Impact of frailty on survival glioblastoma, IDH-wildtype patients.

PURPOSE: Frailty increases the risk of mortality among patients. We studied the prognostic significance of frailty using the modified 5-item frailty index (5-mFI) in patients harboring a newly diagnosed supratentorial glioblastoma, IDH-wildtype. METHODS: We retrospectively reviewed records of patients surgical treated at a single neurosurgical institution at the standard radiochemotherapy era (January 2006 - December 2021). Inclusion criteria were: age ≥ 18, newly diagnosed glioblastoma, IDH-wildtype, supratentorial location, available data to assess the 5-mFI index. RESULTS: A total of 694 adult patients were included. The median overall survival was longer in the non-frail subgroup (5-mFI < 2, n = 538 patients; 14.3 months, 95%CI 12.5-16.0) than in the frail subgroup (5-mFI ≥ 2, n = 156 patients; 4.7 months, 95%CI 4.0-6.5 months; p < 0.001). 5-mFI ≥ 2 (adjusted Hazard Ratio (aHR) 1.31; 95%CI 1.07-1.61; p = 0.009) was an independent predictor of a shorter overall survival while age ≤ 60 years (aHR 0.78; 95%CI 0.66-0.93; p = 0.007), KPS score ≥ 70 (aHR 0.71; 95%CI 0.58-0.87; p = 0.001), unilateral location (aHR 0.67; 95%CI 0.52-0.87; p = 0.002), total removal (aHR 0.54; 95%CI 0.44-0.64; p < 0.0001), and standard radiochemotherapy protocol (aHR 0.32; 95%CI 0.26-0.38; p < 0.0001) were independent predictors of a longer overall survival. Frailty remained an independent predictor of overall survival within the subgroup of patients undergoing a first-line oncological treatment after surgery (n = 549) and within the subgroup of patients who benefited from a total removal plus adjuvant standard radiochemotherapy (n = 209). CONCLUSION: In newly diagnosed supratentorial glioblastoma, IDH-wildtype patients treated at the standard combined radiochemotherapy era, frailty, defined using a 5-mFI score ≥ 2 was an independent predictor of overall survival.

Tetraparesis following thoracic spine surgery in a patient with Klippel-Feil syndrome and ABCB4 mutation: a case report.

BACKGROUND: Klippel-Feil syndrome is a rare condition described in 1912 by Maurice Klippel and André Feil. It is defined as a congenital cervical fusion of at least two vertebrae, associated with a classical triad of clinical signs: short neck, low posterior hairline, and limited range of movement. However, Klippel-Feil syndrome manifests with a vast spectrum of phenotypes, ranging from no symptoms to complete triad, with or without other associated malformations. Most commonly, CCF results from sporadic mutations, even though autosomal recessive, autosomal dominant, or even X-linked inheritance can be detected. The ATP-binding cassette subfamily B member 4 is only expressed in the liver and is involved in biliary phospholipid secretion. The clinical spectrum includes various hepatobiliary pathologies, including low phospholipid-associated cholelithiasis, and has never been associated with musculoskeletal anomalies. CASE PRESENTATION: A 55-year-old male Caucasian patient presenting with low phospholipid-associated cholelithiasis syndrome with ATP-binding cassette subfamily B member 4 mutation and liver cirrhosis was referred to our clinic for a liver transplant. A period of 6 months before, the patient underwent a T7-T9 posterior fixation for a T8 osteoporotic fracture. Postoperatively, he was tetraparetic, whereas he was neurologically intact before the operation. At admission to our hospital, he was still tetraparetic and presented with clinical signs of cervical myelopathy. Moreover, he suffered a limitation of cervical range of motion in all directions, short neck, and low posterior hairline. Imaging showed multiple cervical and thoracic vertebral bodies fusion, as well as cervical spine stenosis. Based on the available data, we diagnosed a type 3 Klippel-Feil syndrome according to Samartzis' classification. CONCLUSIONS: The heterogeneity of KFS and the various potential hereditary links that are known indicate that it is important to highlight all potential cases related to known genetic defects. At present, no association between ATP-binding cassette subfamily B member 4 mutation and congenital cervical fusions has been reported. The other important clinical focus of this case is the appearance of spontaneous tetraparesis after thoracic spine surgery. This mechanism remains unclear, but considering different spinal anatomy it might have been due to difficult intubation and patient's positioning during his previous operation.

