The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study.

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.

Degeneration of Lumbar Intervertebral Discs: Characterization of Anulus Fibrosus Tissue and Cells of Different Degeneration Grades.

Intervertebral disc (IVD) herniation and degeneration is a major source of back pain. In order to regenerate a herniated and degenerated disc, closure of the anulus fibrosus (AF) is of crucial importance. For molecular characterization of AF, genome-wide Affymetrix HG-U133plus2.0 microarrays of native AF and cultured cells were investigated. To evaluate if cells derived from degenerated AF are able to initiate gene expression of a regenerative pattern of extracellular matrix (ECM) molecules, cultivated cells were stimulated with bone morphogenetic protein 2 (BMP2), transforming growth factor ß1 (TGFß1) or tumor necrosis factor-α (TNFα) for 24 h. Comparative microarray analysis of native AF tissues showed 788 genes with a significantly different gene expression with 213 genes more highly expressed in mild and 575 genes in severe degenerated AF tissue. Mild degenerated native AF tissues showed a higher gene expression of common cartilage ECM genes, whereas severe degenerated AF tissues expressed genes known from degenerative processes, including matrix metalloproteinases (MMP) and bone associated genes. During monolayer cultivation, only 164 differentially expressed genes were found. The cells dedifferentiated and altered their gene expression profile. RTD-PCR analyses of BMP2- and TGFß1-stimulated cells from mild and severe degenerated AF tissue after 24 h showed an increased expression of cartilage associated genes. TNFα stimulation increased MMP1, 3, and 13 expression. Cells derived from mild and severe degenerated tissues could be stimulated to a comparable extent. These results give hope that regeneration of mildly but also strongly degenerated disc tissue is possible.

Chemokine CCL25 Induces Migration and Extracellular Matrix Production of Anulus Fibrosus-Derived Cells.

Intervertebral disc degeneration is a major source of back pain. For intervertebral disc regeneration after herniation a fast closure of anulus fibrosus (AF) defects is crucial. Here, the use of the C-C motif chemokine ligand 25 (CCL)25 in comparison to differentiation factors such as transforming growth factor (TGF)ß3, bone morphogenetic protein (BMP)2, BMP7, BMP12, and BMP14 (all in concentrations of 10, 50 and 100 ng/mL) was tested in an in vitro micro mass pellet model with isolated and cultivated human AF-cells (n = 3) to induce and enhance AF-matrix formation. The pellets were differentiated (serum-free) with supplementation of the factors. After 28 days all used factors induced proteoglycan production (safranin O staining) and collagen type I production (immunohistochemical staining) in at least one of the tested concentrations. Histomorphometric scoring revealed that TGFß3 delivered the strongest induction of proteoglycan production in all three concentrations. Furthermore, it was the only factor able to facilitate collagen type II production, even higher than in native tissue samples. CCL25 was also able to induce proteoglycan and collagen type I production comparable to several BMPs. CCL25 could additionally induce migration of AF-cells in a chemotaxis assay and therefore possibly aid in regeneration processes after disc herniation by recruiting AF-cells.

The SCIentinel study--prospective multicenter study to define the spinal cord injury-induced immune depression syndrome (SCI-IDS)--study protocol and interim feasibility data.

