Development and first results of a national databank on care and treatment outcome after traumatic brain injury.

PURPOSE: In absence of comprehensive data collection on traumatic brain injury (TBI), the German Society for Neurosurgery (DGNC) and the German Society for Trauma Surgery (DGU) developed a TBI databank for German-speaking countries. METHODS: From 2016 to 2020, the TBI databank DGNC/DGU was implemented as a module of the TraumaRegister (TR) DGU and tested in a 15-month pilot phase. Since its official launch in 2021, patients from the TR-DGU (intermediate or intensive care unit admission via shock room) with TBI (AIS head ≥ 1) can be enrolled. A data set of > 300 clinical, imaging, and laboratory variables, harmonized with other international TBI data collection structures is documented, and the treatment outcome is evaluated after 6- and 12 months. RESULTS: For this analysis, 318 patients in the TBI databank could be included (median age 58 years; 71% men). Falls were the most common cause of injury (55%), and antithrombotic medication was frequent (28%). Severe or moderate TBI were only present in 55% of patients, while 45% suffered a mild injury. Nevertheless, intracranial pathologies were present in 95% of brain imaging with traumatic subarachnoid hemorrhages (76%) being the most common. Intracranial surgeries were performed in 42% of cases. In-hospital mortality after TBI was 21% and surviving patients could be discharged after a median hospital stay of 11 days. At the 6-and 12 months follow-up, a favorable outcome was achieved by 70% and 90% of the participating TBI patients, respectively. Compared to a European cohort of 2138 TBI patients treated in the ICU between 2014 and 2017, patients in the TBI databank were already older, frailer, fell more commonly at home. CONCLUSION: Within five years, the TBI databank DGNC/DGU of the TR-DGU could be established and is since then prospectively enrolling TBI patients in German-speaking countries. With its large and harmonized data set and a 12-month follow-up, the TBI databank is a unique project in Europe, already allowing comparisons to other data collection structures and indicating a demographic change towards older and frailer TBI patients in Germany.

The Long-Term Sequelae of Traumatic Brain Injury Over 10 Years of Follow-Up­A Matched Cohort Study Based on Routine Data of a Statutory Health Insurance Carrier

BACKGROUND: The acute effects of traumatic brain injury (TBI) are well documented, but there is no systematic quantification of its long-term sequelae in Germanlanguage literature. The purpose of this article is to compare the frequency of conditions linked to prior TBI with their frequency in the non-brain-injured population. METHODS: A matched cohort study was carried out on the basis of routine data from the BARMER statutory health insurance carrier. The exposure group consisted of patients treated over the period 2006-2009 for TBI at a variety of treatment intensities, including persons with multiple organ trauma. The control group consisted of BARMER insurees without prior TBI who were matched with the patients in the exposure group for age, sex, and pre-existing diseases. Late sequelae were sought in the routine data for a period of ten years after the injury. The outcome rates of the exposure and control groups were compared with Kaplan-Meier estimators and Poisson regression. RESULTS: 114 296 persons with TBI in the period 2006-2009 were included in the study. The mortality within ten years of TBI was 305 per 1000 individuals. The relative mortality in the exposure group was higher than that in control individuals of the same age and sex, with an incidence rate ratio (IRR) of 1.67 (95% confidence interval, [1.60; 1.74]). Immobility, dementia, epilepsy, endocrine disorders, functional disorders, depression, anxiety, cognitive deficits, headache, and sleep disorders were also more common in the exposure group. Persons with TBI requiring highintensity treatment displayed the highest relative incidence rates of the conditions studied over 10 years of follow-up. Persons who had been admitted to the hospital because of TBI had higher relative incidence rates for epilepsy and dementia than those who had been cared for on an outpatient basis. CONCLUSION: Adverse sequelae of TBI can still be seen ten years after the exposure. These patients die earlier than persons without TBI and suffer earlier and more frequently from associated conditions.

