Andreas Hug

From Bench to Beside to Cure Spinal Cord Injury: Lost in Translation?

Despite intense efforts to overcome the inhospitable milieu for axonal regeneration within the damaged spinal cord an evidence-based repair strategy promoting relevant functional improvement is still not available for spinal cord injured individuals. Nevertheless, several preclinical axonal regenerative strategies were developed all the way to phase I/II clinical trials, which have recently been terminated. The aim of this chapter is to critically review translated preclinical treatment strategies with respect to their conformity with previously published guidelines and requirements for preclinical studies leading to clinical trials in human subjects with spinal cord injury (SCI). Cell-based strategies (macrophage and embryonic stem cell grafting) and the administration of C3 transferase inhibitors and anti-Nogo-A antibodies were investigated. Overall, these four approaches comply with preclinical quality standards to varying degree. For future preclinical analyses, several additive components such as defined criteria for robustness of observed effects, a clear confirmation of underlying structural mechanisms, and the implementation of appropriate preclinical rehab approaches should be considered in order to increase the quality and consequently the likelihood of respective therapeutic strategies to succeed in human individuals suffering from SCI.

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.

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.

Wirbelsäulen- und Rückenmarktraumen

Die Verletzungen der Wirbelsaule gehoren im Allgemeinen in das Fachgebiet der Unfallchirurgie und Orthopadie. Sie konnen aber neurochirurgische und neurologische Bedeutung bekommen, wenn die Gewalteinwirkung auf die Wirbelsaule auch zu einer vorubergehenden funktionellen Ruckenmarkschadigung fuhrt, wenn Luxationen und Frakturen die Nervenwurzeln ladieren oder wenn das Ruckenmark direkt mechanisch bzw. indirekt vaskular eine Substanzschadigung erleidet. Unfallmechanisch handelt es sich meist um Sturze, oft mit Stauchung der Wirbelsaule, seltener um die Folgen von Schlag oder Stos auf die Wirbelsaule und um Verschuttungen. Eine grose Aufmerksamkeit haben in letzter Zeit die Beschleunigungsverletzungen der Halswirbelsaule (»whiplash injury«) bei Verkehrsunfallen gewonnen.

Spinal Cord Neurophysiology

Neurophysiological techniques and their clinical value in a spinal cord injury (SCI) specific context are discussed in this chapter. Since spontaneous neurological recovery is much better in clinical incomplete compared to complete cases, the rational for a detailed analysis of motor and sensory pathways after SCI is based on the intention to find markers of lesional incompleteness. For this reason, neurophysiological techniques are applied to investigate parameters of connectivity (e.g., somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs)) and the impact of that connectivity (e.g., reflex studies, patterns of muscle activation in polyelectromyography).

Entwicklungsstörungen und Fehlbildungen des Nervensystems

Entwicklungsstorungen des Nervensystems kommen genetisch, als Folge von intrauterinen Infektionen, metabolischen Funktionsstorungen, und, heute am haufigsten, als Folge von Intoxikationen, der Uberdosierung von Medikamenten oder durch Alkohol zustande. Ein weiterer wichtiger Schadigungsmechanismus sind pra- und perinatale Sauerstoffmangelzustande und Infektionen, die auch ohne zugrunde liegende Fehlbildungen des Hirngewebes zu psychomotorischen Entwicklungsverzogerungen fuhren konnen. Die groste Risikogruppe sind hier Fruh- und Mangelgeborene.