A Study of 323 Asymptomatic Volunteers

Background The understanding of the individual shape and mobility of the lumbar spine are key factors for the prevention and treatment of low back pain. The influence of age and sex on the total lumbar lordosis and the range of motion as well as on different lumbar sub-regions (lower, middle and upper lordosis) in asymptomatic subjects still merits discussion, since it is essential for patient-specific treatment and evidence-based distinction between painful degenerative pathologies and asymptomatic aging. Methods and Findings A novel non-invasive measuring system was used to assess the total and local lumbar shape and its mobility of 323 asymptomatic volunteers (age: 20–75 yrs; BMI <26.0 kg/m2; males/females: 139/184). The lumbar lordosis for standing and the range of motion for maximal upper body flexion (RoF) and extension (RoE) were determined. The total lordosis was significantly reduced by approximately 20%, the RoF by 12% and the RoE by 31% in the oldest (>50 yrs) compared to the youngest age cohort (20–29 yrs). Locally, these decreases mostly occurred in the middle part of the lordosis and less towards the lumbo- sacral and thoraco-lumbar transitions. The sex only affected the RoE. Conclusions During aging, the lower lumbar spine retains its lordosis and mobility, whereas the middle part flattens and becomes less mobile. These findings lay the ground for a better understanding of the incidence of level- and age-dependent spinal disorders, and may have important implications for the clinical long-term success of different surgical interventions

Clinical decision-making on spinal cord injury-associated pneumonia: a nationwide survey in Germany

Study design: Survey study. Objectives: Spinal cord injury (SCI)-associated pneumonia (SCI-AP) is associated with poor functional recovery and a major cause of death after SCI. Better tackling SCI-AP requires a common understanding on how SCI-AP is defined. This survey examines clinical algorithms relevant for diagnosis and treatment of SCI-AP. Setting: All departments for SCI-care in Germany. Methods: The clinical decision-making on SCI-AP and the utility of the Centers for Disease Control and Prevention (CDC) criteria for diagnosis of ‘clinically defined pneumonia’ were assessed by means of a standardized questionnaire including eight case vignettes of suspected SCI-AP. The diagnostic decisions based on the case information were analysed using classification and regression trees (CART). Results: The majority of responding departments were aware of the CDC-criteria (88%). In the clinical vignettes, 38–81% of the departments diagnosed SCI-AP in accordance with the CDC-criteria and 7–41% diagnosed SCI-AP in deviation from the CDC-criteria. The diagnostic agreement was not associated with the availability of standard operating procedures for SCI-AP management in the departments. CART analysis identified radiological findings, fever, and worsened gas exchange as most important for the decision on SCI-AP. Frequently requested supplementary diagnostics were microbiological analyses, C-reactive protein, and procalcitonin. For empirical antibiotic therapy, the departments used (acyl-)aminopenicillins/β-lactamase inhibitors, cephalosporins, or combinations of (acyl-)aminopenicillins/β-lactamase inhibitors with fluoroquinolones or carbapenems. Conclusions: This survey reveals a diagnostic ambiguity regarding SCI-AP despite the awareness of CDC-criteria and established SOPs. Heterogeneous clinical practice is encouraging the development of disease-specific guidelines for diagnosis and management of SCI-AP

protocol of a prospective, longitudinal study

Background Natural killer (NK) cells comprise the main components of lymphocyte-mediated nonspecific immunity. Through their effector function they play a crucial role combating bacterial and viral challenges. They are also thought to be key contributors to the systemic spinal cord injury-induced immune-deficiency syndrome (SCI-IDS). SCI-IDS increases susceptibility to infection and extends to the post-acute and chronic phases after SCI. Methods and design The prospective study of NK cell function after traumatic SCI was carried out in two centers in Berlin, Germany. SCI patients and control patients with neurologically silent vertebral fracture also undergoing surgical stabilization were enrolled. Furthermore healthy controls were included to provide reference data. The NK cell function was assessed at 7 (5–9) days, 14 days (11–28) days, and 10 (8–12) weeks post-trauma. Clinical documentation included the American Spinal Injury Association (ASIA) impairment scale (AIS), neurological level of injury, infection status, concomitant injury, and medications. The primary endpoint of the study is CD107a expression by NK cells (cytotoxicity marker) 8–12 weeks following SCI. Secondary endpoints are the NK cell’s TNF-α and IFN-γ production by the NK cells 8–12 weeks following SCI. Discussion The protocol of this study was developed to investigate the hypotheses whether i) SCI impairs NK cell function throughout the post-acute and sub-acute phases after SCI and ii) the degree of impairment relates to lesion height and severity. A deeper understanding of the SCI-IDS is crucial to enable strategies for prevention of infections, which are associated with poor neurological outcome and elevated mortality. Trial registration DRKS00009855

