Extramuscular recording of spontaneous EMG activity and transcranial electrical elicited motor potentials in horses : characteristics of different subcutaneous and surface electrode types and practical guidelines

Introduction Adhesive surface electrodes are worthwhile to explore in detail as alternative to subcutaneous needle electrodes to assess myogenic evoked potentials (MEP) in human and horses. Extramuscular characteristics of both electrode types and different brands are compared in simultaneous recordings by also considering electrode impedances and background noise under not mechanically secured (not taped) and taped conditions. Methods In five ataxic and one non-ataxic horses, transcranial electrical MEPs, myographic activity, and noise were simultaneously recorded from subcutaneous needle (three brands) together with pre-gelled surface electrodes (five brands) on four extremities. In three horses, the impedances of four adjacent-placed surface-electrode pairs of different brands were measured and compared. The similarity between needle and surface EMGs was assessed by cross-correlation functions, pairwise comparison of motor latency times (MLT), and amplitudes. The influence of electrode noise and impedance on the signal quality was assessed by a failure rate (FR) function. Geometric means and impedance ranges under not taped and taped conditions were derived for each brand. Results High coherencies between EMGs of needle-surface pairs degraded to 0.7 at moderate and disappeared at strong noise. MLTs showed sub-millisecond simultaneous differences while sequential variations were several milliseconds. Subcutaneous MEP amplitudes were somewhat lower than epidermal. The impedances of subcutaneous needle electrodes were below 900 omega and FR = 0. For four brands, the FR for surface electrodes was between 0 and 80% and declined to below 25% after taping. A remaining brand (27G DSN2260 Medtronic) revealed impedances over 100 k omega and FR = 100% under not taped and taped conditions. Conclusion Subcutaneous needle and surface electrodes yield highly coherent EMGs and TES-MEP signals. When taped and allowing sufficient settling time, adhesive surface-electrode signals may approach the signal quality of subcutaneous needle electrodes but still depend on unpredictable conditions of the skin. The study provides a new valuable practical guidance for selection of extramuscular EMG electrodes. This study on horses shares common principles for the choice of adhesive surface or sc needle electrodes in human applications such as in intraoperative neurophysiological monitoring of motor functions of the brain and spinal cord

Comparison of muscle MEPs from transcranial magnetic and electrical stimulation and appearance of reflexes in horses

Introduction Transcranial electrical (TES) and magnetic stimulation (TMS) are both used for assessment of the motor function of the spinal cord in horses. Muscular motor evoked potentials (mMEP) were compared intra-individually for both techniques in five healthy horses. mMEPs were measured twice at increasing stimulation intensity steps over the extensor carpi radialis (ECR), tibialis cranialis (TC), and caninus muscles. Significance was set atp< 0.05. To support the hypothesis that both techniques induce extracranially elicited mMEPs, literature was also reviewed. Results Both techniques show the presence of late mMEPs below the transcranial threshold appearing as extracranially elicited startle responses. The occurrence of these late mMEPs is especially important for interpretation of TMS tracings when coil misalignment can have an additional influence. Mean transcranial motor latency times (MLT; synaptic delays included) and conduction velocities (CV) of the ECR and TC were significantly different between both techniques: respectively, 4.2 and 5.5 ms (MLTTMS--MLTTES), and -7.7 and -9.9 m/s (CVTMS-CVTES). TMS and TES show intensity-dependent latency decreases of, respectively, -2.6 (ECR) and -2.7 ms (TC)/30% magnetic intensity and -2.6 (ECR) and -3.2 (TC) ms/30V. When compared to TMS, TES shows the lowest coefficients of variation and highest reproducibility and accuracy for MLTs. This is ascribed to the fact that TES activates a lower number of cascaded interneurons, allows for multipulse stimulation, has an absence of coil repositioning errors, and has less sensitivity for varying degrees of background muscle tonus. Real axonal conduction times and conduction velocities are most closely approximated by TES. Conclusion Both intracranial and extracranial mMEPs inevitably carry characteristics of brainstem reflexes. To avoid false interpretations, transcranial mMEPs can be identified by a stepwise latency shortening of 15-20 ms when exceeding the transcranial motor threshold at increasing stimulation intensities. A ring block around the vertex is advised to reduce interference by extracranial mMEPs. mMEPs reflect the functional integrity of the route along the brainstem nuclei, extrapyramidal motor tracts, propriospinal neurons, and motoneurons. The corticospinal tract appears subordinate in horses. TMS and TES are interchangeable for assessing the functional integrity of motor functions of the spinal cord. However, TES reveals significantly shorter MLTs, higher conduction velocities, and better reproducibility

