Parkinson's disease and somatosensory evoked potentials: apomorphine-induced transient potentiation of frontal components.

We recorded somatosensory evoked potentials (SEPs) to median nerve stimulation from parietal and frontal districts in 32 patients with Parkinson's disease by evaluating latency/amplitude characteristics of the parietal P14-N20-P25 and of the frontal P20-N30-P40 wave complexes before and 10, 20, 30, and 60 minutes after subcutaneous administration of apomorphine chloride. The frontal complex N30-P40 was smaller than normal in 17 patients in baseline recordings. Following apomorphine, the parietal responses did not significantly vary in amplitude, but the frontal complex showed a remarkable amplitude potentiation in 22 of 32 patients (68.7%, p < 0.001), 19 of whom were also improving clinically. Amplitude potentiation was evident 10 minutes after apomorphine and faded away nearly in parallel with the end of its clinical efficacy. There were no SEP changes in three healthy controls after apomorphine.

Effects of motor imagery on motor cortical output topography in Parkinson's disease.

BACKGROUND: The motor impairment in Parkinson's disease (PD) could partly reflect a failure to activate processes of motor imagery. OBJECTIVE: To verify any selective changes of motor output during motor imagery, lateralized to the hemisphere contralateral to the clinically affected side of hemiparkinsonian patients. METHODS: Transcranial magnetic stimulation (TMS) was used to map the cortical representations of the contralateral abductor digiti minimi muscle (ADM) during rest, contraction, and motor imagery in a group of patients with hemi-PD and in a group of healthy volunteers. Seven patients with hemi-PD and seven healthy subjects were examined. Focal TMS was applied over a grid of 20 scalp positions on each hemiscalp. Maps were characterized by area (number of excitable positions), volume (the sum of motor evoked potential amplitudes at all scalp positions), and center of gravity (a map position representing an amplitude-weighted calculation of the excitable area). RESULTS: In healthy control subjects, the area of cortical representation of ADM was symmetrically increased in both hemispheres by mental simulation of movement and real muscle contraction. In patients with hemi-PD, there was a hemispheric asymmetry in the area of cortical representation elicited by motor imagery. The area was reduced in the clinically affected hemisphere. The volume of cortical representation was increased under all conditions and in both hemispheres in patients with PD. However, largely because the volume was so high at rest in patients, the increment in volume associated with contraction was smaller than in control subjects. CONCLUSION: This study demonstrates the presence of a tonic hyperactivation of motor cortical circuitry in PD in conjunction with an abnormality of either motor imagery or the process by which motor imagery engages the sensorimotor cortices in the clinically affected hemisphere.

Transcranial magnetic stimulation reveals an interhemispheric asymmetry of cortical inhibition in focal epilepsy.

Transcranial magnetic stimulation (TCS) was applied to both hemispheres of 16 patients affected by criptogenic focal epilepsy to evaluate the interhemispheric symmetry of the motor cortex excitability. The amplitude of the motor evoked potentials (MEPs) and the duration of the post-MEP silent period (SP) were measured at threshold (THR) and at increasing TCS stimulation intensities. The THR was significantly higher in patients than in 16 age-matched control subjects (p < 0.01). No interhemispheric differences were found in MEP amplitude. In controls, the correlation between SP duration and increasing TCS stimulus intensity was linear with a symmetrical progression of the SP duration over the two hemispheres. In patients this linear SP progression was lacking on the 'epileptic' hemisphere: the SP duration did not increase following TCS > 40% above THR, indicating abnormal interhemispheric asymmetry. This finding suggests a selective dysfunction of inhibition in the epileptic hemisphere as signaled by an abnormal SP duration in response to progressively higher TCS intensities.

Hand motor cortical area reorganization in stroke: a study with fMRI, MEG and TCS maps.

