Edemas of the face and lymphoscintigraphic examination.

Facial edemas not secondary to surgery and/or radiotherapy for head and neck cancer are relatively uncommon. Our aim is to report a retrospective analysis of the lymphoscintigraphic and SPECT-CT investigations obtained in patients with such facial edema. Retrospective review of exams (planar imagings in all and with SPECT-CT in 5) obtained after the subcutaneous injection of 99mTc HSA Nanosized colloids between the eyebrows in five men and seven women. Four main lymphatic pathways were identified on sequential planar imagings: para-nasal left and right and supra- ocular left and right. For eleven patients, the absence of visualization of lymphatic drainage and/or their delayed appearance correlated well with the localisation of the edematous areas. In two patients with post-traumatic and post- surgical edemas, SPECT-CT showed one deep left sided cervical lymph node (LN) in front of the first cervical vertebra. This lymphoscintigraphic approach represents a simple and valuable way to assess the lymphatic drainage pathways of the face and to establish the diagnosis of facial lymphedema.

Randomized trial of intravenous immunoglobulin maintenance treatment regimens in chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND AND PURPOSE: High peak serum immunoglobulin G (IgG) levels may not be needed for maintenance intravenous immunoglobulin (IVIg) treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and such high levels may cause side effects. More frequent lower dosing may lead to more stable IgG levels and higher trough levels, which might improve efficacy. The aim of this trial is to investigate whether high frequent low dosage IVIg treatment is more effective than low frequent high dosage IVIg treatment. METHODS: In this randomized placebo-controlled crossover trial, we included patients with CIDP proven to be IVIg-dependent and receiving an individually established stable dose and interval of IVIg maintenance treatment. In the control arm, patients received their individual IVIg dose and interval followed by a placebo infusion at half the interval. In the intervention arm, patients received half their individual dose at half the interval. After a wash-out phase patients crossed over. The primary outcome measure was handgrip strength (assessed using a Martin Vigorimeter). Secondary outcome indicators were health-related quality of life (36-item Short-Form Health Survey), disability (Inflammatory Rasch-built Overall Disability Scale), fatigue (Rasch-built Fatigue Severity Scale) and side effects. RESULTS: Twenty-five patients were included and were treated at baseline with individually adjusted dosages of IVIg ranging from 20 to 80 g and intervals ranging from 14 to 35 days. Three participants did not complete the trial; the main analysis was therefore based on the 22 patients completing both treatment periods. There was no significant difference in handgrip strength change from baseline between the two treatment regimens (coefficient -2.71, 95% CI -5.4, 0.01). Furthermore, there were no significant differences in any of the secondary outcomes or side effects. CONCLUSIONS: More frequent lower dosing does not further improve the efficacy of IVIg in stable IVIg-dependent CIDP and does not result in fewer side effects.

Biomechanical loading of the porcine femorotibial joint during maximal movements: An exploratory, ex vivo study.

Thus far, there is a lack of scientific investigation regarding the hypothesis that biomechanical factors contribute to the cross-species pathogenesis of osteochondrosis (OC). Therefore, the aim of this pilot study was to investigate whether high (peak) pressures occur in the porcine femorotibial (FT) joint. In this experimental, ex vivo study, the right hind limbs of seven weaned piglets were subjected to maximal joint excursions, as a priori radiologically estimated. Subsequently, the intra-articular pressures were measured using sensors placed in both the medial and the lateral compartments of the FT joint. The overall highest individual peak pressure was found in the lateral FT joint during maximal extension (2611 kPa; group mean ± standard deviation (SD) 982.3 ± 988.2 kPa). In the medial FT joint, the highest individual peak pressure was found during maximal adduction (1481 kPa; group mean ± SD 664.9 ± 393.2 kPa). Moreover, nearly 30% of the ex vivo peak pressures were above published thresholds for cartilage catabolism (>500 kPa/0.5 MPa), but not for interfering with cell viability (>5 MPa). In conclusion, this ex vivo study on FT joint pressures in weaned piglets showed that FT joint movements at maximal excursions are related to concomitant internal peak joint pressures. More studies should be performed to evaluate the possible biomechanical relation of these observations with osteochondrosis, which would allow the design of preventive measures in the pig industry, to avoid extreme limb movements and concomitant joint peak pressures in vivo.

