Effects of high resistance muscle training on corticospinal output during motor fatigue assessed by transcranial magnetic stimulation.

Introduction: Central fatigue refers to a reduced drive of motor cortical output during exercise, and performance can be enhanced after training. However, the effects of training on central fatigue remain unclear. Changes in cortical output can be addressed non-invasively using transcranial magnetic stimulation (TMS). The aim of the study was to compare responses to TMS during a fatiguing exercise before and after a 3 weeks lasting resistance training, in healthy subjects. Methods: The triple stimulation technique (TST) was used to quantify a central conduction index (CCI = amplitude ratio of central conduction response and peripheral nerve response) to the abductor digiti minimi muscle (ADM) in 15 subjects. The training consisted of repetitive isometric maximal voluntary contractions (MVC) of ADM for 2 min twice a day. Before and after this training, TST recordings were obtained every 15 s during an 2 min exercise of MVC of the ADM, where subjects performed repetitive contractions of the ADM, and repeatedly during a recovery period of 7 min. Results: There was a consistent decrease of force to approximately 40% of MVC in all experiments and in all subjects, both before and after training. In all subjects, CCI decreased during exercise. While before training, theCCI decreased to 49% (SD 23.7%) after 2 min of exercise, it decreased after training onlyto 79% (SD 26.4%) after exercise (p < 0.01). Discussion: The training regimen increased the proportion of target motor units that could be activated by TMS during a fatiguing exercise. The results point to a reduced intracortical inhibition, which may be a transient physiological response to facilitate the motor task. Possible underlying mechanisms at spinal and supraspinal sites are discussed.

Endovascular therapy in patients with large vessel occlusion due to cardioembolism versus large-artery atherosclerosis.

BACKGROUND AND AIMS: To investigate whether stroke aetiology affects outcome in patients with acute ischaemic stroke who undergo endovascular therapy. METHODS: We retrospectively analysed patients from the Bernese Stroke Centre Registry (January 2010-September 2018), with acute large vessel occlusion in the anterior circulation due to cardioembolism or large-artery atherosclerosis, treated with endovascular therapy (±intravenous thrombolysis). RESULTS: The study included 850 patients (median age 77.4 years, 49.3% female, 80.1% with cardioembolism). Compared with those with large-artery atherosclerosis, patients with cardioembolism were older, more often female, and more likely to have a history of hypercholesterolaemia, atrial fibrillation, current smoking (each p < 0.0001) and higher median National Institutes of Health Stroke Scale (NIHSS) scores on admission (p = 0.030). They were more frequently treated with stent retrievers (p = 0.007), but the median number of stent retriever attempts was lower (p = 0.016) and fewer had permanent stent placements (p ⩽ 0.004). Univariable analysis showed that patients with cardioembolism had worse 3-month survival [72.7% versus 84%, odds ratio (OR) = 0.51; p = 0.004] and modified Rankin scale (mRS) score shift (p = 0.043) and higher rates of post-interventional heart failure (33.5% versus 18.5%, OR = 2.22; p < 0.0001), but better modified thrombolysis in cerebral infarction (mTICI) score shift (p = 0.025). Excellent (mRS = 0-1) 3-month outcome, successful reperfusion (mTICI = 2b-3), symptomatic intracranial haemorrhage and Updated Charlson Comorbidity Index were similar between groups. Propensity-matched analysis found no statistically significant difference in outcome between stroke aetiology groups. Stroke aetiology was not an independent predictor of favourable mRS score shift, but lower admission NIHSS score, younger age and independence pre-stroke were (each p < 0.0001). Stroke aetiology was not an independent predictor of heart failure, but older age, admission antithrombotics and dependence pre-stroke were (each ⩽0.027). Stroke aetiology was not an independent predictor of favourable mTICI score shift, but application of stent retriever and no permanent intracranial stent placement were (each ⩽0.044). CONCLUSION: We suggest prospective studies to further elucidate differences in reperfusion and outcome between patients with cardioembolism and large-artery atherosclerosis.

