Untargeted blood serum proteomics identifies novel proteins related to neurological recovery after human spinal cord injury.

BACKGROUND: The discovery of new prognostic biomarkers following spinal cord injury (SCI) is a rapidly growing field that could help uncover the underlying pathological mechanisms of SCI and aid in the development of new therapies. To date, this search has largely focused on the initial days after the lesion. However, during the subacute stage of SCI (weeks to months after the injury), there remains potential for sensorimotor recovery, and numerous secondary events develop in various organs. Additionally, the confounding effects of early interventions after the injury are less likely to interfere with the results. METHODS: In this study, we conducted an untargeted proteomics analysis to identify biomarkers of recovery in blood serum samples during the subacute phase of SCI patients, comparing those with strong recovery to those with no recovery between 30 and 120 days. We analyzed the fraction of serum that is depleted of the most abundant proteins to unmask proteins that would otherwise go undetected. Linear models were used to identify peptides and proteins related to neurological recovery and we validated changes in some of these proteins using Enzyme-linked Immunosorbent Assay (ELISA). RESULTS: Our findings reveal that differences in subacute recovery after SCI (from 30 to 120 days) are associated with an enrichment in proteins involved in inflammation, coagulation, and lipid metabolism. Technical validation using commercial ELISAs further confirms that high levels of SERPINE1 and ARHGAP35 are associated with strong neurological recovery, while high levels of CD300a and DEFA1 are associated with a lack of recovery. CONCLUSIONS: Our study identifies new candidates for biomarkers of neurological recovery and for novel therapeutic targets after SCI.

High-resolution ultrasound of the supra- and infraclavicular levels of the brachial plexus including the axillary nerve: imaging anatomy based on multiplanar reconstructions and technical guide.

PURPOSE: The diagnosis of peripheral nerve injuries remains challenging. Electromyography and nerve conduction studies do not allow precise localization of the lesion and differentiation between lesions in continuity and non-continuity in cases with complete axonotmesis. Improved ultrasound technology allows the examination of almost the entire peripheral nervous system. The complex sono-anatomy of the brachial plexus outside of the standard scanning planes makes it difficult to access this region. METHODS: On the basis of the Visible Human Project of the National Institutes of Health (NIH), multiplanar reconstructions were created with the 3D Slicer open-source software in the various planes of the ultrasound cross-sections. The ultrasound examination itself and the guidance of the ultrasound probe in relation to the patient were recorded as video files and were synchronized through the audio channel. Subsequently, image matching was performed. RESULTS: Multiplanar reconstructions facilitate visualization of anatomical regions which are challenging to access thereby enabling physicians to evaluate the course of the peripheral nerve of interest in dynamic conditions. Sonographically visible structures could be reproducibly identified in single-frame analysis. CONCLUSION: With precise knowledge of the ultrasound anatomy, the nerve structures of the brachial plexus can also be dynamically assessed almost in their entire course. An instructional video on ultrasound of the brachial plexus supplements this manuscript and has been published on Vimeo.com.

Prospective observational cohort study on epidemiology, treatment and outcome of patients with traumatic brain injury (TBI) in German BG hospitals.

OBJECTIVES: Since 2000/2001, no large-scale prospective studies addressing traumatic brain injury (TBI) epidemiology in Germany have been published. Our aim was to look for a possible shift in TBI epidemiology described in other European countries, to look for possible changes in TBI management and to identify predictors of 1-year outcome especially in patients with mild TBI. DESIGN: Observational cohort study. SETTING: All patients suffering from a TBI of any degree between 1 October 2014 and 30 September 2015, and who arrived in one of the seven participating BG hospitals within 24 hours after trauma, were included. PARTICIPANTS: In total, 3514 patients were included. OUTCOME MEASURES: Initial care, acute hospital care and rehabilitation were documented using standardised documentation forms. A standardised telephone interview was conducted 3 and 12 months after TBI in order to obtain information on outcome. RESULTS: Peaks were identified in males in the early 20s and mid-50s, and in both sexes in the late 70s, with 25% of all patients aged 75 or older. A fall was the most frequent cause of TBI, followed by traffic accidents (especially bicyclists). The number of head CT scans increased, and the number of conventional X-rays of the skull decreased compared with 2000/2001. Besides, more patients were offered rehabilitation than before. Though most TBI were classified as mild, one-third of the patients participating in the telephone interview after 12 months still reported troubles attributed to TBI. Negative predictors in mild TBI were female gender, intracranial bleeding and Glasgow Coma Scale (GCS) 13/14. CONCLUSION: The observed epidemiologic shift in TBI (ie, elderly patients, more falls, more bicyclists) calls for targeted preventive measures. The heterogeneity behind the diagnosis 'mild TBI' emphasises the need for defining subgroups not only based on GCS.

