Goal attainment in mobility after acute rehabilitation of mobility-restricting paralysis syndromes with regard to the ambulatory therapeutic level of participation NeuroMoves : A German national multicenter observational cohort study.

BACKGROUND: A central goal of rehabilitation in patients with paralysis syndromes after stroke or spinal cord injury (SCI) is to restore independent mobility as a pedestrian or wheelchair user. However, after acute rehabilitation, the mobility frequently deteriorates in the ambulatory setting, despite the delivery of rehabilitative interventions such as physical therapy or the prescription of assistive devices. The aim of the NeuroMoves study is to identify factors that are associated with changes of mobility in the ambulatory setting after acute inpatient rehabilitation, with a particular focus on participation according to the ICF (International Classification of Functioning, Disability and Health). METHODS: The NeuroMoves study is intended as a national multicenter observational cohort study with 9 clinical sites in Germany. A total of 500 patients with mobility-restricting paralysis syndromes (i.e. stroke or SCI) are to be recruited during acute inpatient rehabilitation prior to discharge to the ambulatory setting. Patients will have 8 months of follow-up in the ambulatory setting. Three study visits at the clinical sites (baseline, midterm, and final) are planned at 4-months intervals. The baseline visit is scheduled at the end of the acute inpatient rehabilitation. During the visits, demographical data, neurological, functional, quality of life, and implementation measures will be assessed. At baseline, each study participant receives an activity tracker (sensor for recording ambulatory mobility) along with a tablet computer for home use over the 8 months study duration. While mounted, the activity tracker records mobility data from which the daily distance covered by walking or wheelchair use can be calculated. Customized applications on the tablet computer remind the study participants to answer structured questionnaires about their health condition and treatment goals for physical therapy. Using the study participants' tablet, therapists will be asked to answer structured questionnaires concerning treatment goals and therapeutic measures they have applied. The primary analysis concerns the association between mobility (daily distance covered) and the degree of participation-oriented rehab interventions. Further exploratory analyses are planned. DISCUSSION: The findings could inform healthcare decision-making regarding ambulatory care in Germany focusing on mobility-promoting interventions for patients with mobility-restricting paralysis syndromes. STUDY REGISTRATION: German Clinical Trials Register, DRKS-ID: DRKS00020487 (18.02.2020).

Sepsis in mechanically ventilated patients with spinal cord injury: a retrospective analysis.

STUDY DESIGN: Retrospective analysis. OBJECTIVES: Sepsis, one of the most frequent and life-threatening complications on intensive care units (ICUs), is associated with a need for mechanical ventilation (MV) as well as adverse respiratory outcomes in hospitalized individuals. However, it has poorly been investigated in patients with spinal cord injury (SCI); a population at high risk for pulmonary and infectious complications. SETTING: Spinal Cord Injury Center, Heidelberg University Hospital. METHODS: Over a 5-year period, 182 individuals with SCI requiring MV during their ICU stay were analyzed. Data assessment included demographics, medical characteristics, focus and causative pathogen of sepsis, length of stay, weaning outcomes, and mortality. RESULTS: Sepsis was recorded in 28 patients (15%), containing a subgroup of individuals suffering from infectious SCI and co-occurring primary sepsis with Staphylococcus aureus as the predominant microorganism. In most individuals, sepsis was found as secondary complication, which was associated with pulmonary foci, Gram-negative bacteria, and high mortality. More than 80% of individuals with secondary sepsis required induction of MV due to respiratory failure. Furthermore, respiratory failure was found to be independent of sepsis focus, spectrum of causative pathogens, SCI etiology, or severity of injury. Subsequent weaning from the respirator was prolonged in more than 90% with a high proportion of weaning failure. CONCLUSIONS: Sepsis predominantly occurs as a secondary complication after SCI and is associated with detrimental outcomes. Although the lung is frequently affected as a failing organ, not all sepsis foci are pulmonary. Awareness of both actual sepsis focus and causative pathogen is central to initiate an adequate sepsis treatment.

Impact of spine alignment on the rotator cuff in long-term wheelchair users.

