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.

Assessment of spine length in scoliosis patients using EOS imaging: a validity and reliability study.

PURPOSE: Knowledge about spinal length and subsequently growth of each individual patient with adolescent idiopathic scoliosis (AIS) helps with accurate timing of both conservative and surgical treatment. Radiographs taken by a biplanar low-dose X-ray device (EOS) have no divergence in the vertical plane and can provide three-dimensional (3D) measurements. Therefore, this study investigated the criterion validity and reliability of EOS spinal length measurements in AIS patients. METHODS: Prior to routine EOS radiograph, a radiographic calibrated metal beads chain (MBC) was attached on the back of 120 patients with AIS to calibrate the images. Spinal lengths were measured from vertebra to vertebra on EOS anteroposterior (AP), lateral view and on the combined 3D EOS view (EOS 3D). These measurements were compared with MBC length measurements. Secondly, intra- and interobserver reliability of length measurements on EOS-images were determined. RESULTS: 50 patients with accurately positioned MBC were included for analysis. The correlations between EOS and MBC were highest for the 3D length measurements. Compared to EOS 3D measurements, the total spinal length was systematically measured 4.3% (mean difference = 1.97 ± 1.12 cm) and 1.9% (mean difference = 0.86 ± 0.63 cm) smaller on individual EOS two-dimensional (2D) AP and lateral view images, respectively. Both intra- and interobserver reliability were excellent for all length measurements on EOS-images. CONCLUSION: The results of this study indicate a good validity and reliability for spinal length measurements on EOS radiographs in AIS patients. EOS 3D length measure method is preferred above spinal length measurements on individual EOS AP or lateral view images.

Assessment of pedicle size in patients with scoliosis using EOS 2D imaging: a validity and reliability study.

PURPOSE: Free-hand pedicle screw insertion methods are widely used for screw insertion during scoliosis surgery. Preoperative knowledge about the pedicle size helps to maximize screw containment and minimize the risk of pedicle breach. Radiographs taken by a biplanar low-dose X-ray device (EOS) have no divergence in the vertical plane. The criterion validity and reliability of preoperative EOS images for pedicle size measurements in patients with idiopathic scoliosis (IS) was investigated in this study. METHODS: Sixteen patients who underwent surgical treatment for IS were prospectively included. Intra- and extracortical pedicle height and width measurements on EOS images were compared with reconstructed intra-operative 3D images of the isthmus of included pedicles. Secondly, intra- and interobserver reliability of pedicle size measurements on EOS images was determined. RESULTS: The total number of analyzed pedicles was 203. The correlation between the EOS and 3D scan measurements was very strong for the intra- and extracortical pedicle height and strong for the intra- and extracortical pedicle width. There are, however, significant, but likely clinically irrelevant differences (mean absolute differences < 0.43 mm) between the two measure methods for all four measurements except for extracortical pedicle height. For pedicles classified as Nash-Moe 0, no significant differences in intra- and extracortical pedicle width were observed. Both intra- and interobserver reliability was excellent for all pedicle size measurements on EOS images. CONCLUSION: The results of this study indicate a good validity and reliability for pedicle size measurements on EOS radiographs. Therefore, EOS radiographs may be used for a preoperative estimation of pedicle size and subsequent screw diameter in patients with IS.

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.

Is remaining intervertebral disc tissue interfering with bone generation during fusion of two vertebrae?

STUDY DESIGN: laboratory research. BACKGROUND: Through the increasing number of minimally invasive procedures in spinal fusion surgery, the complete removal of intervertebral disc (IVD) tissue has become more a challenge. Remaining IVD may interfere with the biological process of bone formation. OBJECTIVE: In order to establish whether complete removal of IVD tissue will improve or inhibit the fusion process, the effects of different concentrations of extracts of inflamed disc tissue on the mitochondrial activity of mesenchymal stem cells (MSCs), and the capacity to mineralize their extracellular matrix by osteoblasts and differentiated MSCs were tested in vitro. METHODS: A MTT assay was conducted to measure the mitochondrial activity of MSCs, and an Alizarin Red S staining quantification assay to measure the deposition of calcium by osteoblasts and differentiated, bone marrow-derived MSCs. RESULTS: A significantly higher mitochondrial activity was shown in MSCs co-cultured with extracts of IVD tissue (10%, 50%, and 100%) compared with the control group after 48 hours of incubation, indicating that the IVD tissue extracts stimulated the mitochondrial activity of MSCs. This effect appeared to be inversely proportional to the concentration of IVD tissue extract. No significant differences in mineralization by human osteoblasts or differentiated MSCs were found between the samples incubated with IVD tissue extracts (3% and 33%) and the control samples. CONCLUSION: Our findings indicate that remaining IVD tissue has more of a stimulating than inhibiting effect on the activity of MSCs. Even if inflammatory cytokines are produced, these do not result in a net inhibition of cellular activity or osteogenic differentiation of MSCs.

