Trunk extensor muscle endurance and its relationship to action potential conduction velocity and spectral parameters estimated using high-density electromyography.

Trunk extensor muscle fatigue typically manifests as a decline in spectral content of surface electromyography. However, previous research on the relationship of this decline with trunk extensor muscle endurance have shown inconsistent results. The decline of spectral content mainly reflects the decrease in average motor unit action potential conduction velocity (CV). We evaluated whether the rate of change in CV, as well as two approaches employing the change in spectral content, are related to trunk extensor muscle endurance. Fourteen healthy male participants without a low-back pain history performed a non-strictly controlled static forward trunk bending trial until exhaustion while standing. For 13 participants, physiologically plausible CV estimates were obtained from high-density surface electromyography bilaterally from T6 to L5. Laterally between L1 and L2, the linear rate of CV change was strongly correlated to endurance time (R2 = 0.79), whereas analyses involving the linear rate of change in spectral measures showed a lower (R2 = 0.38) or no correlation. For medial electrode locations, estimating CV and its relationship with endurance time was less successful, while the linear rate of change in spectral measures correlated moderately to endurance time (R2 = 0.44; R2 = 0.56). This study provides guidance on monitoring trunk extensor muscle fatigue development using electromyography.

Enhanced low-threshold motor unit capacity during endurance tasks in patients with spinal muscular atrophy using pyridostigmine.

OBJECTIVE: To investigate the electrophysiological basis of pyridostigmine enhancement of endurance performance documented earlier in patients with spinal muscular atrophy (SMA). METHODS: We recorded surface electromyography (sEMG) in four upper extremity muscles of 31 patients with SMA types 2 and 3 performing endurance shuttle tests (EST) and maximal voluntary contraction (MVC) measurements during a randomized, double blind, cross-over, phase II trial. Linear mixed effect models (LMM) were used to assess the effect of pyridostigmine on (i) time courses of median frequencies and of root mean square (RMS) amplitudes of sEMG signals and (ii) maximal RMS amplitudes during MVC measurements. These sEMG changes over time indicate levels of peripheral muscle fatigue and recruitment of new motor units, respectively. RESULTS: In comparison to a placebo, patients with SMA using pyridostigmine had fourfold smaller decreases in frequency and twofold smaller increases in amplitudes of sEMG signals in some muscles, recorded during ESTs (p < 0.05). We found no effect of pyridostigmine on MVC RMS amplitudes. CONCLUSIONS: sEMG parameters indicate enhanced low-threshold (LT) motor unit (MU) function in upper-extremity muscles of patients with SMA treated with pyridostigmine. This may underlie their improved endurance. SIGNIFICANCE: Our results suggest that enhancing LT MU function may constitute a therapeutic strategy to reduce fatigability in patients with SMA.

Low back muscle action potential conduction velocity estimated using high-density electromyography.

While a decreasing spectral content of surface electromyography reflects low back muscle fatigue development, reliability of these decreases may be insufficient. Decreasing frequency content is largely determined by decreasing average motor unit action potential conduction velocities (CV), which is considered a more direct measure of muscle fatigue development. However, for the low back muscles it has been proven difficult to identify propagating potentials and consequently estimate the CV. The aim of this study was to estimate the low back muscle CV from high-density multi-channel electromyography by using peak-delay and cross-correlation methods. Fourteen healthy male participants without a history of low-back pain performed a 30 degrees lumbar flexion trial until exhaustion while standing. For 10 out of the 14 participants (118 out of 560 sites) realistic CV estimates were obtained using both methods, the majority likely over the iliocostalis lumborum muscle. Between-method CV differences appeared to be small. Close to the spine a considerable number of sites (79) yielded systematically overestimated low back muscle CV values. Estimating low back muscle CV may allow additional insight into low back muscle fatigue development and potentially improve its monitoring using (high-density) surface electromyography.

Motor Unit and Capillary Recruitment During Fatiguing Arm-Cycling Exercise in Spinal Muscular Atrophy Types 3 and 4.

