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1.
Int J Mol Sci ; 25(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39273353

RESUMEN

Cerebral palsy (CP) is a common neurodevelopmental disorder characterized by pronounced motor dysfunction and resulting in physical disability. Neural precursor cells (NPCs) have shown therapeutic promise in mouse models of hypoxic-ischemic (HI) perinatal brain injury, which mirror hemiplegic CP. Constraint-induced movement therapy (CIMT) enhances the functional use of the impaired limb and has emerged as a beneficial intervention for hemiplegic CP. However, the precise mechanisms and optimal application of CIMT remain poorly understood. The potential synergy between a regenerative approach using NPCs and a rehabilitation strategy using CIMT has not been explored. We employed the Rice-Vannucci HI model on C57Bl/6 mice at postnatal day (PND) 7, effectively replicating the clinical and neuroanatomical characteristics of hemiplegic CP. NPCs were transplanted in the corpus callosum (CC) at PND21, which is the age corresponding to a 2-year-old child from a developmental perspective and until which CP is often not formally diagnosed, followed or not by Botulinum toxin injections in the unaffected forelimb muscles at PND23, 26, 29 and 32 to apply CIMT. Both interventions led to enhanced CC myelination and significant functional recovery (as shown by rearing and gait analysis testing), through the recruitment of endogenous oligodendrocytes. The combinatorial treatment indicated a synergistic effect, as shown by newly recruited oligodendrocytes and functional recovery. This work demonstrates the mechanistic effects of CIMT and NPC transplantation and advocates for their combined therapeutic potential in addressing hemiplegic CP.


Asunto(s)
Modelos Animales de Enfermedad , Hipoxia-Isquemia Encefálica , Ratones Endogámicos C57BL , Células-Madre Neurales , Recuperación de la Función , Animales , Células-Madre Neurales/trasplante , Ratones , Hipoxia-Isquemia Encefálica/terapia , Hipoxia-Isquemia Encefálica/patología , Parálisis Cerebral/terapia , Cuerpo Calloso , Terapia por Ejercicio/métodos , Masculino , Femenino
2.
Neurobiol Dis ; 200: 106640, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39159895

RESUMEN

Degenerative cervical myelopathy (DCM) describes a spectrum of disorders that cause progressive and chronic cervical spinal cord compression. The clinical presentation can be complex and can include locomotor impairment, hand and upper extremity dysfunction, pain, loss of bladder and bowel function, as well as gastrointestinal dysfunction. Once diagnosed, surgical decompression is the recommended treatment for DCM patients with moderate to severe impairment. Our body is composed of a large community of microorganisms, known as the microbiota. Traumatic and non-traumatic spinal cord injuries (SCIs) can induce changes in the gut microbiota and gut microbiota derived metabolites. These changes have been reported as important disease-modifying factors after injury. However, whether gut dysbiosis is associated with functional neurological recovery after surgical decompression has not been examined to date. Here, DCM was induced in C57BL/6 mice by implanting an aromatic polyether material underneath the C5-6 laminae. The extent of gut dysbiosis was assessed by gas chromatography and 16S rRNA sequencing from fecal samples before and after decompression. Neuromotor activity was assessed using the Catwalk test. Our results show that DCM pre- and post- surgical decompression is associated with gut dysbiosis, without altering short chain fatty acids (SCFAs) levels. Significant differences in Clostridia, Verrumicrobiae, Lachnospiracea, Firmicutes, Bacteroidales, and Clostridiaceae were observed between the DCM group (before decompression) and after surgical decompression (2 and 5 weeks). The changes in gut microbiota composition correlated with locomotor features of the Catwalk. For example, a longer duration of ground contact and dysfunctional swing in the forelimbs, were positively correlated with gut dysbiosis. These results show for the first time an association between gut dysbiosis and locomotor deterioration after delayed surgical decompression. Thus, providing a better understanding of the extent of changes in microbiota composition in the setting of DCM pre- and post- surgical decompression.