BACKGROUND: Infections are the leading cause of death in the acute phase following spinal cord injury and qualify as independent risk factor for poor neurological outcome ("disease modifying factor"). The enhanced susceptibility for infections is not stringently explained by the increased risk of aspiration in tetraplegic patients, neurogenic bladder dysfunction, or by high-dose methylprednisolone treatment. Experimental and clinical pilot data suggest that spinal cord injury disrupts the balanced interplay between the central nervous system and the immune system. The primary hypothesis is that the Spinal Cord Injury-induced Immune Depression Syndrome (SCI-IDS) is 'neurogenic' including deactivation of adaptive and innate immunity with decreased HLA-DR expression on monocytes as a key surrogate parameter. Secondary hypotheses are that the Immune Depression Syndrome is i) injury level- and ii) severity-dependent, iii) triggers transient lymphopenia, and iv) causes qualitative functional leukocyte deficits, which may endure the post-acute phase after spinal cord injury. METHODS/DESIGN: SCIentinel is a prospective, international, multicenter study aiming to recruit about 118 patients with acute spinal cord injury or control patients with acute vertebral fracture without neurological deficits scheduled for spinal surgery. The assessment points are: i) <31 hours, ii) 31-55 hours, iii) 7 days, iv) 14 days, and v) 10 weeks post-trauma. Assessment includes infections, concomitant injury, medication and neurological classification using American Spinal Injury Association impairment scale (AIS) and neurological level. Laboratory analyses comprise haematological profiling, immunophenotyping, including HLA-DR expression on monocytes, cytokines and gene expression of immune modulators. We provide an administrative interim analysis of the recruitment schedule of the trial. DISCUSSION: The objectives are to characterize the dysfunction of the innate and adaptive immune system after spinal cord injury and to explore its proposed 'neurogenic' origin by analyzing its correlation with lesion height and severity. The trial protocol considers difficulties of enrolment in an acute setting, and loss to follow up. The administrative interim analysis confirmed the feasibility of the protocol. Better understanding of the SCI-IDS is crucial to reduce co-morbidities and thereby to attenuate the impact of disease modifying factors to protect neurological "outcome at risk". This putatively results in improved spinal cord injury medical care. TRIAL REGISTRATION DRKS-ID: DRKS00000122 (German Clinical Trials Registry).

The analysis of segmental mobility with different lumbar radiographs in symptomatic patients with a spondylolisthesis.

PURPOSE: Lumbar flexion-extension radiographs in standing position (SFE) are the most commonly used imaging method to evaluate segmental mobility. Many surgeons use SFE to disclose abnormal vertebral motion and base their decision for surgical fusion on its results. We tested the hypothesis that imaging in standing and recumbent position (SRP) reveals a higher sagittal translation (ST) and sagittal rotation (SR) in symptomatic patients than with SFE. MATERIALS AND METHODS: We analysed images of 100 symptomatic patients with a low-grade spondylolisthesis that underwent surgical fusion. To determine the ST and SR in SRP, we compared the images taken in the recumbent position in the CT with images taken in the standing position during the routine plain radiography. RESULTS: The measurement of ST revealed an absolute value of 2.3 ± 1.5 mm in SFE and 4.0 ± 2.0 mm in SRP and differed significantly (p = 0.001). The analysis of the relative value showed an ST of 5.9 ± 3.9% in SFE and 7.8 ± 5.4% in SRP (p = 0.008). The assessment of ST in flexion and in a recumbent position (FRP) revealed the highest ST (4.6 ± 2.5 mm or 9.2 ± 5.7%). Comparison of SR showed the highest rotation in SFE (6.1° ± 3.8°), however, compared to SRP (5.4° ± 3.3°), it missed the level of significance (p = 0.051). CONCLUSIONS: For evaluation of ST in symptomatic patients with spondylolisthesis SRP appears to be more suitable than SFE, while a pathological SR is better revealed in SFE. The analysis of SRP might offer a complementary method to detect or exclude pathological mobility in more cases.

Anterior cervical discectomy and fusion: comparison of titanium and polyetheretherketone cages.

BACKGROUND: Titanium (TTN) cages have a higher modulus of elasticity when compared with polyetheretherketone (PEEK) cages. This suggests that TTN-cages could show more frequent cage subsidence after anterior cervical discectomy and fusion (ACDF) and therefore might lead to a higher loss of correction. We compared the long term results of stand-alone PEEK- and TTN-cages in a comparable patient collective that was operated under identical operative settings. METHODS: From 2002 to 2007 154 patients underwent single-level ACDF for degenerative disc disease (DDD). Clinical and radiological outcome were assessed in 86 eligible patients after a mean of 28.4 months. 44 patients received a TTN- and 42 patients a PEEK-cage. RESULTS: Solid arthrodesis was found in 93.2% of the TTN-group and 88.1% of the PEEK-group. Cage subsidence was observed in 20.5% of the TTN- and 14.3% of the PEEK-group. A significant segmental lordotic correction was achieved by both cage-types. Even though a loss of correction was found at the last follow-up in both groups, it did not reach the level of statistical significance. Statistical analysis of these results revealed no differences between the TTN- and PEEK-group.When assessed with the neck disability index (NDI), the visual analogue scale (VAS) of neck and arm pain and Odom's criteria the clinical data showed no significant differences between the groups. CONCLUSIONS: Clinical and radiological outcomes of ACDF with TTN- or PEEK-cages do not appear to be influenced by the chosen synthetic graft. The modulus of elasticity represents only one of many physical properties of a cage. Design, shape, size, surface architecture of a cage as well as bone density, endplate preparation and applied distraction during surgery need to be considered as further important factors.