BACKGROUND: Exercise intolerance is an important impairment in patients with SMA, but little is known about the mechanisms underlying this symptom. OBJECTIVE: To investigate if reduced motor unit and capillary recruitment capacity in patients with SMA contribute to exercise intolerance. METHODS: Adolescent and adult patients with SMA types 3 and 4 (n = 15) and age- and gender matched controls (n = 15) performed a maximal upper body exercise test. We applied respiratory gas analyses, non-invasive surface electromyography (sEMG) and continuous wave near-infrared spectroscopy (CW-NIRS) to study oxygen consumption, arm muscle motor unit- and capillary recruitment, respectively. RESULTS: Maximal exercise duration was twofold lower (p < 0.001) and work of breathing and ventilation was 1.6- and 1.8-fold higher (p < 0.05) in patients compared to controls, respectively. Regarding motor unit recruitment, we found higher normalized RMS amplitude onset values of sEMG signals from all muscles and the increase in normalized RMS amplitudes was similar in the m. triceps brachii, m. brachioradialis and m. flexor digitorum in SMA compared to controls. Median frequency, onset values were similar in patients and controls. We found a similar decrease in median frequencies of sEMG recordings from the m. biceps brachii, a diminished decrease from the m. brachioradialis and m. flexor digitorum, but a larger decrease from the m. triceps brachii. With respect to capillary recruitment, CW-NIRS recordings in m. biceps brachii revealed dynamics that were both qualitatively and quantitatively similar in patients and controls. CONCLUSION: We found no evidence for the contribution of motor unit and capillary recruitment capacity of the upper arm muscles in adolescent and adult patients with SMA types 3 and 4 as primary limiting factors to premature fatigue during execution of a maximal arm-cycling task.

Motor unit reserve capacity in spinal muscular atrophy during fatiguing endurance performance.

OBJECTIVE: To investigate the availability of any motor unit reserve capacity during fatiguing endurance testing in patients with spinal muscular atrophy (SMA). METHODS: We recorded surface electromyography (sEMG) of various muscles of upper- and lower extremities of 70 patients with SMA types 2-4 and 19 healthy controls performing endurance shuttle tests (ESTs) of arm and legs. We quantitatively evaluated the development of fatigability and motor unit recruitment using time courses of median frequencies and amplitudes of sEMG signals. Linear mixed effect statistical models were used to evaluate group differences in median frequency and normalized amplitude at onset and its time course. RESULTS: Normalized sEMG amplitudes at onset of upper body ESTs were significantly higher in patients compared to controls, yet submaximal when related to maximal voluntary contractions, and showed an inverse correlation to SMA phenotype. sEMG median frequencies decreased and amplitudes increased in various muscles during execution of ESTs in patients and controls. CONCLUSIONS: Decreasing median frequencies and increasing amplitudes reveal motor unit reserve capacity in individual SMA patients during ESTs at submaximal performance intensities. SIGNIFICANCE: Preserving, if not expanding motor unit reserve capacity may present a potential therapeutic target in clinical care to reduce fatigability in individual patients with SMA.

Single finger movements in the aging hand: changes in finger independence, muscle activation patterns and tendon displacement in older adults.

With aging, hand mobility and manual dexterity decline, even under healthy circumstances. To assess how aging affects finger movement control, we compared elderly and young subjects with respect to (1) finger movement independence, (2) neural control of extrinsic finger muscles and (3) finger tendon displacements during single finger flexion. In twelve healthy older (age 68-84) and nine young (age 22-29) subjects, finger kinematics were measured to assess finger movement enslaving and the range of independent finger movement. Muscle activation was assessed using a multi-channel electrode grid placed over the flexor digitorum superficialis (FDS) and the extensor digitorum (ED). FDS tendon displacements of the index, middle and ring fingers were measured using ultrasound. In older subjects compared to the younger subjects, we found: (1) increased enslaving of the middle finger during index finger flexion (young: 25.6 ± 12.4%, elderly: 47.0 ± 25.1%; p = 0.018), (2) a lower range of independent movement of the index finger (youngmiddle = 74.0%, elderlymiddle: 45.9%; p < 0.001), (3) a more evenly distributed muscle activation pattern over the finger-specific FDS and ED muscle regions and (4) a lower slope at the beginning of the finger movement to tendon displacement relationship, presenting a distinct period with little to no tendon displacement. Our study indicates that primarily the movement independence of the index finger is affected by aging. This can partly be attributed to a muscle activation pattern that is more evenly distributed over the finger-specific FDS and ED muscle regions in the elderly.

