Influence of electrode site and size on variability of magnetic evoked potentials.

Successive magnetic evoked potentials (MEPs) concern varying motor neurons. We investigated whether this MEP-specific source of variability depends on electrode site and size. Amplitude variability (standard deviation) was largest over the center of the hypothenar muscles. Latencies were longer at distal and proximal sites than at the center site. Large electrodes (10 cm2) did not decrease this source of amplitude variability compared with EEG electrodes, in contrast to other sources of variability.

Cortical excitability of the biceps muscle after intercostal-to-musculocutaneous nerve transfer.

OBJECTIVE: Restoration of volitional control over elbow flexion has been demonstrated in patients who have undergone intercostal-to-musculocutaneous nerve transfer. We investigated the cortical area involved in the control over elbow flexion after intercostal-to-musculocutaneous nerve transfer. METHODS: Maps of magnetically excitable cortical areas of the affected arms of five patients were compared with maps of their healthy arms and maps of both arms of four healthy control subjects. The intercostal cortical area was also studied, requiring needle electromyography mapping (n = 1). RESULTS: The cortical areas of affected arms were smaller and less excitable than those of healthy arms. The locations of these areas could not be distinguished from that of the normal cortical biceps area but seemed to differ from that of the intercostal cortical area. CONCLUSION: The existence of a biceps-like cortical area related to the reinnervated muscle can be explained in two ways. Interneurons from the original biceps area might excite the cortical neurons controlling the intercostal muscles. Alternatively, corticospinal neurons of the original biceps area may project directly onto spinal intercostal motor neurons. Cerebral plasticity does occur in intercostal-to-musculocutaneous nerve transfers and may be crucial for their clinical success.

Differential effects of unilateral magnetic cortical stimulation on reaction time.

Data from patients with brain lesions suggested that the right hemisphere is involved in the intention of simple movements, while the left is involved in more complex tasks. The contributions of each hemisphere to a reaction time (RT) task were assessed with cortical magnetic stimulation in five healthy right-handed subjects. Subjects were asked to push buttons with both hands as fast as possible after a visual start stimulus. At three different delays (25, 50 and 75 ms) after the start signal, a magnetic stimulus of 20, 40 or 60% of maximum intensity was given to either the right or the left hemisphere. Delay, intensity and side of stimulation varied in random order. Repeated measures analysis of variance showed two main effects: firstly, RT was longer on the body side innervated by the stimulated than by the non-stimulated hemisphere. Thus, cortical stimulation delayed the execution of a motor task, as shown previously. Secondly, there was an interaction between side of stimulation and delay of the cortical stimulus. At a delay of 25 ms, right-sided stimulation resulted in longer RTs than left-sided stimulation. At delays of 50 and 75 ms, the reverse proved true. In both cases the effect held for both hands. According to these results, the right hemisphere is predominantly involved in the early phases of an RT task, while the left hemisphere is more involved in later phases of processing. The results show that cortical magnetic stimulation can be used to investigate differential contributions of the hemispheres to motor tasks in vivo.

Interictal cortical excitability to magnetic stimulation in familial hemiplegic migraine.

We studied interictal cortical excitability with magnetic stimulation in controls, in patients with migraine with aura, and in patients with familial hemiplegic migraine (FHM), in which ictal hemiparesis occurs. Amplitudes (p < 0.05) and amplitude ratios (p < 0.01) revealed heightened excitability in migraine with aura when compared to controls. In patients with FHM, mean thresholds were higher (p < 0.001) and conduction times longer (p < 0.01) than in controls. In FHM, amplitudes were lower on the ictally paretic side of the body than on the other (p < 0.05). Patients with FHM may have increased interictal cortical excitability, complicated by decreased excitability of the affected side.

Interictal cortical hyperexcitability in migraine patients demonstrated with transcranial magnetic stimulation.

