Pharmacological Treatment of Degenerative Cervical Myelopathy: A Critical Review of Current Evidence.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

A twitter analysis of patient and family experience in pediatric spine surgery.

BACKGROUND: There is little data on patient and caregiver perceptions of spine surgery in children and youth. This study aims to characterize the personal experiences of patients, caregivers, and family members surrounding pediatric spine surgery through a qualitative and quantitative social media analysis. METHODS: The Twitter application programming interface was searched for keywords related to pediatric spine surgery from inception to March 2022. Relevant tweets and accounts were extracted and subsequently classified using thematic labels. Tweet metadata was collected to measure user engagement via multivariable regression. Sentiment analysis using Natural Language Processing was performed on all tweets with a focus on tweets discussing the personal experiences of patients and caregivers. RESULTS: 2424 tweets from 1847 individual accounts were retrieved for analysis. Patients and caregivers represented 1459 (79.0%) of all accounts. Posts discussed the personal experiences of patients and caregivers in 83.5% of tweets. Pediatric spine surgery research was discussed in few posts (n=90, 3.7%). Within the personal experience category, 975 (48.17%) tweets were positive, 516 (25.49%) were negative, and 533 (26.34%) were neutral. Presence of a tag (beta: -6.1, 95% CI -9.7 to -2.5) and baseline follower count (beta<0.001, 95% CI <0.001 to <0.001) significantly affected tweet engagement negatively and positively, respectively. CONCLUSIONS: Patients and caregivers actively discuss topics related to pediatric spine surgery on Twitter. Posts discussing personal experience are most prevalent, while posts on research are scarce, unlike previous social media studies. Pediatric spine surgeons can leverage this dialogue to better understand the worries and needs of patients and their families.

Economic comparisons of endoscopic spine surgery: a systematic review.

PURPOSE: Full-endoscopic techniques are minimally invasive surgery alternatives to traditional spinal surgery. We performed a systematic review of the literature to assess the costs of these techniques compared to traditional approaches. METHODS: A systematic review of the literature was performed for economic evaluations that compare endoscopic decompressions of the lumbar spine for stenosis or disc herniation to open or microsurgical decompressions. The search was performed in the following databases: Medline, Embase Classic, Embase, and Central Cochrane library, from January 1, 2005, to October 22, 2022. The included studies were each evaluated according to a formal assessment checklist to evaluate the quality of economic evaluations based on 35 criteria. RESULT: A total of 1153 studies were identified, with 9 articles included in the final analysis. In evaluating the quality of economic evaluations, the study with the fewest met criteria scored 9/35 and the study with the most met criteria scored 28/35. Only 3 studies completed cost-effectiveness analyses. Surgical procedure duration varied between studies, but hospital length of stays were consistently shorter with endoscopy. While endoscopy was more frequently associated with higher operating costs, studies that measured healthcare and societal costs found endoscopy to be advantageous. CONCLUSION: Endoscopic spine surgery was found to be cost-effective in treating patients with lumbar stenosis and disc herniation when compared to standard microscopic approaches from a societal perspective. More well-designed economic evaluations investigating the cost-effectiveness of endoscopic spine procedures are needed to further support these findings.

Perception of frailty in spinal metastatic disease: international survey of the AO Spine community.

OBJECTIVE: Frailty has not been clearly defined in the context of spinal metastatic disease (SMD). Given this, the objective of this study was to better understand how members of the international AO Spine community conceptualize, define, and assess frailty in SMD. METHODS: The AO Spine Knowledge Forum Tumor conducted an international cross-sectional survey of the AO Spine community. The survey was developed using a modified Delphi technique and was designed to capture preoperative surrogate markers of frailty and relevant postoperative clinical outcomes in the context of SMD. Responses were ranked using weighted averages. Consensus was defined as ≥ 70% agreement among respondents. RESULTS: Results were analyzed for 359 respondents, with an 87% completion rate. Study participants represented 71 countries. In the clinical setting, most respondents informally assess frailty and cognition in patients with SMD by forming a general perception based on clinical condition and patient history. Consensus was attained among respondents regarding the association between 14 preoperative clinical variables and frailty. Severe comorbidities, extensive systemic disease burden, and poor performance status were most associated with frailty. Severe comorbidities associated with frailty included high-risk cardiopulmonary disease, renal failure, liver failure, and malnutrition. The most clinically relevant outcomes were major complications, neurological recovery, and change in performance status. CONCLUSIONS: The respondents recognized that frailty is important, but they most commonly evaluate it based on general clinical impressions rather than using existing frailty tools. The authors identified numerous preoperative surrogate markers of frailty and postoperative clinical outcomes that spine surgeons perceived as most relevant in this population.