BACKGROUND: We investigated the impact of poor seated posture on the prevalence of rotator cuff tears (RCTs) among wheelchair-dependent individuals with long-standing paraplegia. METHODS: The study included 319 patients. Lateral radiographs of the spine were collected from a database and analyzed to assess the global spinopelvic alignment (SPA). Magnetic resonance images of both shoulders were obtained to detect the presence of cuff tears. Patients were divided into 2 groups: Group RCT-I included all patients with cuff tears (right, left, or bilateral), whereas group RCT-II consisted exclusively of patients with bilateral cuff tears. We used the classification systems developed by Kendall et al and Roussouly et al to assess the sagittal spine alignment and SPA, respectively. Univariate and multivariate analyses were performed. To fit both models (groups RCT-I and RCT-II) to the data, the 4 spine curves according to Roussouly et al were subdivided into 2 groups: Group SPA-I included both type 1 and type 2, whereas group SPA-II included both type 3 and type 4. RESULTS: Magnetic resonance images showed a cuff tear in 192 patients (60.19%) (group RCT-I). Among those, 37 patients (11.60%) had tears in both shoulders (group RCT-II). In group RCT-I, 70.31% of the patients had a kyphotic-lordotic posture. The kyphotic-lordotic posture, a longer duration, and a more rostral neurologic level of injury were highly associated with cuff tear prevalence. In group RCT-II, the multivariate analysis showed that only the duration of spinal cord injury was significantly associated with RCTs. CONCLUSION: Thoracic hyperkyphosis was associated with a markedly high rate of RCTs. The data from this study may provide support for developing preventive strategies.

C-reactive protein in the detection of post-stroke infections: systematic review and individual participant data analysis.

We conducted a systematic review and individual participant data meta-analysis to explore the role of C-reactive protein (CRP) in early detection or prediction of post-stroke infections. CRP, an acute-phase reactant binds to the phosphocholine expressed on the surface of dead or dying cells and some bacteria, thereby activating complement and promoting phagocytosis by macrophages. We searched PubMed up to May-2015 for studies measuring CRP in stroke and evaluating post-stroke infections. Individual participants' data were merged into a single database. CRP levels were standardized and divided into quartiles. Factors independently associated with post-stroke infections were determined by logistic regression analysis and the additional predictive value of CRP was assessed by comparing areas under receiver operating characteristic curves and integrated discrimination improvement index. Data from seven studies including 699 patients were obtained. Standardized CRP levels were higher in patients with post-stroke infections beyond 24 h. Standardized CRP levels in the fourth quartile were independently associated with infection in two different logistic regression models, model 1 [stroke severity and dysphagia, odds ratio = 9.70 (3.10-30.41)] and model 2 [age, sex, and stroke severity, odds ratio = 3.21 (1.93-5.32)]. Addition of CRP improved discrimination in both models [integrated discrimination improvement = 9.83% (0.89-18.77) and 5.31% (2.83-7.79), respectively], but accuracy was only improved for model 1 (area under the curve 0.806-0.874, p = 0.036). In this study, CRP was independently associated with development of post-stroke infections, with the optimal time-window for measurement at 24-48 h. However, its additional predictive value is moderate over clinical information. Combination with other biomarkers in a panel seems a promising strategy for future studies.

Dynamic contrast-enhanced ultrasound and elastography assess deltoid muscle integrity after reverse shoulder arthroplasty.

BACKGROUND: The outcome after reverse shoulder arthroplasty (RSA) depends on the condition of the deltoid muscle, which we assessed with new ultrasound modalities and electromyography (EMG). Contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) were applied to assess perfusion and elasticity of the deltoid muscle compared with the clinical and functional outcome. METHODS: The study recruited 64 patients (mean age, 72.9 years) treated with RSA between 2004 and 2013. The deltoid muscle was examined with EMG and ultrasound imaging. Functional scores such as Constant score and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score were assessed. Among other CEUS parameters, the wash-in perfusion index, time to peak, and rise time were compared between the operated-on and contralateral shoulders as well as between patients with above-average and below-average outcome. The stiffness of the deltoid muscle was analyzed with ARFI. RESULTS: After RSA, deltoid perfusion (wash-in perfusion index, Δ = -12% ± 22%, P = .0001) and shoulder function (Constant score, Δ = -14 ± 24, P < .0001) were both inferior compared with the contralateral side. This perfusion deficit was associated with a limited range of motion (time to peak and anteversion: r = -0.290, P = .022). Deltoid perfusion was higher in patients with above-average outcome (rise time, Δ = 33% ± 13%, P = .038). The operated-on deltoid muscles showed higher stiffness than the contralateral muscles (ARFI, Δ = 0.2 ± 0.9 m/s, P = .0545). EMG excluded functionally relevant axillary nerve injuries in the study population. CONCLUSIONS: CEUS revealed reduced mean perfusion of the deltoid muscle after RSA. Reduced perfusion was associated with limited range of motion and below-average outcome. Functional shoulder impairment after RSA might be predicted by noninvasive CEUS as a surrogate parameter for the integrity of the deltoid muscle.

Provision and use of assistive products in patients after stroke and spinal cord injury in Germany: a qualitative interview study.

