed the operation for personal issues. After other 3 months, the tumor showed enhancement with 4.5 of MTD and 17.4 mm/year of VDE. We speculate that the descending parabola is due to initial mass effect and hypoxia of the tumor core. We also underline the crucial role of the VDE determining, in order to predict the nature of the lesion and address the most effective treatment for each patient.

The Targeted Therapies Era Beyond the Surgical Point of View: What Spine Surgeons Should Know Before Approaching Spinal Metastases.

In the last few years, the treatment of spinal metastases has significantly changed. This is due to the advancements in surgical technique, radiotherapy, and chemotherapy which have enriched the multidisciplinary management. Above all, the field of molecular biology of tumors is in continuous and prosperous evolution. In this review, the molecular markers and new approaches that have radically modified the chemotherapeutic strategy of the most common metastatic neoplasms will be examined together with clinical and surgical implications. The experience and skills of several different medical professionals are mandatory: an interdisciplinary oncology team represents the winning strategy in the treatment of patients with spinal metastases.

Supratotal Resection of Glioblastoma: Is Less More?

BACKGROUND: A relationship between the extent of resection (EOR) and survival has been demonstrated in patients with glioblastomas (GBMs). However, despite gross total resection (GTR) of the enhancing nodule (EN), GBMs usually relapse, generally near the surgical cavity. OBJECTIVE: The aim of this study was to determine the prognostic role of FLAIR resection of GBMs by analyzing pre- and post-operative MRIs to estimate the EOR of EN, FLAIR-hyperintense regions and total tumor volume (TTV). METHODS: Radiologic and clinical outcomes were analyzed retrospectively. Pre- and post-operative EN volume, pre- and postoperative FLAIR volume (POFV), and pre- and postoperative TTV were analyzed. EOR was then calculated for each component. Time-dependent ROC curves and cut-off values for pre- and post-operative volumes and EOR were calculated. A Kaplan-Meier analysis with the log-rank test and Cox regression analysis were then used to analyze progression-free survival (PFS) and overall survival (OS). RESULTS: We did not find any correlation between EOR of FLAIR-altered regions and patient survival. On the other hand, there were statistically significant relationships between the prognosis and both a preoperative EN volume less than 31.35 cm3 (p=0.032) and a postoperative EN volume less than 0.57 cm3 (p=0.015). Moreover, an EOR of EN greater than 96% was significantly associated with the prognosis (p=0.0051 for OS and p=0.022 for PFS). CONCLUSION: Our retrospective, multi-center study suggests that survival in patients with GBM is not affected by the extent of resection of FLAIR-hyperintense areas.

Cortical Bone Trajectory Screw Placement Accuracy with a Patient-Matched 3-Dimensional Printed Guide in Lumbar Spinal Surgery: A Clinical Study.

BACKGROUND: Cortical bone trajectory (CBT) screw is an attractive technique in terms of fixation strength and less invasiveness. However, the insertion of a pedicle screw penetrating cortical bone on the ideal trajectory is technically demanding. The use of 3-dimensional (3D) patient-matched guides may facilitate the use of this technique. In this technical note and case series, the use of a patient-matched 3D targeting guide for a circumferential fixation with CBT screws is described. METHODS: Eleven patients with a mean age of 49 years were treated. The MySpine MC (Medacta International SA, Castel San Pietro, Switzerland) technology was used to place CBT screws. A computed tomography (CT) scan-derived 3D model of the patient vertebra was created after the surgeons planned the best custom CBT screw trajectory. Then, scaffolds were printed and used during surgery to guide the screw through the patient pedicle. An intersomatic arthrodesis was also performed. RESULTS: The images of the planned trajectory were superimposed on the postoperative CT scan, confirming the accuracy of the trajectory. The mean deviation from the planned pedicle midpoint was 0.91 mm; 85.2% of the screws were placed within 2° from the planned trajectory. There were 2 grade A (<2 mm) and no grade B or C perforations. The actual entry point was always within 2 mm from the planned entry point. CONCLUSIONS: This technical note and case series is the first clinical description on the use of a patient-matched guide for posterior CBT screw placement. The use of these devices could also improve placement accuracy and decrease the risk of nerve damage.

Mesenchymal Stem Cells for Spinal Cord Injury: Current Options, Limitations, and Future of Cell Therapy

Spinal cord injury (SCI) constitutes an inestimable public health issue. The most crucial phase in the pathophysiological process of SCI concerns the well-known secondary injury, which is the uncontrolled and destructive cascade occurring later with aberrant molecular signaling, inflammation, vascular changes, and secondary cellular dysfunctions. The use of mesenchymal stem cells (MSCs) represents one of the most important and promising tested strategies. Their appeal, among the other sources and types of stem cells, increased because of their ease of isolation/preservation and their properties. Nevertheless, encouraging promise from preclinical studies was followed by weak and conflicting results in clinical trials. In this review, the therapeutic role of MSCs is discussed, together with their properties, application, limitations, and future perspectives.

