Cryoneurolysis versus radiofrequency ablation outcome on pain experience in chronic low back pain (COPE): a single-blinded randomised controlled trial.

OBJECTIVE: A comparison of cryoneurolysis or radio frequency (RF) with placebo in patients with facetogenic chronic low back pain (LBP) for patient global impression of change (PGIC), pain intensity, function and quality of life, with 1-year follow-up. DESIGN: Single-centre, single-blinded placebo-controlled randomised controlled trial. SETTING: Single-centre study. PARTICIPANTS: Inclusion from March 2020 to September 2022: consenting adults over 18 years of age, LBP>3 months, average Numeric Rating Scale LBP≥4 average last 14 days and a positive response to a diagnostic medial branch block (>50% pain reduction after 60 min). INTERVENTIONS: 120 patients were block randomised 1:1:1 to cryoneurolysis, RF or placebo of the medial branch nerves. Physical therapy was added after 4 weeks for all groups. MAIN OUTCOME MEASURES: Primary outcome was PGIC 4 weeks after the intervention. Secondary outcomes included pain intensity (Numeric Rating Scale, NRS), quality of life (Short Form 36, EQ-5D-5L), disability (Oswestry Disability Index), depression (Major Depression Inventory) and catastrophising (Pain Catastrophising Scale). Outcomes were measured at 4 weeks, 3, 6 and 12 months. RESULTS: There was no statistically significant difference in PGIC at 4 weeks between cryoneurolysis and placebo (risk ratio (RR) 2; 95% CI 0.75 to 5.33, p=0.17) and RF and placebo (RR 1.6; 95% CI 0.57 to 4.49, p=0.37), except PGIC for cryoneurolysis at 6-month follow-up (RR 5.1; 95% CI 1.20 to 22.03, p=0.03). No statistically significant differences were found in secondary follow-up endpoints. CONCLUSIONS: Denervation of the medial branch nerve by either cryoneurolysis or RF compared with placebo did not demonstrate significant improvement in PGIC, pain intensity, function and quality of life in patients with facetogenic chronic LBP at short-term or long-term follow-up. TRIAL REGISTRATION NUMBER: NCT04786145.

Glial fibrillary acidic protein is a robust biomarker in cerebrospinal fluid and peripheral blood after traumatic spinal cord injury: a prospective pilot study.

PURPOSE: Biochemical biomarkers to determine the injury severity and the potential for functional recovery of traumatic spinal cord injury (TSCI) are highly warranted; however, it remains to be clarified whether cerebrospinal fluid (CSF) or peripheral blood (PB) is the ideal sample media. This study aims to measure and compare biomarker concentrations in CSF and PB and to explore associations between biomarker concentrations and injury severity, i.e., American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade, and biomarker concentrations and clinical outcome, i.e., AIS grade improvement and Spinal Cord Independent Measure version III (SCIM-III) score. METHODS: From 2018 to 2020, we conducted a single-center prospective pilot study of TSCI patients (n=15) and healthy controls (n=15). Sample collection and clinical outcome assessment were performed at median 13 h [IQR: 19], 9 days [IQR: 2], and 148 days [IQR: 49] after TSCI. Concentrations of neuron-specific enolase (NSE); glial fibrillary acid protein (GFAP); neurofilament light chain (NfL); interferon-γ (IFN-γ); interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, and IL-13; and tumor necrosis factor α (TNF-α) were measured and associated to clinical outcomes. RESULTS: The biomarker concentrations were higher in CSF than PB. CSF concentrations of GFAP, NSE, IFN-y, TNF-a, IL-2, IL-12p70, IL-4, IL-10, and IL-13 and PB concentrations of GFAP and IFN-y were significantly associated with AIS grade, but not with AIS grade improvement or SCIM-III score. CONCLUSIONS: Our results support GFAP as a potential diagnostic biomarker that may be measured in CSF as well as PB.

The inflammatory response and blood-spinal cord barrier integrity in traumatic spinal cord injury: a prospective pilot study.