PURPOSE: Mobility impairments are a common consequence of stroke and spinal cord injury (SCI). Assistive products (APs) such as wheelchairs are often needed for activities and participation. The aim of the study was to explore the provision and use of APs in Germany and to identify associated factors underlying this practice. MATERIALS AND METHODS: Semi-structured interviews were conducted with 19 professionals from outpatient neurorehabilitation services (three general practitioners, five physical therapists, five occupational therapists, one speech therapist, one neuropsychologist, two outpatient nurses, one rehab technician and one social worker), two patient advocates (long-term survivors, each stroke and SCI) and 20 patients (10 each after stroke and SCI with mobility impairment, and first-ever affected). Analysis was performed by qualitative content analysis. RESULTS: Reported experiences were mixed, varying from high satisfaction to unusable APs and unmet needs. Identified factors associated with these experiences were related to care pathways, care coordination, inter-professional collaboration, professionals' knowledge and patient information, cost coverage, and approval procedures. CONCLUSION: Overall, patients seem satisfied with the APs they receive, but patients with more severe mobility impairments in particular experience deficits in the provision and use of APs. Further research is needed to develop and test strategies for the provision and use of APs.

Interprofessional collaboration between the multiple stakeholders and the involvement of end users is needed to realise the full potential of specific assistive products (APs).A care pathway should be implemented for the provision of appropriate APs.Professionals' expertise in both APs and end user empowerment needs to be improved.The approval process of the public health insurance should be accelerated and geared more towards the individual needs of patients.

Elevated high-sensitivity cardiac troponin T serum concentration in subjects with spinal cord injury.

BACKGROUND: The biochemical analysis of high-sensitivity cardiac troponins (hs-cTn) from peripheral blood specimens has been established as biomarker for myocardial injury. Independently of myocardial injury, increased serum hs-cTn concentrations have been described in patients with myopathies. The relevance and frequency of noncardiac hs-cTn elevations in spinal cord injury (SCI) is unknown. Our study aimed to 1) determine the frequency of increased hs-cTn concentrations of supposedly noncardiac origin above the 99th percentile (upper reference limit, URL) in an unselected SCI population and 2) compare the two protagonist analytes cTnT and cTnI with respect to these noncardiac elevations. METHODS: In this monocentric, cross-sectional study, we sampled blood from n = 30 SCI subjects without cardiac symptoms to test for hs-cTnT and hs-cTnI serum concentrations. RESULTS: 18/30 (60%) of SCI subjects showed increased hs-cTnT concentrations above the URL of 14 ng/l (p < 0.001). In 4 subjects (22.2%) concentrations were >50 ng/l. Moreover, 3 of these four subjects fulfilled the 6-h troponin dynamics criterion for acute myocardial injury in serial hs-cTnT testing. In contrast, no subject demonstrated increased hs-cTnI concentrations according to the URL of 40 ng/l. 6-h troponin dynamics were also unremarkable for hs-cTnI testing. CONCLUSIONS: SCI subjects frequently have increased hs-cTnT concentrations without clinical and hs-cTnI evidence of myocardial injury. Clinicians must be aware of cTnT "skeletal muscle false-positives" in SCI, which applies to elevated baseline cTnT concentrations and troponin dynamics in serial measurements. In case of diagnostic uncertainty, simultaneous analysis of cTnI might be helpful.

Current practice of outpatient rehabilitation services in patients with mobility-impaired paralysis due to stroke or spinal cord injury: a qualitative interview study in Germany.

PURPOSE: When mobility deficits persist after stroke or spinal cord injury (SCI), outpatient neurorehabilitation services are required. This study aimed to explore the current practice of German outpatient neurorehabilitation services and identify factors associated to this practice. METHODS: This was a qualitative observational study in which semi-structured interviews were conducted with professionals from outpatient neurorehabilitation services and mobility-impaired patients. A qualitative content analysis with a data-driven coding process was used. RESULTS: Three general practitioners, five physical, five occupational, and one speech therapist, one neuropsychologist, two outpatient nurses, one rehabilitation technician, one social worker, two patient advocates (long-term survivors, each stroke and SCI), and 20 patients (10 after stroke, 10 after SCI, all first-ever affected since approximately one year) participated. The reported experiences ranged from high satisfaction to perceived deficits in participation-oriented, evidence-based, and coordinated care. Identified associated factors were: (a) availability of specialised therapists and professional education, (b) outpatient service catalogue, (c) cost coverage, (d) setting rehabilitation goals, and (e) physician as care coordinator. CONCLUSION: Areas of improvement identified focused on: setting rehabilitation goals towards participation, training therapists on evidence-based treatments and shared decision-making, updating the outpatient service catalogue, and implementing coordination actions. Implementation of these recommendations should be evaluated.