Cortical excitability to magnetic stimulation was investigated interictally in 10 patients with migraine with aura, 10 with migraine without aura and in 10 healthy volunteers. Thresholds, latencies and amplitudes of the magnetic-evoked potentials (MEPs) were measured from threshold to 100% stimulus intensity in 10% steps. Compound motor action potentials (CMAPs) evoked with supramaximal electrical stimulation of the ulnar nerve were used to calculate MEP/CMAP amplitude ratios. Thresholds and latencies of MEPs did not differ between patients and controls. MEP/CMAP amplitude ratios were significantly increased at all intensities in patients with migraine with aura (RM-ANOVA, p < 0.01) and without aura (p < 0.05) compared with controls. In migraine patients, MEP amplitudes and MEP/CMAP amplitude ratios were positively related to the frequency of migraine attacks (Spearman's r = 0.47, p < 0.01 and r = 0.56, p < 0.002, respectively). MEP parameters were not related to the side of the headache nor the aura, in either type of migraine, implying that both hemispheres are equally involved in migraine. Migraine with aura and, to a lesser extent, migraine without aura, are associated with increased interictal cortical excitability.

Botulinum toxin versus trihexyphenidyl in cervical dystonia: a prospective, randomized, double-blind controlled trial.

BACKGROUND: Botulinum toxin type A (BTA) is replacing trihexyphenidyl as the treatment of choice for idiopathic cervical dystonia (ICD), but there has never been a direct comparative study. METHODS: This trial compares the effectiveness of BTA with that of trihexyphenidyl in a prospective, randomized, double-blind design. Sixty-six consecutive patients with ICD were randomized to treatment with trihexyphenidyl tablets plus placebo injection or placebo tablets plus BTA injections. Tablets were administered daily according to a fixed schedule. Dysport or saline was injected under EMG guidance at study entry and again after 8 weeks. Patients were assessed for efficacy at baseline and after 12 weeks by different clinical rating scales. RESULTS: Sixty-four patients completed the study, 32 in each group. Mean dose of BTA was 292 mouse units (first session) and 262 mouse units (second session). Mean dose of trihexyphenidyl was 16.25 mg. The changes on the Disability section of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-Disability) (primary outcome), Tsui Scale, and the General Health Perception Subscale were significantly in favor of BTA. More patients treated with BTA had an improvement of at least three points on the TWSTRS-Disability (14 versus 6) and on the Tsui Scale (23 versus 12). Adverse effects were significantly less frequent in the BTA group. CONCLUSION: BTA is significantly more effective in the treatment of ICD, with less adverse effects.

Cortical excitability and response variability of transcranial magnetic stimulation.

The magnetic evoked potential (MEP) following transcranial magnetic stimulation is subject to several sources of variability. In this study, relationships between stimulus intensity and MEP latency, amplitude, duration, and area of the hypothenar muscles were assessed in 12 right- and 14 left-handed subjects. Effects of handedness, coil orientation, intensity of stimulation, and intersubject variability on these relationships were analyzed. The intraindividual variability was analyzed as the standard deviation (SD) and the coefficient of variation (CV) of four trials. The mean response threshold was significantly lower (p < 0.0001) for preferential stimulation (32%) than for nonpreferential stimulation (45%). With increasing stimulus intensities, MEP amplitudes still increased at 100% intensity in some subjects while in others the stimulus response-relations saturated. MEP amplitudes at an intensity of 20% above threshold ranged between 6 and 100% of MEP amplitude at maximum intensity. Differences between dominant and non-dominant hands were not seen, regardless of handedness. The SD of latency, amplitude, duration, or area depended on stimulus intensity. The CV however, was influenced by the intensity of stimulation: The CV for amplitude decreased from 46% at threshold to 10% at higher intensities. The variability of the MEP amplitude is only related to stimulus intensity when it is expressed in relation to it but not when it is expressed in absolute terms. The stimulus-response relation offers a more extensive measure of cortical excitability than the use of thresholds alone for the measurement of cortical excitability. The question can be raised whether high intensities should be used for clinical testing rather than threshold-related intensities.

The movement-related cortical potential is abnormal in patients with idiopathic torsion dystonia.

