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Abstract BACKGROUND: Degenerative cervical myelopathy encompasses a group of conditions resulting in progressive spinal cord injury through static and dynamic compression. Although a constellation of changes can present on magnetic resonance imaging (MRI), the clinical significance of these findings remains a subject of controversy and discussion. OBJECTIVE: To investigate the relationship between clinical presentation and quantitative MRI features in patients with degenerative cervical myelopathy. METHODS: A secondary analysis of MRI and clinical data from 114 patients enrolled in a prospective, multicenter study was conducted. MRIs were assessed for maximum spinal cord compression (MSCC), maximum canal compromise (MCC), signal changes, and a signal change ratio (SCR). MRI features were compared between patients with and those without myelopathy symptoms with the use of t tests. Correlations between MRI features and duration of symptoms were assessed with the Spearman ρ. RESULTS: Numb hands and Hoffmann sign were associated with greater MSCC (P < .05); broad-based, unstable gait, impairment of gait, and Hoffmann sign were associated with greater MCC (P < .05); and numb hands, Hoffmann sign, Babinski sign, lower limb spasticity, hyperreflexia, and T1 hypointensity were associated with greater SCR (P < .05). Patients with a T2 signal hyperintensity had greater MSCC and MCC (P < .001). CONCLUSION: MSCC was associated with upper limb manifestations, and SCR was associated with upper limb, lower limb, and general neurological deficits. Hoffmann sign occurred more commonly in patients with a greater MSCC, MCC and SCR. The Lhermitte phenomenon presented more commonly in patients with a lower SCR and may be an early indicator of mild spinal cord involvement. Research to validate these findings is required.

ABSTRACT OBJECTIVE After randomizing 100 failed back surgery syndrome patients to receive spinal cord stimulation (SCS) plus conventional medical management (CMM) or CMM alone, the results of the 6-month Prospective Randomized Controlled Multicenter Trial of the Effectiveness of Spinal Cord Stimulation (i.e., PROCESS) showed that SCS offered superior pain relief, health-related quality of life, and functional capacity. Because the rate of crossover favoring SCS beyond 6 months would bias a long-term randomized group comparison, we present all outcomes in patients who continued SCS from randomization to 24 months and, for illustrative purposes, the primary outcome (>50% leg pain relief) per randomization and final treatment. METHODS Patients provided data on pain, quality of life, function, pain medication use, treatment satisfaction, and employment status. Investigators documented adverse events. Data analysis included inferential comparisons and multivariate regression analyses. RESULTS The 42 patients continuing SCS (of 52 randomized to SCS) reported significantly improved leg pain relief (P < 0.0001), quality of life (P ≤ 0.01), and functional capacity (P = 0.0002); and 13 patients (31%) required a device-related surgical revision. At 24 months, of 46 of 52 patients randomized to SCS and 41 of 48 randomized to CMM who were available, the primary outcome was achieved by 17 (37%) randomized to SCS versus 1 (2%) to CMM (P = 0.003) and by 34 (47%) of 72 patients who received SCS as final treatment versus 1 (7%) of 15 for CMM (P = 0.02). CONCLUSION At 24 months of SCS treatment, selected failed back surgery syndrome patients reported sustained pain relief, clinically important improvements in functional capacity and health-related quality of life, and satisfaction with treatment.

Acquired copper deficiency has been recognised as a rare cause of anaemia and neutropenia for over half a century. Copper deficiency myelopathy (CDM) was only described within the last decade, and represents a treatable cause of non-compressive myelopathy which closely mimics subacute combined degeneration due to vitamin B12 deficiency. Here, 55 case reports from the literature are reviewed regarding their demographics, aetiology, haematological and biochemical parameters, spinal imaging, treatment and outcome. The pathophysiology of disorders of copper metabolism is discussed. CDM most frequently presented in the fifth and sixth decades and was more common in women (F:M = 3.6:1). Risk factors included previous upper gastrointestinal surgery, zinc overload and malabsorption syndromes, all of which impair copper absorption in the upper gastrointestinal tract. No aetiology was established in 20% of cases. High zinc levels were detected in some cases not considered to have primary zinc overload, and in this situation the contribution of zinc to the copper deficiency state remained unclear. Cytopenias were found in 78%, particularly anaemia, and a myelodysplastic syndrome may have been falsely diagnosed in the past. Spinal MRI was abnormal in 47% and usually showed high T2 signal in the posterior cervical and thoracic cord. In a clinically compatible case, CDM may be suggested by the presence of one or more risk factors and/or cytopenias. Low serum copper and caeruloplasmin levels confirmed the diagnosis and, in contrast to Wilson’s disease, urinary copper levels were typically low. Treatment comprised copper supplementation and modification of any risk factors, and led to haematological normalisation and neurological improvement or stabilisation. Since any neurological recovery was partial and case numbers of CDM will continue to rise with the growing use of bariatric gastrointestinal surgery, clinical vigilance will remain the key to minimising neurological sequelae. Recommendations for treatment and prevention are made.