The anatomical and functional correlates of the hand sensorimotor areas was investigated in a stroke patient with a malacic lesion in the left fronto-parieto-temporal cortex. The patient presented hemiplegia and motor aphasia 12 months earlier, followed by an excellent motor recovery. Transcranial magnetic stimulation mapping, functional magnetic resonance and magnetoencephalography were used as methods of functional imaging and all yielded consistent results. In particular, an asymmetrical enlargement and posterior shift of the sensorimotor areas localized in the affected hemisphere were found with all three techniques. Aspects related to brain 'plasticity' for functional recovery are discussed.

Follow-up of interhemispheric differences of motor evoked potentials from the 'affected' and 'unaffected' hemispheres in human stroke.

We analysed motor-evoked potentials (MEPs) from the hand muscles during focal transcranial magnetic stimulation (TCS) in both the affected (AH) and the unaffected (UH) hemispheres of 17 monohemispheric stroke patients followed-up in subacute stage. Recording sessions were performed at 2 (T1 session) and 4 (T2 session) months from acute stroke. Clinical and functional scores were evaluated. An age-sex matched group of 20 healthy subjects have been referenced. In T1, relaxed MEPs from AH were smaller than UH (p<0.001) and normals (p<0.001). In T2, an increase of AH relaxed-MEPs amplitude was observed, combined with an improvement of clinical and functional scores (p<0.001). On the other hand, the amplitude of contracted MEPs from the AH in T1 was larger than in the normal group. This parameter decreased toward normal limits in T2, provided that the amplitude of the MEPs from the AH improved, while it further increased when TCS of the AH continued to fail in eliciting MEPs. This phenomenon was statistically combined with clinical improvement of disability and neurological scores. Recovery of the excitability AH threshold with progressive 'balancing' of the UH hyperresponsiveness represents a good prognostic parameter for clinical outcome of hand motor function.

Evoked alpha- and mu-rhythm in humans: a neuromagnetic study.

We present the results of a neuromagnetic study on the spatial structure of brain rhythms enhanced by photic and somatosensory stimulation, as measured on the occipital, rolandic and frontorolandic regions in humans. It emerges that, while it is always possible to drive the cerebral activity during sustained stimulation at any given frequency, only certain specific frequencies can produce prolonged synchronization (i.e. the oscillating activity elicited by the repetitive stimulation continues well beyond its termination). In both studied modalities we were able to localize equivalent sources for the synchronized responses; their relationship with the known evoked responses is discussed. In the visual modality the synchronization was characterized by a potentiation of the subjects' alpha-rhythm. In the somatosensory modality synchronization was reflecting two different activities: one probably related to the rolandic mu-rhythm, the second suggesting the presence of two widely separated and time correlated sources possibly driven by a unique, deep clock. Possible implications for other studies of the dominant brain rhythms, or experimental checks on specific brain models, as well as of the visual and somatosensory evoked responses are discussed.

Single fibre motor evoked potentials to brain, spinal roots and nerve stimulation. Comparisons of the 'central' and 'peripheral' response jitter to magnetic and electric stimuli.

Single fibre motor evoked potentials to magnetic and electric non-invasive stimulation of brain, spinal cord and peripheral nerve were recorded in 8 healthy volunteers. The 'central motor jitter' and the 'peripheral motor jitter' were respectively calculated and a comparison between the magnetic and electric modalities was made. The highest degree of latency variability was observed for both magnetic and electric central motor jitter, whilst the peripheral motor jitter to nerve stimulation was as low as the neuromuscular one (range 16-60 microsecond). The magnetic 'central motor jitter' (range 94-1024 microsecond) was much larger than the electric one (range 55-280 microsecond), which was in the order of jitter calculated on H-reflex studies; moreover, the former was organized in a bi- or trimodal distribution. On the contrary, no significant differences were observed between the two modalities when the jitter to nerve stimulation was taken into account. Possible contributions of corticocortical circuitries containing several synaptic interruptions during magnetic as opposed to electric transcranial stimulation, is discussed.

