Cost-effectiveness of posterior versus anterior surgery for cervical radiculopathy: results from a multicentre randomised non-inferiority trial (FACET).

PURPOSE: For cervical nerve root compression, anterior cervical discectomy with fusion (anterior surgery) or posterior foraminotomy (posterior surgery) are safe and effective options. Posterior surgery might have a more beneficial economic profile compared to anterior surgery. The purpose of this study was to analyse if posterior surgery is cost-effective compared to anterior surgery. METHODS: An economic evaluation was performed as part of a multicentre, noninferiority randomised clinical trial (Foraminotomy ACDF Cost-effectiveness Trial) with a follow-up of 2 years. Primary outcomes were cost-effectiveness based on arm pain (Visual Analogue Scale (VAS; 0-100)) and cost-utility (quality adjusted life years (QALYs)). Missing values were estimated with multiple imputations and bootstrap simulations were used to obtain confidence intervals (CIs). RESULTS: In total, 265 patients were randomised and 243 included in the analyses. The pooled mean decrease in VAS arm at 2-year follow-up was 44.2 in the posterior and 40.0 in the anterior group (mean difference, 4.2; 95% CI, - 4.7 to 12.9). Pooled mean QALYs were 1.58 (posterior) and 1.56 (anterior) (mean difference, 0.02; 95% CI, - 0.05 to 0.08). Societal costs were €28,046 for posterior and €30,086 for the anterior group, with lower health care costs for posterior (€12,248) versus anterior (€16,055). Bootstrapped results demonstrated similar effectiveness between groups with in general lower costs associated with posterior surgery. CONCLUSION: In patients with cervical radiculopathy, arm pain and QALYs were similar between posterior and anterior surgery. Posterior surgery was associated with lower costs and is therefore likely to be cost-effective compared with anterior surgery.

Feasibility and optimal choice of stimulation parameters for supramaximal stimulation of motor evoked potentials.

PURPOSE: The aim was to investigate the feasibility and optimal stimulation parameters for supramaximal stimulation of muscle recorded transcranial electrical stimulation motor evoked potentials (mTc-MEP). METHODS: Forty-seven consecutive patients that underwent scoliosis surgery were included. First, the feasibility of supramaximal stimulation was assessed for two settings (setting 1: pulse duration 0.075ms, interstimulus interval (ISI) 1.5ms; setting 2: pulse duration 0.300ms, ISI 3ms). Thereafter, three mTc-MEP parameters were considered for both settings; (1) elicitability, (2) amplitude, and (3) if supramaximal stimulation was achieved with ≥ 20 V below maximum output. Finally, ISIs (1ms-4ms) were optimized for setting 1. RESULTS: Nine patients (19.15%) were excluded. Of the remaining patients, supramaximal stimulation was achieved in all patients for setting 1, and in 26 (68.42%) for setting 2. In one patient, mTc-MEPs were elicitable in more muscles for setting (1) Amplitudes were not significantly different. Stimulation voltage could be increased ≥ 20 V in all 38 patients for setting 1 and in 10 (38.46%) for setting (2) Optimal ISI's differed widely. CONCLUSION: We recommend using setting 1 when monitoring mTc-MEPs with supramaximal stimulation, after which an individualized ISI optimization can be performed. Moreover, when using supramaximal stimulation, short ISI's (i.e. 1ms or 1.5ms) can be the optimal ISI for obtaining the highest mTc-MEP amplitude.

The influence of depth of anesthesia and blood pressure on muscle recorded motor evoked potentials in spinal surgery. A prospective observational study protocol.

