[Show abstract][Hide abstract] ABSTRACT: Background Cervical Disc Arthroplasty (CDA) seems to be an alternative to Anterior Cervical Decompression and Fusion (ACDF) and was developed to minimize the risk of Adjacent Segment Disease (ASD). The ROTAIO Cervical Disc Prosthesis represents a new unconstrained implant with a variable centre of rotation which should enable physiological facet-guided movement. The aim of this current study was to evaluate the clinical outcomes after arthroplasty using ROTAIO Cervical Disc Prosthesis. Method Twenty-seven female and 18 male patients (n = 45) with a mean age of 43.7 ± 7.8 years were prospectively followed up for a maximum of 24 month. Clinical outcomes were assessed by Neck Disability Index (NDI), visual analogue scale (VAS) scores for neck and arm pain, patients´ overall satisfaction and the usage of analgesics. Additionally, radiographic information including ROM of the functional spinal unit (FSU) and signs of adjacent segment disease were recorded. Results NDI and VAS scores showed significant improvement 6 months after surgery and at last follow-up (p < 0.001). Concerning overall satisfaction 95.7 % of the patients showed good to excellent results at the last visit and a significant reduction of analgesic usage was observed (p < 0.001). Radiographic measurements showed a mean increase of ROM up to 8.40° in the treated FSU at last follow-up (p < 0.001). No signs of anterior migration or dislocation of the prosthesis and no subsidence was recorded radiographically. There were no major complications and a low rate of secondary procedures (2.2 %). Conclusion In the 24-months follow-up the ROTAIO Cervical Disc Prosthesis provided excellent clinical and radiographical results and seems to be safe and effective for the treatment of symptomatic single-level degenerative disc disease.
Preview · Article · Dec 2016 · BMC Musculoskeletal Disorders
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Animal data suggest an association between neuroinflammation and secondary brain injury including axonal injury after aneurysmal subarachnoid hemorrhage (aSAH). We sought to study the association between brain extracellular interleukin (IL)-6 and TAU-protein levels as a surrogate marker for neuroinflammation and axonal injury in patients with poor grade aSAH.
Prospectively collected data from 26 consecutive poor-grade aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD) were retrospectively analyzed. IL-6 and TAU-protein levels were analyzed using ELISA from a single CMD-sample every 24 hours and correlated with brain metabolic and hemodynamic parameters. Patients were dichotomized to high-grade (N=10) or low-grade (N=16) neuroinflammation according to their median CMD-IL-6 levels. Data were analyzed using generalized estimating equations to account for multiple within-subject measurements.
Perilesional probe location (P=0.02) and aSAH related intracerebral hemorrhage (aICH) volume (P=0.003) at admission were associated with high-grade neuroinflammation. Brain extracellular TAU-protein levels (P=0.001), metabolic distress and delayed cerebral infarction (DCI; P=0.001) were linked to high-grade neuroinflammation. Relative or absolute phosphor-TAU levels were not correlated with CMD-IL-6 levels. High-grade neuroinflammation was a predictor for worse outcome three months after ictus, independently from probe location, initial Hunt&Hess grade and age (P=0.01).
Neuroinflammation after aSAH is associated with intraparenchymal bleeding, deranged cerebral metabolism and TAU-protein release. The impact of potential anti-inflammatory treatment strategies on secondary brain injury after aSAH has to be investigated in future studies.
No preview · Article · Feb 2016 · Current drug targets
[Show abstract][Hide abstract] ABSTRACT: Background:
The treatment of intracranial aneurysms may be associated with cerebral ischemia. We hypothesize that pre-interventional remote ischemic preconditioning (RIPC) reduces ischemic cerebral tissue damage in patients undergoing elective intracranial aneurysm treatment.
