Study protocol for a randomised controlled multicentre study: the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) in patients with cervical radiculopathy.

INTRODUCTION: Cervical radiculopathy due to discogenic or spondylotic stenosis of the neuroforamen can be surgically treated by an anterior discectomy with fusion (ACDF) or a posterior foraminotomy (FOR). Most surgeons prefer ACDF, although there are indications that FOR is as effective as ACDF, has a lower complication rate and is less expensive. A head-to-head comparison of the 2 surgical techniques in a randomised controlled trial has not yet been performed. The study objectives of the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) study are to compare clinical outcomes, complication rates and cost-effectiveness of FOR to ACDF. METHODS AND ANALYSIS: The FACET study is a prospective randomised controlled trial conducted in 7 medical centres in the Netherlands. The follow-up period is 2 years. The main inclusion criterion is a radiculopathy of the C4, C5, C6 or C7 nerve root, due to a single-level isolated cervical foraminal stenosis caused by a soft disc and/or osteophytic component, requiring operative decompression. A sample size of 308 patients is required to test the hypothesis of clinical non-inferiority of FOR versus ACDF. Primary outcomes are: 'operative success', the measured decrease in radiculopathy assessed by the visual analogue scale and 'patient success', assessed by the modified Odom's criteria. Secondary outcomes are: Work Ability Index (single-item WAI), quality of life (EuroQol 5 Dimensions 5 level Survey, EQ-5D-5L), Neck Disability Index (NDI) and complications. An economic evaluation will assess cost-effectiveness. In addition, a budget impact analysis will be performed. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Ethics Committee of the University Medical Center Groningen. Results of this study will be disseminated through national and international papers. The participants and relevant patient support groups will be informed about the results of the study. TRIAL REGISTRATION NUMBER: NTR5536, pre-results.

Reproducibility and variability of dynamic cerebral autoregulation during passive cyclic leg raising.

Dynamic cerebral autoregulation (dCA) estimates require mean arterial blood pressure (MABP) fluctuations of sufficient amplitude. Current methods to induce fluctuations are not easily implemented or require patient cooperation. In search of an alternative method, we evaluated if MABP fluctuations could be increased by passive cyclic leg raising (LR) and tested if reproducibility and variability of dCA parameters could be improved. Middle cerebral artery cerebral blood flow velocity (CBFV), MABP and end tidal CO2 (PetCO2) were obtained at rest and during LR at 0.1 Hz in 16 healthy subjects. The MABP-CBFV phase difference and gain were determined at 0.1 Hz and in the low frequency (LF) range (0.06-0.14 Hz). In addition the autoregulation index (ARI) was calculated. The LR maneuver increased the power of MABP fluctuations at 0.1 Hz and across the LF range. Despite a clear correlation between both phase and gain reproducibility and MABP variability in the rest condition, only the reproducibility of gain increased significantly with the maneuver. During the maneuver patients were breathing faster and more irregularly, accompanied by increased PetCO2 fluctuations and increased coherence between PetCO2 and CBFV. Multiple regression analysis showed that these concomitant changes were negatively correlated with the MABP-CBFV phase difference at 0.1 Hz Variability was not reduced by LR for any of the dCA parameters. The clinical utility of cyclic passive leg raising is limited because of the concomitant changes in PetCO2. This limits reproducibility of the most important dCA parameters. Future research on reproducibility and variability of dCA parameters should incorporate PetCO2 variability or find methods to keep PetCO2 levels constant.

Pitfalls in the diagnosis of reversible cerebral vasoconstriction syndrome and primary angiitis of the central nervous system.

A case of a 51-year-old woman with reversible cerebral vasoconstriction syndrome (RCVS) without an associative cause is reported. Initially the diagnosis primary angiitis of the central nervous system (PACNS) was considered. Both diagnosis are rare and can mimic each other. Distinction between both can be difficult, but is necessary because of different treatment options. Clinical features and diagnostic assessments to distinguish RCVS from PACNS and the potential pitfalls are discussed.

Measuring disability in stroke: relationship between the modified Rankin scale and the Barthel index.

