Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND OBJECTIVES: The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH. METHODS: The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade (p = 0.10). RESULTS: Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56). DISCUSSION: This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.

Accurate placement of thoracolumbar pedicle screws using a handheld iOS-based navigation device: a prospective intra-patient agreement study.

BACKGROUND: Accurate pedicle screw placement is a challenge with reported misplacement rates of 10% and higher. A handheld navigation device (HND) may provide accuracy equal to CT-based navigation (CT-Nav) but without the cost and complexity. OBJECTIVE: To study the accuracy of a handheld navigation device for pedicle screw placement. STUDY DESIGN: This prospective cross-sectional study with consistently applied reference standard enrolled 20 patients undergoing 92 pedicle screw placements. PATIENTS: Patients who underwent pedicle screw placement between May 2022 and September 2022. OUTCOME MEASURES: Pedicle screw placement accuracy per Gertzbein-Robbins. METHODS: Once the screw pilot hole was established, the proposed trajectory of the HND was compared with that proposed by CT-Nav. Postoperatively, screw accuracy was graded according to Gertzbein-Robbins by a blinded radiologist based on CT scans. Accuracy was compared between the two systems and published control for fluoroscopy assisted and CT-Nav placement using Bayesian posterior distribution. RESULTS: The trajectory proposed by the HND and CT-Nav were in agreement in 98.9% (95% Exact CI; 94.09%-99.97%). The HND accuracy was 98.9% with 91 screws rated "A" and 1 rated "C". Non-inferiority to fluoroscopic placement was achieved because the one-sided normal-approximation 95% CI Lower Bound (LB) of 95.3% is greater than the Performance Goal (PG) of 83.4%. Post-hoc analysis demonstrated that the probability of superiority of the HND relative to the historical accuracy rate of 91.5% for fluoroscopy assisted procedures is >0.999 and that the HND's accuracy rate is within 4.5% of CT-Nav of 95.5% is >0.999. No adverse events or intra-operative complications associated with HND were observed. There was 1 (1.1%) intra-operative repositioning and no re-operations for any reason. CONCLUSIONS: The accuracy rate of the HND was 98.9%, and the proposed trajectory matched with CT-Nav in 98.9% of the time. This is superior to the historical published accuracy rate for fluoroscopy-assisted procedures and equivalent to the historical published accuracy rate for CT-Nav. CLINICAL TRIAL REGISTRATION NUMBER: Dutch trial register NL74268.058.20.

Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post-Hoc Analysis of the ULTRA Trial.

BACKGROUND AND OBJECTIVES: The ULTRA-trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at six months. An expected proportion of the included patients had non-aneurysmal subarachnoid hemorrhage In this post-hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at six months. METHODS: The ULTRA-trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013 and January 20, 2020. After confirmation of subarachnoid hemorrhage on non-contrast computer tomography, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care, or usual care only. In this post-hoc analysis, we included all ULTRA-participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at six months, assessed by the modified Rankin Scale, dichotomized into good (0-3) and poor (4-6) outcome. RESULTS: Of the 813 ULTRA-trial patients who had an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio (aOR) 0·92; 95% confidence interval (C.I.) 0·69 to 1·24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) aOR 0.76, 95% C.I. 0.57-1.03, all-cause mortality at 30 days aOR 0.91, 95% C.I. 0.65-1.28), all-cause mortality at six months aOR 1.10 (95% C.I. 0.80-1.52). DISCUSSION: Ultra-early and short-term tranexamic acid treatment did not improve clinical outcome at six months in patients with aneurysmal subarachnoid hemorrhage and therefore, cannot be recommended. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24th, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.

Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial.

BACKGROUND: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months. METHODS: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812. FINDINGS: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups. INTERPRETATION: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale. FUNDING: Fonds NutsOhra.

The European Robotic Spinal Instrumentation (EUROSPIN) study: protocol for a multicentre prospective observational study of pedicle screw revision surgery after robot-guided, navigated and freehand thoracolumbar spinal fusion.