Asunto(s)
Descompresión Quirúrgica , Disbiosis , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Animales , Descompresión Quirúrgica/métodos , Microbioma Gastrointestinal/fisiología , Ratones , Enfermedades de la Médula Espinal/cirugía , Masculino , Vértebras Cervicales/cirugía , Compresión de la Médula Espinal/cirugía
3.
PLoS Med ; 21(8): e1004447, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39173109

RESUMEN

BACKGROUND: Degenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further "how" these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research. METHODS AND FINDINGS: A minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). In total, 28 outcomes and 6 domains (Pain, Neurological Function, Life Impact, Radiology, Economic Impact, and Adverse Events) were entered into the final COS. Thirty two outcomes and 4 domains (Individual, Disease, Investigation, and Intervention) were entered into the final CDE. Finally, 4 outcome instruments (mJOA, NDI, SF-36v2, and SAVES2) were identified for the CMS, with a recommendation for trials evaluating outcomes after surgery, to include baseline measurement and at 6 months from surgery. CONCLUSIONS: The AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS.


Asunto(s)
Vértebras Cervicales , Consenso , Técnica Delphi , Enfermedades de la Médula Espinal , Humanos , Vértebras Cervicales/cirugía , Enfermedades de la Médula Espinal/cirugía , Evaluación de Resultado en la Atención de Salud/métodos , Resultado del Tratamiento , Proyectos de Investigación
4.
Spinal Cord Ser Cases ; 10(1): 59, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39153987

RESUMEN

STUDY DESIGN: Clinical case series. OBJECTIVE: To describe the cause, treatment and outcome of 6 cases of perioperative spinal cord injury (SCI) in high-risk adult deformity surgery. SETTING: Adult spinal deformity patients were enrolled in the multi-center Scoli-RISK-1 cohort study. METHODS: A total of 272 patients who underwent complex adult deformity surgery were enrolled in the prospective, multi-center Scoli-RISK-1 cohort study. Clinical follow up data were available up to a maximum of 2 years after index surgery. Cases of perioperative SCI were identified and an extensive case review was performed. RESULTS: Six individuals with SCI were identified from the Scoli-RISK-1 database (2.2%). Two cases occurred intraoperatively and four cases occurred postoperatively. The first case was an incomplete SCI due to a direct intraoperative insult and was treated postoperatively with Riluzole. The second SCI case was caused by a compression injury due to overcorrection of the deformity. Three cases of incomplete SCI occurred; one case of postoperative hematoma, one case of proximal junctional kyphosis (PJK) and one case of adjacent segment disc herniation. All cases of post-operative incomplete SCI were managed with revision decompression and resulted in excellent clinical recovery. One case of incomplete SCI resulted from infection and PJK. The patient's treatment was complicated by a delay in revision and the patient suffered persistent neurological deficits up to six weeks following the onset of SCI. CONCLUSION: Despite the low incidence in high-risk adult deformity surgeries, perioperative SCI can result in devastating consequences. Thus, appropriate postoperative care, follow up and timely management of SCI are essential.


Asunto(s)
Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/epidemiología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/cirugía , Masculino , Femenino , Persona de Mediana Edad , Adulto , Incidencia , Complicaciones Posoperatorias/epidemiología , Anciano , Resultado del Tratamiento , Estudios de Cohortes , Estudios Prospectivos
5.
Clin Spine Surg ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39101583

RESUMEN

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To evaluate for areas of consensus and divergence of opinion within the spine community regarding the management of cervical spondylotic conditions and acute traumatic central cord syndrome (ATCCS) and the influence of the patient's age, disease severity, and myelomalacia. SUMMARY OF BACKGROUND DATA: There is ongoing disagreement regarding the indications for, and urgency of, operative intervention in patients with mild degenerative myelopathy, moderate to severe radiculopathy, isolated axial symptomatology with evidence of spinal cord compression, and ATCCS without myelomalacia. METHODS: A survey request was sent to 330 attendees of the Cervical Spine Research Society (CSRS) 2021 Annual Meeting to assess practice patterns regarding the treatment of cervical stenosis, myelopathy, radiculopathy, and ATCCS in 16 unique clinical vignettes with associated MRIs. Operative versus nonoperative treatment consensus was defined by a management option selected by >80% of survey participants. RESULTS: Overall, 116 meeting attendees completed the survey. Consensus supported nonoperative management for elderly patients with axial neck pain and adults with axial neck pain without myelomalacia. Operative management was indicated for adult patients with mild myelopathy and myelomalacia, adult patients with severe radiculopathy, elderly patients with severe radiculopathy and myelomalacia, and elderly ATCCS patients with pre-existing myelopathic symptoms. Treatment discrepancy in favor of nonoperative management was found for adult patients with isolated axial symptomatology and myelomalacia. Treatment discrepancy favored operative management for elderly patients with mild myelopathy, adult patients with mild myelopathy without myelomalacia, elderly patients with severe radiculopathy without myelomalacia, and elderly ATCCS patients without preceding symptoms. CONCLUSIONS: Although there is uncertainty regarding the treatment of mild myelopathy, operative intervention was favored for nonelderly patients with evidence of myelomalacia or radiculopathy and for elderly patients with ATCCS, especially if pre-injury myelopathic symptoms were present. LEVEL OF EVIDENCE: Level V.