Robot-assisted endoscopic third ventriculostomy under intraoperative CT imaging guidance.

BACKGROUND: The robot-assisted neurosurgical procedures have recently benefited of the evolution of intraoperative imaging, including mobile CT unit available in the operating room. This facilitated use paved the way to perform more neurosurgical procedures under robotic assistance. Endoscopic third ventriculocisternostomy requires both a safe transcortical trajectory and a smooth manipulation. METHOD: We describe our technique of robot-assisted endoscopic third ventriculocisternostomy combining robotic assistance and intraoperative CT imaging. CONCLUSION: Robot-assisted endoscopic third ventriculocisternostomy using modern intraoperative neuroimaging can be easily implemented and prevented erroneous trajectory and abrupt endoscopic movements, reducing surgically induced brain damages.

Pediatric Posterior Fossa ATRT: A Case Report, New Treatment Strategies and Perspectives.

Posterior fossa atypical teratoid rhabdoid tumor (ATRT) is a rare childhood tumor usually associated with a dismal prognosis. Although upfront surgical gross total resection (GTR) has classically been the first line of treatment, new multimodal treatments, including two-stage surgery, are showing promising results in terms of overall survival (OS) and complication rate. We present a case of a 9-month-old child treated with two-staged surgery and chemotherapy. When deemed risky, multimodal treatments, including staged surgeries, can be a safe alternative to reduce surgical mortality and morbidity. At 23 months old, the patient had normal global development and no major impact on quality of life. We, therefore, discuss the most recent advancements from a treatment perspective, including molecular targeting.

Current Advances in Papillary Craniopharyngioma: State-Of-The-Art Therapies and Overview of the Literature.

Craniopharyngiomas are commonly classified as low-grade tumors, although they may harbor a malignant behavior due to their high rate of recurrence and long-term morbidity. Craniopharyngiomas are classically distinguished into two histological types (adamantinomatous and papillary), which have been recently considered by the WHO classification of CNS tumors as two independent entities, due to different epidemiological, radiological, histopathological, and genetic patterns. With regard to papillary craniopharyngioma, a BRAF V600 mutation is detected in 95% of cases. This genetic feature is opening new frontiers in the treatment of these tumors using an adjuvant or, in selected cases, a neo-adjuvant approach. In this article, we present an overview of the more recent literature, focusing on the specificities and the role of oncological treatment in the management of papillary craniopharyngiomas. Based on our research and experience, we strongly suggest a multimodal approach combining clinical, endocrinological, radiological, histological, and oncological findings in both preoperative workup and postoperative follow up to define a roadmap integrating every aspect of this challenging condition.

Combined sclerotherapy followed by surgical resection of a large extracranial venous malformation in a 14-month-old child: preoperative workup and technical note.

INTRODUCTION: Venous malformations affect around 2 per 10,000 newborn and are the most common type of congenital vascular malformation. They are always present at birth and are often misdiagnosed with hemangiomas. Accurate diagnosis and adequate targeted therapy through a multidisciplinary approach is advocated for a successful treatment, considering a combination of modalities in complex cases. We present here the workup and treatment of a venous malformation in a 14 month old child by combining a preoperative sclerotherapy with sodium tetradecyl sulfate (STS) followed by complete surgical excision respecting the calvarium. CASE PRESENTATION: A large right extracranial fronto-parietal venous malformation and scalloping of the underlying calvarium, attached to the pericranium, surgically excised after preoperative sclerotherapy with STS in a 14-month-old child. RESULTS: The patient had an uneventful postoperative course with complete resection of the lesion, satisfying cosmetic appearance and no complications. Histopathological examination confirmed a venous malformation. CONCLUSION: We demonstrated the workup and the rationale of the combined sclerotherapy followed by surgical resection of a large growing extracranial venous malformation. Preoperative direct contrast injection and sclerotherapy allowed to rule out significative extracranial to intracranial venous inflow and reduce blood loss for the surgical procedure, respectively. Complete removal of the malformation minimized the impact on future growth of the calvarium.