Professionals need to be trained in setting rehabilitation goals and treatments. The continuing education should be based on current evidence and address interprofessionalism. Academization and continuing education in scientific work for therapists should be advanced.Professionals should educate patients about rehabilitation goals and set rehabilitation goals together, both interprofessional coordinated and with the patient (shared decision-making). Activity and participation should be the central aspects. Rehabilitation clinicians should give instructions to therapists on what to do if rehabilitation goals are not worked on.Rehabilitation clinicians should encourage interprofessional collaboration and information exchange where this is not the case. The exchange of information between outpatient professionals should be promoted through appropriate measures, that is, interprofessional meetings could be introduced.The outpatient service catalogue should be revised regarding evidence-based and participation-oriented treatments and enable appropriate cost coverage.

Fast-track intubation for accelerated interventional stroke treatment.

BACKGROUND: As intravenous thrombolysis frequently fails to recanalize occluded proximal intracerebral arteries, interventional recanalization therapy is increasingly being considered as treatment option in acute ischemic stroke patients. The optimal periprocedural patient management for these interventions is currently unknown. The aim of this study was to identify factors delaying door-to-treatment times, and to evaluate the effect of a fast-track intubation standard operating procedure (I-SOP) on door-to-angiography time. METHODS: First, we retrospectively reviewed records of 48 acute stroke patients who were treated by interventional recanalization of intracranial occlusions between 2006 and 2009 at our institution. Time to angiography was defined as time from hospital admission to the beginning of the angiographic procedure. Second, an I-SOP for fast-track intubation was implemented and effects on door-to-angiography time were prospectively analyzed in 23 consecutive patients. RESULTS: In the retrospective dataset (n = 48), the mean door-to-angiography time was 2.2 ± 0.1 h (mean ± SEM). A clinically relevant time loss attributable to the intubation procedure was suggested by a 51 ± 21 min shorter door-to-angiography time for patients already intubated prior to admission (P = 0.0189). Additional factors associated with a prolonged door-to-angiography time were: door-to-diagnosis time (P < 0.001), onset-to-door time (P = 0.0117), and male gender (mean difference +27 ± 15 min, P = 0.0822). In the prospective dataset (n = 23), I-SOP implementation reduced mean door-to-angiography time by 25 ± 10 min (P = 0.0164). CONCLUSIONS: In acute stroke patients, intubation prior to interventional recanalization therapy can delay treatment initiation. The implementation of an I-SOP accelerates interventional treatment initiation.

Reduced efficacy of circulating costimulatory cells after focal cerebral ischemia.

BACKGROUND AND PURPOSE: Cerebral ischemia is ensued by a cellular immune depression syndrome. The postischemic functional capacity of T lymphocytes is controversial, and interactions between leukocyte subsets are largely unknown. Understanding the immunologic interplay between antigen-presenting cells and lymphocytes as well as between distinct lymphocyte subsets after stroke might be of clinical/therapeutic significance because animal data argue for a cerebroprotective effect of, for example, CD4+CD25+ regulatory T cells. METHODS: Ex vivo CD4+ T cell proliferation was analyzed in experimental and human stroke using fluorescence activated cell sorter analysis. To investigate suppressive effects of CD4+CD25+ regulatory T cells as well as the influence of costimulatory cells on CD4+ T cell proliferation, subsets were magnetically sorted before proliferation assay setup. RESULTS: After stroke: (1) proliferation of mouse and human CD4+ T cells on T cell receptor stimulation was unaltered; (2) the suppressive effect of CD4+CD25+ regulatory T cells in mouse and man was unaltered; and (3) efficacy of circulating costimulatory cells from stroke animals was reduced by a mean of 0.6 (SEM 0.1, P=0.001) CD4+ T cell division numbers compared with sham-treated animals. CONCLUSIONS: Reduced costimulatory efficacy of circulating costimulatory cells in mice is an important feature of stroke-induced immunodepression. Understanding the interplay of costimulatory cells and responder T cells (eg, CD4+ T cells or CD4+CD25+ regulatory T cells) after stroke may offer new insights into the prevention of secondary inflammatory damage to the brain and help to guide new therapeutic strategies.

Point-of-care reversal treatment in phenprocoumon-related intracerebral hemorrhage.