Neurophysiological follow-up of motor cortical output in stroke patients.

BACKGROUND AND PURPOSE: Transcranial magnetic stimulation (TMS) has been employed in following up a population of 20 stroke patients in a post-acute, apparently stabilized stage. Neurophysiological and clinical data were recorded in 5 different recording sessions, from the beginning of a neuro-rehabilitation treatment (T0, at about 5 weeks from the ictal event.), followed up for about 4 months (T4), with the purpose to study any modification of the cortical motor output in the course of a neuro-rehabilitation treatment. METHODS: Motor evoked potentials (MEPs) were simultaneously recorded from 10 muscles of both upper limbs (affected and not-affected); meanwhile, clinical and functional scores were gathered. Spinal responsiveness was investigated via H-reflex and F-wave recordings. RESULTS: We describe a pattern of improving changes still taking place four months after the stroke, even if the maximal amelioration burden was concentrated between T0 and T1 and T1 and T2 recording sessions (T0/admission to T2/42 days from T0=about 80 days from stroke occurrence). In particular, the excitability threshold (ETh) was progressively decreasing in the affected hemisphere (AH; P<0.001 between T0 and T4), while MEPs amplitude and latency tended toward normality, more in the resting state than during voluntary contraction. Slopes of neurophysiological and clinical data evolution were taken and trends of amelioration described. CONCLUSIONS: These findings suggest that rearrangements of motor cortical neural circuitries are still operating after several months from an acute vascular monohemispheric insult, coupled with a clinical improvement in disability and neurological scores. The steepest part of the slopes were evident in the first 80 days, suggesting that this period is the one in which plastic changes of cortical motor areas are mainly active.

Neuromagnetic imaging studies discriminate proprioceptive and cutaneous cortical inputs during median nerve stimulation in man.

The localizing capabilities of the neuromagnetic imaging technique have been used to non-invasively discriminate mainly proprioceptive from cutaneous afferences to the contralateral hemisphere in human volunteers during separate median nerve stimulation at wrist and digits. The high time-resolution achieved in the localization of the equivalent sources of the early latency (15-30 ms) evoked fields permitted to follow their apparent movement as represented by an early and deep dipole (15 ms, about 5 cm deep, probably a subcortical source), a shallower one (20 ms, about 1.5 cm), and an intermediate one (23 ms, about 3 cm). These sources are supposed to be the manifestation of time-lagged parallel proprioceptive and cutaneous afferences from the thalamic ventro basal complex to different primary sensory areas in the postcentral gyrus. Both deeper and shallower dipoles could not be identified during selective stimulation of cutaneous afferents from the digital branches of the median nerve.

An electrophysiological study of D2 dopaminergic actions in normal human retina: a tool in Parkinson's disease.

A peculiar deficit of electrophysiological retinal responses to pattern reversal grating stimuli has been reported in Parkinson's disease (PD) patients. A similar abnormality has been reproduced by means of non-selective dopaminergic antagonists in normal humans. Aim of this study was to verify, by means of a selective D2 antagonist (sulpiride) administered to normal subjects, whether a D2 blockade affects the visual electrophysiological performances with the same trend as observed in PD patients. Patterns electroretinogram (PERG) responses to 1 cycle per degree (c/d) of spatial frequency at 1 (transient) and 7.5 (steady state) Hz of temporal modulation of a square-wave grating pattern reversal have been recorded in 19 healthy volunteers before and after the administration of 100 mg i.m. of sulpiride. The data are consistent for the following conclusion: a selective D2 antagonist reduces steady state and delays transient retinal responses as expected for a PD mimicking agent.

Simultaneous motor output and sensory input: cortical interference site resolved in humans via neuromagnetic measurements.