The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI

Oncosurgical results of multilevel thoracolumbar en-bloc spondylectomy for primary tumors and solitary spinal metastases

Einleitung: Die optimale chirurgische Behandlung von primär malignen Wirbelsäulentumoren sowie solitären Wirbelsäulenmetastasen biologisch günstiger Entitäten ist die weite Resektion mit angemessenen tumorfreien Resektionsrändern. Hierbei gilt das Erreichen von tumorfreien Resektionsrändern als Vorrausetzung für eine suffiziente lokale und systemische Tumorkontrolle. Die praktische Umsetzung dieses grundlegenden Konzeptes auf die chirurgische Therapie von Wirbelsäulentumoren gestaltet sich aufgrund der besonderen anatomischen Gegebenheiten schwierig, so dass lange Zeit lediglich „piecemeal resections“ und intraläsionale Kürretagen angewandt wurden. Es konnte gezeigt werden, dass diese operativen Techniken zur Tumorzelldissemination mit residualer Tumormasse und erhöhtem Risiko eines lokalen sowie systemischen Tumorrezidives führen. Die Einführung der totalen En-bloc-Spondylektomie (TES) als chirurgische Therapieoption bot die Möglichkeit eines neuen therapeutischen Ansatzes, welcher die radikalen onkochirurgischen Konzepte der Extremitätenchirurgie auf die Wirbelsäule übertragbar macht und somit das Erreichen von marginalen bis weiten Resektionsgrenzen ermöglicht. Diese Arbeit soll die chirurgische Technik der multisegmentalen En-bloc-Spondylektomie beschreiben, das onkochirurgische Outcome dieses Verfahrens von Patienten mit primären Wirbelsäulentumoren und solitären Metastasen analysieren und die Methode der dorsoventralen Defektrekonstruktion mittels Carbon-Composite- Cagesystemen untersuchen. Material und Methoden: In diese Studie wurden 9 Männer und 11 Frauen aufgenommen. Das mittlere Alter des Patientenkollektivs lag bei 54 ±16 Jahren. Histologisch konnten 10 verschiedene Tumorentitäten unterschieden werden. Insgesamt erkrankten 15 Patienten an einem primären Wirbelsäulentumor. 5 Patienten erlitten solitäre Wirbelsäulenmetastasen eines außerhalb der Wirbelsäule lokalisierten Primärtumors (durchschnittlicher Tokuhashi-Score: 11, durchschnittlicher Tomita-Score: 2). Alle eingeschlossenen Patienten hatten thorakolumbale Tumorlokalisationen. Am häufigsten waren die Tumore hierbei im Bereich der BWS (n = 13) vertreten, gefolgt von der LWS (n=4) und dem thorakolumbalen Übergang (n = 3). Alle Patienten wiesen eine extrakompartimentale Tumorlokalisation (Tomita Typ 6) auf. 6 Patienten zeigten zudem eine Tumorbeteiligung der umliegenden Strukturen. Im Rahmen des präoperativen Stagings konnte bei 3 Patienten eine Tumorbeteiligung des Zwerchfells, bei 2 Patienten eine Invasion des Thoraxwand und in 1 Fall eine pulmonale, im Verlauf konstante Läsion (stable disease) diagnostiziert werden. Alle Patienten wurden präoperativ mit einer CT-Thorax/Abdomen-Bildgebung sowie einer Skelettszintigraphie auf systemische Tumormanifestationen untersucht. Zur lokalen Bildgebung wurden alle Patienten mit konventionellen Röntgenaufnahmen im Stehen und einer MRT-Bildgebung sowie eines FDG-PET-CT diagnostiziert. Bei 7 Patienten erfolgte in der Anamnese eine Voroperation im zu resezierenden Wirbelsäulenbereich, die zwischen 5 und 27 Monaten zurücklag. Entsprechend der unterschiedlichen Tumorentitäten erhielten Patienten nach Vorstellung im interdisziplinären Tumorboard vor Durchführung der En-bloc- Resektion neoadjuvante Radio- oder Chemotherapien. Alle Patienten erhielten eine multisegmentale En-bloc-Spondylektomie. Hierbei wurde bei 8 Patienten eine Resektion rein von dorsal durchgeführt. 