SUMMARY1. We observed in a previous study on the human foot dorsiflexor muscles that the fatigue-induced decline in motor output during sustained maximal voluntary contractions (MVCs) was temporarily counteracted during the initial phase of superimposed high-frequency (150 Hz) muscle vibration, whereas prolonged muscle vibration seemed to accentuate the fatigue-induced decline in gross EMG activity and motor unit firing rates. A more extensive investigation of this late effect of muscle vibration on MVCs was performed in the present study.2. Prolonged periods of superimposed muscle vibration caused a reduction of EMG activity, motor unit firing rates and contraction force in both intermittent and sustained MVCs. This vibration-induced effect had the following main characteristics: (i) it developed slowly during the course of about 1 min of sustained vibration and subsided within 10-20 s after the end of vibration; (ii) it was much more pronounced in some subjects than in others (not age-dependent) and it was accentuated by preceding muscle exercise; (iii) it affected primarily the subject's ability to generate and/or maintain high firing rates in high-threshold motor units.3. Since the effect developed while vibration at the same time exerted a tonic excitatory influence on the a-motoneurone pool (as evidenced by the presence of a tonic vibration reflex) it is argued that the vibration-induced suppression of motor output in MVCs probably does not depend on a-motoneurone inhibition, but on a reduced accessibility of these neurones to the voluntary commands. It is suggested that contributing mechanisms might be vibration-induced presynaptic inhibition and/or 'transmitter depletion' in the group I a excitatory pathways which constitute the afferent link of the y-loop.

1. In the present study on human foot dorsiflexor muscles we have examined the effects of high-frequency (150 Hz) muscle vibration on weak or moderate voluntary contractions (maintained by constant effort) and on maximal voluntary contractions (MCVs) of (i) non-fatigued muscles, (ii) muscles fatigued by sustained MVCs and (iii) muscles deprived of gamma-fibre innervation by partial anaesthetic nerve block. The motor outcome of the voluntary dorsiflexion efforts was assessed by measuring the firing rates of single motor units in the anterior tibial (TA) muscle, the mean voltage EMG activity from the pretibial muscles and foot dorsiflexion force. 2. With the subject instructed to exert constant effort in maintaining a weak or moderate contraction, superimposed vibration caused an enhancement of EMG activity and contraction force. 3. Previous claims that muscle vibration has no facilitatory effect on motor output in MVCs were found to hold true for non-fatigued but not for fatigued muscles. Thus, the fatigue-induced decline in EMG activity and motor unit firing rates was counteracted by short periods (less than 10-20 s) of superimposed vibration. However, with longer vibration periods it seemed as if the initial facilitation converted into an opposite effect which accentuated the fatigue-induced decline in motor output and contraction force. 4. Like muscle fatigue, a partial anesthetic block of the deep peroneal nerve, supposedly interrupting transmission in gamma-motor fibres, caused a reduction of MVC motor unit firing rates which could be counteracted by muscle vibration. In prolonged MVCs performed during the block, motor unit firing rates did not show the normal progressive decline from an initially high level, but stayed at a relatively constant low level throughout the contraction period. 5. Even though alternative interpretations are possible, the results agree with the hypotheses (i) that in sustained MVCs, fatigue processes occur not only in extrafusal but also in intrafusal muscle fibres, (ii) that the intrafusal fatigue leads to a reduction of the voluntary drive conveyed to the alpha-motoneurones via the gamma-loop and (iii) that vibration-induced activity in group Ia afferents can act as a substitute for the diminished fusimotor drive.

Muscle cramps induced by voluntary contraction and by electrical stimulation of the peripheral nerve were studied electrophysiologically in 10 healthy subjects. The aim was to verify that cramps can be evoked by electrical stimulation of peripheral nerve and to clarify the physiological mechanism responsible by analyzing the effect of muscular stretching on cramps. Our results showed: (1) Cramps can be induced even after peripheral nerve block by electrical stimulation distal to the block. (2) No cramps were recorded during or following maximal voluntary contraction without muscular shortening, while 7 of 10 subjects showed a true cramp following maximal effort with shortening of the muscle. (3) Muscle stretching caused a sudden interruption of cramps induced by either voluntary contraction or electrical stimulation of the peripheral nerve, even after the induction of nerve block. (4) The lengthening state of the muscle can strongly influence the possibility of evoking cramps by electrical stimulation of nerve. Our study verifies the experimental model proposed by Lambert in 1969, emphasizing the relevance of frequency of stimulation and confirming the hypothesis that cramps are of peripheral origin. The effects of muscle stretch and lengthening on cramp interruption and development also have a peripheral mechanism.

