Quality of life in stroke survivors: first results from the reliability and validity of the Italian version of the Stroke Impact Scale 3.0.

The purpose of this study was to establish the reliability and validity of the Italian version of the Stroke Impact Scale 3.0 (SIS 3.0), a specific and multidimensional instrument that assesses quality of life (QOL) in stroke survivors. Forty-five patients treated in three Rehabilitation Hospitals of the Lazio Region were included in the study. Patients were assessed using the SIS 3.0, the SF-36, the Barthel Index, the Mini Mental State Examination, the Hospital Anxiety and Depression Scale, the NIH Stroke Scale, the Modified Rankin Scale, and the Instrumental Activities of Daily Living. Results showed good internal consistency of the SIS 3.0 (Cronbach's alpha 0.86-0.98), and a good test-retest reliability (r > 0.70, p < 0.000) except for the Emotion and Social Participation subscales. At the re-test, 15 days after the first administration, SIS 3.0 showed a good responsiveness to change, documenting clinical improvement in stroke survivors. Significant correlations between the other instruments and the SIS 3.0 allowed to establish the concurrent validity of the SIS 3.0. Although the small sample size the Italian version of the SIS 3.0 showed good internal consistency and test retest reliability, as well as validity and responsiveness to changes. Since the SIS 3.0 is a specific tool to measure QOL in stroke survivors, its Italian version could be successfully used also in Italian population to better identify predictors of QOL and evaluate the effectiveness of health interventions.

Differential Influence of Carotid Stenosis and White Matter Disease on Motor and Cognitive Activation.

BACKGROUND: Cognitive and motor performance can be supported, especially in older subjects, by different types of brain activations, which can be accurately studied by functional magnetic resonance imaging (fMRI). Vascular risk factors (VRFs) are extremely important in the development of cognitive impairment, but few studies have focused on the fMRI cortical activation characteristics of healthy subjects with and without silent cerebrovascular disease including white matter hyperintensities (WMH) and carotid stenosis (CS) performing cognitive tasks. METHODS: Thirty-five volunteers with and without asymptomatic unilateral carotid stenosis above 70% and variable degrees of WMH underwent performance of a simple motor and cognitive task during an fMRI session. RESULTS: While the performance of the motor task resulted in a cortical activation dependent of age but not of WMH and carotid stenosis, performance of the cognitive task was accompanied by a significantly increased activation independently correlated with age, presence of WMH as well as of carotid stenosis. CONCLUSIONS: in this study, cognitive domains regulating attention and working memory appear to be activated with a pattern influenced by the presence of carotid stenosis as well as by white matter hyperintensities. The impairment of these cognitive abilities is of high relevance in Alzheimer's disease pathology. The fMRI pattern shown in patients with asymptomatic but significant carotid stenosis might be related to chronic cerebrovascular hypoperfusion, a critical pathophysiological mechanisms in AD. In these patients, carotid endoarterectomy should be considered also for AD prevention and might be recommended.

Pharmacologic reversal of cortical hyperexcitability in patients with ALS.

OBJECTIVE: To reverse the profile of abnormal intracortical excitability in patients with ALS by administering drugs that promote GABAergic transmission. BACKGROUND: Transcranial magnetic stimulation (TMS) has revealed abnormalities of cortical inhibition in ALS, a reduction of the silent period, and the absence of intracortical inhibition normally occurring in response to paired TMS. Impaired inhibitory transmission could play a role in the physiopathology of this illness. METHODS: Using paired TMS with conditioning stimuli from 1-to-6-msec-interstimulus intervals, we investigated 16 patients with ALS. The protocol included: (1) the "drug-free" profile of paired TMS; (2) paired TMS 30 minutes after the intake of diazepam (3.5 mg); (3) paired TMS after 3 weeks' treatment with gabapentin (GBP) (600 mg/day) or riluzole (50 mg/twice a day). RESULTS: Intracortical inhibition is lost in patients with ALS, and this abnormal profile is reversed by diazepam or sustained treatment with GBP. We also noted that motor-evoked potential amplitudes to single stimuli increased (p<0.01) after diazepam and GBP. CONCLUSIONS: The demonstration of pharmacologic reversal of hyperexcitability in patients with ALS makes a potentially significant contribution toward understanding the pathophysiology of a disease that has so far eluded an effective cure.