Neuromagnetic measurements were carried out during median nerve stimulation at the wrist in complete relaxation (a) and during active contraction of the hand muscles (b). Firstly, activity of the generator source responsible for the major component of the sensory evoked magnetic fields (SEFs) was mapped and localized during condition (a) and (b). Then the subtraction maps ((a)-(b)) were obtained and the virtual 'dipole' responsible for the 'interference' (less than or equal to SEFs amplitude) between the afferent input and the motor output was tridimensionally localized in a position compatible with the knee and the convexity of the postcentral gyrus.

Neuromagnetic somatosensory homunculus: a non-invasive approach in humans.

The somatosensory homunculus has been identified during stimulation of median (at wrist and elbow), femoral, tibial and pudendal nerves of the left hemibody via the neuromagnetic imaging technique. The somatic representations of different body districts have been localized in the somatosensory cortex, by means of an equivalent dipole localization algorhythm. Dipole locations agree with the well-known somatotopic organization obtained with invasive techniques. The proposed method is, therefore, an important investigating tool for studies on normal and diseased subjects.

Intracortical excitatory and inhibitory phenomena to paired transcranial magnetic stimulation in healthy human subjects: differences between the right and left hemisphere.

Intracortical inhibition (ICI) and facilitation (ICF) to paired magnetic stimuli reflect the activation of interneuronal circuits within the motor cortex. Intersubjects physiological variability of these phenomena, partly limits the usefulness of such method. Therefore, interhemispheric ICI/ICF differences might represent a more sensitive and less variable neurophysiological parameter to test the motor cortex excitability. Motor evoked potentials from the hand muscles were recorded in ten healthy subjects in a paired-pulse paradigm. Interstimulus intervals (ISIs) from 1 to 50 ms were used. The time course of ICI and ICF in the two hemispheres is consistent with minimal interhemispheric asymmetries. The interhemispheric differences of ICI and ICF could be a valuable neurophysiological marker for the diagnosis, prognosis and follow-up of neurological diseases characterized by monohemispheric damage and lateralized motor deficits.

A method to monitor motor cortical excitability in human stroke through motor evoked potentials.

We describe a procedure aimed to analyse Motor Evoked Potentials (MEPs) interhemispheric differences in motor excitability in a monohemispheric subacute stroke population. This protocol has specifically been oriented to scan for any differences in MEPs amplitude at rest and during contractions from a hand muscle, Abductor Digiti Minimi (ADM), after focal Transcranial Magnetic Stimulation (TMS) in both Affected (AH) and Unaffected (UH) Hemispheres. Stroke patients can be included in the protocol if they have suffered acute stroke during the two to four month period to the admission in our rehabilitation hospital. The purpose of this protocol is to establish whether any clear pattern of interhemispheric responsiveness exists and/or to define any possible correlation between MEPs and clinical data. Disability and neurological scores are evaluated to allow a numerical comparison with electrophysiological data. Two recording sessions are planned: the first when the selected patient is admitted (T1) and the second after 8 weeks (T2). Such a period has been arbitrarily chosen because it represents a reliable time after the first recording in order to observe clinical amelioration if present. Criteria for reproducibility of experimental conditions are illustrated.

Neurophysiological evaluation of tactile space perception deficits through transcranial magnetic stimulation.

We describe a procedure useful to investigate the contralateral space perception deficits frequently encountered in patients with unilateral right brain damage. In particular, we focused on the phenomenon of extinction, i.e., the failure to perceive a contralesional stimulus only when a symmetrical contralateral stimulus is simultaneously applied. Fifteen right brain- and 15 left brain-damaged patients were examined. Somatosensory perception was evaluated by using a dedicated electronic device able to provide electrical stimuli of variable intensity to digits of one or both hands. The electrical stimulator was able to trigger a magnetic brain stimulator connected with a focal figure of eight coil. Threshold electrical stimuli were delivered to one or both hands of the patients, who were asked to indicate whether they perceived the stimulus (i) and to localise it (them). The electrical stimulator was connected with a magnetic stimulator with an interstimulus interval (ISI) of 40 msec (electrical stimulation preceding the transcranial one). Focal threshold transcranial magnetic stimulation (TMS) was applied to frontal and parietal scalp sites of the unaffected hemisphere. At each interpulse interval we found that TMS of the unaffected hemisphere was associated to a decrease in the level of contralesional extinction. Our method demonstrates that a basic deficit underlying neglect and extinction of contralateral space in unilaterally brain damaged patients is the interhemispheric imbalance between the two hemispheres in directing contralateral attention. A transient interference with the function of the unaffected hemisphere can improve these deficits, suggesting a possible application of TMS in the daily clinical practice for speeding up recovery from neglect.

