Machine learning-based cluster analysis identifies four unique phenotypes of patients with degenerative cervical myelopathy with distinct clinical profiles and long-term functional and neurological outcomes.

BACKGROUND: Degenerative cervical myelopathy (DCM), the predominant cause of spinal cord dysfunction among adults, exhibits diverse interrelated symptoms and significant heterogeneity in clinical presentation. This study sought to use machine learning-based clustering algorithms to identify distinct patient clinical profiles and functional trajectories following surgical intervention. METHODS: In this study, we applied k-means and latent profile analysis (LPA) to identify patient phenotypes, using aggregated data from three major DCM trials. The combination of Nurick score, NDI (neck disability index), neck pain, as well as motor and sensory scores facilitated clustering. Goodness-of-fit indices were used to determine the optimal cluster number. ANOVA and post hoc Tukey's test assessed outcome differences, while multinomial logistic regression identified significant predictors of group membership. FINDINGS: A total of 1047 patients with DCM (mean [SD] age: 56.80 [11.39] years, 411 [39%] females) had complete one year outcome assessment post-surgery. Latent profile analysis identified four DCM phenotypes: "severe multimodal impairment" (n = 286), "minimal impairment" (n = 116), "motor-dominant" (n = 88) and "pain-dominant" (n = 557) groups. Each phenotype exhibited a unique symptom profile and distinct functional recovery trajectories. The "severe multimodal impairment group", comprising frail elderly patients, demonstrated the worst overall outcomes at one year (SF-36 PCS mean [SD]: 40.01 [9.75]; SF-36 MCS mean [SD], 46.08 [11.50]) but experienced substantial neurological recovery post-surgery (ΔmJOA mean [SD]: 3.83 [2.98]). Applying the k-means algorithm yielded a similar four-class solution. A higher frailty score and positive smoking status predicted membership in the "severe multimodal impairment" group (OR 1.47 [95% CI 1.07-2.02] and 1.58 [95% CI 1.25-1.99, respectively]), while undergoing anterior surgery and a longer symptom duration were associated with the "pain-dominant" group (OR 2.0 [95% CI 1.06-3.80] and 3.1 [95% CI 1.38-6.89], respectively). INTERPRETATION: Unsupervised learning on multiple clinical metrics predicted distinct patient phenotypes. Symptom clustering offers a valuable framework to identify DCM subpopulations, surpassing single patient reported outcome measures like the mJOA. FUNDING: No funding was received for the present work. The original studies were funded by AO Spine North America.

Imaging protocols for non-traumatic spinal cord injury: current state of the art and future directions.

INTRODUCTION: Non-traumatic spinal cord injury (NTSCI) is a term used to describe damage to the spinal cord from sources other than trauma. Neuroimaging techniques such as computerized tomography (CT) and magnetic resonance imaging (MRI) have improved our ability to diagnose and manage NTSCIs. Several practice guidelines utilize MRI in the diagnostic evaluation of traumatic and non-traumatic SCI to direct surgical intervention. AREAS COVERED: The authors review practices surrounding the imaging of various causes of NTSCI as well as recent advances and future directions for the use of novel imaging modalities in this realm. The authors also present discussions around the use of simple radiographs and advanced MRI modalities in clinical settings, and briefly highlight areas of active research that seek to advance our understanding and improve patient care. EXPERT OPINION: Although several obstacles must be overcome, it appears highly likely that novel quantitative imaging features and advancements in artificial intelligence (AI) as well as machine learning (ML) will revolutionize degenerative cervical myelopathy (DCM) care by providing earlier diagnosis, accurate localization, monitoring for deterioration and neurological recovery, outcome prediction, and standardized practice. Some intriguing findings in these areas have been published, including the identification of possible serum and cerebrospinal fluid biomarkers, which are currently in the early phases of translation.

Riluzole for Degenerative Cervical Myelopathy: A Secondary Analysis of the CSM-PROTECT Trial.

Importance: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. Intervention: Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. Main Outcomes and Measures: The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). Results: Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, -0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). Conclusions and Relevance: In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.

Elderly Patients Show Substantial Improvement in Health-Related Quality of Life After Surgery for Degenerative Cervical Myelopathy Despite Medical Frailty: An Ambispective Analysis of a Multicenter, International Data Set.