INTRODUCTION: Robotic guidance (RG) and computer-assisted navigation (NV) have seen increased adoption in instrumented spine surgery over the last decade. Although there exists some evidence that these techniques increase radiological pedicle screw accuracy compared with conventional freehand (FH) surgery, this may not directly translate to any tangible clinical benefits, especially considering the relatively high inherent costs. As a non-randomised, expertise-based study, the European Robotic Spinal Instrumentation Study aims to create prospective multicentre evidence on the potential comparative clinical benefits of RG, NV and FH in a real-world setting. METHODS AND ANALYSIS: Patients are allocated in a non-randomised, non-blinded fashion to the RG, NV or FH arms. Adult patients that are to undergo thoracolumbar pedicle screw instrumentation for degenerative pathologies, infections, vertebral tumours or fractures are considered for inclusion. Deformity correction and surgery at more than five levels represent exclusion criteria. Follow-up takes place at 6 weeks, as well as 12 and 24 months. The primary endpoint is defined as the time to revision surgery for a malpositioned or loosened pedicle screw within the first postoperative year. Secondary endpoints include patient-reported back and leg pain, as well as Oswestry Disability Index and EuroQOL 5-dimension questionnaires. Use of analgesic medication and work status are recorded. The primary analysis, conducted on the 12-month data, is carried out according to the intention-to-treat principle. The primary endpoint is analysed using crude and adjusted Cox proportional hazards models. Patient-reported outcomes are analysed using baseline-adjusted linear mixed models. The study is monitored according to a prespecified monitoring plan. ETHICS AND DISSEMINATION: The study protocol is approved by the appropriate national and local authorities. Written informed consent is obtained from all participants. The final results will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: Clinical Trials.gov registry NCT03398915; Pre-results, recruiting stage.

Reoperation After Primary Lumbar Discectomy with or without Implantation of a Bone-Anchored Annular Closure Device: Surgical Strategies and Clinical Outcomes.

OBJECTIVE: To determine whether presence of a bone-anchored annular closure device (ACD) impacts reoperation strategies and subsequent outcomes. METHODS: Patients with large annular defects after single-level limited lumbar discectomy were randomly allocated to receive an ACD or discectomy alone (controls) and were followed for at least 3 years. RESULTS: Among 550 patients, reoperation risk was lower with ACD (11.0% vs. 19.3%). The types of reoperations and operative time were similar in each group, and the ACD did not interfere with surgical planning or operative technique. Fusion success was 87% with ACD versus 85% for controls. Perioperative complications occurred in 22% and 19% of reoperations, respectively. Leg pain and back function were improved with ACD versus controls after fusion procedures, and no group differences were observed after non-fusion reoperations. CONCLUSIONS: In patients undergoing post-discectomy reoperation, patients with an ACD were treated with similar operative techniques, were not exposed to additional surgical risks, and reported comparable clinical outcomes versus those without an ACD.

Comparison of treatments for lumbar disc herniation: Systematic review with network meta-analysis.