Extramuscular Recording of Spontaneous EMG Activity and Transcranial Electrical Elicited Motor Potentials in Horses:Characteristics of Different Subcutaneous and Surface Electrode Types and Practical Guidelines

Introduction: Adhesive surface electrodes are worthwhile to explore in detail as alternative to subcutaneous needle electrodes to assess myogenic evoked potentials (MEP) in human and horses. Extramuscular characteristics of both electrode types and different brands are compared in simultaneous recordings by also considering electrode impedances and background noise under not mechanically secured (not taped) and taped conditions. Methods: In five ataxic and one non-ataxic horses, transcranial electrical MEPs, myographic activity, and noise were simultaneously recorded from subcutaneous needle (three brands) together with pre-gelled surface electrodes (five brands) on four extremities. In three horses, the impedances of four adjacent-placed surface-electrode pairs of different brands were measured and compared. The similarity between needle and surface EMGs was assessed by cross-correlation functions, pairwise comparison of motor latency times (MLT), and amplitudes. The influence of electrode noise and impedance on the signal quality was assessed by a failure rate (FR) function. Geometric means and impedance ranges under not taped and taped conditions were derived for each brand. Results: High coherencies between EMGs of needle-surface pairs degraded to 0.7 at moderate and disappeared at strong noise. MLTs showed sub-millisecond simultaneous differences while sequential variations were several milliseconds. Subcutaneous MEP amplitudes were somewhat lower than epidermal. The impedances of subcutaneous needle electrodes were below 900 Ω and FR = 0. For four brands, the FR for surface electrodes was between 0 and 80% and declined to below 25% after taping. A remaining brand (27G DSN2260 Medtronic) revealed impedances over 100 kΩ and FR = 100% under not taped and taped conditions. Conclusion: Subcutaneous needle and surface electrodes yield highly coherent EMGs and TES-MEP signals. When taped and allowing sufficient settling time, adhesive surface-electrode signals may approach the signal quality of subcutaneous needle electrodes but still depend on unpredictable conditions of the skin. The study provides a new valuable practical guidance for selection of extramuscular EMG electrodes. This study on horses shares common principles for the choice of adhesive surface or sc needle electrodes in human applications such as in intraoperative neurophysiological monitoring of motor functions of the brain and spinal cord

Trapezius Motor Evoked Potentials From Transcranial Electrical Stimulation and Transcranial Magnetic Stimulation:Reference Data, Characteristic Differences and Intradural Motor Velocities in Horses

Reason for Performing Study: So far, only transcranial motor evoked potentials (MEP) of the extensor carpi radialis and tibialis cranialis have been documented for diagnostic evaluation in horses. These allow for differentiating whether lesions are located in either the thoraco-lumbar region or in the cervical myelum and/or brain. Transcranial trapezius MEPs further enable to distinguish between spinal and supraspinal located lesions. No normative data are available. It is unclear whether transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) are interchangeable modalities. Objectives: To provide normative data for trapezius MEP parameters in horses for TES and TMS and to discern direct and indirect conduction routes by neurophysiological models that use anatomical geometric characteristics to relate latency times with peripheral (PCV) and central conduction velocities (CCV). Methods: Transcranial electrical stimulation-induced trapezius MEPs were obtained from twelve horses. TES and TMS-MEPs (subgroup 5 horses) were compared intra-individually. Trapezius MEPs were measured bilaterally twice at 5 intensity steps. Motoneurons were localized using nerve conduction models of the cervical and spinal accessory nerves (SAN). Predicted CCVs were verified by multifidus MEP data from two horses referred for neurophysiological assessment. Results: Mean MEP latencies revealed for TES: 13.5 (11.1–16.0)ms and TMS: 19.7 (12–29.5)ms, comprising ∼100% direct routes and for TMS mixed direct/indirect routes of L:23/50; R:14/50. Left/right latency decreases over 10 > 50 V for TES were: –1.4/–1.8 ms and over 10 > 50% for TMS: –1.7/–3.5 ms. Direct route TMS-TES latency differences were 1.88–4.30 ms. 95% MEP amplitudes ranges for TES were: L:0.26–22 mV; R:0.5–15 mV and TMS: L:0.9 – 9.1 mV; R:1.1–7.9 mV. Conclusion: This is the first study to report normative data characterizing TES and TMS induced- trapezius MEPs in horses. The complex trapezius innervation leaves TES as the only reliable stimulation modality. Differences in latency times along the SAN route permit for estimation of the location of active motoneurons, which is of importance for clinical diagnostic purpose. SAN route lengths and latency times are governed by anatomical locations of motoneurons across C2-C5 segments. TES intensity-dependent reductions of trapezius MEP latencies are similar to limb muscles while MEP amplitudes between sides and between TES and TMS are not different. CCVs may reach 180 m/s

