Novel Methods to Measure Height and Volume in Healthy and Degenerated Lumbar Discs in MRIs: A Reliability Assessment Study.

BACKGROUND: In the regeneration and therapy of degenerated intervertebral discs, the height, volume or categorizing assessments, such as Pfirrmann classification, are used to quantify the discs themselves and the effects of therapy. Here, the question of transferability, in the sense of reliability, of the results arises in the common exchange. METHODS: We have investigated two established and a newly developed (9-point measurement), easy to use methods for height measurement and volume measurement on degenerated and healthy lumbar intervertebral discs of 66 patients regarding inter- and intra-observer reliability. RESULTS: In overview, we found very different reliabilities. While the intra-observer reliability showed good to excellent agreement for both healthy and degenerated lumbar discs for the height and volume measurements, the inter-observer reliability was low or moderate in some cases. The 9-point method for height determination consistently showed better reliability for both healthy and degenerated discs, for both intra- and inter-observer reliability, compared to the two established methods. CONCLUSIONS: We recommend using the 9-point measurement as the method to communicate lumbar disc height, both for healthy and degenerated discs. Due to the partly low or moderate reliability, significant differences in the measured heights can already occur, which can lead to a worsened comparability.

Giant intracranial aneurysms of the posterior circulation and their relation to the brainstem: analysis of risk factors for neurological deficits.

OBJECTIVE: Giant posterior circulation aneurysms (GPCirAs) usually cause substantial mass effect on the brainstem, which may lead to neurological deficits. So far, there has been no systematic investigation of factors associated with such deficits in GPCirA. The authors aim to examine the risk factors for cranial nerve deficit (CND), motor deficit, and disability in patients with GPCirA. METHODS: Using MR images obtained in 30 patients with unruptured GPCirA, the authors examined GPCirA volume, presence of hydrocephalus or partial thrombosis (PT) of the aneurysm, and the degree of brainstem displacement measured by the distance between the McRae line and the tip of the GPCirA (∆MT). They evaluated associations between these factors and neurological deficits. RESULTS: Thirty GPCirAs in 30 patients were included. The prevalence of CNDs was 50%. Patients with CNDs significantly differed from those without CNDs in terms of age (mean 51.0 years [SD 15.0 years] vs 69.0 years [SD 21.0 years], p = 0.01) and in ∆MT (median 50.7 mm [IQR 39.2-53.9 mm] vs 39.0 mm [IQR 32.3-45.9 mm], p = 0.02). The prevalence of motor deficits was 33.3%. Patients with motor deficits showed a larger ∆MT (median 50.5 mm [IQR 40.8-54.6 mm]) compared with those without (∆MT: median 39.1 mm [IQR 32.8-50.5 mm], p = 0.04). GPCirA volume was larger in patients with poor modified Rankin Scale (mRS) scores (median 14.9 cm3 [IQR 8.6-18.7 cm3]) than in those with mRS scores of 0-2 (median 6.8 cm3 [IQR 4.4-11.7 cm3], p = 0.03). After adjusting for patient age and the occurrence of hydrocephalus or PT, the authors found that higher degrees of disability were significantly associated with aneurysm volume (OR 1.13, 95% CI 1.0-1.3; p = 0.04), but not with ∆MT. The occurrence of CND or motor deficit was not associated with any of the examined variables. There was no correlation between GPCirA volume and ∆MT (rs = 0.01, p = 0.96). The prevalence of neurological deficits did not differ between GPCirA at the basilar apex, the basilar trunk, the vertebrobasilar junction, or the vertebral artery. CONCLUSIONS: In this study, the neurological condition of the patients was associated only with GPCirA volume and not with the degree of brainstem displacement, the occurrence of PT or hydrocephalus, or the exact location of the GPCirA. These findings highlight the clinical relevance of GPCirA volume and suggest that factors such as brainstem displacement or PT should play less of a role when finding arguments for or against treatment of GPCirA.Clinical trial registration no.: NCT02066493 (clinicaltrials.gov).

Protective effects of alpha phenyl-tert-butyl nitrone and ascorbic acid in human adipose derived mesenchymal stem cells from differently aged donors.

