Im September 2023 wurde die überarbeitete S3-Leitlinie Versorgung peripherer Nervenverletzungen publiziert. Multimodale schmerztherapeutische Behandlungsstrategien haben hierbei Eingang in die Leitlinie gefunden und schließen systemische und lokal-medikamentöse, physiotherapeutische und ergotherapeutische Maßnahmen mit ein. Eine zentrale Fragestellung bewertete dabei die viel diskutierte Behandlungsoption mittels perineuraler Lokalanästhesie. Um die Effektivität lokaler Infiltrationen bei der Behandlung von neuropathischen Schmerzen nach einer Nervenverletzung darzustellen, erfolgen eine systematische Literaturrecherche und Evidenzbewertung mittels Metaanalyse. Nach Formulierung einer entsprechenden PICO(„patient/population, intervention, comparison and outcomes“)-Frage (Infobox 1) innerhalb der Leitliniengruppe erfolgte eine selektive Literaturanalyse zu klinischen Studien in Datenbanken (PubMed, Cochrane Central Register of Controlled Trials – CENTRAL) bis zum 31.07.2023. Zwei Reviewer bewerteten die Literatur und prüften systematische Reviews auf zusätzliche Literaturverweise. Insgesamt wurden 357 Publikationen identifiziert. Nach Entfernung von Duplikaten (n = 15) wurden n = 327 Publikationen bewertet. In der vertiefenden Literaturanalyse wurde schlussendlich eine relevante Studie identifiziert und in die Evidenzbewertung eingeschlossen. Lokalanästhetikainfiltrationen stellen eine Therapieoption von Neuropathien nach Amputationen dar. Ein RCT (Randomisierte kontrollierte Studie) zeigte über 4 Wochen nach mehrtägiger perineuraler Lokalanästhetikainfiltration eine Reduktion von Schmerzen und schmerzbedingter Funktionseinschränkung. Weitere Studien sind erforderlich, um einen höheren Evidenzgrad zur Effektivität dieser Therapieform ableiten zu können.

BACKGROUND:Chronic pain is still a relevant medical and socioeconomic problem. The treatment focuses not only on pain reduction but also on functional treatment goals. Neuropathic pain includes biological, social and psychological aspects. In September 2023, the updated S3 guidelines for the management of peripheral nerve injuries were published. Multimodal pain management strategies encompassing systemic and local pharmacological, physiotherapeutic and occupational therapeutic interventions, are part of the guidelines. A central question addressed the widely debated treatment option using perineural local anaesthetics. OBJECTIVE:The aim of the study was to evaluate the effectiveness of local anaesthetic infiltration in the treatment of neuropathic pain following nerve injuries through a systematic literature review and evaluation of the evidence by a meta-analysis. MATERIAL AND METHODS:After formulating a PICO (patient/population, intervention, comparison and outcomes) question (Infobox 1) within the guideline group, a selective literature analysis of controlled trials in databases (PubMed, Cochrane Central Register of Controlled Trials-CENTRAL) was conducted until 31 July 2023. The literature was assessed by two reviewers and systematic reviews were examined for additional references. The studies were assessed using the Risk of Bias Tool 2.0 of the Cochrane Collaboration for randomized trials and the evidence was classified according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. RESULTS:A total of 357 publications were identified in the literature search. After removing duplicates (n = 15) 327 publications were evaluated. The literature analysis showed heterogeneity with respect to the pain localization, local anaesthetics and reported outcomes. In an in-depth literature analysis one relevant study was identified and included in the evaluation of the evidence. This study enrolled and randomized 144 patients between December 2013 and October 2018 and evaluated the effectivity of the continuous infusion of local anaesthetics (lidocaine 2% with epinephrine 2.5 µg/ml as an initial bolus in both study groups followed by an infusion of ropivacaine 0.5% in the intervention group over 6 days) on the intensity of the phantom pain in comparison to the placebo group with a continuous infusion of saline over 6 days. The mean pain intensity and pain-related dysfunctions were reduced in the intervention group after 4 weeks. In the intervention group 25 patients and in the placebo group 40 patients received the crossover treatment after 4 weeks. CONCLUSION:Infiltration with local anaesthetics represents a potential therapeutic option for neuropathic pain and phantom pain after amputations. A randomized, blinded, placebo-controlled study from 2021 demonstrated lower pain intensity and a reduction in pain-related functional limitations after 4 weeks of continuous perineural local anesthetic infiltration. Further studies are necessary to establish a higher level of evidence regarding the effectiveness of minimally invasive pain treatment with local anaesthetics. In particular, long-term follow-up is necessary to be able to draw conclusions with respect to the analgesic efficacy of infiltration with local anaesthetics.