OBJECTIVE: Rapid reversal of the anticoagulatory effect of vitamin K antagonists represents the primary emergency treatment for oral anticoagulant-related intracerebral hemorrhage (OAC-ICH). Predicting the amount of prothrombin complex concentrate (PCC) needed to reverse OAC in individual patients is difficult, and repeated international normalized ratio (INR) measurements in central laboratories (CLs) are time-consuming. Accuracy and effectiveness of point-of-care INR coagulometers (POCs) for INR reversal in OAC-ICH have not been evaluated. METHODS: In phase 1, the agreement of emergency POC and CL INR measurements was determined. In phase 2, stepwise OAC reversal was performed with PCC using a predetermined dosing schedule. Concordance of POC and CL INR measurements during reversal and time gain due to POC were determined. RESULTS: In phase 1 (n = 165), Bland-Altman analysis showed close agreement between POCs and CLs (mean INR deviation 0.04). In phase 2 (n = 26), POCs caused a median initial net time gain of 24 minutes for the start of treatment with PCC. Median time for POC-documented complete OAC reversal was 28 minutes, compared with 120 minutes for CLs. Bland-Altman analysis between POCs and CLs revealed a mean INR deviation of 0.13 during stepwise PCC administration. POCs tended to slightly overestimate the INR, especially at higher INR levels. Remarkably, POC-guided reversal led to a median reduction of 30.5% of PCC dose compared with the a priori dose calculation. Hematomas enlarged in 20% of patients. INTERPRETATION: POC INR monitoring is a fast, effective, and economic means of PCC dose-titration in OAC-ICH. Larger studies examining the clinical efficacy of this procedure are warranted.

Usefulness of serum procalcitonin levels for the early diagnosis of stroke-associated respiratory tract infections.

BACKGROUND: Patients with extensive brain infarcts are at increased risk for stroke-associated respiratory tract infections (SARTI), which cause worse outcome. The benefit of general antibiotic prophylaxis is controversial. Early diagnosis of SARTI may improve patient selection for antimicrobial therapy. Procalcitonin (PCT) is widely recognized as serum marker for bacterial infections. Its diagnostic value with respect to SARTI has not been assessed systematically. METHODS: Serum PCT levels were analyzed in ischemic stroke patients (n = 50) at day 1 (d1) and day 4 (d4) after stroke onset. PCT test performance was assessed by receiver operator characteristics (ROC) curve analysis. Multivariable logistic regression analysis was applied to identify early predictors for SARTI. RESULTS: Higher d4 serum PCT levels were associated with SARTI; ROC curve analysis revealed an area under the curve (AUC) of 0.79 (95%-confidence interval (CI) 0.61-0.96). A 0.25-ng/ml cutoff resulted in a test sensitivity and specificity of 42 and 96%, respectively. Positive (LR+) and negative (LR-) likelihood ratios were 10.8 and 0.6, respectively. In predicting SARTI, multivariable logistic regression analysis controlling for infarct volume ruled out an independent explanatory effect of serum PCT. Greater infarct volume (odds ratio (OR) 1.06, 95%-CI 1.02-1.1) prevailed as independent SARTI-predictor. CONCLUSIONS: In the absence of clinical signs, post-stroke screening for SARTI using serum PCT levels is not useful since test sensitivity is low. If the clinical suspicion for SARTI is strong, serum PCT-testing (>0.25 ng/ml) may improve diagnostic accuracy by improving specificity.

In chronic complete spinal cord injury supraspinal changes detected by quantitative MRI are confined to volume reduction in the caudal brainstem.

There is much controversy about the potential impact of spinal cord injury (SCI) on brain anatomy and function, which is mirrored in the substantial divergence of findings between animal models and human imaging studies. Given recent advances in quantitative magnetic resonance imaging (MRI) we sought to tackle the unresolved question about the link between the presumed injury associated volume differences and underlying brain tissue property changes in a cohort of chronic complete SCI patients. Using the established computational anatomy methods of voxel-based morphometry (VBM) and voxel-based quantification (VBQ), we performed statistical analyses on grey and white matter volumes as well as on parameter maps indicative for myelin, iron, and free tissue water content in the brain of complete SCI patients (n = 14) and healthy individuals (n = 14). Our regionally unbiased white matter analysis showed a significant volume reduction of the dorsal aspect at the junction between the most rostral part of the spinal cord and the medulla oblongata consistent with Wallerian degeneration of proprioceptive axons in the dorsal column tracts in SCI subjects. This observation strongly correlated with spinal cord atrophy assessed by quantification of the spinal cord cross-sectional area at the cervical level C2/3. These findings suggest that Wallerian degeneration of the dorsal column tracts represents a main contributor to the observed spinal cord atrophy, which is highly consistent with preclinical histological evidence of remote changes in the central nervous system secondary to SCI. Structural changes in other brain regions representing remote changes in the course of chronic SCI could neither be confirmed by conventional VBM nor by VBQ analysis. Whether and how MRI based brain morphometry and brain tissue property analysis will inform clinical decision making and clinical trial outcomes in spinal cord medicine remains to be determined.