Biomechanical evaluation of two minimal access interbody cage designs in a cadaveric model.

BACKGROUND: Different interbody grafts have been employed and evaluated for spinal fusion surgery. The Memory Metal Minimal Access Cage (MAC) is a hollow horseshoe shaped interbody fusion concept which provides a potentially major advantage with their small cage contact area and large graft space in comparison with other vertical cages. METHODS: This Biomechanical Cadaveric Study evaluates the primary stability and the amount of acute subsidence occurring in two new MAC cage designs; the Niti-l and Niti-s. Both cages were made of nitinol in the form of a wedge-shaped horseshoe with spikes on the edges. Differences were the higher weight and larger tranverse section area of the Niti-l due to his specific design with two different layers of thickness. Biomechanical axial compression tests were performed on ten fresh-frozen T11-L5 vertebral bodies. RESULTS: A direct relation between force at failure and BMD was found (p < 0.001). The displacements in the vertebral body at an axial force of 800 N were 1.91 mm and 1.88 mm for the NiTi-l and NiTi-s cage, respectively. The mean failure load for the NiTi-l cages was 2043 N, and 1866 N for de NiTi-s cages. No significant difference was established between the two cages. CONCLUSION: The biomechanical strength of both NiTi-l and NiTi-s cages is good and comparable to each other with a limited amount of short-term subsidence after the initial implantation of the cage spikes into the bone.

Long-term evaluation of intraoperative neurophysiological monitoring-assisted tethered cord surgery.

PURPOSE: Patients with tethered spinal cord have been investigated for short-term effects after tethered spinal cord surgery in the past. However, little is known about the long-term effects in this patient group. In this retrospective, longitudinal, observational study, a patient sample of a previous report of 65 patients was reassessed to observe the long-term effects of intraoperative neurophysiological monitoring-assisted tethered cord surgery. METHODS: With the use of patient charts and a survey, patients were scored on four domains: (1) neurological deficits, (2) urological deficits, (3) pain symptoms, and (4) orthopedic deficits. Measurements were performed at four moments in time: (1) preoperatively, (2) postoperatively, (3) follow-up 1 (4.6 years), and (4) follow-up 2 (11.2 years). Besides this, a subgroup analysis and a quality of life questionnaire were performed. RESULTS: When observing the symptom domains in the long-term, the pain domain appeared to improve most postoperatively after which it remained stable over time. The neurological and urological domains showed a stable, slightly decreasing trend in the long-term follow-up. The orthopedic domain showed a significant increase of the number of patients with scoliosis during the long-term follow-up. CONCLUSIONS: Lasting effects of stability in the neurological, urological, and pain domains were observed. Close monitoring during follow-up might contribute to early recognition of progressive scoliosis, in spite of detethering, in a risk group defined by females who underwent tethered cord surgery at or under the age of 12 years old with either lipomyelomeningocele, split cord malformation, or myelomeningocele. Detethering does not appear to protect these patients against progressive scoliosis.

Altered head orientation patterns in children with idiopathic scoliosis in conditions with sensory conflict.

PURPOSE: Idiopathic scoliosis (IS) is the most common spinal deformity in adolescents. Defective postural equilibrium may be a contributing factor. The information of the three sensory systems combined enables the formation of a central representation of head position and body posture. Comparison of head angles of girls with and without scoliosis may result in a difference in head orientation. METHODS: 25 girls with IS and 16 girls without scoliosis (NS) between the age of 10-16 years stand in a special constructed box on a roll-tilting platform (tilt -14° to +14°). RESULTS: NS and IS subjects behave quite similarly if there is no sensory conflict, but if there is conflict, the differences between the two groups are greater, especially within the 13- to 14-year-old category. CONCLUSIONS: The differences between groups for different age categories suggest that the process of development of sensory integration for estimation of verticality appears to be different for girls with scoliosis.

The memory metal minimal access cage: a new concept in lumbar interbody fusion-a prospective, noncomparative study to evaluate the safety and performance.

