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.

Complications of degenerative lumbar spondylolisthesis and stenosis surgery in patients over 80 s: comparative study with over 60 s and 70 s. Experience with 678 cases.

PURPOSE: Degenerative spondylolisthesis (DS) is a debilitating condition that carries a high economic burden. As the global population ages, the number of patients over 80 years old demanding spinal fusion is constantly rising. Therefore, neurosurgeons often face the important decision as to whether to perform surgery or not in this age group, commonly perceived at high risk for complications. METHODS: Six hundred seventy-eight elder patients, who underwent posterolateral lumbar fusion for DS (performed in three different centers) from 2012 to 2020, were screened for medical, early and late surgical complications and for the presence of potential preoperative risk factors. Patients were divided in three categories based on their age: (1) 60-69 years, (2) 70-79 years, (3) 80 and over. Multiple logistic regression was used to determine the predictive power of age and of other risk factors (i.e., ASA score; BMI; sex; presence or absence of insulin-dependent and -independent diabetes, use of anticoagulants, use of antiaggregants and osteoporosis) for the development of postoperative complications. RESULTS: In univariate analysis, age was significantly and positively correlated with medical complications. However, when controls for other risk factors were added in the regressions, age never reached significance, with the only noticeable exception of cerebrovascular accidents. ASA score and BMI were the two risk factors that significantly correlated with the higher numbers of complication rates (especially medical). CONCLUSION: Patients of different age but with comparable preoperative risk factors share similar postoperative morbidity rates. When considering octogenarians for lumbar arthrodesis, the importance of biological age overrides that of chronological.

Freeze-Dried Secretome (Lyosecretome) from Mesenchymal Stem/Stromal Cells Promotes the Osteoinductive and Osteoconductive Properties of Titanium Cages.

Titanium is one of the most frequently used materials in bone regeneration due to its good biocompatibility, excellent mechanical properties, and great osteogenic performance. However, osseointegration with host tissue is often not definite, which may cause implant failure at times. The present study investigates the capacity of the mesenchymal stem cell (MSC)-secretome, formulated as a ready-to-use and freeze-dried medicinal product (the Lyosecretome), to promote the osteoinductive and osteoconductive properties of titanium cages. In vitro tests were conducted using adipose tissue-derived MSCs seeded on titanium cages with or without Lyosecretome. After 14 days, in the presence of Lyosecretome, significant cell proliferation improvement was observed. Scanning electron microscopy revealed the cytocompatibility of titanium cages: the seeded MSCs showed a spread morphology and an initial formation of filopodia. After 7 days, in the presence of Lyosecretome, more frequent and complex cellular processes forming bridges across the porous surface of the scaffold were revealed. Also, after 14 and 28 days of culturing in osteogenic medium, the amount of mineralized matrix detected by alizarin red was significantly higher when Lyosecretome was used. Finally, improved osteogenesis with Lyosecretome was confirmed by confocal analysis after 28 and 56 days of treatment, and demonstrating the production by osteoblast-differentiated MSCs of osteocalcin, a specific bone matrix protein.

Degenerative Lumbar Stenosis Surgery: Predictive Factors of Clinical Outcome-Experience with 1001 Patients.

BACKGROUND: Degenerative lumbar spinal stenosis (DLSS) carries a high risk of morbidity and represents a financial burden to society. A late diagnosis can lead to severe disability. Although lumbar decompressive surgery has been widely used worldwide, the proper preoperative factors to define the ideal candidates for decompression are missing. METHODS: A total of 1001 patients who had undergone decompressive surgery from 2012 to 2019 for DLSS were screened for the presence of 9 clinical and radiological parameters. For all cases, the differences between the baseline and postoperative Oswestry disability index were calculated and the results categorized as 5 different classes (ranging from very poor outcomes to excellent outcomes) according to the specific scores. Generalized ordinal logistic regression was then used to analyze the significance of the 9 parameters (coded as dummy variables) in predicting the outcome as measured by Oswestry disability index improvement after surgery. RESULTS: Of the 9 parameters, 8 were found to be significant predictors. The radiological grade of compression was the strongest, followed by polyneuropathy, obesity, symptom duration, gait autonomy, radicular deficits, American Society of Anesthesiologists score, and level of surgery. In contrast, previous back surgery was not predictive of the outcome. CONCLUSIONS: Our findings have indicated that the ideal candidate for surgery will have the following preoperative characteristics: Schizas grade D, no signs of peripheral polyneuropathy, body mass index <30 kg/m2, symptom duration of <2 years, gait autonomy <100 m, no radicular deficits, 1 level of stenosis, and an American Society of Anesthesiologists score of 1, 2, or 3.