Adipose-derived mesenchymal stem cells (ADSCs) are multipotent stem cells that promote therapeutic effects and are frequently used in autologous applications. Little is known about how ADSCs respond to genotoxic stress and whether or not donor age affects DNA damage and repair. In this study, we used the comet assay to assess DNA damage and repair in human ADSCs derived from young (20-40 years), middle-aged (41-60 years), and older (61+ years) donors following treatment with H2O2 or UV light. Tail lengths in H2O2-treated ADSCs were substantially higher than the tail lengths in UV-treated ADSCs. After 30 minutes of treatment with H2O2, ADSCs preconditioned with alpha phenyl-tert-butyl nitrone (PBN) or ascorbic acid (AA) showed a significant reduction in % tail DNA. The majority of ADSCs treated with PBN or AA displayed low olive tail movements at various timepoints. In general and indicative of DNA repair, % tail length and % tail DNA peaked at 30 minutes and then decreased to near-control levels at the 2 hour and 4 hour timepoints. Differently aged ADSCs displayed comparable levels of DNA damage in the majority of these experiments, suggesting that the age of the donor does not affect the DNA damage response in cultured ADSCs.

Migrational changes of mesenchymal stem cells in response to cytokines, growth factors, hypoxia, and aging.

Mesenchymal stem cells (MSCs) are non-immunogenic, multipotent cells with at least trilineage differentiation potential. They promote wound healing, improve regeneration of injured tissue, and mediate numerous other health effects. MSCs migrate to sites of injury and stimulate repair either through direct differentiation or indirectly through the stimulation of endogenous repair mechanisms. Using the in vitro scratch assay, we show that the inflammatory cytokines, chemokines, and growth factors TNF-α, SDF-1, PDGF, and bFGF enhance migration of rat MSCs under normoxic conditions, while TNF-α, IFN-γ, PDGF, and bFGF promote MSC migration under hypoxic conditions. This indicates that the oxygen concentration affects how MSCs will migrate in response to specific factors and, consistent with this, differential expression of cytokines was observed under hypoxic versus normoxic conditions. Using the transwell migration assay, we find that TNF-α, IFN-γ, bFGF, IGF-1, PDGF, and SDF-1 significantly increase transmigration of rat MSCs compared to unstimulated medium. MSCs derived from aged rats exhibited comparable migration to MSCs derived from young rats under hypoxic and normoxic conditions, even after application with specific factors. Similarly, migration in MSCs from aged, human donors did not statistically differ compared to migration in MSCs derived from human umbilical cord tissue or younger donors.

Perianeurysmal edema in giant intracranial aneurysms in relation to aneurysm location, size, and partial thrombosis.

OBJECT: The underlying mechanisms causing intracranial perianeurysmal edema (PAE) are still poorly understood. Since PAE is most frequently observed in giant intracranial aneurysms (GIAs), the authors designed a study to examine the occurrence of PAE in relation to the location, size, and partial thrombosis (PT) of GIAs along with the clinical impact of PAE. METHODS: Magnetic resonance imaging data for patients with a diagnosis of unruptured GIA from the international multicenter Giant Intracranial Aneurysm Registry were retrospectively analyzed with regard to location and size of the GIA, PAE volume, and the presence of PT. The occurrence of PAE was correlated to clinical findings. RESULTS: Imaging data for 69 GIAs were eligible for inclusion in this study. Perianeurysmal edema was observed in 33.3% of all cases, with the highest frequency in GIAs of the middle cerebral artery (MCA; 68.8%) and the lowest frequency in GIAs of the cavernous internal carotid artery (ICA; 0.0%). Independent predictors of PAE formation were GIA volume (OR 1.13, p = 0.02) and the occurrence of PT (OR 9.84, p = 0.04). Giant intracranial aneurysm location did not predict PAE occurrence. Giant aneurysms with PAE were larger than GIAs without PAE (p < 0.01), and GIA volume correlated with PAE volume (rs = 0.51, p = 0.01). Perianeurysmal edema had no influence on the modified Rankin Scale score (p = 0.30 or the occurrence of aphasia (p = 0.61) or hemiparesis (p = 0.82). CONCLUSIONS: Perianeurysmal edema was associated with GIA size and the presence of PT. As no PAE was observed in cavernous ICA aneurysms, even though they exerted mass effect on the brain and also displayed PT, the dura mater may serve as a barrier protecting the brain from PAE formation.

Quantifying unruptured giant intracranial aneurysms by measuring diameter and volume--a comparative analysis of 69 cases.