A comparative study of brachial plexus sonography and magnetic resonance imaging in chronic inflammatory demyelinating neuropathy and multifocal motor neuropathy.

BACKGROUND AND PURPOSE: To compare the performance of neuroimaging techniques, i.e. high-resolution ultrasound (HRUS) and magnetic resonance imaging (MRI), when applied to the brachial plexus, as part of the diagnostic work-up of chronic inflammatory demyelinating neuropathy (CIDP) and multifocal motor neuropathy (MMN). METHODS: Fifty-one incident, treatment-naive patients with CIDP (n = 23) or MMN (n = 28) underwent imaging of the brachial plexus using (i) a standardized MRI protocol to assess enlargement or T2 hyperintensity and (ii) bilateral HRUS to determine the extent of nerve (root) enlargement. RESULTS: We found enlargement of the brachial plexus in 19/51 (37%) and T2 hyperintensity in 29/51 (57%) patients with MRI and enlargement in 37/51 (73%) patients with HRUS. Abnormal results were only found in 6/51 (12%) patients with MRI and 12/51 (24%) patients with HRUS. A combination of the two imaging techniques identified 42/51 (83%) patients. We found no association between age, disease duration or Medical Research Council sum-score and sonographic nerve size, MRI enlargement or presence of T2 hyperintensity. CONCLUSIONS: Brachial plexus sonography could complement MRI in the diagnostic work-up of patients with suspected CIDP and MMN. Our results indicate that combined imaging studies may add value to the current diagnostic consensus criteria for chronic inflammatory neuropathies.

Relaxation of the MCL after an Open-Wedge High Tibial Osteotomy results in decreasing contact pressures of the knee over time.

PURPOSE: The objective of this study was to investigate the effect of a medial open-wedge osteotomy (OWO) and the release of the superficial medial collateral ligament (MCL) on the tibiofemoral cartilage pressure, the MCL tension and the valgus laxity of the knee. METHODS: Seven fresh-frozen, human cadaveric knees were used. Medial and lateral mean contact pressure (CP), peak contact pressure (peakCP), and contact area (CA) were measured using a pressure-sensitive film (I-Scan; Tekscan, Boston, MA). The MCL tension was measured using a custom-made device. These measurements were continuously recorded for 5 min after an OWO of 10°. After the osteotomy, the valgus laxity was measured with a handheld Newtonmeter. For one knee, the measurements were continued for 24 h. At the end, a complete release of the superficial MCL was performed and the measurements were repeated at 10°. RESULTS: There was relaxation of the MCL after the osteotomy; the tension dropped in 5 min with 10.7% (mean difference 20.5 N (95% CI 16.1-24.9)), and in 24 h, the tension decreased by 24.2% (absolute difference 38.8 N) (one knee). After the osteotomy, the mean CP, peakCP and CA increased in the medial compartment (absolute difference 0.17 MPa (95% CI 0.14-0.20), 0.27 MPa (95% CI 0.24-0.30), 132.9mm2 (95% CI 67.7-198.2), respectively), and decreased in the lateral compartment (absolute difference 0.02 MPa (95% CI 0.03 -0.01), 0.08 MPa (95% CI 0.11 - 0.04), 47.0 mm2 (95% CI -105.8 to 11.8), respectively). Only after a release of the superficial MCL, the mean CP, peak CP and CA significantly decreased in the medial compartment (absolute difference 0.17, 0.27 MPa, 119.8 mm2, respectively), and increased in the lateral compartment (absolute difference 0.02, 0.11 MPa, 52.4 mm2, respectively). After the release of the superficial MCL, a mean increase of 7.9° [mean difference - 0.1° (95% CI -1.9 to 1.6)] of the valgus laxity was found. CONCLUSIONS: A release of the superficial MCL helps achieve the goal of reducing medial cartilage pressure in an OWO. There was considerable relaxation of the MCL after an OWO that resulted in a decrease of the mean CP in the medial and lateral compartments of the knee over time. However, cartilage pressure shifted from the medial to the lateral compartment only after release of the superficial MCL. The release of the superficial MCL caused a significant increase in the valgus laxity, which could influence stability after an OWO. LEVEL OF EVIDENCE: I.

