Stefan Kroppenstedt

Regeneration of intervertebral disc tissue by resorbable cell-free polyglycolic acid-based implants in a rabbit model of disc degeneration.

Study Design. Different biologic strategies exist to treat degenerative disc disease. Tissue engineering approaches favor autologous chondrocyte transplantation. In our one-step-approach, a resorbable cell-free polyglycolic acid (PGA)-based implant is immersed in serum from whole blood and implanted into the disc defect directly after discectomy. Objectives. The aim of our study was to investigate the capacity of a cell-free implant composed of a PGA felt, hyaluronic acid, and serum to recruit disc cells and stimulate repair tissue formation in vivo after microdiscectomy in a rabbit model. Summary of the Background Data. Disc tissue has a limited ability to regenerate after the degeneration process was once initiated. Therefore, we developed a cell-free resorbable implant that is able to attract local cells into the defect and induce proper repair tissue formation. Methods. The cell-free implant consisting of PGA and hyaluronic acid was immersed in allogenic serum and implanted into the disc defect after discectomy in New Zealand white rabbits. One week and 6 months after the operation, the disc height index and the T2-weighted signal intensity index were determined using plane radiographs and magnetic resonance imaging. Finally, discs were explanted and investigated histologically. Animals with discectomy only served as controls. Results. In our animal studies, we could demonstrate that the T2-weighted signal intensity of the operated discs decreased in both groups 1 week after surgery. However, after 6 months, the T2-weighted signal intensity index increased by 45% in the implanted group whereas the index decreased further by 11% in the sham group. This corresponded to changes in the disc height index. Furthermore, the histologic examinations indicated cell migration into the defect and showed tissue regeneration. Conclusion. The implantation of a cell-free PGA-hyaluronic acid implant immersed in serum after discectomy induces regeneration, resulting in improvement of the disc water content and preservation of the disc height 6 months after surgery.

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.

Neuroprotective Effect of Melatonin on Cortical Impact Injury in the Rat

Summary The pineal hormone melatonin is a highly efficient physiological scavenger of free radicals involved in secondary brain damage. A variety of experimental studies have demonstrated a neuroprotective effect for melatonin, based on its antioxidant activity. The purpose of the present study was to investigate the time-dependency and a possible protective effect of exogenous melatonin in the cortical impact model in rats. The protective effect was quantified determining contusion volume, brain edema and brain water content. 45 anesthetized male Sprague-Dawley rats (250–350 mg) were subjected to cortical impact injury of moderate severity (7 m/s, deformation 2 mm). Melatonin (100 mg/kg bw i.p.), or a vehicle was injected 20 min before trauma, immediately after, and 1 and 2 hours after trauma during daytime and nighttime. Posttraumatic lesion volume using hematoxylin-eosin staining, hemispheric swelling, brain water content, cerebral perfusion pressure and intracranial pressure 24 hours after injury were investigated. Melatonin, given during nighttime, significantly reduced contusion volume corresponding to a mean reduction of contusion volume of 27% (placebo, n=7: 41.9±5.2 mm3, melatonin, n=8: 30.5±4.2 mm3, p<0.05). Given during daytime, the reduction in contusion volume was not significant (placebo, n=8: 42.1±5.1 mm3, melatonin, n=8: 35.9±2.2 mm3, reduction of 15%, p=0.08, n.s.). Hemispheric swelling was unchanged by melatonin treatment. Mean arterial blood pressure and rectal temperature remained stable before and after the cortical impact injury and injection of melatonin. This study shows that melatonin significantly reduces contusion volume with major effects during night.

Atypical cervical spondylotic myelopathy mimicking intramedullary tumor.

