Abnormal facilitation of the response to transcranial magnetic stimulation in patients with Parkinson's disease.

We studied the facilitation of the motor evoked potential (MEP) elicited with transcranial magnetic stimulation by increasing the stimulus intensity and the degree of voluntary activation of the target muscle in patients with Parkinson's disease (PD) and in normal volunteers. The threshold intensity for eliciting MEPs with the muscle at rest did not differ in PD patients and normal subjects. At rest, stimuli of similar intensity, related to the individual's threshold, elicited MEPs with amplitudes consistently larger in patients than in normal subjects, although when we compared the averaged MEP amplitude across all stimulus intensities, the differences reached only borderline statistical significance. Voluntary muscle activation elicited a smaller increase in the MEP area in PD patients than in normal subjects. Increasing the degree of voluntary muscle activation at fixed stimulus intensities elicited a smaller increase of MEP amplitude, duration, and area in PD patients than in normal subjects. These results suggest that control of the excitability of the motor system is abnormal in PD patients, with enhancement of excitability at rest and weak energization during voluntary muscle activation.

Akinesia in Parkinson's disease. I. Shortening of simple reaction time with focal, single-pulse transcranial magnetic stimulation.

We studied the effects of transcranial magnetic stimulation (TMS) of the motor cortex on simple reaction time (RT) in 10 patients with Parkinson's disease compared with 10 age-matched normal controls. The subjects flexed their right elbow rapidly in response to a visual go-signal. In random trials, TMS was applied to the left motor cortex at varying delays after the go-signal. In trials without TMS, RT was longer in the patients. However, in the trials with subthreshold TMS, RT in the patients became as fast as RT in trials without TMS in the controls. This shortening was associated with normalization of the voluntary triphasic EMG pattern and the pre-movement cortical excitability increase.

Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation.

We studied the effects of repetitive transcranial stimulation of the motor cortex (rTMS) on choice reaction time (cRT), movement time (MT), and error rate (ER) in a serial reaction-time task in six medicated patients with Parkinson's disease (PD) and 10 age-matched normal controls. In normal subjects, subthreshold 5-Hz rTMS did not significantly change cRT, slightly shortened MT, but increased ER. In the patients, rTMS significantly shortened cRT and MT without affecting ER. These effects did not impair procedural learning. Performance on a grooved peg-board test was improved by rTMS in the same PD patients, especially when they were off medications, but worsened in the normal subjects. Repetitive, subthreshold motor cortex stimulation can improve performance in patients with PD and could be useful therapeutically.

No evidence of hearing loss in humans due to transcranial magnetic stimulation.

Prompted by the description of hearing loss in rabbits exposed to the acoustic artifact of magnetic stimulation, we compared the results of audiologic studies before and after exposure to transcranial magnetic stimulation in humans. We found no evidence of temporary or permanent threshold shifts in any of the subjects, even in those exposed to transcranial magnetic stimulation repeatedly for several years. Risk of hearing loss from the acoustic artifact of magnetic stimulation, as evaluated by audiograms, tympanograms, acoustic reflexes, and auditory evoked potentials, seems to be small in humans.

Rapid reversible modulation of human motor outputs after transient deafferentation of the forearm: a study with transcranial magnetic stimulation.

Reorganization of corticospinal pathways after spinal cord injury and amputations leads to increased excitability of motor pathways targeting muscles proximal to the level of interruption of efferents from the CNS. To study the timing of these changes, we have recorded motor evoked potentials (MEPs) in the arm muscles of three normal subjects before, during, and after anesthetic block of the forearm and hand. The amplitudes of MEPs from biceps, which was the muscle immediately proximal to the block, gradually increased with anesthesia and then returned to preanesthesia levels within approximately 20 minutes after anesthesia was ended. MEPs from the contralateral arm were unaffected. Such rapid changes strongly suggest unmasking of preexisting synaptic connections, due to disinhibition at cortical or subcortical levels, as the mechanism underlying acute modulation of motor outputs.