The endoscopic surgical resection of intrasellar lesions conserves the hormonal function: a negative correlation to the microsurgical technique.

BACKGROUND: The endonasal endoscopic approach is still currently under investigation for sellar tumor surgery: a higher resection rate is to be expected and complications should be minimized. The authors report their surgical results of endonasal endoscopic neurosurgery with special focus on postoperative hypopituitarism in comparison to microsurgical procedures. METHODS: Sixty patients received endoscopic endonasal transsphenoidal procedures for sellar pathologies. All patients were followed up prospectively. A second group of 60 patients received microsurgical transsphenoidal procedures for sellar pathologies in our neurosurgical department before and were prospectively followed until now. Special attention was paid to hormonal insufficiency and medical substitution. RESULTS: Sixty-eight percent (41 of 60) of the patients who underwent microsurgical procedures showed a new persisting pituitary insufficiency postoperatively. Twenty-three patients (55.5%) were substituted with thyroxine, hydrocortisone and sexual hormones and one patient (2.5%) also with ADH cause of global pituitary insufficiency. In 19 cases without any hormonal insufficiency after microsurgical procedures nine patients (47%) showed remnant tumor in follow-up MRI. The patients who underwent endoscopic procedures for pituitary adenomas revealed significant (P<0.01) less new persistent hormonal insufficiency with 13% of all cases (8/60). Five patients (62.5%) were substituted with thyroxine and hydrocortisone, two patients (25%) substituted with thyroxine, hydrocortisone and sexual hormones and one patient also with ADH because of global pituitary insufficiency. Thereby, in follow-up MRI and hormonal testing, radical tumor resection was detected in 92% in the endoscopic group. CONCLUSIONS: This study seems to indicate that a better intraoperative identification and preservation of pituitary gland is possible in endoscopic transsphenoidal surgery with consecutive lower postoperative hypopituitarism rate.

The Incidence and Management of Moderate to Severe Head Injury.

BACKGROUND: The comprehensive expansion of the Trauma Register of the German Trauma Society (Deutsche Gesellschaft für Unfallchirurgie; TR-DGU) now enables, for the first time, studies on traumatic brain injury (TBI) with special attention to care processes, clinical course, and outcomes of treatment on discharge or transfer from the acute-care hospital. METHODS: Retrospective analysis of patients documented in the TR-DGU in the period 2013-2017 who had moderate to severe head injury as defined by the Abbreviated Injury Scale (AIS). RESULTS: In the period 2013-2017, 41 101 patients with moderate to severe TBI were treated in TR-DGU-associated hospitals in Germany (n = 605 hospitals), corresponding to 8220 cases per year and thus to a population-wide incidence of 10.1 cases per 100 000 persons per year. TBI was present as an isolated injury in 39.1% of cases. The mean age of the patients was 60 years (median; range 0-104 years), and the male-to-female ratio was 2:1. 97.5% of the patients had blunt trauma. Falls from a low height were the most common cause of TBI (38.7%). 43.6% of the patients were intubated before arriving at the hospital, and more than 95% underwent cranial tomographic imaging within 22 minutes of arrival (standard deviation [SD] = 17 minutes). 18.4% underwent an emergency neurosurgical procedure. The in-hospital mortality was 23.5%, corresponding to a population-wide mortality from TBI of 2.4 per 100 000 persons per year. More than half of the patients recovered well or with only mild disability; 14.9% had persistent severe disability or remained in a vegetative state. CONCLUSION: Putting these figures in the appropriate international context requires the acquisition of comparable data in multiple countries and is the main task of international TBI consortia.

Quality Indicators in Cranial Neurosurgery: Which Are Presently Substantiated? A Systematic Review.

