Development and maintenance of posture is essential behavior for overground mammalian locomotion. Dopamine and noradrenaline strongly influence locomotion, and their dysregulation initiates the development of motor impairments linked to neurodegenerative disease. However, the precise cellular and circuit mechanisms are not well defined. Here, we investigated the role of catecholaminergic neuromodulation in a mouse model of spinal muscular atrophy (SMA). SMA is characterized by severe motor dysfunction and postural deficits. We identify progressive loss of catecholaminergic synapses from spinal neurons that occur via non-cell autonomous mechanisms. Importantly, the selective restoration of survival motor neuron (SMN) in either catecholaminergic or serotonergic neurons is sufficient to correct impairments in locomotion. However, only combined SMN restoration in both catecholaminergic and serotonergic neurons or pharmacological treatment with l-dopa improve the severe postural deficits. These findings uncover the synaptic and cellular mechanisms responsible for the postural and motor symptoms in SMA and identify catecholaminergic neuromodulation as a potential therapeutic target.

Abstract Purpose To investigate whether and how extra‐synovial autografts can enhance the reconstruction of chronic and large rotator cuff tears in a rabbit subscapularis model. Methods Twenty rabbits were used to create a large subscapularis tear bilaterally. Six weeks later, the right shoulder of each rabbit was operated to repair the tear with an extra‐synovial autograft, whereas the left shoulder did not undergo any surgery. At 6 and 12 weeks after the second procedure, the specimens underwent biomechanical and histological evaluation. Six more rabbits were used only as a normal reference. Results Biomechanical evaluation demonstrated that the ultimate load to failure of the Graft group (184.1 ± 35.7 N) was significantly higher (p = 0.04) than that of the Defect group (144.5 ± 32.2 N) at 12 weeks after repair, rising to 76% of the normal subscapularis tendon tensile strength. Histological analysis revealed an enhanced healing environment with neoangiogenesis and decreased inflammatory response at the repair site. Moreover, the tendon maturing score of the Graft group increased substantially from 6 (15.8 ± 0.9) to 12 (23.1 ± 0.6) weeks after repair (p = 0.01). Conclusion In vivo data support the efficacy of extra‐synovial autograft interposition in repairing chronic and large rotator cuff tears in a rabbit subscapularis model. The autografts were capable of enhancing the biomechanical properties of the repaired tendons, as evidenced by increased tensile strength, and forming new connective tissue simulating a fibrocartilage zone, as revealed by histological evaluation. Level of Evidence N/A.

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by deficiency of the survival motor neuron (SMN) protein. Although SMA is a genetic disease, environmental factors contribute to disease progression. Common pathogen components such as lipopolysaccharides (LPS) are considered significant contributors to inflammation and have been associated with muscle atrophy, which is considered a hallmark of SMA. In this study, we used the SMNΔ7 experimental mouse model of SMA to scrutinize the effect of systemic LPS administration, a strong pro-inflammatory stimulus, on disease outcome. Systemic LPS administration promoted a reduction in SMN expression levels in CNS, peripheral lymphoid organs, and skeletal muscles. Moreover, peripheral tissues were more vulnerable to LPS-induced damage compared to CNS tissues. Furthermore, systemic LPS administration resulted in a profound increase in microglia and astrocytes with reactive phenotypes in the CNS of SMNΔ7 mice. In conclusion, we hereby show for the first time that systemic LPS administration, although it may not precipitate alterations in terms of deficits of motor functions in a mouse model of SMA, it may, however, lead to a reduction in the SMN protein expression levels in the skeletal muscles and the CNS, thus promoting synapse damage and glial cells’ reactive phenotype.