Randomized Trial of Sacroiliac Joint Arthrodesis Compared with Conservative Management for Chronic Low Back Pain Attributed to the Sacroiliac Joint.

BACKGROUND: Sacroiliac joint pain is increasingly recognized as a cause of low back pain. We compared the safety and effectiveness of minimally invasive sacroiliac joint arthrodesis using triangular titanium implants and conservative management in patients with chronic sacroiliac joint pain. METHODS: This study was a prospective, multicenter randomized controlled trial of adults with chronic sacroiliac joint pain assigned to either conservative management or sacroiliac joint arthrodesis with triangular titanium implants. The study end points included self-rated low back pain (visual analog scale [VAS]), back dysfunction (Oswestry Disability Index [ODI]), and quality of life. Ninety percent of subjects in both groups completed the study. RESULTS: Between June 6, 2013, and May 15, 2015, 103 subjects were randomly assigned to conservative management (n = 51) or sacroiliac joint arthrodesis (n = 52). At 2 years, the mean low back pain improved by 45 points (95% confidence interval [CI], 37 to 54 points) after sacroiliac joint arthrodesis and 11 points (95% CI, 2 to 20 points) after conservative management, with a mean difference between groups of 34 points (p < 0.0001). The mean ODI improved by 26 points (95% CI, 21 to 32 points) after sacroiliac joint arthrodesis and 8 points (95% CI, 2 to 14 points) after conservative management, with a mean difference between groups of 18 points (p < 0.0001). Parallel improvements were seen in quality of life. In the sacroiliac joint arthrodesis group, the prevalence of opioid use decreased from 56% at baseline to 33% at 2 years (p = 0.009), and no significant change was observed in the conservative management group (47.1% at baseline and 45.7% at 2 years). Subjects in the conservative management group, after crossover to the surgical procedure, showed improvements in all measures similar to those originally assigned to sacroiliac joint arthrodesis. In the first 6 months, the frequency of adverse events did not differ between groups (p = 0.664). By month 24, we observed 39 severe adverse events after sacroiliac joint arthrodesis, including 2 cases of sacroiliac joint pain, 1 case of a postoperative gluteal hematoma, and 1 case of postoperative nerve impingement. The analysis of computed tomographic (CT) imaging at 12 months after sacroiliac joint arthrodesis showed radiolucencies adjacent to 8 implants (4.0% of all implants). CONCLUSIONS: For patients with chronic sacroiliac joint pain due to joint degeneration or disruption, minimally invasive sacroiliac joint arthrodesis with triangular titanium implants was safe and more effective throughout 2 years in improving pain, disability, and quality of life compared with conservative management. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma Patients.

PURPOSE: Glioblastoma (GBM) is the most common primary brain tumor. The identification of blood biomarkers reflecting the tumor status represents a major unmet need for optimal clinical management of patients with GBM. Their high number in body fluids, their stability, and the presence of many tumor-associated proteins and RNAs make extracellular vesicles potentially optimal biomarkers. Here, we investigated the potential role of plasma extracellular vesicles from patients with GBM for diagnosis and follow-up after treatment and as a prognostic tool. EXPERIMENTAL DESIGN: Plasma from healthy controls (n = 33), patients with GBM (n = 43), and patients with different central nervous system malignancies (n = 25) were collected. Extracellular vesicles were isolated by ultracentrifugation and characterized in terms of morphology by transmission electron microscopy, concentration, and size by nanoparticle tracking analysis, and protein composition by mass spectrometry. An orthotopic mouse model of human GBM confirmed human plasma extracellular vesicle quantifications. Associations between plasma extracellular vesicle concentration and clinicopathologic features of patients with GBM were analyzed. All statistical tests were two-sided. RESULTS: GBM releases heterogeneous extracellular vesicles detectable in plasma. Plasma extracellular vesicle concentration was higher in GBM compared with healthy controls (P < 0.001), brain metastases (P < 0.001), and extra-axial brain tumors (P < 0.001). After surgery, a significant drop in plasma extracellular vesicle concentration was measured (P < 0.001). Plasma extracellular vesicle concentration was also increased in GBM-bearing mice (P < 0.001). Proteomic profiling revealed a GBM-distinctive signature. CONCLUSIONS: Higher extracellular vesicle plasma levels may assist in GBM clinical diagnosis: their reduction after GBM resection, their rise at recurrence, and their protein cargo might provide indications about tumor, therapy response, and monitoring.