BACKGROUND: Owing to the rising costs of health care delivery, the quality of delivered care has become a central issue across all medical specialties. Consequently, there is increasing pressure to create standardized frameworks for measuring quality of care. In the field of cranial neurosurgery, health care administrators have begun applying quality measures that are easily available but might be inaccurate in measuring the quality of care. METHODS: We performed a systematic literature review on quality indicators (QIs) that are presently used in this field, aiming to elucidate which QIs are scientifically founded and thus potentially justifiable as measures of quality. We found a total of 8 QIs, and methodologically evaluated published studies according to the AIRE (Appraisal of Indicators through Research and Evaluation) criteria. These criteria include length of hospital stay, all-cause readmission rate, and unplanned reoperation rate. RESULTS: Our review indicates that these presently used or proposed QIs for neurosurgery lack scientific rigor and are restricted to rudimentary measures, and that further research is necessary. CONCLUSIONS: Neurosurgeons need to define their own QIs and actively participate in the validation of these QIs to provide the best possible patient outcomes. More reliable clinical registries, obligatory for all neurosurgical services, should be established as a basis for establishing such indicators, with risk adjustment being an important element of any such indicators.

Selective Brain Hypothermia Mitigates Brain Damage and Improves Neurological Outcome after Post-Traumatic Decompressive Craniectomy in Mice.

Hypothermia and decompressive craniectomy (DC) have been considered as treatment for traumatic brain injury. The present study investigates whether selective brain hypothermia added to craniectomy could improve neurological outcome after brain trauma. Male CD-1 mice were assigned into the following groups: sham; DC; closed head injury (CHI); CHI followed by craniectomy (CHI+DC); and CHI+DC followed by focal hypothermia (CHI+DC+H). At 24 h post-trauma, animals were subjected to Neurological Severity Score (NSS) test and Beam Balance Score test. At the same time point, magnetic resonance imaging using a 9.4 Tesla scanner and subsequent volumetric evaluation of edema and contusion were performed. Thereafter, the animals were sacrificed and subjected to histopathological analysis. According to NSS, there was a significant impairment among all the groups subjected to trauma. Animals with both trauma and craniectomy performed significantly worse than animals with craniectomy alone. This deleterious effect disappeared when additional hypothermia was applied. BBS was significantly worse in the CHI and CHI+DC groups, but not in the CHI+DC+H group, compared to the sham animals. Edema and contusion volumes were significantly increased in CHI+DC animals, but not in the CHI+DC+H group, compared to the DC group. Histopathological analysis showed that neuronal loss and contusional blossoming could be attenuated by application of selective brain hypothermia. Selective brain cooling applied post-trauma and craniectomy improved neurological function and reduced structural damage and may be therefore an alternative to complication-burdened systemic hypothermia. Clinical studies are recommended in order to explore the potential of this treatment.

Factors Affecting Outcome in Treatment of Chronic Subdural Hematoma in ICU Patients: Impact of Anticoagulation.

BACKGROUND: The use of anticoagulants and older age are the main risk factors for chronic subdural hematoma (CSDH). Because the age of the population and use of anticoagulants are increasing, a growing number of CSDH cases is expected. To address this issue, we analyzed the impact of anticoagulants on postsurgical outcome in patients in the intensive care unit (ICU). METHODS: Demographic data, coagulation parameters, surgical details, radiologic appearance of hematoma, Glasgow Coma Scale (GCS) score on admission, and Glasgow Outcome Scale (GOS) score on discharge were retrieved and retrospectively analyzed in 98 patients with CSDH treated in the neurosurgical ICU using correlation coefficient tests and multivariate analysis test. RESULTS: Overall outcome was good (GOS score 4 and 5) in 55.1% of patients. Overall mortality was 9.1%. There was a correlation between GCS score on admission and GOS score. There was no correlation between hematoma thickness/radiologic appearance and impaired coagulation. Disturbance in thrombocyte function (usually resulting from aspirin intake) correlated with improved outcome, whereas warfarin-related coagulopathy correlated with poor recovery. Nevertheless, patients with thrombocytopathy presented with better initial GCS scores. Neither hematoma size nor recurrence rate affected the outcome. CONCLUSIONS: The size of CSDH was not associated with poor outcome and is not necessarily determined by the use of anticoagulants. Coagulopathy does not rule out a good outcome, but the impact of anticoagulation on treatment results in CSDH varies between the main groups of drugs (warfarin vs. antiplatelet drugs). Patients in good neurologic condition on ICU admission have better chances of recovery.

