Carbamazepine and oxcarbazepine in adult patients with Dravet syndrome: Friend or foe?

PURPOSE: In newly diagnosed patients with Dravet syndrome sodium channel blockers are usually avoided. However, in many adult patients the diagnosis was made long after the initiation of therapy. The purpose of our study was to acquire information concerning the potential risks and benefits of (ox)carba(ma)zepine withdrawal in adult patients with genetically confirmed Dravet syndrome. METHOD: We identified 16 adults with Dravet syndrome, living in a tertiary care facility for people with epilepsy and an intellectual disability. We reviewed clinical history, genetic findings, the type and duration of sodium channels blockers that were used, seizure types and frequency, and the effect of a change in these medications. RESULTS: The study population consisted of 9 men and 7 women. Median age was 35 years (range 20-61 years). An attempt to withdraw carbamazepine (CBZ) was made in 9 patients. In 3 of these patients an increase in tonic-clonic seizures was observed. An attempt to withdraw oxcarbazepine (OXC) was made in 3 patients, leading to a complete stop in 2 patients. 3 of the 4 deaths in the withdrawal-group were related to epilepsy. CONCLUSION: In adult patients with Dravet syndrome withdrawal of CBZ or OXC is not without risks. We suggest that (ox)carba(ma)zepine withdrawal should be considered in these patients but only if there is a good reason to do so and only if they are closely monitored.

High-density surface EMG study on the time course of central nervous and peripheral neuromuscular changes during 8 weeks of bed rest with or without resistive vibration exercise.

The aim of the present study was to assess the time course and the origin of adaptations in neuromuscular function as a consequence of prolonged bed rest with or without countermeasure. Twenty healthy males volunteered to participate in the present study and were randomly assigned to either an inactive control group (Ctrl) or to a resistive vibration exercise (RVE) group. Prior to, and seven times during bed rest, we recorded high-density surface electromyogram (sEMG) signals from the vastus lateralis muscle during isometric knee extension exercise at a range of contraction intensities (5-100% of maximal voluntary isometric torque). The high-density sEMG signals were analyzed for amplitude (root mean square, RMS), frequency content (median frequency, F(med)) and muscle fiber conduction velocity (MFCV) in an attempt to describe bed rest-induced changes in neural activation properties at the levels of the motor control and muscle fibers. Without countermeasures, bed rest resulted in a significant progressive decline in maximal isometric knee extension strength, whereas RMS remained unaltered throughout the bed rest period. In line with observed muscle atrophy, both F(med) and MFCV declined during bed rest. RVE training during bed rest resulted in maintained maximal isometric knee extension strength, and a strong increase ( approximately 30%) in maximal EMG amplitude, from 10 days of bed rest on. Exclusion of other factors led to the conclusion that the RVE training increased motor unit firing rates as a consequence of an increased excitability of motor neurons. An increased firing rate might have been essential under training sessions, but it did not affect isometric voluntary torque capacity.

Influence of motoneuron firing synchronization on SEMG characteristics in dependence of electrode position.

The frequency content of the surface electromyography (SEMG) signal, expressed as median frequency (MF), is often assumed to reflect the decline of muscle fiber conduction velocity in fatigue. MF also decreases when motor unit firings synchronize, and we hypothesized that this effect can explain the electrode-dependent pattern in our previous recordings from the trapezius muscle. An existing motoneuron (MN) model describes the afterhyperpolarization following a spike as an exponential function on which membrane noise is superimposed. Splitting the noise into a common and an individual component extended the model to a MN pool with a tunable level of firing synchrony. An analytical volume conduction model was used to generate motor unit action potentials to simulate SEMG. A realistic level of synchrony decreased the MF of the simulated bipolar SEMG by approximately 30% midway between endplate position and tendon but not above the endplate. This is in accordance with experimental data from the biceps brachii muscle. It was concluded that the pattern of decrease of MF during sustained contractions indeed reflects MN synchronization.

Impaired motor cortical inhibition in Parkinson's disease: motor unit responses to transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS)-induced corticospinal volleys can be investigated in detail by analysing the firing pattern modulation of active motor units (MUs) at close to threshold stimulation strengths. In amyotropic lateral sclerosis (ALS) these volleys are dispersed and prolonged, attributed to altered motor cortical excitability. Impaired intracortical inhibition, as found in ALS, is not unique to this disease, but is also a well-established finding in Parkinson's disease (PD). The present study explored whether reduced inhibition in the motor cortex in PD is accompanied by similar changes in motor unit firing modulation by TMS as are found in ALS. TMS was applied to the contralateral motor cortex during a low-force voluntary elbow flexion while 126-channel surface electromyography (SEMG) was recorded from the brachial biceps muscle. A recently developed method for SEMG decomposition was used to extract the firing pattern of up to five simultaneously active MUs. Sixteen MUs in 7 PD patients and 17 MUs in 5 healthy control subjects were analysed and peristimulus time histograms (PSTHs) and interspike interval change functions (IICFs) were calculated. The IICF provides an estimate of the modulation of the postsynaptic membrane potential at the spinal motoneuron, evoked by the stimulus. In PD the duration of the PSTH peak was significantly increased and the synchrony was decreased. The excitatory phase at 20-50 ms of the IICF was broader in PD, reflecting a longer duration of the TMS-evoked excitatory postsynaptic potential. It is proposed that these results are due to prolonged corticospinal volleys resulting from impaired intracortical inhibition.