Early Decompression (<8 Hours) Improves Functional Bladder Outcome and Mobility After Traumatic Thoracic Spinal Cord Injury.

BACKGROUND: There is accumulating evidence of a potential beneficial effect of early surgical intervention after acute cervical spinal cord injury (SCI). However, around one third of all SCIs affect the thoracic spine. This cohort has not been extensively investigated, mainly because of less sensitive clinical readout measures. Apart from regaining full sensorimotor function, improvements in bladder and bowel management remain of the highest priority for patients with chronic paraplegia. Therefore, this study investigates the effect of early decompression (here defined as <8 hours) versus delayed management on neurologic and functional outcome. METHODS: We retrospectively analyzed data from the institutional database, in which follow-up data were collected prospectively according to the European Multicenter Study about Spinal Cord Injury standards. Within a 13-year period, we identified 43 patients who met inclusion and exclusion criteria. Of these, 32 (74%) were managed surgically within the first 8 hours. There was a trend toward a higher rate of patients with clinically complete SCI in the early group at baseline. RESULTS: After 1 year, we did not observe a benefit on the neurologic outcome as assessed via the American Spinal Injury Association Impairment Scale grade. Functional outcome was evaluated using the Spinal Cord Independence Measure (SCIM). The early decompressed group demonstrated significantly improved SCIM 6 (i.e., bladder management) (P < 0.045) and SCIM 9-11 subitems (i.e., mobility, transfer) (P < 0.019). CONCLUSIONS: Early decompression was an independent predictor for improved functional bladder outcome and mobility after 1 year. This effect needs to be studied in future prospective, multicenter studies.

Influence of Preoperative Magnetic Resonance Imaging on Surgical Decision Making for Patients with Acute Traumatic Cervical Spinal Cord Injury: A Survey Among Experienced Spine Surgeons.

OBJECTIVE: Early decompression after acute spinal cord injury (SCI) is recommended. Acute care is crucial, but optimal management is unclear. The aim of this study was to investigate the role of preoperative magnetic resonance imaging (MRI) in addition to computed tomography (CT) in surgical decision making for acute cervical SCI. METHODS: All patients with cervical SCI between 2008 and 2016 who had preoperative CT and MRI (n = 63) at the Trauma Center Murnau, Germany, were included. We administered a survey to 10 experienced spine surgeons (5 neurosurgeons, 5 trauma surgeons) regarding the surgical management. First, the surgeons were shown clinical information and CT scans. Two months later, the survey was repeated with additional MRI. Corresponding percentages of change and agreement were obtained for each rater and survey item. Finally, results from both parts of the survey were compared with the definitive treatment option (i.e., real-world decision). RESULTS: MRI modified surgical timing in a median of 41% of patients (interquartile range 38%-56%). In almost every fifth patient (17%), no surgery would have been indicated with CT alone. The advocated surgical approach was changed in almost half of patients (median 48%, interquartile range 33%-49%). Surgically addressed levels were changed in a median of 57% of patients (interquartile range 56%-60%). MRI led to higher agreement with the real-world decision concerning addressed levels (median 35% vs. 73%), timing (median 51% vs. 57%), and approach (median 44% vs. 65%). CONCLUSIONS: Preoperative MRI influenced surgical decision making substantially in our cohort and has become a new standard for patients with cervical SCI in our institution if medically possible.