BACKGROUND: Intracranial aneurysms (IA) are usually quantified according to their largest diameter. However, volumetry has recently been increasingly conducted as well, especially in giant intracranial aneurysms (GIAs). Since so far the true value of GIA volumetry is unknown, we designed a trial to examine correlations between GIA diameter and volume with special focus on clinical implications. METHODS: Magnetic resonance imaging of 69 unruptured GIAs in 66 patients was retrospectively evaluated. The largest diameter and volume were measured. Also, potential associations to the patients' clinical conditions were examined. RESULTS: Comparing GIA sizes of our patient cohort produced different results depending on whether GIA diameter or volume was measured. Measuring the diameter identified posterior circulation GIAs as the largest ones (39.2 mm, IQR 37.3-48.3), while measuring the volume found GIAs of the MCA to be the largest ones (12.3 cm(3), IQR 7.2-27.8). A correlation of GIA diameter and volume was only found in anterior circulation GIAs, which were predominantly saccular in shape, but not in those of the posterior circulation, of which most were fusiform. Neither GIA diameter nor GIA volume but only GIA location was associated with neurological deficits. CONCLUSION: Diameter and volume measurements are not interchangeable modes of GIA quantification. Our data suggest that the idea of distinguishing different sizes of GIA may be clinically less relevant than examining their location, shape or mass effect.

Morphometrical dimensions of the sheep thoracolumbar vertebrae as seen on digitised CT images.

The sheep spine is widely used as a model for preclinical research in human medicine to test new spinal implants and surgical procedures. Therefore, precise morphometric data are needed. The present study aimed to provide computed tomographic (CT) morphometry of sheep thoracolumbar spine. Five adult normal Merino sheep were included in this study. Sheep were anaesthetised and positioned in sternal recumbency. Subsequently, transverse and sagittal images were obtained using a multi-detector-row helical CT scanner. Measurements of the vertebral bodies, pedicles, intervertebral disc and transverse processes were performed with dedicated software. Vertebral bodies and the spinal canal were wider than they were deep, most obviously in the lumbar vertebrae. The intervertebral discs were as much as 57.4% thicker in the lumbar than in the thoracic spine. The pedicles were higher and longer than they were wide over the entire thoracolumbar spine. In conclusion, the generated data can serve as a CT reference for the ovine thoracolumbar spine and may be helpful in using sheep spine as a model for human spinal research.

Is sheep lumbar spine a suitable alternative model for human spinal researches? Morphometrical comparison study.

Sheep are commonly used as a model for human spinal orthopaedic research due to their similarity in morphological and biomechanical features. This study aimed to document the volumes of vertebral bodies and compare the generated results as well as morphometry of the sheep lumbar spine to human published data. For this purpose, computed tomography scans were carried out on five adult Merino sheep under general anaesthesia. Transverse 5 mm thick images were acquired from L1 to L6 using a multi-detector-row helical CT scanner. Volume measurements were performed with dedicated software. Four spinal indices and Pavlov's ratio were calculated. Thereafter, the generated data were compared to published literature on humans. The mean vertebral body volume showed an increase towards the caudal vertebrae, but there were no significant differences between the vertebral levels (P>0.05). Compared to humans, sheep vertebral body volumes were 48.6% smaller. The comparison of absolute values between both species revealed that sheep had smaller, longer and narrower vertebral bodies, thinner intervertebral discs, narrower spinal canal, longer transverse processes, shorter dorsal spinous processes and narrower, higher pedicles with more lateral angulations. The comparison of the spinal indices showed a good similarity to human in terms of the vertebral endplates and spinal canal. The results of this study may be helpful for using the sheep as a model for human orthopaedic spinal research if anatomical differences are taken into account.

Clinical evaluation of a new multiparameter neuromonitoring device: measurement of brain tissue oxygen, brain temperature, and intracranial pressure.