6.
EBioMedicine ; 106: 105226, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38968776

RESUMEN

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.


Asunto(s)
Aprendizaje Automático , Fenotipo , Humanos , Masculino , Femenino , Análisis por Conglomerados , Persona de Mediana Edad , Anciano , Enfermedades de la Médula Espinal/diagnóstico , Enfermedades de la Médula Espinal/cirugía , Vértebras Cervicales/cirugía , Resultado del Tratamiento , Adulto
8.
J Clin Med ; 13(14)2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39064141

RESUMEN

Spinal cord injury (SCI) is a debilitating condition that is associated with long-term physical and functional disability. Our understanding of the pathogenesis of SCI has evolved significantly over the past three decades. In parallel, significant advances have been made in optimizing the management of patients with SCI. Early surgical decompression, adequate bony decompression and expansile duraplasty are surgical strategies that may improve neurological and functional outcomes in patients with SCI. Furthermore, advances in the non-surgical management of SCI have been made, including optimization of hemodynamic management in the critical care setting. Several promising therapies have also been investigated in pre-clinical studies, with some being translated into clinical trials. Given the recent interest in advancing precision medicine, several investigations have been performed to delineate the role of imaging, cerebral spinal fluid (CSF) and serum biomarkers in predicting outcomes and curating individualized treatment plans for SCI patients. Finally, technological advancements in biomechanics and bioengineering have also found a role in SCI management in the form of neuromodulation and brain-computer interfaces.

9.
J Neurotrauma ; 41(17-18): 2158-2167, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39041612

RESUMEN

Cervical spine injuries (CSIs) are heterogeneous in nature and often lead to long-term disability and morbidity. However, there are few recent and comprehensive epidemiological studies on CSI. The objective of this study was to characterize recent trends in CSI patient demographics, incidence, etiology, and injury level. The National Electronic Injury Surveillance System was used to extract data on CSIs from 2002 to 2022. Weighted national estimates of CSI incidence were computed using yearly population estimates interpolated from U.S. census data. Data analysis involved extracting additional information from patient narratives to categorize injury etiology (i.e., fall) and identify CSI level. K-means clustering was performed on cervical levels to define upper versus lower cervical injuries. Appropriate summary statistics including mean with 95% confidence intervals and frequency were reported for age, sex, race, ethnicity, etiology, and disposition. Age between groups was compared using an independent weighted Z-test. All categorical variables were compared using Pearson chi-squared tests with Bonferroni correction for multiple comparisons. Ordinary least squares linear regression was used to quantify the rate of change of various metrics with time. A total of 11,822 patient records met the study criteria. The mean age of patients was 62.4 ± 22.7 years, 52.4% of whom were male and 61.4% of whom were White, 7.4% were Black, 27.8% were not specified, and the remaining comprised a variety of ethnicities. The most common mechanism of CSI was a fall (67.3%). There was a significant increase in the incidence of cervical injuries between 2003 and 2022 (p < 0.001). Unbiased K-means clustering defined upper cervical injuries as C1-C3 and lower cervical injuries as C4-C7. The mean age of patients with upper CSIs was 72.3 ± 19.6, significantly greater than the age of those with lower CSIs (57.1 ± 23.1, p < 0.001). Compared with lower CSI, White patients were more likely to have an upper CSI (67.4% vs. 73.7%; p < 0.001). While Black/African American (7.5% vs. 3.8%) and Hispanic (2.5% vs. 1.0%) patients were more likely to have a lower CSI (p < 0.001). Our study identified a significant increase in the incidence of CSIs over time, which was associated with increasing patient age. Our study detected a pragmatic demarcation of classifying upper injuries as C1-C3 and lower cervical injuries as C4-C7. Upper injuries were seen more often in older, White females who were treated and admitted, and lower injuries were seen more often in young, Black male patients who were released without admission.