Summary: Purpose:We investigated 15 patients with juvenile myoclonic epilepsy (JME) by subjecting them to single and paired transcranial magnetic stimulation to test the hypothesis that motor cortical inhibition may be abnormal in this form of benign epilepsy.Methods: Different conditioning paradigms of paired transcranial magnetic stimulation were used with interstimulus intervals (ISIS) of varying lengths (1 to 400 milliseconds) to investigate changes in balance between excitatory and inhibitory intracortical circuits.Results: Motor evoked potential (MEP) inhibition at ISIs of 1 to 4 milliseconds was significantly lower in JME patients than in age-matched healthy controls (p < 0.001), whereas no significant differences in MEP inhibition were noted at long ISIs (100 to 150 milliseconds). This pattern was observed in both hemispheres in seven of seven patients studied bilaterally and was present in both treated and untreated patients. There were no group differences between JME patients and controls in intracortical facilitation, motor threshold, MEP amplitude, and cortical silent period.Conclusions: We documented a different pattern of MEP inhibition in JME patients, suggesting impaired functioning of inhibitory interneuronal circuits, which may account for the hyperexcitability of the motor system in this form of epilepsy.

We systematically reviewed the literature to evaluate the prevalence of phosphenes and the phosphene threshold (PT) values obtained during single-pulse transcranial magnetic stimulation (TMS) in adults with migraine. Controlled studies measuring PT by single-pulse TMS in adults with migraine with or without aura (MA, MwA) were systematically searched. Prevalence of phosphenes and PT values were assessed calculating mean difference (MD) and odds ratio (OR) with 95 % confidence intervals (CI). Ten trials (277 migraine patients and 193 controls) were included. Patients with MA had statistically significant lower PT compared with controls when a circular coil was used (MD −28.33; 95 % CI −36.09 to −20.58); a similar result was found in MwA patients (MD −17.12; 95 % CI −23.81 to −10.43); using a figure-of-eight coil the difference was not statistically significant. There was a significantly higher phosphene prevalence in MA patients compared with control subjects (OR 4.21; 95 % CI 1.18–15.01). No significant differences were found either in phosphene reporting between patients with MwA and controls, or in PT values obtained with a figure-of-eight coil in MA and MwA patients versus controls. Overall considered, these results support the hypothesis of a primary visual cortex hyper-excitability in MA, providing not enough evidence for MwA. A significant statistical heterogeneity reflects clinical and methodological differences across studies, and higher temporal variabilities among PT measurements over time, related to unstable excitability levels. Patients should therefore be evaluated in the true interictal period with an adequate headache-free interval. Furthermore, skull thickness and ovarian cycle should be assessed as possible confounding variables, and sham stimulation should be performed to reduce the rate of false positives. Phosphene prevalence alone cannot be considered a measure of cortical excitability, but should be integrated with PT evaluation.

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Summary:Purpose: Transcranial magnetic stimulation (TMS) of the brain allows the pharmacologic effects of anticonvulsant drugs (AEDs) on the excitability of motor corticospinal pathways to be evaluated in patients with epilepsy and normal subjects. However, no study has yet documented the changes in motor excitability in patients treated with lamotrigine (LTG). We aimed to study the effects of loading doses of LTG on TMS recordings in patients with epilepsy at the beginning of their treatment.Methods: We investigated single-pulse TMS in six patients with complex partial seizures. The TMS recordings were performed in five sessions before and during 5 weeks of treatment. Motor threshold, motor-evoked potential (MEP) amplitude, cortical silent period, and peripheral conduction velocity were used as parameters of evaluation. LTG was started with a dosage of 25 mglday until a daily maintenance dosage of 200 mg/day was reached.Results: The motor threshold activation of thenar muscles was significantly increased by LTG after 2 weeks of treatment and was increased in a parallel way to the loading dose of the drug at week 3 and 5 of treatment. The MEP size recorded from the thenar muscles did not show significant changes at high-or low-intensity stimulation. The cortical silent period remained unchanged at low-and high-intensity stimulation. The absolute latency of MEPs after cortical and cervical stimulation was unchanged, as was the central motor conduction time.Conclusions: Our study documents that loading doses of LTG, administered as monotherapy, progressively increases patients' motor thresholds over short periods.

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