Background: Functional magnetic resonance imaging (fMRI) is a valuable tool for the presurgical evaluation of patients undergoing neurosurgeries. Although many pre-processing steps have been modified according to advances in recent years, statistical analysis has remained largely the same since the first days of fMRI. In this study, we examined the ability of Independent Component Analysis (ICA) to separate the activation of a language task in fMRI, and we compared it with the results of the General Lineal Model (GLM). Methods: Sixty patients undergoing evaluation for brain surgery due to various brain lesions and/or epilepsy and 20 control subjects completed an fMRI language mapping protocol that included three tasks, resulting in 259 fMRI scans. Depending on brain lesion characteristics, patients were allocated to (1) static/chronic not-expanding lesions (Group 1) and (2) progressive/expanding lesions (Group 2). GLM and ICA statistical maps were evaluated by fMRI experts to assess the performance of each technique. Results: In the control group, ICA and GLM maps were similar without any superiority of either technique. In Group 1 and Group 2, ICA performed statistically better than GLM, with a p-value of < 0.01801 and < 0.0237, respectively. This indicated that ICA performs as well as GLM when the subjects are able to cooperate well (less movement, good task performance), but ICA could outperform GLM in the patient groups. When both techniques were combined, 240 out of 259 scans produced reliable results, showing that the sensitivity of task-based fMRI can be increased when both techniques are integrated with the clinical setup. Conclusion: ICA may be slightly more advantageous, compared to GLM, in patients with brain lesions, across the range of pathologies included in our population and independent of symptoms chronicity. Our findings suggest that GLM analysis may be more susceptible to brain activity perturbations induced by a variety of lesions or scanner-induced artifacts due to motion or other factors. In our research, we demonstrated that ICA is able to provide fMRI results that can be used in surgery, taking into account patient and task-wise aspects that differ from those when fMRI is used in research.

Diffusion tensor imaging (DTI)-tractography and functional magnetic resonance imaging (fMRI) have dynamically entered the presurgical evaluation context of brain surgery during the past decades, providing novel perspectives in surgical planning and lesion access approaches. However, their application in the presurgical setting requires significant time and effort and increased costs, thereby raising questions regarding efficiency and best use. In this work, we set out to evaluate DTI-tractography and combined fMRI/DTI-tractography during intra-operative neuronavigation in resective brain surgery using lesion-related preoperative neurological deficit (PND) outcomes as metrics. We retrospectively reviewed medical records of 252 consecutive patients admitted for brain surgery. Standard anatomical neuroimaging protocols were performed in 127 patients, 69 patients had additional DTI-tractography, and 56 had combined DTI-tractography/fMRI. fMRI procedures involved language, motor, somatic sensory, sensorimotor and visual mapping. DTI-tractography involved fiber tracking of the motor, sensory, language and visual pathways. At 1 month postoperatively, DTI-tractography patients were more likely to present either improvement or preservation of PNDs (p = 0.004 and p = 0.007, respectively). At 6 months, combined DTI-tractography/fMRI patients were more likely to experience complete PND resolution (p < 0.001). Low-grade lesion patients (N = 102) with combined DTI-tractography/fMRI were more likely to experience complete resolution of PNDs at 1 and 6 months (p = 0.001 and p < 0.001, respectively). High-grade lesion patients (N = 140) with combined DTI-tractography/fMRI were more likely to have PNDs resolved at 6 months (p = 0.005). Patients with motor symptoms (N = 80) were more likely to experience complete remission of PNDs at 6 months with DTI-tractography or combined DTI-tractography/fMRI (p = 0.008 and p = 0.004, respectively), without significant difference between the two imaging protocols (p = 1). Patients with sensory symptoms (N = 44) were more likely to experience complete PND remission at 6 months with combined DTI-tractography/fMRI (p = 0.004). The intraoperative neuroimaging modality did not have a significant effect in patients with preoperative seizures (N = 47). Lack of PND worsening was observed at 6 month follow-up in patients with combined DTI-tractography/fMRI. Our results strongly support the combined use of DTI-tractography and fMRI in patients undergoing resective brain surgery for improving their postoperative clinical profile.