Asunto(s)
Vértebras Cervicales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Vértebras Cervicales/lesiones , Adulto , Anciano , Estados Unidos/epidemiología , Incidencia , Adulto Joven , Adolescente , Niño , Traumatismos Vertebrales/epidemiología , Preescolar , Anciano de 80 o más Años , Lactante , Vigilancia de la Población/métodos
10.
JAMA Netw Open ; 7(6): e2415643, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38904964

RESUMEN

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.


Asunto(s)
Vértebras Cervicales , Riluzol , Humanos , Riluzol/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Método Doble Ciego , Vértebras Cervicales/cirugía , Anciano , Enfermedades de la Médula Espinal/cirugía , Enfermedades de la Médula Espinal/tratamiento farmacológico , Espondilosis/cirugía , Espondilosis/tratamiento farmacológico , Resultado del Tratamiento , Fármacos Neuroprotectores/uso terapéutico
11.
Neurosurgery ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38912784

RESUMEN

BACKGROUND AND OBJECTIVES: Return-to-work (RTW) is an important outcome for employed patients considering surgery for cervical spondylotic myelopathy (CSM). We conducted a post hoc analysis of patients as-treated in the Cervical Spondylotic Myelopathy Surgical Trial, a prospective, randomized trial comparing surgical approaches for CSM to evaluate factors associated with RTW. METHODS: In the trial, patients were randomized (2:3) to either anterior surgery (anterior cervical decompression/fusion [ACDF]) or posterior surgery (laminoplasty [LP], or posterior cervical decompression/fusion [PCDF], at surgeon's discretion). Work status was recorded at 1, 3, 6, and 12 months postoperatively. For patients working full-time or part-time on enrollment, time to RTW was compared across as-treated surgical groups using discrete-time survival analysis. Multivariate logistic regression was used to assess predictors of RTW. Clinical outcomes were compared using a linear mixed-effects model. RESULTS: A total of 68 (42%) of 163 patients were working preoperatively and were analyzed. In total, 27 patients underwent ACDF, 29 underwent PCDF, and 12 underwent LP. 45 (66%) of 68 patients returned to work by 12 months. Median time to RTW differed by surgical approach (LP = 1 month, ACDF = 3 months, PCDF = 6 months; P = .02). Patients with longer length-of-stay were less likely to be working at 1 month (odds ratio 0.51; 95% CI, 0.29-0.91; P = .022) and 3 months (odds ratio 0.39; 95% CI, 0.16-0.96; P = .04). At 3 months, PCDF was associated with lower Short-Form 36 physical component summary scores than ACDF (estimated mean difference [EMD]: 6.42; 95% CI, 1.4-11.4; P = .007) and LP (EMD: 7.98; 95% CI, 2.7-13.3; P = .003), and higher Neck Disability Index scores than ACDF (EMD: 12.48; 95% CI, 2.3-22.7; P = .01) and LP (EMD: 15.22; 95% CI, 2.3-28.1; P = .014), indicating worse perceived physical functioning and greater disability, respectively. CONCLUSION: Most employed patients returned to work within 1 year. LP patients resumed employment earliest, while PCDF patients returned to work latest, with greater disability at follow-up, suggesting that choice of surgical intervention may influence occupational outcomes.

