Comparison of Endoscopic Facet Joint Denervation to the Percutaneous Technique Regarding Efficacy in Patients With Low Back Pain: A Randomized Controlled Trial.

STUDY DESIGN: This was a single-center prospective randomized controlled study. OBJECTIVE: The aim was to compare the efficacy of endoscopic facet joint denervation (FJD) with that of the percutaneous technique in terms of pain, functional disability, and quality of life in patients with low back pain (LBP). SUMMARY OF BACKGROUND DATA: Different controlled studies in patients with LBP have shown short-term benefits from percutaneous FJD. Observational studies have demonstrated that endoscopic FJD may be more effective. As the superiority of the endoscopic technique has not been clearly demonstrated in previous studies, a prospective randomized controlled study was conducted. MATERIALS AND METHODS: For this study, 40 patients with LBP lasting more than 6 months duration and at least 50% pain reduction on the visual analog scale after medial branch block under fluoroscopy, were assigned randomly to receive percutaneous or endoscopic FJD. The primary outcome was pain, as indicated by visual analog scale. Secondary outcomes were functional disability, as assessed by the Oswestry Disability Index (ODI), Roland-Morris Disability Questionnaire (RDQ), and quality of life, as assessed by the Short Form Health Survey (SF-36). RESULTS: After the intervention, the pain level decreased significantly in both groups ( P <0.001); however, the effect was still significant in the endoscopic group (EG) and diminished to lower than the statistical significance in the percutaneous group (PG) after 12 months. The ODI and RDQ scores also improved significantly in both groups ( P <0.001). However, the ODI and RDQ were significantly better ( P <0.001) in the EG after 12 months. In the SF-36, we observed significant improvement in both groups three months after the intervention. The effect decreased after six months in the PG and was predominantly not demonstrable after 12 months, whereas in the EG there was still a strong significant improvement on all scales ( P <0.001) after 12 months. CONCLUSION: Percutaneous and endoscopic FJD reduced pain and improved functionality and quality of life. However, the effects decreased or disappeared in the PG after 12 months, whereas there was still a strong significant improvement in the EG.

Preliminary Results of Endoscopic Radiofrequency Treatment of the Sacroiliac Joint Syndrome.

BACKGROUND AND STUDY: The sacroiliac joint (SIJ) may be the primary source of pain in 15 to 25% of patients with axial low back pain. Furthermore, 75% of patients who have had fusion surgery develop SIJ pain within 10 years. Treatment options include SIJ blocks, radiofrequency (RF) denervation, and fusion. The RF techniques range from ablation of the nerves supplying the joint, creating lesions to the joint itself, or a combination of both techniques. However, different clinical studies could only identify a limited or, in some cases, no effect in decreasing of pain intensity and duration of the effect. METHODS: In this retrospective study, we selected 23 patients with SIJ pain, with a duration of more than 12 months and a 50% pain reduction on the Numeric Rating Scale (NRS) after diagnostic block. All patients received endoscopic ablation of the medial branch L5/S1 and the lateral branches, exiting the sacral foramina on S1/S2 and S2/S3 on both sides while using only one incision on each side. Telephone interviews were conducted with all patients. The outcome was determined with Odom's criteria, percent reduction NRS, subjective assessment of the patient, and duration of the effect. RESULTS: According to Odom's criteria, 79% of the patients showed acceptable to excellent results and confirmed that denervation helped them to manage their daily lives better. The average pain reduction in the responder group was 57% with an average duration of 13.4 months. CONCLUSION: In this retrospective study, we could demonstrate the practicability and effectiveness of endoscopic SIJ denervation in the treatment of SIJ pain using only one incision for three levels on each side. Further studies should investigate if this procedure is more effective than percutaneous RF.

Endoscopic 4-MHz Radiofrequency Treatment of Facet Joint Syndrome Is More Than Just Denervation: One Incision for Three Facets.

