Olivier Scheidegger

Muscle membrane dysfunction in critical illness myopathy assessed by velocity recovery cycles

OBJECTIVE To test the hypothesis that muscle fibers are depolarized in patients with critical illness myopathy by measuring velocity recovery cycles (VRCs) of muscle action potentials. METHODS VRCs were recorded from brachioradialis muscle by direct muscle stimulation in 10 patients in intensive care with evidence of critical illness myopathy (CIM). Two sets of recordings were made, mean 3.9 d apart, and compared with those from 10 age-matched controls. RESULTS Muscle supernormality was reduced in the patients by 50% compared with controls (P<0.002) and relative refractory period was increased by 59% (P<0.01). Supernormality was correlated with plasma potassium levels (R=-0.753, P<0.001), and the slope of this relationship was much steeper than previously reported for non-critically ill patients with renal failure (P<0.01). CONCLUSIONS The abnormal excitability properties indicate that the muscle fibers in CIM were depolarized, and/or that sodium channel inactivation was increased. The heightened sensitivity to potassium is consistent with the hypothesis that an endotoxin reduces sodium channel availability in depolarized muscle fibers. SIGNIFICANCE VRCs provide a practicable means to monitor muscle membrane changes in intensive care and to investigate the pathogenesis of CIM.

Localizing Seizure-Onset Zones in Presurgical Evaluation of Drug-Resistant Epilepsy by Electroencephalography/fMRI: Effectiveness of Alternative Thresholding Strategies

BACKGROUND AND PURPOSE: Simultaneous EEG/fMRI is an effective noninvasive tool for identifying and localizing the SOZ in patients with focal epilepsy. In this study, we evaluated different thresholding strategies in EEG/fMRI for the assessment of hemodynamic responses to IEDs in the SOZ of drug-resistant epilepsy. MATERIALS AND METHODS: Sixteen patients with focal epilepsy were examined by using simultaneous 92-channel EEG and BOLD fMRI. The temporal fluctuation of epileptiform signals on the EEG was extracted by independent component analysis to predict the hemodynamic responses to the IEDs. We applied 3 different threshold criteria to detect hemodynamic responses within the SOZ: 1) PA, 2) a fixed threshold at P < .05 corrected for multiple comparison (FWE), and 3) FAV (4000 ± 200 activated voxels within the brain). RESULTS: PA identified the SOZ in 9 of 16 patients; FWE resulted in concordant BOLD signal correlates in 11 of 16, and FAV in 13 of 16 patients. Hemodynamic responses were detected within the resected areas in 5 (PA), 6 (FWE), and 8 (FAV) of 10 patients who remained seizure-free after surgery. CONCLUSIONS: EEG/fMRI is a noninvasive tool for the presurgical work-up of patients with epilepsy, which can be performed during seizure-free periods and is complementary to the ictal electroclinical assessment. Our findings suggest that the effectiveness of EEG/fMRI in delineating the SOZ may be further improved by the additional use of alternative analysis strategies such as FAV.

Corticospinal output during muscular fatigue differs in multiple sclerosis patients compared to healthy controls

Background: In multiple sclerosis (MS), fatigue is a common and often disabling symptom. It has multiple causes with central motor fatigue playing an important role. Objective: The objective of this study was to analyse the central motor conduction changes in relation to muscle contraction force during muscle fatigue and recovery in MS patients compared to healthy controls. Methods: A total of 23 MS patients with fatigue and 13 healthy subjects were assessed during 2 minutes of fatiguing exercise of the abductor digiti minimi muscle of the hand and the subsequent 7 minutes of recovery. Central motor conduction was quantified by transcranial magnetic stimulation using the triple stimulation protocol and calculating a central conduction index (CCI). Results: Force declined to 36% of the pre-exercise level (SD 16%; p < 0.01) in MS patients and to 44% (SD 9%, p < 0.01) in healthy subjects (group differences, not statistically significant). The decline of the CCI was significantly less marked in patients (–20%, SD 26%, p < 0.05) than in healthy subjects (–57%, SD 15%, p < 0.05; group differences, p < 0.05). The decline of force and CCI were not correlated in either group. Conclusions: During a fatiguing exercise, the decline in central motor conduction is significantly less pronounced in MS patients than healthy subjects, although the reduction of force is similar.