STUDY DESIGN: Systematic review with network meta-analysis. OBJECTIVE: To compare patient outcomes of lumbar discectomy with bone-anchored annular closure (LD + AC), lumbar discectomy (LD), and continuing conservative care (CC) for treatment of lumbar disc herniation refractory to initial conservative management. SUMMARY OF BACKGROUND DATA: Several treatment options are available to patients with refractory symptoms of lumbar disc herniation, but their comparative efficacy is unclear. METHODS: A systematic review was performed to compare efficacy of LD + AC, LD, and CC for treatment of lumbar disc herniation. Outcomes included leg pain, back pain, disability (each reported on a 0-100 scale), reherniation, and reoperation. Data were analyzed using random effects network meta-analysis. RESULTS: This review included 14 comparative studies (8 randomized) involving 3947 patients-11 studies of LD versus CC (3232 patients), 3 studies of LD + AC versus LD (715 patients), and no studies of LD + AC versus CC. LD was more effective than CC in reducing leg pain (mean difference [MD] -10, P < .001) and back pain (MD -7, P < .001). LD + AC was more effective than LD in reducing risk of reherniation (odds ratio 0.38, P < .001) and reoperation (odds ratio 0.33, P < .001). There was indirect evidence that LD + AC was more effective than CC in reducing leg pain (MD -25, P = .003), back pain (MD -20, P = .02), and disability (MD -13, P = .02) although the treatment effect was smaller in randomized trials. CONCLUSIONS: Results of a network meta-analysis show LD is more effective than CC in alleviating symptoms of lumbar disc herniation refractory to initial conservative management. Further, LD + AC lowers risk of reherniation and reoperation versus LD and may improve patient symptoms more than CC.

Maintaining endotracheal tube cuff pressure at 20 mmHg during anterior cervical spine surgery to prevent dysphagia: a double-blind randomized controlled trial.

PURPOSE: Anterior cervical spine surgery is associated with postoperative dysphagia, sore throat and dysphonia. It is unclear, whether this is caused by increased endotracheal tube (ETT) cuff pressure after retractor placement. This study aims to assess the effect of ETT cuff pressure adjustment on postoperative dysphagia, sore throat and dysphonia. METHODS: In this, single-centre, observer and patient-blinded randomized controlled trial patients treated with anterior cervical spine surgery were randomized to adjustment of the ETT cuff pressure to 20 mmHg after placement of the retractor versus no adjustment. Primary outcome was the incidence and severity of postoperative dysphagia. Secondary outcomes were sore throat and dysphonia. Outcomes were evaluated on day one and 2 months after the operation. RESULTS: Of 177 enrolled patients, 162 patients (92.5%) could be evaluated. The incidence of dysphagia was 75.9% on day one and 34.6% 2 months after surgery. Dysphagia in the intervention and control group was present in 77.8% versus 74.1% of patients on day one (odds ratio (OR) 1.2, 95% confidence interval (CI) (0.6-2.5)) and 28.4% versus 40.7% of patients after 2 months (OR 0.6, 95% CI 0.3-1.1), respectively. Severity of dysphagia, sore throat and dysphonia was similar in both groups. CONCLUSIONS: Anterior cervical spine surgery is accompanied by a high incidence of postoperative dysphagia, lasting until at least 2 months after surgery in over a third of our patients. Adjusting ETT cuff pressure to 20 mmHg after retractor placement, as compared to controls, did not lower the risk for both short- and long-term dysphagia. Netherlands National Trial Registry Number: NTR 3542. These slides can be retrieved under electronic supplementary material.

Porous silicon nitride spacers versus PEEK cages for anterior cervical discectomy and fusion: clinical and radiological results of a single-blinded randomized controlled trial.

PURPOSE: Anterior cervical discectomy with fusion is a common procedure for treating radicular arm pain. Polyetheretherketone (PEEK) plastic is a frequently used material in cages for interbody fusion. Silicon nitride is a new alternative with desirable bone compatibility and imaging characteristics. The aim of the present study is to compare silicon nitride implants with PEEK cages filled with autograft harvested from osteophytes. METHODS: The study is a prospective, randomized, blinded study of 100 patients with 2 years follow-up. The primary outcome measure was improvement in the Neck Disability Index. Other outcome measures included SF-36, VAS arm pain, VAS neck pain, assessment of recovery, operative characteristics, complications, fusion and subsidence based on dynamic X-ray and CT scan. RESULTS: There was no significant difference in NDI scores between the groups at 24 months follow-up. At 3 and 12 months the NDI scores were in favor of PEEK although the differences were not clinically relevant. On most follow-up moments there was no difference in VAS neck and VAS arm between both groups, and there was no statistically significant difference in patients' perceived recovery during follow-up. Fusion rate and subsidence were similar for the two study arms and about 90% of the implants were fused at 24 months. CONCLUSIONS: Patients treated with silicon nitride and PEEK reported similar recovery rates during follow-up. There was no significant difference in clinical outcome at 24 months. Fusion rates improved over time and are comparable between both groups.

