Josef Elek

Attenuation of pathological tremors by functional electrical stimulation I: Method

In this study we explored the possibility of suppressing pathological tremors using closed-loop functional electrical stimulation (FES) to activate the tremorogenic muscles out-of-phase. A displacement signal monitored with a transducer was filtered so as to be “tuned” to the tremor frequency at the wrist or elbow. The filtered signal was used to amplitude-modulate the electrical stimulation. The design process was based on measurements of the open-loop frequency response characteristics of the forearm and hand to stimulation of the elbow and wrist flexors and extensors in a number of subjects. These data allowed us to identify closed-loop configurations, which attenuated 2–5 Hz tremors substantially, while only minimally attenuating functional movements in the 0–1 Hz range. There was a fairly delicate balance between efficacy and the risk of instability. However, designs were identified that offered enough tremor suppression and adequate immunity to muscle/load variations for the technique to be considered seriously for clinical application.

Attenuation of Pathological Tremors by Functional Electrical Stimulation II: Clinical Evaluation

In this study we evaluated a technique for tremor suppression with functional electrical stimulation (FES), the technical details of which were described in the previous paper. Three groups of patients were investigated: those with essential tremor, parkinsonian tremor, and cerebellar tremor associated with multiple sclerosis. In each group, tremor was attenuated by significant amounts (essential tremor: 73%; parkinsonian tremor: 62%; cerebellar tremor: 38%). These attenuations were in good accord with predictions based on the dynamic analyses and filter designs derived in the previous paper. With filters “tuned” to the lower mean tremor frequency encountered in the cerebellar patients, more attenuation was possible in this group as well. We identified some practical limitations in the clinical application of the technique in its present form. The most important was that in daily use, only one antagonist pair of muscles can realistically be controlled. At first sight, this restricts the usefulness of the system to patients with single-joint tremors. However, the concomitant use of mechanical orthoses may broaden the scope of application.

Remote F-wave changes after local botulinum toxin application.

OBJECTIVE Although the therapeutic effects of botulinum toxin A can be explained by its action at the neuromuscular junction, central or more proximal effects have also been discussed. METHODS Eleven patients with torticollis spasmodicus and 3 patients with writers cramp were studied before and 1 and 5 weeks after the first treatment with botulinum toxin. We measured compound muscle action potentials (CMAPs), motor conduction velocities (MCVs), the shortest (SFL) and the mean F-wave latencies (MFL) and F-wave persistence (30 trials) of untreated muscles for each side (ulnar nerve-abductor digiti minimi muscle, peroneal nerve-tibialis anterior muscle). RESULTS CMAPs and MCVs showed no significant changes. For both nerves, however, SFL and MFL were prolonged slightly 1 week after treatment and returned to about baseline after 5 weeks (t test). The F-wave persistence was reduced 1 week after treatment for the right ulnar and both peroneal nerves (t test). CONCLUSIONS These results are not likely due to an impairment of neuromuscular transmission. Instead, we propose a decreased excitability of alpha-motoneurons supplying non-treated muscles. A reduction of muscle spindle activity or changes of the recurrent inhibition are discussed as possible causes.

Assessment of human motor unit twitches — a comparison of spike-triggered averaging and intramuscular microstimulation☆

We recorded twitches of single motor units (MUs) in the human first dorsal interosseus muscle using either spike-triggered averaging (STA; 236 MUs in 12 normal subjects) or low-rate intramuscular microstimulation of motor axons (IMS; 200 MUs in 20 normal subjects). We analysed twitch force (TF), maximal rate of rise of force (MRRF), contraction time (CT) and half-relaxation time (HRT). MRRF, CT and HRT were significantly smaller with STA than with IMS whereas TFs were fairly similar. Higher stimulus rates (up to 14 Hz) in IMS resembling the voluntary MU firing rates in STA were associated with a decrease of all twitch parameters because of partial fusion of the twitches (20 MUs). Concerning MRRF, CT and HRT, the reduced values matched those obtained by STA, suggesting that the underestimation of these parameters in STA can be mainly attributed to partial fusion. The reduction of TF with high rate IMS but not with STA reveals that other factors such as MU synchronization and non-linear force summation of MU contractions must counteract the effects of partial fusion in STA. We conclude that both STA and IMS are appropriate for assessing TFs in man while the time-dependent parameters MRRF, CT and HRT will be underestimated with STA.

Mechanical implications of paired motor unit discharges in pathological and voluntary tremor

Paired motor unit discharges (PDs), i.e., two discharges of the same motor unit (MU) with short interval, and their relation to tremor amplitude were studied in the first dorsal interosseous muscle (FDI) of patients with parkinsonian or essential tremor and in normal subjects mimicking tremor. In both pathological and voluntary tremor, interdischarge intervals of PDs were inversely correlated with the amplitude of the subsequent tremor beat, i.e., PDs with shorter intervals were followed by higher tremor beats. To further assess their mechanical impact, PDs were simulated by applying paired stimuli to MUs of the FDI in normal subjects using intramuscular microstimulation. Following paired stimuli, summation of twitch responses was more than linear. This was also the case with the paired stimuli applied at a tremor-like repetition rate (5 Hz). These findings stress the importance of PDs for tremor expression.

Parameters of human motor unit twitches obtained by intramuscular microstimulation

Intramuscular microstimulation of motor axons was used to study twitch responses of 209 motor units (MUs) in the first dorsal interosseus muscle (FDI) of 20 normal subjects. Twitch peak force (TF), maximum rate of rise of force (MRRF), contraction time (CT) and one-half relaxation time (HRT) were determined. The distributions of TF (mean 16.0 mN, median 10.3 mN) and MRRF (mean 0.88 N s-1, median 0.66 N s-1) were skewed to the right with the majority of the values lying in the lower ranges, whereas CT (mean 63 ms, median 62 ms) and HRT (mean 61 ms, median 58 ms) were approximately normally distributed. TF was significantly correlated with MRRF, but not with CT in contrast with studies of cat gastrocnemius muscle. TF values were similar to those obtained by spike-triggered averaging in the same muscle. The method proved to be reliable and appropriate for use in patients. Examples of MU twitch parameters from three patients with chronic partial denervation of the FDI are described.

Activation of high-threshold motor units in man by transcranial magnetic stimulation

Motor units (MUs) with low voluntary recruitment thresholds are the first to be activated by transcranial magnetic stimulation. It is not clear, however, if high-threshold MUs can also be activated and if they contribute to motor evoked potentials (MEPs). We therefore studied 11 high-threshold motor units in the first dorsal interosseous muscle of 11 healthy subjects. Voluntary recruitment thresholds ranged from 22 to 41% (29.5 +/- 5.6%; mean +/- S.D.) of maximal muscle force. When MUs were driven at their recruitment thresholds, transcranial magnetic stimuli were applied to the vertex. Peri-stimulus time histograms of MU discharges were constructed. All MUs studied revealed a period of increased firing probability at 19-27 ms after the stimulus (primary peak). Stimulus intensities were lower by 10-57% of the maximal stimulator output than required to produce near maximal MEPs in conventional surface EMG recordings in the same subjects. We conclude that high-threshold MUs can be activated by transcranial magnetic stimulation and that they contribute to conventionally recorded MEPs.