Optimal focal transcranial magnetic activation of the human motor cortex: effects of coil orientation, shape of the induced current pulse, and stimulus intensity.

We studied the effects of coil orientation, stimulus intensity, and shape of the induced current pulse on the amplitudes of motor evoked potentials in the left abductor pollicis brevis of 10 normal adults who had transcranial magnetic stimulation. The optimal direction of currents induced in the brain is approximately perpendicular to the central sulcus, flowing diagonally from back to front. The most effective coil orientation depends on the shape of the induced current pulse and, when the first and second phases of the pulse are of similar size, also on the intensity of stimulation. Optimal mapping of the human motor cortex with magnetic stimulation requires knowledge of the influences of all these factors.

Median nerve somatosensory evoked potentials: studies on latency variability as a function of subject height, limb length and nerve conduction velocity.

Report on the results of regression analysis studies concerning median nerve somatosensory evoked potentials (SEPs) latencies, as dependent variables, and subject height, limb length and nerve conduction velocity (NCV), as independent variables. The tests were performed on 23 normal volunteers. Absolute SEP latencies could be predicted by a linear regression model when the independent variable was arm length; when it was subject height, however, both exponential and polynomial models proved better, the latter showing the best coefficients of determination, R 2. Multiple linear regression with two independent variables (arm length and NCV) was found to be better than simple linear regression for predicting P/N13 latency. The regression line for EP-P/N13 latency on height was found to be a polynomial curve; although the regression was found to be significant by the "F" test (alpha = 1%), the model had a low R 2 value (0.41). The same applies to the P/N13-N19 interpeak latency regression curve, but the regression was significant for alpha = 5% in that case. Although interwave latencies are the most useful parameters for clinical interpretation of median SEPs, absolute latencies may occasionally be important, and should be corrected for body size. In unusually tall subjects, it might be useful to double-check EP-P/N13 interwave latency prolongation by estimating the maximum expected P/N13 latency, using a model that takes into account both limb length and NCV.

[Evoked potentials in multiple sclerosis: recent experience at the Locomotor System Diseases Hospital]. / Potenciais evocados na esclerose múltipla: experiência recente do HDAL-SARAH.

Description of main abnormal findings in eight patients with a suspected diagnosis of multiple sclerosis who underwent multimodality evoked potentials studies at HDAL-SARAH--Hospital for Diseases of the Locomotor System, in Brasilia--, during three years (1987-1989). Four of those patients have also been studied with magnetic resonance imaging techniques, and in all of them the results were also typical of demyelinating disease of the central nervous system. The most useful evoked potentials were pattern-shift visual (VEP) and somatosensory (SSEP), which yielded much more information than did brainstem auditory (BAEP) components. This is in agreement with results previously described in the literature. It is concluded that multimodality evoked potentials studies are an easily obtainable and valuable diagnostic tool in multiple sclerosis.

Electrophysiologic studies in leprosy.

The author reviews the literature on electromyography and nerve conduction velocity studies in leprosy. It is concluded that these studies can be helpful in the early diagnosis of neural involvement, in the elucidation of pathophysiological mechanisms, and in the follow-up of patients under medical and/or surgical treatment.

[Multimodal evoked potentials: standardized study of 51 individuals in a Brazilian population]. / Potenciais evocados multimodais: Estudos normativos em 51 indivíduos de uma população brasileira.

The authors report the results of normative studies of pattern-shift visual, brainstem auditory and somatosensory evoked potentials of upper and lower limbs carried out in a sample of 51 normal subjects of a Brazilian population. Normal values were thus established for the main components of each modality of evoked potentials, with special emphasis on those having more clinical utility. The results were compared to the data available in the literature.

[Bilateral palpebral ptosis with unilateral paralysis of upward gaze: a case report]. / Ptose palpebral bilateral com paralisia unilateral do olhar vertical para cima: registro de caso.