Study protocol of the TIRED study:A randomised controlled trial comparing either graded exercise therapy for severe fatigue or cognitive behaviour therapy with usual care in patients with incurable cancer

Background: Fatigue is a common and debilitating symptom for patients with incurable cancer receiving systemic treatment with palliative intent. There is evidence that non-pharmacological interventions such as graded exercise therapy (GET) or cognitive behaviour therapy (CBT) reduce cancer-related fatigue in disease-free cancer patients and in patients receiving treatment with curative intent. These interventions may also result in a reduction of fatigue in patients receiving treatment with palliative intent, by improving physical fitness (GET) or changing fatigue-related cognitions and behaviour (CBT). The primary aim of our study is to assess the efficacy of GET or CBT compared to usual care (UC) in reducing fatigue in patients with incurable cancer. Methods: The TIRED study is a multicentre three-armed randomised controlled trial (RCT) for incurable cancer patients receiving systemic treatment with palliative intent. Participants will be randomised to GET, CBT, or UC. In addition to UC, the GET group will participate in a 12-week supervised exercise programme. The CBT group will receive a 12-week CBT intervention in addition to UC. Primary and secondary outcome measures will be assessed at baseline, post-intervention (14 weeks), and at follow-up assessments (18 and 26 weeks post-randomisation). The primary outcome measure is fatigue severity (Checklist Individual Strength subscale fatigue severity). Secondary outcome measures are fatigue (EORTC-QLQ-C30 subscale fatigue), functional impairments (Sickness Impact Profile total score, EORTC-QLQ-C30 subscale emotional functioning, subscale physical functioning) and quality of life (EORTC-QLQ-C30 subscale QoL). Outcomes at 14 weeks (primary endpoint) of either treatment arm will be compared to those of UC participants. In addition, outcomes at 18 and 26 weeks (follow-up assessments) of either treatment arm will be compared to those of UC participants. Discussion: To our knowledge, the TIRED study is the first RCT investigating the efficacy of GET and CBT on reducing fatigue during treatment with palliative intent in incurable cancer patients. The results of this study will provide information about the possibility and efficacy of GET and CBT for severely fatigued incurable cancer patients

Evaluation of the diagnostic value of transcranial electrical stimulation (TES) to assess neuronal functional integrity in horses