Infarct volume is a major determiner of post-stroke immune cell function and susceptibility to infection.

BACKGROUND AND PURPOSE: Acute ischemic stroke in humans is associated with profound alterations in the immune system. Hallmarks of this stroke-induced immunodepression syndrome are: lymphocytopenia, impairment of T helper cell and monocyte function. We studied which stroke-specific factors predict these immunologic alterations and subsequent infections. METHODS: Leukocyte/lymphocyte subsets were assessed serially by white blood cell count and fluorescence-activated cell sorter analysis in ischemic stroke patients (n=50) at baseline, day 1, and day 4 after stroke onset and compared to an age-matched control group (n=40). Concomitantly, monocytic human leukocyte antigen-DR expression and the in vitro function of blood monocytes measured by the production of tumor necrosis factor-alpha upon stimulation with lipopolysaccharide were assessed. Associations of these immunologic parameters with stroke specific factors (National Institutes of Health Stroke Scale, infarct size) were explored. Multivariable logistic regression analysis was applied to identify early predictors for poststroke respiratory and urinary tract infections. RESULTS: Infarct volume was the main factor associated with lymphocytopenia on day 1 and day 4 poststroke. Particularly, blood natural killer cell counts were reduced after stroke. Monocyte counts increased after ischemia paralleled by a profound deactivation predominantly after extensive infarcts. Reduced T helper cell counts, monocytic human leukocyte antigen-DR expression, and monocytic in vitro production of tumor necrosis factor-alpha were associated with infections in univariate analyses. However, only stroke volume prevailed as independent early predictor for respiratory infections (OR 1.03; CI 1.01 to 1.04). CONCLUSIONS: Infarct volume determines the extent of lymphocytopenia, monocyte dysfunction, and is a main predictor for subsequent infections.

The spectrum of systemic immune alterations after murine focal ischemia: immunodepression versus immunomodulation.

BACKGROUND AND PURPOSE: Therapeutic modification of the postischemic immune processes is a key target of current experimental stroke research. For successful translation into the clinical setting, experimental studies must account for the impact of different strokes on the immune system including susceptibility to infection. Herein, we characterize the impact of 3 ischemia models on systemic immunological and microbiological parameters. METHODS: In C57Bl/6 mice (n=235), the middle cerebral artery was occluded (MCAO) either permanently by distal coagulation or transiently by an intraluminal filament for 30 minutes or 90 minutes. Differential leukocyte counts were performed in blood and lymphatic organs. Lymphocyte subpopulations and apoptotic cells were characterized by flow cytometry. Blood cytokine concentrations were measured by ELISA. Microbiological cultures were grown from blood and lung samples. RESULTS: Only extensive infarcts induced leukopenia 24 hours, 3 days and 7 days after MCAO and decreased lymphocyte counts in spleen, lymph nodes and thymus. In contrast, small infarcts led to no significant changes in differential blood count or reduction of overall cell counts in lymphatic organs. Splenic lymphocyte apoptosis and blood cytokine production was significantly increased after extensive lesions compared to mild ischemia. Hypothermia and weight loss occurred only in mice with large infarcts which also suffered from pneumonia and sepsis. In contrast to infarct size, location and side of the infarct did not affect physiological parameters and immune cell alterations. CONCLUSIONS: Postischemic systemic immunomodulation and infectious complications differ substantially among stroke models. Translational studies of immunomodulatory therapies for stroke must account for this heterogeneity.

Ulnar nerve integrity predicts 1-year outcome in cervical spinal cord injury.