Effect of Mexiletine on Muscle Stiffness in Patients With Nondystrophic Myotonia Evaluated Using Aggregated N-of-1 Trials.

Importance: In rare diseases it is difficult to achieve high-quality evidence of treatment efficacy because of small cohorts and clinical heterogeneity. With emerging treatments for rare diseases, innovative trial designs are needed. Objective: To investigate the effectiveness of mexiletine in nondystrophic myotonia using an aggregated N-of-1 trials design and compare results between this innovative design and a previously conducted RCT. Design, Setting, and Participants: A series of aggregated, double-blind, randomized, placebo-controlled N-of-1-trials, performed in a single academic referral center. Thirty Dutch adult patients with genetically confirmed nondystrophic myotonia (38 patients screened) were enrolled between February 2014 and June 2015. Follow-up was completed in September 2016. Interventions: Mexiletine (600 mg daily) vs placebo during multiple treatment periods of 4 weeks. Main Outcomes and Measures: Reduction in daily-reported muscle stiffness on a scale of 1 to 9, with higher scores indicating more impairment. A Bayesian hierarchical model aggregated individual N-of-1 trial data to determine the posterior probability of reaching a clinically meaningful effect of a greater than 0.75-point difference. Results: Among 30 enrolled patients (mean age, 43.4 [SD, 15.24] years; 22% men; 19 CLCN1 and 11 SCN4A genotype), 27 completed the study and 3 dropped out (1 because of a serious adverse event). In 24 of the 27 completers, a clinically meaningful treatment effect was found. In the Bayesian hierarchical model, mexiletine resulted in a 100% posterior probability of reaching a clinically meaningful reduction in self-reported muscle stiffness for the nondystrophic myotonia group overall and the CLCN1 genotype subgroup and 93% posterior probability for the SCN4A genotype subgroup. In the total nondystrophic myotonia group, the median muscle stiffness score was 6.08 (interquartile range, 4.71-6.80) at baseline and was 2.50 (95% credible interval [CrI], 1.77-3.24) during the mexiletine period and 5.56 (95% CrI, 4.73-6.39) during the placebo period; difference in symptom score reduction, 3.06 (95% CrI, 1.96-4.15; n = 27) favoring mexiletine. The most common adverse event was gastrointestinal discomfort (21 mexiletine [70%], 1 placebo [3%]). One serious adverse event occurred (1 mexiletine [3%]; allergic skin reaction). Using frequentist reanalysis, mexiletine compared with placebo resulted in a mean reduction in daily-reported muscle stiffness of 3.12 (95% CI, 2.46-3.78), consistent with the previous RCT treatment effect of 2.69 (95% CI, 2.12-3.26). Conclusions and Relevance: In a series of N-of-1 trials of mexiletine vs placebo in patients with nondystrophic myotonia, there was a reduction in mean daily-reported muscle stiffness that was consistent with the treatment effect in a previous randomized clinical trial. These findings support the efficacy of mexiletine for treatment of nondystrophic myotonia as well as the feasibility of N-of-1 trials for assessing interventions in some chronic rare diseases. Trial Registration: ClinicalTrials.gov Identifier: NCT02045667.

Distinct neural control of intrinsic and extrinsic muscles of the hand during single finger pressing.