Study Design/Objective. A single-centre, prospective, non-comparative study of 25 patients to evaluate the performance and safety of the Memory Metal Minimal Access Cage (MAC) in Lumbar Interbody Fusion. Summary of Background Data. Interbody fusion cages in general are designed to withstand high axial loads and in the meantime to allow ingrowth of new bone for bony fusion. In many cages the contact area with the endplate is rather large leaving a relatively small contact area for the bone graft with the adjacent host bone. MAC is constructed from the memory metal Nitinol and builds on the concept of sufficient axial support in combination with a large contact area of the graft facilitating bony ingrowth and ease in minimal access implantation due to its high deformability. Methods. Twenty five subjects with a primary diagnosis of disabling back and radicular leg pain from a single level degenerative lumbar disc underwent an interbody fusion using MAC and pedicle screws. Clinical performance was evaluated prospectively over 2 years using the Oswestry Disability Index (ODI), Short Form 36 questionnaire (SF-36) and pain visual analogue scale (VAS) scores. The interbody fusion status was assessed using conventional radiographs and CT scan. Safety of the device was studied by registration of intra- and post-operative adverse effects. Results. Clinical performance improved significantly (P < .0018), CT scan confirmed solid fusion in all 25 patients at two year follow-up. In two patients migration of the cage occurred, which was resolved uneventfully by placing a larger size at the subsequent revision. Conclusions. We conclude that the Memory Metal Minimal Access Cage (MAC) resulted in 100% solid fusions in 2 years and proved to be safe, although two patients required revision surgery in order to achieve solid fusion.

ACE inhibition preserves heparan sulfate proteoglycans in the glomerular basement membrane of rats with established adriamycin nephropathy.

The gradual onset of the antiproteinuric effects of ACE inhibition suggests that structural effects on the glomerular basement membrane (GBM) may be involved in their renoprotective action. To test this hypothesis, we studied the effects of lisinopril (5 mg/kg/24 h) on proteinuria, focal glomerulosclerosis (FGS) and glomerular heparan sulfate (HS) proteoglycan (HSPG) GBM staining in rats with established Adriamycin nephrosis. Treatment was started 6 weeks after disease induction. As expected, lisinopril reduced blood pressure, proteinuria and the FGS score. In control rats, Adriamycin nephrosis was associated with significantly impaired GBM staining for both HSPG core protein (assessed from BL-31 staining) and HS staining (assessed from JM-403 staining) 12 weeks after disease induction. In rats treated with lisinopril (5 mg/kg/24 h) GBM staining was significantly better preserved for HS as well as for HSPG core protein. These data suggest that structural effects on the GBM, improving glomerular permselectivity, may be involved in the renoprotective effects of ACE inhibition in proteinuria-induced renal damage.

Dose of doxorubicin determines severity of renal damage and responsiveness to ACE-inhibition in experimental nephrosis.

Nephrosis induced by doxorubicin (adriamycin) is an experimental model of glomerulosclerosis with relative stable proteinuria which is commonly used for pharmacological intervention studies. It is induced by a single or a double dose of doxorubicin, with doses that vary considerably among investigators from 2 to 7.5 mg/kg. Intervention studies with ACE-inhibitors in this model have provided conflicting results. We hypothesized that these discrepancies might be due to different properties of the doxorubicin model, related to the dose of doxorubicin used to induce proteinuria. We tested this hypothesis by inducing doxorubicin nephrosis with 1, 2 and 3 mg/kg, and evaluating the response to intervention with lisinopril. The 1-mg/kg doxorubicin dose did not induce significant proteinuria. The 2- and the 3-mg/ kg dose resulted in a proteinuria of 684+/-215 mg/24 h and 736+/-277 mg/24 h 6 weeks after induction, respectively (Mean+/-SD). Treatment with lisinopril 2 mg/kg/day reduced proteinuria to 160+/-170 mg/24 h(p<0.01) in the 2-mg/kg doxorubicin group, whereas in the 3-mg/kg doxorubicin group, proteinuria did not respond to lisinopril (529+/-264 mg/24 h). In time control rats, proteinuria remained stable. Renal damage developed in both time control groups, with a glomerulosclerosis score of 29+/-22 in the 2-mg/kg group and 84+/-41 in the 3-mg/kg doxorubicin group. Lisinopril resulted in a significantly lower glomerulosclerosis score in the 2-mg/kg doxorubicin group only (16+/-15, p<0.05), whereas the 3-mg/kg group showed no significant reduction (56+/-29, NS). In conclusion, the dose of doxorubicin used to induce nephrosis is an important determinant not only of the severity of the ensuring renal damage, but also of the response to intervention by ACE-inhibition. These findings have an impact on the interpretation of intervention studies in this model.

Effect of proteinuria reduction on prevention of focal glomerulosclerosis by angiotensin-converting enzyme inhibition is modifiable.

