Ollier Disease, Acute Myeloid Leukemia, and Brain Glioma: IDH as the Common Denominator.

Ollier disease (OD), acute myeloid leukemia (AML), and brain glioma (BG) are three apparently completely different neoplasms in terms of histopathology, clinic, natural history, and management, but they can affect the same patient. This study aimed to identify the common molecular pathways involved in the pathogenesis of all three diseases and discuss their current and potential role as therapeutic targets. A detailed and comprehensive systematic literature review according to PRISMA guidelines on OD patients harboring BG and/or AML was made. In addition, the unique case of a patient affected by all three considered diseases has been added to our case series. Demographic, pathological, treatment, and outcome data were analyzed and discussed, mainly focusing on the molecular findings. Twenty-eight studies reported thirty-three patients affected by OD and BG, and only one study reported one patient with OD and AML, while only our patient harbored all three pathologies. The IDH R132H mutation was the only genetic alteration shared by all three pathologies and was simultaneously detected in enchondromas and brain glioma in 100% (3/3) of OD patients with BG and also in the neoplastic blood cells of the single patient hosting all three diseases. The IDH1-R132H gene mutation is the etiopathogenetic common denominator among three apparently different tumors coexisting in the same patient. The adoption of mutant-specific IDH1 inhibitor molecules could represent a potential panacea for these conditions in the era of targeted therapies. Further studies with larger clinical series are needed to confirm our results and hypothesis.

Integrative approaches in spinal cord stimulation: Neuropathic pain management and motor recovery in spinal cord injury. A narrative review.

Introduction: Spinal cord stimulation is a widespread treatment of chronic neuropathic pain from different conditions. Several novel and improving technologies have been recently developed to increase the effect of neuromodulation in patients refractory to pharmacological therapy. Research question: To explore spinal cord stimulation's mechanisms of action, indications, and management. Material and methods: The paper initially explores the mechanism of action of this procedure based on the generation of an electric field between electrodes placed on the posterior dural surface of the spinal cord probably interfering with the transmission of pain stimuli to the brain. Subsequently, the most consolidated criteria for selecting patients for surgery, which constitute a major issue of debate, were defined. Thereafter, the fundamental patterns of stimulation were summarized by exploring the advantages and side effects. Lastly, the most common side effects and the related management were discussed. Results: Proper selection of the patient is of paramount importance to achieve the best results from this specific neuromodulation treatment. Regarding the different types of stimulation patterns, no definite evidence-based guidelines exist on the most appropriate approach in relation to the specific type of neuropathic pain. Both burst stimulation and high-frequency stimulation are innovative techniques that reduce the risk of paresthesias compared with conventional stimulation. Discussion and conclusion: Novel protocols of stimulation (burst stimulation and high frequency stimulation) may improve the trade-off between therapeutic benefits and potential side effects. Likewise, decreasing the rates of hardware-related complications will be also useful to increase the application of neuromodulation in clinical settings.

Articular arthrodesis with the facet wedge technique for the treatment of unstable lumbar degenerative disease and associated conditions: A retrospective study of 96 patients.

Background: Lumbar articular fusion with the facet wedge (FW) technique is gaining increasing interest among surgeons for the treatment of vertebral instability due to its limited invasiveness and ease of use. Studies on cadavers have reported biomechanical properties similar to pedicle screws. Yet, the evidence supporting their use is still limited and moreover focused only on spinal degenerative disease. Methods: 96 cases of lumbar articular fusion with the FW techniques performed at 3 different centers between 2014 and 2022 were retrospectively analyzed based on the specific surgical indications: 1) degenerative spondylolisthesis/unstable lumbar stenosis; 2) synovial cysts; 3) adjacent segment disease (ASD). Medical records were reviewed to identify rates of complications and measures of functional outcome (ODI, low back pain VAS and modified Macnab scale) were collected both at baseline and at the follow-up visits. Wilcoxon signed-rank test was adopted to test for significant functional improvements. Results: Significative clinical improvements were observed from baseline to follow-up regarding ODI and VAS scores. Overall rate of moderate and severe complications (according to Landriel-Ibañez scale) was 7.9%. Only 3.4% of patients with degenerative disease developed ASD requiring reoperations. Only one case of radicular deficit and one of device mobilization were reported. 2/4 cases of synovial cysts treated with unilateral fusions developed contralateral complications. 9 out of 16 (56.25%) patients who underwent long-term postoperative CT scans presented adequate degree of articular fusion. Conclusion: FW technique is easy, safe, and effective. Its low rate of complications justifies its use for cases of mild lumbar instability.

A Benefit/Risk Assessment of Intrathecal Ziconotide in Chronic Pain: A Narrative Review.