Single finger force tasks lead to unintended activation of the non-instructed fingers, commonly referred to as enslaving. Both neural and mechanical factors have been associated with this absence of finger individuality. This study investigates the amplitude modulation of both intrinsic and extrinsic finger muscles during single finger isometric force tasks. Twelve participants performed single finger flexion presses at 20% of maximum voluntary contraction, while simultaneously the electromyographic activity of several intrinsic and extrinsic muscles associated with all four fingers was recorded using 8 electrode pairs in the hand and two 30-electrode grids on the lower arm. The forces exerted by each of the fingers, in both flexion and extension direction, were recorded with individual force sensors. This study shows distinct activation patterns in intrinsic and extrinsic hand muscles. Intrinsic muscles exhibited individuation, where the agonistic and antagonistic muscles associated with the instructed fingers showed the highest activation. This activation in both agonistic and antagonistic muscles appears to facilitate finger stabilisation during the isometric force task. Extrinsic muscles show an activation independent from instructed finger in both agonistic and antagonistic muscles, which appears to be associated with stabilisation of the wrist, with an additional finger-dependent modulation only present in the agonistic extrinsic muscles. These results indicate distinct muscle patterns in intrinsic and extrinsic hand muscles during single finger isometric force pressing. We conclude that the finger specific activation of intrinsic muscles is not sufficient to fully counteract enslaving caused by the broad activation of the extrinsic muscles.

Changes in H-Reflex Recruitment After Trans-Spinal Direct Current Stimulation With Multiple Electrode Configurations.

Trans-spinal direct current stimulation (tsDCS) is an electro-modulatory tool with possible application in the rehabilitation of spinal cord injury. TsDCS generates a small electric field, aiming to induce lasting, functional neuromodulation in the targeted neuronal networks. Earlier studies have shown significant modulatory effects after application of lumbar tsDCS. However, for clinical application, a better understanding of application specific factors is required. Our goal was to investigate the effect of different electrode configurations using lumbar spinal tsDCS on spinal excitability. We applied tsDCS (2.5 mA, 15 min) in 10 healthy subjects with three different electrode configurations: (1) Anode and cathode placed over vertebra T11, and the posterior left shoulder respectively (LSC-S) (one polarity), and (2) Both electrodes placed in equal distance (ED) (7 cm) above and below vertebra T11, investigated for two polarities (ED-Anodal/Cathodal). The soleus H-Reflex is measured before, during and after tsDCS in either electrode configuration or a sham condition. To account for genetic predispositions in response to direct current stimulation, subject BDNF genotype was assessed. Stimulation in configuration ED-Cathodal induced an amplitude reduction of the H-reflex, 30 min after tsDCS with respect to baseline, whereas none of the other configurations led to significant post intervention effects. BDNF genotype did not correlate with post intervention effects. Furthermore, we failed to replicate effects shown by a previous study, which highlights the need for a better understanding of methodological and subject specific influences on tsDCS outcome. The H-reflex depression after tsDCS (Config. ED-Cathodal) provides new insights and may foster our understanding of the working mechanism of tsDCS.

On the electrode positioning for bipolar EMG recording of forearm extensor and flexor muscle activity after transcranial magnetic stimulation.

After stroke, motor pathways are often affected, leading to paresis. It remains difficult to reliably predict motor recovery of the upper extremity, for which transcranial magnetic stimulation (TMS) may add to clinical examination. Placement of the surface electromyography (sEMG) electrodes in TMS is essential for information about specific muscle groups and corticospinal pathways. This study primarily aimed to determine the optimal sEMG electrode positions for recording activity of forearm flexor and extensor muscles. The first goal was to optimize sensitivity in measuring any motor evoked potentials (MEP), because they may be reduced or absent in stroke patients. The second goal was adequate distinction between forearm flexor and extensor muscle groups. For optimal flexibility in choosing montages, a multichannel sEMG set-up with 37 electrodes encircled the forearm. The determination of optimal pairs was based upon electrical peripheral nerve stimulation. We found pairs with the highest compound nerve action potential (CMAP) amplitudes and pairs that optimally distinguished between the flexor and extensor muscles. Large interelectrode distances lead to responses with larger amplitudes and therefore sensitively measure any remaining corticomuscular connections. As a follow-up, specific muscle group responses can be targeted with smaller interelectrode distances. In conclusion, this study helps to identify better electrode locations for the use of clinical TMS studies.

Activity patterns of extrinsic finger flexors and extensors during movements of instructed and non-instructed fingers.