Moderately degenerated lumbar motion segments: Are they truly unstable?

The two main load bearing tissues of the intervertebral disc are the nucleus pulposus and the annulus fibrosus. Both tissues are composed of the same basic components, but differ in their organization and relative amounts. With degeneration, the clear distinction between the two tissues disappears. The changes in biochemical content lead to changes in mechanical behaviour of the intervertebral disc. The aim of the current study was to investigate if well-documented moderate degeneration at the biochemical and fibre structure level leads to instability of the lumbar spine. By taking into account biochemical and ultrastructural changes to the extracellular matrix of degenerating discs, a set of constitutive material parameters were determined that described the individual tissue behaviour. These tissue biomechanical models were then used to simulate dynamic behaviour of the degenerated spinal motion segment, which showed instability in axial rotation, while a stabilizing effect in the other two principle bending directions. When a shear load was applied to the degenerated spinal motion segment, no sign of instability was found. This study found that reported changes to the nucleus pulposus and annulus fibrosus matrix during moderate degeneration lead to a more stable spinal motion segment and that such biomechanical considerations should be incorporated into the general pathophysiological understanding of disc degeneration and how its progress could affect low back pain and its treatments thereof.

Functional biomechanical performance of a novel anatomically shaped polycarbonate urethane total meniscus replacement.

PURPOSE: To evaluate the functional biomechanical performance of a novel anatomically shaped, polycarbonate urethane total meniscus implant. METHODS: Five human cadaveric knees were flexed between 0° and 90° under compressive loads mimicking a squat movement. Anteroposterior (AP) laxity tests were performed in 30° and 90° flexion. Meniscal kinematics and knee laxity were quantified using roentgen stereophotogrammetric analysis. Tibial cartilage contact mechanics were determined in 90° flexion. Measurements were repeated for the native medial meniscus, the implant, after total medial meniscectomy and allograft transplantation. RESULTS: The implant and allograft displayed increased posterior and medial displacements compared to the native meniscus, yet no differences were found between the implant and allograft. Meniscal condition did not affect rotational laxity. Compared to the native joint, AP laxity for the implant was increased in 30° flexion, but not in 90°. The implant reduced the mean contact pressure compared to meniscectomy but could not restore contact pressures to native meniscus levels. Compared to the native meniscus, the implant significantly increased the peak pressure, while the contact area was reduced. Contact mechanics of the implant and allograft were never statistically different. CONCLUSIONS: Biomechanical performance was similar for the implant and allograft. However, both meniscal replacements could not restore outcomes to native meniscus levels or sufficiently improve outcomes after meniscectomy. This was presumably caused by the mobility allowed by the suture-only horn fixation. The similarity of implant and allograft performance suggests that the novel implant has the biomechanical potential to serve as an alternative to meniscal allograft transplantation.

Short Term Evaluation of an Anatomically Shaped Polycarbonate Urethane Total Meniscus Replacement in a Goat Model.

PURPOSE: Since the treatment options for symptomatic total meniscectomy patients are still limited, an anatomically shaped, polycarbonate urethane (PCU), total meniscus replacement was developed. This study evaluates the in vivo performance of the implant in a goat model, with a specific focus on the implant location in the joint, geometrical integrity of the implant and the effect of the implant on synovial membrane and articular cartilage histopathological condition. METHODS: The right medial meniscus of seven Saanen goats was replaced by the implant. Sham surgery (transection of the MCL, arthrotomy and MCL suturing) was performed in six animals. The contralateral knee joints of both groups served as control groups. After three months follow-up the following aspects of implant performance were evaluated: implant position, implant deformation and the histopathological condition of the synovium and cartilage. RESULTS: Implant geometry was well maintained during the three month implantation period. No signs of PCU wear were found and the implant did not induce an inflammatory response in the knee joint. In all animals, implant fixation was compromised due to suture breakage, wear or elongation, likely causing the increase in extrusion observed in the implant group. Both the femoral cartilage and tibial cartilage in direct contact with the implant showed increased damage compared to the sham and sham-control groups. CONCLUSION: This study demonstrates that the novel, anatomically shaped PCU total meniscal replacement is biocompatible and resistant to three months of physiological loading. Failure of the fixation sutures may have increased implant mobility, which probably induced implant extrusion and potentially stimulated cartilage degeneration. Evidently, redesigning the fixation method is necessary. Future animal studies should evaluate the improved fixation method and compare implant performance to current treatment standards, such as allografts.