PURPOSE: Triggering of inflammatory responses and disruption of blood-spinal cord barrier (BSCB) integrity are considered pivotal events in the pathophysiology of traumatic spinal cord injury (TSCI). Yet, these events are poorly understood and described in humans. This study aims to describe inflammatory responses and BSCB integrity in human TSCI. METHODS: Fifteen TSCI patients and fifteen non-TSCI patients were prospectively recruited from Aarhus University Hospital, Denmark. Peripheral blood (PB) and cerebrospinal fluid (CSF) were collected at median day 0 [IQR: 1], median day 9 [IQR: 2], and median day 148 [IQR: 49] after injury. PB and CSF were analyzed for immune cells by flow cytometry, cytokines by multiplex immunoassay, and BSCB integrity by IgG Index. RESULTS: Eleven TSCI patients completed follow-up. Results showed alterations in innate and adaptive immune cell counts over time. TSCI patients had significantly increased cytokine concentrations in CSF at the first and second follow-up, while only concentrations of interleukin (IL)-4, IL-8, and tumor necrosis factor-α remained significantly increased at the third follow-up. In PB, TSCI patients had significantly increased IL-6, IL-8, and IL-10 concentrations and significantly decreased interferon-γ concentrations at the first follow-up. Results further showed increased IgG Index indicative of BSCB disruption in seven TSCI patients at the first follow-up, five TSCI patients at the second follow-up, and two patients at the third follow-up. CONCLUSIONS: Our results suggest that TSCI mainly triggers innate inflammatory responses that resolves over time, although with some degree of non-resolving inflammation, particularly in CSF. Our results cannot confirm BSCB disruption in all TSCI patients.

Cerebrospinal fluid and peripheral blood proteomics in Traumatic Spinal Cord Injury: A prospective pilot study.

•Proteomics enable profiling of inflammatory responses after spinal cord injury.•Proteins are differentially expressed over time.•Proteins are differentially expressed in cerebrospinal fluid and peripheral blood.•A poor relationship exists between protein expression and neurological outcome.

Advanced magnetic resonance imaging of chronic whiplash patients: a clinical practice-based feasibility study.

BACKGROUND: Whiplash injury is common following road traffic crashes affecting millions worldwide, with up to 50% of the injured developing chronic symptoms and 15% having a reduced working capability due to ongoing disability. Many of these patients receive treatment in primary care settings based upon clinical and diagnostic imaging findings. Despite the identification of different types of injuries in the whiplash patients, clinically significant relationships between injuries and chronic symptoms remains to be fully established. This study investigated the feasibility of magnetic resonance imaging (MRI) techniques including quantitative diffusion weighted imaging and measurements of cerebrospinal fluid (CSF) flow as novel non-invasive biomarkers in a population of healthy volunteers and chronic whiplash patients recruited from a chiropractic clinic for the purpose of improving our understanding of whiplash injury. METHODS: Twenty chronic whiplash patients and 18 healthy age- and gender matched control subjects were included [mean age ± SD (sex ratio; females/males), case group: 37.8 years ± 9.1 (1.22), control group: 35.1 years ± 9.2 (1.25)]. Data was collected from May 2019 to July 2020. Data from questionnaires pertaining to the car crash, acute and current symptoms were retrieved and findings from clinical examination and MRI including morphologic, diffusion weighted and phase-contrast images were recorded. The apparent diffusion coefficient and fractional anisotropy were calculated, and measurement and analysis of CSF flow was conducted. Statistical analyses included Fisher's exact test, Mann Whitney U test and analysis of variance between groups. RESULTS: The studied population was described in detail using readily available clinical tools. No statistically significant differences were found between the groups on MRI. CONCLUSIONS: This study did not show that MRI-based measures of morphology, spinal cord and nerve root diffusion or cerebrospinal fluid flow are sensitive biomarkers to distinguish between chronic whiplash patients and healthy controls. The detailed description of the chronic whiplash patients using readily available clinical tools may be of great relevance to the clinician. In the context of feasibility, clinical practice-based advanced imaging studies with a technical setup similar to the presented can be expected to have a high likelihood of successful completion.