Modulating the activity of human nociceptors with a SCN10A promoter-specific viral vector tool.

Despite the high prevalence of chronic pain as a disease in our society, there is a lack of effective treatment options for patients living with this condition. Gene therapies using recombinant AAVs are a direct method to selectively express genes of interest in target cells with the potential of, in the case of nociceptors, reducing neuronal firing in pain conditions. We designed a recombinant AAV vector expressing cargos whose expression was driven by a portion of the SCN10A (NaV1.8) promoter, which is predominantly active in nociceptors. We validated its specificity for nociceptors in mouse and human dorsal root ganglia and showed that it can drive the expression of functional proteins. Our viral vector and promoter package drove the expression of both excitatory or inhibitory DREADDs in primary human DRG cultures and in whole cell electrophysiology experiments, increased or decreased neuronal firing, respectively. Taken together, we present a novel viral tool that drives expression of cargo specifically in human nociceptors. This will allow for future specific studies of human nociceptor properties as well as pave the way for potential future gene therapies for chronic pain.

Regional and age-related diversity of human mature oligodendrocytes.

Morphological and emerging molecular studies have provided evidence for heterogeneity within the oligodendrocyte population. To address the regional and age-related heterogeneity of human mature oligodendrocytes (MOLs) we applied single-cell RNA sequencing to cells isolated from cortical/subcortical, subventricular zone brain tissue samples, and thoracolumbar spinal cord samples. Unsupervised clustering of cells identified transcriptionally distinct MOL subpopulations across regions. Spinal cord MOLs, but not microglia, exhibited cell-type-specific upregulation of immune-related markers compared to the other adult regions. SVZ MOLs showed an upregulation of select number of development-linked transcription factors compared to other regions; however, pseudotime trajectory analyses did not identify a global developmental difference. Age-related analysis of cortical/subcortical samples indicated that pediatric MOLs, especially from under age 5, retain higher expression of genes linked to development and to immune activity with pseudotime analysis favoring a distinct developmental stage. Our regional and age-related studies indicate heterogeneity of MOL populations in the human CNS that may reflect developmental and environmental influences.

Systemic considerations for the surgical treatment of spinal metastatic disease: a scoping literature review.

Systemic assessment is a pillar in the neurological, oncological, mechanical, and systemic (NOMS) decision-making framework for the treatment of patients with spinal metastatic disease. Despite this importance, emerging evidence relating systemic considerations to clinical outcomes following surgery for spinal metastatic disease has not been comprehensively summarised. We aimed to conduct a scoping literature review of this broad topic. We searched MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Web of Science, and CINAHL databases from Jan 1, 2000, to July 31, 2021. 61 articles were included, accounting for a total of 22 335 patients. Preoperative systemic variables negatively associated with postoperative clinical outcomes included demographics (eg, older age [>60 years], Black race, male sex, low or elevated body-mass index, and smoking status), medical comorbidities (eg, cardiac, pulmonary, hepatic, renal, endocrine, vascular, and rheumatological), biochemical abnormalities (eg, hypoalbuminaemia, atypical blood cell counts, and elevated C-reactive protein concentration), low muscle mass, generalised motor weakness (American Spinal Cord Injury Association Impairment Scale grade and Frankel grade) and poor ambulation, reduced performance status, and systemic disease burden. This is the first comprehensive scoping review to broadly summarise emerging evidence relevant to the systemic assessment component of the widely used NOMS framework for spinal metastatic disease decision making. Medical, surgical, and radiation oncologists can consider these findings when prognosticating spinal metastatic disease-related surgical outcomes on the basis of patients' systemic condition. These factors might inform a shared decision-making approach with patients and their families.

Ultrasound-based navigated pedicle screw insertion without intraoperative radiation: feasibility study on porcine cadavers.