Ipsilateral motor activation in patients with cerebral gliomas.

OBJECTIVE: The aim of this study is to provide neurophysiologic evidence of ipsilateral hemispheric activation in patients affected by intracerebral gliomas via the use of transcranial magnetic stimulation. BACKGROUND: The mechanisms involved in such ipsilateral activation have yet to be established, but they may involve preexisting routes that either are suppressed or undetected in the normal brain. Ipsilateral pathways may act in reserve, activated by the impairment of contralateral control. This hypothesis is suggested by the fact that the considerable size of the tumors in our patients is not matched by a proportionate loss of motor performance in the limbs contralateral to the affected hemisphere. However, it remains possible that ipsilateral motor-evoked potentials (iMEPs) may reflect reorganizational changes without significant functional effects. METHODS: The effects of such activation were investigated using both focal and nonfocal coils stimulating cortical motor areas, with MEPs recorded from both left and right thenar muscles. Fifteen healthy control subjects and seven patients were examined. RESULTS: iMEPs were generally absent in normal subjects, but in contrast they were obtained in the patients by stimulating the healthy hemisphere using both round and figure-of-eight coils. Distinct from contralateral MEPs, iMEPs are obtained with higher thresholds (range, 60 to 80% of stimulator output) and display longer latencies (20.9 msec versus 19.4 msec). CONCLUSIONS: Taken in conjunction with recent research using functional imaging brain exploration and a variety of clinical, anatomic, and neurophysiologic studies, our results reflect a growing awareness of ipsilateral motor control and its potential compensatory role when contralateral routes are damaged.

Cerebral plasticity after stroke as revealed by ipsilateral responses to magnetic stimulation.

The present study aims to provide neurophysiological evidence of ipsilateral activation during motor recovery in patients after stroke. The effects of cortical reorganization were investigated using magnetic brain stimulation in order to record motor evoked potentials (MEPs) both from contralateral and ipsilateral hands. Ten healthy subjects and 13 patients were examined. The patients had suffered their first hemispheric stroke and consequent motor deficit. While ipsilateral responses (iMEPs) were absent in normal subjects, they were obtained from both ipsilateral and contralateral hands in patients. The ipsilateral MEP differed from contralateral MEP in the following respects: (1) elicitation during contraction; (2) a shorter latency; (3) a lower amplitude. The presence of optimal iMEPs (lower excitability threshold, larger amplitude) in recovered hands points to a role for the undamaged hemisphere, and in particular to the involvement of secondary motor areas. We suggest that iMEPs in general may be a marker of brain plasticity, and that the specific type described here appear in the context of fast autochthonous motor recovery.

Central motor tract propagation in man: studies with non-invasive, unifocal, scalp stimulation.

Motor-evoked potentials (MEPs) to unifocal, anodal scalp stimulation have been recorded in 45 healthy volunteers from proximal and distal upper limb muscles. Optimal responses were obtained through a pericranial cathode consisting of 6 or more regularly spaced, interconnected plaques whose impedance was carefully balanced with that of a 0.8-cm2 stimulating anode on the scalp. Individual rectangular pulses with threshold intensity (70-86 mA) 100-200 microseconds in duration, with rise-decay times shorter than 50 microseconds resulted more efficient in eliciting individual MEPs in the target muscle. The foci of maximal response for hand and shoulder muscles were localized. The scalp-to-cervical cord conduction time along the motor tracts governing the hand muscles was 5.21 +/- 0.42 ms. This index was highly correlated with the subject's height and stable in time when repeatedly tested. Collision between orthodromically and antidromically propagated motor impulses was obtained by simultaneous stimulation of scalp and median nerve at wrist. Response facilitation was achieved by means of prestimulus voluntary contraction of the target muscle, continuous vibration of its tendon or scalp stimulation with paired shocks. Facilitation of MEPs was obtained by prestimulating the ipsilateral motor cortex 8-24 ms before the stimulation of the one contralateral to the target muscle. This was considered at least in part mediated by transcallosal connections. An efferent volley secondary to scalp stimulation was recorded for the nerve trunk with the near-nerve technique. Segmental and suprasegmental mechanisms underlying MEP facilitation provoked by phasic and tonic contractions of the target muscle have been investigated.