Skeletal Muscle Quantitative Nuclear Magnetic Resonance Imaging and Spectroscopy as an Outcome Measure for Clinical Trials

Recent years have seen tremendous progress towards therapy of many previously incurable neuromuscular diseases. This new context has acted as a driving force for the development of novel non-invasive outcome measures. These can be organized in three main categories: functional tools, fluid biomarkers and imagery. In the latest category, nuclear magnetic resonance imaging (NMRI) offers a considerable range of possibilities for the characterization of skeletal muscle composition, function and metabolism. Nowadays, three NMR outcome measures are frequently integrated in clinical research protocols. They are: 1/ the muscle cross sectional area or volume, 2/ the percentage of intramuscular fat and 3/ the muscle water T2, which quantity muscle trophicity, chronic fatty degenerative changes and oedema (or more broadly, “disease activity”), respectively. A fourth biomarker, the contractile tissue volume is easily derived from the first two ones. The fat fraction maps most often acquired with Dixon sequences have proven their capability to detect small changes in muscle composition and have repeatedly shown superior sensitivity over standard functional evaluation. This outcome measure will more than likely be the first of the series to be validated as an endpoint by regulatory agencies. The versatility of contrast generated by NMR has opened many additional possibilities for characterization of the skeletal muscle and will result in the proposal of more NMR biomarkers. Ultra-short TE (UTE) sequences, late gadolinium enhancement and NMR elastography are being investigated as candidates to evaluate skeletal muscle interstitial fibrosis. Many options exist to measure muscle perfusion and oxygenation by NMR. Diffusion NMR as well as texture analysis algorithms could generate complementary information on muscle organization at microscopic and mesoscopic scales, respectively. 31P NMR spectroscopy is the reference technique to assess muscle energetics non-invasively during and after exercise. In dystrophic muscle, 31P NMR spectrum at rest is profoundly perturbed, and several resonances inform on cell membrane integrity. Considerable efforts are being directed towards acceleration of image acquisitions using a variety of approaches, from the extraction of fat content and water T2 maps from one single acquisition to partial matrices acquisition schemes. Spectacular decreases in examination time are expected in the near future. They will reinforce the attractiveness of NMR outcome measures and will further facilitate their integration in clinical research trials.

Optimized quantitative magnetic resonance spectroscopy for clinical routine

Several practical obstacles in data handling and evaluation complicate the use of quantitative localized magnetic resonance spectroscopy (qMRS) in clinical routine MR examinations. To overcome these obstacles, a clinically feasible MR pulse sequence protocol based on standard available MR pulse sequences for qMRS has been implemented along with newly added functionalities to the free software package jMRUI‐v5.0 to make qMRS attractive for clinical routine. This enables (a) easy and fast DICOM data transfer from the MR console and the qMRS‐computer, (b) visualization of combined MR spectroscopy and imaging, (c) creation and network transfer of spectroscopy reports in DICOM format, (d) integration of advanced water reference models for absolute quantification, and (e) setup of databases containing normal metabolite concentrations of healthy subjects. To demonstrate the work‐flow of qMRS using these implementations, databases for normal metabolite concentration in different regions of brain tissue were created using spectroscopic data acquired in 55 normal subjects (age range 6–61 years) using 1.5T and 3T MR systems, and illustrated in one clinical case of typical brain tumor (primitive neuroectodermal tumor). The MR pulse sequence protocol and newly implemented software functionalities facilitate the incorporation of qMRS and reference to normal value metabolite concentration data in daily clinical routine. Magn Reson Med, 2013.

Widespread grey matter changes and hemodynamic correlates to interictal epileptiform discharges in pharmacoresistant mesial temporal epilepsy

Focal onset epilepsies most often occur in the temporal lobes. To improve diagnosis and therapy of patients suffering from pharmacoresistant temporal lobe epilepsy it is highly important to better understand the underlying functional and structural networks. In mesial temporal lobe epilepsy (MTLE) widespread functional networks are involved in seizure generation and propagation. In this study we have analyzed the spatial distribution of hemodynamic correlates (HC) to interictal epileptiform discharges on simultaneous EEG/fMRI recordings and relative grey matter volume (rGMV) reductions in 10 patients with MTLE. HC occurred beyond the seizure onset zone in the hippocampus, in the ipsilateral insular/operculum, temporo-polar and lateral neocortex, cerebellum, along the central sulcus and bilaterally in the cingulate gyrus. rGMV reductions were detected in the middle temporal gyrus, inferior temporal gyrus and uncus to the hippocampus, the insula, the posterior cingulate and the anterior lobe of the cerebellum. Overlaps between HC and decreased rGMV were detected along the mesolimbic network ipsilateral to the seizure onset zone. We conclude that interictal epileptic activity in MTLE induces widespread metabolic changes in functional networks involved in MTLE seizure activity. These functional networks are spatially overlapping with areas that show a reduction in relative grey matter volumes.