For high-risk spinal surgeries, intraoperative neurophysiological monitoring (IONM) is used to detect and prevent intraoperative neurological injury. The motor tracts are monitored by recording and analyzing muscle transcranial electrical stimulation motor evoked potentials (mTc-MEPs). A mTc-MEP amplitude decrease of 50-80% is the most common warning criterion for possible neurological injury. However, these warning criteria often result in false positive warnings. False positives may be caused by inadequate depth of anesthesia and blood pressure on mTc-MEP amplitudes. The aim of this paper is to validate the study protocol in which the goal is to investigate the effects of depth of anesthesia (part 1) and blood pressure (part 2) on mTc-MEPs. Per part, 25 patients will be included. In order to investigate the effects of depth of anesthesia, a processed electroencephalogram (pEEG) monitor will be used. At pEEG values of 30, 40 and 50, mTc-MEP measurements will be performed. To examine the effect of blood pressure on mTc-MEPs the mean arterial pressure will be elevated from 60 to 100 mmHg during which mTc-MEP measurements will be performed. We hypothesize that by understanding the effects of depth of anesthesia and blood pressure on mTc-MEPs, the mTc-MEP monitoring can be interpreted more reliably. This may contribute to fewer false positive warnings. By performing this study after induction and prior to incision, this protocol provides a unique opportunity to study the effects of depths of anesthesia and blood pressure on mTc-MEPs alone with as little confounders as possible. Trial registration number NL7772.

Intraoperative neurophysiological monitoring during scoliosis surgery in patients with Duchenne muscular dystrophy.

PURPOSE: Little is known about the reliability and value of intraoperative neurophysiological monitoring (IONM) in patients with Duchenne muscular dystrophy (DMD) undergoing scoliosis correction surgery. The aim of this study was to investigate the feasibility of IONM and the cortical excitability in these patients. METHODS: Fifteen patients with DMD and scoliosis and 15 patients with adolescent idiopathic scoliosis (AIS) underwent scoliosis correction surgery with the use of IONM. IONM consisted of transcranial electrical stimulation motor evoked potential (Tc-MEP) and somatosensory evoked potential (SSEP) monitoring. The highest Tc-MEP amplitudes were collected to test the feasibility. Preoperative compound muscle action potentials (CMAPs) and transcranial magnetic stimulation (TMS)-MEPs were recorded to test the cortical excitability. SSEPs were scored as elicitable or not elicitable. RESULTS: Tc-MEP amplitudes were significantly lower in the DMD group for both the gastrocnemius and tibialis anterior muscles. However, the abductor hallucis muscle had similar amplitudes in both the DMD as the AIS group. TMS/CMAP and Tc-MEP/CMAP ratios were similar in the DMD and AIS group (P = 0.126 and P = 0.792 respectively). CONCLUSIONS: Tc-MEP and SSEP monitoring is feasible, particularly when Tc-MEPs are recorded from the abductor hallucis muscle in patients with DMD. Similar TMS/CMAP and Tc-MEP/CMAP ratios show that there were no differences observed in cortical excitability between the groups. IONM seems a feasible and valuable neurophysiological tool to signal possible surgically induced damage to the spinal cord during scoliosis correction surgery in patients with DMD.

SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery.

BACKGROUND: Meningiomas are the most frequently occurring primary intracranial tumours in adults. Surgical removal can only be curative by complete resection; however surgical access can be challenging due to anatomical localization and local invasion of bone and soft tissues. Several intraoperative techniques have been tried to improve surgical resection, including intraoperative fluorescence guided imaging; however, no meningioma-specific (fluorescent) targeting has been developed yet. Here, we aimed to identify the most promising biomarkers for targeted intra-operative fluorescence guided meningioma surgery. METHODS: One hundred forty-eight meningioma specimens representing all meningioma grades were analysed using immunohistochemistry (IHC) on tissue microarrays (TMAs) to determine expression patterns of meningioma biomarkers epithelial membrane antigen (EMA), platelet-derived growth factor ß (PDGF-ß), vascular endothelial growth factor α (VEGF-α), and somatostatin receptor type 2 (SSTR-2). Subsequently, the most promising biomarker was selected based on TArget Selection Criteria (TASC). Marker expression was examined by IHC in 3D cell culture models generated from freshly resected tumour material. RESULTS: TMA-IHC showed strongest staining for SSTR-2. All cases were positive, with 51.4% strong/diffuse, 30.4% moderate/diffuse and only 18.2% focal/weak staining patterns. All tested biomarkers showed at least weak positivity in all meningiomas, regardless of WHO grade. TASC analysis showed that SSTR-2 was the most promising target for fluorescence guided imaging, with a total score of 21 (out of 22). SSTR-2 expression was determined on original patient tumours and 3D cultures of three established cultures. CONCLUSIONS: SSTR-2 expression was highly sensitive and specific in all 148 meningiomas, regardless of WHO grade. According to TASC analysis, SSTR-2 is the most promising receptor for meningioma targeting. After establishing in vitro meningioma models, SSTR-2 cell membrane expression was confirmed in two of three meningioma cultures as well. This indicates that specific fluorescence in an experimental setting can be performed for the further development of targeted fluorescence guided meningioma surgery and near-infrared fluorescent tracers targeting SSTR-2.