Decompressive Craniectomy Increases Brain Lesion Volume and Exacerbates Functional Impairment in Closed Head Injury in Mice.

Decompressive craniectomy has been widely used in patients with head trauma. The randomized clinical trial on an early decompression (DECRA) demonstrated that craniectomy did not improve the neurological outcome, in contrast to previous animal experiments. The goal of our study was to analyze the effect of decompressive craniectomy in a murine model of head injury. Male mice were assigned into the following groups: sham, decompressive craniectomy, closed head injury (CHI), and CHI followed by craniectomy. At 24 h post-trauma, animals underwent the Neurological Severity Score test (NSS) and Beam Balance Score test (BBS). At the same time point, magnetic resonance imaging was performed, and volume of edema and contusion was assessed, followed by histopathological analysis. According to NSS, animals undergoing both trauma and craniectomy presented the most severe neurological impairment. Also, balancing time was reduced in this group compared with sham animals. Both edema and contusion volume were increased in the trauma and craniectomy group compared with sham animals. Histopathological analysis showed that all animals that underwent trauma presented substantial neuronal loss. In animals treated with craniectomy after trauma, a massive increase of edema with hemorrhagic transformation of contusion was documented. Decompressive craniectomy applied after closed head injury in mice leads to additional structural and functional impairment. The surgical decompression via craniectomy promotes brain edema formation and contusional blossoming in our model. This additive effect of combined mechanical and surgical trauma may explain the results of the DECRA trial and should be explored further in experiments.

Control of an electromechanical hydrocephalus shunt--a new approach.

Hydrocephalus is characterized by an excessive accumulation of cerebrospinal fluid (CSF). Therapeutically, an artificial pressure relief valve (so-called shunt) is implanted which opens in case of increased intracranial pressure (ICP) and drains CSF into another body compartment. Today, available shunts are of a mechanical nature and drainage depends on the pressure drop across the shunt. According to the latest data, craniospinal compliance is considered to be even more important than mean ICP alone. In addition, ICP is not constant but varies due to several influences. In fact, heartbeat-related ICP waveform patterns depend on volume changes in the cranial vessels during a heartbeat and changes its shape as a function of craniospinal compliance. In this paper, we present an electromechanical shunt approach, which changes the CSF drainage as a function of the current ICP waveform. A series of 12 infusion tests in patients were analyzed and revealed a trend between the compliance and specific features of the ICP waveform. For waveform analysis of patient data, an existing signal processing algorithm was improved (using a Moore machine) and was implemented on a low-power microcontroller within the electromechanical shunt. In a test rig, the ICP waveforms were replicated and the decisions of the ICP analysis algorithm were verified. The proposed control algorithm consists of a cascaded integral controller which determines the target ICP from the measured waveform, and a faster inner-loop integral controller that keeps ICP close to the target pressure. Feedforward control using measurement data of the patient's position was implemented to compensate for changes in hydrostatic pressure during change in position. A model-based design procedure was used to lay out controller parameters in a simple model of the cerebrospinal system. Successful simulation results have been obtained with this new approach by keeping ICP within the target range for a healthy waveform.

Automated intracranial pressure-controlled cerebrospinal fluid external drainage with LiquoGuard.