Surgical Treatment of Spinal Meningiomas in the Elderly (≥75 Years): Which Factors Affect the Neurological Outcome? An International Multicentric Study of 72 Cases.

(1) Background: With the increasing life expectancy in the Western world, an increasing number of old patients presents with spinal meningioma. Considering the benign nature of these tumors, the functional outcome remains of great importance, since more people reach old age in general conditions of well-being and satisfactory autonomy. (2) Methods: We conducted an international multicenter retrospective study to investigate demographic, clinical and radiological data in a population of elderly patients (≥75 years of age) undergoing surgery for SM from January 2000 to December 2020 in four European referral centers. The aim was to identify prognostic and predictive factors for a good postoperative functional outcome. (3) Results: 72 patients were included in the study. Complete tumor resection (Simpson I or II) was achieved in 67 (95.7%) cases. Intraoperative complications were reported in 7 (9.9%) patients while postoperative complications were found in 12 (16.7%). An excellent general postoperative status (McCormick I and II) was achieved in 65.3%. Overall, surgical resection had a good impact on patients' functional outcome (86.1% either showing an improvement or maintaining a good preoperative status). Uni- and multivariate analyses found that both age and preoperative modified McCormick independently correlated with relative outcome (coeff = −0.058, p = 0.0251; coeff = 0.597, p < 0.0001) and with postoperative status (coeff = 0.058, p = 0.02507; coeff = 0.402, p = 0.00027), respectively. (4) Conclusions: Age and preoperative modified McCormick were found to be independent prognostic factors. Nevertheless, advanced age (≥75), per se, did not seem to contraindicate surgery, even in those with severe preoperative neurological deficits. The functional results sustain the need for surgical resection of SM in the elderly.

Supratentorial Pediatric Midline Tumors and Tumor-like Lesions: Clinical Spectrum, Natural History and Treatment Options.

Childhood Central Nervous System tumors account for 25% of all pediatric tumors. Large availability and broadening of indications to imaging has made incidental findings more common. Among these, midline lesions have different clinical relevance depending on their intrinsic pattern of behaviour and on their specific location. In this narrative review we describe the natural history and treatment options of midline lesions in children.

Severe Basilar impression in osteogenesis imperfecta treated with halo gravity traction, occipitocervicothoracic fusion, foramen magnum and upper cervical decompression and expansive duroplasty: a technical note.

Osteogenesis imperfecta (OI) is a rare bone disease due to an abnormal synthesis of 1-type collagen. OI is frequently associated with basilar impression (BI), defined by the elevation of the clivus and floor of the posterior fossa with subsequent migration of the upper cervical spine and the odontoid peg into the base of the skull. Bone intrinsic fragility leading to fractures and deformity, brainstem compression and impaired CSF circulation at cranio-vertebral junction (CVJ) makes the management of these conditions particularly challenging. Different surgical strategies, including posterior fossa decompression with or without instrumentation, transoral or endonasal decompression with posterior occipito-cervical fusion, or halo gravity traction with posterior instrumentation have been reported, but evidence about best modalities treatment is still debated. In this technical note, we present a case of a 16-years-old patient, diagnosed with OI and BI, treated with halo traction, occipito-cervico-thoracic fixation, foramen magnum and upper cervical decompression, and expansive duroplasty. We focus on technical aspects, preoperative work up and postoperative follow up. We also discuss advantages and limitations of this strategy compared to other surgical techniques.