Bispectral index values and propofol concentrations at loss and return of consciousness in patients with frontal brain tumours and control patients.

BACKGROUND: The influence of frontal brain tumours on bispectral index (BIS) measurements and propofol requirements is unknown. The primary aim of our study was to determine whether BIS values recorded at loss and return of consciousness (LOC and ROC, respectively) differ between patients with unilateral frontal brain tumours and control patients. Secondary goals were to compare propofol requirements for LOC and to determine whether there were significant inter-hemispheric differences between BIS values in tumour and control patients. METHODS: We enrolled 20 patients with a frontal brain tumour and 20 control patients. Bilateral BIS measurements were done during induction of propofol anaesthesia, during recovery of consciousness, and during a second induction of anaesthesia. The isolated-forearm test was used to determine the moments of LOC1, ROC, and LOC2. Arterial blood samples were obtained every 4 min for determination of measured propofol concentrations. RESULTS: The median BIS values recorded at LOC1, ROC, and LOC2 did not differ between the groups. There were no significant inter-hemispheric differences in BIS in tumour and control patients. The median [inter-quartile range (IQR)] total propofol doses at LOC1 were 82 (75-92) and 78 (68-91) mg in tumour and control patients, respectively. The median (IQR) measured plasma propofol concentrations at LOC1 were 12 (9-14) and 13 (11-15) µg ml(-1) in the tumour and control groups, respectively. CONCLUSIONS: The presence of a frontal brain tumour did not affect ipsilateral BIS values, and so need not influence the placement of unilateral BIS electrodes if BIS monitoring is used to titrate propofol anaesthesia.

Multislice CT angiography in the selection of patients with ruptured intracranial aneurysms suitable for clipping or coiling.

INTRODUCTION: We sought to establish whether CT angiography (CTA) can be applied to the planning and performance of clipping or coiling in ruptured intracranial aneurysms without recourse to intraarterial digital subtraction angiography (IA-DSA). METHODS: Over the period April 2003 to January 2006 in all patients presenting with a subarachnoid haemorrhage CTA was performed primarily. If CTA demonstrated an aneurysm, coiling or clipping was undertaken. IA-DSA was limited to patients with negative or inconclusive CTA findings. We compared CTA images with findings at surgery or coiling in patients with positive CTA findings and in patients with negative and inconclusive findings in whom IA-DSA had been performed. RESULTS: In this study, 224 consecutive patients (mean age 52.7 years, 135 women) were included. In 133 patients (59%) CTA demonstrated an aneurysm, and CTA was followed directly by neurosurgical (n = 55) or endovascular treatment (n = 78). In 31 patients (14%) CTA findings were categorized as inconclusive, and in 60 (27%) CTA findings were negative. One patient received surgical treatment on the basis of false-positive CTA findings. In 17 patients in whom CTA findings were inconclusive, IA-DSA provided further diagnostic information required for correct patient selection for any therapy. Five ruptured aneurysms in patients with a nonperimesencephalic SAH were negative on CTA, and four of these were also false-negative on IA-DSA. On a patient basis the positive predictive value, negative predictive value, sensitivity, specificity and accuracy of CTA for symptomatic aneurysms were 99%, 90%, 96%, 98% and 96%, respectively. CONCLUSION: CTA should be used as the first diagnostic modality in the selection of patients for surgical or endovascular treatment of ruptured intracranial aneurysms. If CTA renders inconclusive results, IA-DSA should be performed. With negative CTA results the complementary value of IA-DSA is marginal. IA-DSA is not needed in patients with negative CTA and classic perimesencephalic SAH. Repeat IA-DSA or CTA should still be performed in patients with a nonperimesencephalic SAH.