Strokectomy and Extensive Cerebrospinal Fluid Drainage for the Treatment of Space-Occupying Cerebellar Ischemic Stroke.

BACKGROUND: Cerebellar ischemia may lead to space-occupying edema, resulting in potentially fatal complications. Different surgical procedures are available to create space for the swollen ischemic brain; however, the type and timing of surgical treatments remain topics of debate in the literature. Here we report a case series of patients treated with a unilateral craniotomy to perform a cerebellar strokectomy and extensive cerebrospinal fluid (CSF) drainage without osteodural posterior fossa decompression. METHODS: We retrospectively analyzed the clinical and radiographic data of 11 patients with posterior fossa ischemia who underwent surgery at one of our institutions. A statistical analysis was performed to identify potential predictive factors for functional outcome. RESULTS: The mean patient age was 64.7 years. The involved vascular territory was the Posterior inferior cerebellar artery in 9 patients (82%) and the anterior inferior cerebellar artery/superior cerebellar artery in 2 patients (18%). The mean Glasgow Coma Scale score was 13.6 on admission, but 9.3 immediately before surgery. The surgical procedure was performed in a mean of 36.8 minutes after the radiologic diagnosis of space-occupying edema. Clinical outcome at 6 months was good (modified Rankin Scale [mRS] score ≤2) in 9 patients (82%). Surgery-related complications occurred in 2 patients (18%), and these was a single death (9%) not related to the procedure or posterior fossa compression. Matching patients with their mRS outcome evaluation, the sole variable significantly associated with good outcome was age at admission (62.1 vs. 76.5 years; P < 0.05). CONCLUSIONS: Unilateral suboccipital craniotomy with strokectomy and extensive CSF drainage may allow for satisfactory decompression of the ischemic posterior fossa with acceptable morbidity and mortality rates, especially in younger patients.

Endoscopic transorbital surgery for spheno-orbital lesions: how I do it.

BACKGROUND: The endoscopic transorbital approach has been recently proposed for the surgical management of spheno-orbital lesions as an alternative to craniotomy surgeries. METHOD: We analyze the technical nuances and what we have changed as our experience increased after the first operations performed for 12 different spheno-orbital lesions. CONCLUSION: The endoscopic transorbital approach is useful for the treatment of selected spheno-orbital lesions and could represent an interesting option in experienced hands. More studies are needed to fully understand its potentialities and limitations.

1-Year Results of a Randomized Controlled Trial of Conservative Management vs. Minimally Invasive Surgical Treatment for Sacroiliac Joint Pain.

BACKGROUND: Low back pain (LBP) emanating from the sacroiliac joint (SIJ) is a common finding. Devices to fuse the SIJ are now commercially available, but high-quality evidence supporting their effectiveness is limited. OBJECTIVES: To compare the safety and effectiveness of conservative management (CM) to minimally invasive sacroiliac joint fusion (SIJF) in patients with chronic LBP originating from the SIJ. STUDY DESIGN: Prospective, multicenter randomized controlled trial. SETTING: One hundred three adults in spine clinics with chronic LBP originating from the SIJ. METHODS: Patients were randomly assigned to CM (n = 51) or SIJF using triangular titanium implants (n = 52). CM consisted of optimization of medical therapy, individualized physiotherapy, and adequate information and reassurance as part of a multifactorial treatment. The primary outcome was the difference in change in self-rated LBP at 6 months using a 0 - 100 visual analog scale (VAS). Other effectiveness and safety endpoints, including leg pain, disability using Oswestry Disability Index (ODI), quality of life using EQ-5D, and SIJ function using active straight leg raise test (ASLR), were assessed up to 12 months. RESULTS: At 12 months, mean LBP improved by 41.6 VAS points in the SIJF group vs. 14.0 points in the CM group (treatment difference of 27.6 points, P < 0.0001). Mean ODI improved by 25.0 points in the SIJF group vs. 8.7 points in the CM group (P < 0.0001). Mean improvements in leg pain and EQ-5D scores were large after SIJF and superior to those after CM. CM patients were allowed to crossover to SIJF after 6 months. Patients who crossed to surgical treatment had no pre-crossover improvement in pain and ODI scores; after crossover, improvements were as large as those originally assigned to SIJF. One case of postoperative nerve impingement occurred in the surgical group. Two SIJF patients had recurrent pain attributed to possible device loosening and one had postoperative hematoma. In the CM group, one crossover surgery patient had recurrent pain requiring a revision surgery. LIMITATIONS: The primary limitation was lack of blinding and the subjective nature of self-assessed outcomes. CONCLUSIONS: For patients with chronic LBP originating from the SIJ, minimally invasive SIJF with triangular titanium implants was safe and more effective than CM in relieving pain, reducing disability, and improving patient function and quality of life. Our findings will help to inform decisions regarding its use as a treatment option in this patient population.Key words: Sacroiliac joint dysfunction, pelvic girdle pain, randomized controlled trial, quality of life, spine implants.