BACKGROUND: Navigation systems for spinal fusion surgery rely on intraoperative computed tomography (CT) or fluoroscopy imaging. Both expose patient, surgeons and operating room staff to significant amounts of radiation. Alternative methods involving intraoperative ultrasound (iUS) imaging have recently shown promise for image-to-patient registration. Yet, the feasibility and safety of iUS navigation in spinal fusion have not been demonstrated. PURPOSE: To evaluate the accuracy of pedicle screw insertion in lumbar and thoracolumbar spinal fusion using a fully automated iUS navigation system. STUDY DESIGN: Prospective porcine cadaver study. METHODS: Five porcine cadavers were used to instrument the lumbar and thoracolumbar spine using posterior open surgery. During the procedure, iUS images were acquired and used to establish automatic registration between the anatomy and preoperative CT images. Navigation was performed with the preoperative CT using tracked instruments. The accuracy of the system was measured as the distance of manually collected points to the preoperative CT vertebral surface and compared against fiducial-based registration. A postoperative CT was acquired, and screw placements were manually verified. We report breach rates, as well as axial and sagittal screw deviations. RESULTS: A total of 56 screws were inserted (5.50 mm diameter n=50, and 6.50 mm diameter n=6). Fifty-two screws were inserted safely without breach. Four screws (7.14%) presented a medial breach with an average deviation of 1.35±0.37 mm (all <2 mm). Two breaches were caused by 6.50 mm diameter screws, and two by 5.50 mm screws. For vertebrae instrumented with 5.50 mm screws, the average axial diameter of the pedicle was 9.29 mm leaving a 1.89 mm margin in the left and right pedicle. For vertebrae instrumented with 6.50 mm screws, the average axial diameter of the pedicle was 8.99 mm leaving a 1.24 mm error margin in the left and right pedicle. The average distance to the vertebral surface was 0.96 mm using iUS registration and 0.97 mm using fiducial-based registration. CONCLUSIONS: We successfully implanted all pedicle screws in the thoracolumbar spine using the ultrasound-based navigation system. All breaches recorded were minor (<2 mm) and the breach rate (7.14%) was comparable to existing literature. More investigation is needed to evaluate consistency, reproducibility, and performance in surgical context. CLINICAL SIGNIFICANCE: Intraoperative US-based navigation is feasible and practical for pedicle screw insertion in a porcine model. It might be used as a low-cost and radiation-free alternative to intraoperative CT and fluoroscopy in the future.

Adult Spinal Deformity Surgery and Frailty: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: Adult spinal deformity (ASD) can be a debilitating condition with a profound impact on patients' health-related quality of life (HRQoL). Many reports have suggested that the frailty status of a patient can have a significant impact on the outcome of the surgery. The present review aims to identify all pre-operative patient-specific frailty markers that are associated with postoperative outcomes following corrective surgery for ASD of the lumbar and thoracic spine. METHODS: A systematic review of the literature was performed to identify findings regarding pre-operative markers of frailty and their association with postoperative outcomes in patients undergoing ASD surgery of the lumbar and thoracic spine. The search was performed in the following databases: PubMed, Embase, Cochrane and CINAHL. RESULTS: An association between poorer performance on frailty scales and worse postoperative outcomes. Comorbidity indices were even more frequently employed with similar patterns of association between increased comorbidity burden and postoperative outcomes. Regarding the assessment of HRQoL, worse pre-operative ODI, SF-36, SRS-22 and NRS were shown to be predictors of post-operative complications, while ODI, SF-36 and SRS-22 were found to improve post-operatively. CONCLUSIONS: The findings of this review highlight the true breadth of the concept of "frailty" in ASD surgical correction. These parameters, which include frailty scales and various comorbidity and HRQoL indices, highlight the importance of identifying these factors preoperatively to ensure appropriate patient selection while helping to limit poor postoperative outcomes.

Neck angioedema after anterior cervical discectomy and fusion with coexistent epiglottic cyst.

BACKGROUND: We present a case and reviewed the literature regarding airway obstruction and angioedema after an anterior cervical discectomy and fusion (ACDF). CASE DESCRIPTION: A 60-year-old female with degenerative cervical myelopathy and a previously undiagnosed epiglottic cyst underwent a C5-C6 ACDF; notably, the anesthesiologist found an epiglottic cyst when the patient was first intubated. Two hours postoperatively, the patient acutely developed severe neck swelling with airway obstruction due to angioedema. She was immediately treated with hydrocortisone and required a tracheostomy. The edema decreased markedly in the next 12 h and by the 3rd postoperative day it resolved. Three months later, she had no residual medical sequelae. CONCLUSION: Patients with epiglottic cysts who need cervical spine surgery should either first have the cyst treated or should be closely monitored postoperatively.

Syringobulbia: A delayed complication following spinal cord injury - case report.