BACKGROUND AND STUDY AIMS: Low back pain is well documented as an extremely common health problem. The most frequently used treatment is radiofrequency denervation for chronic low back pain. However, different clinical studies could only show a limited to no improvement regarding the decrease of pain intensity and duration of the effect. The main reasons for these limited effects seem to be due to the size of the lesion and difficulties in locating the exact placement of the cannula near the medial branch as well as or additional pathologies. Using an endoscope, it is possible to coagulate the facet joints and the medial branch under visual control and consider other pathologies such as extraspinal synovial cysts. PATIENTS: In this retrospective study, we included 28 patients with low back pain, with a duration > 6 months and a 50% pain reduction on the numeric analog scale (NAS) after a diagnostic block. All patients received endoscopic facet joint denervation of three facets on the left and right side using only one incision on each side with an exploration of the surrounding tissue. Telephone interviews were conducted with all patients. The outcome was determined with Odom's criteria, percentage reduction NAS, subjective assessment of the patient, and duration of the effect. RESULTS: According to Odom's criteria, 68% of the patients showed "acceptable" to "excellent" results and confirmed that denervation helped them manage their daily lives better. The average pain reduction in the responder group was 47% with an average duration of 7.8 months. CONCLUSION: In this retrospective study, we demonstrated the practicability and effectiveness of the endoscopic facet joint denervation procedure in the treatment of chronic low back pain using only one incision for three facets. Further studies should investigate if this procedure is more effective than percutaneous radiofrequency denervation.

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 ).

Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell-free resorbable polymer scaffolds.

Degeneration of intervertebral discs (IVDs) occurs frequently and is often associated with lower back pain. Recent treatment options are limited and treat the symptoms rather than regenerate the degenerated disc. Cell-free, freeze-dried resorbable polyglycolic acid (PGA)-hyaluronan implants were used in an ovine IVD degeneration model. The nucleus pulposus of the IVD was partially removed, endoscopically. PGA-hyaluronan implants were immersed in autologous sheep serum and implanted into the disc defect. Animals with nucleotomy only served as controls. The T2-weighted/fat suppression sequence signal intensity index of the operated discs, as assessed by magnetic resonance imaging (MRI), showed that implantation of the PGA-hyaluronan implant improved (p = 0.0066) the MRI signal compared to controls at 6 months after surgery. Histological analysis by haematoxylin and eosin and safranin O staining showed the ingrowth of cells with typical chondrocytic morphology, even cell distribution, and extracellular matrix rich in proteoglycan. Histomorphometric analyses confirmed that the implantation of the PGA-hyaluronan scaffolds improved (p = 0.027) the formation of regenerated tissue after nucleotomy. Disc heights remained stable in discs with nucleotomy only as well as after implantation of the implant. In conclusion, implantation of cell-free polymer-based implants after nucleotomy induces nucleus pulposus tissue regeneration and improves disc water content in the ovine model.

Towards biological anulus repair: TGF-ß3, FGF-2 and human serum support matrix formation by human anulus fibrosus cells.

Closure and biological repair of anulus fibrosus (AF) defects in intervertebral disc diseases is a therapeutic challenge. The aim of our study was to evaluate the anabolic properties of bioactive factors on cartilaginous matrix formation by AF cells. Human AF cells were harvested from degenerated lumbar AF tissue and expanded in monolayer culture. AF cell differentiation and matrix formation was initiated by forming pellet cultures and stimulation with hyaluronic acid (HA), human serum (HS), fibroblast growth factor-2 (FGF-2), transforming growth factor-ß3 (TGF-ß3) and TGF-ß3/FGF-2 for up to 4 weeks. Matrix formation was assessed histologically by staining of proteoglycan, type I and type II collagens and by gene expression analysis of typical extracellular matrix molecules and of catabolic matrix metalloproteinases MMP-2 and MMP-13. AF cells, stimulated with HS, FGF-2 and most pronounced with TGF-ß3 or TGF-ß3/FGF-2 formed a cartilaginous matrix with significantly enhanced expression of matrix molecules and of MMP-13. Stimulation of AF cells with TGF-ß3 was accompanied by induction of type X collagen, known to occur in hypertrophic cartilage cells having mineralizing potential. HA did not show any chondro-inductive characteristics. These findings suggest human serum, FGF-2 and TGF-ß3 as possible candidates to support biological treatment strategies of AF defects.

A 3D environment for anulus fibrosus regeneration.