The sensitivity of cartilage contact pressures in the knee joint to the size and shape of an anatomically shaped meniscal implant.

Since meniscal geometry affects the cartilage contact pressures, it is essential to carefully define the geometry of the synthetic meniscal implant that we developed. Recently, six independent modes of size- and shape-related geometry variation were identified through 3D statistical shape modeling (SSM) of the medial meniscus. However, this model did not provide information on the functional importance of these geometry characteristics. Therefore, in this study finite element simulations were performed to determine the influence of anatomically-based meniscal implant size and shape variations on knee cartilage contact pressures. Finite element simulations of the knee joint were performed for a total medial meniscectomy, an allograft, the average implant geometry, six implant sizes and ten shape variations. The geometries of the allograft and all implant variations were based on the meniscus SSM. Cartilage contact pressures and implant tensile strains were evaluated in full extension under 1200N of axial compression. The average implant induced cartilage peak pressures intermediate between the allograft and meniscectomy and also reduced the cartilage area subjected to pressures >5MPa compared to the meniscectomy. The smaller implant sizes resulted in lower cartilage peak pressures and compressive strains than the allograft, yet high implant tensile strains were observed. Shape modes 2, 3 and 6 affected the cartilage contact stresses but to a lesser extent than the size variations. Shape modes 4 and 5 did not result in changes of the cartilage stress levels. The present study indicates that cartilage contact mechanics are more sensitive to implant size than to implant shape. Down-sizing the implant resulted in more favorable contact mechanics, but caused excessive material strains. Further evaluations are necessary to balance cartilage contact pressures and material strains to ensure cartilage protection and longevity of the implant.

Releasing the circumferential fixation of the medial meniscus does not affect its kinematics.

BACKGROUND: Meniscal functioning depends on the fixation between the meniscal horns and the surrounding tissues. It is unknown, however, whether the integration between the outer circumference of the medial meniscus and the knee capsule/medial collateral ligament also influences the biomechanical behavior of the meniscus. Therefore, we aimed to determine whether detaching and resuturing the circumferential fixation of the medial meniscus influence its kinematic pattern. METHODS: Human cadaveric knee joints were flexed (0°-30°-60°-90°) in a knee loading rig, in neutral orientation and under internal and external tibial torques. Roentgen stereophotogrammetric analysis was used to determine the motion of the meniscus in anteroposterior (AP) and mediolateral (ML) directions. Three fixation conditions were evaluated: (I) intact, (II) detached and (III) resutured. RESULTS: Detaching and resuturing the circumferential fixation did not alter the meniscal motion pattern in either the AP or ML direction. Applying an additional internal tibial torque caused the medial meniscus to move slightly anteriorly, and an external torque caused a little posterior translation with respect to the neutral situation. These patterns did not change when the circumferential fixation condition was altered. CONCLUSIONS: This study demonstrated that the motion pattern of the medial meniscus is independent of its fixation to the knee capsule and medial collateral ligament. CLINICAL RELEVANCE: The outcomes of this study can be deployed to design the fixation strategy of a permanent meniscus prosthesis. As peripheral fixation is a complicated step during meniscal replacement, the surgical procedure is considerably simplified when non-resorbable implants do not require circumferential fixation.

3D geometry analysis of the medial meniscus--a statistical shape modeling approach.

