Anja Tschugg

A prospective multicenter phase I/II clinical trial to evaluate safety and efficacy of NOVOCART Disc plus autologous disc chondrocyte transplantation in the treatment of nucleotomized and degenerative lumbar disc to avoid secondary disease: study protocol for a randomized controlled trial

BackgroundIntervertebral disc degeneration is emphasized as an important cause of low back pain. Current surgical treatment provides relief to the accompanying pain and disability but does not restore the biological function of the intervertebral disc. NOVOCART™ Disc plus, an autologous cell compound for autologous disc chondrocyte transplantation, was developed to reduce the degenerative sequelae after lumbar disc surgery or to prophylactically avoid degeneration in adjacent discs.Methods/designThis is a multicenter, randomized, controlled, clinical phase I/II combination study. A total of 120 adult patients are allocated in a ratio of 2:1:1. Sample size and power calculations were performed to detect the minimal clinically important difference of 10 units, with an expected standard deviation of 12 in the Oswestry Disability Index, which is the primary outcome parameter. Secondary outcome parameters include the visual analog scale and the EQ-5D questionnaire. Changes in physical and mental health are evaluated using the Short Form-12 (SF-12). Moreover, radiological and functional outcomes are evaluated. The major inclusion criterion is a single lumbar disc herniation that requires sequestrectomy. Transplantation is performed 90xa0days thereafter. Study data generation (study sites) and data storage, processing, and statistical analysis are clearly separated.DiscussionIn this phase-I/II study, NDplus is being investigated for its clinical applicability, safety, and efficacy in the repair of herniated, nucleotomized discs, and of adjacent degenerated discs, if present. To date, autologous disc chondrocytes have not been transplanted into degenerative discs without previous disc herniation. As such, this is the first study to investigate a therapeutic as well as a prophylactic approach to treat degenerative discs of the lumbar spine.Trial registrationEudraCT No: 2010-023830-22, ID NCT01640457, 8 November 2010

Comparison of posterior foraminotomy and anterior foraminotomy with fusion for treating spondylotic foraminal stenosis of the cervical spine: study protocol for a randomized controlled trial (ForaC)

BackgroundCervical radiculopathy caused by spondylotic foraminal stenosis may require surgical treatment. Surgical options include anterior cervical foraminotomy and fusion or posterior cervical foraminotomy. Controversy remains regarding the preferable surgical approach. Pertinent clinical evidence is limited to low-quality observational reports. Therefore, treatment decisions are predominantly based on the individual surgeon’s preference and skill. The study objective is to evaluate the efficacy and safety of posterior foraminotomy in comparison to anterior foraminotomy with fusion for the treatment of spondylotic foraminal stenosis.Methods/designThis is a multicenter randomized, controlled, parallel group superiority trial. A total of 88 adult patients are allocated in a ratio of 1:1. Sample size and power calculations were performed to detect the minimal clinically important difference of 14 points, with an expected standard deviation of 20 in the primary outcome parameter, Neck Disability Index, with a power of 80%, based on an assumed maximal dropout rate of 20%. Secondary outcome parameters include the Core Outcome Measures Index, which investigates pain, back-specific function, work disability, social disability and patient satisfaction. Changes in physical and mental health are evaluated using the Short Form-12 (SF-12) questionnaire. Moreover, radiological and health economic outcomes are evaluated. Follow-up is performed 3, 6, 12, 24, 36, 48 and 60xa0months after surgery. Major inclusion criteria are cervical spondylotic foraminal stenosis causing radiculopathy of C5, C6 or C7 and requiring decompression of one or two neuroforaminae. Study data generation (study sites) and data storage, processing and statistical analysis (Department of Medical Statistics, Informatics and Health Economics) are clearly separated. Data will be analyzed according to the intention-to-treat principle.DiscussionThe results of the ForaC study will provide surgical treatment recommendations for spondylotic foraminal stenosis and will contribute to the understanding of its short- and long-term clinical and radiological postoperative course. This will hopefully translate into improvements in surgical treatment and thus, clinical practice for spondylotic foraminal stenosis.Trial registrationCurrent Controlled Trials: ISRCTN82578069.