Hypoxic ischemic (HI) brain injury that occurs during neonatal period has been correlated with severe neuronal damage, behavioral deficits and infant mortality. Previous evidence indicates that N-acetylcysteine (NAC), a compound with antioxidant action, exerts a potential neuroprotective effect in various neurological disorders including injury induced by brain ischemia. The aim of the present study was to investigate the role of NAC as a potential therapeutic agent in a rat model of neonatal HI brain injury and explore its long-term behavioral effects. To this end, NAC (50 mg/kg/dose, i.p.) was administered prior to and instantly after HI, in order to evaluate hippocampal and cerebral cortex damage as well as long-term functional outcome. Immunohistochemistry was used to detect inducible nitric oxide synthase (iNOS) expression. The results revealed that NAC significantly alleviated sensorimotor deficits and this effect was maintained up to adulthood. These improvements in functional outcome were associated with a significant decrease in the severity of brain damage. Moreover, NAC decreased the short-term expression of iNOS, a finding implying that iNOS activity may be suppressed and that through this action NAC may exert its therapeutic action against neonatal HI brain injury.

BACKGROUND:Patients on antithrombotics experiencing mild traumatic brain injury (mTBI) may benefit from a routine repeat CT scan to detect delayed intracranial hemorrhage (dICH).OBJECTIVES:The primary outcome was the incidence of dICH on routine repeat CT scans of mTBI patients on antithrombotics within an intra-hospital observation period of up to 48 hours. The secondary outcomes were potential risk factors, readmissions, neurosurgical interventions, and mortality.METHODS:A systematic review and a meta-analysis of single proportions were performed according to the PRISMA and PRESS guidelines. The risk of bias was assessed using Newcastle-Ottawa Scale.RESULTS:Eighteen studies with 4613 patients were included. The pooled incidence of dICH was 2% [95% CI 1-2%] with similar rates between different antithrombotic regimens, even in combination. Of the 67 patients with dICH reported (1.45%), eleven required surgery (0.24%), while six died (0.13%). Loss of consciousness was a risk factor of dICH (risk ratio 3.04 [95%CI 0.96; 9.58]). A total of 48 patients were reported for readmission without associated death or surgical intervention.CONCLUSION:The contribution of this routine repeat CT scan should be questioned due to the low incidence, the limited clinical significance, and the unsubstantiated clinical benefit of early or systematic detection of dICH.

Background and Purpose— Acute stroke treatment is challenging, and stroke remains a major cause of death and disability. The purpose of this meta-analysis is to investigate the effects of postacute stroke intravenous administration of the neuroprotectant magnesium sulfate (MgSO 4 ) on global outcome, functional outcome, and mortality 90 days poststroke (ischemic and nonischemic). Methods— We searched in Pubmed, Science Direct, CENTRAL, and ClinicalTrials.gov, up to November 11, 2017, and we conducted a systematic review and meta-analysis of randomized controlled trials. We synthesized results by using random-effects model, weighted mean differences, standardized mean differences, and odds ratios. Results— Seven randomized controlled trials (4347 patients) met our criteria. Compared with placebo, treatment did not improve functional outcome defined as Barthel Index >60 (odds ratio =1.05; 95% CI, 0.92–1.19) and >95 (odds ratio =0.95; 95% CI, 0.76–1.20), 90 days poststroke. It also did not improve global outcome measured with modified Rankin Scale (standardized mean difference =−0.01; 95% CI, −0.12 to 0.10), 90 days poststroke. In an additional subgroup meta-analysis that exclusively included ischemic stroke patients, intravenous MgSO 4 resulted in lower modified Rankin Scale score (improved global outcome; weighted mean difference =−0.96; 95% CI, −1.34 to −0.58; I 2 =0%], 90 days poststroke. Finally, mortality stayed unaltered (odds ratio =1.10; 95% CI, 0.94–1.29). Conclusions— The findings of our meta-analysis showed that intravenous MgSO 4 generally did not improve global/functional outcomes and mortality at 90 days after stroke (combined ischemic stroke and nonischemic stroke). The finding of favorable neurological outcome, selectively in ischemic stroke patients, should be viewed with extreme caution given the limited number of patients included in this subgroup meta-analysis.

