Reconstruction of large cranial defects with poly-methyl-methacrylate (PMMA) using a rapid prototyping model and a new technique for intraoperative implant modeling

Background Reconstruction of large cranial defects after craniectomy can be accomplished by free-hand poly-methyl-methacrylate (PMMA) or industrially manufactured implants. The free-hand technique often does not achieve satisfactory cosmetic results but is inexpensive. In an attempt to combine the accuracy of specifically manufactured implants with low cost of PMMA. Methods Forty-six consecutive patients with large skull defects after trauma or infection were retrospectively analyzed. The defects were reconstructed using computer-aided design/computer-aided manufacturing (CAD/CAM) techniques. The computer file was imported into a rapid prototyping (RP) machine to produce an acrylonitrile-butadiene-styrene model (ABS) of the patient's bony head. The gas-sterilized model was used as a template for the intraoperative modeling of the PMMA cranioplasty. Thus, not the PMMA implant was generated by CAD/CAM technique but the model of the patients head to easily form a well-fitting implant. Cosmetic outcome was rated on a six-tiered scale by the patients after a minimum follow-up of three months. Results The mean size of the defect was 74.36cm2. The implants fitted well in all patients. Seven patients had a postoperative complication and underwent reoperation. Mean follow-up period was 41 months (range 2–91 months). Results were excellent in 42, good in three and not satisfactory in one patient. Costs per implant were approximately 550 Euros. Conclusion PMMA implants fabricated in-house by direct molding using a bio-model of the patients bony head are easily produced, fit properly and are inexpensive compared to cranial implants fabricated with other RP or milling techniques

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)

Background: Cervical 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/design: This 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 60 months 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. Discussion: The 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 registration Current Controlled Trials: ISRCTN8257806

Effects of initial boost with TGF-beta 1 and grade of intervertebral disc degeneration on 3D culture of human annulus fibrosus cells

Background: Three-dimensional (3D) culture in porous biomaterials as well as stimulation with growth factors are known to be supportive for intervertebral disc cell differentiation and tissue formation. Unless sophisticated releasing systems are used, however, effective concentrations of growth factors are maintained only for a very limited amount of time in in vivo applications. Therefore, we investigated, if an initial boost with transforming growth factor-beta 1 (TGF-beta 1) is capable to induce a lasting effect of superior cartilaginous differentiation in slightly and severely degenerated human annulus fibrosus (AF) cells. Methods: Human AF tissue was harvested during surgical treatment of six adult patients with lumbar spinal diseases. Grading of disc degeneration was performed with magnet resonance imaging. AF cells were isolated and expanded in monolayer culture and rearranged three-dimensionally in a porous biomaterial consisting of stepwise absorbable poly-glycolic acid and poly-(lactic-co-glycolic) acid and a supportive fine net of non-absorbable polyvinylidene fluoride. An initial boost of TGF-beta 1 or TGF-beta 1 and hyaluronan was applied and compared with controls. Matrix formation was assessed at days 7 and 21 by (1) histological staining of the typical extracellular matrix molecules proteoglycan and type I and type II collagens and by (2) real-time gene expression analysis of aggrecan, decorin, biglycan, type I, II, III, and X collagens as well as of catabolic matrix metalloproteinases MMP-2 and MMP-13. Results: An initial boost with TGF-beta 1 or TGF-beta 1 and hyaluronan did not enhance the expression of characteristic AF matrix molecules in our 3D culture system. AF cells showed high viability in the progressively degrading biomaterial. Stratification by grade of intervertebral disc degeneration showed that AF cells from both, slightly degenerated, or severely degenerated tissue are capable of significant up-regulations of characteristic matrix molecules in 3D culture. AF cells from severely degenerated tissue, however, displayed significantly lower up-regulations in some matrix molecules such as aggrecan. Conclusions: We failed to show a supportive effect of an initial boost with TGF-beta 1 in our 3D culture system. This underlines the need for further investigations on growth factor releasing systems

Biomechanical testing of a polymer-based biomaterial for the restoration of spinal stability after nucleotomy