Quality of life after different surgical procedures for the treatment of spinal metastases: results of a single-center prospective case series.

OBJECTIVE The performance of surgery for spinal metastases is rapidly increasing. Different surgical procedures, ranging from stabilization alone to stabilization combined with corpectomy, are thereby performed for various indications. Little is known about the impact of these different procedures on patient quality of life (QOL), but this factor is crucial when discussing the various therapeutic options with patients and their families. Thus, the authors of this study investigated the effect of various surgical procedures for spinal metastases on patient QOL. METHODS The authors prospectively followed a cohort of 113 patients with spinal metastases who were referred to their clinic for surgical evaluation between July 2012 and July 2014. Quality of life was assessed using the EQ-5D at intake and at 3, 6, 9, and 12 months after treatment. RESULTS Nineteen patients were treated conservatively, 41 underwent decompressive surgery with or without stabilization, 47 underwent a piecemeal corpectomy procedure with stabilization and expandable cage reconstruction, and 6 had a stabilization procedure without decompression. Among all surgical patients, the mean EQ-5D score was significantly increased from 0.44 pretreatment to 0.59 at 3 months after treatment (p < 0.001). Mean EQ-5D scores at 1 year after surgery further increased to 0.84 following decompression with stabilization, 0.74 after corpectomy with stabilization, and 0.94 after stabilization without decompression. Frankel scores also improved after surgery. There were no significant differences in improvements in EQ-5D scores and Frankel grades among the different surgical procedures. In addition, mortality and complication rates were similar. CONCLUSIONS Quality of life can improve significantly after various extensive and less extensive surgical procedures in patients with spinal metastases. The relatively invasive corpectomy procedure, as compared with alternative less invasive techniques, does not negatively affect outcome.

Juvenile chronic arthritis and the craniovertebral junction in the paediatric patient: review of the literature and management considerations.

INTRODUCTION: Juvenile chronic arthritis (JCA) is a systemic disease of childhood affecting particularly joints. JCA is a heterogeneous group of inflammatory joint disorders with onset before the age of 16 years and is comprised of 7 subtype groups. The pathogenesis of JCA seen in the cervical spine is synovial inflammation, hyperaemia, and pannus formation at the occipitoatlantoaxial joints resulting in characteristic craniovertebral junction findings. Treatment of craniovertebral junction instability as a result of JCA is a challenge. The best treatment strategy may be difficult because of various radiological and clinical severities. A review of the literature and management considerations is presented. REVIEW: No randomised controlled trial or systematic review on this subject has been published. Only experts' opinions, case reports, and case series have been described. Thirty-four studies have been reviewed in this study. Involvement of the cervical spine in patients with JCA can lead to pain and functional disability. The subtypes that usually affect the cervical spine are the polyarticular type and systemic onset type and rarely the pauciarticular type. The most common cervical spine changes related to JCA are as follows: (1) apophyseal joint ankylosis at C2-C3, (2) atlantoaxial subluxation, (3) atlantoaxial impaction, (4) atlantoaxial rotatory fixation, and (5) growth disturbances of the cervical spine. The incidence of severe subluxations has decreased in the last decade as result of antirheumatoid drugs and biologicals. However, neurological compromise still occurs in JCA patients necessitating surgical treatment. CONCLUSION: Whenever the cervical spine is involved in rheumatoid arthritis patients without neurological deficits, conservative treatment is legitimate. Once patients develop neurological signs and symptoms, surgical treatment should be considered with particular focus to age, severity of the disease, and general health condition. Skilled anaesthesia is crucial and the surgical procedure should only be carried out in centres with experience in craniovertebral junction abnormalities.