This study is a single-center, prospective, randomized, double-blind explorative trial. Patients with an unruptured intracranial aneurysm admitted to Innsbruck Medical University Hospital for coiling or clipping will be consecutively randomized to either the intervention group (= RIPC by inflating an upper extremity blood-pressure cuff for 3 x 5 min to 200 mmHg) or the control group after induction of anesthesia. Participants will be randomized 1:1 to either the preconditioning group or the sham group using a random allocation sequence and block randomization. The precalculated sample size is n = 24 per group. The primary endpoint is the area-under-the-curve concentration of serum biomarkers (S100B, NSE, GFAP, MMP9, MBP, and cellular microparticles) in the first five days after treatment. Secondary endpoints are the number and volume of new ischemic lesions in magnetic resonance imaging and clinical outcome evaluated with the National Institutes of Health Stroke Scale, the modified Rankin Scale, and neuropsychological tests at six and twelve months. All outcome variables will be determined by observers blinded to group allocation. This study was approved by the local institutional Ethics Committee (UN5164), version 3.0 of the study protocol, dated 20 October 2013.
This study uses the elective treatment of intracranial aneurysms as a paradigmatic situation to explore the neuroprotective effects of RIPC. If effects are demonstrable in this pilot trial, a larger, prospective phase III trial will be considered.
[Show abstract][Hide abstract] ABSTRACT: Study design
Prospective, non-blinded, non-randomization.
Pain scales are commonly used to assess the condition of spine patients, although the degree of correlation between different pain scores, and between the scores and the patients’ functional status is, at best, variable. Pain usually limits physical activities, but there is a lack of a widely accepted tool for investigating pain-related physical impairment in everyday routine work. The purpose of this study was to evaluate and correlate the visual analog scale (VAS) and the “timed up and go” (TUG) test in patients after lumbar spondylodesis.
Thirty-eight patients with degenerative lumbar disease who were treated with monosegmental or bisegmental spondylodesis were included on a consecutive and prospective basis. The VAS and TUG were assessed preoperatively and during the first 12 weeks postoperatively. Special attention was paid to the early follow-up after surgical intervention. Correlations between the two tests were assessed.
The VAS showed gradual reduction after surgery, reaching statistical significance on the sixth postoperative day, with significant changes over time from the first to third, third to sixth postoperative days and from the sixth postoperative day to 2 weeks after surgery. In contrast, the TUG demonstrated a significant deterioration in function on the first and third postoperative days, returning to baseline levels thereafter (at postoperative days 6 and 14). Significant improvement in function in comparison with the preoperative status was established after 4 weeks and continued until the last follow-up examination. The TUG showed significant differences between all visits along the timeline. A correlation between the two tests was only observed on the first day after surgery.
In summary, the TUG appeared to be significantly more sensitive for describing the course after spine surgery. The TUG represents an appropriate performance-based functional test that is not time-consuming. Assessment of both pain and functionality is, therefore, needed to evaluate patients adequately.
No preview · Article · Dec 2015 · European Spine Journal
[Show abstract][Hide abstract] ABSTRACT: A 33-year-old man presented with moderate low-back pain and L-5 radiculopathy that progressed to severe paresis of L-5. On initial imaging, a corresponding spinal lesion was overlooked. Further CT and contrast-enhanced MRI demonstrated a presacral mass along the L-5 root far extraforaminally. A herniated disc was suspected, but with standard imaging a schwannoma could not be ruled out. The presacral L-5 root was explored via a microsurgical lateral extraforaminal transmuscular approach. To the best of the authors' knowledge, there have been no reports of sequestered extraforaminal lumbosacral disc herniations that herniated into the presacral region.
No preview · Article · Dec 2015 · Journal of Neurosurgery Spine
[Show abstract][Hide abstract] ABSTRACT: There is a substantial amount of evidence from animal models that early brain injury (EBI) may play an important role for secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Cerebral microdialysis (CMD) allows online measurement of brain metabolites including the pro-inflammatory-cytokine interleukin-6 (IL-6) and matrix-metalloproteinase-9 (MMP-9) which is indicative for disruption of the blood-brain-barrier.