The geometry-dependent functioning of the meniscus indicates that detailed knowledge on 3D meniscus geometry and its inter-subject variation is essential to design well functioning anatomically shaped meniscus replacements. Therefore, the aim of this study was to quantify 3D meniscus geometry and to determine whether variation in medial meniscus geometry is size- or shape-driven. Also we performed a cluster analysis to identify distinct morphological groups of medial menisci and assessed whether meniscal geometry is gender-dependent. A statistical shape model was created, containing the meniscus geometries of 35 subjects (20 females, 15 males) that were obtained from MR images. A principal component analysis was performed to determine the most important modes of geometry variation and the characteristic changes per principal component were evaluated. Each meniscus from the original dataset was then reconstructed as a linear combination of principal components. This allowed the comparison of male and female menisci, and a cluster analysis to determine distinct morphological meniscus groups. Of the variation in medial meniscus geometry, 53.8% was found to be due to primarily size-related differences and 29.6% due to shape differences. Shape changes were most prominent in the cross-sectional plane, rather than in the transverse plane. Significant differences between male and female menisci were only found for principal component 1, which predominantly reflected size differences. The cluster analysis resulted in four clusters, yet these clusters represented two statistically different meniscal shapes, as differences between cluster 1, 2 and 4 were only present for principal component 1. This study illustrates that differences in meniscal geometry cannot be explained by scaling only, but that different meniscal shapes can be distinguished. Functional analysis, e.g. through finite element modeling, is required to assess whether these distinct shapes actually influence the biomechanical performance of the meniscus.

Mutations in RYR1 are a common cause of exertional myalgia and rhabdomyolysis.

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are a common cause of neuromuscular disease, ranging from various congenital myopathies to the malignant hyperthermia (MH) susceptibility trait without associated weakness. We sequenced RYR1 in 39 unrelated families with rhabdomyolysis and/or exertional myalgia, frequent presentations in the neuromuscular clinic that often remain unexplained despite extensive investigations. We identified 9 heterozygous RYR1 mutations/variants in 14 families, 5 of them (p.Lys1393Arg; p.Gly2434Arg; p.Thr4288_Ala4290dup; p.Ala4295Val; and p.Arg4737Gln) previously associated with MH. Index cases presented from 3 to 45 years with rhabdomyolysis, with or without exertional myalgia (n=12), or isolated exertional myalgia (n=2). Rhabdomyolysis was commonly triggered by exercise and heat and, less frequently, viral infections, alcohol and drugs. Most cases were normally strong and had no personal MH history. Inconsistent additional features included heat intolerance, and cold-induced muscle stiffness. Muscle biopsies showed mainly subtle changes. Familial RYR1 mutations were confirmed in relatives with similar or no symptoms. These findings suggest that RYR1 mutations may account for a substantial proportion of patients presenting with unexplained rhabdomyolysis and/or exertional myalgia. Associated clinico-pathological features may be subtle and require a high degree of suspicion. Additional family studies are paramount in order to identify potentially MH susceptible relatives.

The additional yield of combined nerve/muscle biopsy in vasculitic neuropathy.

BACKGROUND: vasculitic neuropathy can be confirmed by demonstrating vasculitis in a nerve biopsy, but it is uncertain to what extent combined (i.e. nerve/muscle) biopsy improves the yield. METHODS: a random-effects meta-analysis was performed to assess the additional yield of combined biopsy in vasculitic neuropathy. Medline, Embase, LILACS and ISI were searched from January 1980 until January 2009 for relevant articles on the yield of nerve, muscle or combined biopsy to diagnose vasculitic neuropathy. Fourteen (15%) studies were included. Methodological quality was scored using a modified Quality Assessment for Diagnostic Accuracy Studies tool. RESULTS: in patients clinically suspected of vasculitic neuropathy, the additional yield of definite vasculitis in combined biopsy was 5.1% (95% CI 1.1-9.2%; P = 0.013). In patients diagnosed with vasculitic neuropathy, the additional yield of definite vasculitis in combined biopsy was 15% (95% CI 2.1-28%; P = 0.023). CONCLUSIONS: there is a modest additional yield of definite vasculitis in combined biopsy compared to nerve biopsy alone. Because of methodological flaws in analysed studies, the findings should be validated in a prospective study.