Maintaining endotracheal tube cuff pressure at 20 mm Hg to prevent dysphagia after anterior cervical spine surgery; protocol of a double-blind randomised controlled trial.

BACKGROUND: In anterior cervical spine surgery a retractor is obligatory to approach the spine. Previous studies showed an increase of endotracheal tube cuff pressure after placement of a retractor. It is known that high endotracheal tube cuff pressure increases the incidence of postoperative dysphagia, hoarseness, and sore throat. However, until now no evidence supports the fact whether adjusting the endotracheal tube cuff pressure during anterior cervical spine surgery will prevent this comorbidity. We present the design of a randomized controlled trial to determine whether adjusting endotracheal tube cuff pressure after placement of a retractor during anterior cervical spine surgery will prevent postoperative dysphagia. METHODS/DESIGN: 177 patients (aged 18-90 years) scheduled for anterior cervical spine surgery on 1 or more levels will be included. After intubation, endotracheal tube cuff pressure is manually inflated to 20 mm Hg in all patients. Patients will be randomized into two groups. In the control group endotracheal tube cuff pressure is not adjusted after retractor placement. In the intervention group endotracheal tube cuff pressure after retractor placement is maintained at 20 mm Hg and air is withdrawn when cuff pressure exceeds 20 mm Hg. Endotracheal tube cuff pressure is measured after intubation, before and after placement and removal of the retractor. Again air is inflated if cuff pressure sets below 20 mmHg after removal of the retractor. The primary outcome measure is postoperative dysphagia. Other outcome measures are postoperative hoarseness, postoperative sore throat, degree of dysphagia, length of hospital stay, and pneumonia. The study is a single centre double blind randomized trial in which patients and research nurses will be kept blinded for the allocated treatment during the follow-up period of 2 months. DISCUSSION: Postoperative dysphagia occurs frequently after anterior cervical spine surgery. This may be related to high endotracheal tube cuff pressure. Whether adaptation and maintaining the pressure after placement of the retractor will decrease the incidence of dysphagia, has to be determined by this trial. TRIAL REGISTRATION: Netherlands Trial Register (NTR) 3542: http://www.trialregister.nl.

The CASCADE trial: effectiveness of ceramic versus PEEK cages for anterior cervical discectomy with interbody fusion; protocol of a blinded randomized controlled trial.

BACKGROUND: Anterior cervical discectomy with interbody fusion cages is considered the standard surgical procedure in patients with cervical disc herniation. However, PEEK or metal cages have some undesirable imaging characteristics, leading to a search for alternative materials not creating artifacts on images; silicon nitride ceramic. Whether patients treated with silicon nitride ceramic cages have similar functional outcome as patients treated with PEEK cages is not known. We present the design of the CASCADE trial on effectiveness of ceramic cages versus PEEK cages in patients with cervical disc herniation and/or osteophytes. METHODS/DESIGN: Patients (age 18-75 years) with monoradicular symptoms in one or both arms lasting more than 8 weeks, due to disc herniation and/or osteophytes, are eligible for the trial. The study is designed as a randomized controlled equivalence trial in which patients are blinded to the type of cage for 1 year. The total follow-up period is 2 years. The primary outcome measure is improvement in the Neck and Disability Index (NDI). Secondary outcomes measures include improvement in arm pain and neck pain (VAS), SF-36 and patients' perceived recovery. The final elements of comparison are perioperative statistics including operating time, blood loss, length of hospital stay, and adverse events. Lateral plane films at each follow-up visit and CT scan (at 6 months) will be used to judge fusion and the incidence of subsidence. Based on a power of 90% and assuming 8% loss to follow-up, 100 patients will be randomized into the 2 groups. The first analysis will be conducted when all patients have 1 year of follow-up, and the groups will be followed for 1 additional year to judge stability of outcomes. DISCUSSION: While the new ceramic cage has received the CE Mark based on standard compliance and animal studies, a randomized comparative study with the golden standard product will provide more conclusive information for clinicians. Implementation of any new device should only be done after completion of randomized controlled effectiveness trials.