Magnetic stimulation-induced modulations of motor unit firings extracted from multi-channel surface EMG.

The noninvasive assessment of motor unit (MU) firing patterns on the basis of topographical information from 128-channel high-density surface electromyography (SEMG) is reported. First, multi-channel MU action potential (MUAP) templates are obtained by clustering detected firing events according to the surface topography of the MUAP. Second, a template-matching algorithm is used to find all firings of a MU, including the superimpositions of MUAPs. From a single recording, the firing pattern of up to five MUs could be derived. The modulation of MU firing by transcranial magnetic stimulation was analyzed in peri-stimulus time histograms. The results are similar to previous results of transcranial magnetic stimulation (TMS) obtained by needle electromyographic (EMG) recordings. The method can be used to investigate MU firing patterns in patients with central motor disorders. An additional advantage of the technique, apart from its noninvasiveness, is the structural and functional information that it provides on the MUs, which is not obtained by needle EMG.

Surface EMG mapping of the human trapezius muscle: the topography of monopolar and bipolar surface EMG amplitude and spectrum parameters at varied forces and in fatigue.

OBJECTIVES: To investigate the factors affecting the topography of trapezius muscle EMG, multichannel recordings were made at different forces of isometric shoulder elevation and during fatiguing exercise. METHODS: Twenty-eight channels of monopolar EMG were recorded from an array of 4 x 7 electrodes placed on the upper trapezius muscle. From the monopolar EMG and the bipolar derivations the root mean square (RMS(monopolar), RMS(bipolar)) and power spectrum median frequency (MF(monopolar), MF(bipolar)) were calculated. RESULTS: The maximum RMS(monopolar) was located above the middle part of the trapezius muscle, where a minimum was found for RMS(bipolar). The cranial-caudal RMS distribution shifted upwards when the force was increased from 50 to 100% MVC and during fatigue. MF(bipolar) showed a peak above the endplate region, where the MF(monopolar) was low. During fatigue the normalized MF slope was independent of the cranial-caudal electrode position, but MF(monopolar) decreased most strongly at positions above the endplate region, where MF(bipolar) decreased less. CONCLUSIONS: While the changes in MF reflected metabolic properties and volume conduction phenomena in the muscle, changes in RMS reflected a compensation for the fatigue processes within the muscle. The RMS changes in fatigue can be explained by the direction of the fibres involved in shoulder elevation.

Surface EMG of shoulder and back muscles and posture analysis in secretaries typing at visual display units.

OBJECTIVE: A study was carried out to investigate temporal changes of activation of shoulder and back muscles in workers at visual display units by means of surface EMG. Moreover, postural parameters were recorded to distinguish fatigue-related from posture-related changes of the myoelectrical activity. METHODS: Nine healthy female office workers typed texts spoken from tape during three 1-h-long sessions. After the first and again after the second hour there was a break of 15 min. Sixteen-channel surface EMG was bipolarly recorded from the erector spinae, trapezius, deltoid and sternocleidomastoid muscles. Root mean square (RMS) and power spectrum median frequency of the EMG were calculated. Sitting posture was assessed using an eight-channel movement analysis system with ultrasound markers. The position of the seventh cervical spinous process and the left and the right acromion were analysed synchronously with the EMG characteristics using regression analysis. RESULTS: The normalised RMS of the left and right trapezius muscle increased, while the median frequency did not change. The increase of the normalised RMS was significantly lower when the linear influence of posture was excluded. On average, the distance between C7 and the left and right acromion decreased within each working an hour. C7 became lower on average by 5.5 mm within an hour, whereas the acromions became lower by only 1.7 mm (left) and 3.3 mm (right). CONCLUSION: The increase in trapezius muscle activity was partly related to a lifting of the shoulders to compensate a slight slumping of the back. Another part of the EMG activity increase has to be attributed to fatigue, to attention-related activity or to the combination of both. Therefore, training of the back muscles and a varied organisation of work might have a preventive effect with respect to musculoskeletal complaints in VDU workers.

Magnetic stimulation of the dorsal premotor cortex modulates the Simon effect.

In choice reaction tasks, subjects typically respond faster when the relative spatial positions of stimulus and response match than when they do not match. A prominent explanation attributes this 'Simon effect' to automatic response activation elicited by spatial correspondence, which facilitates or competes with the controlled selection of the response demanded by the stimulus. To test this account, we applied repetitive transcranial magnetic stimulation (rTMS) on the dorsal premotor cortex (PMd), as this area may subserve the inhibitory control of automatic response activation. Temporary interference with PMd was predicted to release the automatic activation from inhibition and thereby enhance the Simon effect. The results confirmed a modulation for trials following an incompatible trial, providing new evidence for competition between automatic and controlled response activation as a mechanism underlying the Simon effect.