Medical imaging allows for the visualization of spinal cord compression sites; however, it is impossible to assess the impact of visible stenotic sites on neuronal functioning, which is crucial information to formulate a correct prognosis and install targeted therapy. It is hypothesized that with the transcranial electrical stimulation (TES) technique, neurological impairment can be reliably diagnosed. Objective: To evaluate the ability of the TES technique to assess neuronal functional integrity in ataxic horses by recording TES-induced muscular evoked potentials (MEPs) in three different muscles and to structurally involve multiple ancillary diagnostic techniques, such as clinical neurological examination, plain radiography (RX) with ratio assessment, contrast myelography, and post-mortem gross and histopathological examination. Methods: Nine ataxic horses, showing combined fore and hindlimb ataxia (grades 2–4), were involved, together with 12 healthy horses. TES-induced MEPs were recorded bilaterally at the level of the trapezius (TR), the extensor carpi radialis (ECR), and tibialis cranialis (TC) muscles. Two Board-certified radiologists evaluated intra- and inter-sagittal diameter ratios on RX, reductions of dorsal contrast columns, and dural diameters (range skull-T1). Post-mortem gross pathological and segmental histopathological examination was also performed by a Board-certified pathologist. Results: TES-MEP latencies were significantly prolonged in both ECR and TC in all ataxic horses as opposed to the healthy horses. The TR showed a mixed pattern of normal and prolonged latency times. TES-MEP amplitudes were the least discriminative between healthy and ataxic horses. Youden’s cutoff latencies for ataxic horses were 24.6 ms for the ECR and 45.5 ms for the TC (sensitivity and specificity of 100%). For healthy horses, maximum latency values were 22 and 37 ms, respectively. RX revealed spinal cord compression in 8 out of 9 involved ataxic horses with positive predictive values of 0–100%. All ataxic horses showed multi-segmental Wallerian degeneration. All pathological changes recorded in the white matter of the spinal cord were widely dispersed across all cervical segments, whereas gray matter damage was more localized at the specific segmental level. Conclusion: TES-MEP latencies are highly sensitive to detect impairment of spinal cord motor functions for mild-to-severe ataxia (grades 2–4)

Evaluation of the diagnostic value of transcranial electrical stimulation (TES) to assess neuronal functional integrity in horses

Medical imaging allows for the visualization of spinal cord compression sites; however, it is impossible to assess the impact of visible stenotic sites on neuronal functioning, which is crucial information to formulate a correct prognosis and install targeted therapy. It is hypothesized that with the transcranial electrical stimulation (TES) technique, neurological impairment can be reliably diagnosed.ObjectiveTo evaluate the ability of the TES technique to assess neuronal functional integrity in ataxic horses by recording TES-induced muscular evoked potentials (MEPs) in three different muscles and to structurally involve multiple ancillary diagnostic techniques, such as clinical neurological examination, plain radiography (RX) with ratio assessment, contrast myelography, and post-mortem gross and histopathological examination.MethodsNine ataxic horses, showing combined fore and hindlimb ataxia (grades 2–4), were involved, together with 12 healthy horses. TES-induced MEPs were recorded bilaterally at the level of the trapezius (TR), the extensor carpi radialis (ECR), and tibialis cranialis (TC) muscles. Two Board-certified radiologists evaluated intra- and inter-sagittal diameter ratios on RX, reductions of dorsal contrast columns, and dural diameters (range skull-T1). Post-mortem gross pathological and segmental histopathological examination was also performed by a Board-certified pathologist.ResultsTES-MEP latencies were significantly prolonged in both ECR and TC in all ataxic horses as opposed to the healthy horses. The TR showed a mixed pattern of normal and prolonged latency times. TES-MEP amplitudes were the least discriminative between healthy and ataxic horses. Youden’s cutoff latencies for ataxic horses were 24.6 ms for the ECR and 45.5 ms for the TC (sensitivity and specificity of 100%). For healthy horses, maximum latency values were 22 and 37 ms, respectively. RX revealed spinal cord compression in 8 out of 9 involved ataxic horses with positive predictive values of 0–100%. All ataxic horses showed multi-segmental Wallerian degeneration. All pathological changes recorded in the white matter of the spinal cord were widely dispersed across all cervical segments, whereas gray matter damage was more localized at the specific segmental level.ConclusionTES-MEP latencies are highly sensitive to detect impairment of spinal cord motor functions for mild-to-severe ataxia (grades 2–4)

Physics with the KLOE-2 experiment at the upgraded DAϕ\phiNE

Investigation at a $\phi$--factory can shed light on several debated issues in particle physics. We discuss: i) recent theoretical development and experimental progress in kaon physics relevant for the Standard Model tests in the flavor sector, ii) the sensitivity we can reach in probing CPT and Quantum Mechanics from time evolution of entangled kaon states, iii) the interest for improving on the present measurements of non-leptonic and radiative decays of kaons and eta/eta$^\prime$ mesons, iv) the contribution to understand the nature of light scalar mesons, and v) the opportunity to search for narrow di-lepton resonances suggested by recent models proposing a hidden dark-matter sector. We also report on the $e^+ e^-$ physics in the continuum with the measurements of (multi)hadronic cross sections and the study of gamma gamma processes.Comment: 60 pages, 41 figures; added affiliation for one of the authors; added reference to section