12.
Eur Spine J ; 33(8): 3109-3116, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38825607

RESUMEN

BACKGROUND: Cervical posterior instrumentation and fusion is often performed to avoid post-laminectomy kyphosis. However, larger comparative analyses of cervical laminectomy with or without fusion are sparse. METHODS: A retrospective, two-center, comparative cohort study included patients after stand-alone dorsal laminectomy with (n = 91) or without (n = 46) additional fusion for degenerative cervical myelopathy with a median follow-up of 59 (interquartile range (IQR) 52) months. The primary outcome was the C2-7 Cobb angle and secondary outcomes were Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA) scale, revision rates, T1 slope and C2-7 sagittal vertical axis (C2-7 SVA) at final follow-up. Logistic regression analysis adjusted for potential confounders (i.e. age, operated levels, and follow-up). RESULTS: Preoperative C2-7 Cobb angle and T1 slope were higher in the laminectomy group, while the C2-7 SVA was similar. The decrease in C2-7 Cobb angle from pre- to postoperatively was more pronounced in the laminectomy group (- 6° (IQR 20) versus -1° (IQR 7), p = 0.002). When adjusting for confounders, the decrease in C2-7 Cobb angle remained higher in the laminectomy group (coefficient - 12 (95% confidence interval (CI) -18 to -5), p = 0.001). However, there were no adjusted differences for postoperative NDI (- 11 (- 23 to 2), p = 0.10), mJOA, revision rates, T1 slope and C2-7 SVA. CONCLUSION: Posterior cervical laminectomy without fusion is associated with mild loss of cervical lordosis of around 6° in the mid-term after approximately five years, however without any clinical relevance regarding NDI or mJOA in well-selected patients (particularly in shorter segment laminectomies of < 3 levels).


Asunto(s)
Vértebras Cervicales , Cifosis , Laminectomía , Fusión Vertebral , Humanos , Laminectomía/efectos adversos , Laminectomía/métodos , Masculino , Vértebras Cervicales/cirugía , Vértebras Cervicales/diagnóstico por imagen , Femenino , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Persona de Mediana Edad , Cifosis/cirugía , Cifosis/diagnóstico por imagen , Cifosis/etiología , Estudios Retrospectivos , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/epidemiología , Enfermedades de la Médula Espinal/cirugía , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/etiología , Resultado del Tratamiento
13.
Neurosurgery ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38832791

RESUMEN

BACKGROUND AND OBJECTIVES: The palliative impact of spine surgery for metastatic disease is evolving with improvements in surgical technique and multidisciplinary cancer care. The goal of this study was to prospectively evaluate long-term clinical outcomes including health-related quality-of-life (HRQOL) measures, using spine cancer-specific patient-reported-outcome (PRO) measures, in patients with symptomatic spinal metastases who underwent surgical management. METHODS: The Epidemiology, Process, and Outcomes of Spine Oncology (EPOSO, ClinicalTrials.gov identifier: NCT01825161) trial is a prospective-observational cohort study that included 10 specialist centers in North America and Europe. Patients aged 18 to 75 years who underwent surgery for spinal metastases were included. Prospective assessments included both spine tumor-specific and generic PRO tools which were collected for a minimum of 2 years post-treatment or until death. RESULTS: Two hundred and eighty patients (51.8% female, mean age 57.9 years) were included. At presentation, the mean Charlson Comorbidity Index was 6.0, 35.7% had neurological deficits as defined by the American Spinal Cord Injury Association scores, 47.2% had high-grade epidural spinal cord compression (2-3), and 89.6% had impending or frank instability as measured by a Spinal Instability Neoplastic Score of ≥7. The most common primary tumor sites were breast (20.2%), lung (18.8%), kidney (16.2%), and prostate (6.5%). The median overall survival postsurgery was 501 days, and the 2-year progression-free-survival rate was 38.4%. Compared with baseline, significant and durable improvements in HRQOL were observed at the 6-week, 12-week, 26-week, 1-year, and 2-year follow-up assessments from a battery of PRO questionnaires including the spine cancer-specific, validated, Spine Oncology Study Group Outcomes Questionnaire v2.0, the Short Form 36 version 2, EuroQol-5 Dimension (3L), and pain numerical rating scale score. CONCLUSION: Multi-institutional, prospective-outcomes data confirm that surgical decompression and/or stabilization provides meaningful and durable improvements in multiple HRQOL domains, including spine-specific outcomes based on the Spine Oncology Study Group Outcomes Questionnaire v2.0, for patients with metastatic spine disease.

14.
Int J Mol Sci ; 25(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38891894

RESUMEN

Traumatic spinal cord injury (SCI) is a life-threatening and life-altering condition that results in debilitating sensorimotor and autonomic impairments. Despite significant advances in the clinical management of traumatic SCI, many patients continue to suffer due to a lack of effective therapies. The initial mechanical injury to the spinal cord results in a series of secondary molecular processes and intracellular signaling cascades in immune, vascular, glial, and neuronal cell populations, which further damage the injured spinal cord. These intracellular cascades present promising translationally relevant targets for therapeutic intervention due to their high ubiquity and conservation across eukaryotic evolution. To date, many therapeutics have shown either direct or indirect involvement of these pathways in improving recovery after SCI. However, the complex, multifaceted, and heterogeneous nature of traumatic SCI requires better elucidation of the underlying secondary intracellular signaling cascades to minimize off-target effects and maximize effectiveness. Recent advances in transcriptional and molecular neuroscience provide a closer characterization of these pathways in the injured spinal cord. This narrative review article aims to survey the MAPK, PI3K-AKT-mTOR, Rho-ROCK, NF-κB, and JAK-STAT signaling cascades, in addition to providing a comprehensive overview of the involvement and therapeutic potential of these secondary intracellular pathways following traumatic SCI.