BACKGROUND: Accurate predictors of neurological recovery after cervical spinal cord injury are needed. Particularly, to tailor adequate rehabilitation plans. However, objective and quantifiable predictors are sparse. METHODS: Within the prospective European Multicenter Study about Spinal Cord Injury (EMSCI) registry, cervical spinal cord injury patients are monitored at fixed follow up visits (2, 4, 12, 24, and 48 weeks after injury) clinically and with ulnar nerve electroneurography. Associations of ulnar nerve compound muscle action potential amplitudes (CMAP) with American Spinal Cord Injury Association (ASIA) impairment scale (AIS) grades over time were analyzed using linear mixed modeling. Applying logistic regression, the prognostic value of within 4-week ulnar nerve CMAP for 1-year AIS was analyzed. To account for missing data, (1) last observation carried forward and (2) multiple imputation methods were applied. For model derivation, our centers' cohort (EMSCI-HD) was analyzed. For model validation the cohort of other centers (EMSCI-nonHD) was used. RESULTS: In the EMSCI-HD cohort, the median age (interquartile range (IQR)) was 52 (34-67) years. 58% were male. The initial AIS distribution was: A = 31%, B = 17%, C = 30%, and D = 22%). In the EMSCI-nonHD cohort, the median age was 49 (32-65) years. Compared to the EMSCI-HD cohort more patients were male (79%, p = 0.0034). The AIS distribution was: A = 33%, B = 13%, C = 21%, and D = 33%).In complete-case mixed model analyses (EMSCI-HD: n = 114; EMSCI-nonHD: n = 508) higher ulnar nerve CMAP were associated with better AIS grades over the entire follow up period. In complete-case logistic regression (EMSCI-HD: n = 90; EMSCI-nonHD: n = 444) higher ulnar nerve CMAP was an independent predictor of better AIS grades. The odds ratio for within 4-week ulnar nerve CMAP to predict 1-year AIS grade D versus A-C in the EMSCI-HD cohort was 1.24 per millivolt (confidence interval 1.07-1.44). The model was validated in an independent cervical spinal cord injury (EMSCI-nonHD) cohort (odds ratio 1.09, confidence interval 1.03-1.17). CONCLUSIONS: In cervical spinal cord injury, the consideration of early ulnar nerve CMAP improves prognostic accuracy, which is of particular importance in patients with clinical grading uncertainties.

The cognitive impact of chronic low back pain: Positive effect of multidisciplinary pain therapy.

OBJECTIVES: Little is known about the affected cognitive problems in chronic low back pain patients. For this patient cohort research mostly focused on memory of pain, rather than cognitive difficulties related to pain. Chronic pain may be associated with specific (yet undefined) cognitive deficits that affect everyday behaviour. We set out to compare the cognitive function of patients with chronic low back pain (cLBP) in the course of multidisciplinary pain treatments before and after therapy. METHODS: Thirty-three patients with cLBP and 25 healthy controls between 20 and 70 years were recruited into the study. The inclusion criteria for patients were: (1) a history of at least 12 weeks of chronic myofascial low back pain without radicular pain sensation before enrolment; (2) grade II and higher chronicity according to von Korff; (3) no opioid medication. The patients recruited had a mean pain duration of 7.13±7.16 years and reported a mean pain intensity of 6.62±2.04 (visual analogue score, VAS). Their mean back function according to the Funktionsfragebogen Hannover (FFbH, a questionnaire comparable with the Health Assessment Questionnaire) was 52.39±20.23%. At three time points (before therapy, 3 weeks and 6 months after therapy) the study subjects were assessed prospectively with a battery of visual memory tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). These included choice reaction time (CRT), pattern recognition memory (PRM) and spatial span (SSP). In parallel, the Trail-Making Test (TMT-A, TMT-B) and the Wechsler Adult Intelligence Scale (WAIS-III) were used to evaluate intelligence and cognitive flexibility. RESULTS: At the beginning of MDPT (T1), it took patients with cLBP significantly longer than HC to complete TMT-A (38.29±19.99s vs 30.25±14.19s, p=0.047) and TMT-B (72.10±26.98s vs 55.99±22.14s, p=0.034). There were no significant differences between patients and HC in CRT, PRM and SSP. Three weeks (T2) and 6 months (T3) after MDPT, TMT-A reaction time of patients significantly improved by 6.5s and 8.1ms (38.3 ±19.9s vs 31.8±12.3s, p=0.02 and 31.8±12.3s vs 30.2±8.9s, p=0.021, respectively). The patients' working memory was also better 6 months after MDPT (48.8±11.1% at T1, 51.2±11.9% at T2, 57.1±10.9% at T3, p=0.008). Significant correlations among pain, depression/anxiety, medication and neuropsychological tests were found. CONCLUSIONS: These findings show that patients with cLBP have slowed speeds of information processing and working memory, but no alteration in attention and recognition memory. There are clearly interactions of cognitive function with pain, depression, anxiety, and medication. MDPT may improve the impaired cognitive function of patients with cLBP. IMPLICATION: Health professionals should contemplate the results from this study when planning therapy strategies especially when prescribing pain medications such opioids to patients with chronic low back pain.

Dynamic contrast-enhanced ultrasound (CEUS) after open and minimally invasive locked plating of proximal humerus fractures.