BackgroundWhilst the dangers of ‘legal highs’ have been widely publicised in the media, very few cases of the neurological syndrome associated with the inhalation of nitrous oxide (N2O) have been reported. Here we set out to raise awareness of subacute degeneration of the spinal cord arising from recreational N2O use so that formal surveillance programs and public health interventions can be designed.MethodsCase series documenting the clinical and investigational features of ten consecutive cases of subacute degeneration of the spinal cord presenting to a hospital with a tertiary neurosciences service in East London.ResultsSensory disturbance in the lower (± upper) limbs was the commonest presenting feature, along with gait abnormalities and sensory ataxia. MRI imaging of the spine showed the characteristic features of dorsal column hyperintensity on T2 weighted sequences. Serum B12 levels may be normal because subacute degeneration of the spinal cord in this situation is triggered by functional rather than absolute B12 deficiency.DiscussionA high index of suspicion is required to prompt appropriate investigation, make the diagnosis and commence treatment early. This is the largest reported series of patients with subacute degeneration of the spinal cord induced by recreational use of N2O. However, the number of patients admitted to hospital likely represents the ‘tip of the iceberg’, with many less severe presentations remaining undetected. After raising awareness, attention should focus on measuring the extent of the problem, the groups affected, and devising ways to prevent potentially long-term neurological damage.

Patients with cervical myelopathy may manifest impairments in functional activities and balance control caused by compression of the spinal cord. The objective of the current study was to determine long-term changes in the upright balance control of patients with cervical myelopathy who had undergone cervical decompression surgery. This is a prospective cohort study from the preoperative phase to 3 months, 6 months, and 1 year postsurgery. Fifty-three patients with cervical myelopathy were recruited for the cervical myelopathy group and 22 age-matched healthy controls were recruited for the control group. Functional assessments including Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire-Lower Extremity Function (JOACMEQ-LEF) and 10-second step test; as well as balance assessments including postural sway (center-of-pressure: COP) were performed for both groups. The JOACMEQ-LEF (p = 0.036) scores of the myelopathy group improved postoperatively, and a significant decrease in COP variables of postural sway was observed. The upright posture was less stable in the myelopathy group than in the control group (p < 0.05) both before and after surgery. The effect size and standard response mean of the COP variables ranged from −0.49 to 0.03 at 3 months, 6 months, and 1 year postsurgery. The upright balance control had improved significantly 6 months after decompression surgery. However, the balance control of the patients who had undergone decompression surgery remained less stable than that of the age-matched healthy controls. Balance training should be initiated before 6 months postsurgery to accelerate balance control recovery in patients with cervical myelopathy.

Background Cervical spondylosis (CS), including myelopathy and radiculopathy, is the most common degenerative cervical spine disease. This study aims to evaluate the clinical outcomes of unilateral biportal endoscopy (UBE) compared to those of conventional anterior cervical decompression and fusion (ACDF) for treating unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs. Methods A prospective, randomized, controlled, noninferiority trial was conducted. The sample consisted of 131 patients who underwent UBE or ACDF was conducted between September 2021 and September 2022. Patients with cervical nerve roots or coexisting spinal cord compression symptoms and imaging-defined unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs were randomized into two groups: a UBE group ( n  = 63) and an ACDF group ( n  = 68). The operative time, blood loss, length of hospital stay after surgery, and perioperative complications were recorded. Preoperative and postoperative modified Japanese Orthopaedic Association (mJOA) scale scores, visual analog scale (VAS) scores, neck disability index (NDI) scores, and recovery rate (RR) of the mJOA were utilized to evaluate clinical outcomes. Results The hospital stay after surgery was significantly shorter in patients treated with UBE than in those treated with ACDF ( p  < 0.05). There were no significant differences in the neck or arm VAS score, NDI score, mJOA score, or mean RR of the mJOA between the two groups ( p  < 0.05). Only mild complications were observed in both groups, with no significant difference ( p  = 0.30). Conclusion UBE can significantly relieve pain and disability without severe complications, and most patients are satisfied with this technique. Consequently, this procedure can be used safely and effectively as an alternative to ACDF for treating unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs. Trial registration This study was registered in the Chinese Clinical Trial Registry on 02/08/2023 ( http://www.chictr.org.cn , #ChiCTR2300074273).