Comparison of outcomes and complications between one- and two-level anterior cervical discectomy and fusion: a population-based study of 410 patients.

OBJECTIVE: The objective of this study was to compare outcomes and patient satisfaction, and secondly to compare complication rates between one- and two-level anterior cervical discectomy and fusion (ACDF) for cervical radiculopathy. METHODS: Data from patients receiving one- or two-level ACDF for cervical radiculopathy at two institutions were prospectively collected and retrospectively analysed. Patients were separated into one-level ACDF and two-level ACDF. Comparison analyses of patient-reported outcome measures (PROMs) comprising Visual Analogue Scale for neck pain (VAS-NP) and arm pain (VAS-AP), Neck Disability Index (NDI), and EQ-5D 3-level version (EQ-5D-3L) were performed between baseline and 1-year follow-up and between groups as well as achievement of minimal clinically important differences (MCID) in PROMs and satisfaction. Additionally, complications were compared between groups. RESULTS: A total of 410 patients (270 one-level and 140 two-level) were included. PROMs improved significantly from baseline to 1-year follow-up (p < 0.001) in both groups. When comparing PROMs between one- and two-level ACDF, a trend towards greater improvement was observed in patients undergoing one-level ACDF, notably in EQ-5D-3L (p = 0.073). Significantly more patients in the one-level group achieved MCID in VAS-NP compared to patients in the two-level group (56% vs 44%, p = 0.025). Two hundred and ninety-six (67%) patients reported to be satisfied, but the one-level group trended to be more satisfied (70% vs. 62%). One-level ACDF further demonstrated a trend of more favourable complication profiles; however, complication rates were low in both groups. The risk of intraoperative complications was 2.4%, postoperative complications in-hospital were 1.2%, and patient-reported postoperative events post-discharge 42%. CONCLUSIONS: One- and two-level ACDF are effective procedures for degenerative cervical nerve root compression. Yet, significantly more patients in the one-level group achieved MCID in neck pain compared to patients in the two-level group.

Predictors of patient satisfaction following anterior cervical discectomy and fusion for cervical radiculopathy.

OBJECTIVE: To evaluate whether preoperative patient-reported outcome measures (PROMs) and immediate postoperative arm pain improvement can predict patient satisfaction following anterior cervical spine surgery. METHODS: A retrospective analysis of prospectively collected data from 193 patients with cervical radiculopathy undergoing surgery at Aarhus University Hospital was performed. Standardized questionnaires were used to assess demographics, clinical outcomes and complications preoperatively, postoperatively and at 1-year follow-up. PROMs covered Visual Analogue Scale for arm pain (VAS-AP) and neck pain (VAS-NP), Neck Disability Index (NDI), EQ-5D 3-level version (EQ-5D-3L), and satisfaction. Immediate upper extremity pain status was assembled from medical records. RESULTS: PROMs significantly improved (p < 0.001) and most patients (66%) were satisfied with the surgical result at follow-up. Complications and complaints occurred in 3.6% intraoperatively, 1.5% postoperatively in-hospital, and 43% postoperatively post-discharge. Patients with a symptom duration exceeding 24 months had significantly decreased odds of being satisfied compared to patients with a symptom duration less than 3 months (OR: 0.32, 95% CI: 0.10-0.98, p = 0.046). Neither baseline PROMs nor immediate pain improvement significantly predicted patient satisfaction. Despite being non-significant, patients experiencing immediate pain improvement had increased odds of being satisfied compared to patients not experiencing immediate improvement (OR: 1.62, 95% CI: 0.65-4.05). CONCLUSIONS: Prolonged symptom duration and immediate pain improvement may have an impact on patient satisfaction.

Early clinical predictors of functional recovery following traumatic spinal cord injury: a population-based study of 143 patients.