Study Design. Case report and a review of the literature. Objective. We report the case of a young man with a short course of progressive cervical myelopathy (CM). Cervical magnetic resonance imaging (MRI) revealed a stenosis of the cervical spinal canal at C4–C6 and an atypically enlarged intramedullary high intensity extending from C1–T1 (T2-weighted) with contrast enhancement at C4–C5 (T1-weighted). Neurologic and radiologic diagnosis therefore favored a tumor of the spinal cord. Summary of Background Data. CM is a clinical diagnosis of mostly degenerative origin in older patients that features circumscribed high-intensity signals near the point of compression in T2-weighted MRI. Contrast enhancement in those high-intense areas is rarely described in the literature, and the differentiation from neoplastic and infective lesions might be very difficult in these cases. Methods. Retrospective case study with follow-up examination and MRI-control 3 months after surgery. Results. The patient was decompressed and stabilized from dorsally, and a biopsy was taken. The exact diagnosis of a myelopathy and an exclusion of a neoplastic origin succeeded through histopathological examination. Three months after first surgery, the patient had improved significantly and underwent an additional anterior stabilization, while the MRI remained almost unchanged. Conclusion. In case of a fast progressive CM with atypical radiographic appearance initial decompression with inspection of the spinal cord and a short-term clinical follow-up with an MRI control might be the procedure of choice, if a clear diagnosis for a causative treatment cannot be made. In still suspicious cases, a biopsy could be considered to exclude a neoplastic or inflammatory process.

Norepinephrine is Superior to Dopamine in Increasing Cortical Perfusion Following Controlled Cortical Impact Injury in Rats

Following traumatic brain injury catecholamines are routinely applied to increase cerebral perfusion. To date, it remains controversial if infusion of catecholamines is associated with diminished cerebral perfusion due to catecholamine-mediated vasoconstriction. The aims of the present study were to investigate the effects of norepinephrine and dopamine on cortical perfusion and brain edema following controlled cortical impact injury (CCII) in rats. Four hours after CCII, rats (n = 22) received either norepinephrine or dopamine with the aim of increasing MABP to 120 mm Hg for 90 minutes. Control rats were given NaCl. Cortical perfusion was measured before, during, and after catecholamine infusion using Laser Doppler flowmetry. Brain swelling was determined directly after the study period (8 hrs after CCII). Following CCII cortical perfusion was reduced by 40% compared to pre-trauma values in all rats. Parallel to the increases in MABP, cortical perfusion was significantly elevated under norepinephrine and dopamine, respectively (p < 0.05). Despite similar MABP values this increase was mostly sustained under norepinephrine. In control rats cortical perfusion remained diminished. Brain swelling was similar in all groups. Both norepinephrine and dopamine significantly increased cortical perfusion following CCII. Norepinephrine, however, was superior to dopamine in CBF. Based on increased CBF and unchanged brain swelling catecholamine-mediated vasoconstriction does not seem to occur under the present study design.

Application of titanium and polyetheretherketone cages in the treatment of pyogenic spondylodiscitis

OBJECTIVE Surgical treatment of a pyogenic spondylodiscitis (PSD) involves a fixation and debridement of the affected segment combined with a specific antibiotic therapy. To achieve a proper stability and to avoid pseudarthrosis and kyphotic malposition many surgeons favour the interposition of an anterior graft. Besides autologous bone grafts titanium (TTN) cages have gained acceptance in the treatment of PSD. Polyetheretherketone (PEEK) cages have a more favourable modulus of elasticity than TTN. We compared both cage types. Primary endpoints were the rate of reinfection and radiological results. METHODS From 2004 to 2013 51 patients underwent surgery for PSD with fixation and TTN or PEEK cage-implantation. While lumbar patients underwent a partial discectomy by the posterior approach, discs of the cervical and thoracic patients had been totally removed from anterior. Clinical and radiological parameters were assessed in 37 eligible patients after a mean of 20.4 months. 21 patients received a PEEK- and 16 patients a TTN-cage. RESULTS A reinfection after surgery and 3 months of antibiotic therapy was not observed. Solid arthrodesis was found in 90.5% of the PEEK-group and 100% of the TTN-group. A segmental correction could be achieved in both groups. Nonetheless, a cage subsidence was observed in 70.3% of all cases. Comparison of radiological results revealed no differences between both groups. CONCLUSIONS A debridement and fixation with anterior column support in combination with an antibiotic therapy appear to be the key points for successful treatment of PSD. The application of TTN- or PEEK-cages does not appear to influence the radiological outcome or risk of reinfection, neither does the extent of disc removal in this clinical subset.