Earlier Decompression (< 8 Hours) Results in Better Neurological and Functional Outcome after Traumatic Thoracolumbar Spinal Cord Injury.

The optimal timing of surgical intervention following spinal cord injury (SCI) remains under debate. Recent studies indicate a potential neurological and functional benefit of early surgery (< 8 h) after cervical SCI. For thoracolumbar SCI syndromes, fewer studies exist. Bladder and bowel dysfunction are highly relevant for these patients and impair their quality of life. Hence, we performed a retrospective study on patients with thoracolumbar SCI who were operated on at our institution and who met inclusion as well as exclusion criteria (n = 58 patients). Follow-up data were collected prospectively within a fixed time schedule over 1 year according to the European Multicenter Study about Spinal Cord Injury protocol. Early decompression was defined as within the first 8 h after injury and was performed in 35 patients. After the follow-up period, the early decompression group showed improved American Spinal Injury Association Impairment Scale (AIS) grades (p < 0.040) and a higher AIS conversion (p < 0.021). Further, these patients demonstrated a higher total Spinal Cord Independence Measure (SCIM) difference (p < 0.005). Special emphasis was placed on the functional bladder and bowel outcome. Here, we observed improved bladder outcome (i.e., SCIM-6 sub-item; p < 0.021) and a trend towards better functional bowel management (i.e., SCIM-7; p < 0.090). Linear regression models showed that early surgery was an independent predictor for higher AIS shifts and improved total SCIM difference. Our data suggests that prompt surgical management after thoracolumbar SCI might have a positive impact on the functional and neurological outcome.

Experiences with a temporary synthetic skin substitute after decompressive craniectomy: a retrospective two-center analysis.

BACKGROUND: Decompressive craniectomy is a commonly performed procedure. It reduces intracranial pressure, improves survival, and thus might have a positive impact on several neurosurgical diseases and emergencies. Sometimes primary skin closure is not possible due to cerebral herniation or extensive skin defects. In order to prevent further restriction of the underlying tissue, a temporary skin expansion might be necessary. METHODS AND MATERIAL: We retrospectively reviewed patients in need for a temporary skin substitute because skin closure was not possible after craniectomy without violating brain tissue underneath in a time period of 6 years (2011-2016). With this study, we present initial experiences of Epigard (Biovision, Germany) as an artificial temporary skin replacement. We performed this analysis at two level-1 trauma centers (Trauma Center Murnau, Germany; University Hospital of St. Poelten, Austria). Demographic data, injury and surgical characteristics, and complication rates were analyzed via chart review. We identified nine patients within our study period. Six patients suffered from severe traumatic brain injury and developed pronounced cerebral herniation in the acute or subacute phase. Three patients presented with non-traumatic conditions (one atypical intracerebral hemorrhage and two patients with extensive destructive tumors invading the skull and scalp). RESULTS: A total of 20 Epigard exchanges (range 1-4) were necessary before skin closure was possible. A CSF fistula due to a leaky Epigard at the interface to the skin was observed in two patients (22%). Additional complications were four wound infections, three CNS infections, and three patients developed a shunt dependency. Three patients died within the first month after injury. CONCLUSIONS: Temporary skin closure with Epigard as a substitute is feasible for a variety of neurosurgical conditions. The high complication and mortality rate reflect the complexity of the encountered pathologies and need to be considered when counseling the patient and their families.

Correction to: Experiences with a temporary synthetic skin substitute after decompressive craniectomy: a retrospective two-center analysis.

Incorrect given and family of Miron Yousif.

Disc herniation caused by a viscoelastic nucleus after total lumbar disc replacement-a case report.