Intraregional differences of perioperative management strategy for lumbar disc herniation: is the Devil really in the details?

BACKGROUND: This study intends to evaluate whether regional common habits or differences in case-volume between surgeons are significative variables in the perioperative management of patients undergoing surgery for lumbar disc herniation. METHODS: An e-mail survey was sent to all neurosurgeons working in Lombardy, Italy's most populated region. The survey consisted of 17 questions about the perioperative management of lumbar disc herniation. RESULTS: Forty-seven percent (47%) out of 206 Lombard neurosurgeons answered the survey. Although in some respects there is clear evidence in current literature on which is the best practice to adopt for an optimal management strategy, we noticed substantial differences between respondents, not only between hospitals but also between surgeons from the same hospital. Still, no differences were evident in a high vs low case-volume comparison. CONCLUSION: We identified no regional clusterization as for practical principles in the perioperative management of lumbar disc herniation and neither was case-volume a significative variable. Other causes may be relevant in the variability between the perioperative management and the outcomes achieved by different specialists.

Systemic Sarcoidosis Unmasked by Cushing's Disease Surgical Treatment.

Diseases responsive to glucocorticoids, like sarcoidosis, are rarely masked by Cushing's syndrome. An ACTH secreting pituitary adenoma is a possible cause of Cushing's syndrome and its resection can make a subclinical sarcoidosis clear. Only few cases of sarcoidosis following the treatment of hypercortisolism are reported in literature. We report a case of sarcoidosis after the resection of an ACTH secreting pituitary adenoma.

Tension pneumocephalus secondary to osteoradionecrosis of the clivus.

We report the case of a 36 year-old man with relapsing undifferentiated nasopharyngeal carcinoma treated with a re-irradiation Cyberknife, who subsequently developed tension pneumocephalus due to a cerebrospinal fluid leakage located at the clivus. The fistula was caused by osteonecrosis of the skull base secondary to the tumor invasion and to the sequelae of the radiotherapy. An endoscopic endonasal technique was used in order to repair the defect, with a peduncolated nasoseptal flap harvested to perform the skull base reconstruction. In this paper, we discuss the importance of identifying this possible complication related to radiotherapy in the management of neoplasm along the skull base; moreover, the role of endoscopy in the diagnosis and treatment of skull base fistulas is also described and commented.

Low-Cost Fluorescein Detection System for High-Grade Glioma Surgery.

BACKGROUND: Intraoperative fluorescein detection has been used in the fields of vascular and oncologic neurosurgery since 1948. Modifications of the optics in order to enhance the fluorescence contrast under microscopic view have been developed by many authors. The industries, during the past 10 years, provided commercial high-cost optimized apparatuses. Reviewing the literature, we found that the prototypical techniques were definitely inexpensive but lacked reliability, reproducibility, and standard legal norms. METHODS: We describe the developing of a fluorescein detection system that could be economic, simple, effective, and law abiding. RESULTS: We employed a commercial violet-blue filter designed for fluorescein excitation in endoscopic procedures and used commercial photographic yellow optical filters for fluorescence detection. All the instrumentation is cleared for clinical use, and its cost is up to 200 times lower than commercial apparatuses. CONCLUSION: Our results show a good distinction of fluorescein-stained structures, with overall acceptable operating light conditions.