The fingers of the human hand cannot be controlled fully independently. This phenomenon may have a neurological as well as a mechanical basis. Despite previous studies, the neuromechanics of finger movements are not fully understood. The aims of this study were (1) to assess the activation and coactivation patterns of finger specific flexor and extensor muscle regions during instructed single finger flexion and (2) to determine the relationship between enslaved finger movements and respective finger muscle activation. In 9 healthy subjects (age 22-29), muscle activation was assessed during single finger flexion using a 90 surface electromyography electrode grid placed over the flexor digitorum superficialis (FDS) and the extensor digitorum (ED). We found (1) no significant differences in muscle activation timing between fingers, (2) considerable muscle activity in flexor and extensor regions associated with the non-instructed fingers and (3) no correlation between the muscle activations and corresponding movement of non-instructed fingers. A clear disparity was found between the movement pattern of the non-instructed fingers and the activity pattern of the corresponding muscle regions. This suggests that mechanical factors, such as intertendinous and myofascial connections, may also affect finger movement independency and need to be taken into consideration when studying finger movement.

Tendon displacements during voluntary and involuntary finger movements.

In the human hand, independent movement control of individual fingers is limited. One potential cause for this is mechanical connections between the tendons and muscle bellies corresponding to the different fingers. The aim of this study was to determine the tendon displacement of the flexor digitorum superficialis (FDS) of both the instructed and the neighboring, non-instructed fingers during single finger flexion movements. In nine healthy subjects (age 22-29 years), instructed and non-instructed FDS finger tendon displacement of the index, middle and ring finger was measured using 2D ultrasound analyzed with speckle tracking software in two conditions: active flexion of all finger joints with all fingers free to move and active flexion while the non-instructed fingers were restricted. Our results of the free movement protocol showed an average tendon displacement of 27 mm for index finger flexion, 21 mm for middle finger flexion and 17 mm for ring finger flexion. Displacements of the non-instructed finger tendons (≈12 mm) were higher than expected based of the amount of non-instructed finger movement. In the restricted protocol, we found that, despite minimal joint movements, substantial non-instructed finger tendon displacement (≈9 mm) was still observed, which was interpreted as a result of tendon strain. When this strain component was subtracted from the tendon displacement of the non-instructed fingers during the free movement condition, the relationship between finger movement and tendon displacement of the instructed and non-instructed finger became comparable. Thus, when studying non-instructed finger tendon displacement it is important to take tendon strain into consideration.

Cerebellar theta burst stimulation does not improve freezing of gait in patients with Parkinson's disease.

Freezing of gait (FOG) in Parkinson's disease (PD) likely results from dysfunction within a complex neural gait circuitry involving multiple brain regions. Herein, cerebellar activity is increased in patients compared to healthy subjects. This cerebellar involvement has been proposed to be compensatory. We hypothesized that patients with FOG would have a reduced ability to recruit the cerebellum to compensate for dysfunction in other brain areas. In this study cerebellar activity was modified unilaterally by either excitatory or inhibitory theta burst stimulation (TBS), applied during two separate sessions. The ipsilateral cerebellar hemisphere, corresponding to the body side most affected by PD, was stimulated. Seventeen patients with PD showing 'off' state FOG participated. The presence of FOG was verified objectively upon inclusion. We monitored gait and bimanual rhythmic upper limb movements before and directly after TBS. Gait was evaluated with a FOG-provoking protocol, including rapid 360° turns and a 10-m walking test with small fast steps. Upper limb movement performance was evaluated with a repetitive finger flexion-extension task. TBS did not affect the amount of freezing during walking or finger tapping. However, TBS did increase gait speed when walking with small steps, and decreased gait speed when walking as fast as possible with a normal step size. The changes in gait speed were not accompanied by changes in corticospinal excitability of M1. Unilateral cerebellar TBS did not improve FOG. However, changes in gait speed were found which suggests a role of the cerebellum in PD.

Variable and Asymmetric Range of Enslaving: Fingers Can Act Independently over Small Range of Flexion.