BACKGROUND: Traumatic spinal cord injuries (TSCI) are associated with uncertainty regarding the prognosis of functional recovery. The aim of the present study was to evaluate the potential of early clinical variables to predict the degree of functional independence assessed by Spinal Cord Independence Measure III (SCIM-III) up to 1 year after injury. METHODS: Prospectively collected data from 143 SCI patients treated in Western Denmark during 2012-2019 were retrospectively analysed. Data analysis involved univariate methods and multivariable linear regression modelling total SCIM-III scores against age, gender, body mass index (BMI), comorbidity, American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades A-B and C-D, ASIA Motor Score (AMS), timing of surgical treatment and occurrence of medical complications. Statistical significance was set at p < .05. RESULTS: Univariate analyses indicated that variables significantly associated with decreased functional independence included increased age (p = .023), increased BMI (p = .012), pre-existing comorbidity (p = .001), AIS grades A-B (p < .001), decreased AMS (p < .001) and occurrence of medical complications (p < .001). However, in the multivariable regression model were pre-existing comorbidity (p = .010), AIS grades A-B (p < .001), low AMS (p < .001) and late surgical treatment (p = .018) significant predictors of decreased functional independence 1 year after injury. CONCLUSION: TSCI patients with greatest potential for functional recovery up to 1 year after injury seem to be patients that immediately after trauma present with few or no comorbidities, who sustain motor-incomplete injuries and undergo early decompressive surgery.

A Brief Overview of the Cerebrospinal Fluid System and Its Implications for Brain and Spinal Cord Diseases.

A comprehensive understanding of the cerebrospinal fluid (CSF) system is essential for our understanding of health and disease within the central nervous system (CNS). The system of CSF refers to all components involved in CSF production, movement, and absorption. In recent years, extensive research has resulted in vastly improved understanding of the CSF system in health and disease. Yet, several aspects remain to be fully clarified, notably along the spinal cord as the preponderance of research has focused on the brain. This review briefly summarizes the CSF system and its implications for CNS diseases and highlights the knowledge gaps that require further research.

Outcome and negative events in thoracic disc herniation surgery: a Danish registry study.

BACKGROUND: Thoracic disc herniation (TDH) is a surgically demanding entity. Various surgical approaches have been developed and advanced in an attempt to achieve sufficient outcomes and reduce consecutive complication rates. Still, controversy exists regarding selecting the best surgical approach. This retrospective study aims to support decision-making regarding surgical approach. METHODS: We performed a retrospective analysis of 71 patients who underwent thoracic discectomy at Aarhus University Hospital, Denmark, between 1996 and 2015. Patients were divided into two groups depending on whether a lateral approach or a posterior approach was used. Data on demographics, symptomatology, peri- and post-operative events, length of hospitalization and discharge disposition were assembled from medical records. RESULTS: Lateral and posterior approach had an approximately equal peri-operative event rate (39% versus 36%), whereas the lateral approach was associated with a higher post-operative event rate in-hospital and post-discharge than the posterior approach (50% versus 18%; 45% versus 40%). The overall probability of improvement in clinical outcome regardless approach at follow-up was 77% in the short-term and 80% in the long-term. Odds of clinical improvement at any time point was 29% higher with the lateral approach than with the posterior approach (OR = 1.29, 95% CI: 0.52-3.21, p = .76). Adjusting for time, the odds of clinical improvement at short-term follow-up was twice as high for the lateral than for the posterior approach (OR = 2.16, 95% CI: 0.16-30.11); however, the trend seems to fade away over time (OR = 1.10, 95% CI: 0.07-17.55). CONCLUSIONS: The probability of improving after TDH surgery is good. However, a clear conclusion regarding the best surgical approach cannot be established; thus, surgeons should consider pros and cons of each approach when allocating a patient to surgery.

[Cerebrospinal fluid flow dynamics and the potential of phase-contrast MRI in syringomyelia].