[Neurological Evaluation of Neuropathic Pain]. / Neurologische Evaluation des neuropathischen Schmerzes.

Neurological Evaluation of Neuropathic Pain Abstract. Neuropathic pain arises after lesions of the central or peripheral nervous system. The treatment of nociceptive pain - pain in which the somatosensory nervous system is intact - is different from neuropathic pain. Patient history and detailed neurological examination describe the patient's specific pain phenotype, and with additional diagnostic tests the structural damage or functional impairment of the somatosensory nervous system can be identified. Some of these tests have been validated in the assessment of neuropathic pain and comprise MR and ultrasound imaging, histopathological examinations, and neurophysiological studies.

Vestibulo-cochlear function in inflammatory neuropathies.

OBJECTIVE: We aimed to quantify peripheral-vestibular deficits that may contribute to imbalanced stance/gait in patients with inflammatory neuropathies. METHODS: Twenty-one patients (58 ±â€¯15 y [mean age ±â€¯1SD]; chronic-inflammatory-demyelinating-polyneuropathy = 10, Guillain-Barré Syndrome = 5, Anti-MAG peripheral neuropathy = 2, multifocal-motor-neuropathy = 4) were compared with 26 healthy controls. All subjects received video-head-impulse testing (vHIT), caloric irrigation and cervical/ocular vestibular-evoked myogenic-potentials (VEMPs). The Yardley vertigo-symptom-scale (VSS) was used to rate vertigo/dizziness. Postural stability was assessed using the functional gait-assessment (FGA). Pure-tone audiograms (n = 18), otoacoustic emissions (n = 12) and auditory brainstem responses were obtained (n = 12). RESULTS: Semicircular-canal hypofunction was noted in 9/21 (43%) patients (vHIT = 6; caloric irrigation = 5), whereas otolith function was impaired in 12/21 (57%) (oVEMPs = 8; cVEMPs = 5), resulting in vestibular impairment of at least one sensor in 13/21 (62%). On average, 2.4 ±â€¯1.1 vestibular end organs (each side: anterior/posterior/horizontal canal, utriculus, sacculus; total = 10) were affected. The VSS-scores were higher in patients (16.8 ±â€¯8.6 vs. 9.5 ±â€¯6.2, p = 0.002) but did not correlate with the number of affected organs. Auditory neuropathy was found in 1/12 (8%) patients. CONCLUSION: Impairment of one or more vestibular end organs was frequent, but usually mild, possibly contributing to imbalance of stance/gait in inflammatory neuropathies. SIGNIFICANCE: While our data does not support routine vestibular testing in inflammatory neuropathies, this may be considered in selected cases.

The matricellular protein CYR61 interferes with normal pancreatic islets architecture and promotes pancreatic neuroendocrine tumor progression.

The significance of matricellular proteins during development and cancer progression is widely recognized. However, how these proteins actively contribute to physiological development and pathological cancer progression is only partially elucidated. In this study, we investigated the role of the matricellular protein Cysteine-rich 61 (CYR61) in pancreatic islet development and carcinogenesis. Transgenic expression of CYR61 in ß cells (Rip1CYR mice) caused irregular islets morphology and distorted sorting of α cells, but did not alter islets size, number or vascularization. To investigate the function of CYR61 during carcinogenesis, we crossed Rip1CYR mice with Rip1Tag2 mice, a well-established model of ß cell carcinogenesis. Beta tumors in Rip1Tag2CYR mice were larger, more invasive and more vascularized compared to tumors in Rip1Tag2 mice. The effect of CYR61 on angiogenesis was fully abrogated by treating mice with the anti-VEGFR2 mAb DC101. Results from in vitro assays demonstrated that CYR61 modulated integrin α6ß1-dependent invasion and adhesion without altering its expression. Taken together, these results show that CYR61 expression in pancreatic ß cells interferes with normal islet architecture, promotes islet tumor growth, invasion and VEGF/VERGFR-2-dependent tumor angiogenesis. Taken together, these observations demonstrate that CYR61 acts as a tumor-promoting gene in pancreatic neuroendocrine tumors.