Timing of aneurysm surgery in subarachnoid haemorrhage--an observational study in The Netherlands.

BACKGROUND: There is still lack of evidence on the optimal timing of surgery in patients with aneurysmal subarachnoid haemorrhage. Only one randomised clinical trial has been done, which showed no difference between early and late surgery. Other studies were observational in nature and most had methodological drawbacks that preclude clinically meaningful conclusions. We performed a retrospective observational study on the timing of aneurysm surgery in The Netherlands over a two-year period. METHOD: In eight hospitals we identified 1,500 patients with an aneurysmal subarachnoid haemorrhage. They were subjected to predefined inclusion criteria. We included all patients who were admitted and were conscious at any one time between admission and the end of the third day after the haemorrhage. We categorised the clinical condition on admission according the World Federation of Neurological Surgeons (WFNS) grading scale. Early aneurysm surgery was defined as operation performed within three days after onset of subarachnoid haemorrhage; intermediate surgery as performed on days four to seven, and late surgery as performed after day seven. Outcome was classified as the proportion of patients with poor outcome (death or dependent) two to four months after onset of subarachnoid haemorrhage. We calculated crude odds ratios with late surgery as reference. We distinguished between management results (reconstructed intention to treat analysis) and surgical results (on treatment analysis). The results were adjusted for the major prognosticators for outcome after subarachnoid haemorrhage. FINDINGS: We included 411 patients. There were 276 patients in the early surgery group, 36 in the intermediate surgery group and 99 in the late surgery group. On admission 78% were in good neurological condition (WFNS I-III). MANAGEMENT RESULTS: Overall, 93 patients (34%) operated on early had a poor outcome, 13 (36%) of those with intermediate surgery and 37 (37%) in the late surgery group had a poor outcome. For patients in good clinical condition on admission and planned for early surgery the adjusted odds ratio (OR) was 1.3 (95% CI 0.5 to 3.0). The adjusted OR for patients admitted in poor neurologicalcondition (WFNS IV-V) and planned for early surgery was 0.1 (95% CI 0.0 to 0.6). SURGICAL RESULTS: For patients in good clinical condition on admission who underwent early operation the adjusted OR was 1.1 (95% CI 0.4 to 3.2); it was 0.2 (95% CI 0.0 to 0.9) for patients admitted in poor clinical condition. CONCLUSIONS: In this observational study we found no significant difference in outcome between early and late operation for patients in good clinical condition on admission. For patients in poor clinical condition on admission outcome was significantly better after early surgery. The optimal timing of surgery is not yet settled. Ideally, evidence on this issue should come from a randomised clinical trial. However, such a trial or even a prospective study are unlikely to be ever performed because of the rapid development of endovascular coiling.

Direct costs of modern treatment of aneurysmal subarachnoid hemorrhage in the first year after diagnosis.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the current direct costs of modern management of patients with aneurysmal subarachnoid hemorrhage in the first year after diagnosis. METHODS: During a 1-year period, we studied all admitted patients with subarachnoid hemorrhage from a population of 2 million people. We calculated the direct costs of treatment, which included the costs of medical and nursing care and the related travel expenses of patients. We calculated true costs for all major healthcare resources. National census data, if available, and standard charges were used to determine healthcare resource expenses. RESULTS: Hospital admissions and diagnostic and therapeutic interventions in 110 patients accounted for 85% of all costs; 64% of the total direct medical costs during admission were the medical, nursing, and overhead costs alone. Patients discharged directly to home generated 4% of the total budget, whereas admission to a nursing home accounted for the remaining 11% of the total costs. Of the diagnostic and therapeutic costs, 45% was caused by imaging and 42% by surgery or coiling. Angiography alone accounted for 52% of the total imaging costs and 24% of the total diagnostic and therapeutic costs. Prescribed medication accounted for only 3% of the total budget of diagnostic and therapeutic costs. CONCLUSIONS: Most direct costs during the first year after aneurysmal subarachnoid hemorrhage are caused by the hospital inpatient days, accounting for two thirds of the total costs generated during the first year after the initial bleeding. If new costly treatments succeed in reducing the average length of inpatient hospital stays, then progress in therapy may prove cost effective and might even be cost saving.