Atlantoaxial posterior screw fixation using intra-operative spinal navigation with three-dimensional isocentric C-arm fluoroscopy.

PURPOSE: Intra-operative image acquisition coupled with navigation aims to increase screw placement accuracy, and it is particularly helpful in complex spinal procedures. The aim of this study is to analyze the accuracy and reliability of posterior atlanto-axial fixation using spinal navigation combined with intra-operative 3D isocentric C-arm. METHODS: We retrospectively reviewed all patients presenting with C1-C2 instability and treated by posterior atlanto-axial fixation in our center between December 2016 and September 2018. Screw positioning was guided by intra-operative navigation, registered with surface matching procedure on a previously obtained CT scan and controlled by intra-operative 3D isocentric C-arm. Age, sex, pre- and post-operative neurological status, duration of surgery, presence/absence of vertebral artery injury, and screw placement were retrospectively collected from patients' records. All patients underwent clinical and radiological follow-up at three months after surgery. Radiological assessment of screw positioning was performed by an independent radiologist using the Gertzbein and Robbins grading. RESULTS: N = 11 (7F, 4 M) consecutive patients were included, with a mean age of 72 years (range from 51 to 85). N = 44 navigated screws were inserted and controlled with intra-operative 3D fluoroscopy at the end of the procedure. An acceptable screw positioning (Gertzbein-Robbins grade A and B) was obtained in all cases (100%). No vertebral artery injury was observed. Mean operating time was 123 minutes. At three months, no screw loosening or displacement was observed. CONCLUSION: In our experience, spinal navigation coupled with intra-operative 3D fluoroscopy proved to be reliable and safe for C1-C2 screw placement.

From Focused Ultrasound Tumor Ablation to Brain Blood Barrier Opening for High Grade Glioma: A Systematic Review.

BACKGROUND: Focused Ultrasound (FUS) is gaining a therapeutic role in neuro-oncology considering its novelty and non-invasiveness. Multiple pre-clinical studies show the efficacy of FUS mediated ablation and Blood-Brain Barrier (BBB) opening in high-grade glioma (HGG), but there is still poor evidence in humans, mainly aimed towards assessing FUS safety. METHODS: With this systematic review our aim is, firstly, to summarize how FUS is proposed for human HGG treatment. Secondly, we focus on future perspectives and new therapeutic options. Using PRISMA 2020 guidelines, we reviewed case series and trials with description of patient characteristics, pre- and post-operative treatments and FUS outcomes. We considered nine case series (five about tumor ablation and four about BBB opening) with FUS-treated HGG patients between 1991 and 2021. RESULTS: Sixty-eight patients were considered in total, mostly males (67.6%), with a mean age of 50.5 ± 15.3 years old. Major complication rates were found in the tumor ablation group (26.1%). FUS has been rarely applied for direct tumoral ablation in human HGG patients with controversial results, but at the best of current studies, FUS-mediated BBB opening is showing good results with very low complication rates, paving the way for a new reliable technique to improve local chemotherapy delivery and antitumoral immune response. CONCLUSIONS: FUS can become a complementary technique to surgical resection and standard radiochemotherapy in recurrent HGG. Ongoing trials could provide in the near future more data on FUS-mediated BBB opening impact on progression-free survival, overall survival and potential drug-delivery capacities.

Spinal Meningiomas: Influence of Cord Compression and Radiological Features on Preoperative Functional Status and Outcome.