Peripheral Nerve Society Guideline on the classification, diagnosis, investigation, and immunosuppressive therapy of non-systemic vasculitic neuropathy: executive summary.

Non-systemic vasculitic neuropathy (NSVN) is routinely considered in the differential diagnosis of progressive axonal neuropathies, especially those with asymmetric or multifocal features. Diagnostic criteria for vasculitic neuropathy, classification criteria for NSVN, and therapeutic approaches to NSVN are not standardized. The aim of this guideline was to derive recommendations on the classification, diagnosis, investigation, and treatment of NSVN based on the available evidence and, where evidence was not available, expert consensus. Experts on vasculitis, vasculitic neuropathy, and methodology systematically reviewed the literature for articles addressing diagnostic issues concerning vasculitic neuropathy and NSVN as well as treatment of NSVN and the small-to-medium vessel primary systemic vasculitides using MEDLINE, EMBASE, and the Cochrane Library. The selected articles were analyzed and classified. The group initially reached consensus on a classification of vasculitides associated with neuropathy. Non-diabetic radiculoplexus neuropathy was incorporated within NSVN. The consensus definition of pathologically definite vasculitic neuropathy required that vessel wall inflammation be accompanied by vascular damage. Diagnostic criteria for pathologically probable vasculitic neuropathy included five predictors of definite vasculitic neuropathy: vascular deposits of IgM, C3, or fibrinogen by direct immunofluorescence; hemosiderin deposits; asymmetric nerve fiber loss; prominent active axonal degeneration; and myofiber necrosis, regeneration, or infarcts in peroneus brevis muscle biopsy (Good Practice Points from class II/III evidence). A case definition of clinically probable vasculitic neuropathy in patients lacking biopsy proof incorporated clinical features typical of vasculitic neuropathy: sensory or sensory-motor involvement, asymmetric/multifocal pattern, lower-limb predominance, distal-predominance, pain, acute relapsing course, and non-demyelinating electrodiagnostic features (Good Practice Points from class II/III evidence). Proposed exclusionary criteria for NSVN--favoring the alternate diagnosis of systemic vasculitic neuropathy--were clinicopathologic evidence of other-organ involvement; anti-neutrophil cytoplasmic antibody (ANCAs); cryoglobulins; sedimentation rate ≥100 mm/h; and medical condition/drug predisposing to systemic vasculitis (Good Practice Points supported by class III evidence). Three class III studies on treatment of NSVN were identified, which were insufficient to permit a level C recommendation. Therefore, the group reviewed the literature on treatment of primary small-to-medium vessel systemic vasculitides prior to deriving Good Practice Points on treatment of NSVN. Principal treatment recommendations were: (1) corticosteroid (CS) monotherapy for at least 6 months is considered first-line; (2) combination therapy should be used for rapidly progressive NSVN and patients who progress on CS monotherapy; (3) immunosuppressive options include cyclophosphamide, azathioprine, and methotrexate; (4) cyclophosphamide is indicated for severe neuropathies, generally administered in IV pulses to reduce cumulative dose and side effects; (5) in patients achieving clinical remission with combination therapy, maintenance therapy should be continued for 18-24 months with azathioprine or methotrexate; and (6) clinical trials to address all aspects of treatment are needed.

The realistic yield of lower leg SNAP amplitudes and SRAR in the routine evaluation of chronic axonal polyneuropathies.