Voluntary movements, such as the self-paced finger extension task used in the present experiments, are preceded by a slowly rising negative electroencephalographic potential [the movement-related cortical potential (MRCP)]. The early NS1 component of the potential was no different in patients with primary dystonia affecting the arm (n = 6) compared with matched controls. In contrast, the peak amplitude of the MRCP was smaller in the patients, despite the fact that the movements made by the two groups were very similar; it was of equal size over both left and right hemispheres, rather than being larger on the side contralateral to the movement. These results are similar to those observed by others in patients with symptomatic dystonia secondary to lesions of the basal ganglia or their output pathways and may reflect abnormal basal ganglia input to motor areas of cortex before the onset of a self-paced movement.

CMAP variability as a function of electrode site and size.

The site of the recording electrode influences the amplitude of the compound muscle action potential (CMAP) and its variation over a length of nerve. The effects of large electrodes on this source of intraindividual variability were assessed. Right median nerves of 20 healthy subjects were studied, and recordings made at three sites (at 1-cm intervals) using five electrode sizes (0.01, 1, 2, 4, and 10 cm2). Site-induced variability was defined as the standard deviation (SDi) and coefficient of variation (CVi) of the measurements of the three sites. Site induced variability of all parameters (latency, duration, amplitude, area, MNCV, and the percentile changes of duration, amplitude, and area over the forearm) decreased significantly with electrode size. Decreases were most pronounced for amplitude and area: CVi fell from 29% and 30% (0.01-cm2 electrode) to 10% and 8% (10 cm2). It is argued that large electrodes record activity of more motor units than small electrodes, and that their measurement fields overlap to a greater extent. The use of large electrodes is recommended in order to reduce site-induced CMAP variability.

Influence of recording site on CMAP amplitude on its variation over a length of nerve.

The distinctions between blocking, abnormal temporal dispersion, and normal conduction require delineation of the normal change in amplitude of the compound muscle action potential (CMAP) over a length of nerve. Effects of the recording site on CMAP amplitude and on its variation were studied in median and ulnar nerves of 13 healthy subjects. CMAPs were recorded from three sites: halfway along the muscles and 1 cm distal and proximal. Elbow-wrist amplitude percentages (CMAP%) were calculated. CMAP amplitudes varied considerably between sites and subjects. Amplitudes were maximal at the middle site in only 16 of 26 nerves. The site of maximal amplitude could not be identified on the basis of thumb anatomy. CMAP% was not related to CMAP amplitude, and differed by up to 32% between adjacent sites. CMAP formation involves spatial factors (electrode site, limb position, and limb anatomy), temporal factors (dispersion), and their interaction, explaining why CMAP% can exceed 100%. The site of the recording electrode affects CMAP amplitude and CMAP% to clinically relevant degrees. Standardization of the recording site may improve reliability of CMAP% studies.

Primary orthostatic tremor: further observations in six cases.

The clinical and physiological features of six new patients with primary orthostatic tremor are described. We suggest that use of the term primary orthostatic tremor be confined to the clinical syndrome in which unsteadiness when standing is the predominant complaint and accompanied by characteristic electrophysiological findings of a rapid (frequency around 16 Hz), regular leg tremor which is not influenced by peripheral feedback, is synchronous between homologous leg muscles, and in certain postures of the upper limbs, between muscles of the arm and leg. The fast frequency of muscle activity in primary orthostatic tremor of the legs causes unsteadiness when standing (presumably due to partially fused muscle contraction) but only a fine ripple of muscle activity is visible. In contrast, the slower frequency of other leg tremors, for example essential tremor, results in obvious leg movement which is evident in many leg postures, is variable over time and can be reset by a peripheral nerve stimulus. Essential tremor and orthostatic tremor do not respond to the same therapies, suggesting differences in the pharmacological profiles of the two conditions. Accordingly, there are clinical, physiological and pharmacological differences between primary orthostatic and essential tremor. Whether these factors are sufficient to regard these tremors as separate conditions is discussed.

Magnetic stimulation of the brain: starting or stopping.

A very brief magnetic pulse is able to stimulate cortical neurons through the intact scalp. It can elicit movement of a limb by activation of pyramidal cells either directly or via interneurons. When making a voluntary movement, a corresponding program of the task is thought to be compiled beforehand. In patients with ideomotor apraxia who can not perform a task, a lesion of the left hemisphere is frequently found. A magnetic cortical stimulus given directly before a movement is executed is known to delay the onset without altering the pattern. When it will become feasible to deliver a localized stimulus to one hemisphere, this will induce a temporary pause in that area and thus simulating a lesion in intact brain. In this way information can be gathered on the localization of voluntary action in intact brains.