Twenty-six consecutive poor-grade aSAH patients with multimodal neuromonitoring were analyzed for brain hemodynamic and metabolic changes including CMD-IL-6 and CMD-MMP-9 levels. Statistical analysis was performed using a generalized estimating equation with an autoregressive function.
The baseline metabolic central nervous system (CNS) profile revealed brain metabolic distress and an excitatory response which improved over the following 5 days (P <0.001). Brain tissue hypoxia (PbtO2 < 20 mmHg) was common (>60% of patients) in the first 24 hours of neuromonitoring and improved thereafter (P <0.05). Baseline CMD-IL-6 and CMD-MMP-9-levels were elevated in all patients (median = 4059 pg/ml, interquartile range (IQR) = 1316 to 12456 pg/ml and median = 851 pg/ml, IQR = 98 to 25860 pg/ml) and significantly decreased over the days (P <0.05). A higher pro-inflammatory response was associated with the development of delayed cerebral ischemia (P = 0.04), whereas admission disease severity and early brain tissue hypoxia were associated with higher CMD-MMP-9 levels (P <0.03). Brain metabolic distress and increased IL-6 levels were associated with poor functional outcome (mRS >3, P ≤0.01). All models were adjusted for probe location, aneurysm securing procedure and disease severity as appropriate.
Multimodal neuromonitoring techniques allow insight into pathophysiologic changes in the early phase after aSAH. The results may be used as endpoints for future interventions targeting early brain injury in poor-grade aSAH patients.
[Show abstract][Hide abstract] ABSTRACT: Background
Intervertebral disc (IVD) disorders are often accompanied by painful inflammatory and immunopathological processes. Nucleus pulposus (NP) cells play a pivotal role in maintenance of IVD by organizing the expression of anabolic, catabolic, anti-catabolic and inflammatory cytokines. Human NP cells have been targeted by gene therapeutic approaches using lentiviral or adenoviral systems that could be critical due to genome incorporation or immunological side effects. Adeno-associated viruses (AAVs), which do not express any viral gene and are not linked with any known disease in humans, are attractive gene delivery vectors. However, their lack of specific tissue tropism and preexisting immune response are main problems for therapeutic applications. Heretofore, AAVs have not been studied in human IVD research. Therefore, we attempted to identify NP cell specific AAV serotype by targeting human NP cells with different self-complementary AAV (scAAV) serotypes.
Identification and characterization of the proper serotype is crucial to establish less immunogenic and safer gene therapeutic approaches of IVD disorders.
Preoperative magnetic resonance imaging (MRI) was used for grading of IVD degeneration. NP cells were isolated, cultured with low-glucose and transduced with green fluorescent protein (GFP) packing scAAV serotypes (scAAV1-8) in a dose-dependent manner. scAAV titers were determined by quantitative polymerase chain reaction (qPCR). Transduction efficiencies were determined by fluorescence microscopy and fluorescence-activated cell sorting within 48 days of post-transduction. The 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine NP cell viability. Three-dimensional (3D) cell culture and enzyme-linked immunosorbant assay (ELISA) were performed to examine the expression levels of inflammatory, catabolic and matrix proteins in NP cells.
scAAV6, scAAV2 and scAAV3 showed high and prolonged transgene GFP expressions with transdution efficiencies of 98.6 %, 91.5 % and 89.6 % respectively (p ≤ 0.002). Unlike scAAV6, the serotypes scAAV2 and scAAV3 declined the viability of NP cells by about 25 % and 10 % respectively (p ≤ 0.001). Moreover, scAAV6 did not affect the expression of the inflammatory, catabolic and matrix proteins.
As original primary research evaluating AAVs in degenerative human IVDs, this study identified scAAV6 as a proper serotype for high, stable and non-immunogenic target gene expression in human NP cells. The data could be very important to design efficient and safer gene therapeutic approaches of IVD disorders.
Preview · Article · Nov 2015 · BMC Musculoskeletal Disorders
[Show abstract][Hide abstract] ABSTRACT: Biomechanical investigation.