BACKGROUND AND OBJECTIVES: We assessed the relationship between Modified Frailty Index-5 (mFI-5) and neurological outcomes, as well as health-related quality of life (HRQoL) measures, in elderly patients with degenerative cervical myelopathy (DCM) after surgery. METHODS: Data from 3 major DCM trials (the Arbeitsgemeinschaft für Osteosynthesefragen Spine Cervical Spondylotic Myelopathy-North America, Cervical Spondylotic Myelopathy-International, and CSM-PROTECT studies) were combined, involving 1047 subjects with moderate to severe myelopathy. Patients older than 60 years with 6-month and 1-year postoperative data were analyzed. Neurological outcome was assessed using the modified Japanese Orthopaedic Association score, while HRQoL was measured using the 36-Item Short Form Health Survey (SF-36) (both Physical Component Summary [SF-36 PCS] and Mental Component Summary [SF-36 MCS] scores) and the Neck Disability Index. Frail (mFI ≥2) and nonfrail (mFI = 0-1) cohorts were compared using univariate paired statistics. RESULTS: The final analysis included 261 patients (62.5% male), with a mean age of 71 years (95% CI 70.7-72). Frail patients (mFI ≥2) had lower baseline modified Japanese Orthopaedic Association scores (10.45 vs 11.96, P < .001), SF-36 PCS scores (32.01 vs 36.51, P < .001), and SF-36 MCS scores (39.32 vs 45.24, P < .001). At 6-month follow-up, SF-36 MCS improved by a mean (SD) of 7.19 (12.89) points in frail vs 2.91 (11.11) points in the nonfrail group (P = .016). At 1 year after surgery, frail patients showed greater improvement in both SF-36 PCS and SF-36 MCS composite scores compared with nonfrail patients (7.81 vs 4.49, P = .038, and 7.93 vs 3.01, P = .007, respectively). Bivariate regression analysis revealed that higher mFI-5 scores correlated with more substantial improvement in overall mental status at 6 months and 1 year (P = .024 and P = .009, respectively). CONCLUSION: mFI-5 is a clinically helpful signature to reflect the HRQoL status among elderly patients with DCM. Despite preoperative medical frailty, elderly patients with DCM experience significant HRQoL improvement after surgery. These findings enable clinicians to identify elderly patients with modifiable comorbidities and provide informed counseling on anticipated outcomes. LEVEL OF EVIDENCE: II.

Early surgical intervention for acute spinal cord injury: time is spine.

Acute traumatic spinal cord injury (tSCI) is a devastating occurrence that significantly contributes to global morbidity and mortality. Surgical decompression with stabilization is the most effective way to minimize the damaging sequelae that follow acute tSCI. In recent years, strong evidence has emerged that supports the rationale that early surgical intervention, within 24 h following the initial injury, is associated with a better prognosis and functional outcomes. In this review, we have summarized the evidence and elaborated on the nuances of this concept. Additionally, we have reviewed further concepts that stem from "time is spine," including earlier cutoffs less than 24 h and the challenging entity of central cord syndrome, as well as the emerging concept of adequate surgical decompression. Lastly, we identify barriers to early surgical care for acute tSCI, a key aspect of spine care that needs to be globally addressed via research and policy on an urgent basis.

Degenerative cervical myelopathy: Where have we been? Where are we now? Where are we going?

Degenerative cervical myelopathy (DCM), a recently coined term, encompasses a group of age-related and genetically associated pathologies that affect the cervical spine, including cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament (OPLL). Given the significant contribution of DCM to global disease and disability, there are worldwide efforts to promote research and innovation in this area. An AO Spine effort termed 'RECODE-DCM' was initiated to create an international multistakeholder consensus group, involving patients, caregivers, physicians and researchers, to focus on launching actionable discourse on DCM. In order to improve the management, treatment and results for DCM, the RECODE-DCM consensus group recently identified ten priority areas for translational research. The current article summarizes recent advancements in the field of DCM. We first discuss the comprehensive definition recently refined by the RECODE-DCM group, including steps taken to arrive at this definition and the supporting rationale. We then provide an overview of the recent advancements in our understanding of the pathophysiology of DCM and modalities to clinically assess and diagnose DCM. A focus will be set on advanced imaging techniques that may offer the opportunity to improve characterization and diagnosis of DCM. A summary of treatment modalities, including surgical and nonoperative options, is then provided along with future neuroprotective and neuroregenerative strategies. This review concludes with final remarks pertaining to the genetics involved in DCM and the opportunity to leverage this knowledge toward a personalized medicine approach.