Background and Purpose-Acute stroke treatment is challenging, and stroke remains a major cause of death and disability. The purpose of this meta-analysis is to investigate the effects of postacute stroke intravenous administration of the neuroprotectant magnesium sulfate (MgSO4) on global outcome, functional outcome, and mortality 90 days poststroke (ischemic and nonischemic). Methods-We searched in Pubmed, Science Direct, CENTRAL, and ClinicalTrials.gov, up to November 11, 2017, and we conducted a systematic review and meta-analysis of randomized controlled trials. We synthesized results by using random-effects model, weighted mean differences, standardized mean differences, and odds ratios. Results-Seven randomized controlled trials (4347 patients) met our criteria. Compared with placebo, treatment did not improve functional outcome defined as Barthel Index >60 (odds ratio =1.05; 95% CI, 0.92-1.19) and >95 (odds ratio =0.95; 95% CI, 0.76-1.20), 90 days poststroke. It also did not improve global outcome measured with modified Rankin Scale (standardized mean difference =-0.01; 95% CI, -0.12 to 0.10), 90 days poststroke. In an additional subgroup meta-analysis that exclusively included ischemic stroke patients, intravenous MgSO4 resulted in lower modified Rankin Scale score (improved global outcome; weighted mean difference =-0.96; 95% CI, -1.34 to -0.58; I-2=0%], 90 days poststroke. Finally, mortality stayed unaltered (odds ratio = 1.10; 95% CI, 0.94-1.29). Conclusions-The findings of our meta-analysis showed that intravenous MgSO4 generally did not improve global/functional outcomes and mortality at 90 days after stroke (combined ischemic stroke and nonischemic stroke). The finding of favorable neurological outcome, selectively in ischemic stroke patients, should be viewed with extreme caution given the limited number of patients included in this subgroup meta-analysis.

Introduction-Aim: Newer methods, such as infrared digital pupillometry and electrodermal activity (EDA) measurement have been suggested as good alternatives for analgesia monitoring in critically ill patients. This study analyzed EDA changes due to pain stimulus in sedated adult critical care patients Methods: Skin conductance variability, selected hemodynamic and respiratory parameters, Bispectral index (BIS) and ambient noise level, were monitored during 4 hour routine daytime in an adult ICU. 4h-Measurements were divided into 2 groups, based upon the sedation level of the patients: Group A – Ramsay Sedation Score 2–4 and Group B – Ramsay Sedation Score of 5–6. Selected recordings before and after pain stimulus were performed. The stimulus chosen was the pressure applied to nail bed for 10 sec, which was performed routinely during neurological examination. Patients’ demographics, laboratory exams and severity scores were recorded. Pain status evaluation before every event was also performed by 2 independent observers via Critical Care Pain Observation Tool (CPOT) and Adult Non Verbal Pain Score (ANVPS) Results: In both groups the rate of EDA changes was greater than other monitoring parameters: more in Group A than in Group B. Yet, the difference between groups was not statistically significant. Conclusion: EDA measurements are greater to pain stimuli, than cardiovascular, respiratory or even BIS monitoring. These encouraging results suggest that, further studies are needed to better define EDA role in ICU.