BACKGROUND:Nerve lesions often heal incompletely, leading to lifelong functional impairment and high costs for the health care system. The updated German clinical practice guideline is intended to promote the early recognition of nerve lesions and the timely initiation of proper treatment for optimal restoration of function. METHODS:The recommendations are based on an assessment of all the evidence revealed by a systematic search of the literature, as well as on the expertise of the multiprofessional guideline group. RESULTS:Only a few publications contain high-quality evidence. This version of the guideline contains a more detailed discussion of war injuries, iatrogenic injuries, MR neurography, and specific treatments than the previous version. As for the different methods of nerve replacement, a comparison of autologous transplantation versus the use of conduits and tubes revealed no significant difference between these two methods on the mBMRC scale, and minimal superiority of autologous transplantation with respect to two-point discrimination. As for the use of nerve transfers when nerve reconstruction is not feasible or unlikely to succeed, nerve transfer yielded slightly better results than proximal reconstruction for elbow flexion, but the difference did not reach statistical significance (mBMRC ≥ 3: RR 1.16, 95% confidence interval [1.02; 1.32]). The treatment of neuromas with targeted muscle reinnervation was superior to the classic approach in decreasing both stump pain (MD 2.0 +/- 2.8) and phantom limb pain (MD 3.4 +/- 4.03). CONCLUSION:The delayed or improper treatment of peripheral nerve lesions can lead to severe impairment. Timely diagnosis, the use of appropriate treatments in conformity with the guidelines, and interdisciplinary collaboration among specialists are all essential for optimizing the outcome.

Background: Nerve lesions often heal incompletely, leading to lifelong functional impairment and high costs for the health care system. The updated German clinical practice guideline is intended to promote the early recognition of nerve lesions and the timely initiation of proper treatment for optimal restoration of function. Methods: The recommendations are based on an assessment of all the evidence revealed by a systematic search of the literature, as well as on the expertise of the multiprofessional guideline group. Results: Only a few publications contain high-quality evidence. This version of the guideline contains a more detailed discussion of war injuries, iatrogenic injuries, MR neurography, and specific treatments than the previous version. As for the different methods of nerve replacement, a comparison of autologous transplantation versus the use of conduits and tubes revealed no significant difference between these two methods on the mBMRC scale, and minimal superiority of autologous transplantation with respect to two-point discrimination. As for the use of nerve transfers when nerve reconstruction is not feasible or unlikely to succeed, nerve transfer yielded slightly better results than proximal reconstruction for elbow flexion, but the difference did not reach statistical significance (mBMRC >= 3: RR 1.16, 95% confidence interval [1.02; 1.32]). The treatment of neuromas with targeted muscle reinnervation was superior to the classic approach in decreasing both stump pain (MD 2.0 +/- 2.8) and phantom limb pain (MD 3.4 +/- 4.03). Conclusion: The delayed or improper treatment of peripheral nerve lesions can lead to severe impairment. Timely diagnosis, the use of appropriate treatments in conformity with the guidelines, and interdisciplinary collaboration among specialists are all essential for optimizing the outcome.