INTRODUCTION: LiquoGuard is a new device for intracranial pressure (ICP)-controlled drainage of cerebrospinal fluid (CSF). This present study evaluates the accuracy of ICP measurement via the LiquoGuard device in comparison with Spiegelberg. Thus, we compared data ascertained from simultaneous measurement of ICP using tip-transducer and tip-sensor devices. MATERIAL AND METHODS: A total of 1,764 monitoring hours in 15 patients (range, 52-219 h) were analysed. All patients received an intraventricular Spiegelberg III probe with the drainage catheter connected to the LiquoGuard system. ICP reading of both devices was performed on an hourly basis. Statistical analysis was done by applying Pearson correlation and Wilcoxon-matched pair test (p < 0.05). RESULTS: Mean ICP values were 11 ± 5 mmHg (Spiegelberg) and 10 ± 7 mmHg (LiquoGuard); the values measured with both devices correlated well (p = 0.001; Pearson correlation =0.349; n = 1,764). In two of the 15 patients with slit ventricles, episodes of significant differences in measured values could be observed. Both patients suffering from slit ventricles failed to produce reliable measurement with the external transducer of the LiquoGuard. CONCLUSIONS: LiquoGuard is a valuable new device for ICP-controlled CSF drainage. However, LiquoGuard tends to provide misleading results in slit ventricles. Thus, before these drawbacks are further analysed, the authors recommend additional ICP measurement with internal tip-sensor devices to avoid dangerous erroneous interpretation of ICP data.

Red blood cell transfusion in neurosurgery.

BACKGROUND: The necessity of red blood cell (RBC) transfusions in neurosurgical procedures is under debate. Although detailed recommendations exist for many other surgical disciplines, there are very limited data on the probability of transfusions during neurosurgical procedures. METHODS: Three-thousand and twenty-six consecutive adult patients undergoing neurosurgical procedures at Saarland University Hospital from December 2006 to June 2008 were retrospectively analyzed for administration of RBCs. The patients were grouped into 11 main diagnostic categories for analysis. The transfusion probability and cross-match to transfusion ratio (C/T ratio) were calculated. RESULTS: Overall, the transfusion probability for neurosurgical procedures was 1.7 % (52/3,026). The probability was 6.5 % for acute subdural hematoma (7/108), 6.2 % for spinal tumors (5/80), 4.6 % for intracerebral hemorrhage (ICH, 4/98), 2.8 % for abscess (3/108), 2.4 % for traumatic brain injury (4/162), 2.3 % for cerebral ischemia (1/44), 1.9 % for subarachnoid hemorrhage (SAH) /aneurysms (4/206), 1.4 % for brain tumors (10/718), 0.8 % for hydrocephalus (2/196), 0.4 % for degenerative diseases of the spine (5/1290), including 3.6 % (3/82) for posterior lumbar interbody fusion (PLIF) and 0 % for epidural hematoma (0/15). The transfusion probabilities for clipping and coiling of SAH were 2.9 % (2/68) and 1.7 % (2/120) respectively. CONCLUSIONS: The probability of blood transfusion during neurosurgical procedures is well below the 10 % level which is generally defined as the limit for preoperative appropriation of RBCs. Patients with spinal tumors, acute subdural hematomas or ICH, i.e., patients undergoing large decompressive procedures of bone or soft tissue, had a higher probability of transfusion.

Intraoperative CT in spine surgery.

BACKGROUND: In spinal instrumentation the misplacement of screws, cages and rods may cause neurovascular complications. Therefore a large variety of methods have been used in recent years to reduce such complications especially by navigation techniques and intraoperative three-dimensional fluoroscopy. The aim of this study is to answer the question: will intraoperative CT improve the efficiency of the treatment as well as the safety for the patient at the spinal instrumentation? Specific questions were: are the implants placed correctly and has decompression been performed sufficiently? METHODS: This is a prospective study in 100 patients mostly with degenerative diseases, tumours and trauma. 80 patients were treated by spinal instrumentation. A helical CT (Somatom Emotion 2003) was used, which is firmly bound to the OR table by a track system. RESULTS: 569 implants were used: 159 vertebra body screws and plates, 88 cages, 154 pedicle screws, 73 facet joint screws and 95 rods. There was malpositioning in seven patients (8.75%). 18 of 154 pedicle screws were misplaced, 2 of 88 cages, and 4 of 73 facet joint screws, for a total of 24 (7.6%). CONCLUSIONS: Intraoperative CT is a useful tool to check the correct position of the implants used, the extent of decompression and the realignment as early as possible. It therefore reduces second operations. A postoperative CT is no longer necessary.