BACKGROUND AND PURPOSE: The effectiveness of therapeutic interventions in acute stroke trials is traditionally measured with the modified Rankin scale (mRs) and the Barthel index (BI). The mRs is a global disability scale divided into six steps from total independence to total dependence. The BI assesses ten basal activities of daily living, of which eight assess level of dependence (bathing, grooming, using stairs, dressing, feeding, toilet use, transfers and walking). The aim of this study was to investigate the relationship between the mRs and the total scores and item-scores of the BI. METHODS: During a period of 3 months mRs and BI scores were collected from two multicentre randomised, placebo-controlled trials with lubeluzole (515 and 519 patients). In each patient we compared the mRs grades with the total BI score and the scores on the ten subitems. RESULTS: For both trials there was extensive overlap of BI scores between mRs grades and a wide range in BI scores among patients with mRs grades 3 and 4. We also found discrepancies between the BI item-scores and mRs grades. About 40% of patients with mRs grades 1 (able to carry out all usual activities) and 2 (able to look after own affairs without assistance) were not independent on at least one activity of the BI. In both studies, about 30% of the patients needed help or supervision for walking, although they were classified as mRs 3 (requiring some help but able to walk without assistance). CONCLUSIONS: Investigators in stroke trials use the mRs as a subjective global disability scale, and they do not strictly take into account limitations in performing specific basal activities of daily living, as assessed by the BI, to assign mRs grades.

Safety of routine IV thrombolysis between 3 and 4.5 h after ischemic stroke.

BACKGROUND: The administration of tissue plasminogen activator (t-PA) has been proven effective for ischemic stroke within 3 h after onset. A pooled-analysis of six trials showed that intravenous t-PA still improves outcome when given between 3 to 4.5 h after stroke onset. On the basis of this pooled analysis, t-PA was also routinely offered to our patients between 3-4.5 h. We report the safety and clinical features of this group together with the features of the group given t-PA within 3 h. METHODS: Prospectively patient characteristics, stroke severity, stroke subtype, incidence of symptomatic intracerebral hemorrhage (SICH), in-hospital mortality, and 3-months modified Rankin Scale scores (mRS) were registered. Data was analyzed separately for patients treated within 3 h (early group) and those treated between 3-4.5 h (late group). RESULTS: Among 176 patients who underwent intravenous thrombolysis, 101 were treated in the early group and 75 in the late group. Six (5.9%; 95% CI 2.8%-12.3%) patients in the early group and 4 (5.3%; 95% CI 2.2%-12.9%) in the late group developed SICH (p=1.0). In the early group 13 (12.9%; 95% CI 7.7%-20.8%) patients died within 7 days after admission, compared to 5 (6.7%; 95% CI 3.0%-14.7%) in the late group (p=0.179). In the early group 44 (43.6%; 95% CI 43.3%-53.3%) were independent (mRS< or =2) at three months, compared to 36 (48.0%; 95% CI 37.0%-59.1%) in the late group (p=0.559). CONCLUSION: Our data show no trend of decreased safety of thrombolysis beyond 3 h. Due to a small sample size a harmful effect cannot be excluded but seems unlikely.

Diagnostic value of history and physical examination in patients suspected of lumbosacral nerve root compression.

OBJECTIVE: To evaluate patient characteristics, symptoms, and examination findings in the clinical diagnosis of lumbosacral nerve root compression causing sciatica. METHODS: The study involved 274 patients with pain radiating into the leg. All had a standardised clinical assessment and magnetic resonance (MR) imaging. The associations between patient characteristics, clinical findings, and lumbosacral nerve root compression on MR imaging were analysed. RESULTS: Nerve root compression was associated with three patient characteristics, three symptoms, and four physical examination findings (paresis, absence of tendon reflexes, a positive straight leg raising test, and increased finger-floor distance). Multivariate analysis, analysing the independent diagnostic value of the tests, showed that nerve root compression was predicted by two patient characteristics, four symptoms, and two signs (increased finger-floor distance and paresis). The straight leg raise test was not predictive. The area under the curve of the receiver-operating characteristic was 0.80 for the history items. It increased to 0.83 when the physical examination items were added. CONCLUSIONS: Various clinical findings were found to be associated with nerve root compression on MR imaging. While this set of findings agrees well with those commonly used in daily practice, the tests tended to have lower sensitivity and specificity than previously reported. Stepwise multivariate analysis showed that most of the diagnostic information revealed by physical examination findings had already been revealed by the history items.

Prognostic value of MRI findings in sciatica.

The natural course of sciatica due to disc herniation is generally favourable but individually unpredictable. Some patients recover only after prolonged conservative therapy or surgery. This study aims to ascertain whether magnetic resonance (MR) imaging features can be used to predict outcome of sciatica and help to identify patients unlikely to respond to conservative management. For a transversal diagnostic study 274 primary care patients underwent early MR imaging for leg pain. One hundred and thirty-three patients with sciatica were followed for 3 months, both patients and physicians being unaware of MR imaging findings. At 12 weeks a favourable prognosis was indicated by the following features: annular rupture (P= 0.02) and nerve root compression on MR imaging (P = 0.03). Poor prognosis was indicated by disc herniation in the foramen (P = 0.004). Our findings show that early MR imaging features are related to prognosis. However, the associations are not strong enough to justify routine use of early MR imaging to predict the prognosis of sciatica.