CONTEXT: Syringobulbia is a very rare progressive disorder of central nervous system, with several possible underlying conditions. Rarely, it is also encountered as a late complication of syringomyelia. FINDINGS: In the present manuscript, a case of a paraplegic patient, due to traumatic spinal cord injury (thoracolumbar fracture), presenting after years progressively developing symptoms of the lower cranial nerves and upper extremities, owed to syringomyelia and syringobulbia, the surgical treatment applied and its outcomes are described. We performed a syringo-peritoneal shunting procedure using a T-tube. The patient's symptoms resolved postoperatively and the cavity's size was reduced to a great degree. CONCLUSION/CLINICAL RELEVANCE: The late appearance of cranial nerve deficits or symptoms-signs of the upper extremities in a patient with traumatic thoracic spinal cord injury should raise suspicion that post-traumatic syringomyelia or syringobulbia has occurred. In such cases, radiologic evaluation and early surgical drainage of the cyst as a means of preventing significant delayed neurologic deficit is advocated.

Efficacy, Safety, and Duration of a Frameless Fiducial-Less Brain Biopsy versus Frame-based Stereotactic Biopsy: A Prospective Randomized Study.

BACKGROUND/OBJECTIVE: We compared the efficacy, duration, safety, length of hospital stay of a frameless fiducial-less brain biopsy with those of the standard frame-based stereotactic biopsy. PATIENTS AND METHODS: This prospective cohort study enrolled 56 adult patients: (1) for whom no conclusive diagnosis could be reached noninvasively; (2a) who had lesions involving deep-seated and eloquent areas, multifocal lesions, or lesions for which craniotomy and lesion removal was not indicated, or (2b) were poor candidates for craniotomy (> 80 years of age and/or with serious comorbidities). Frameless and frame-based biopsy were performed in 28 patients each RESULTS: A diagnosis was not made in four cases (14.3%) of the frame-based biopsy group and in three cases (10.7%) of the frameless biopsy group, in spite of accurate targeting (p = 1.0). The mean duration of the whole procedure (preparatory steps outside the operating room [OR], inside the OR, surgery) was 111.3 minutes for the frame-based biopsy and 79.1 minutes for the frameless biopsy (p = 0.001). No statistically significant differences between the two methods were found concerning new neurologic symptoms, new abnormal findings in postoperative computed tomography (CT) and length of postoperative hospital stay (LOS). The smallest diameter of a successfully biopsied lesion was 15 mm for both groups. CONCLUSIONS: The frameless fiducial-less brain biopsy was equally efficacious and safe compared with the standard stereotactic frame-based biopsy. The overall duration of frameless biopsy is shorter than that of frame-based biopsy, mainly because the preparatory steps in frameless biopsy require less time. However, the overall time spent in the OR did not differ between the two groups. The LOS also did not differ significantly.

Minimizing technical failure of percutaneous balloon compression for trigeminal neuralgia using neuronavigation.

UNLABELLED: Objective. Percutaneous balloon compression (PBC) is an effective and safe management for medically refractory trigeminal neuralgia; however, technical failure to cannulate the foramen ovale (FO) using only fluoroscopy is a significant problem in some cases. In this paper, we suggest the use of intraoperative navigation, in cases of reoperation due to prior technical failure to cannulate the FO under fluoroscopy. Methods. A total of 174 patients underwent PBC for TN since 2003. In 9 cases the penetration of the FO was not accomplished. Five of those patients were reoperated on for PBC using navigation from March 2012 to September 2012. SURGICAL TECHNIQUE: preoperatively, a head Computed Tomography (CT) scan is performed and the acquired images are imported into the navigation system. Intraoperatively, a small reference frame is strapped firmly to the patient's forehead, the CT images are registered, and cannulation is performed under the guidance of the navigation system. Results. In all patients, the operation overall was completed successfully. Moreover, all patients reported complete pain relief immediately postoperatively and no complications were recorded overall. Conclusions. We suggest the use of neuronavigation in cases of technical failure of PBC. That technique involves technology with significant advantages helping the successful cannulation of the FO and seems more efficient and safer.

Masseter muscle function after percutaneous balloon compression of trigeminal ganglion for the treatment of trigeminal neuralgia: a neurophysiological follow-up study.