Subcutaneous local anesthesia versus intravenous regional anesthesia for endoscopic carpal tunnel release: a randomized controlled trial.

OBJECT: This study compares the effectiveness of subcutaneous infiltration of a local anesthetic agent (LA) versus intravenous regional anesthesia (IVRA) during endoscopic carpal tunnel release. METHODS: Forty-four patients suffering from severe symptoms restricting normal daily activities-such as persistent loss of feeling in the fingers or hand, or no strength in the thumb in spite of prolonged nonsurgical treatment-and with electromyographically proven carpal tunnel syndrome were enrolled in this study. All underwent endoscopic carpal tunnel release. Twenty-two patients had an endoscopic release of the median nerve under LA (LA Group). The other 22 patients underwent the surgery after intravenous induction of regional anesthesia (IVRA Group). The operating room in-out time and tourniquet time were evaluated in both groups. The patients were also asked to evaluate the pain associated with the tourniquet during surgery using a visual analog scale. The Michigan Hand Outcomes Questionnaire was used to assess the functional outcome preoperatively and at both 2 weeks and 6 months postoperatively. RESULTS: One patient in the LA Group needed an additional application of prilocaine, whereas 3 patients in the IVRA Group needed additional LA and 1 of these required propofol. The tourniquet time and operating room time were significantly lower in the LA Group (p = 0.01 for both). There were no complications related to the endoscopic surgery. The Michigan Hand Outcomes Questionnaire did not show significant differences between the groups at either postoperative follow-up examination. CONCLUSIONS: Endoscopic carpal tunnel release with subcutaneous infiltration of LA was well tolerated and effective. Injection-associated problems such as increased thickness of the synovial layer or impaired endoscopic view did not occur.

Novel immunogenic antigens increase classification accuracy in meningioma to 93.84%.

There is growing evidence that simultaneous analysis of multiple autoantibody reactions can be utilized for diagnosis of neoplasms. Using a set of 57 meningioma-associated antigens, we recently separated meningioma patients from individuals without known disease with an accuracy of 90.3%. Here, we ask whether a largely increased set of immunogenic antigens can further improve this discrimination. We used an array with 1,827 human recombinant clones and measured reactivity of serum autoantibodies against the clones by a novel automated image analysis procedure. We were able to separate meningioma sera from sera of healthy controls with a specificity of 95.62%, a sensitivity of 91.83% and an accuracy of 93.84%. Of the analyzed clones, 23 in-frame clones were highly informative for the classification of meningioma vs. normal sera as shown by their AUC values. These results demonstrate that the accuracy of a serum-based diagnostic can be readily and considerably improved by screening extended sets of proteins.

Prospective study of p-[123I]iodo-L-phenylalanine and SPECT for the evaluation of newly diagnosed cerebral lesions: specific confirmation of glioma.