INTRODUCTION: Closed reduction and locked plate fixation of proximal humerus fractures with the minimally invasive deltoid-splitting approach intends to minimize soft tissue damage although axillary nerve injury has been reported. The aim of this study was to assess the deltoid muscle perfusion with dynamic contrast-enhanced ultrasound (CEUS) as novel technique and evaluate its relation to the functional and neurologic outcome after open (ORIF) and minimally invasive (MIPO) fracture fixation. PATIENTS AND METHODS: 50 patients, 30 with deltopectoral ORIF and 20 with deltoid-splitting MIPO approach were examined 6-49 months after surgery. Only patients with a healthy, contralateral shoulder were selected. Shoulder function, satisfaction as well as psychosocial outcome were assessed with established scores (Constant, DASH, Simple Shoulder Test, ASES, SF-12). Electromyography (EMG) of the deltoid muscle was performed to determine axillary nerve damage. Ultrasound of both shoulders included CEUS and Power Doppler after deltoid muscle activation via active abduction for two minutes. RESULTS: None of the examinations and scores showed significant differences between ORIF and MIPO patients, the psychosocial outcome was similar. The fracture types were equally distributed in both groups. The normalized Constant Score was 76.3±18.6 in the ORIF and 81.6±16.1 in the MIPO group (p=0.373). Deltoid muscle perfusion in CEUS and Power Doppler revealed no differences between both approaches. EMG excluded functionally relevant axillary nerve injuries. Compared with the contralateral shoulder, Constant- and ASES-Scores (p≤0.001 for both ORIF and MIPO) as well as the deltoid CEUS perfusion (ORIF p=0.035; MIPO p=0.030) were significantly worse for both approaches. CONCLUSIONS: Convincing consensus of functional, ultrasonographic and neurologic examinations demonstrated comparable outcomes after deltopectoral and deltoid-splitting approach. The quantification of the deltoid muscle perfusion with CEUS indicates that the proclaimed benefits of the MIPO approach on soft tissue might not be as great as expected.

Imaging of Orthotopic Glioblastoma Xenografts in Mice Using a Clinical CT Scanner: Comparison with Micro-CT and Histology.

PURPOSE: There is an increasing need for small animal in vivo imaging in murine orthotopic glioma models. Because dedicated small animal scanners are not available ubiquitously, the applicability of a clinical CT scanner for visualization and measurement of intracerebrally growing glioma xenografts in living mice was validated. MATERIALS AND METHODS: 2.5x106 U87MG cells were orthotopically implanted in NOD/SCID/ᵞc-/- mice (n = 9). Mice underwent contrast-enhanced (300 µl Iomeprol i.v.) imaging using a micro-CT (80 kV, 75 µAs, 360° rotation, 1,000 projections, scan time 33 s, resolution 40 x 40 x 53 µm) and a clinical CT scanner (4-row multislice detector; 120 kV, 150 mAs, slice thickness 0.5 mm, feed rotation 0.5 mm, resolution 98 x 98 x 500 µm). Mice were sacrificed and the brain was worked up histologically. In all modalities tumor volume was measured by two independent readers. Contrast-to-noise ratio (CNR) and Signal-to-noise ratio (SNR) were measured from reconstructed CT-scans (0.5 mm slice thickness; n = 18). RESULTS: Tumor volumes (mean±SD mm3) were similar between both CT-modalities (micro-CT: 19.8±19.0, clinical CT: 19.8±18.8; Wilcoxon signed-rank test p = 0.813). Moreover, between reader analyses for each modality showed excellent agreement as demonstrated by correlation analysis (Spearman-Rho >0.9; p<0.01 for all correlations). Histologically measured tumor volumes (11.0±11.2) were significantly smaller due to shrinkage artifacts (p<0.05). CNR and SNR were 2.1±1.0 and 1.1±0.04 for micro-CT and 23.1±24.0 and 1.9±0.7 for the clinical CTscanner, respectively. CONCLUSION: Clinical CT scanners may reliably be used for in vivo imaging and volumetric analysis of brain tumor growth in mice.

Single-cell PCR analysis of the immunoglobulin heavy-chain CDR3 region for the diagnosis of leptomeningeal involvement of B-cell malignancies using standard cerebrospinal fluid cytospins.

The diagnosis of leptomeningeal B-cell malignancies is based on the identification of malignant B cells in the cerebrospinal fluid (CSF). We have established a polymerase chain reaction (PCR) approach to characterize the clonally diverse gene encoding the immunoglobulin heavy-chain (IgH) third complementarity determining region (CDR3) of single B cells. We demonstrate that single-cell PCR is readily applicable to individual cells derived from routine CSF cytospins and is a powerful method to discriminate monoclonal neoplastic from polyclonal reactive B-cell responses. Single-cell PCR analysis, as a new tool for the diagnosis and monitoring of neoplastic meningitis associated with B-cell malignancies, is particularly important if cytology, immunocytochemistry, flow cytometry and automated gene scanning of CSF samples are unable to detect malignant monoclonal proliferation.