BackgroundThe use of decompressive craniectomy in traumatic brain injury (TBI) remains a matter of debate. According to the DECRA trial, craniectomy may have a negative impact on functional outcome, while the RescueICP trial revealed a positive effect of surgical decompression, which is evolving over time. This ambivalence of craniectomy has not been studied extensively in controlled laboratory experiments.ObjectiveThe goal of the current study was to investigate the prolonged effects of decompressive craniectomy (both positive and negative) in an animal model.MethodsMale mice were assigned to the following groups: sham, decompressive craniectomy, TBI and TBI followed by craniectomy. The analysis of functional outcome was performed at time points 3d, 7d, 14d and 28d post trauma according to the Neurological Severity Score and Beam Balance Score. At the same time points, magnetic resonance imaging was performed, and brain edema was analyzed.ResultsAnimals subjected to both trauma and craniectomy presented the exacerbation of the neurological impairment that was apparent mostly in the early course (up to 7d) after injury. Decompressive craniectomy also caused a significant increase in brain edema volume (initially cytotoxic with a secondary shift to vasogenic edema and gliosis). Notably, delayed edema plus gliosis appeared also after decompression even without preceding trauma.ConclusionIn prolonged outcomes, craniectomy applied after closed head injury in mice aggravates posttraumatic brain edema, leading to additional functional impairment. This effect is, however, transient. Treatment options that reduce brain swelling after decompression may accelerate neurological recovery and should be explored in future experiments.

The in-vivo optical imaging of the cortical surface provides the ability to record different types of biophysiological signals, e.g., structural information, intrinsic signals, like blood oxygenation coupled reflection changes as well as extrinsic properties of voltage sensitive probes, like fluorescent voltage-sensitive dyes. The recorded data sets have very high temporal and spatial resolutions on a meso- to macroscopic scale, which surpass conventional multi-electrode recordings. Both, intrinsic and functional data sets, each provide unique information about temporal and spatial dynamics of cortical functioning, yet have individual drawbacks. To optimize the informational value it would thus be opportune to combine different types of optical imaging in a near simultaneous recording.Due to the low signal-to-noise ratio of voltage-sensitive dyes it is necessary to reduce stray light pollution below the level of the camera's dark noise. It is thus impossible to record full-spectrum optical data sets. We address this problem by a time-multiplexed illumination, bespoke to the utilized voltage sensitive dye, to record an alternating series of intrinsic and extrinsic frames by a high-frequency CMOS sensor. These near simultaneous data series can be used to compare the mutual influence of intrinsic and extrinsic dynamics (with regards to extracorporeal functional imaging) as well as for motion compensation and thus for minimizing frame averaging, which in turn results in increased spatial precision of functional data and in a reduction of necessary experimental data sets (3R principle).

Introduction Traumatic and non-traumatic spinal cord injury bears a high risk for thromboembolism in the first few months after injury. So far, there is no consented guideline regarding diagnostic and prophylactic measures to prevent thromboembolic events in spinal cord injury. Based on a Pubmed research of related original papers and review articles, international guidelines and a survey conducted in German-speaking spinal cord injury centers about best practice prophylactic procedures at each site, a consensus process was initiated, which included spinal cord medicine experts and representatives from medical societies involved in the comprehensive care of spinal cord injury patients. The recommendations comply with the German S3 practice guidelines on prevention of venous thromboembolism. Recommendations Specific clinical or instrument-based screening methods are not recommended in asymptomatic SCI patients. Based on the severity of neurological dysfunction (motor completeness, ambulatory function) low dose low molecular weight heparins are recommended to be administered up to 24 weeks after injury. Besides, mechanical methods (compression stockings, intermittent pneumatic compression) can be applied. In chronic SCI patients admitted to the hospital, thromboembolism prophylactic measures need to be based on the reason for admission and the necessity for immobilization. Conclusions Recommendations for thromboembolism diagnostic and prophylactic measures follow best practice in most spinal cord injury centers. More research evidence needs to be generated to administer more individually tailored risk-adapted prophylactic strategies in the future, which may help to further prevent thromboembolic events without causing major side effects. The present article is a translation of the guideline recently published online ( https://www.awmf.org/uploads/tx_szleitlinien/179-015l_S1_Thromboembolieprophylaxe-bei-Querschnittlaehmung_2020-09.pdf ).

We seek to understand the relation between invasive high-resolution data and non-invasive measurement in an animal model in an auditory sensory adaptation experimental setting. In a previous study, we estimated the mutual information between the phase of auditory evoked responses (AER) with the phase of local field potentials (LFP) of auditory cortices at different frequency ranges. The results showed a consistently high level of information sharing between the AER activities as well as the responses from the granular layer, which was known as the main thalamo-recipient layer. However, mutual information was fundamentally an undirected measure of information flow. In this study we investigated how well we could characterize direction of information flow, by using Granger causality (GC), between different cortical laminae and functional projections on to the AER activities. We obtained that based on the GC coefficients, we are able to extract the connectivity between different cortical laminae to some extend and also a strong connection between the AER and granular layer. In our future study, we would like to construct a reliable picture of network connectivity, both functionally and anatomically, between different layers at more specified frequencies and much finer temporal resolutions.