Cerebrospinal fluid flow dynamics are not fully understood. However, it is well known, that flow dynamics play a crucial role in development and treatment of a wide variety of diseases in the central nervous system, among them, syringomyelia. Hence, in-depth knowledge of the mechanisms underlying flow dynamics is of great interest to improve diagnostics, prognostics, and to assess treatment efficacy. In this review we argue, that phase-contrast MRI may have these attributes, as it introduces detailed non-invasive qualitative and quantitative information on cerebrospinal fluid flow dynamics.

The incidence and effect of tethered cord release for tethered cord syndrome in patients with myelomeningocele: a population-based study.

OBJECTIVE: The goal of this study was to establish an incidence and assess the effect of tethered cord release for tethered cord syndrome in patients with myelomeningocele. METHODS: The study population was based on the Western Denmark Myelomeningocele Database, which contains all patients born with myelomeningocele in western Denmark since 1970. The study population was cross-referenced in 2015 with a database for surgical procedures containing all surgical procedures performed in the central Denmark region since 1996. Patients alive between 1996 and 2015 were identified. Incidences was calculated and presented for year of age. File reviews were conducted for all patients who underwent the procedure. Follow-up was divided into short-term and long-term follow-up. RESULTS: One hundred sixty-six patients were alive during various time periods between 1996 and 2015. Of these, 45 patients underwent the procedure. Seven underwent reoperation. The median age for the procedure was 12 years and the highest incidence was found at 15 years of age. Incidence was bimodal with highest incidence in children and adolescents. The most common indications were progressive spine deformity (40%), deteriorating ambulation (38%), and deteriorating neurogenic bladder and/or bowel dysfunction (32%). The mean short-term follow-up was 4.7 months and the mean long-term follow-up was 72.6 months. Postoperatively, the majority had improved (27%) or stabilized (27%) at short-term follow-up. At long-term follow-up, most patients were stable (27%) or had deteriorated (24%). For both follow-up terms there was a loss of approximately one-third of all patients. Complications occurred in 17% of the procedures. CONCLUSIONS: In this population-based study, tethered cord release has the highest incidence in children and adolescents. The beneficial effect of the procedure seems to be short term. Due to the uncertainty of a long-term effect of the procedure in patients with myelomeningocele and the registered complications, the authors suggest that this surgical indication should be reserved for well-selected patients.

Cranial nerve palsies due to incidental durotomy in lumbar Spine surgery: a case report.

We present a 65-year old man who underwent a partial laminectomy at L4. During surgery an incidental durotomy (ID) appeared. Postoperatively he developed cranial nerve palsies. Subsequent to surgical closure of the ID, symptoms completely resolved within three months.

Characteristics and outcomes in patients with primary intraspinal tumours.

INTRODUCTION: We report a retrospective cohort study aimed at presenting data on incidence, patient char-ac-teristics, tumour type, level of pathology, clinical status before and after surgery and complications in patients with surgically treated primary intraspinal tumours (PIST) in Western Denmark. METHODS: Population-based data were retrieved from hospital files from 1 January 2010 to 31 December 2015. RESULTS: In total, 78 males and 88 females with PIST were included in the study. Incidence per 100,000 persons per year in the population-based cohort was 2.18. The incidence of malignant PIST was 0.14 and the incidence of non-malignant PIST was 2.03. We found 25 extradural tumours, 100 intradural extramedullary tumours and 41 intramedullary tumours. Eleven were malignant and 155 were benign tumours. Schwannoma, meningioma and ependymoma were more common in adults, whereas haemangioblastoma, neurofibroma and epidermoid cysts were seen in 14 paediatric cases. Motor function disturbances were found in 38% of cases. Sensory disturbances were found in 54% of cases, and worsening of sensory functions was the most frequent post-operative sequela. Ataxia and neurogenic bowel/bladder dysfunction seem to constitute the highest risk in cases of intramedullary tumours. Pain was found in 75% of cases and was the most common symptom among all patients with PITS with a 58% improvement after surgery. Complications were recorded in 12% of cases. CONCLUSIONS: The incidence of PIST seems to be higher in Western Denmark than in other European studies. PIST are rare in children. FUNDING: none. TRIAL REGISTRATION: not relevant.