<p>Abstract</p> <p>Background</p> <p>Surgery for disc herniations can be complicated by two major problems: painful degeneration of the spinal segment and re-herniation. Therefore, we examined an absorbable poly-glycolic acid (PGA) biomaterial, which was lyophilized with hyaluronic acid (HA), for its utility to (a) re-establish spinal stability and to (b) seal annulus fibrosus defects. The biomechanical properties range of motion (ROM), neutral zone (NZ) and a potential annulus sealing capacity were investigated.</p> <p>Methods</p> <p>Seven bovine, lumbar spinal units were tested in vitro for ROM and NZ in three consecutive stages: (a) intact, (b) following nucleotomy and (c) after insertion of a PGA/HA nucleus-implant. For biomechanical testing, spinal units were mounted on a loading-simulator for spines. In three cycles, axial loading was applied in an excentric mode with 0.5 Nm steps until an applied moment of ± 7.5 Nm was achieved in flexion/extension. ROM and NZ were assessed. These tests were performed without and with annulus sealing by sewing a PGA/HA annulus-implant into the annulus defect.</p> <p>Results</p> <p>Spinal stability was significantly impaired after nucleotomy (p < 0.001). Intradiscal implantation of a PGA-HA nucleus-implant, however, restored spinal stability (p < 0.003). There was no statistical difference between the stability provided by the nucleus-implant and the intact stage regarding flexion/extension movements (p = 0.209). During the testing sequences, herniation of biomaterial through the annulus defect into the spinal canal regularly occurred, resulting in compression of neural elements. Sewing a PGA/HA annulus-implant into the annulus defect, however, effectively prevented herniation.</p> <p>Conclusion</p> <p>PGA/HA biomaterial seems to be well suited for cell-free and cell-based regenerative treatment strategies in spinal surgery. Its abilities to restore spinal stability and potentially close annulus defects open up new vistas for regenerative approaches to treat intervertebral disc degeneration and for preventing implant herniation.</p

Clinical and radiological outcome 1-year after cervical total disc replacement using the Signus ROTAIO - Prosthesis.

INTRODUCTION The instantaneous center of rotation (iCOR) of a motion segment has been shown to correlate with its total range of motion (ROM). Importantly, a correlation of the correct placement of cervical total disc replacement (cTDR) to preserve a physiological iCOR has been previously identified. However, changes of these parameters and the corresponding clinical relevance have hardly been analyzed. This study assesses the radiological and clinical correlation of iCOR and ROM following cTDR. MATERIALS/METHODS A retrospective multi-center observational study was conducted and radiological as well as clinical parameters were evaluated preoperatively and 1 year after cTDR with an unconstrained device. Radiographic parameters including flexion/extension X-rays (flex/ex), ROM, iCOR and the implant position in anterior-posterior direction (IP ap), as well as corresponding clinical parameters [(Neck Disability Index (NDI) and the visual analogue scale (VAS)] were assessed. RESULTS 57 index segments of 53 patients treated with cTDR were analyzed. Pre- and post-operative ROM showed no significant changes (8.0° vs. 10.9°; p > 0.05). Significant correlations between iCOR and IP (Pearson's R: 0.6; p < 0.01) as well as between ROM and IP ap (Pearson's R: - 0.3; p = 0.04) were identified. NDI and VAS improved significantly (p < 0.01). A significant correlation between NDI and IP ap after 12 months (Pearson's R: - 0.39; p < 0.01) was found. CONCLUSION Implantation of the tested prosthesis maintains the ROM and results in a physiological iCOR. The exact position of the device correlates with the clinical outcome and emphasize the importance of implant design and precise implant positioning

Brain temperature regulation in poor-grade subarachnoid hemorrhage patients – A multimodal neuromonitoring study

Elevated body temperature (Tcore) is associated with poor outcome after subarachnoid hemorrhage (SAH). Brain temperature (Tbrain) is usually higher than Tcore. However, the implication of this difference (Tdelta) remains unclear. We aimed to study factors associated with higher Tdelta and its association with outcome. We included 46 SAH patients undergoing multimodal neuromonitoring, for a total of 7879 h of averaged data of Tcore, Tbrain, cerebral blood flow, cerebral perfusion pressure, intracranial pressure and cerebral metabolism (CMD). Three-months good functional outcome was defined as modified Rankin Scale ≤2. Tbrain was tightly correlated with Tcore (r = 0.948, p < 0.01), and was higher in 73.7% of neuromonitoring time (Tdelta +0.18°C, IQR −0.01 – 0.37°C). A higher Tdelta was associated with better metabolic state, indicated by lower CMD-glutamate ( p = 0.003) and CMD-lactate ( p < 0.001), and lower risk of mitochondrial dysfunction (MD) (OR = 0.2, p < 0.001). During MD, Tdelta was significantly lower (0°C, IQR −0.2 – 0.1; p < 0.001). A higher Tdelta was associated with improved outcome (OR = 7.7, p = 0.002). Our study suggests that Tbrain is associated with brain metabolic activity and exceeds Tcore when mitochondrial function is preserved. Further studies are needed to understand how Tdelta may serve as a surrogate marker for brain function and predict clinical course and outcome after SAH

Prospective Multicenter Trial of Cervical Arthroplasty With the ROTAIO® Cervical Disc Prosthesis