OBJECT: Biological repair strategies for the treatment of degenerated intervertebral discs are of growing interest. In addition to the development of nucleus pulposus implants to restore disc height and relieve pain, there is growing demand for an appropriate method for reconstructing the anulus fibrosus (AF). The aim of this pilot study was to evaluate the applicability of a resorbable 3D polymer of pure polyglycolic acid (PGA) combined with hyaluronan for the use in cell-free and cell-based regeneration and repair of the AF. METHODS: Adult human AF cells were expanded in vitro using human serum and rearranged three dimensionally in hyaluronan-PGA scaffolds that were stabilized with fibrin for in vitro analyses. The capacity of dedifferentiated AF cells to redifferentiate was evaluated after 2 weeks of culture, using propidium iodide/fluorescein diacetate staining, gene expression analysis of typical marker genes, and histological staining of proteoglycans. RESULTS: The propidium iodide/fluorescein diacetate staining demonstrated that vital human AF cells were evenly distributed within the construct. The induction of typical AF marker genes such as collagen Types I-III indicated the initiation of AF redifferentiation by 3D assembly in hyaluronan-PGA. Histological analysis of the constructs showed initial formation of an AF-like matrix comprising proteoglycans. CONCLUSIONS: The results suggest that the 3D arrangement of human AF cells in resorbable hyaluronan-PGA scaffolds cultured in the presence of human serum is an excellent system for AF cell redifferentiation.

Adequacy of herniated disc tissue as a cell source for nucleus pulposus regeneration.

OBJECT: The object of this study was to characterize the regenerative potential of cells isolated from herniated disc tissue obtained during microdiscectomy. The acquired data could help to evaluate the feasibility of these cells for autologous disc cell transplantation. METHODS: From each of 5 patients (mean age 45 years), tissue from the nucleus pulposus compartment as well as from herniated disc was obtained separately during microdiscectomy of symptomatic herniated lumbar discs. Cells were isolated, and in vitro cell expansion for cells from herniated disc tissue was accomplished using human serum and fibroblast growth factor-2. For 3D culture, expanded cells were loaded in a fibrin-hyaluronan solution on polyglycolic acid scaffolds for 2 weeks. The formation of disc tissue was documented by histological staining of the extracellular matrix as well as by gene expression analysis of typical disc marker genes. RESULTS: Cells isolated from herniated disc tissue showed significant signs of dedifferentiation and degeneration in comparison with cells from tissue of the nucleus compartment. With in vitro cell expansion, further dedifferentiation with distinct suppression of major matrix molecules, such as aggrecan and Type II collagen, was observed. Unlike in previous reports of cells from the nucleus compartment, the cells from herniated disc tissue showed only a weak redifferentiation process in 3D culture. However, propidium iodide/fluorescein diacetate staining documented that 3D assembly of these cells in polyglycolic acid scaffolds allows prolonged culture and high viability. CONCLUSIONS: Study results suggested a very limited regenerative potential for cells harvested from herniated disc tissue. Further research on 2 major aspects in patient selection is suggested before conducting reasonable clinical trials in this matter: 1) diagnostic strategies to predict the regenerative potential of harvested cells at a radiological or cell biology level, and 2) clinical assessment strategies to elucidate the metabolic state of the targeted disc.

Engineering of polymer-based grafts with cells derived from human nucleus pulposus tissue of the lumbar spine.

Intervertebral disc degeneration is considered a major source of low back pain. We therefore examined an absorbable polyglycolic acid (PGA) biomaterial for its utility to support disc tissue regeneration. Microdiscectomy for lumbar disc herniation was performed in six patients. Intervertebral disc cells were isolated and in vitro cell expansion was accomplished using human serum and FGF2. In a fibrin-hyaluronan solution, disc cells were loaded on PGA scaffolds and cultured for 2 weeks. Formation of disc tissue was documented by histological staining of the extracellular matrix as well as gene expression analysis of typical disc marker genes. The use of human serum and FGF2 ensures efficient isolation and expansion of human disc cells. During this phase, dedifferentiation of the disc cells was observed. Subsequent 3D tissue culture of disc cells in PGA scaffolds, however, is accompanied by the induction of typical disc marker genes, resulting in tissue containing glycosaminoglycans and collagens. Propidium iodide/fluorescein diacetate (PI/FDA) staining documented that 3D assembly of disc cells in PGA scaffolds allows prolonged culture and high viability of disc cells. Disc cells from tissue of the nucleus compartment can be reliably isolated and expanded in vitro with FGF. In combination with a fibrin-hyaluronan solution and loaded on a PGA scaffold, disc cells from expansion culture commence a redifferentiation process. PGA-based scaffolds could be useful as temporal matrices for regenerative disc repair approaches.