This study describes ex vivo evaluation of the range of motion (ROM) to characterize the stability and need for additional dorsal fixation after cervical single-level, two-level or multilevel corpectomy (CE) to elucidate biomechanical differences between anterior-only and supplemental dorsal instrumentation.
Twelve human cervical cadaveric spines were loaded in a spine tester with pure moments of 1.5 Nm in lateral bending (LB), flexion/extension (FE), and axial rotation (AR), followed by two cyclic loading periods for three-level corpectomies. After each cyclic loading session, flexibility tests were performed for anterior-only instrumentation (group_1, six specimens) and circumferential instrumentation (group_2, six specimens).
The flexibility tests for all circumferential instrumentations showed a significant decrease in ROM in comparison with the intact state and anterior-only instrumentations. In comparison with the intact state, supplemental dorsal instrumentation after three-level CE reduced the ROM to 12 % (±10 %), 9 % (±12 %), and 22 % (±18 %) in LB, FE, and AR, respectively. The anterior-only construct outperformed the intact state only in FE, with a significant ROM reduction to 57 % (±35 %), 60 % (±27 %), and 62 % (±35 %) for one-, two- and three-level CE, respectively.
The supplemental dorsal instrumentation provided significantly more stability than the anterior-only instrumentation regardless of the number of levels resected and the direction of motion. After cyclic loading, the absolute differences in stability between the two instrumentations remained significant while both instrumentations showed a comparable increase of ROM after cyclic loading. The large difference in the absolute ROM of anterior-only compared to circumferential instrumentations supports a dorsal support in case of three-level approaches.
No preview · Article · Aug 2015 · European Spine Journal
[Show abstract][Hide abstract] ABSTRACT: We conducted a systematic review of the literature to evaluate the safety and efficacy of surgical treatment of previously coiled aneurysms.
A comprehensive review of the literature for studies on surgical treatment of previously coiled aneurysms was conducted. For each study, the following data were extracted: patient demographics, initial clinical status, location and size of aneurysms, time interval between initial/last endovascular procedure and surgery, surgical indications, and microsurgical technique. We performed subgroup analyses to compare direct clipping versus coil removal and clipping versus parent vessel occlusion, early (<4 weeks post-coiling) versus late surgery and anterior versus posterior circulation.
Twenty-six studies with 466 patients and 471 intracranial aneurysms were included. All of the studies were retrospective and non-comparative case-series. Patients undergoing direct clipping had lower perioperative morbidity (5.0 %, 95 % CI = 2.6-7.4 %) when compared to those undergoing coil removal and clipping (11.1 %, 95 % CI = 5.3-17.0 %) or parent vessel occlusion (13.1 %, 95 % CI = 4.6-21.6 %) (p = 0.05). Patients receiving early surgery (<4 weeks post-coiling) had significantly lower rates of good neurological outcome (77.1 %, 95 % CI = 69.3-84.8 %) when compared to those undergoing late surgery (92.1 %, 95 % CI = 89.0-95.2 %) (p < 0.01). There were higher rates of long-term neurological morbidity in the posterior circulation group (23.1 vs. 4.7 %, p < 0.01) as well as long-term neurological mortality (4.4 vs. 2.8 %, p < 0.01).
Our meta-analysis suggests that surgical treatment is safe and effective. Our data indicate that aneurysms that are amenable to direct clipping have superior outcomes. Late surgery was also associated with better clinical outcomes. Surgery of recurrent posterior circulation aneurysms was associated with high rates of morbidity and mortality. Given the characteristics of the included studies, the quality of evidence of this meta-analysis is limited.
No preview · Article · Jul 2015 · Acta Neurochirurgica
[Show abstract][Hide abstract] ABSTRACT: Meningiomas are known to be associated with female sex hormones. Worsening neurological symptoms or newly diagnosed meningiomas have been described in the context of elevated levels of sex hormones, for example, in pregnancy. To the authors' knowledge, tumor shrinkage after the normalization of hormones has not been described, even if it is known that neurological deficits due to meningioma compression may improve after giving birth. A 32-year-old female patient presented with severe headache and vision disturbances at the end of her second pregnancy. Magnetic resonance imaging revealed an extended mass at the lateral left-sided sphenoid wing that was suspected to be a meningioma. After delivery, the patient's symptoms improved, and MRI obtained 2 months postpartum showed significant shrinkage of the lesion. Significant tumor shrinkage can occur after pregnancy. Thus, repeat imaging is indicated in these patients.