Cervical Interfacet Spacers to Promote Indirect Decompression and Enhance Fusion in Degenerative Spine: A Review.

BACKGROUND: Among the posterior techniques, the use of cervical interfacet spacers (CISs) represents a promising technology whose potentialities are still being studied. The purpose of the present review was to assess the available data on CISs. METHODS: A search on PubMed was performed. The search terms were "cervical interfacet spacers," "facet spacers," "DTRAX facet system," "Goel facet spacer," "pseudarthrosis," "cervical lordosis," "iatrogenic kyphosis," "cervical foraminal decompression," "cervical biomechanics," "atlantoaxial instability," and "subaxial instability." RESULTS: Mechanical studies have shown that stand-alone CISs promoted stiffness in all directions, except for extension. Foraminal distraction was recorded in 86% of the cases. Clinical studies have shown that the use of CISs could promote successful arthrodesis, given the large surface area affected by fusion and decreasing the need for autografts. The effectiveness for the treatment of radiculopathy has been confirmed by several clinical studies. In a series of 154 levels of implanted CISs, no evidence of significant loss of cervical lordosis was identified. CISs could help in enhancing fusion in C1-C2 fixation. CONCLUSIONS: Biomechanical studies on specimens showed a positive trend in increasing stiffness of the cervical spine, despite some controversial results. In clinical studies, facet distraction was shown to be a safe and valid option for clinical indirect decompression, although longer follow-up is required for confirmation. No evidence of the loss of cervical lordosis has been recorded. The long-term effects and CIS use in revision procedures as adjuvant implants to treat pseudarthrosis or atlantoaxial instability are currently under investigation, and further studies are needed.

The Endoscopic Endonasal Approach to Craniovertebral Junction Pathologies: Surgical Skills and Anatomical Study.

INTRODUCTION: Surgical anterior decompression is the treatment of choice for symptomatic irreducible ventral craniovertebral junction (CVJ) compression. Along with the classic transoral approach, the endoscopic endonasal approach has evolved and is gaining growing success. MATERIALS AND METHODS: In this work we discuss the surgical technique, give a complete step-by-step description of dissection of the craniovertebral junction and report a specific case of endoscopic endonasal odontoidectomy with use of a high-definition (HD) three-dimensional (3D) endoscope. DISCUSSION: The extended endonasal approach exploits an anatomical corridor to the odontoid process, involving only a small incision in the nasopharynx and sparing palate integrity. The most important limitation of the technique is 2D visualization, which hinders correct recognition of anatomical structures. CONCLUSION: The endoscopic endonasal route to the odontoid process has proven to be a feasible, safe and well-tolerated procedure. Anatomical study is very important for better understanding of the 3D anatomy of the CVJ and relation of critical neurovascular structures to specific bony and muscular landmarks.

Intraoperative neurophysiological monitoring during spinal surgery: technical review in open and minimally invasive approaches.

Neurophysiological monitoring is of undoubted value for the intraoperative safety of neurosurgical procedures. Widely developed and used for cranial surgery, it is equally as effective, though perhaps less commonly employed, for spinal pathology. The most frequently used techniques for intraoperative monitoring during spinal surgery include somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs) and electromyography, which can either be spontaneous free-running (sEMG) or triggered (tEMG). The knowledge of the benefits and limitations of each modality is essential in optimising the value of intraoperative monitoring during spinal procedures. This review will analyse the single techniques, their anatomical and physiological basis, their use in spinal surgery as reliable indicators of functional injury, their limits and their application to specific procedures in minimally invasive surgery, such as the lateral transpsoas access for interbody fusion and the divergent trajectory for cortico-pedicular screws. In these particular techniques, because of reduced visual exposure, neuromonitoring is indeed essential to exploit the full potential of minimally invasive surgery, while avoiding damage to nervous structures.

Intraoperative ultrasound and 5-ALA: the two faces of the same medal?

BACKGROUND: High Grade Gliomas (HGG) still remain the most demanding neuro-oncological challenge. Several studies have confirmed that the extent of resection (EOR) correlates with increased survival in patients with HGGs. The Gross Total Resection (GTR) of HGGs can be difficult and challenging. For this reason, technologies to improve EOR have been of interest. The aim of this paper is to analyze advantages and limitations of both intra-operative fluorescence and intra-operative ultrasound (IOUS) resection techniques. METHODS: Our work deals with the comparison of one group of 15 patients treated with both tools (study group) with a control group of 15 patients in where only fluorescence was used. Post operative outcome are valued using Karnofsky Performance Status scale (KPS) while EOR are valued with MRI within 24 h after surgery. RESULTS: The difference between the postoperative KPS and between EOR in the 2 groups resulted not statistically significant considering p<0.05. In our experience 5-ALA has a limited sensitivity before starting resection while shows it's central role in identifying the tumor remnants after its removal. Conversely, IOUS is very useful in identifying the tumor before starting resection. After the tumor removal, the sensitivity of the ultrasound in identifying tumor remnants in the margins of the cavity decreased significantly. However, in one case, at the end of resection, we have not visualized any fluorescent tissue but we detect a residual of tumor using the IOUS. CONCLUSIONS: In our preliminary experience we observe that there are no significative advantages using IOUS plus 5-ALA. However we feel that IOUS is useful in first step of resection and fluorescence in the latest steps of operation. Therefore these two technologies could be considered the two faces of the same medal because they can help the surgeon to detect the tumor in all step of tumor removal.