Endoscopic Management of Spontaneous Clival Cerebrospinal Fluid Leaks: Case Series and Literature Review.

OBJECTIVE: Spontaneous cerebrospinal fluid leaks are most commonly located along the anterior skull base. Sphenoidal localization is less common, and clival localization is even rarer. We analyzed a group of patients with spontaneous leaks and selected patients with clival localization. This article discusses surgical management of these entities and provides a brief literature review regarding spontaneous clival leaks. METHODS: Of a cohort of 67 patients who presented to our departments with a spontaneous leak during the period 2005-2014, a retrospective data analysis was performed on 6 patients with clival localization of the defect. A skull base repair with a multilayered reconstruction was performed in 3 patients, and a single-layered reconstruction using a pedicled nasoseptal flap was performed in 3 patients. RESULTS: The patients included 6 women with a mean age of 60 years (range, 36-91 years). The mean length of the follow-up period was 69.5 months (range, 22-114 months). The overall success rate of the primary endoscopic repair was 83.3% (5 of 6 patients); this increased to 100% after revision surgery. CONCLUSIONS: This series, although numerically limited, suggests that a minimally invasive endoscopic repair of idiopathic clival leaks may be accomplished with an acceptable rate of morbidity and excellent outcomes. Moreover, the pedicled nasoseptal flap has been confirmed to be the "workhorse" for the reconstruction of clival defects.

ACTH-dependent Cushing's Syndrome: Diagnostic Pitfalls in Concomitant Non-secreting Pituitary Adenomas.

OBJECTIVES: To describe the possible pitfalls in correctly interpreting clinical, radiological and biochemical findings in ACTH-dependent Cushing's syndrome. METHODS: We describe a case of a pituitary adenoma visualized at MRI not correlated with an ACTH-dependent Cushing's syndrome. RESULTS: Radiological imaging and hormonal testing can be misleading in suspected pituitary ACTH-related Cushing's syndrome. CONCLUSION: Correct interpretation of the initial clinical presentation can help in the proper diagnosis and treatment of ACTH-dependent Cushing's syndrome. LEARNING POINTS: Occult neoplasia should always be excluded in cases of severe ACTH-dependent Cushing's syndrome.A positive MRI result can be misleading. Ectopic ACTH-dependent syndrome is generally associated with a peculiar phenotype.

First impressions about Adherus, a new dural sealant.

PURPOSE: The aim of the study is to report our first impressions about Adherus, a novel dural sealant, used in neurosurgical endoscopic transnasal procedures. METHODS: We retrospectively reviewed the clinical and surgical records of the first 11 patients with intraoperative high-flow cerebrospinal fluid leak treated with the aid of Adherus at our center between February and October 2014. The healing at the level of the dural plasty was monitored and evaluated radiologically and with regular endoscopic inspections. RESULTS: With a median follow-up of 210 days, no postoperative CSF leak or surgical site infections were found in any of the cases. CONCLUSIONS: Based on our preliminary experience, this new dural sealant seems to provide an effective aid in dural plasty during endoscopic transphenoidal procedures.

Chordoid glioma: a rare radiologically, histologically, and clinically mystifying lesion.

Chordoid glioma (CG) is a rare central nervous system neoplasm (WHO grade II) of uncertain origin whose typical localization is in the anterior part of the third ventricle. Its clinical, radiological, and histological features may vary and furthermore mimic other kind of benign lesions usually associated with a better outcome. We report a case of a 43-year-old female who underwent gross total removal of a lesion of the third ventricle causing hydrocephalus. The imaging studies and the intraoperative examination led at first to a hypothesis of meningioma. Early surgical and neurological outcomes were good. The patient underwent multiple complications related to hypothalamic dysfunctions and thrombohemorragic issues and eventually died because of systemic infections. Definitive examination was of chordoid glioma of the third ventricle. Reviewing literature, we evaluated possible pitfalls in radiological and histological diagnosis as well as in surgical and medical treatment of CGs. Despite their benign presentation, a high incidence of multiple possible severe complications is reported. Early alertness and combined treatment strategies could improve overall CGs treatment strategies.