Zusammenfassung. Exekutive Dysfunktionen treten besonders bei Erkrankungen, die zu einer Schadigung des prafrontalen und/oder orbitofrontalen Kortex oder subkortikaler Strukturen (insbesondere des ...

Intracranial, functional optical imaging (OI) of intrinsic signals (like blood oxygenation coupled reflection changes) and of extrinsic properties of voltage sensitive probes (like voltage-sensitive dyes) belongs to a group of invasive neuroimaging techniques with very high temporal and spatial resolutions on a meso-to macroscopic scale. Voltage sensitive dye imaging (VSDI) images brain activity with low temporal delays, but the raw signal has a poor signal to noise ratio. An important pre-processing step for many biomedical imaging techniques is image registration and motion compensation. We can apply motion compensation successfully for optical imaging of intrinsic signals but VSDI recordings have low spatial contrast and often do not contain fine grained texture details which are crucial for successful image based motion compensation. In this work, we design a semi-synthetic dataset based on real recordings and a dummy voltage sensitive dye response for the evaluation of advanced motion compensation strategies for VSDI. This dataset aims to be used as a benchmark for the development of novel motion compensation strategies for VSDI and to derive error bounds of the methodologies with respect to motion.

BACKGROUND: Entrapment neuropathies include a wide field of locations. In most cases, the microsurgical decompression is still the therapy of choice. However, the role of venous stasis and ischemia is still discussed controversially. Here the authors evaluated the visualization of microvessels and the microperfusion at peripheral nerves with a contact endoscope during the surgical decompression for the first time. METHODS: Eight patients were subjected to endoscopic or endoscopically assisted peripheral nerve decompression. In 3 patients with nerve tumors, the tumor carrying nerve was inspected endoscopically proximal and distal to the tumor site before and after resection. Microcirculation was assessed by a contact endoscope, allowing a 150-fold magnification, at superficial areas proximal and distal to the compression site. The electronically stored records were analyzed retrospectively using image processing software. Vessel diameter, red blood cell velocity, and blood flow, before and after decompression, were extracted. RESULTS: The contact endoscope was easy to handle intraoperatively without problems. All minimally invasive procedures were performed without complications. In the offline computer-assisted analysis, single arterioles and veins were visualized showing decreased red blood cell velocity prior to decompression. After surgical treatment, a statistically significant increase of blood flow was observed. CONCLUSIONS: Basically, the application of a contact endoscope for visualization of peripheral nerves' microcirculation is feasible. The observed effect of increased blood flow after decompression should be compared with the clinical outcome in a further prospective randomized study.

Acetazolamide (ACZ), carbonic anhydrase inhibitor, has been successfully applied in several neurosurgical conditions for diagnostic or therapeutic purposes. Furthermore, neuroprotective and anti-edematous properties of ACZ have been postulated. However, its use in traumatic brain injury (TBI) is limited, since ACZ-caused vasodilatation according to the Monro-Kellie doctrine may lead to increased intracranial blood volume / raise of intracranial pressure. We hypothesized that these negative effects of ACZ will be reduced or prevented, if the drug is administered after already performed decompression. To test this hypothesis, we used a mouse model of closed head injury (CHI) and decompressive craniectomy (DC). Mice were assigned into following experimental groups: sham, DC, CHI, CHI+ACZ, CHI+DC, and CHI+DC+ACZ (n = 8 each group). 1d and 3d post injury, the neurological function was assessed according to Neurological Severity Score (NSS) and Beam Balance Score (BBS). At the same time points, brain edema was quantified by MRI investigations. Functional impairment and edema volume were compared between groups and over time. Among the animals without skull decompression, the group additionally treated with acetazolamide demonstrated the most severe functional impairment. This pattern was reversed among the mice with decompressive craniectomy: CHI+DC treated but not CHI+DC+ACZ treated animals showed a significant neurological deficit. Accordingly, radiological assessment revealed most severe edema formation in the CHI+DC group while in CHI+DC+ACZ animals, volume of brain edema did not differ from DC-only animals. In our CHI model, the response to acetazolamide treatment varies between animals with decompressive craniectomy and those without surgical treatment. Opening the cranial vault potentially creates an opportunity for acetazolamide to exert its beneficial effects while vasodilatation-related risks are attenuated. Therefore, we recommend further exploration of this potentially beneficial drug in translational research projects.