Objective Anterior Cervical Discectomy and Arthroplasty (ACDA) is an established treatment for degenerative cervical disc disease and seems to be an alternative to fusion in minimizing the risk of Adjacent Segment Disease (ASD). The ROTAIO® cervical disc prosthesis is a novel unconstrained implant with a variable center of rotation aiming at physiological motion. The objective of this multicenter prospective trial was to evaluate clinical outcome and complications within 2 years. Material and Methods 120 patients (72 females and 48 males with a median age of 43.0 years; range: 23 to 60 years) underwent ACDA (ROTAIO®, SIGNUS Medical, Alzenau, Germany) and were prospectively followed for 24 months. Preoperative complaints were mainly associated with radiculopathy (n=104) or myelopathy (n=16). There were 108 monosegmental and 12 bisegmental procedures including 6 hybrid constructs. Clinical outcome was evaluated at 3, 12 and 24 months by the Visual Analogue Scale (VAS) for head, neck and arm pain, the Neck Disability Index (NDI), the Work Limitation Questionnaire (WL-26), the Patient`s Satisfaction Index (PSI) and a Quality of Life Questionnaire (SF-36). The Nurick Score, the Modified Japanese Orthopaedic Association Score (mJOA) plus a Composite Success Rate have been additionally applied. Finally, complications, the patient`s overall satisfaction and the amount of analgesics were assessed. Results Highly significant clinical improvements were observed according to NDI and VAS (p<0.0001 (arm); p<0.001 (neck); p=0.002 (head)) at all postoperative time points. Analgetic medication could be reduced after 3 months in 91.3%, after 12 months in 87.1% and after 24 months in 95.2% of patients. Doctor`s visits for cervical spine problems have been reduced in 93.8% after 24 months. Patient`s overall satisfaction was high after 3, 12 and 24 months with 83.5%, 78.4% and 79.1% of patients, while 4.1%, 6.8% and 7.0% respectively were not satisfied. The composite success rate was 77.5% after 12 months and 76.9% after 24 months. There were no major complications in this series. Slight subsidence of the prosthesis was observed in 2 patients and 3 patients demonstrated fusion after 24 months. 2 patients developed symptomatic foraminal stenosis, so that implant removal and fusion was performed. Conclusion The ROTAIO® cervical disc prosthesis is a safe and efficient treatment option for symptomatic degenerative disc disease demonstrating excellent clinical results at 2 years. Outcome proves to be stable over time with very low revision rates

Duroplasty for injured cervical spinal cord with uncontrolled swelling: protocol of the DISCUS randomized controlled trial

Background Cervical traumatic spinal cord injury is a devastating condition. Current management (bony decompression) may be inadequate as after acute severe TSCI, the swollen spinal cord may become compressed against the surrounding tough membrane, the dura. DISCUS will test the hypothesis that, after acute, severe traumatic cervical spinal cord injury, the addition of dural decompression to bony decompression improves muscle strength in the limbs at 6 months, compared with bony decompression alone. Methods This is a prospective, phase III, multicenter, randomized controlled superiority trial. We aim to recruit 222 adults with acute, severe, traumatic cervical spinal cord injury with an American Spinal Injury Association Impairment Scale grade A, B, or C who will be randomized 1:1 to undergo bony decompression alone or bony decompression with duroplasty. Patients and outcome assessors are blinded to study arm. The primary outcome is change in the motor score at 6 months vs. admission; secondary outcomes assess function (grasp, walking, urinary + anal sphincters), quality of life, complications, need for further surgery, and mortality, at 6 months and 12 months from randomization. A subgroup of at least 50 patients (25/arm) also has observational monitoring from the injury site using a pressure probe (intraspinal pressure, spinal cord perfusion pressure) and/or microdialysis catheter (cord metabolism: tissue glucose, lactate, pyruvate, lactate to pyruvate ratio, glutamate, glycerol; cord inflammation: tissue chemokines/cytokines). Patients are recruited from the UK and internationally, with UK recruitment supported by an integrated QuinteT recruitment intervention to optimize recruitment and informed consent processes. Estimated study duration is 72 months (6 months set-up, 48 months recruitment, 12 months to complete follow-up, 6 months data analysis and reporting results). Discussion We anticipate that the addition of duroplasty to standard of care will improve muscle strength; this has benefits for patients and carers, as well as substantial gains for health services and society including economic implications. If the addition of duroplasty to standard treatment is beneficial, it is anticipated that duroplasty will become standard of care. Trial registration IRAS: 292031 (England, Wales, Northern Ireland) - Registration date: 24 May 2021, 296518 (Scotland), ISRCTN: 25573423 (Registration date: 2 June 2021); ClinicalTrials.gov number : NCT04936620 (Registration date: 21 June 2021); NIHR CRN 48627 (Registration date: 24 May 2021)