Time is spine: What's over the horizon.

The overarching theme in the early treatment of acute spinal cord injury (SCI) is to reduce the extent of secondary damage to facilitate early neurological and functional recovery. Although multiple studies have brought us innovative and potential new therapies to treat SCI, ameliorating neural damage remains a formidable challenge. Knowledge translation of clinical and basic research studies has shown that surgical intervention is a valuable treatment modality; however, the role, timing and optimal technique in surgery remains a topic of great controversy. While evidence to support the concept of ultra-early surgery for acute SCI continues to emerge, current protocols and international guidelines that encourage reducing time from trauma to surgery support the concept of "Time is Spine". The present article provides a critical narrative review of the current best practice, with a particular focus on the timing of surgical intervention, which shapes our understanding of how time is of the essence in the management of acute SCI.

Current Practice of Acute Spinal Cord Injury Management: A Global Survey of Members from the AO Spine.

STUDY DESIGN: Cross-sectional, international survey. OBJECTIVES: To examine current international practices as well as knowledge, adoption, and barriers to guideline implementation for acute spinal cord injury (SCI) management. METHODS: A survey was distributed to members of AO Spine. The questionnaire was structured to obtain demographic data and preferred acute SCI practices surrounding steroid use, hemodynamic management, and timing of surgical decompression. RESULTS: 593 members completed the survey including orthopaedic surgeons (54.3%), neurosurgeons (35.6%), and traumatologists (8.4%). Most (61.2%) respondents were from low and middle-income countries (LMICs). 53.6% of physicians used steroids for the treatment of acute SCIs. Respondents from LMICs were more likely to administer steroids than HICs (178 vs. 78; P < .001). 331 respondents (81.5%) answered that patients would receive mean arterial pressure (MAP) targeted treatment. In LMICs, SCI patients were less likely to be provided with MAP-targeted treatment (76.9%) as compared to HICs (89%; P < .05). The majority of respondents (87.8%) reported that patients would benefit from early decompression. Despite overwhelming evidence and surgeons' responses that would offer early surgery, 62.4% of respondents stated they encounter logistical barriers in their institutions. This was particularly evident in LMICs, where 57.9% of respondents indicated that early intervention was unlikely to be accomplished, while only 21.1% of respondents from HICs stated the same (P < .001). CONCLUSION: This survey highlights challenges in the implementation of standardized global practices in the management of acute SCI. Future research efforts will need to refine SCI guidelines and address barriers to guideline implementation.

Increasing awareness of degenerative cervical myelopathy: a preventative cause of non-traumatic spinal cord injury.

Degenerative cervical myelopathy (DCM) is a common non-traumatic spinal cord disorder and characterized by progressive neurological impairment. Generally, it is still underdiagnosed and referral to spine specialists is often late, when patients already present with incomplete cervical spinal cord injury (SCI). To improve early diagnosis and accelerate referral, diagnostic criteria for DCM are required. Recently, AO Spine RECODE- DCM (REsearch Objectives and Common Data Elements for Degenerative Cervical Myelopathy) (aospine.org/recode), an international, interdisciplinary and interprofessional initiative, including patients with DCM, was funded with the aim to accelerate knowledge discovery that can change outcomes. In this perspective we advocate for the participation of SCI specialists in this process, where the expertise and perspective on this disorder and requirements for the diagnostic and therapeutic work up is well developed.

Primary parasagittal myoepithelioma in a paediatric patient: review of the literature and illustrative case.

Myoepithelial tumours are a rare form of salivary gland neoplasm, and their occurrence in the central nervous system is exceedingly rare. The authors report the case of an 18-year-old Filipino man presenting with headache and weakness, and on imaging showing an extensive parasagittal tumour at the left posterior parietal area with extracalvarial extension. There was no systemic disease. The patient underwent surgery to excise the tumour, with histopathology showing findings consistent with myoepithelioma. There was no further treatment, given the benign histology of the lesion, but there was recurrence after 8 months. Repeat surgery was done for the patient and he is for adjuvant radiotherapy. This appears to be the 10th reported case of a central nervous myoepithelioma, and the first case in the Philippines of a primary parasagittal myoepithelioma in a paediatric patient. Further information is needed to provide diagnostic and therapeutic recommendations.