BACKGROUND: Proteinuria is associated with a progressive loss of renal function; we recently found that both intrarenal effects of proteinuria and the state of systemic nephrosis play an independent role in proteinuria-induced renal damage. Reduction of proteinuria is an important mechanism underlying the renoprotective effect of angiotensin-converting enzyme inhibition (ACEi). Both the reduction of proteinuria and the attenuation of the systemic state of nephrosis may be involved in the renoprotection by ACEi. METHODS: This article entails a post hoc analysis of a previous study on the renoprotective effect of ACEi lisinopril in adriamycin nephrosis. It was attempted to modify therapeutic efficacy of ACEi by increasing lisinopril dose and by dietary sodium restriction, respectively. In this analysis, we aimed to delineate the contribution of proteinuria reduction and the reduction of other intermediate parameters such as hyperlipidemia and blood pressure on the protection against focal glomerulosclerosis (FGS). RESULTS: We found that in adriamycin nephrosis, ACEi significantly reduced proteinuria, lipids, and blood pressure and provided protection against FGS. Treatment modification by increasing the lisinopril dose resulted in a further reduction of FGS without significant effects on intermediate parameters (proteinuria, hyperlipidemia, and blood pressure), whereas surprisingly, treatment modification by sodium restriction resulted in a further attenuation of intermediate parameters, without additional protection against FGS. CONCLUSIONS: The renoprotective benefit of an obtained attenuation of intermediate parameters is modified by other factors. Further optimization of renoprotective therapy requires identification of such factors and explicit consideration of therapeutic efficacy on intermediate parameters as well as hard end points.

Proteinuria and progression of renal disease: therapeutic implications.

The relationship between proteinuria and progression of renal disease has long been an issue of debate. The present review deals with some of the recent publications on this topic. New concepts are emphasized: the possible causal role of proteinuria in the pathophysiology of progressive renal function loss, and the decrease in urinary protein loss at the beginning of renoprotective therapy as a predictor of renal function outcome during this treatment.

Antiproteinuric effect predicts renal protection by angiotensin-converting enzyme inhibition in rats with established adriamycin nephrosis.

1. The mechanism of renal protection by angiotensin-converting enzyme inhibition is still the subject of debate. Inhibition of proteinuria might play a role. If so, a good antiproteinuric response to angiotensin-converting enzyme inhibition should predict subsequent protection against renal structural damage. This hypothesis has not been tested in models where treatment is started after the renal disease is well established, i.e. models that mimic the clinical situation. 2. We therefore investigated this hypothesis in 96 male Wistar rats with established adriamycin nephrosis. Reduction of proteinuria was achieved by lisinopril (0, 2, 5 and 10 mg day-1 kg-1) on two different sodium diets (0.3% and 0.05% NaCl). Therapy started 6 weeks after adriamycin (at stable proteinuria) and was continued for 6 weeks. 3. Lisinopril reduced blood pressure by 32 +/- 4% and proteinuria by an average of 72 +/- 7%, with stabilization after 2 weeks. Considerable interindividual differences in antiproteinuric response was found. Glomerulosclerosis score was reduced by 15 +/- 5%. All the effects of angiotensin-converting enzyme inhibitors were enhanced by sodium depletion, but sodium depletion in itself did not affect blood pressure (124 +/- 4 mmHg), proteinuria (664 +/- 68 mg/day) or glomerulosclerosis score (30 +/- 5%). Interestingly, the more proteinuria was reduced initially in an individual rat, the less sclerosis was found in the long term in that rat. 4. In conclusion, angiotensin-converting enzyme inhibition lowers proteinuria and prevents glomerulosclerosis in established adriamycin nephrosis. These effects are enhanced by sodium depletion. The individual short-term antiproteinuric effect predicts the protection against ultimate glomerular damage. This is consistent with the hypothesis that reduction of proteinuria is a mechanism by which angiotensin-converting enzyme inhibitors exert renoprotection.

Prognostic value of the short-term antiproteinuric response to ACE inhibition for prediction of GFR decline in patients with nondiabetic renal disease.

In chronic renal disease, the severity of proteinuria is associated with the rate of renal function loss. Proteinuria, therefore, was postulated to play a role in the final common pathway of chronic renal function loss. If so, reduction of proteinuria would improve long-term renal outcome. Improvement of long-term renal function outcome has been obtained in several intervention trials; in these studies; regimens providing better renoprotection were associated with more effective reduction of poteinuria than control regimens. As the reduction of proteinuria is mostly associated with a fall in blood pressure, however, it is difficult to delineate the respective roles of the lowering of blood pressure and of proteinuria. Interestingly, the initial reduction of proteinuria (but not of blood pressure) by antihypertensive treatment appears to predict long-term renal outcome in man as well as in experimental renal disease. This suggests that an intervention strategy aimed not only at the normalization of blood pressure, but also specifically at elimination of proteinuria, might be able to improve long-term renal outcome in proteinuric patients. If so, this would provide further evidence in support of the hypothesis that proteinuria is causally involved in the progression of long-term renal function loss.