Pre-movement facilitation of motor-evoked potentials in man during transcranial stimulation of the central motor pathways.

Motor evoked potentials (MEPs) following trans-cranial stimulation (TCS) through unifocal electric or magnetic impulses have been evaluated in the pre-movement period in 8 healthy volunteers. By utilizing a simple reaction time paradigm, progressive amplitude increments and latency decrements of MEPs have been demonstrated in the 100 ms preceding the onset of EMG activity in the muscle examined. By employing surface and depth recordings from various muscles of hand and forearm contralateral to the TCS, it was observed that in the 'early' period of pre-EMG facilitation (100-60 ms before EMG onset) TCS solely recruited the same low-threshold motor units which are fired first during self-paced contractions. In the 'middle and late' epochs of pre-EMG facilitation, TCS served when MEPs were recorded from a relaxed muscle, during TCS of progressively higher intensity. Multiple muscle recordings showed that pre-EMG facilitation was remarkably limited to the muscular group of the hand primarily involved in the intended movement.

Age-related changes of motor evoked potentials in healthy humans: non-invasive evaluation of central and peripheral motor tracts excitability and conductivity.

A comparative analysis of the corticospinal tract nervous propagation and excitability threshold was carried out in young (25 subjects, age range 16-35 years) and in elderly (40 subjects, 51-86 years) populations of healthy volunteers. Motor evoked potentials (MEPs) were recorded from the hand and foot muscles following transcranial magnetic stimulation (TCS) during complete relaxation and active contraction of the target muscles. Threshold intensities corresponded to the stimulator's output eliciting liminal MEPs in about 50% of stimuli during relaxation. It was found that threshold values of magnetic TCS were significantly higher in the elderly (44 +/- 6.4% vs 39 +/- 3.5% for the hand; 66 +/- 10.1% vs 56 +/- 6.7% for the foot; P < 0.001) than in the young subjects. Moreover, this index progressively increased with age (P < 0.001), whilst the propagation time along the central motor tracts did not parallel such an age-related trend.

Electric vs magnetic trans-cranial stimulation of the brain in healthy humans: a comparative study of central motor tracts 'conductivity' and 'excitability'.

Motor evoked potentials (MEPs) were elicited in the thenar muscles of 11 healthy volunteers via individual electric unifocal and magnetic trans-cranial stimuli (TCS). The effects of TCS strength, of the muscular state (relaxed, contracted) as well as of the amplitude-latency characteristics and the duration of the motor tracts central conduction times (CCTs) to hand muscles, were evaluated and compared between the two types of brain excitation. MEPs with the shortest latency (18.91 +/- 1.31 ms) were recorded in the voluntarily contracted muscle during electric TCS, whilst those with maximal latency (23.3 +/- 1.63 ms) were found after magnetic TCS with an intensity at threshold for eliciting an MEP of about 0.1 mV in the relaxed muscle. Mean CCTs for electric and magnetic TCS calculated in the contracted target muscles, were respectively 5.07 +/- 0.51 and 6.34 +/- 0.46 ms. MEPs with larger amplitudes and durations were observed during magnetic TCS, being maximal when suprathreshold stimuli were delivered. A restricted range of liminar values of magnetic TCS was obtained by defining the threshold for raising motor responses in complete muscle relaxation, indicating that magnetic pulses might represent a useful probe for testing the 'excitability' of the motor tracts.

Brain excitability and electroencephalographic activation: non-invasive evaluation in healthy humans via transcranial magnetic stimulation.