Asunto(s)
Transducción de Señal , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/metabolismo , Humanos , Animales , Serina-Treonina Quinasas TOR/metabolismo
15.
Expert Rev Neurother ; 24(7): 691-709, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38879824

RESUMEN

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.


Asunto(s)
Imagen por Resonancia Magnética , Neuroimagen , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/diagnóstico por imagen , Neuroimagen/métodos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X , Aprendizaje Automático , Inteligencia Artificial
16.
Eur Spine J ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858267

RESUMEN

BACKGROUND CONTEXT: Postoperative infection after spinal deformity correction in pediatric patients is associated with significant costs. Identifying risk factors associated with postoperative infection would help surgeons identify high-risk patients that may require interventions to minimize infection risk. PURPOSE: To investigate risk factors associated with 30-day postoperative infection in pediatric patients who have received posterior arthrodesis for spinal deformity correction. STUDY DESIGN/SETTING: Retrospective review of prospectively collected data. PATIENT SAMPLE: The National Surgical Quality Improvement Program Pediatric database for years 2016-2021 was used for this study. Patients were included if they received posterior arthrodesis for scoliosis or kyphosis correction (CPT 22,800, 22,802, 22,804). Anterior only approaches were excluded. OUTCOME MEASURES: TThe outcome of interest was 30-day postoperative infection. METHODS: Patient demographics and outcomes were analyzed using descriptive statistics. Multivariable logistic regression analysis using likelihood ratio backward selection method was used to identify significant risk factors for 30-day infection to create the Pediatric Scoliosis Infection Risk Score (PSIR Score). ROC curve analysis, predicted probabilities, and Hosmer Lemeshow goodness-of-fit test were done to assess the scoring system on a validation cohort. RESULTS: A total of 31,742 patients were included in the study. The mean age was 13.8 years and 68.7% were female. The 30-day infection rate was 2.2%. Reoperation rate in patients who had a post-operative infection was 59.4%. Patients who had post-operative infection had a higher likelihood of non-home discharge (X2 = 124.8, p < 0.001). In our multivariable regression analysis, high BMI (OR = 1.01, p < 0.001), presence of open wound (OR = 3.18, p < 0.001), presence of ostomy (OR = 1.51, p < 0.001), neuromuscular etiology (OR = 1.56, p = 0.009), previous operation (OR = 1.74, p < 0.001), increasing ASA class (OR = 1.43, p < 0.001), increasing operation time in hours (OR = 1.11, p < 0.001), and use of only minimally invasive techniques (OR = 4.26, p < 0.001) were associated with increased risk of 30-day post-operative infection. Idiopathic etiology (OR = 0.53, p < 0.001) and intraoperative topical antibiotic use (B = 0.71, p = 0.003) were associated with reduced risk of 30-day postoperative infection. The area under the curve was 0.780 and 0.740 for the derivation cohort and validation cohort, respectively. CONCLUSIONS: To our knowledge, this is the largest study of risk factors for infection in pediatric spinal deformity surgery. We found 5 patient factors (BMI, ASA, osteotomy, etiology, and previous surgery, and 3 surgeon-controlled factors (surgical time, antibiotics, MIS) associated with risk. The Pediatric Scoliosis Infection Risk Score (PSIR) Score can be applied for risk stratification and to investigate implementation of novel protocols to reduce infection rates in high-risk patients.