The variability in the numerous tasks in which we use our hands is very large. However, independent movement control of individual fingers is limited. To assess the extent of finger independency during full-range finger flexion including all finger joints, we studied enslaving (movement in non-instructed fingers) and range of independent finger movement through the whole finger flexion trajectory in single and multi-finger movement tasks. Thirteen young healthy subjects performed single- and multi-finger movement tasks under two conditions: active flexion through the full range of movement with all fingers free to move and active flexion while the non-instructed finger(s) were restrained. Finger kinematics were measured using inertial sensors (PowerGlove), to assess enslaving and range of independent finger movement. Although all fingers showed enslaving movement to some extent, highest enslaving was found in adjacent fingers. Enslaving effects in ring and little finger were increased with movement of additional, non-adjacent fingers. The middle finger was the only finger affected by restriction in movement of non-instructed fingers. Each finger showed a range of independent movement before the non-instructed fingers started to move, which was largest for the index finger. The start of enslaving was asymmetrical for adjacent fingers. Little finger enslaving movement was affected by multi-finger movement. We conclude that no finger can move independently through the full range of finger flexion, although some degree of full independence is present for smaller movements. This range of independent movement is asymmetric and variable between fingers and between subjects. The presented results provide insight into the role of finger independency for different types of tasks and populations.

Functional connectivity in the neuromuscular system underlying bimanual coordination.

Neural synchrony has been suggested as a mechanism for integrating distributed sensorimotor systems involved in coordinated movement. To test the role of corticomuscular and intermuscular coherence in bimanual coordination, we experimentally manipulated the degree of coordination between hand muscles by varying the sensitivity of the visual feedback to differences in bilateral force. In 16 healthy participants, cortical activity was measured using EEG and muscle activity of the flexor pollicis brevis of both hands using high-density electromyography (HDsEMG). Using the uncontrolled manifold framework, coordination between bilateral forces was quantified by the synergy index RV in the time and frequency domain. Functional connectivity was assessed using corticomuscular coherence between muscle activity and cortical source activity and intermuscular coherence between bilateral EMG activity. The synergy index increased in the high coordination condition. RV was higher in the high coordination condition in frequencies between 0 and 0.5 Hz; for the 0.5- to 2-Hz frequency band, this pattern was inverted. Corticomuscular coherence in the beta band (16-30 Hz) was maximal in the contralateral motor cortex and was reduced in the high coordination condition. In contrast, intermuscular coherence was observed at 5-12 Hz and increased with bimanual coordination. Within-subject comparisons revealed a negative correlation between RV and corticomuscular coherence and a positive correlation between RV and intermuscular coherence. Our findings suggest two distinct neural pathways: 1) corticomuscular coherence reflects direct corticospinal projections involved in controlling individual muscles; and 2) intermuscular coherence reflects diverging pathways involved in the coordination of multiple muscles.

The coil orientation dependency of the electric field induced by TMS for M1 and other brain areas.

BACKGROUND: The effectiveness of transcranial magnetic stimulation (TMS) depends highly on the coil orientation relative to the subject's head. This implies that the direction of the induced electric field has a large effect on the efficiency of TMS. To improve future protocols, knowledge about the relationship between the coil orientation and the direction of the induced electric field on the one hand, and the head and brain anatomy on the other hand, seems crucial. Therefore, the induced electric field in the cortex as a function of the coil orientation has been examined in this study. METHODS: The effect of changing the coil orientation on the induced electric field was evaluated for fourteen cortical targets. We used a finite element model to calculate the induced electric fields for thirty-six coil orientations (10 degrees resolution) per target location. The effects on the electric field due to coil rotation, in combination with target site anatomy, have been quantified. RESULTS: The results confirm that the electric field perpendicular to the anterior sulcal wall of the central sulcus is highly susceptible to coil orientation changes and has to be maximized for an optimal stimulation effect of the motor cortex. In order to obtain maximum stimulation effect in areas other than the motor cortex, the electric field perpendicular to the cortical surface in those areas has to be maximized as well. Small orientation changes (10 degrees) do not alter the induced electric field drastically. CONCLUSIONS: The results suggest that for all cortical targets, maximizing the strength of the electric field perpendicular to the targeted cortical surface area (and inward directed) optimizes the effect of TMS. Orienting the TMS coil based on anatomical information (anatomical magnetic resonance imaging data) about the targeted brain area can improve future results. The standard coil orientations, used in cognitive and clinical neuroscience, induce (near) optimal electric fields in the subject-specific head model in most cases.

Combined N-of-1 trials to investigate mexiletine in non-dystrophic myotonia using a Bayesian approach; study rationale and protocol.