BACKGROUND: Ziconotide is an intrathecal drug administered for the treatment of chronic pain. The current literature lacks an exhaustive benefit/risk assessment on this drug. We herein focus on Ziconotide's pharmacology and clinical applications. METHODS: Literature research was conducted to identify studies on Ziconotide administration for the treatment of chronic pain, published between January 1990 and March 2023 and located via PubMed, Embase, Medline, Cinahl, and Web of Science, using the following keywords: Ziconotide, Omega conotoxin, Prialt, SNX-111, intrathecal therapy, and neuropathic pain. Only publications written in English were selected. RESULTS: Among the 86 selected studies, we found 4 Randomized Controlled Trials (RCTs) and 3 prospective long-term studies concerning the intrathecal use of Ziconotide as a monotherapy in chronic pain. Other studies described the intrathecal infusion of Ziconotide combined with other drugs. Overall, Ziconotide has been proved to have strong efficacy for relieving chronic pain, although patients with co-morbid psychiatric disorders require a careful monitoring when treated with Ziconotide. CONCLUSIONS: Overall, the use of Ziconotide, as a monotherapy or in conjunction with other therapies for the treatment of chronic pain, was reported to be efficacious. Overall, its use in patients with chronic pain refractory to other pharmacologic agents outweighs the possible adverse consequences, thus resulting in a favorable benefit/risk assessment.

Proposal of a new score system (Cervical Surgical Score) for management of degenerative cervical myelopathy.

BACKGROUND: To date, no shared algorithms with the aim of guiding surgical strategy in complex cases of degenerative cervical myelopathy (DCM) exist. Our purpose is to present the Cervical Surgical Score (CSS) which could help in identifying complex DCM cases, suggesting a surgical strategy. METHODS: We created the CSS based on multidisciplinary and literature-focused discussions, based on eight parameters including number of levels of cervical pathology and myelopathy, type and predominance of compression and grade of clinical myelopathy. We prospectively enrolled surgical DCM patients in a 15-months period, collecting clinical and radiological data. During outpatient clinic a specific surgical indication was offered to DCM patients. To validate the score, each outpatient clinic surgical indication was compared a posteriori to the one that resulted from multidisciplinary CSS scoring, focusing on patients for which both an anterior and posterior approach were considered suitable. RESULTS: A total of 100 patients operated on for DCM at our Institution between December 2021 and February 2023 were prospectively enrolled. In 53% of patients the pathology was present at more than two levels. According to CSS calculation, 14% of patients resulted in the "grey zone", where both an anterior and posterior approach were deemed feasible. Among them, in 42.8% of cases the CSS allowed a modification of the originally planned surgery. Looking at outcome, an improvement of m-JOA score in 62% of patients was disclosed. CONCLUSIONS: This preliminary study showed the reliability and usefulness of CSS in detecting complex DCM cases, requiring further analysis by expert spine surgeons, suggesting a surgical strategy.

Exoscopic-assisted posterior approach for the removal of thoracic dumbbell schwannoma: Three-dimensional operative video.

"Dumbbell" tumors are described as benign neoplasms presenting both intraspinal and extraspinal extensions, connected through the intervertebral foramen (McCormick, 1996) [1]. About 90 % of such tumors are histologically classified as schwannomas that most frequently arise in the thoracic region (Takamura and et al., 1997) [2]. Diagnosis is usually achieved as soon as the dimensional increase of the intracanal portion results in nerve or spinal cord compression (Ishikawa and et al., 2002) [3]. How to obtain a complete surgical resection of tumors with large or ventrally located extraforaminal components with a minimally invasive approach is still debated (Payer and et al., 2006) [4]. The single-stage posterior removal of the tumor is the most performed approach for lesions presenting with a small extra-foraminal component (Payer and et al., 2006) [4]. However, due to the reduced visual surgical field and poor control of the surrounding structures that could be obtained with an operative microscopic (OM) view, the application of this approach still appears to be limited to lesions with a large extraspinal component. An alternative surgical approach is the lateral transthoracic transpleural approach, which, however, carries greater risks of complications and often requires assistance from a thoracic surgeon. During the last decade, the exoscope was developed as a hybrid optical instrument, standing between the OM and the endoscope, merging the pros and cons of both visualization technologies, providing a wide viewing angle, high-resolution images, and non-monoaxial view. In this work we present a case of a 60-years old male patient with a 6-month history of dorsal pain and mild left limb paresthesia resistant to conservative treatment in which for the first time a single stage exoscopic-assisted (Olympus ORBEYE 4K-3D exoscope) posterior approach was used to remove entirely a thoracic dumbbell schwannoma with large extraspinal involvement.

Small spheno-ethmoidal meningoencephalocele versus ethmoidal mucocele in spontaneous intracranial hypotension.