Comparison of sagittal vertical axis and decompression on the clinical outcome of cervical spondylotic myelopathy.

OBJECTIVE: Decompression and cervical balance are major goals in the surgical treatment of cervical spondylotic myelopathy (CSM). Cervical balance is assumed to be a key factor for neurological recovery and pain reduction. Surgical reduction of C2-7 sagittal vertical axis (SVA) correlates with clinical improvement. However, it remains unclear, how much or even if correction is necessary for clinical improvement as long as surgery results in successful decompression. We aim to evaluate the role of radiological cervical balance parameter on the short-term course of CSM. METHODS: This is a retrospective study with prospectively collected data of 90 patients. The authors identified 45 patients suffering from CSM that underwent decompressive surgery and instrumentation and showed an increased C2-7 sagittal vertical axis (SVA) after surgery. 45 consecutive patients with a decreased C2-7 SVA were selected as a control group. RESULTS: Surgery improved the clinical outcome of both groups significantly. No differences could be seen comparing neck pain and neurological improvement between both groups. An increased C2-7 SVA did not correlate with an inferior clinical outcome. T1-slope correlated with the Cobb-angle. CONCLUSIONS: Decompression and stabilization appear to be key elements of surgical treatment of CSM. In short terms, clinical improvement does not appear to affect patients negatively who show a larger C2-7 SVA after surgery. Optimal C2-7 SVA and necessity for a specific C2-7 correction is unclear. The term "balance" remains a complex entity without clear definition.

Polymethylmethacrylate-assisted ventral discectomy: rate of pseudarthrosis and clinical outcome with a minimum follow-up of 5 years.

BACKGROUND: Polymethylmethacrylate (PMMA) assisted ventral discectomy has been criticized for high rates of graft migration and pseudarthrosis when compared with various other fusion procedures for the treatment of cervical degenerative disc disease (DDD), therefore rendering it not the preferred choice of treatment today. Recently however spine surgery has been developing towards preservation rather than restriction of motion, indicating that fusion might not be necessary for clinical success. This study presents a long term comparison of clinical and radiological data from patients with pseudarthrosis and solid arthrodesis after PMMA assisted ventral discectomy was performed. METHODS: From 1986 to 2004 416 patients underwent ventral discectomy and PMMA interposition for DDD. The clinical and radiological outcome was assessed for 50 of 127 eligible patients after a mean of 8.1 years. Based on postoperative radiographs the patients were dichotomized in those with a pseudarthrosis (group A) and those with solid arthrodesis (group B). RESULTS: Pseudarthrosis with movement of more than 2 of the operated segment was noted in 17 cases (group A). In 33 cases no movement of the vertebral segment could be detected (group B). The analysis of the clinical data assessed through the neck disability index (NDI), the visual analogue scale (VAS) of neck and arm pain and Odom's criteria did not show any significant differences between the groups.Patients from group B showed a trend to higher adjacent segment degeneration (ASD) than group A (p = 0.06). This correlated with the age of the patients. CONCLUSIONS: PMMA assisted discectomy shows a high rate of pseudarthrosis. But the clinical long-term success does not seem to be negatively affected by this.

Arachnoid cysts of the middle cranial fossa accompanied by subdural effusions--experience with 60 consecutive cases.