12 Patienten benötigten zum ventralen Release einen kombinierten, sequentiellen ventrodorsalen Zugangsweg. Zusammenfassend wurden in dieser Studie insgesamt 51 Wirbelkörpersegmente reseziert. Am häufigsten mit n = 9 erfolgte die En-bloc-Resektion von 3 Segmenten. Die sehr aufwändige En-bloc-Exzision von 4 Segmenten wurde nur bei 3 Patienten durchgeführt. Die mittlere Operationsdauer lag insgesamt bei 10 h. Der mittlere in OP-Saugern erfasste und in Bauchtüchern und Kompressen abgeschätzte Blutverlust betrug 6100 ml (range: 500 – 19000 ml). Im Mittel betrug die Dauer der intensivmedizinischen Betreuung 3,5 +/- 3,0 Tage (range: 2-9 Tage). Ergebnisse: Die histologischen Beurteilungen ergaben keine intraläsionalen Resektionen. Insgesamt wurden 7 Resektionen als weit und 13 als marginal bewertet. Bei 11 Patienten traten im intra- und postoperativen Verlauf Komplikationen auf. Hierunter waren Wundheilungsstörungen, Wundinfekte, Verletzungen des Ductus thoracicus und neurologische Komplikationen zu nennen. Zur Defektrekonstruktion wurde in allen Fällen dorsale Schrauben-Stab-Systeme der Firma CoLigne benutzt. Die dorsale Stabilisierung schloss je nach Anzahl der resezierten Segmente entweder 2 oder 3 Wirbelkörper kranial und kaudal ein. Entsprechend der resezierten Tumorgröße wurde zur zusätzlichen ventralen Abstützung ein Carbon-Composite-Cage verwendet. Das vorliegende Patientenkollektiv wurde im Mittel 21,3 Monate nachbeobachtet (range: 5 – 49 Monate). Hierbei wurden die Ereignisse wie tumorbedingtes Versterben (dead of disease, DOD), lokales oder systemisches Tumorrezidiv (alive with disease, AWD) und tumorfreies Überleben (no evidence of disease, NED) festgehalten. Im Nachbeobachtungszeitraum verstarb kein Patient an anderweitigen Erkrankungen. Zum Ende der Nachuntersuchung waren 18 Patienten am Leben. Hierbei verstarben eine 27-jährige Patientin nach 28 Monaten an einem Nierenzellkarzinom und ein weiterer Patient nach 12 Monaten aufgrund eines Chondrosarkoms. Im lokalrezidivfreien Überleben erlitt ein Patient mit Neurofibrosarkom, welcher eine marginale Resektion erhalten hatte, 8 Monate nach Indexoperation ein lokales Rezidiv im Bereich der Thoraxwand. Insgesamt entwickelten 7 Patienten im Verlauf der Nachbeobachtung metastatische Absiedlungen, vor allem im Bereich der Lunge. Hiervon traten 5 Fälle in der Gruppe der Primärtumore und 2 Fälle bei Patienten mit Metastasen auf. Im Mittel wurde dies nach 9,7 Monaten (range: 3 bis 23 Monate) beobachtet. Es existierten keine tumor- oder behandlungsassoziierten Faktoren, die die lokale Kontrolle neben der Durchführung der En-bloc-Resektion entscheidend beeinflussten.OBJECTIVE: Assess the clinical and radiologic outcome after multilevel en-bloc spondylectomy and reconstruction. SUMMARY OF BACKGROUND DATA: Monolevel en- bloc spondylectomies have proven their oncosurgical effectiveness while reports on multilevel resections for extracompartmental tumor localizations are rare. METHODS: Patients treated by multilevel en-bloc spondylectomy and restoration with a carbon composite vertebral body replacement system were investigated. Patient charts, and clinical follow-up investigations were analyzed for histopathological tumor origin, preoperative symptoms, surgical peri- and postoperative data, applied adjuvant therapies, as well as the course of disease. Solitary metastases time until occurrence and prognostic scores were evaluated (Tomita/Tokuhashi Score). CT-scans were performed and analyzed at follow up. Oncological status was evaluated including local recurrence rates, cumulative disease specific, and metastases-free survival. RESULTS: Multilevel (2-5 segments) en-bloc spondylectomy of the thoracolumbar spine was performed in 20 patients (15 sarcomas and 5 solitary spinal metastases 9 male/11 female, mean age at surgery: 54 ± 16 years.). Wide and marginal surgical margins were achieved in 7 and 13 patients, respectively. Mean follow-up period was 21.3 (5-49) months. No implant breakage or loosening was observed. Local recurrence occurred in one patient. Thirteen of the 18 surviving patients showed no evidence of the disease, two died of systemic disease. CONCLUSION: Multilevel en-bloc spondylectomy offers a radical resection option for extracompartmental tumor involvement. It provides oncologically adequate resection margins with low local recurrence. However, the procedures are complex; the patient's stress is high and metastatic disease developed in one-third of patients. A judicious patient selection and a realistic feasibility evaluation must precede the decision for surgery. Reconstruction using a carbon composite cage system showed low complication rates and offers advantages for oncosurgical procedures