Neurologic outcome of surgical and conservative treatment of rheumatoid cervical spine subluxation: a systematic review.

OBJECTIVE: Rheumatoid arthritis commonly involves the upper cervical spine and can cause significant neurologic morbidity and mortality. However, there is no consensus on the optimal timing for surgical intervention: whether surgery should be performed prophylactically or once neurologic deficits have become apparent. METHODS: A systematic review of the literature was performed to analyze neurologic outcome (Ranawat) and survival time (Kaplan-Meier) after surgical or conservative treatment using the MOOSE (Meta-analysis Of Observational Studies in Epidemiology) and GRADE (Grading of Recommendations, Assessment, Development and Evaluation system) criteria. RESULTS: Twenty-five observational studies were selected. No randomized controlled trials (RCTs) could be found. All of the studies had a high risk of bias. Twenty-three studies reported the neurologic outcome after surgery for 752 patients. Neurologic deterioration rarely occurred in Ranawat I and II patients. Ranawat III patients did not fully recover. The 10-year survival rates were 77%, 63%, 47%, and 30% for Ranawat I, II, IIIA, and IIIB, respectively. The Ranawat IIIB patients had a significantly worse outcome. Another 185 patients treated conservatively were described in 7 studies. Neurologic deterioration rarely occurred in Ranawat I patients, but was almost inevitable in Ranawat II, IIIA, and IIIB patients. The Kaplan-Meier analysis showed a 10-year overall survival rate of 40%. CONCLUSION: There are no RCTs that compared surgery with conservative treatment. In observational studies, surgical neurologic outcomes were better than conservative treatment in all patients with cervical spine involvement, and in asymptomatic patients with no neurologic impairment (Ranawat I) the outcomes were similar; however, the evidence is weak. Survival time of surgical and conservative treatment could not be compared.

Rationale and design of The Delphi Trial--I(RCT)2: international randomized clinical trial of rheumatoid craniocervical treatment, an intervention-prognostic trial comparing 'early' surgery with conservative treatment [ISRCTN65076841].

BACKGROUND: Rheumatoid arthritis is a chronic inflammatory disease, which affects 1% of the population. Hands and feet are most commonly involved followed by the cervical spine. The spinal column consists of vertebrae stabilized by an intricate network of ligaments. Especially in the upper cervical spine, rheumatoid arthritis can cause degeneration of these ligaments, causing laxity, instability and subluxation of the vertebral bodies. Subsequent compression of the spinal cord and medulla oblongata can cause severe neurological deficits and even sudden death. Once neurological deficits occur, progression is inevitable although the rapidity of progression is highly variable. The first signs and symptoms are pain at the back of the head caused by compression of the major occipital nerve, followed by loss of strength of arms and legs. The severity of the subluxation can be observed with radiological investigations (MRI, CT) with a high sensitivity. The authors have sent a Delphi Questionnaire about the current treatment strategies of craniocervical involvement by rheumatoid arthritis to an international forum of expert rheumatologists and surgeons. The timing of surgery in patients with radiographic instability without evidence of neurological deficit is an area of considerable controversy. If signs and symptoms of myelopathy are present there is little chance of recovery to normal levels after surgery. DESIGN: In this international multicenter randomized clinical trial, early surgical atlantoaxial fixation in patients with rheumatoid arthritis and radiological abnormalities without neurological deficits will be compared with prolonged conservative treatment. The main research question is whether early surgery can prevent radiological and neurological progression. A cost-effectivity analysis will be performed. 250 patients are needed to answer the research question. DISCUSSION: Early surgery could prevent serious neurological deficits, but may have peri-operative morbidity and loss of rotation of the head and neck. The objective of this study is to identify the best timing of surgery for patients at risk for the development of neurological signs and symptoms.