Excitability changes of the central motor tracts as a function of the electroencephalographic (EEG) characteristics has been investigated in 10 healthy volunteers. Transcranial magnetic stimulation (TCS) was administered to the right motor cortex with an intensity 5-10% above threshold for the elicitation of motor evoked potentials (MEPs) in the left forearm muscles. Simultaneously, the right median nerve was stimulated to provoke an H-reflex in the forearm flexors and EEG activity was recorded from the left hemiscalp. Subjects were completely relaxed and were asked at random either to keep the eyes closed while maintaining mental inactivity (A) or to open their eyes and perform mental arithmetics (B). Latencies and amplitudes of MEPs and H-reflexes were statistically matched with the spectral content of the EEG. In condition A, MEPs of 119 +/- 61 microV, with up to 36% of missing responses and background EEG activity dominated by rhythms in the alpha range were found. In condition B, MEPs of 219 +/- 66 microV (P less than 0.001), with less than 16% of missing responses, 'blocking' of the background alpha rhythms, and a potentiation of the faster ones' relative power were observed. Changes of the H-reflex characteristics were neither statistically significant nor related to MEP amplitude and EEG spectral profile fluctuations.

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.

Magnetic transcranial stimulation in healthy humans: influence on the behavior of upper limb motor units.

Aim of the study was to analyze the characteristics of motor action potentials recruitment during magnetic trans-cranial stimulation (TCS) of the brain. Coaxial needle recordings from hand and upper limb musculature, as well as surface electrodes were employed in 20 healthy controls during magnetic TCS with regular and figure-of-8 coil in different experimental protocols including: (a) simple reaction time paradigm during which TCS at subthreshold intensity for eliciting MEPs in relaxation was delivered at various intervals between the signal to move and the onset of the voluntary EMG burst; (b) suprathreshold TCS was randomly delivered while the subject was voluntarily firing at a regular rate one 'low' and/or 'high threshold' motor unit action potential (MUAP). The pre- and post-TCS MUAPs recruitment as well as their firing rates were compared; (c) recordings with two separate needles picking up individual MUAPs from the same or from two different muscles were obtained in order to test 'synchrony' of MUAP's discharge before and after TCS; (d) the influence of the time-interval separating the last discharged MUAP from TCS was evaluated. (e) differences between simultaneous surface and depth recordings were examined. The following results were obtained. (a) The same low-amplitude MUAP which is first voluntarily recruited at the onset of the EMG burst is the one initially fired by TCS in the pre-movement period. Latency shortenings and amplitude enlargement of surface MEPs were observed with faster reaction times. Such changes were coupled to the recruitment of high-threshold MUAPs being larger in amplitude and briefer in latency than the initial one. (b) When using suprathreshold TCS, MEPs followed by silent periods were found. The SP was followed by a rebound acceleration of the MUAPs firing rate compared with pre-TCS levels. Besides rebound acceleration, new MUAPs of larger amplitude than the original (= pre-stimulus) ones were recruited beyond the voluntary control. This phenomenon-together with longer SPs- was progressively more pronounced with stronger stimuli. (c) TCS was affecting the 'synchrony' of MUAPs. (d) If the latency difference between the last pre-stimulus spike and the TCS was exceeding the half-cycle of the MUAP 'natural' firing, the SP was longer in duration. (e) SPs not preceded by MEPs were clearly present in depth recordings. Surface recordings mainly reflected the behavior of high-threshold and large MUAPs.

The effect of benzodiazepines and flumazenil on motor cortical excitability in the human brain.

In the present study, the effects of benzodiazepines (diazepam) were evaluated in terms of cortical excitability changes, as tested with transcranial magnetic simulation (TMS). In particular, analyzed were drug-induced changes regarding two selected parameters of TMS: (1) the cortical excitability threshold and (2) the silent period duration (SP). For this purpose, we evaluated the effects of long-term therapy with diazepam in the patients affected by anxiety disorders and the changes induced by single oral doses of diazepam in both healthy controls and patients. In addition, we tested cortical excitability changes in two 'extreme conditions' where a considerable concentration of serum benzodiazepine-like activity was reached, as represented by diazepam overdose and idiopathic recurrent stupor (IRS). In both groups of patients, a significant increment of motor threshold was found, while in the overdose patients, the SP was also increased. The administration of flumazenil in these two conditions was followed by a prompt reversal effect, consisting of a return to normal cortical excitability parameters. The long-term usage of diazepam in patients with anxiety disorders is associated with significantly increased threshold; the increased value of these parameters was temporarily further enhanced by the administration of a single oral dose of diazepam, which, in normal control subjects, is not associated with changes of cortical excitability. The results of this study reveal that different physio-pathological conditions induced by the influence of benzodiazepine and its antagonist are reflected in excitability changes which attest to the involvement and modification of cortical GABAergic activity.