Degenerative disc disease (DDD) is highly prevalent. If conservative treatment fails, spinal fusion procedures are commonly performed. Total disc replacement (TDR) might be a surgical option for a distinct subset of patients with DDD. Several prostheses have been or are still available. Despite some promising initial clinical results, there is still limited experience with hardware-related adverse events. This report highlights an unreported complication after TDR with a viscoelastic device. Literature about long-term outcome and safety of this particular TDR is scarce. Hence, there exists limited experience with TDR-related complications with such a failure mode. We report a 34-year-old male presented to us with an acute S1 radiculopathy on the right. His past medical history was significant for prior TDR at the level L5/S1 at another hospital 2 years prior to this acute episode. Imaging studies revealed an intraspinal mass compromising the right S1 nerve root. This mass mimicked a disc herniation and sequestrectomy was performed. Intraoperatively, the prolapsed sequester turned out to be part of the viscoelastic nucleus of the disc prosthesis. Interbody fusion combined with posterior instrumentation was ultimately performed. The patient did well afterwards, but is currently (2 years later) developing adjacent segment disease with facet syndromes. Since TDR might be beneficial for certain patients, spine surgeons should be aware of potential device-related complications.

Spinal Meninges and Their Role in Spinal Cord Injury: A Neuroanatomical Review.

Current recommendations support early surgical decompression and blood pressure augmentation after traumatic spinal cord injury (SCI). Elevated intraspinal pressure (ISP), however, has probably been underestimated in the pathophysiology of SCI. Recent studies provide some evidence that ISP measurements and durotomy may be beneficial for individuals suffering from SCI. Compression of the spinal cord against the meninges in SCI patients causes a "compartment-like" syndrome. In such cases, intentional durotomy with augmentative duroplasty to reduce ISP and improve spinal cord perfusion pressure (SCPP) may be indicated. Prior to performing these procedures routinely, profound knowledge of the spinal meninges is essential. Here, we provide an in-depth review of relevant literature along with neuroanatomical illustrations and imaging correlates.

Different sequelae of electrical brain injury - MRI patterns.

PURPOSE: Electrical injury to the central nervous system may lead to neurologic compromise via pleiotropic mechanisms. It may cause current-related, thermal or nonthermal damage followed by secondary mechanisms. METHODS: We herein report a case of a 20-year old man, who experienced a low-voltage electric injury due to an occupational accident. RESULTS: Magnetic resonance imaging (MRI) one week after the insult allowed differentiation of pathophysiologic features including thermal, nonthermal and hypoxic cerebral lesions. CONCLUSION: The capability of MRI assessing a variety of lesions for diagnostic and potentially prognostic reasons is presented.

Increased intrathecal pressure after traumatic spinal cord injury: an illustrative case presentation and a review of the literature.

PURPOSE: Early surgical management after traumatic spinal cord injury (SCI) is nowadays recommended. Since posttraumatic ischemia is an important sequel after SCI, maintenance of an adequate mean arterial pressure (MAP) within the first week remains crucial in order to warrant sufficient spinal cord perfusion. However, the contribution of raised intraparenchymal and consecutively increased intrathecal pressure has not been implemented in treatment strategies. METHODS: Case report and review of the literature. RESULTS: Here we report a case of a 54-year old man who experienced a thoracic spinal cord injury after a fall. CT-examination revealed complex fractures of the thoracic spine. The patient underwent prompt surgical intervention. Intraoperatively, fractured parts of the ascending Th5 facet joint were displaced into the spinal cord itself. Upon removal, excessive protruding of medullary tissue was observed over several minutes. This demonstrates the clinical relevance of increased intrathecal pressure in some patients. CONCLUSION: Monitoring and counteracting raised intrathecal pressure should guide clinical decision-making in the future in order to ensure optimal spinal cord perfusion pressure for every affected individual.

A prospective randomized multicenter phase I/II clinical trial to evaluate safety and efficacy of NOVOCART disk plus autologous disk chondrocyte transplantation in the treatment of nucleotomized and degenerative lumbar disks to avoid secondary disease: safety results of Phase I-a short report.