Full-text · Article · Jul 2015 · Journal of Neurosurgery
[Show abstract][Hide abstract] ABSTRACT: Previous studies have demonstrated gender differences in pain perception in quantitative sensory testing. Thus, we hypothesized that there are differences in men and women with lumbar disc herniation awaiting lumbar sequestrectomy. To elucidate the differences in pain perception between men and women, we carried out a prospective clinical monocentric trial using quantitative sensory testing.
With institutional ethical approval, patients with radiculopathy awaiting lumbar sequestrectomy were examined the day before surgery. Preoperative pain was assessed using quantitative sensory testing and a series of questionnaires including Beck Depression Inventory and a numeric rating scale (NRS) for back and leg pain. Statistical analysis was performed using the Kolmogorov-Smirnov test for normal distribution. The unpaired Student's t-test, Mann-Whitney U test, and Fisher's exact test were used to analyze intergroup differences in the clinical and demographic characteristics and in clinical outcome variables.
Fifty patients (20 women and 30 men) were included in the study. The groups did not differ in NRS for back and leg pain. Heat and pressure pain thresholds were found to be lower in women than in men (p≤0.05). Subgroup analyses revealed decreased wind-up ratio in male patients with prior periradicular steroid application (p≤0.05).
Our results clearly indicate that sex differences in pain perception not only exist in healthy subjects, but also in patients with lumbar disc herniation. Therefore, it is essential to provide different treatment modalities to women and men.
No preview · Article · Jun 2015 · Journal of Women's Health
[Show abstract][Hide abstract] ABSTRACT: Background Cerebrospinal fluid (CSF) leaks are a well-known complication of transsphenoidal surgery. Several autologous and artificial grafts have been used to close the sellar floor in an attempt to prevent postoperative CSF rhinorrhea. Objective To evaluate and describe a sandwich technique to close the sellar floor using autologous bone, absorbable gelatin sponge, and coated collagen fleece. Methods We reviewed 50 consecutive patients between April 2010 and August 2011 who underwent transsphenoidal surgery ending with reconstruction of the sellar floor with a particular sandwich technique. Patients with an intraoperative CSF leak received an additional lumbar drain. Results There were no cases of CSF rhinorrhea at postoperative follow-up after 6 weeks and no revision surgery. Conclusion The proposed sandwich technique for closure of the sellar floor to the sphenoid sinus is a suitable alternative to autologous grafts and seems to be effective in preventing CSF rhinorrhea.
Georg Thieme Verlag KG Stuttgart · New York.