Analysis of a performance-based functional test in comparison with the visual analog scale for postoperative outcome assessment after lumbar spondylodesis

Study designProspective, non-blinded, non-randomization.PurposePain 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.MethodsThirty-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 12xa0weeks postoperatively. Special attention was paid to the early follow-up after surgical intervention. Correlations between the two tests were assessed.ResultsThe 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 2xa0weeks 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 4xa0weeks 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.ConclusionIn 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.

Gender differences after lumbar sequestrectomy: a prospective clinical trial using quantitative sensory testing

BackgroundQuantitative sensory testing (QST) gained popularity to evaluate the time course of recovery in sensory dysfunction and the results of different treatment options. Concerning sex differences in lumbar spine surgery, female gender seems to play a major role as a negative prognostic factor in different spinal disorders. For this purpose, we hypothesised that there are also comparable differences in pain patterns in men and women after lumbar sequestrectomy using QST.MethodsWe applied the QST protocol of the German Research Network on Neuropathic Pain in 53 patients (21 women and 32 men) with a single lumbar disc herniation confirmed on MRI treated by a lumbar sequestrectomy. Further evaluation included a detailed medical history, a physical examination, and various questionnaires: Beck-Depression-Inventory, Oswestry Disability Index, Core Outcome Measure Index, painDETECT-Questionnaire and EQ-5D thermometer.ResultsOur analyses showed lower heat thresholds in females preoperatively, that adjusted to that of males 1xa0week postoperatively. Pressure pain thresholds were lower in women as well, but differed between genders throughout the study. Vibration perception deficits resolve earlier in female than in male patients. Both, women and men, had an excellent overall improvement, postoperatively.ConclusionOur results clearly revealed pre- and postoperative differences in pain perception between genders. These differences have to be taken into account in the evaluation of outcome between genders. Therefore, QST seems to be a good method to evaluate the time course of recovery after surgery.

Management of spinal infection: a review of the literature

Spinal infection (SI) is defined as an infectious disease affecting the vertebral body, the intervertebral disc, and/or adjacent paraspinal tissue and represents 2–7% of all musculoskeletal infections. There are numerous factors, which may facilitate the development of SI including not only advanced patient age and comorbidities but also spinal surgery. Due to the low specificity of signs, the delay in diagnosis of SI remains an important issue and poor outcome is frequently seen. Diagnosis should always be supported by clinical, laboratory, and imaging findings, magnetic resonance imaging (MRI) remaining the most reliable method. Management of SI depends on the location of the infection (i.e., intraspinal, intervertebral, paraspinal), on the disease progression, and of course on the patient’s general condition, considering age and comorbidities. Conservative treatment mostly is reasonable in early stages with no or minor neurologic deficits and in case of severe comorbidities, which limit surgical options. Nevertheless, solely medical treatment often fails. Therefore, in case of doubt, surgical treatment should be considered. The final result in conservative as well as in surgical treatment always is bony fusion. Furthermore, both options require a concomitant antimicrobial therapy, initially applied intravenously and administered orally thereafter. The optimal duration of antibiotic therapy remains controversial, but should never undercut 6xa0weeks. Due to a heterogeneous and often comorbid patient population and the wide variety of treatment options, no generally applicable guidelines for SI exist and management remains a challenge. Thus, future prospective randomized trials are necessary to substantiate treatment strategies.

Preoperative sport improves the outcome of lumbar disc surgery: a prospective monocentric cohort study