Electrodermal activity (EDA) is considered a measure of autonomous nervous system activity. This study performed an exploratory analysis of the EDA changes during blood pooling for arterial blood gas analysis in sedated adult critical care patients and correlated the variations to other monitored parameters. EDA, along with other parameters, were monitored during 4 h routine daytime intensive care nursing and treatment in an adult ICU. 4 h measurements were divided into two groups based upon the sedation level. Selected recordings before and after blood pooling for arterial blood gases analysis (stress event) was performed. Nine stress events from Group A and 17 from Group B were included for further analysis. Patients' demographics, laboratory exams, and severity scores were recorded. For both sedation levels, EDA changes are much greater than any other monitoring parameters used. The changes are noticed in both measurement (15 s and 60 s), even though in the 60 s measurement only selected EDA parameters are significantly changed after the start of the procedure. EDA measurements are more sensitive to a given stress event than cardiovascular or respiratory parameters. However, the present results could only be considered as a pilot study. More studies are needed in order to identify the real stress-load and clinical significance of such stimuli, which are considered otherwise painless in those patients.

Abstract Background: Endotracheal suctioning of respiratory secretions is one of the most common causes of pain and discomfort in Intensive Care Unit environment. The electrical properties of the skin, also known as electrodermal activity (EDA), are considered as an indirect measure of autonomous nervous system. Aim: This study explores EDA changes during endotracheal suction in sedated adult critical care patients; and compares these changes to other monitoring parameters. Materials and methods: Skin conductance variability, selected hemodynamic and respiratory parameters, bispectral index (BIS) and ambient noise level, were monitored during 4 hour routine daytime intensive care nursing and treatment in an adult Intensive Care Unit. 4h-measurements were divided into 2 groups, based upon the sedation level (group A: Ramsay sedation scale 2-4 and group B: 5-6 respectively) of the patients. Selected recordings before and after endotracheal suction (stress events) were performed. Seven stress events from Group A and 17 from Group B were included for further analysis. Patients’ demographics, laboratory exams and severity scores were recorded. Pain status evaluation before every event was also performed via 2 independent observers. Results: In both groups the rate of EDA changes was greater than in other monitoring parameters. Yet, in group A only selected parameters were significantly changed after the start of the procedure, while in group B, every parameter showed significant change (p<0.05). Groups were similar for other co-founding factors. Conclusion: EDA measurements are more sensitive to stress stimuli, than cardiovascular, respiratory or even BIS monitoring. Deeper sedation seems to affect more the intensity of EDA changes during suction.

Editor, In recognition of the rarity of metastatic melanomas in the brain of the morphological variant of the balloon‐cell type,[1‐3] we report a new case of balloon cell melanoma (BCM) metastatic to the convexity of the left temporal lobe. A 54‐year‐old male presented with difficulty in speech comprehension. Νeurological examination disclosed mild sensory dysphasia, with no other localizing signs. Neuroimaging revealed a space‐occupying lesion of the left temporal lobe, showing strong enhancement with gadolinium in T1‐weighted images [Figure 1]. The patient was subjected to a left temporal craniotomy and total resection of the lesion, which was clearly visible in the cortex and with no connection to the meninges. Histopathological examination revealed diffuse infiltration of the brain tissue by large, tightly packed, pale neoplastic cells, occasionally of giant size, with an abundant, clear, foamy cytoplasm and relatively uniform nuclei with minimal‐to‐mild atypia, and few mitoses [Figure 2a and b]. These characteristic balloon cells were amelanotic. The neoplasm was arranged in a solid pattern infiltrating the brain matter. Immunohistochemically, the tumor cells were positive for Vimentin, S100, Melan‐A, and HMB‐45 [Figure 2c and d], but negative for cytokeratins AE1/AE3 and 8/18, PAX8, calretinin, and synaptophysin. The medical history of the patient included a surgically excised cutaneous melanoma without BCM features. He was initially subjected to resection of a lesion in the left forearm with complementary lymph node dissection in the left axilla. Metastasis was then

Total disc replacement (TDR) is widely used as alternative treatment to fusion for symptomatic cervical disc degenerative diseases. Its advantages (ie, functional improvement, preservation of motion and possibly protection of the adjacent segment) are supported by literature data. The influence of the size of prosthesis on surgical outcomes has been less studied and we could not find any data on its correlation with preoperative disc height.