18.
Eur J Neurol ; 31(7): e16297, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38713645

RESUMEN

BACKGROUND AND PURPOSE: Simultaneous assessment of neurodegeneration in both the cervical cord and brain across multiple centres can enhance the effectiveness of clinical trials. Thus, this study aims to simultaneously assess microstructural changes in the cervical cord and brain above the stenosis in degenerative cervical myelopathy (DCM) using quantitative magnetic resonance imaging (MRI) in a multicentre study. METHODS: We applied voxelwise analysis with a probabilistic brain/spinal cord template embedded in statistical parametric mappin (SPM-BSC) to process multi parametric mapping (MPM) including effective transverse relaxation rate (R2*), longitudinal relaxation rate (R1), and magnetization transfer (MT), which are indirectly sensitive to iron and myelin content. Regression analysis was conducted to establish associations between neurodegeneration and clinical impairment. Thirty-eight DCM patients (mean age ± SD = 58.45 ± 11.47 years) and 38 healthy controls (mean age ± SD = 41.18 ± 12.75 years) were recruited at University Hospital Balgrist, Switzerland and Toronto Western Hospital, Canada. RESULTS: Remote atrophy was observed in the cervical cord (p = 0.002) and in the left thalamus (0.026) of the DCM group. R1 was decreased in the periaqueductal grey matter (p = 0.014), thalamus (p = 0.001), corpus callosum (p = 0.0001), and cranial corticospinal tract (p = 0.03). R2* was increased in the primary somatosensory cortices (p = 0.008). Sensory impairments were associated with increased iron-sensitive R2* in the thalamus and periaqueductal grey matter in DCM. CONCLUSIONS: Simultaneous assessment of the spinal cord and brain revealed DCM-induced demyelination, iron deposition, and atrophy. The extent of remote neurodegeneration was associated with sensory impairment, highlighting the intricate and expansive nature of microstructural neurodegeneration in DCM, reaching beyond the stenosis level.


Asunto(s)
Médula Cervical , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Médula Cervical/diagnóstico por imagen , Médula Cervical/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/patología , Enfermedades Neurodegenerativas/diagnóstico por imagen , Enfermedades Neurodegenerativas/patología
19.
Brain Spine ; 4: 102825, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756860

RESUMEN

Introduction: It was not even a century ago when a spinal cord injury (SCI) would inevitably result in a fatal outcome, particularly for those with complete SCI. Throughout history, there have been extensive endeavours to change the prospects for SCI patients by performing surgery, even though many believed that there was no way to alter the catastrophic course of SCI. To this day, the debate regarding the efficacy of surgery in improving the neurological outcome for SCI patients persists, along with discussions about the timing of surgical intervention. Research question: How have the historical surgical results shaped our perspective on the surgical treatment of SCI? Material and methods: Narrative literature review. Results: Throughout history there have been multiple surgical attempts to alter the course of SCI, with conflicting results. While studies suggest a potential link between timing of surgery and neurological recovery, the exact impact of immediate surgery on individual cases remains ambiguous. It is becoming more evident that, alongside surgical intervention, factors specific to both the patient and their surgical treatment will significantly influence neurological recovery. Conclusion: Although a growing number of studies indicates a potential correlation of surgical timing and neurological outcome, the precise influence of urgent surgery on an individual basis remains uncertain. It is increasingly apparent that, despite surgery, patient- and treatment-specific factors will also play a role in determining the neurological outcome. Notably, these very factors have influenced the results in previous studies and our views concerning surgical timing.

20.
Front Neurosci ; 18: 1372920, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38812974

RESUMEN

Traumatic spinal cord injuries (SCIs) continue to be a major healthcare concern, with a rising prevalence worldwide. In response to this growing medical challenge, considerable scientific attention has been devoted to developing neuroprotective and neuroregenerative strategies aimed at improving the prognosis and quality of life for individuals with SCIs. This comprehensive review aims to provide an up-to-date and thorough overview of the latest neuroregenerative and neuroprotective therapies currently under investigation. These strategies encompass a multifaceted approach that include neuropharmacological interventions, cell-based therapies, and other promising strategies such as biomaterial scaffolds and neuro-modulation therapies. In addition, the review discusses the importance of acute clinical management, including the role of hemodynamic management as well as timing and technical aspects of surgery as key factors mitigating the secondary injury following SCI. In conclusion, this review underscores the ongoing scientific efforts to enhance patient outcomes and quality of life, focusing on upcoming strategies for the management of traumatic SCI. Each section provides a working knowledge of the fundamental preclinical and patient trials relevant to clinicians while underscoring the pathophysiologic rationale for the therapies.

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