Off Label Use of Botulinum Toxin in Children under Two Years of Age: A Systematic Review

toxin

Velocity of Lordosis Angle during Spinal Flexion and Extension

The importance of functional parameters for evaluating the severity of low back pain is gaining clinical recognition, with evidence suggesting that the angular velocity of lordosis is critical for identification of musculoskeletal deficits. However, there is a lack of data regarding the range of functional kinematics (RoKs), particularly which include the changing shape and curvature of the spine. We address this deficit by characterising the angular velocity of lordosis throughout the thoracolumbar spine according to age and gender. The velocity of lumbar back shape changes was measured using Epionics SPINE during maximum flexion and extension activities in 429 asymptomatic volunteers. The difference between maximum positive and negative velocities represented the RoKs. The mean RoKs for flexion decreased with age; 114°/s (20–35 years), 100°/s (36–50 years) and 83°/s (51–75 years). For extension, the corresponding mean RoKs were 73°/s, 57°/s and 47°/s. ANCOVA analyses revealed that age and gender had the largest influence on the RoKs (p<0.05). The Epionics SPINE system allows the rapid assessment of functional kinematics in the lumbar spine. The results of this study now serve as normative data for comparison to patients with spinal pathology or after surgical treatment.ISSN:1932-620

Traumatic spinal cord injury

Traumatic spinal cord injury (SCI) has devastating consequences for the physical, social and vocational well-being of patients. The demographic of SCIs is shifting such that an increasing proportion of older individuals are being affected. Pathophysiologically, the initial mechanical trauma (the primary injury) permeabilizes neurons and glia and initiates a secondary injury cascade that leads to progressive cell death and spinal cord damage over the subsequent weeks. Over time, the lesion remodels and is composed of cystic cavitations and a glial scar, both of which potently inhibit regeneration. Several animal models and complementary behavioural tests of SCI have been developed to mimic this pathological process and form the basis for the development of preclinical and translational neuroprotective and neuroregenerative strategies. Diagnosis requires a thorough patient history, standardized neurological physical examination and radiographic imaging of the spinal cord. Following diagnosis, several interventions need to be rapidly applied, including haemodynamic monitoring in the intensive care unit, early surgical decompression, blood pressure augmentation and, potentially, the administration of methylprednisolone. Managing the complications of SCI, such as bowel and bladder dysfunction, the formation of pressure sores and infections, is key to address all facets of the patient's injury experience

Traumatic spinal cord injury

Traumatic spinal cord injury (SCI) has devastating consequences for the physical, social and vocational well-being of patients. The demographic of SCIs is shifting such that an increasing proportion of older individuals are being affected. Pathophysiologically, the initial mechanical trauma (the primary injury) permeabilizes neurons and glia and initiates a secondary injury cascade that leads to progressive cell death and spinal cord damage over the subsequent weeks. Over time, the lesion remodels and is composed of cystic cavitations and a glial scar, both of which potently inhibit regeneration. Several animal models and complementary behavioural tests of SCI have been developed to mimic this pathological process and form the basis for the development of preclinical and translational neuroprotective and neuroregenerative strategies. Diagnosis requires a thorough patient history, standardized neurological physical examination and radiographic imaging of the spinal cord. Following diagnosis, several interventions need to be rapidly applied, including haemodynamic monitoring in the intensive care unit, early surgical decompression, blood pressure augmentation and, potentially, the administration of methylprednisolone. Managing the complications of SCI, such as bowel and bladder dysfunction, the formation of pressure sores and infections, is key to address all facets of the patient's injury experience