Radiological Comparison of Instrumented Posterior Lumbar Interbody Fusion With One or Two Closed-box Plasmapore Coated Titanium Cages: Follow-up Study Over More Than Seven Years

Study Design. A retrospective clinical study with a follow-up of more than 7 years was conducted. Objective. To compare interbody fusion, segmental lordosis and changes in disc and foramen height in patients who had received instrumented posterior lumbar interbody fusion (PLIF) with 1 or 2 closed-box titanium cages. Summary of Background Data. PLIF using 2 cages is a popular surgical method for treating degenerative lumbar spinal diseases. Implantation of a single cage in instrumented PLIF is still controversial. Methods. From 1994 to 1997, 46 patients with degenerative lumbar spinal disease underwent single-level instrumented PLIF surgery using 1 (n = 22) or 2 (n = 24) interbody rectangular-shaped titanium blocks coated with Plasmapore (Prospace, B. Braun Aesculap AG, Tuttlingen). Mean follow-up was 8 years, ranging from 7 to 10 years. Anteroposterior and lateral radiographs of the patients were taken immediately after surgery and at the last follow-up examination. Segmental stability, change in segmental height, foramen height, and segmental lordosis were evaluated in both groups. Results. Eight years after surgery, segmental stability (1-cage: 95.5%; 2 cages: 95.8%; P > 0.05), change in segmental height (1-cage: −1.9% ± 3.7%; 2-cage: −2.4% ± 3.6%; P > 0.05), foramen height (1-cage: −3.7% ± 9.9%; 2-cage: −6.6% ± 6.5%; P > 0.05) and segmental lordosis (1-cage: −2.4° ± 4.8; 2-cage −1.0° ± 4.0; P > 0.05) did not differ significantly between the 2 groups. Due to adjacent segment syndrome, 3 patients with a previous 2-cage PLIF received additional fusion surgery. Conclusion. In the long-term, instrumented PLIF with a single closed-box titanium cage shows similar radiologic results compared to fusion with 2 titanium cages. Implantation of a single titanium closed-box cage in an instrumented PLIF seems to be adequate in case of degenerative lumbar spinal disease.

Cortical hypoperfusion precedes hyperperfusion following controlled cortical impact injury.

Impaired cerebral perfusion contributes to tissue damage following traumatic brain injury. In this longitudinal study persistence of reduced cortical perfusion employing laser doppler flowmetry was investigated following controlled cortical impact injury (CCII). Before, 30 minutes, 6, 24, and 48 hours after CCII, perfusion in pericontusional cortex was determined by moving a laser doppler probe in 50 x 0.2 mm steps over the traumatized hemisphere in 5 rats. Arterial blood gases and mean arterial blood pressure were monitored. Mean arterial blood pressure and arterial blood gases remained stable during the entire experiments. At 30 minutes and 6 hours following CCII, cortical perfusion was significantly diminished by 24% and 43% (p < 0.05), respectively compared to pre-trauma levels. At 24 and 48 hours after CCII, pericontusional blood flow was significantly increased by 64% and 123%. Cortical hypoperfusion found within the early phase following trauma is reversible and precedes a long lasting phase of hyperperfusion. Changes in tissue mediators (endothelin, acidosis, NO) could account for these findings.

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 ).

Delayed formation of a devastating granulomatous process after metal-on-metal lumbar disc arthroplasty.

Study Design. A case report. Objective. We report the case of a female patient with a delayed and devastating complication after lumbar total disc arthroplasty (TDA). Summary of Background Data. The formation of granulomatous tissue surrounding arthroplasty devices has been described after hip replacements, but has been reported only in a few cases after spinal surgery. Methods. Retrospective case study of a female patient with a delayed complication after lumbar TDA with a metal-on-metal device for degenerative disc disease at level L4–L5 and with follow-up examination 8 months after surgery. Results. About 11 months after lumbar arthroplasty surgery, the patient developed back pain and progressive weakness of both legs. A computed tomographic scan revealed soft tissue surrounding the TDA device and infiltrating the spinal canal. The revision surgery (posterior fixation and decompression) did not improve the clinical situation. The progressive growth of soft tissue led to a high-grade paraparesis and occlusion of the left ureter as well as of both common iliac veins and the infrarenal part of the vena cava inferior. The TDA device was removed. Another posterior surgery with extensive instrumentation was necessary to treat the destruction of vertebral bodies L4 and L5 2 months after the last surgery. The histopathological analysis revealed a granulomatous necrotizing inflammation. After the last revision surgery, the patients back pain decreased. At her last follow-up, no further growth of the soft tissue mass could be found. Conclusion. Metal-on-Metal TDA devices can induce a tumor-like growth with devastating consequences. The reduction of device motion by posterior stabilizing surgery does not seem to stop the growth of the granulomatous mass. The device has to be removed.