OBJECTIVE: We aimed to evaluate by longitudinal neurophysiological examinations the natural course of masseter muscle weakness that developed after percutaneous balloon compression (PBC) of the trigeminal ganglion for the treatment of idiopathic trigeminal neuralgia. METHODS: The affected side of 15 patients (mean age 69.5±4.5 years) who underwent unilateral PBC were studied before, 1 month, 6 months and 12 months after surgery by means of: (1) motor evoked potentials (MEPs) of the masseter muscle elicited by transcranial magnetic stimulation of the contralateral motor cortex and of the ipsilateral trigeminal motor branch; and (2) concentric needle electromyography of masseter muscle. RESULTS: The latencies of MEPs' to cortical and nerve stimulation became significantly prolonged 1 month after PBC, whereas, thereafter, they demonstrated a gradual shortening towards preoperative values. The interference electromyographic pattern 1 month post-PBC study was reduced in all patients, but it improved in follow-up, returning 12-months postoperatively to complete in 13 and nearly complete in two patients. CONCLUSION: Masseter muscle weakness should be expected in all cases after PBC of the trigeminal ganglion. SIGNIFICANCE: As verified by repeated studies, the results of which favoured a focal demyelination process of trigeminal motor branch, muscle dysfunction appears to be reversible over a period of 6-12 months.

Postconcussion syndrome after mild traumatic brain injury in Western Greece.

BACKGROUND: The prevalence of postconcussion syndrome (PCS) in the first weeks after mild traumatic brain injury varies from 40% to 80%. However, as many as 50% of patients report symptoms for up to 3 months and 10% to 15% for more than a year. The objective of this study is to analyze the characteristics and estimate the prevalence of PCS in an adult Greek population. METHODS: This prospective study was performed in the University Hospital of Patras in Western Greece. Patients with mild traumatic brain injury (n = 539) were randomly recruited on admission between May 2006 and May 2008. Overall, 223 patients (223 of 539, 41.5%) met the Colorado Medical Society guidelines for concussion; 141 men (63%) and 82 women (37%) with a median age of 30 years (range, 18.5-57.5 years) were included in the study. Patient follow-up consisted of telephone interviews at 1 month, 3 months, and 6 months postinjury, when they were asked about experiencing common postconcussion symptoms (International Classification of Diseases-10th revision criteria). RESULTS: The rate of PCS at 1 month, 3 months, and 6 months postinjury was estimated to be 10.3%, 6%, and 0.9%, respectively. The syndrome was more frequent among women (17%) and individuals with bleeding diathesis (26%) compared with men (6.4%) and patients without clotting disorders (8.5%), respectively. In addition, higher rates of PCS affected patients who sustained assaults compared with other types of accidents. CONCLUSIONS: The prevalence of PCS was remarkably higher in previous studies. Cultural differences regarding symptom expectation and the lack of compensation might explain the low rate of chronic symptoms in Greeks.

Vegetative state and minimally conscious state: a review of the therapeutic interventions.

BACKGROUND/AIMS: The purpose of the present article is a systematic review of the proposed medical or surgical treatments in patients in chronic vegetative state (VS) or minimally conscious state (MCS), as well as of their mechanisms of action and limitations. METHODS: For this review, we have agreed to include patients in VS or MCS having persisted for over 6 months in posttraumatic cases, and over 3 months in nontraumatic cases, before the time of intervention. Searches were independently conducted by 2 investigators between May 2009 and September 2009 in the following databases: Medline, Web of Science and the Cochrane Library. The electronic search was complemented by cross-checking the references of all relevant articles. Overall, 16 papers were eligible for this systematic review. RESULTS: According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases. CONCLUSION: The treatments proposed for disorders of consciousness have not yet gained the level of 'evidence-based treatments'; moreover, the studies to date have led to inconclusiveness. The published therapeutic responses must be substantiated by further clinical studies of sound methodology.

Meige's syndrome: A cranial dystonia treated with bilateral pallidal deep brain stimulation.

BACKGROUND: Meige's syndrome is a rare form of segmental dystonia characterized by blepharospasm and oromandibular dystonia. Medical treatment including botulinum toxin injections usually present disappointing results. The experience on Deep Brain Stimulation (DBS) in the treatment of Meige's syndrome and other segmental dystonias is still limited. At the moment, only a few cases of pallidal DBS have been reported to improve this rare form of dystonia. CASE DESCRIPTION: We report on a case of a woman with a 7-year history of Meige's syndrome, which rendered her functionally blind. The treatment with botulinum toxin injections failed to improve her symptoms, whereas stereotactic bilateral DBS of the pallidum led to a dramatic clinical improvement. Clinical assessment using the Burke-Fahn-Mardsen Dystonia Rating Scale (BFMDRS) in a double-blind manner, showed an improvement of 70% in the Movement score and 93.33% in the Disability score (84% reduction of the total score) on the 3 and 6 month follow-up. CONCLUSIONS: Stereotactic pallidal DBS might be considered as a potential treatment in the management of Meige's syndrome.