NOVOCART® Disk plus, an autologous cell compound for autologous disk chondrocyte transplantation, was developed to reduce the degenerative sequel after lumbar disk surgery or to prophylactically avoid degeneration in adjacent disks, if present. The NDisc trial is an ongoing multi-center, randomized study with a sequential phase I study within the combined phase I/II trial with close monitoring of tolerability and safety. Twenty-four adult patients were randomized and treated with the investigational medicinal product NDisc plus or the carrier material only. Rates of adverse events in Phase I of this trial were comparable with those expected in the early time course after elective disk surgery. There was one reherniation 7 months after transplantation, which corresponds to an expected reherniation rate. Immunological markers like CRP and IL-6 were not significantly elevated and there were no imaging abnormalities. No indications of harmful material extrusion or immunological consequences due to the investigational medicinal product NDplus were observed. Therefore, the study appears to be safe and feasible. Safety analyses of Phase I of this trial indicate a relatively low risk considering the benefits that patients with debilitating degenerative disk disease may gain.

Early Decompression (< 8 h) after Traumatic Cervical Spinal Cord Injury Improves Functional Outcome as Assessed by Spinal Cord Independence Measure after One Year.

There is an ongoing controversy about the optimal timing for surgical decompression after acute traumatic cervical spinal cord injury (SCI). For this reason, we performed a retrospective study of patients who were operated on after traumatic cervical SCI at the Trauma Center Murnau, Germany, and who met inclusion as well as exclusion criteria (n = 70 patients). Follow-up data were collected prospectively according to the European Multicenter Study about Spinal Cord Injury (EMSCI) protocol over a period of 1 year. Early decompression was defined as within the first 8 h after the insult (n = 35 patients). Primary outcome was the difference in the SCIM (Spinal Cord Independence Measure) 1 year after the trauma. After the follow-up period, patients who were decompressed earlier had a significantly higher SCIM difference (45.8 vs. 27.1, p < 0.005). A regression analysis showed that timing of decompression, age, as well as basal AIS (American Spinal Injury Association Impairment Scale) and basal SCIM scores were independent predictors for a better functional outcome (SCIM). Further, patients from the early decompression group had better AIS grades (p < 0.006) and a higher AIS conversion rate (p < 0.029). Additionally, this cohort also had a better total motor performance as well as upper extremity motor function after 1 year (p < 0.025 and p < 0.002). The motor and neurological levels of patients who were operated on within 8 h were significantly more caudal (p < 0.003 and p < 0.014) after 1 year. The present study suggests that early decompression after traumatic cervical SCI might have a positive impact on the functional and neurological outcome of affected individuals.

A prospective multicenter phase I/II clinical trial to evaluate safety and efficacy of NOVOCART Disc plus autologous disc chondrocyte transplantation in the treatment of nucleotomized and degenerative lumbar disc to avoid secondary disease: study protocol for a randomized controlled trial.

BACKGROUND: Intervertebral disc degeneration is emphasized as an important cause of low back pain. Current surgical treatment provides relief to the accompanying pain and disability but does not restore the biological function of the intervertebral disc. NOVOCART™ Disc plus, an autologous cell compound for autologous disc chondrocyte transplantation, was developed to reduce the degenerative sequelae after lumbar disc surgery or to prophylactically avoid degeneration in adjacent discs. METHODS/DESIGN: This is a multicenter, randomized, controlled, clinical phase I/II combination study. A total of 120 adult patients are allocated in a ratio of 2:1:1. Sample size and power calculations were performed to detect the minimal clinically important difference of 10 units, with an expected standard deviation of 12 in the Oswestry Disability Index, which is the primary outcome parameter. Secondary outcome parameters include the visual analog scale and the EQ-5D questionnaire. Changes in physical and mental health are evaluated using the Short Form-12 (SF-12). Moreover, radiological and functional outcomes are evaluated. The major inclusion criterion is a single lumbar disc herniation that requires sequestrectomy. Transplantation is performed 90 days thereafter. Study data generation (study sites) and data storage, processing, and statistical analysis are clearly separated. DISCUSSION: In this phase-I/II study, NDplus is being investigated for its clinical applicability, safety, and efficacy in the repair of herniated, nucleotomized discs, and of adjacent degenerated discs, if present. To date, autologous disc chondrocytes have not been transplanted into degenerative discs without previous disc herniation. As such, this is the first study to investigate a therapeutic as well as a prophylactic approach to treat degenerative discs of the lumbar spine. TRIAL REGISTRATION: EudraCT No: 2010-023830-22, ID NCT01640457 , 8 November 2010.