Correlation of phasic muscle strength and corticomotoneuron conduction time in multiple sclerosis.

Central motor conduction times for the adductor pollicis muscle, the twitch force of that muscle to scalp magnetic motor cortex stimulation, and the maximum force of phasic voluntary contraction of the same muscle were measured in 15 patients with multiple sclerosis. Two tests of manual dexterity of the same hand also were studied: the Purdue pegboard test, and the maximal frequency of a scissors movement of the thumb and index finger. The patients had normal strength or minimal weakness of the intrinsic muscles of the hand on clinical examination. The mean central motor conduction times for the adductor pollicis muscle for the patients were longer than normal, the peak twitch force of the adductor pollicis muscle evoked by cortical stimulation and the maximum force of a phasic voluntary contraction of the adductor pollicis muscle were smaller than normal. There were strong correlations between all these measures. Central motor conduction time in the patients was inversely correlated with voluntary phasic force and the twitch force after cortical stimulation. That is, the longer the central motor conduction time, the weaker the force. Prolonged central motor conduction time is likely to be accompanied by conduction block in corticomotoneuron pathways. The correlation of central motor conduction time with voluntary phasic force and the twitch force most likely reflects the degree of conduction block and temporal dispersion rather than delay in conduction per se. These results indicate that objective assessments of phasic muscle strength may reveal correlations with central motor conduction time that are not evident on conventional clinical examination which assesses tonic muscle contraction strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid elbow movements in patients with torsion dystonia.

Rapid, self paced and self terminated elbow flexion movements were studied in a group of 10 patients with dystonia affecting the arms. The movements were slower and for small amplitude movements, more variable than those recorded in normal subjects. The duration of the first agonist burst was prolonged, even when compared with normal subjects deliberately moving slowly. Cocontraction of agonist and antagonist muscles during ballistic movements was common and may contribute to the bradykinesia. These findings are compared with similar studies of other diseases of the motor system. Unlike many other conditions which also reduce the speed of ballistic voluntary movements, the patients with dystonia in the present study showed a normal symmetry of acceleration and deceleration times. One interpretation of this finding is that aspects of the basic motor programmes are relatively preserved in this condition and account for the surprising retention of motor skills shown by some patients with dystonia.

Which factors influence age at onset and rate of progression in Huntington's disease?

Fifty-one families of patients affected with Huntington's chorea were interviewed with respect to age at onset, symptoms at onset and course of the disease. The interview further comprised questions pertinent to line of transmission, socio-economic status, housing, previous illnesses and pregnancy and stillbirth. Since the study was set up as a fishing expedition detailed quantitative information was gathered on many life-style factors including eating, drinking and smoking habits. In adult age onset cases earlier age at onset correlated with lower rate of progression. Line of transmission was of no influence on age at onset in cases with onset above 20 years. No statistically significant relationship was found between any factor studied and age at onset, except for the intake of milk. Higher previous milk intake was associated with earlier ages at onset. This finding is critically discussed. No difference was found between the respective ages at onset of conduct disorders and affective disorders. This suggests that they are both associated with the Huntington gene.

Horizontal and vertical saccadic eye movement abnormalities in Huntington's chorea.

With a newly developed infrared reflection technique, voluntary saccadic eye movements (VOLS), visually evoked saccades (VES) and unsuppressed visually evoked reflex saccades (USVERS) were measured in 11 patients with Huntington's chorea. Abnormalities, including latency increase, peak velocity decrease and undershoot dysmetria with multiple step saccades were found in all types of saccadic eye movements. Peak velocity decrease and undershoot dysmetria can be explained by dysfunction of the brainstem reticular formation in Huntington's chorea. USVERS and square wave jerks occurred abnormally frequently and showed direction-dependent differences. Both were more frequent in horizontal than in vertical direction. Frequency of USVERS and square-wave jerks tended to be correlated. These findings point to disinhibited superior colliculi as a possible common supranuclear origin of USVERS and square-wave jerks in Huntington's chorea.