BACKGROUND: Subdural effusions (SDEs) can complicate arachnoid cysts of the middle cranial fossa (ACMFs). While there is a consensus that at least in adults asymptomatic ACMFs should not be operated, those with concomitant subdural and/or intracystic effusions are clinically apparent in the majority of cases and should be surgically treated. But it remains unclear, which surgical procedure is best. METHODS: Since 1980, 60 out of 343 patients with an ACMF presented with accompanying SDEs. Four categories of SDEs were differentiated radiologically. This collective was controlled in a follow-up study up to 60 months after conservative or operative treatment by clinical and radiological means. RESULTS: In 54 of the 60 patients, we saw an indication for surgical treatment. Twenty-nine patients received a burr hole, 13 cases were treated by craniotomy, seven by endoscopical means, three patients underwent shunting and two combined procedures. Six patients were treated conservatively. An excellent final clinical outcome was observed in 55 cases. While craniotomy succeeded best to reduce the cyst volume in postoperative CT, the final clinical outcome did not differ significantly compared with burr hole trepanation. CONCLUSIONS: Patients with small effusions can be treated conservatively in selected cases. Based on our experience, we prefer a differentiated therapy. As first procedure, burr hole and subdural drainage were performed, leaving the cyst alone, seeming sufficient for the majority of cases. Craniotomy or endoscopical means should be reserved as treatment of choice for special cases, depending on category and acuteness of SDE and size/localisation of the ACMF.

Comparison between anterior and posterior decompression with instrumentation for cervical spondylotic myelopathy: sagittal alignment and clinical outcome.

OBJECT: A variety of anterior, posterior, and combined approaches exist to decompress the spinal cord, restore sagittal alignment, and avoid kyphosis, but the optimal surgical strategy remains controversial. The authors compared the anterior and posterior approach used to treat multilevel cervical spondylotic myelopathy (CSM), focusing on sagittal alignment and clinical outcome. METHODS: The authors studied 48 patients with CSM who underwent multilevel decompressive surgery using an anterior or posterior approach with instrumentation (24 patients in each group), depending on preoperative sagittal alignment and direction of spinal cord compression. In the anterior group, a 1-2-level corpectomy was followed by placement of an expandable titanium cage. In the posterior group, a multilevel laminectomy and posterior instrumentation using lateral mass screws was performed. Postoperative radiography and clinical examinations were performed after 1 week, 12 months, and at last follow-up (range 15-112 months, mean 33 months). The radiological outcome was evaluated using measurement of the cervical and segmental lordosis. RESULTS: Both the posterior multilevel laminectomy (with instrumentation) and the anterior cervical corpectomy (with instrumentation) improved clinical outcome. The anterior group had a significantly lower preoperative cervical and segmental lordosis than the posterior group. The cervical and segmental lordosis improved in the anterior group by 8.8 and 6.2 degrees, respectively, and declined in the posterior group by 6.5 and 3.8 degrees, respectively. The loss of correction was higher in the anterior than in the posterior group (-2.0 vs -0.7 degrees, respectively) at last follow-up. CONCLUSIONS: These results demonstrate that both anterior and posterior decompression (with instrumentation) are effective procedures to improve the neurological outcome of patients with CSM. However, sagittal alignment may be better restored using the anterior approach, but harbors a higher rate of loss of correction. In cases involving a preexisting cervical kyphosis, an anterior or combined approach might be necessary to restore the lordotic cervical alignment.

Proliferation, Migration, and ECM Formation Potential of Human Annulus Fibrosus Cells Is Independent of Degeneration Status.

OBJECTIVE: The objective was to evaluate the proliferating, migratory and extracellular matrix (ECM) forming potential of annulus fibrosus cells derived from early (edAFC) or advanced (adAFC) degenerative tissue and their usability as a possible cell source for regenerative approaches for AF closure. DESIGN: EdAFC (n = 5 Pfirrman score of 2-3) and adAFC (n = 5 Pfirrman score of 4-5) were isolated from tissue of patients undergoing spine stabilizing surgery. Cell migration on stimulation with human serum (HS), platelet-rich plasma (PRP), and transforming growth factor ß-3 (TGFB3) was assessed by migration assay and proliferation was assessed on stimulation with HS. Induction of ECM synthesis was evaluated by gene expression analysis of AF-related genes in three-dimensional scaffold cultures that have been stimulated with 5% PRP or 10 ng/mL TGFB3 and histologically by collagen type I, type II, alcian blue, and safranin-O staining. RESULTS: EdAFC and adAFC were significantly attracted by 10% HS and 5% PRP. Additionally, both cell groups proliferated under stimulation with HS. Stimulation with 10 ng/mL TGFB3 showed significant induction of gene expression of collagen type II and aggrecan, while 5% PRP decreased the expression of collagen type I. Both cell groups showed formation of AF-like ECM after stimulation with TGFB3, whereas stimulation with PRP did not. CONCLUSIONS: Our study demonstrated that AF cells retain their potential for proliferation, migration, and ECM formation independent of the degeneration status of the tissue. Proliferation, migration, and ECM synthesis of the endogenous AF cells can be supported by different supplements. Hence, endogenous AF cells might be a suitable cell source for a regenerative repair approaches.