A lumbar disc herniation resulting in surgery may be an incisive event in a patient’s everyday life. The patient’s recovery after sequestrectomy may be influenced by several factors. There is evidence that regular physical activity can lower pain perception and improve the outcome after surgery. For this purpose, we hypothesized that patients performing regular sports prior to lumbar disc surgery might have less pain perception and disability thereafter. Fifty-two participants with a single lumbar disc herniation confirmed on MRI treated by a lumbar sequestrectomy were included in the trial. They were categorized into two groups based on their self-reported level of physical activity prior to surgery: group NS, no regular physical activity and group S, with regular physical activity. Further evaluation included a detailed medical history, a physical examination, and various questionnaires: Visual Analog Scale (VAS), Beck-Depression-Inventory (BDI), Oswestry Disability Index (ODI), Core Outcome Measure Index (COMI), and the EuroQoL-5Dimension (EQ- 5D). Surgery had an excellent overall improvement of pain and disability (pxa0<xa00.005). The ODI, COMI, and EQ-5D differed 6xa0months after intervention (pxa0<xa00.05) favoring the sports group. Leg and back pain on VAS was also significantly less in group B than in group A, 12xa0months after surgery (pxa0<xa00.05). Preoperative regular physical activity is an important influencing factor for the overall satisfaction and disability after lumbar disc surgery. The importance of sports may have been underestimated for surgical outcomes.

Analysis of the Literature on Cervical Spine Fractures in Ankylosing Spinal Disorders

Study Design: Narrative literature review. Objective: The numbers of low-energy cervical fractures seen in patients suffering from ankylosing spondylitis (also known as Bechterew disease) or diffuse idiopathic skeletal hyperostosis (also known as Forestier disease) have greatly increased over recent decades. These fractures tend to be particularly overlooked, leading to delayed diagnosis and secondary neurological deterioration. The aim of the present evaluation was to summarize current knowledge on cervical fractures in patients with ankylosing spinal disorders (ASDs). Methods: The literature was analyzed through an extensive PubMed search focusing on cervical fractures, especially with delayed diagnosis. Results: In ASDs, it was mainly the cervical spine that was found to be affected by fractures. Fifty percent of ASD patients had neurological deficits at admission, with a high probability of secondary deterioration due to an initially missed diagnosis. Multislice high-resolution imaging techniques should be the radiological standard of care if a vertebral fracture is suspected. Nevertheless, many of these spinal fractures are overlooked, leading to feared secondary deterioration of existing unstable fractures. Long posterior instrumentations were found to be the treatment of choice, followed by anterior and combined anterior-posterior instrumentations. Conclusions: Delayed diagnosis of cervical fractures in ASDs contributes to initially misinterpreted clinical symptoms, inadequate imaging techniques, and a lack of knowledge about this disease entity due to its peculiarities. Thorough assessment of the patients’ neurological morbidity at admission might reduce the occurrence of the associated fractures. The biomechanical behavior of ASD fractures is completely different from that of non-ASD fractures, so that the treatment strategy for these patients should be at least surgical, in combination with long dorsal instrumentations or combined anterior-posterior approaches.

Cement-augmented screws in a cervical two-level corpectomy with anterior titanium mesh cage reconstruction: a biomechanical study.

Study designBiomechanical investigation.PurposeCervical two-level corpectomies with anterior-only instrumentation are associated with a high rate of implant-related complications. These procedures, therefore, often require an additional dorsal instrumentation to prevent screw loosening. Cement augmentation of the anterior screws in two-level corpectomies might stabilize the construct, so that a second dorsal procedure could be avoided. To evaluate the screw anchorage in cervical anterior-only procedures, an ex vivo evaluation of the range of motion (ROM) in two-level corpectomies (C4 and C5), with and without cement augmentation of the anterior screws, was carried out in this study.MethodsTwelve human cervical cadaveric spines (C2–T1) were divided into two groups of six specimens each. Corpectomies were performed in C4 and C5, with grafting and anterior instrumentation with and without cement augmentation of the anterior screw-and-plate system (0.3–0.5xa0mL cement/screw). Flexibility tests with pure moments (1.5xa0Nm) were carried out before and after three cyclic loading periods of 5000 cycles with increasing eccentric forces (100, 200, and 300xa0N).ResultsAfter corpectomy and instrumentation, the control group and the augmented group showed a significant reduction in ROM in comparison with the native states with average ROMs of 49% (±17%) and 24% (±10%), respectively (Pxa0=xa00.006). The ROM in the control group increased significantly in all motion directions in the course of cyclic loading and approached native values after the third cyclic loading period, with an overall ROM of 78% (±22%). In contrast, the augmented group maintained a significantly decreased ROM in all motion directions during cyclic loading, with a final ROM of 32% (±14%) after the third period of cyclic testing. Inter-group comparison demonstrated a significant difference between the two groups in the course of cyclic loading. The cement-augmented group outperformed the control group in all motion directions, with a significantly lower ROM after all three cyclic loading periods.ConclusionsA two-level corpectomy with cement-augmentation results in a significantly reduced ROM. In comparison with the conventional anterior screw-and-plate fixation, it represents a significantly stabilized two-level anterior construct. This might be a treatment option for patients with a two-level corpectomy associated with reduced bone mineral density, to avoid an additional dorsal instrumentation.