The authors report a case of bilateral ptosis with miosis, paralysis of upward gaze and of smooth pursuit movements to the right, as well as a slowly regressive state of lassitude. This syndrome followed a haemorrhagic brain stem infarction. After a review of the pathophysiology of ptosis and of vertical eye movements, together with analysis of data provided by computerized tomography studies--since the case was not fatal--explanations are offered for each clinical sign and it is proposed that the lesion, a paramedian, slightly deviated to the right haemorrhagic focus in the midbrain, with a diameter of 15 mm, might have involved several structures, namely the rostral interstitial nucleus of the medial longitudinal fasciculus, the mesencephalic reticular formation, as well as cortico-nuclear and sympathetic pathways.

Abnormal acute changes in upper limb muscle cortical representation areas in the patients with writer's cramp during co-activation of distal and proximal muscles.

AIM: We analysed cortical muscle representation areas during single muscle activation and during the co-activation of several upper arm muscles in the patients with writer's cramp to determine the possible occurrence of abnormal dynamic somatotopic changes in M1, in addition to the static map abnormalities already described in this form of dystonia. METHODS: Using transcranial magnetic stimulation, we assessed cortical representations of medial deltoid, extensor carpi radialis and the first dorsal interosseus muscles in eight patients with writer's cramp and in eight healthy control subjects. Cortical maps were obtained during distal muscles' activation either in isolation or in conjunction with voluntary medial deltoid co-activation. RESULTS: This study showed a difference in the organization of cortical representations of these muscles between the patients with dystonia and control subjects. The first dorsal interosseus and the extensor carpi radialis cortical representation areas were larger in the dystonic group. The cortical representations became larger when the medial deltoid was simultaneously co-activated, and this effect was not observed in the control group. In the dystonic group, the three cortical muscle representations largely overlapped and their centres of gravity were closer. CONCLUSION: Patients with dystonia showed not only a different spatial organization of muscle cortical representation areas, but also abnormal acute somatotopic changes during proximal muscle co-activation. Task-specific motor impairment in writer's cramp may result not only from lack of cortical inhibition and the well-known anomalous cortical organization observed in these patients, but also from abnormal patterns of proximo-distal functional muscle coupling.

Writer's cramp: cortical excitability in tasks involving proximo-distal coordination.

AIM: The aim of this work was to analyse how writer's cramp patients coordinate each element of the proximal to distal upper arm muscle chain during voluntary movement. METHODS: Using transcranial magnetic stimulation, we have assessed motor cortex excitability properties in patients by recording motor-evoked potentials and silent periods in both the extensor carpi radialis (ECR) and the first dorsal interosseus muscles (FDI), activated either in isolation, or in conjunction with voluntary medial deltoid (MD) co-activation during performance of precise tasks. Ten dystonic patients and ten healthy controls were tested. RESULTS: In both test groups, the ECR muscle displayed a similar active motor threshold, but the excitability curves reached higher plateau values, when the proximal MD muscle was co-activated. In the dystonic group, the FDI muscle excitability curves reached higher plateau values when the MD was co-activated, whereas co-activation had no effect on the control group. In the control group, silent periods, in both the ECR and the FDI were longer when the MD was co-activated. This effect was not observed in the dystonic group. CONCLUSION: In the dystonic group, facilitation of the FDI was observed during a task involving proximo-distal coordination. No differences in silent periods were observed when the muscle was activated alone. Our results suggest that such abnormal facilitation is not only an impairment of the central inhibitory mechanisms reported for dystonic patients, but, in addition, represents true abnormality in cortical muscle activation strategies.

Central fatigue as revealed by postexercise decrement of motor evoked potentials.