BACKGROUND: To obtain evidence for the clinical and cost-effectiveness of treatments for patients with rare diseases is a challenge. Non-dystrophic myotonia (NDM) is a group of inherited, rare muscle diseases characterized by muscle stiffness. The reimbursement of mexiletine, the expert opinion drug for NDM, has been discontinued in some countries due to a lack of independent randomized controlled trials (RCTs). It remains unclear however, which concessions can be accepted towards the level 1 evidence needed for coverage decisions, in rare diseases. Considering the large number of rare diseases with a lack of treatment evidence, more experience with innovative trial designs is needed. Both NDM and mexiletine are well suited for an N-of-1 trial design. A Bayesian approach allows for the combination of N-of-1 trials, which enables the assessment of outcomes on the patient and group level simultaneously. METHODS/DESIGN: We will combine 30 individual, double-blind, randomized, placebo-controlled N-of-1 trials of mexiletine (600 mg daily) vs. placebo in genetically confirmed NDM patients using hierarchical Bayesian modeling. Our results will be compared and combined with the main results of an international cross-over RCT (mexiletine vs. placebo in NDM) published in 2012 that will be used as an informative prior. Similar criteria of eligibility, treatment regimen, end-points and measurement instruments are employed as used in the international cross-over RCT. DISCUSSION: The treatment of patients with NDM with mexiletine offers a unique opportunity to compare outcomes and efficiency of novel N-of-1 trial-based designs and conventional approaches in producing evidence of clinical and cost-effectiveness of treatments for patients with rare diseases. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02045667.

The Physical Workload of Surgeons: A Comparison of SILS and Conventional Laparoscopy.

BACKGROUND: As extensively reported in the literature, laparoscopic surgery has many advantages for the patient. Surgeons, however, experience increased physical burden when laparoscopic surgery is compared with open surgery. Single-incision laparoscopic surgery (SILS) has been said to further enhance the patient's benefits of endoscopic surgery. Because in this surgical technique only 1 incision is made instead of the 3 to 5, as in conventional laparoscopic surgery (CLS), it is claimed to further reduce discomfort and pain in patients. Yet little is known about its impact on surgeons. This study aims to contribute by indicating the possible differences in physical workload between single-incision laparoscopy and CLS. METHODS: A laparoscopic box trainer was used to simulate a surgical setting. Participants performed 2 series of 3 different tasks in the box: one in the conventional way, the other through SILS. Surface electromyography was recorded from 8 muscles bilaterally. Furthermore, questionnaires on perceived workload were completed. RESULTS: Differences were found in the back, neck, and shoulder muscles, with significantly higher muscle activity in the musculus (M) longissimus, M trapezius pars descendens, and the M deltoideus pars clavicularis. Questionnaires did not indicate any significant differences in perceived workload. CONCLUSION: Performing SILS versus CLS increases the objectively measured physical workload of surgeons particularly in the back, neck, and shoulder muscles.

Myotonic discharges discriminate chloride from sodium muscle channelopathies.

Non-dystrophic myotonic syndromes represent a heterogeneous group of clinically quite similar diseases sharing the feature of myotonia. These syndromes can be separated into chloride and sodium channelopathies, with gene-defects in chloride or sodium channel proteins of the sarcolemmal membrane. Myotonia has its basis in an electrical instability of the sarcolemmal membrane. In the present study we examine the discriminative power of the resulting myotonic discharges for these disorders. Needle electromyography was performed by an electromyographer blinded for genetic diagnosis in 66 non-dystrophic myotonia patients (32 chloride and 34 sodium channelopathy). Five muscles in each patient were examined. Individual trains of myotonic discharges were extracted and analyzed with respect to firing characteristics. Myotonic discharge characteristics in the rectus femoris muscle almost perfectly discriminated chloride from sodium channelopathy patients. The first interdischarge interval as a single variable was longer than 30 ms in all but one of the chloride channelopathy patients and shorter than 30 ms in all of the sodium channelopathy patients. This resulted in a detection rate of over 95%. Myotonic discharges of a single muscle can be used to better guide toward a molecular diagnosis in non-dystrophic myotonic syndromes.