PURPOSE: The differentiation between gliomas, metastases and gliotic or inflammatory lesions by imaging techniques remains a challenge. Gliomas frequently exhibit increased uptake of radiolabelled amino acids and are thus amenable to PET or SPECT imaging. Recently, p-[123I]iodo-L-phenylalanine (IPA) was validated for the visualization of glioma by SPECT and received orphan drug status. Here we investigated its diagnostic performance for differentiating indeterminate brain lesions. METHODS: This prospective open study included 67 patients with newly diagnosed brain lesions suspicious for glioma (34 without and 33 with contrast enhancement in the MRI scan). Patients received 250 MBq IPA intravenously after overnight fasting. SPECT images at 30 min and 3 h post-injection were iteratively reconstructed and visually interpreted after image fusion with an MRI brain scan (fluid-attenuated inversion recovery sequence or T1-weighted contrast-enhanced image). Findings were correlated with results of stereotactic or open biopsies or serial imaging. RESULTS: Twenty-seven low-grade (2 WHO I, 25 WHO II) and 24 high-grade gliomas (1 WHO III, 23 WHO IV), 3 metastases originating from lung cancer as well as 13 non-neoplastic lesions were proven. All non-neoplastic lesions and all metastases were negative with IPA SPECT. Forty gliomas were true-positive (TP) and 11 false-negative (FN) findings (8 WHO II, 1 WHO III, 2 WHO IV) occurred. There were no false-positive (FP) findings. For the differentiation of primary brain tumours and non-neoplastic lesions, sensitivity and specificity were 78 and 100%. In 34 lesions without contrast enhancement in MRI, IPA SPECT resulted in 17 TP, 8 true-negative, 9 FN and no FP findings (sensitivity 65%, specificity 100%). CONCLUSION: In patients with suspected glioma, IPA SPECT shows a high specificity, but especially in low-grade gliomas FN findings may occur. Due to the high positive predictive value a positive finding allows a suspected glioma to be confirmed.

The effects of selective brain hypothermia and decompressive craniectomy on brain edema after closed head injury in mice.

Intractable brain edema remains one of the main causes of death after traumatic brain injury (TBI). Brain hypothermia and decompressive craniectomy have been considered as potential therapies. The goal of our experimental study was to determine if selective hypothermia in combination with craniectomy could modify the development of posttraumatic brain edema. Male CD-1 mice were anesthetized with halothane and randomly assigned into the following groups: sham-operated (n = 5), closed head injury (CHI) alone (n = 5), CHI followed by craniectomy at 1 h post-TBI (n = 5) and CHI + craniectomy and selective hypothermia (focal brain cooling using cryosurgery device) maintained for 5 h (n = 5). Animals were sacrificed at 7 h posttrauma and brains were removed, sagittally dissected and dried. The brain water content of separate hemispheres was calculated from the weight difference before and after drying. In the CHI alone group there was no significant increase in brain water content in both the ipsi- and contralateral hemispheres (80.59 +/- 1% and 78.74 +/- 0.9% in the CHI group vs. 79.31 +/- 0.7% and 79.01 +/- 0.3% in the sham group, respectively). Brain edema was significantly increased ipsilaterally in the trauma + craniectomy group (82.11 +/- 0.6%, p < 0.05), but not in the trauma + craniectomy + hypothermia group (81.52 +/- 1.1%, p > 0.05) as compared to the sham group (79.31 +/- 0.7%). These data suggest that decompressive craniectomy leads to an increase in brain water content after CHI. Additional focal hypothermia may be an effective approach in the treatment of posttraumatic brain edema.

Improving seroreactivity-based detection of glioma.

Seroreactivity profiling emerges as valuable technique for minimal invasive cancer detection. Recently, we provided first evidence for the applicability of serum profiling of glioma using a limited number of immunogenic antigens. Here, we screened 57 glioma and 60 healthy sera for autoantibodies against 1827 Escherichia coli expressed clones, including 509 in-frame peptide sequences. By a linear support vector machine approach, we calculated mean specificity, sensitivity, and accuracy of 100 repetitive classifications. We were able to differentiate glioma sera from sera of the healthy controls with a specificity of 90.28%, a sensitivity of 87.31% and an accuracy of 88.84%. We were also able to differentiate World Health Organization grade IV glioma sera from healthy sera with a specificity of 98.45%, a sensitivity of 80.93%, and an accuracy of 92.88%. To rank the antigens according to their information content, we computed the area under the receiver operator characteristic curve value for each clone. Altogether, we found 46 immunogenic clones including 16 in-frame clones that were informative for the classification of glioma sera versus healthy sera. For the separation of glioblastoma versus healthy sera, we found 91 informative clones including 26 in-frame clones. The best-suited in-frame clone for the classification glioma sera versus healthy sera corresponded to the vimentin gene (VIM) that was previously associated with glioma. In the future, autoantibody signatures in glioma not only may prove useful for diagnosis but also offer the prospect for a personalized immune-based therapy.

p15 promoter methylation - a novel prognostic marker in glioblastoma patients.