The short- and mid-term effect of dynamic interspinous distraction in the treatment of recurrent lumbar facet joint pain.

Owing to failure to achieve positive long-term effects, the currently performed treatment methods for lumbar facet joint syndrome (LFJS) are still under debate. Interspinous distraction devices unload the facet joints. Thus, these devices might be an alternative surgical treatment method for LFJS. The aim of this study was to evaluate the clinical and radiological outcome of an interspinous distraction device for the treatment of LFJS. Subjects had verified single level LFJS at level L4-5. They received percutaneous facet joint denervation (PFJD). If pain persisted, they were offered implantation of an interspinous device (Coflex) and/or repeat PFJD. Clinical and radiological outcome was determined before and after PFJD or surgery up to 2 years afterwards in all cases. Forty-one patients with LFJS at L4-5 underwent PFJD. Twenty patients with persisting pain underwent a subsequent surgery for implantation of an interspinous device. Five patients with recurrent pain at 6-12 months opted for an additional PFJD. Three obese patients (body weight > 100 kg) had persistent pain at 3 months after surgery and received additionally dorsal semi-dynamic stabilization. The clinical outcome improved significantly in the surgically treated patients; however, it did not differ compared with patients receiving PFJD only after 24 months.Radiological evaluation revealed a restricted range of motion (ROM) of the operated and an elevated ROM of the adjacent segment. Surgical or device-related complications were not observed. In conclusions, the implantation of an interspinous Coflex device in case of recurrent facet joint pain succeeds to improve facet joint pain in clinical shortand mid-term settings. However, it does not exceed the outcome of denervated patients.

The influence of cage positioning and cage type on cage migration and fusion rates in patients with monosegmental posterior lumbar interbody fusion and posterior fixation.

In posterior lumbar interbody fusion, cage migrations and lower fusion rates compared to autologous bone graft used in the anterior lumbar interbody fusion procedure are documented. Anatomical and biomechanical data have shown that the cage positioning and cage type seem to play an important role. Therefore, the aim of the present study was to evaluate the impact of cage positioning and cage type on cage migration and fusion. We created a grid system for the endplates to analyze different cage positions. To analyze the influence of the cage type, we compared "closed" box titanium cages with "open" box titanium cages. This study included 40 patients with 80 implanted cages. After pedicle screw fixation, 23 patients were treated with a "closed box" cage and 17 patients with an "open box" cage. The follow-up period averaged 25 months. Twenty cages (25%) showed a migration into one vertebral endplate of <3 mm and four cages (5%) showed a migration of > or =3 mm. Cage migration was highest in the medio-medial position (84.6%), followed by the postero-lateral (42.9%), and the postero-medial (16%) cage position. Closed box cages had a significantly higher migration rate than open box cages, but fusion rates did not differ. In conclusion, cage positioning and cage type influence cage migration. The medio-medial cage position showed the highest migration rate. Regarding the cage type, open box cages seem to be associated with lower migration rates compared to closed box cages. However, the cage type did not influence bone fusion.

Long-term results following titanium cranioplasty of large skull defects.