Antimicrobial effect and biocompatibility of novel metallic nanocrystalline implant coatings.

AIM: The present in vitro study was designed to evaluate the surface characteristics, biocompatibilities and antimicrobial effects of experimental titanium implant surfaces, coated by nanocrystalline silver, copper, and bismuth. Biocompatible and antimicrobial implant modifications could result in reduced biofilm formation on implant surfaces and therefore in less periimplant inflammation. FINDINGS: Titanium discs (thickness 1 mm and 12 mm in diameter) were coated by pulsed magnetron-sputtering of nanocrystalline metals (bismuth, copper, and silver). Bismuth coatings revealed higher surface roughness values in comparison to silver and copper coatings via atomic force microscopy. Ion release after 168 h in culture medium was analyzed by inductively coupled plasma-mass spectrometry and showed significant different amounts of released copper (>120 000 µg/L), silver (550 µg/L) or bismuth (80 µg/L). No cytotoxic effect on HaCaT cell proliferation was detected on the uncoated Ti/TiO2 reference surfaces, the bismuth coatings and silver coatings. In contrast, copper-coated discs showed a strong cytotoxic effect. All three coatings exhibited antimicrobial effects by trend in the fluorometric Resazurin testing and significant localized antibacterial effects in live/dead microscopy after incubation of the specimens for 150 min in bacterial solution of S. epidermidis. CONCLUSIONS: The tested metallic implant coatings (silver and bismuth) allowed surface modifications that may improve therapeutic approaches to biofilm prevention on dental implants. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1571-1579, 2016.

Complex 360°-reconstruction and stabilization of the cervical spine due to osteomyelitis.

Osteomyelitis of the cervical spine may lead to profound bony destruction. The presented case developed multilevel osteomyelitic destruction of the cervical spine after decompression due to cervical myelopathy. He could be cured by a multiple-stage procedure: step one: debridement and removal of all anterior implants with vacuum-assisted closure combined with dorsal instrumentation from C0 to T3; step two: anterior reconstruction with expandable titanium cages and plate. The patient regained walking with the aid of a walking frame. The following recommendations are given: multiple stage procedure, extensive debridement and stabilization via an anterior and posterior approach, use of titanium implants.

Clinical and economic consequences of antibiotic-impregnated cerebrospinal fluid shunt catheters.

OBJECT: The authors evaluated the safety and efficacy of antibiotic-impregnated shunt catheters (AISCs) and determined the cost-benefit ratio related to the fact that AISCs increase the implant costs of a shunt procedure by approximately $400 per patient. METHODS: The control group comprised 98 adults with chronic hydrocephalus and 22 children, who were treated without AISCs (non-AISCs). In the treatment group, AISCs (Bactiseal, Codman, Johnson & Johnson) were implanted in 171 adults and 26 children. The minimum follow-up period was 6 months. RESULTS: Important risk factors for shunt infections (such as age, comorbidity, cause of hydrocephalus, operating time, and duration of external cerebrospinal fluid drainage prior to shunt placement) did not differ between the study and control groups. In the pediatric AISC group, the frequency of premature, shunt-treated infants and the incidence of external ventricular drainage prior to shunt insertion were actually higher than those in the non-AISC group. When using AISCs, the shunt infection rate dropped from 4 to 0.6% and from 13.6 to 3.8% in the adult and the pediatric cohort, respectively. Overall the infection rate decreased from 5.8 to 1%, which was statistically significant (p = 0.0145). The average costs of a single shunt infection were $17,300 and $13,000 in children and adults, respectively. The cost-benefit calculation assumed to have saved shunt infection-related costs of approximately $50,000 in 197 AISC-treated patients due to the reduction in shunt infection rate in this group compared with costs in the control group. Despite the incremental implant costs associated with the use of AISCs, the overall reduction in infection-related costs made the use of AISCs cost beneficial in the authors' department. CONCLUSIONS: From clinical and economic perspectives, AISCs are seemingly a valuable addition in hydrocephalus therapy.