Ipsilateral activation of the unaffected motor cortex in patients with hemiparetic stroke.

BACKGROUND AND PURPOSE: Recent research has shown that following stroke patients can display ipsilateral activity reflecting a functional link between the undamaged hemisphere and the affected upper limb on the same side of the body. In the present study the capacity for ipsilateral activation is documented during recovery by using transcranial magnetic stimulation (TMS) and transcranial Doppler (TCD). METHODS: Fourteen patients affected by hemispheric stroke were examined with TMS and TCD within 48 h of onset, and again 6 months later. Neurological signs were scored with reference to the NIHSS, and patients executed a thumb to finger opposition task so as to further estimate the motor deficit. Twenty healthy volunteers represented the control population. RESULTS: (1) Both TMS and TCD yielded homogeneous results showing ipsilateral activity between affected hands and undamaged hemispheres. On stimulating the motor cortex 3 cm anterior and 3 cm lateral to Cz, a scalp site remote from the primary motor area, ipsilateral motor evoked potentials (iMEPs) from hand muscles were found in recovered patients. (2) In 8 controls iMEPs with smaller amplitudes than patients could be obtained by stimulating only the left hemisphere. (3) TCD revealed increased blood flow velocity in the ipsilateral MCA by activating the recovering hand (10.5+/-3.3%; P<0.001). CONCLUSION: TMS reveals a specific area in the motor cortex from which ipsilateral MEPs can be elicited and both TMS and TCD indicate that an ipsilateral corticospinal tract can be accessible in some adult controls or becomes unmasked after cerebral damage.

Motor cortex excitability in chronic fatigue syndrome.

OBJECTIVE: To use transcranial magnetic stimulation (TMS) to define motor cortical excitability in chronic fatigue syndrome (CFS) subjects during a repetitive, bilateral finger movement task. METHODS: A total of 14 CFS patients were tested and compared with 14 age-matched healthy control subjects. TMS of the motor cortex (5% above threshold) was used to elicit motor evoked potentials (MEPs). Subjects performed regular (3-4/s) repetitive bilateral opening-closing movements of the index finger onto the thumb. MEPs of the first dorsal interosseus (FDI) were measured before, immediately following exercise periods of 30, 60 and 90 s, and after 15 min of rest. RESULTS: Performance, defined by rate of movement, was significantly slower in CFS subjects (3.5/s) than in controls (4. 0/s) independent of the hand measured. The rate, however, was not significantly affected by the exercise duration for either group. The threshold of TMS to evoke MEPs from the FDI muscle was significantly higher in CFS than in control subjects, independent of the hemisphere tested. A transient post-exercise facilitation of MEP amplitudes immediately after the exercise periods was present in controls independent of the hemisphere tested, but was absent in CFS subjects. A delayed facilitation of MEPs after 15-30 min of rest was restricted to the non-dominant hemisphere in controls; delayed facilitation was absent in CFS subjects. CONCLUSIONS: Individuals with CFS do not show the normal fluctuations of motor cortical excitability that accompany and follow non-fatiguing repetitive bimanual finger movements.

Delayed facilitation of motor cortical excitability following repetitive finger movements.