OBJECT: Decompressive craniectomy is an established procedure to lower intracranial pressure. Therefore, cranioplasty remains a necessity in neurosurgery as well. If the patient's own bone flap is not available, the surgeon can choose between various alloplast grafts. A review of the literature proves that 4-13.8% of polymethylmethacrylate plates and 2.6-10% of hydroxyapatite-based implants require replacement. In this retrospective study of large skull defects, the authors compared computer-assisted design/computer-assisted modeled (CAD/CAM) titanium implants for cranioplasty with other frequently used materials described in literature. METHODS: Twenty-six patients underwent cranioplasty with CAD/CAM titanium implants (mean diameter 112 mm). With the aid of visual analog scales, the patients' pain and cosmesis were evaluated 6-12 years (mean 8.1 years) after insertion of the implants. RESULTS: None of the implants had to be removed. Of all patients, 68% declared their outcomes as excellent, 24% as good, 0.8% as fair, and 0% as poor. There was no resulting pain in 84% of the patients, and 88% were satisfied with the cosmetic result, noting > 75 mm on the visual analog scale of cosmesis. All patients would have chosen cranioplasty again, stating an improvement in their quality of life by the calvarial reconstruction. Nevertheless, follow-up images obtained in 4 patients undergoing removal of meningiomas was only suboptimal. CONCLUSIONS: With the aid of CAD technology, all currently used alloplastic materials are suited even for large skull defect cranioplasty. Analysis of the authors' data and the literature shows that cranioplasty with CAD/CAM titanium implants provides the lowest rate of complications, reasonable costs, and acceptable postoperative imaging. Polymethylmethacrylate is suited for primary cranioplasty or for long-term follow-up imaging of tumors. Titanium implants seem to be the material of choice for secondary cranioplasty of large skull defects resulting from decompressive craniectomy after trauma or infarction. Expensive HA-based ceramics show no obvious advantage over titanium or PMMA.

Neurophysiological intraoperative monitoring in neurosurgery: aid or handicap? An international survey.

OBJECT: Neurophysiological intraoperative monitoring (IOM) is regarded as a useful tool to provide information about physiological changes during surgery in eloquent areas of the nervous system, to increase safety and reduce morbidity. Nevertheless, numerous older studies report that very few patients benefit from IOM, and that there are high rates of false-positive and false-negative changes of neurophysiological parameters during surgery. There is an ongoing discussion about the effectiveness of neurophysiological IOM. This questionnaire study was performed to evaluate the attitude of neurosurgeons toward neurophysiological IOM and the availability of this tool. METHODS: One hundred fifty neurosurgeons from 60 institutions in 16 countries were asked to answer anonymously a questionnaire with 11 questions. The questionnaire covered aspects of personal experience, the neurosurgical institution, and availability of neurophysiological IOM as well as asking the surgeon's opinion of the procedure. RESULTS: One hundred nine questionnaires were returned (73%). Seven questionnaires were excluded because of failure to complete the form correctly or completely, leaving 102 respondents from 44 institutions in 16 countries in the study; 79.5% of the included institutions provided neurophysiological IOM. Young neurosurgeons did not put more trust in IOM than experienced neurosurgeons. With growing IOM experience, surgeons seem to allow less influence of the findings on the course of their operation. At large institutions in which > 1500 operations per year are done, IOM is performed by the neurosurgeons themselves in most cases. In institutions with fewer operations, the IOM team consists mostly of nonneurosurgeons. Regardless of the availability of neurophysiological IOM, all surgeons stated that IOM is gaining increasing importance. CONCLUSIONS: Neurophysiological IOM represents an established tool in neurosurgery. Although the importance of IOM is emphasized by the majority of neurosurgeons, the relevance of this tool to the course of the operation changes with increasing neurophysiological IOM experience.

Vestibular ganglion neurons survive hair cell defects in jerker, shaker, and Varitint-waddler mutants and downregulate calretinin expression.

Bipolar neurons (BNs) in the vestibular ganglion (VG) connect vestibular hair cells with the central nervous system (CNS). Disturbed function and cell loss in central vestibular target areas or in the vestibular periphery involve BNs either retro- or anterogradely. However, the impact of central vestibular disturbances or hair cell defects on the maintenance of BNs is poorly understood. In the present study the volume of the VG, the size and total number of BNs, and the number of BNs expressing the calcium-binding protein calretinin (Calr) were quantified stereologically in the cerebellar mutants purkinje cell degeneration (pcd/pcd), weaver (wv/wv), and Lurcher (Lc/+), and in the vestibular mutants jerker (je/je), shaker-1 (sh/sh), and Varitint-waddler (Va/+). In all the different mutant mice investigated the total number of BNs did not differ from that of wildtypes. In contrast, the number of Calr-positive BNs was significantly reduced in je/je (23%) and sh/sh (33%) mutants. Reduced cell size was apparent in sh/sh mutants and the volume of the VG significantly decreased in je/je mice. Calr was virtually absent from calyx endings in the vestibular periphery of je/je, sh/sh, and Va/+ mutants, whereas in wildtypes and cerebellar mutants many calyces displayed intense Calr labeling. These results imply that the survival of BNs is apparently unaffected by the peripheral and central target defects found in the mutants investigated. Whether the decrease in Calr expression may reflect biochemical adaptations in response to input disturbances or a specific loss of large BNs is discussed.