BACKGROUND: Radiological parameters predicting the postoperative neurological outcome after resection of a spinal meningioma (SM) are poorly studied, with controversial results. METHODS: Observational multicenter cohort (2011-2018) of adult patients undergoing surgery for resection of SM. Tumor-canal volume ratio (TCR), the areas related to the cord and tumor occupancy at maximum compression, the presence of dural tail, calcifications, signs of myelopathy, and postoperative cord expansion were compared with the modified McCormick scale (mMCS) preoperative and at follow-up. RESULTS: In the cohort (n = 90 patients), cord and tumor occupancy as well as cord compression and tumor volume showed a correlation with preoperative mMCS (p < 0.05, R -0.23; p < 0.001, R 0.35; p < 0.005, R -0.29; p < 0.001, R 0.42). Cord occupancy had a strong correlation with cord compression (p < 0.001, R 0.72). Tumor occupancy and TCR were correlated with relative outcome at follow-up (p < 0.005 R 0.3; p < 0.005 R 0.29). No correlation was found between cord re-expansion and clinical outcome at follow-up. Finally, a correlation was shown between preoperative signs of cord myelopathy and mMCS (p < 0.05 R 0.21) at follow-up. CONCLUSIONS: Larger tumors showed lower preoperative functional status and a worse clinical outcome. Moreover, preoperative T2 cord signal changes are correlated with a poorer outcome.

Foramen magnum meningiomas: a systematic review and meta-analysis.

Foramen magnum meningiomas (FMMs) account for 1.8-3.2% of all meningiomas. With this systematic review and meta-analysis, our goal is to detail epidemiology, clinical features, surgical aspects, and outcomes of this rare pathology. Using PRISMA 2015 guidelines, we reviewed case series, mixed series, or retrospective observational cohorts with description of surgical technique, patient and lesion characteristics, and pre- and postoperative clinical status. A meta-analysis was performed to search for correlations between meningioma characteristics and rate of gross total resection (GTR). We considered 33 retrospective studies or case series, including 1053 patients, mostly females (53.8%), with a mean age of 52 years. The mean follow-up was of 51 months (range 0-258 months). 65.6% of meningiomas were anterior, and the mean diameter was of 29 mm, treated with different surgical approaches. Postoperatively, 17.2% suffered complications (both surgery- and non-surgery-related) and 2.5% had a recurrence. The Karnofsky performance score improved in average after surgical treatment (75 vs. 81, p < 0.001). Our meta-analysis shows significant rates of GTR in cohorts with a majority of posterior and laterally located FMM (p = 0.025) and with a mean tumor less than 25 mm (p < 0.05). FMM is a rare and challenging pathology whose treatment should be multidisciplinary, focusing on quality of life. Surgery still remains the gold standard and aim at maximal resection with neurological function preservation. Adjuvant therapies are needed in case of subtotal removal, non-grade I lesions, or recurrence. Specific risk factors for recurrence, other than Simpson grading, need further research.

Role of Robotics in Improving Surgical Outcome in Spinal Pathologies.

BACKGROUND: The desire to improve accuracy and safety and to favor minimally invasive techniques has given rise to spinal robotic surgery, which has seen a steady increase in utilization in the past 2 decades. However, spinal surgery encompasses a large spectrum of operative techniques, and robotic surgery currently remains confined to assistance with the trajectory of pedicle screw insertion, which has been shown to be accurate and safe based on class II and III evidence. The role of robotics in improving surgical outcomes in spinal pathologies is less clear, however. METHODS: This comprehensive review of the literature addresses the role of robotics in surgical outcomes in spinal pathologies with a focus on the various meta-analysis and prospective randomized trials published within the past 10 years in the field. RESULTS: It appears that robotic spinal surgery might be useful for increasing accuracy and safety in spinal instrumentation and allows for a reduction in surgical time and radiation exposure for the patient, medical staff, and operator. CONCLUSION: Robotic assisted surgery may thus open the door to minimally invasive surgery with greater security and confidence. In addition, the use of robotics facilitates tireless repeated movements with higher precision compared with humans. Nevertheless, it is clear that further studies are now necessary to demonstrate the role of this modern tool in cost-effectiveness and in improving clinical outcomes, such as reoperation rates for screw malpositioning.