Background: Massive rotator cuff tear repair is frequently complicated by unsatisfactory clinical results due to possible tendon retraction, muscle atrophy, and fatty degeneration. The objective of this study was the development of a chronic massive tear in a rat model and the evaluation of the muscle force in vivo and of the histologic changes in a 3-dimensional manner.Methods: To simulate massive rotator cuff tears, both the supraspinatus (SS) and the infraspinatus (IS) tendons were surgically detached from the right humerus of 15 male adult Sprague-Dawley rats. Twelve weeks postoperatively, all animals underwent isometric tension recordings of both the SS and IS muscles. Histologic analysis and image deconvolution processing were performed to estimate the presence and the distribution of atrophy in 3 dimensions.Results: An overall 30% and 35% reduction in muscle force of the SS and IS muscles, respectively, was observed compared with the left uninjured shoulder (P < .005). Histologic analysis revealed that the degeneration and the fatty infiltration were more evident near the tendon and at the dorsal side in both muscle groups.Conclusions: These results show that functional impairment of SS and IS muscles after chronic massive tendon tears could be attributed to the decrease in muscle force production during their repair on the greater tuberosity and, second, to the comparatively greater degeneration of their dorsal part. (C) 2014 Journal of Shoulder and Elbow Surgery Board of Trustees.

We studied pain, neurological, and functional outcomes of one and two-levels cervical arthroplasties using a semi-constrained prosthesis for symptomatic cervical degenerative discopathies. Retrospective analysis of 95 patients in a multicentric registry over 2 years FU. Implant-related complications, subsequent surgery and neurological deterioration were not observed. After two years, improvement of > 20% of the NDI was observed in 81.8%, of > 20% of the neck pain in 75.5% and of 20% in arm pain in 77.6%. A > 15% QOL improvement (SF 36 questionnaire) was recorded in 76.5% (physical) and in 77,6% (mental). Greater benefits of cervical arthroplasty were observed in patients under 50 without previous surgeries and with preoperative NDI > 30%, confirming a safe and effective technique.

Introduction: Various experimental models exist in order to induce a spinal cord lesion and to monitor the potential recovery of the animals, with or without any therapeutic means. From the behavioral point of view, the Basso-Beattie-Bresnahan (BBB) score is the most popular scale, used consistently to evaluate the effect of the traumatism onto the motor behavior of the animals. Although it is well established and it is regarded as the “gold standard” in the literature, in case of partial lesions, with high rate of spontaneous recovery, more elaborate tests may be indicated. Materials-methods: In this study we performed spinal cord hemisection at the midthoracic level in adult Wistar rats, which were evaluated postoperatively with BBB, as well as with a more extended behavioral protocol, comprising grid walking and footprint analysis. Results: Although BBB score improved, grid walking, stride length, step length and limb rotation did not reach statistical significance. Conclusion: More sensitive motor behavior protocols are needed to corroborate the results of the BBB test and to detect subtle defects in sensorimotor coordination. This is especially true in cases of partial lesions, due to a high rate of spontaneous gross motor recovery.

ABSTRACTIntroduction: Quantitative descriptions of fiber type organization in hind limb muscles are incomplete or rare. Methods: Fiber morphometrics for both rat tibialis anterior (TA) muscles were measured in 3 dimensions. Results: Slow oxidative fiber area and perimeter varied in all zones. Fast oxidative glycolytic fibers (FOG) were predominant in the mediolateral and posterior zones, and fast glycolytic fibers (FG) predominated in the anterior zone. The mean area of FOG and succinate dehydrogenase intermediate fibers was lowest in the anterior zone. Mean area of FG was highest in the proximal and distal parts of the muscle. The area and perimeter of fast fibers differed significantly between the right and left limbs in the medial zone. In the middle and lateral zones, they differed at the proximal and distal parts. Conclusions: This detailed analysis in a high resolution, 3‐dimensional map provides an essential tool for understanding the structure and function of TA muscles. Muscle Nerve 48: 951–957, 2013