The influence of sagittal profile alteration and final lordosis on the clinical outcome of cervical spondylotic myelopathy. A Delta-Omega-analysis.

PURPOSE: Decompression and maintaining or restoring a cervical lordosis are major goals in the surgical treatment of cervical spondylotic myelopathy (CSM). Numerous studies support the assumption that cervical lordosis is a key factor for neurological recovery and pain reduction. However, even kyphotic patients can be asymptomatic. The balance of the spine is subject of an increasing number of publications. The main purpose of the study was to evaluate the validity of lordotic alignment on the course of CSM and to set this parameter in context with well-validated tools, namely the modified Japanese Orthopaedic Association scoring system (mJOAS) and the visual analogue scale (VAS), to predict and measure the clinical outcome after surgery. METHODS: This is a retrospective study with prospectively collected data of a heterogeneous cohort. The authors analyzed the records of 102 patients suffering from CSM that underwent decompressive surgery and instrumentation. Clinical outcome was assessed by using the mJOAS, VAS and Odom's criteria. The radiological analysis involved comparison of pre- and postoperative radiographs. The patients were divided into subgroups to be able to compare the influence of various amounts of correction (3 Delta-groups: <0°, 1-7° and ≥8°) and final lordosis (4 Omega-groups: 0-7°, 8-14°, 15-21°, ≥22°). RESULTS: 219 levels were fused in 102 patients. Surgery improved the clinical outcome of all groups significantly. A lordotic profile was achieved in all analyzed groups. Patients that showed small lordosis after surgery (<8°) did not have an inferior clinical outcome compared to patients with larger cervical lordosis (>14°). The comparison of Odom's criteria showed that preoperatively kyphotic patients benefitted more from surgery than lordotic patients (p = 0.029), but no differences could be seen comparing neck pain and neurological improvement. The improvement of pain and neurological impairment measured by VAS and mJOAS supports the statistical impact and validity of the data despite comparatively small numbers of patients. The lack of postoperative kyphosis is a major limitation of the study to encompass the impact of sagittal alignment on clinical outcome. CONCLUSIONS: Decompression and stabilization appear to be key elements of surgical treatment of CSM. While the achievement of cervical lordosis remains a major goal of surgery, clinical improvement is not hindered in patients who show small lordosis. However, kyphosis should be eliminated in symptomatic patients. The terms "balance" and "physiologic lordosis" remain complex entities without clear definition. To check the results of our study controlled randomized trials to validate and determine the exact role of cervical balance on the course of CSM would be helpful.

Empty polyetheretherketone (PEEK) cages in anterior cervical diskectomy and fusion (ACDF) show slow radiographic fusion that reduces clinical improvement: results from the prospective multicenter "PIERCE-PEEK" study.

BACKGROUND: Anterior cervical diskectomy and fusion (ACDF) is a well-established surgical treatment for radiculopathy and myelopathy. Previous studies showed that empty PEEK cages have lower radiographic fusion rates, but the clinical relevance remains unclear. This paper's aim is to provide high-quality evidence on the outcomes of ACDF with empty PEEK cages and on the relevance of radiographic fusion for clinical outcomes. METHODS: This large prospective multicenter clinical trial performed single-level ACDF with empty PEEK cages on patients with cervical radiculopathy or myelopathy. The main clinical outcomes were VAS (0-10) for pain and NDI (0-100) for functioning. Radiographic fusion was evaluated by two investigators for three different aspects. RESULTS: The median (range) improvement of the VAS pain score was: 3 (1-6) at 6 months, 3 (2-8) at 12 months, and 4 (2-8) at 18 months. The median (range) improvement of the NDI score was: 12 (2-34) at 6 months, 18 (4-46) at 12 months, and 22 (2-44) at 18 months. Complete radiographic fusion was reached by 126 patients (43%) at 6 months, 214 patients (73%) at 12 months, and 241 patients (83%) at 18 months. Radiographic fusion was a highly significant (p < 0.001) predictor of the improvement of VAS and NDI scores. CONCLUSION: This study provides strong evidence that ACDF is effective treatment, but the overall rate of radiographic fusion with empty PEEK cages is slow and insufficient. Lack of complete radiographic fusion leads to less improvement of pain and disability. We recommend against using empty uncoated pure PEEK cages in ACDF. TRIAL REGISTRATION: ISRCTN42774128. Retrospectively registered 14 April 2009.