OBJECTIVE: The study presented evaluated the first clinical use of a new multiparameter catheter measuring intracranial pressure (ICP), partial pressure of brain tissue oxygen (ptiO2), and brain temperature (TBr) (Neurovent PTO). To assess the validity of measured ptiO2 a second probe, which represents the current golden standard of ptiO2 measurement, was implanted (Licox system). METHODS: Thirty patients with indicated invasive measurement of ICP under intensive care unit conditions were included. Using a double lumen bolt, ptiO2 was measured simultaneously with Licox and Neurovent PTO. Ex vivo tests on both probes were conducted independently by the manufacturer of the Neurovent PTO (Raumedic AG, Germany). RESULTS: The average of individual mean ptiO2 measurements showed no relevant differences between the Licox (19.5+/-7.1) and Neurovent multiparameter probe (21.7+/-9.5). Twenty-eight Licox probes out of 30 showed proper functioning over the desired monitoring period. Raumedic multiparameter probes displayed a higher malfunction/handling error frequency (2 device errors, 11 handling errors). A comparison of the ptiO2 data between the Licox and Raumedic systems according to Bland and Altman was possible in 18 out of 30 patients and showed acceptable results (mean difference -1.24 mm Hg; limits of agreement: -25.1 to +22.6 mm Hg). A total of 95.2% of 96,083 recordings was within the calculated limits of agreement. Ex vivo tests of the probes after explantation revealed stable ICP and TBr function of the Raumedic probe. Precision of Zero ptiO2 did not differ between the probes, whereas precision of the 150 mm Hg ptiO2 was greater in the Raumedic probes. CONCLUSIONS: Combining 3 different neuromonitoring functions in 1 probe might ease monitoring by making a second (ptiO2) probe unnecessary. Interpretation of our data is limited by several factors: (1) monocentric study; (2) reduced mechanical probe stability, handling difficulties with the double lumen bolt; (3) design changes to improve mechanical stability will require further study; (4) conflict of interest with Raumedic because of its support for the study. The conclusion drawn from our study is that the new multiparameter probe evaluated does measure ICP, TBr, and ptiO2. But all the initial data given in this paper have to be interpreted cautiously. A new study will be necessary when the mechanical stability of the new probe has been improved.

Posterior lumbar interbody fusion using rhBMP-2.

The use of biological technologies for the treatment of degenerative spinal diseases has undergone rapid clinical and scientific development. BMP strategies have gained wide support for an inherent potential to improve the ossification process. It has been extensively studied in combination with various techniques for spinal stabilisation from both anterior and posterior approach. We studied the fusion process after implantation of rhBMP-2 in 17 patients with degenerative lumbar spine diseases in combination with dorsal fixation with pedicle screws and poly-ether-ether-ketone (PEEK) interbody cages. We used 12 mg rhBMP-2 carried by collagen sponge, 6 mg in every cage. Patient follow up consisted of pre-operative radiographic and clinical evaluation. Similar post-operative evaluations were performed at 3 and 6 months. Clinical assessment demonstrated clear improvement in all patients despite evidence of vertebral endplate osteoclastic activity in the 3-month radiographs. The 6-month radiograph, however, confirmed evidence of fusion, and no untoward results or outcomes were noted. While previous studies have shown exclusively positive results in both fusion rates and process, our study demonstrated an intermediate morphology at 3 months during the ossification process using Induct Os in combination with peek-cages using a PLIF-technique. The transient resorption of bone surrounding the peek cage did not result in subsidence, pain or complication, and fusion was reached in all cases within a 6-month-controlled evaluation. Although there was no negative influence on clinical outcome, the potential for osteoclastic or metabolic resorption bears watching during the post-surgical follow up.

Does brain temperature correlate with intracranial pressure?

OBJECTIVE: A positive correlation between brain temperature and intracranial pressure (ICP) has been proposed for patients under intensive care conditions. DESIGN AND METHODS: Data were recorded at 5-minute intervals in patients under ICP monitoring conditions. Brain temperature: combined ICP/temperature probe (Raumedic), core temperature: indwelling urinary catheter with temperature probe (Rüsch). The correlation between brain temperature and ICP was assessed by computing an estimated mean correlation coefficient (re) and by a time series analysis. PATIENTS: Forty consecutive neurosurgical patients receiving intensive care therapy for trauma, cerebrovascular malformation, and spontaneous hemorrhage were studied. A total of 48,892 measurements (9778 h) were analyzed. No additional interventions were performed. RESULTS: The median ICP was 14 mm Hg (range: -13 to 167). The brain temperature (median 38 degrees C; range 23.2 to 42.1) was 0.3 degrees C (range: -3.6 to 2.6) higher than the core temperature (median 37.7 degrees C; range 16.6 to 42.0), P<0.001. The mean Pearson correlation between ICP and brain temperature in all patients was re=0.13 (P<0.05); the time series analysis (assuming a possible lagged correlation between ICP and brain temperature) revealed a mean correlation of 0.05+/-0.25 (P<0.05). Both correlation coefficients indicate that any relationship between brain temperature and ICP accounts for less than 2% of the variability [coefficient of determination (r)<0.02]. CONCLUSIONS: These data do not support the notion of a clinically useful correlation between brain temperature and ICP.