We have previously shown that the amplitudes of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) were transiently decreased after exercise, indicating fatigue of motor pathways in the central nervous system. The responsible mechanism is apparently decreased efficiency in the generation of the descending volleys in the motor cortex. We also noted a progressive decrement in amplitude from the first to the fourth MEP. To further clarify the mechanism of this phenomenon, 5 subjects were studied with TMS delivered at the rates of 0.1, 0.15, 0.3, 1, 3, and 6 Hz. The effect was best demonstrated at 0.3 Hz, and occurred after both isometric and isotonic exercise. Three of the subjects also had 0.3-Hz percutaneous electrical stimulation of the brainstem, and a decrement in MEP amplitude did not occur. Further, the delivery of TMS during muscle contraction after muscle fatigue failed to produce a decrement. The results are similar to those found at the neuromuscular junction in myasthenia gravis and are consistent with a reduced safety factor of cortical synaptic transmission in central nervous system fatigue.

Non-invasive differentiation of motor cortical representation of hand muscles by mapping of optimal current directions.

Non-invasive mapping of human motor cortex by stimulating different scalp positions with a magnetic coil held at a constant orientation allows differentiation of proximal and distal arm muscles. This study describes a technique for more precise mapping of closely represented muscles using different orientations of a coil that delivers nearly monopolar current pulses. EMG was recorded from abductor pollicis brevis (APB), first dorsal interosseous (FDI), abductor digiti minimi (ADM), and flexor carpi radialis (FCR) of 9 normal volunteers. Stimuli were delivered from a Dantec stimulator through an 8-shaped coil. The center of the coil was kept flat on the scalp on a given position, and the coil rotated at different angles. The amplitudes of the motor evoked potentials were used for calculation of optimal current directions in the brain for activation of each muscle in each position. The optimal current direction for FCR activation pointed antero-medially. ADM, FDI and APB mapped progressively more antero-laterally. The relationship between current directions was constant across subjects and did not change in different scalp positions. This technique improves the spatial resolution of non-invasive cortical mapping and may express the differences in orientations of interneuronal nets in the precentral gyrus.

Topographic mapping of the human motor cortex with magnetic stimulation: factors affecting accuracy and reproducibility.

We recorded motor evoked potentials (MEPs) from deltoid, biceps brachii, abductor pollicis brevis and flexor carpi radialis muscles of 5 normal volunteers during transcranial magnetic stimulation. With the subjects at rest, an 8-shaped magnetic coil was used to deliver 30 stimuli to different scalp positions 0.5 or 1.0 cm apart. The variability in amplitude and latency of MEPs was studied as a function of the scalp position stimulated, the number of stimuli at each position, and the percentage of maximal peripheral M responses (%M) elicited. The results were used to estimate the optimal number of stimuli at each position and the optimal spacing of scalp positions for topographic mapping of the human motor cortex. The amplitude and latency variability of MEPs were higher when suboptimal scalp positions were stimulated. Consequently, a larger number of stimuli were required to determine representative MEP amplitudes at suboptimal positions. In addition, there was an inverse relationship between %M recruited by transcranial magnetic stimuli in different subjects and the variability in MEP amplitude and latency. Latency variability was less pronounced than amplitude variability. Optimal sampling conditions are required to produce the best topographic maps, particularly to show subtle reorganization patterns in the human motor cortex.

Postexercise facilitation of motor evoked potentials elicited by ipsilateral voluntary contraction.

Motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) increase in amplitude when obtained immediately after a period of exercise of the target muscle (postexercise facilitation). We studied postexercise facilitation of MEPs to TMS after periods of voluntary activation of either the ipsilateral or contralateral primary motor cortex (simple finger movements) or supplementary motor area (complex finger movements). Postexercise facilitation of the first dorsal interosseous MEPs occurred ipsilaterally even after simple, unilateral finger movements of the dominant hand. The findings are taken to suggest transcallosal transfer of excitability from the dominant to nondominant cerebral hemisphere, perhaps related to mechanisms involved in bimanual motor coordination.