Full-text · Article · Jun 2015 · Journal of Neurological Surgery. Part A: Central European Neurosurgery
[Show abstract][Hide abstract] ABSTRACT: Cell-based regenerative approaches have been suggested as primary or adjuvant procedures for the treatment of degenerated intervertebral disc (IVD) diseases. Our aim was to evaluate the regenerative and immunogenic properties of mildly and severely degenerated cervical nucleus pulposus (NP) cells with regard to cell isolation, proliferation and differentiation, as well as to cell surface markers and co-cultures with autologous or allogeneic peripheral blood mononuclear cells (PBMC) including changes in their immunogenic properties after 3-dimensional (3D)-culture. Tissue from the NP compartment of 10 patients with mild or severe grades of IVD degeneration was collected. Cells were isolated, expanded with and without basic fibroblast growth factor and cultured in 3D fibrin/poly (lactic-co-glycolic) acid transplants for 21 days. Real-time reverse-transcription polymerase chain reaction (RT-PCR) showed the expression of characteristic NP markers ACAN, COL1A1 and COL2A1 in 2D- and 3D-culture with degeneration- and culture-dependent differences. In a 5,6-carboxyfluorescein diacetate N-succinimidyl ester-based proliferation assay, NP cells in monolayer, regardless of their grade of degeneration, did not provoke a significant proliferation response in T cells, natural killer (NK) cells or B cells, not only with donor PBMC, but also with allogeneic PBMC. In conjunction with low inflammatory cytokine expression, analyzed by Cytometric Bead Array and fluorescence-activated cell sorting (FACS), a low immunogenicity can be assumed, facilitating possible therapeutic approaches. In 3D-culture, however, we found elevated immune cell proliferation levels, and there was a general trend to higher responses for NP cells from severely degenerated IVD tissue. This emphasizes the importance of considering the specific immunological alterations when including biomaterials in a therapeutic concept. The overall expression of Fas receptor, found on cultured NP cells, could have disadvantageous implications on their potential therapeutic applications because they could be the targets of cytotoxic T-cell activity acting by Fas ligand-induced apoptosis.
[Show abstract][Hide abstract] ABSTRACT: Background
Cerebral edema and delayed cerebral infarction (DCI) are common complications after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome. Experimental data suggest that the amino acid taurine is released into the brain extracellular space secondary to cytotoxic edema and brain tissue hypoxia, and therefore may serve as a biomarker for secondary brain injury after aSAH. On the other hand, neuroprotective mechanisms of taurine treatment have been described in the experimental setting.
We analyzed cerebral taurine levels using high-performance liquid chromatography in the brain extracellular fluid of 25 consecutive aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD). Patient characteristics and clinical course were prospectively recorded. Associations with CMD-taurine levels were analyzed using generalized estimating equations with an autoregressive process to handle repeated observations within subjects.
CMD-taurine levels were highest in the first days after aSAH (11.2 ± 3.2 µM/l) and significantly decreased over time (p
No preview · Article · Apr 2015 · Neurocritical Care
[Show abstract][Hide abstract] ABSTRACT: To compare the effectiveness of techniques of posterior decompression that limit the extent of bony decompression or to avoid removal of posterior midline structures of the lumbar spine versus conventional facet-preserving laminectomy for the treatment of patients with degenerative lumbar stenosis.
A comprehensive electronic search of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Web of Science, and the clinical trials registries ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform was conducted for relevant literature up to June 2014.
A total of four high-quality RCTs and six low-quality RCTs met the search criteria of this review. These studies included a total of 733 participants. Three different techniques that avoid removal of posterior midline structures are compared to conventional laminectomy; unilateral laminotomy for bilateral decompression, bilateral laminotomy and split-spinous process laminotomy. Evidence of low or very low quality suggests that different techniques of posterior decompression and conventional laminectomy have similar effects on functional disability and leg pain. Only perceived recovery at final follow-up was better in patients that underwent bilateral laminotomy compared with conventional laminectomy. Unilateral laminotomy for bilateral decompression and bilateral laminotomy resulted in numerically fewer cases of iatrogenic instability, although in both cases, the incidence of instability was low. The difference in severity of postoperative low back pain following bilateral laminotomy and split-spinous process laminotomy was significantly less, but was too small to be clinically important. We found no evidence to show that the incidence of complications, length of the procedure, length of hospital stay and postoperative walking distance differed between techniques of posterior decompression.
The evidence provided by this systematic review for the effects of unilateral laminotomy for bilateral decompression, bilateral laminotomy and split-spinous process laminotomy compared with conventional laminectomy on functional disability, perceived recovery and leg pain is of low or very low quality. Therefore, further research is necessary to establish whether these techniques provide a safe and effective alternative for conventional laminectomy. Proposed advantages of these techniques regarding the incidence of iatrogenic instability and postoperative back pain are plausible, but definitive conclusions are limited by poor methodology and poor reporting of outcome measures among included studies.
Preview · Article · Mar 2015 · Cochrane database of systematic reviews (Online)