Background: Meningoencephalocele is defined as an abnormal sac of brain tissue and meninges extending beyond natural skull margins, often leading to cerebrospinal fluid (CSF) leakage. When this condition arises in the spheno-ethmoidal region, the diagnosis becomes more challenging as it can be mistaken for other nasal pathologies, such as mucocele. Research question: We show in this case report a non-congenital sphenoethmoidal meningoencephalocele causing rhinoliquoral fistula and spontaneous intracranial hypotension. Results: this 65-year-old woman presented with sporadic rhinoliquorrhoea associated with orthostatic headache, nausea and dizziness. Brain MRI revealed a small lesion of an ethmoidal sinus, which was successfully treated with endoscopic endonasal surgery. Histology confirmed the presence of meningoencephalic tissue positive for S100 protein on immunohistochemistry. Conclusions: When dealing with lesions of the paranasal sinuses in contact with the anterior skull base, rhinoliquorrhoea presence suggests meningoencephalocele. In dubious cases, a proper workup, including a thorough clinical history and neurological examination, specific imaging, and a direct search of CSF-like markers, is essential to support the differential diagnosis. In such cases, a transnasal endoscopic surgical approach is recommended to obtain a final histological diagnosis and to perform eventual dural plastic surgery.

Degenerative L4-L5 spondylolisthesis and stenosis surgery: does over-level flavectomy technique influence clinical outcomes and rates of cranial adjacent segment disease?

BACKGROUND: One of the most dreaded long-term complications related to L4-L5 lumbar arthrodesis is the onset of adjacent segment disease, which most frequently occurs at the cranial level. Few studies have compared the rates of cranial adjacent segment disease (CASD) in patients undergoing lumbar fusion associated with total laminectomy at the same level with those undergoing partial laminectomy. No study has examined the role of selective over-level flavectomy (OLF; i.e., L3-L4). METHODS: A total of 299 patients undergoing posterolateral arthrodesis (PLA) for L4-L5 degenerative spondylolisthesis were retrospectively analyzed with a 5-year follow-up. 148 patients underwent PLA + L4-L5 flavectomy + L4 partial laminectomy (control group), while 151 underwent PLA + L4-L5 flavectomy + total L4 laminectomy + L3-L4 flavectomy (OLF group). Rates of reoperations due to CASD were examined utilizing Cox proportional hazard models, while clinical improvement at follow-up (measured in ODI) was analyzed using generalized linear models (GLMs). Adjustments for potential confounders were made (grade of lumbar lordosis, age, sex, BMI, intervertebral disc degeneration, and presurgical cranial spinal stenosis). RESULTS: At 5 years from the operation, 16 patients (10.8%) in the control group had undergone revision surgery for CASD compared to 5 patients (3.3%) in the OLF group (p = 0.013). Survival analysis and GLM demonstrated that the OLF group had a significantly lower incidence of CASD and presented more favorable clinical outcome. There were no differences in the rate of discal degeneration or the onset of Meyerding's grade I degenerative spondylolisthesis at the adjacent segment. BMI was the only other significant predictor of ODI improvement and of the incidence of CASD. CONCLUSIONS: In patients with L4-L5 degenerative spondylolisthesis and stenosis, the OLF technique may lower rates of CASD and improve clinical outcomes by preventing cranial spinal stenosis without increasing iatrogenic instability or accelerating intervertebral disc degenerative changes.

MER and increased operative time are not risk factors for the formation of pneumocephalus during DBS.

Although only recently directional leads have proven their potential to compensate for sub-optimally placed electrodes, optimal lead positioning remains the most critical factor in determining Deep Brain Stimulation (DBS) outcome. Pneumocephalus is a recognized source of error, but the factors that contribute to its formation are still a matter of debate. Among these, operative time is one of the most controversial. Because cases of DBS performed with Microelectrode Recordings (MER) are affected by an increase in surgical length, it is useful to analyze whether MER places patients at risk for increased intracranial air entry. Data of 94 patients from two different institutes who underwent DBS for different neurologic and psychiatric conditions were analyzed for the presence of postoperative pneumocephalus. Operative time and use of MER, as well as other potential risk factors for pneumocephalus (age, awake vs. asleep surgery, number of MER passages, burr hole size, target and unilateral vs. bilateral implants) were examined. Mann-Whitney U and Kruskal-Wallis tests were utilized to compare intracranial air distributions across groups of categorical variables. Partial correlations were used to assess the association between time and volume. A generalized linear model was created to predict the effects of time and MER on the volume of intracranial air, controlling for other potential risk factors identified: age, number of MER passages, awake vs. asleep surgery, burr hole size, target, unilateral vs. bilateral surgery. Significantly different distributions of air volume were noted between different targets, unilateral vs. bilateral implants, and number of MER trajectories. Patients undergoing DBS with MER did not present a significant increase in pneumocephalus compared to patients operated without (p = 0.067). No significant correlation was found between pneumocephalus and time. Using multivariate analysis, unilateral implants exhibited lower volumes of pneumocephalus (p = 0.002). Two specific targets exhibited significantly different volumes of pneumocephalus: the bed nucleus of the stria terminalis with lower volumes (p < 0.001) and the posterior hypothalamus with higher volumes (p = 0.011). MER, time, and other parameters analyzed failed to reach statistical significance. Operative time and use of intraoperative MER are not significant predictors of pneumocephalus during DBS. Air entry is greater for bilateral surgeries and may be also influenced by the specific stimulated target.