Background Cervical spondylotic myelopathy (CSM) is the predominant cause of spinal cord dysfunction in the elderly. The patients are often frail and susceptible to complications. Posterior surgical techniques involving non-fusion are complicated by postlaminectomy kyphosis and instrumented fusion techniques by distal junction kyphosis, pseudarthrosis, or implant failure. The optimal surgical approach is still a matter of controversy. Since anterior and posterior fusion techniques have been compared without presenting any superiority, the objective of this study is to compare stand-alone laminectomy with laminectomy and fusion to determine which treatment has the lowest frequency of reoperations. Methods This is a multicenter randomized, controlled, parallel-group non-inferiority trial. A total of 300 adult patients are allocated in a ratio of 1:1. The primary endpoint is reoperation for any reason at 5 years of follow-up. Sample size and power calculation were performed by estimating the reoperation rate after laminectomy to 3.5% and after laminectomy with fusion to 7.4% based on the data from the Swedish spine registry (Swespine) on patients with CSM. Secondary outcomes are the patient-derived Japanese Orthopaedic Association (P-mJOA) score, Neck Disability Index (NDI), European Quality of Life Five Dimensions (EQ-5D), Numeric Rating Scale (NRS) for neck and arm pain, Hospital Anxiety and Depression Scale (HADS), development of kyphosis measured as the cervical sagittal vertical axis (cSVA), and death. Clinical and radiological follow-up is performed at 3, 12, 24, and 60 months after surgery. The main inclusion criterium is 1–4 levels of CSM in the subaxial spine, C3–C7. The REDcap software will be used for safe data management. Data will be analyzed according to the modified intention to treat (mITT) population, defined as randomized patients who are still alive without having emigrated or left the study after 2 and 5 years. Discussion This will be the first randomized controlled trial comparing two of the most common surgical treatments for CSM: the posterior muscle-preserving selective laminectomy and posterior laminectomy with instrumented fusion. The results of the myelopathy randomized controlled (MyRanC) study will provide surgical treatment recommendations for CSM. This may result in improvements in surgical treatment and clinical practice regarding CSM. Trial registration ClinicalTrials.gov NCT04936074 . Registered on 23 June 2021

Spinal cord injury causes a cascade of physiological responses, which may trigger a subsequent neurotoxic increase in intracellular sodium. This can lead to neurodegeneration, both at and beyond the site of injury, causing clinical symptoms and loss of function. However, in vivo measurements of tissue sodium remain challenging. Here we utilise sodium magnetic resonance spectroscopy ( 23 Na-MRS) at 3T to measure tissue sodium concentration (TSC) and its association with microstructural measures and macromolecular MRI metrics in the cervical spinal cord, distal to the site of injury. Twenty people with cervical myelopathy and twenty healthy controls, were studied. Associations with motor and sensory impairments were explored using ASIA and jOAMEQ scores. No significant difference in TSC in the cervical myelopathy group (39 ± 10 mM) relative to healthy controls (35 ± 13 mM) was found. However, patients had a significantly lower cord-cross-sectional area than controls (70 ± 9 mm 2 vs. 82 ± 9 mm 2 , p  < 0.001). Lower-extremity function positively correlated with intracellular volume fraction ( p  = 0.031). In conclusion, using 23 Na-MRS, TSC in cervical myelopathy patients was successfully measured. Differences in TSC relative to healthy controls did not reach significance, despite a significant reduction in cord-cross-sectional area. However, lower intracellular volume fraction, indicating reduced neurite density distal to the site of injury, was associated with physical impairment.

Canine degenerative myelopathy (DM) is an adult-onset neurodegenerative disease considered a spontaneous model of human amyotrophic lateral sclerosis (ALS). Neuroinflammation occurs in both DM and ALS, and crosstalk between the central nervous system and systemic immunity has been demonstrated in ALS. To investigate this interaction in DM, we analyzed peripheral blood and spinal cord tissues using real-time RT-PCR and immunofluorescence. In peripheral blood, mRNA expression of interleukin (IL)-18 and nod-like receptor protein 3 was significantly increased compared with intervertebral disk herniation controls. IL-10 and caspase-1 were elevated, whereas tumor necrosis factor-α was decreased relative to healthy controls. C–C motif chemokine receptor 2 expression showed a moderate negative correlation with disease duration. Immunofluorescence revealed a few transmembrane protein 119 − and mannose receptor C-type 1 + cells, indicating limited infiltration of peripheral blood-derived macrophages into the spinal cord. Transcriptional analysis of spinal cords with different degrees of degeneration showed increased expression of activated astrocyte markers (serping1 and S100A10) and C–C motif chemokine ligand 2 in moderately to severely degenerated tissues. Furthermore, immunohistochemical analysis revealed increased CCL2 protein expression in the affected spinal cords. These findings suggest that systemic immune activation contributes to spinal neuroinflammation in DM, although its limited cellular infiltration implies a minor role in neurodegeneration.