Robotic cochlear implantation: surgical procedure and first clinical experience

Abstract Conclusion: A system for robotic cochlear implantation (rCI) has been developed and a corresponding surgical workflow has been described. The clinical feasibility was demonstrated through the conduction of a safe and effective rCI procedure. Objectives: To define a clinical workflow for rCI and demonstrate its feasibility, safety, and effectiveness within a clinical setting. Method: A clinical workflow for use of a previously described image guided surgical robot system for rCI was developed. Based on pre-operative images, a safe drilling tunnel targeting the round window was planned and drilled by the robotic system. Intra-operatively the drill path was assessed using imaging and sensor-based data to confirm the proximity of the facial nerve. Electrode array insertion was manually achieved under microscope visualization. Electrode array placement, structure preservation, and the accuracy of the drilling and of the safety mechanisms were assessed on post-operative CT images. Results: Robotic drilling was conducted with an accuracy of 0.2 mm and safety mechanisms predicted proximity of the nerves to within 0.1 mm. The approach resulted in a minimal mastoidectomy and minimal incisions. Manual electrode array insertion was successfully performed through the robotically drilled tunnel. The procedure was performed without complications, and all surrounding structures were preserved.

Reproducibility of sensory nerve conduction studies of the sural nerve using ultrasound-guided needle positioning

In this study we sought to evaluate the reproducibility of sensory nerve conduction studies (NCS) using ultrasound‐guided needle positioning (USNP).

Instrument flight to the inner ear

Image-guided robotic surgery, designed for operating on small structures, is demonstrated for robotic cochlear implantation. Surgical robot systems can work beyond the limits of human perception, dexterity, and scale, making them inherently suitable for use in microsurgical procedures. However, despite extensive research, image-guided robotics applications for microsurgery have seen limited introduction into clinical care to date. Among others, challenges are geometric scale and haptic resolution at which the surgeon cannot sufficiently control a device outside the range of human faculties. Mechanisms are required to ascertain redundant control on process variables that ensure safety of the device, much like instrument flight in avionics. Cochlear implantation surgery is a microsurgical procedure, in which specific tasks are at submillimetric scale and exceed reliable visuo-tactile feedback. Cochlear implantation is subject to intra- and interoperative variations, leading to potentially inconsistent clinical and audiological outcomes for patients. The concept of robotic cochlear implantation aims to increase consistency of surgical outcomes, such as preservation of residual hearing, and to reduce invasiveness of the procedure. We report successful image-guided, robotic cochlear implantation in human. The robotic treatment model encompasses computer-assisted surgery planning, precision stereotactic image guidance, in situ assessment of tissue properties, and multipolar neuromonitoring, all based on in vitro, in vivo, and pilot data. The model is expandable to integrate additional robotic functionalities such as cochlear access and electrode insertion. Our results demonstrate the feasibility and possibilities of using robotic technology for microsurgery on the lateral skull base. It has the potential for benefit in other microsurgical domains for which there is no task-oriented robotic technology available at present.

Epileptogenic Developmental Venous Anomaly Insights From Simultaneous EEG/fMRI

Developmental venous anomalies (DVAs) are associated with epileptic seizures; however, the role of DVA in the epileptogenesis is still not established. Simultaneous interictal electroencephalogram/functional magnetic resonance imaging (EEG/fMRI) recordings provide supplementary information to electroclinical data about the epileptic generators, and thus aid in the differentiation of clinically equivocal epilepsy syndromes. The main objective of our study was to characterize the epileptic network in a patient with DVA and epilepsy by simultaneous EEG/fMRI recordings. A 17-year-old woman with recently emerging generalized tonic–clonic seizures, and atypical generalized discharges, was investigated using simultaneous EEG/fMRI at the university hospital. Previous high-resolution MRI showed no structural abnormalities, except a DVA in the right frontal operculum. Interictal EEG recordings showed atypical generalized discharges, corresponding to positive focal blood oxygen level dependent (BOLD) correlates in the right frontal operculum, a region drained by the DVA. Additionally, widespread cortical bilateral negative BOLD correlates in the frontal and parietal lobes were delineated, resembling a generalized epileptic network. The EEG/fMRI recordings support a right frontal lobe epilepsy, originating in the vicinity of the DVA, propagating rapidly to both frontal and parietal lobes, as expressed on the scalp EEG by secondary bilateral synchrony. The DVA may be causative of focal epilepsies in cases where no concomitant epileptogenic lesions can be detected. Advanced imaging techniques, such as simultaneous EEG/fMRI, may thus aid in the differentiation of clinically equivocal epilepsy syndromes.