Intervertebral disc regeneration after implantation of a cell-free bioresorbable implant in a rabbit disc degeneration model.

Degeneration of the intervertebral disc is the most common cause of lower back pain. Interestingly, all available treatments are limited to treat the symptoms and not the underlying biologic alterations of the disc. Freeze-dried resorbable non-woven polyglycolic acid (PGA) - hyaluronan implants were used in a degenerated disc disease (DDD) model in New Zealand white rabbits. The constructs were immersed in allogenic serum and implanted into the disc defect. Animals with discectomy only served as controls. The T2-weighted/fat suppression sequence signal intensity of the operated discs as assessed by magnet resonance imaging decreased in both groups one week after the operation compared to a healthy disc. After 12 months the implanted group showed an increase of 51% in the signal intensity compared to the 1-week results whereas the signal intensity in the sham group remained on the same level from one week to 12 months. Histological and quantitative immunohistochemical examination after 12 months indicated cell migration into the defect and showed formation of disc repair tissue. In controls, repair tissue containing type II collagen was not evident. In conclusion, the implantation of polymer-based constructs after discectomy induces tissue regeneration resulting in improvement of the disc water content.

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.

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.

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.

Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias.

OBJECTIVE: The influence of the degree of resection on survival in patients with glioblastoma multiforme is still under discussion. The highly controlled 5-aminolevulinic acid study provided a unique platform for addressing this question as a result of the high frequency of "complete" resections, as revealed by postoperative magnetic resonance imaging scans achieved by fluorescence-guided resection and homogeneous patient characteristics. METHODS: Two hundred forty-three patients with glioblastoma multiforme per protocol from the 5-aminolevulinic acid study were analyzed. Patients with complete and incomplete resections as revealed by early magnetic resonance imaging scans were compared. Prognostic factors that might cause bias regarding resection and influence survival (e.g., tumor size, edema, midline shift, location, age, Karnofsky Performance Scale score, National Institutes of Health Stroke Scale score) were used for analysis of overall survival. Time to reintervention (chemotherapy, reoperation) was analyzed further to exclude bias regarding second-line therapies. RESULTS: Treatment bias was identified in patients with complete (n = 122) compared with incomplete resection (n = 121), i.e., younger age and less frequent eloquent tumor location. Other factors, foremost preoperative tumor size, were identical. Patients without residual tumor survived longer (16.7 versus 11.8 mo, P < 0.0001). In multivariate analysis, only residual tumor, age, and Karnofsky Performance Scale score were significantly prognostic. To account for distribution bias, patients were stratified for age (>60 or

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.

Correlation of F-18-fluoro-ethyl-tyrosin uptake with vascular and cell density in non-contrast-enhancing gliomas.

OBJECTIVE: Even without contrast enhancement on MRI scans gliomas can show histological features of anaplasia. These tumors are heterogeneous regarding anaplastic and non-anaplastic areas. Increased amino acid uptake was shown to be associated with dismal prognosis in gliomas. We investigated histological correlates of tumor grading in biopsies obtained from regions with maximum amino acid uptake revealed by F-18-fluoro-ethyl-tyrosin positron emission tomography (FET-PET). METHODS: We included 22 patients with non-contrast enhancing lesions on MRI scans. PET was performed 10 min after FET injection, and the area of maximum FET uptake was chosen as the biopsy target. In 13 patients neuronavigated biopsies were obtained during tumor resection. Nine patients had a stereotactic biopsy. The ratio of maximum standardized uptake value (SUV) to background was calculated. Histological specimens were classified and graded according to world health organization (WHO) criteria. We investigated cell and vascular density, mitotic activity, proliferation index, microvascular proliferation, nuclear pleomorphism, necrosis and immunoreactivity of LAT1 (SLC7A5), an amino acid transporter with prognostic impact in gliomas. RESULTS: 12 of the 22 non-contrast enhancing gliomas corresponded to anaplastic astrocytomas WHO grade III. Vascular and cellular density was correlated highly to the SUV ratio (P = 0.0015 and P = 0.0021, respectively), but with no nuclear pleomorphism, mitotic activity, Mib-1 immunoreactivity, or microvascular proliferation. Thus, no correlation was found between FET uptake and tumor grade. CONCLUSION: FET-PET correlates with vascular and cell density in non-contrast enhancing gliomas. Although tumor grade cannot be predicted, clinical use of FET PET as an indicator for neovascularization should be addressed in future studies.