OBJECTIVE: To assess the realistic yield of lower leg sensory nerve action potential amplitudes (SNAP) and the sural/radial nerve amplitude ratio (SRAR) in the routine evaluation of suspected distal axonal polyneuropathy. METHODS: Investigated were 721 people. In 393 referents without and 328 patients with chronic distal symmetrical polyneuropathy the SRAR, sural, superficial peroneal and dorsal sural SNAP were determined. RESULTS: The dorsal sural SNAP could not be elicited in 26 % of referents. Axonal polyneuropathy was confirmed by an abnormally low value of the sural or superficial peroneal SNAP or SRAR in 70 % of patients, and most often (68 %) by an absent sural or superficial peroneal SNAP. In 9 % of patients there was a normal sural but abnormal superficial peroneal SNAP, and 11 % had an abnormal sural but normal superficial peroneal SNAP. ROC curve analysis demonstrated equal accuracy of the sural and superficial peroneal SNAP. CONCLUSIONS: To confirm distal axonal polyneuropathy in routine clinical practice the sural and superficial peroneal SNAP had equal and complementary yield, whereas the SRAR and dorsal sural SNAP had limited additional yield.

Immunosuppressive treatment for non-systemic vasculitic neuropathy.

BACKGROUND: Non-systemic vasculitic neuropathy is a rare disabling disease that usually has a subacute onset of progressive or relapsing-remitting sensory or sensorimotor deficits. Asymmetry, pain and weakness are key features. The diagnosis can only be made by exclusion of other causes, the absence of systemic vasculitis or other rheumatic diseases, and the demonstration of vasculitis in a nerve or a combined nerve and muscle biopsy. There is a need for efficacious therapy to prevent disease progression and to improve prognosis. OBJECTIVES: To assess if immunosuppressive treatment in non-systemic vasculitic neuropathy reduces disability, and ameliorates neurological symptoms, and if such therapy can be given safely. SEARCH STRATEGY: The Cochrane Neuromuscular Disease Group Trials Register (March 2006), The Cochrane Library (Issue 1, 2006), MEDLINE, EMBASE, LILACS, and ISI were searched from January 1980 until April 2006. In addition, the reference lists of relevant articles, reviews and textbooks were handsearched. SELECTION CRITERIA: All randomised or quasi-randomised trials that examined the efficacy of immunosuppressive treatment for non-systemic vasculitic neuropathy at least one year after the onset of therapy were sought. Participants had to fulfill the following criteria: absence of systemic or neurological disease, exclusion of any recognised cause of the neuropathy by appropriate clinical or laboratory investigations, electrophysiological studies in agreement with axonal neuropathy, confirmation of vasculitis in a nerve or a combined nerve and muscle biopsy. The primary outcome measure was to be improvement in disability. Secondary outcome measures were to be change in the mean disability score, change in muscle strength measured with the Medical Research Council sum score, change in pain or other positive sensory symptoms, number of relapses, and adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed and extracted details of all potentially relevant trials. For included studies pooled relative risks and pooled weighted standardised mean differences were to be calculated to assess treatment efficacy. MAIN RESULTS: Fifty-nine studies were identified and assessed for possible inclusion in the review, but all were excluded because of insufficient quality or lack of relevance. AUTHORS' CONCLUSIONS: No adequate randomised or quasi-randomised controlled clinical trials have been performed on which to base treatment for non-systemic vasculitic neuropathy. Randomised trials of corticosteroids and other immunosuppressive agents are needed.

Feasibility and cost efficiency of a diagnostic guideline for chronic polyneuropathy: a prospective implementation study.

BACKGROUND: Extensive investigations are often performed to reveal the cause of chronic polyneuropathy. It is not known whether a restrictive diagnostic guideline improves cost efficiency without loss of diagnostic reliability. METHODS: In a prospective multicentre study, a comparison was made between the workup in patients with chronic polyneuropathy before and after guideline implementation. RESULTS: Three hundred and ten patients were included: 173 before and 137 after guideline implementation. In all patients, the diagnosis would remain the same if the workup was limited to the investigations in the guideline. After guideline implementation, the time to reach a diagnosis decreased by two weeks. There was a reduction of 33% in the number and costs of routine laboratory investigations/patient, and a reduction of 27% in the total number of laboratory tests/patient, despite low guideline adherence. CONCLUSION: The implementation of a diagnostic guideline for chronic polyneuropathy can reduce diagnostic delay and the number and costs of investigations for each patient without loss of diagnostic reliability. Continuous evaluation strategies after guideline implementation may improve guideline adherence and cost efficiency.