Supratentorial hematoma is the most common mass lesion found in traumatic brain injury (TBI) and is associated with high mortality and disability rates.The annual incidence of the aforementioned is 20 cases per 100,000 populations.

Study Design. Level 3, cohort study. Objective. The aim of this study was to assess long-term clinical outcome, and rate of reoperation following microsurgical subtotal discectomy (MSD). Summary of Background Data. Lumbar disc herniation (LDH) is a common cause of discomfort. Studies with >25 years of follow-up are rare and the reported rate of clinical success and reoperation are not well understood. Methods. Retrospectively, files with complete documentation of preoperative and postoperative neurological status, process during hospitalization, detailed report of MSD, outpatient visit notes, and full contact information of patients who underwent MSD for the treatment of LDH with a minimum follow-up of 25 years were reviewed. Patients were contacted for personal follow-up assessment which included Oswestry Disability Index (ODI), EQ-5D, and MacNab criteria, usage of pain medication for leg and back pain, limitations in daily life, and repeated procedures at the lumbar spine. Results. A total of 355 patients were randomly selected and contacted for final follow-up and 158 patients with a mean follow-up 32 years participated in the study. Clinical success rate was 86.0%, mean ODI was 9% (0–58%), 69.6% of the patients were pain free, 13.9% of patients reported the daily intake of pain medication for back and leg pain. Reoperations were performed in 47 of the patients (29.7%), whereas the rate for recurrent disc herniation at the same level was 8.2%. Reoperation within the first 2 years after initial MSD had negative influence on clinical success. The preoperative physical working status and sex and working status had no influence on the clinical success. Conclusion. The MSD is an effective technique to achieve a high rate of patient satisfaction, and high rate of functional recovery. The overall reoperation rate is 30% within 30 years but only 8.2% of the patients underwent reoperation because of recurrent disc herniation at the same level. Level of Evidence: 3

Both hypothermia and decompressive craniectomy have been considered as a treatment for traumatic brain injury. In previous experiments we established a murine model of decompressive craniectomy and we presented attenuated edema formation due to focal brain cooling. Since edema development is regulated via function of water channel proteins, our hypothesis was that the effects of decompressive craniectomy and of hypothermia are associated with a change in aquaporin-4 (AQP4) concentration. Male CD-1 mice were assigned into following groups (n = 5): sham, decompressive craniectomy, trauma, trauma followed by decompressive craniectomy and trauma + decompressive craniectomy followed by focal hypothermia. After 24 h, magnetic resonance imaging with volumetric evaluation of edema and contusion were performed, followed by ELISA analysis of AQP4 concentration in brain homogenates. Additional histopathological analysis of AQP4 immunoreactivity has been performed at more remote time point of 28d. Correlation analysis revealed a relationship between AQP4 level and both volume of edema (r 2 = 0.45, p < 0.01, **) and contusion (r 2 = 0.41, p < 0.01, **) 24 h after injury. Aggregated analysis of AQP4 level (mean ± SEM) presented increased AQP4 concentration in animals subjected to trauma and decompressive craniectomy (52.1 ± 5.2 pg/mL, p = 0.01; *), but not to trauma, decompressive craniectomy and hypothermia (45.3 ± 3.6 pg/mL, p > 0.05; ns) as compared with animals subjected to decompressive craniectomy only (32.8 ± 2.4 pg/mL). However, semiquantitative histopathological analysis at remote time point revealed no significant difference in AQP4 immunoreactivity across the experimental groups. This suggests that AQP4 is involved in early stages of brain edema formation after surgical decompression. The protective effect of selective brain cooling may be related to change in AQP4 response after decompressive craniectomy. The therapeutic potential of this interaction should be further explored.