Glioblastomas are the most frequent and malignant brain tumors in adults. Surgical cure is virtually impossible and despite radiation and chemotherapy the clinical course is very poor. Epigenetic silencing of MGMT has been associated with a better response to temozolomide-chemotherapy. We previously showed that temozolomide increases the median survival time of patients with tumors harbouring deletions on 9p within the region for p15(INK4b), p16(INK4a), and 10q (MGMT). The aim of this study was to investigate the methylation status of p15, p16, p14ARF and MGMT in glioblastomas (n=27) and to correlate the results with the clinical data. Only patients with KPS >70, radical tumor resection, radiation and temozolomide-chemotherapy after recurrence were included. We observed promoter methylation of MGMT in 56% and of p15 in 37% of the tumors, whereas methylation of p16 and p14ARF were rare. Interestingly, methylation of p15 emerged as a significant predictor of shorter overall survival (16.9 vs. 23.8 months, p=0.025), whereas MGMT promoter methylation had no significant effect on median overall survival under this treatment regimen (22.5 vs. 22.1 months, p=0.49). In the presence of other clinically relevant factors, p15 methylation remains the only significant predictor (p=0.021). Although these results need to be confirmed in larger series as well as under different treatment conditions, our retrospective study shows clear evidence that p15 methylation is an important prognostic factor for survival and underlines that this tumor suppressor, involved in cell cycle control, is an attractive candidate for therapeutic approaches in glioblastomas.

Comparison of bioresorbable and titanium plates in cervical spinal fusion: early radiologic and clinical results.

STUDY DESIGN: This is a prospective, randomized, and controlled study, approved by the local ethical committee of Saarland (Germany), no. 209/06. OBJECTIVE: The aim of this study was to compare clinical results, segmental motility, magnetic resonance imaging (MRI) compatibility, and change of the bone density of a cervical spine segment that was treated with either bioresorbable or titanium plates in single level. SUMMARY AND BACKGROUND DATA: Anterior cervical discectomy and fusion including plate fixation is an accepted technique for treatment of symptomatic degenerative disc disease. Titanium plates have been used but cause imaging artifacts. Radiolucent bioresorbable plates and screws were developed to reduce the imaging artifacts associated with titanium. METHODS: Forty patients with single level cervical radiculopathy were randomized to anterior discectomy and fusion with bioresorbable plate (19 patients, study group) or titanium plate (18 patients, control group). Follow-up used a visual analog scale (VAS) with regard to brachial pain and Neck Disability Index (NDI) for neck pain. Radiostereometry was performed immediately postoperative and after 6 weeks, 3, and 6 months. MRI of the cervical spine was obtained immediately postoperatively at 3 and 6 months to assess hematoma, infection, and swelling. Computed tomography of the operated cervical spine segment was performed to assess bone density, expressed in Hounsfield units. RESULTS: Three-dimensional analysis of segmental motion (medio-lateral, cranio-caudal and anterior-posterior) did not reveal any statistical difference between both groups at any time postoperatively (P>0.05). Fusion rate and speed evaluated on Radiostereometric analysis and computed tomography of cervical spine segment were similar in both groups. MRI of cervical spine did not show any pathology, especially hematoma and infection. The VAS and NDI did not differ between both groups after 6 months (P>0.05). CONCLUSIONS: Anterior plate fixation by using a bioresorbable plate has the same fusion progress and stability as titanium. During the study, no complications like soft tissue swelling and infection occurred.