Cervical corpectomies: results of a survey and review of the literature on diagnosis, indications, and surgical technique

ObjectivesCervical corpectomy is an uncommon procedure and there are only limited data on the procedure’s indications, surgical approaches, and complications. The diagnosis, indications, surgical planning, and complications of cervical corpectomy were therefore surveyed to clarify the treatment strategies used by spinal surgeons in central Europe, with special attention to preoperative planning and decision-making for additional dorsal approaches in multilevel cases.Materials and methodsAn online survey with 18 questions on the preoperative, intraoperative, and postoperative management of cervical corpectomies was conducted. The relevant specialist societies in Germany and Austria provided 1137 contacts for surgeons, and the responses were compared with recent literature reports.ResultsIn all, 302 surgeons (27xa0%) completed the survey, with wide variability in the treatment options offered. Most (51xa0%) perform fewer than five anterior cervical corpectomy and fusion (ACCF) procedures per year; 35xa0% do 5–20 per year. Anterior cervical discectomy and fusion (ACDF) was preferred by 41xa0% of the participants to laminoplasty/laminectomy (19xa0%/16xa0%) and ACCF (12xa0%). Most indications for ACCF involved degenerative (27xa0%), traumatic (17xa0%), and neoplastic (20xa0%) conditions. Intraoperative and postoperative complications were mainly associated with hardware failure. One-third of the surgeons tend to use an additional dorsal approach to increase the corpectomy construct’s stability for either two-level or three-level corpectomies.ConclusionsThere is no current consensus in central Europe on the treatment of complex cervical disease and cervical corpectomy. The procedure is still rare, and the need for additional dorsal fixation is unclear. Further studies are needed in order to establish evidence-based standards for patient care.

Primary acquired spondylodiscitis shows a more severe course than spondylodiscitis following spine surgery: a single-center retrospective study of 159 cases

Spondylodiscitis may arise primarily via hematogenous spread or direct inoculation of virulent organisms during spine surgery. To date, no comparative data investigating the differences between primary and postoperative spondylodiscitis is available. Thus, the purpose of this retrospective study was to investigate differences between these two etiologies. One hundred fifty-nine patients that were treated at our department were included in the retrospective analysis. The patients were categorized into two groups based on the etiology of spondylodiscitis: group NS, primary spondylodiscitis without prior spinal surgery; group S, spondylodiscitis following spinal surgery. Evaluation included magnetic resonance imaging (MRI), laboratory values, clinical outcome, and operativexa0or conservative management. Preoperative MRI showed higher rates of epidural and paraspinalxa0abscess in patients with primary spondylodiscitis (pxa0<xa00.005). Vertebral bone destruction was more severe in group NS (pxa0<xa00.05). Survival rate in group S (98.2%) was higher than in group NS (87.5%, pxa0=xa00.024). The extent of the operative procedure in patients who were surgically treated (n = 116) differed between the two groupsxa0(pxa0<xa00.005). In conclusion, spondylodiscitis is a life-threatening and serious disease and requires long-term treatment. Primary spondylodiscitis is frequently associated with epiduralxa0and paraspinal abscess, vertebral bone destruction and has a higher mortality rate than postoperative spondylodiscitis. Therefore, primary spondylodiscitis shows a more severe course than spondylodiscitis following spine surgery.