Nasal Functions in Three-Dimensional Endoscopic Skull Base Surgery.

OBJECTIVES: Endoscopic transnasal transsphenoidal surgery has become the standard procedure for the majority of skull base diseases, including sellar, parasellar, and clival pathologies. The aim of this study was the objective evaluation of nasal airflow resistances and olfactory function in 3-dimensional (3D) endoscopic transnasal transsphenoidal surgery. METHODS: One hundred patients who underwent 3D transnasal endoscopic surgery for sellar, parasellar, and clival diseases were enrolled. Active anterior rhinomanometry and Sniffin' Sticks tests were performed before endoscopic surgery and at 3 and 6 months postoperatively. RESULTS: No significant difference about nasal airflow resistance and olfactory function was observed between preoperative and postoperative subjective and objective scores. In the group of patients with sellar and parasellar diseases, a worst nasal respiratory function was seen when crusting was present, and a worst olfactory function was observed in patients with synechiae. Nasal functions returned to previous levels when crusting or synechiae solved. No statistically significant correlation was observed between the evaluated nasal functions and the reconstruction with flaps. CONCLUSIONS: The 3D endoscopic transnasal transsphenoidal surgery represents a more and more important tool in skull base surgery. It does not determine nasal respiratory and olfactory alterations after the treatment, without an increase in nasal complaints that could worsen quality of life.

Intra-Operative Ultrasound: Tips and Tricks for Making the Most in Neurosurgery.

PURPOSE: Advances in intraoperative imaging and neuronavigation techniques have positively affected glioma surgery. The desire to reduce brain-shift-related problems while achieving the real-time identification of lesions and residual and anatomical relationships has strongly supported the introduction of intraoperative ultrasound (ioUS) in neuro-oncological surgery. This paper presents tips based on our experience with ioUS in neurosurgery. METHODS: We retrospectively analyzed 264 patients who underwent high-grade glioma (HGG) resection at the University of Turin and 60 patients who were treated at the University of Rome. RESULTS: The main issues are the correct choice of the probe and how to evaluate the anatomy to understand how the information from the three common US planes (axial, sagittal and coronal plane) can be used in each case. It is also important to correctly identify anatomical structures in ioUS imaging. In a normal brain, the sulci, sickle, tentorium, choroid plexus, ependyma and the walls of the vessels are all hyperechoic. In addition, some structures are hypoechoic with a homogeneous acoustic gradient: ventricles, cysts and everything that contains liquor. Tumors are usually hyperechoic in ioUS because of their higher cellularity. Conversely, acute edema that contains fluid is hypoechoic, while chronic edema is hyperechoic. CONCLUSIONS: IoUS is a real-time, accurate and inexpensive imaging method. The difficulties of interpretation can be overcome by experience in US imaging and a better understanding of the interaction between navigation and imaging fusion techniques. Training on a large number of cases is important for the correct assessment of ioUS information to obtain valuable, real-time information during HGG surgery.

Comparison of VEMPs, VHIT and caloric test outcomes after vestibular neurectomy in Menière's disease.

OBJECTIVE: Selective unilateral vestibular neurectomy (VN) is considered a reliable surgical treatment in case of recurrent vertigo in Menière's disease (MD) because of hearing preservation and a minimally invasive posterior fossa retrosigmoid approach. The present study aimed to assess the quality of life and the long-term vestibular function in patients submitted to yearly follow-up after VN because of intractable MD. METHODS: Retrospective series of 15 MD patients undergoing retrosigmoid VN for recurrent vertigo. Outcome measures included cVEMPs and oVEMPs (cervical and ocular vestibular evoked myogenic potentials), VHIT (Video Head Impulse Test) and caloric test, besides to DHI (Dizziness Handicap Inventory) and PTA (Pure Tone Audiometry). RESULTS: Mean DHI score resulted within normal values in 74% of patients, significantly correlated to the duration of the follow-up. In the operated side, cVEMPs and oVEMPs have not been elicited respectively in 11 patients (73%) and 13 patients (87%), whereas it was not possible to evoke any response at bithermal caloric test in 4 cases. The gain of VOR from VHIT resulted always below normal values after VN except in one patient, who has also undergone an episode of posterior BBPV. The difference between average PTA threshold before and after VN resulted not significant. CONCLUSION: The vestibular outcomes prove VN to be an effective and safe surgery in MD; furthermore, the unexpected occurrence of BPPV after VN can justify the presence of neural anastomosis between the inferior vestibular nerve and the cochlear nerve, allowing to still perceive vestibular symptomatology despite of a proper neurectomy.