Ubiquitin reduces contusion volume after controlled cortical impact injury in rats.

Recent data suggest that ubiquitin has anti-inflammatory properties and therapeutic potential after severe trauma and brain injuries. However, direct evidence for its neuroprotective effects has not yet been provided. We hypothesized that ubiquitin treatment is neuroprotective, and thus reduces brain edema formation and cortical contusion volume after closed traumatic brain injuries. To test this hypothesis, a focal cortical contusion was induced using a controlled cortical impact (CCI) model in Sprague-Dawley rats. Animals (n = 27) were randomized to either 1.5 mg/kg ubiquitin or vehicle (placebo) intravenously within 5 min after CCI. Blood pressure, arterial blood gases (ABG) and intracranial pressure (ICP) were monitored. Ubiquitin serum and cerebrospinal fluid levels were measured by ELISA. Brain water content was quantified gravimetrically after 24 h and cerebral contusion volume was determined in triphenyltetrazolium-chloride stained brains after 7 days. All animals recovered to normal activity. ICP and cerebral perfusion pressures were normal at the end of the observation period. Ubiquitin serum and CSF levels at 24 h and 7 days after CCI were similar in both groups. With ubiquitin brain water content of the injured hemisphere was slightly lower (n = 6/group; 79.97 +/- 0.29% vs. 81.11 +/- 0.52%; p = 0.08). Cortical contusion volume was significantly lower with ubiquitin (n = 7-8/group; 32.88 +/- 2.1 mm(3) vs. 43.96 +/- 4.56 mm(3); p = 0.025). This study shows that ubiquitin treatment after brain injury has direct neuroprotective effects, as demonstrated by improved brain morphology 7 days after brain injury. In connection with its beneficial effects in our previous studies, these data suggest ubiquitin as a promising candidate protein therapeutic for the treatment of brain injuries.

Tacrolimus depresses local immune cell infiltration but fails to reduce cortical contusion volume in brain-injured rats.

The immunosuppressant drug tacrolimus (FK-506) failed to show an anti-edematous effect despite suppressing pro-inflammatory cytokines in cerebrospinal fluid following focal traumatic brain injury. By questioning the role of the inflammatory response as a pharmacological target, we investigated the effects of FK-506 on immune cell infiltration in brain-injured rats. Following induction of a cortical contusion, male Sprague-Dawley rats received FK-506 or physiological saline intraperitoneally. Brains were removed at 24 h, 72 h or 7 days, respectively. Frozen brain sections (7 microm) were stained immunohistologically for markers of endothelial activation (intercellular adhesion molecule-1--ICAM-1), neutrophil infiltration (His-48), and microglial and macrophage activation (Ox-6; ED-1), respectively. Immunopositive cells were counted microscopically. Contusion volume (CV) was quantified morphometrically 7 days after trauma. Inflammatory response was confined to the ipsilateral cortex and hippocampal formation, predominating in the contusion and pericontusional cortex. Strongest ICAM-1 expression coincided with sustained granulocyte accumulation at 72h which was suppressed by FK-506. Ox-6+ cells prevailing at 72 h were also significantly reduced by FK-506. ED-1+ cells reaching highest intensity at 7 days were significantly attenuated at 72 h. Cortical CV was not influenced. FK-506 significantly decreased post-traumatic local inflammation which, however, was not associated with a reduction in cortical CV. These results question the importance of post-traumatic local immune cell infiltration in the secondary growth of a cortical contusion.