Lumbar facet cyst tuberculosis: a rare cause of cauda equina compression. Illustrative case.

BACKGROUND: Spinal tuberculosis may present in atypical form to involve only the posterior spinal element with relative sparing of the anterior vertebral body and intervertebral disc. Recognition of this unusual pattern is important to avoid delay in diagnosis and treatment. OBSERVATIONS: The authors report a case of a 59-year-old woman with right-sided radiculopathy and motor weakness. Her lumbosacral magnetic resonance imaging showed a large heterogeneous cyst arising from the right L4-5 facet joint. Laminectomy with excision of the cyst was performed. During surgery, the cyst contained cheese-like material that, on histopathological examination, revealed focal aggregates of tuberculous granuloma. Postoperatively, the patient recovered remarkably with no interval development of instability or any deformity. LESSONS: Facet cyst tuberculosis is rare but should be considered in the differential diagnosis in patients coming from endemic regions. Laminectomy with excision of the cyst along with concurrent antitubercular chemotherapy is a safe and durable treatment option in this case.

Safety and Outcome of Decompressive Hemicraniectomy After Recombinant Tissue Plasminogen Activator Thrombolysis for Acute Ischemic Stroke: A Systematic Review.

BACKGROUND: Decompressive hemicraniectomy (DH) is widely recommended as a surgical treatment for intractable increased intracranial pressure after malignant cerebral infarction. Many patients given recombinant tissue plasminogen activator (rtPA) develop cerebral edema after reperfusion or failed recanalization. However, the safety and efficacy of DH after rtPA administration remain largely unknown. METHODS: A systematic review was performed using PubMed, Embase, Scopus, Cochrane, and HERDIN. Studies were eligible if they included patients who underwent DH after intravenous thrombolysis for acute ischemic stroke. Unweighted odds ratio (OR) for mortality (primary outcome) and good functional outcome defined as modified Rankin Scale score 0-3 or Glasgow Outcome Scale score 4-5 at 3-6 months (secondary outcome) were compared between the DH + rtPA group and DH alone group. RESULTS: Four studies with a total of 98 patients undergoing DH + rtPA were compared with 110 patients undergoing DH alone without previous thrombolysis. Age, vascular risk factors, and cause of stroke were comparable between the 2 groups. Pooled analysis showed that mortality and functional outcomes were not statistically different between the DH + rtPA and DH alone groups (OR, 0.56, P = 0.07 and OR, 0.83, P = 0.30, respectively). Likewise, both minor and major hemorrhagic rates were similar between the 2 groups (37.76% vs. 27.27%; P = 0.053). CONCLUSIONS: DH for malignant cerebral infarction after intravenous rtPA administration is a viable treatment option, with a comparable mortality and functional outcome to those who had DH without previous thrombolysis.

Decompressive hemicraniectomy without clot evacuation in spontaneous intracranial hemorrhage: A systematic review.

OBJECTIVE: Decompressive hemicraniectomy (DH) effectively alleviates increased intracranial pressure (ICP) in patients with traumatic brain injury (TBI) and malignant middle cerebral artery (MCA) infarction. Its role in the management of spontaneous intracranial hemorrhage (SICH) however remains uncertain. This study aims to review the efficacy and safety of DH without clot evacuation in SICH. PATIENTS AND METHODS: A systematic literature search of PubMEd, EMBASE, Scopus and Cochrane Library Central Register of Control Trials was performed. Studies were reviewed independently for methodology, inclusion and exclusion criteria and end points. Primary endpoint was overall mortality. Secondary endpoint was functional outcome using modified Rankin scale (mRs) or Glasgow outcome scale (GOS). RESULTS: Nine studies with a total of 146 patients who underwent DH without clot evacuation include: 1 RCT, 3 cohort, 2 case series, and 3 case-control studies. Age range was 40-60 years, with majority of patients presenting with a relatively depressed preoperative sensorium (GCS 6-8), large hematoma volumes (>50 mL), and deep locations (basal ganglia and thalamus). Pooled analysis showed a favorable outcome in 53 %, a mortality rate of 26 % and a complication rate of 35.8 %. CONCLUSION: DH without clot evacuation may offer functional and mortality benefit in patients with spontaneous ICH, based on limited and heterogeneous studies.