Four-year results of a prospective single-arm study on 200 semi-constrained total cervical disc prostheses: clinical and radiographic outcome.

OBJECTIVE Recent studies have described encouraging outcomes after cervical total disc replacement (cTDR), but there are also critical debates regarding the long-term effects of heterotopic ossification (HO) and the prevalence of adjacent-level degeneration. The aim in this paper was to provide 4-year clinical and radiographic outcome results on the activ C disc prosthesis. METHODS A total of 200 subjects underwent single-level activ C (Aesculap AG) implantation between C-3 and C-7 for the treatment of symptomatic degenerative disc disease. Clinical and radiographic assessments were performed preoperatively, intraoperatively, at discharge, and again at 6 weeks, 6 months, 1 year, 2 years, and 4 years. Radiographic evaluations were done by an independent core laboratory using a specific software for quantitative motion analysis. RESULTS Neck Disability Index (NDI) and visual analog scale (VAS) score for neck and arm pain decreased significantly from baseline to the 4-year follow-up. The mean improvement for NDI was 20, for VAS severity and frequency of neck pain 26.4 and 28, and for VAS severity and frequency of arm pain 30.7 and 35.1, respectively. The neurological situation improved for the majority of patients (86.4%); 76.1% of cases were asymptomatic. Subsequent surgical interventions were reported in 7% of the cases, including device removals in 3%. In 2.5% a subsidence greater than 3 mm was recorded; 1 of these cases also had a migration greater than 3 mm. No device displacement, expulsion, disassembly, loose or fractured device, osteolysis, or facet joint degeneration at the index level was observed. Segmental lordotic alignment changed from -2.4° preoperatively to -6.2° at 4 years, and postoperative height was maintained during the follow-up. Advanced HO (Grade III and IV) was present in 27.1% of the cases; 82.4% showed segmental mobility. A progression of radiographic adjacent-segment degeneration occurred in 28.2%, but only 4.5% required surgical treatment. CONCLUSIONS The activ C is a safe and effective device for cervical disc replacement confirming the encouraging results after cTDR. Clinical trial registration no.: NCT02492724 ( clinicaltrials.gov ).

Transient sacroiliac joint-related pain is a common problem following lumbar decompressive surgery without instrumentation.

OBJECTIVE: Patients with lumbar stenosis profit substantially from decompressive surgery. The change of body position and walking behaviour after successful surgery might lead to changed force effects on the entire spine and on the sacroiliac joint (SIJ). We analyzed the incidence of postoperative SIJ-related pain. METHODS: The authors analyzed the records of 100 consecutive patients from three institutions, who underwent decompressive surgery without instrumentation. The diagnosis of SIJ-related pain was confirmed by periarticular infiltration. The radiological changes of the sacroiliac joint were assessed in plain radiographs in both groups: patients with SIJ pain (group 1) and patients without SIJ pain (group 2) after surgery. RESULTS: 22 patients required medical attention due to SIJ-related pain after surgery. While the walking distance increased substantially in both groups without difference (p=0.150), the analysis of overall satisfaction favoured group 2 (p=0.047). Female patients suffered more from SIJ pain after surgery (p=0.036). Age, severity of radiological changes or number of operated segments appeared not to trigger SIJ-related pain. CONCLUSION: The adaptation of a changed body posture and gait could lead to transient overload of the SIJ and surrounding myofascial structures. The patients should be informed about this possible condition to avoid uncertainty, discontent, unnecessary diagnostics and to induce a quick, specific treatment. Non-diagnosed sacroiliac joint-related pain could be a possible, but reversible reason for the diagnosis of a "failed-back-surgery".