Increasing doses of l-sulpiride reveal dose- and spatial frequency-dependent effects of D2 selective blockade in the human electroretinogram.

The amplitude and phase of the second harmonic (15 Hz) of the electroretinographic responses to three different spatial frequency grating stimuli (0.25, 1 and 4 c/deg), reversed at 7.5 Hz, were studied i normal human subjects, before and 30 min after the systemic administration of three doses (0.071, 0.357 or 1.428 mg/kg) of a selective D2 blocker, l-sulpiride, to three populations of 18, 19, or 20 subjects. The effect of the drug on the pattern electroretinogram (PERG) was clearly dose-dependent, being greatest on the responses to 4 c/deg. The mean decrease in second harmonic amplitude was -13.8% after 0.071 mg/kg of l-sulpiride, -23.5% after 0.357 mg/kg and -28.5% after 1.428 mg/kg. The last two variations were significant at P < 0.01 and P < 0.01 respectively. These data suggest that a dose-dependent effect on the human retinal response to 4 c/deg stimuli exists, probably mediated by a coupling between l-sulpiride and D2 receptors. Lastly, our data suggest that D2 receptors may play an important role in the pathophysiology of visual dysfunction in Parkinson's disease, that has been described to be more significant at medium spatial frequency (2-5 c/deg).

N30 wave amplitude of somatosensory evoked potentials from median nerve in Parkinson's disease: a pharmacological study.

We studied N20 and N30 waves of Somatosensory Evoked Potentials from median nerve stimulation in different pharmacological conditions. N30 wave amplitude was decreased in 33 parkinsonians without therapy in comparison with a group of age-matched normal subjects. In a group of 19 parkinsonians, N30 wave amplitude was significantly augmented during apomorphine infusion and less evidently, but still significantly, during chronic 1-dopa therapy. The administration of an oral dose of haloperidol in 11 normals did not affect significantly the studied parameters. The infusion of apomorphine in 6 psychotic patients with extrapyramidal symptoms secondary to long-term treatment with neuroleptics, determined, together with a clear-cut clinical amelioration, a significant increase of N30 amplitude and N30/N20 ratio. Possible pathophysiological hypothesis of such electrophysiological modifications are discussed.

Analysis of sympathetic skin responses in a group of healthy subjects and in patients affected by sphincter disorders and impotence.

Bilateral palmar and plantar sympathetic skin responses (SSRs) to pudendal and median nerves stimulation have been recorded in a population of 10 healthy adult subjects. A group of 11 patients affected by sphincter disorders and/or impotence of neurological origin (diabetic neuropathy, ischaemic myelopathy, myelitis, cauda aequina syndrome) was investigated and results were compared with normal values obtained from the control group. The technique is focused on the vegetative component of innervation and is shown to give complementary information on sympathetic dysfunction, in addition to traditional techniques relating to somatic innervation (electroneurography, electromyography, somatosensory evoked potentials.

[Neurological complications of schistosomiasis]. / Complicanze neurologiche della schistosomiasi.

The authors describe the neurological complications of schistosomiasis, a widespread tropical infective disease. The neurological symptoms appear in an estimated 3 to 5% of patients; hence the importance for the general practitioner and the neurologist to consider this clinical entity in their practice.