OBJECTIVES: To define motor cortical excitability changes occurring at various times after non-fatiguing bimanual exercise of the index fingers. METHODS: Twenty healthy right-handed subjects were studied with transcranial magnetic stimulation (TMS) of the right non-dominant hemisphere. They performed regular (3-4/s) repetitive opening-closing bilateral movements of the index finger onto the thumb. Motor evoked potentials (MEPs) of the left first dorsal interosseus (FDI) and rate of the repetitive finger movements were determined (1) before exercise, (2) immediately following 3 exercise periods of 30, 60 and 90 s, and (3) over a subsequent 30 min rest period. RESULTS: Rate of movement did not show significant change during any of the exercise periods but did increase significantly when tested after 15 min of rest. MEPs immediately after 30 and 60 s of exercise were facilitated whereas MEPs after 90 s of exercise did not differ from baseline measures. MEP amplitudes were significantly increased after rest of approximately 15 min compared to the baseline MEPs. In contrast, motor potentials evoked by peripheral nerve stimulation were unchanged throughout the experimental test periods. CONCLUSIONS: Motor cortical excitability relating to an intrinsic finger muscle (FDI) was facilitated beginning 15 min after a brief period of non-forceful, repetitive activity of that muscle. This delayed facilitation of motor cortex after exercise may represent a form of short-term potentiation of motor cortical excitability.

Brain excitability changes in the relapsing and remitting phases of multiple sclerosis: a study with transcranial magnetic stimulation.

OBJECTIVE: Recent functional and imaging studies have substantially contributed to extend the concept of multiple sclerosis (MS), classically regarded as a disease limited to the myelin axonal sheath. Several findings, in fact, point to a parallel involvement of neuronal components of the central nervous system (CNS) in the course of MS. In the present study, therefore, we explored, in MS patients, some characteristics of central motor pathways related to changes of neuronal excitability as measured using transcranial magnetic stimulation (TMS). METHODS: Seventy-nine patients affected by relapsing-remitting (RR) MS were examined using single and paired TMS in order to assess excitability changes in the hand motor cortex occurring during relapse and/or remission of the disease. The analyzed parameters were: motor-evoked potential (MEP) threshold, silent period (SP), intracortical inhibition (ICI) with paired pulses from 1 to 6 ms interstimulus intervals (ISIs), and central motor conduction time (CMCT). RESULTS: The analysis of variance exhibited a strong correlation (P<0.001) between the clinical phase and the type of excitability changes: 'relapsing' patients showed increased threshold and reduced SP duration. 'Relapsing' patients also displayed a significant lack of normal intracortical inhibition (ICI). By contrast, 'remitting' patients showed a significant SP prolongation with normal motor thresholds. CONCLUSIONS: The present findings reveal changes in cortical excitability that might play a role in the pathophysiology of MS symptoms. In particular, the relapsing phase of MS has been found to be associated with cortical hyperexcitability irrespective of the site of clinical manifestation or new plaque formation. These results might help to explain the puzzling picture of neurological symptoms observed in MS patients during different phases of the disease. SIGNIFICANCE: Alterations of neuronal components of the CNS play a role in MS.

The effect of riluzole in amyotrophic lateral sclerosis: a study with cortical stimulation.

A population of 31 patients with sporadic amyotrophic lateral sclerosis (ALS) was selected for a prospective open study based on treatment with riluzole. A neurophysiological evaluation was performed by means of single and paired transcranial magnetic stimulation (TMS). The examined parameters, excitability threshold, motor evoked potential (MEP) duration, silent period (SP) duration and time course of intracortical inhibition to paired TMS after 6 months treatment, were matched against those recorded from the patients themselves before the beginning of treatment and from 20 (single TMS) or 10 (paired TMS) age-matched control subjects. Normal behaviour of the SP in response to increasing TMS was found in the treated patients; they showed a significant linear correlation between these two parameters (r=0.96) comparable to that calculated for controls (r=0.98), and significantly different with respect to drug-free patients (r=0.8, P=0.014). A significant reduced size of the 'conditioned' MEPs to paired stimulation was documented in the treated patients compared with the untreated patients (P=0.002). Our neurophysiological contribution to the assessment of the effect of riluzole on the motor cortical inhibitory property in ALS may be considered a setting for controlled trials in extended patient series, even in a pre-clinical phase.

Mechanisms of nervous propagation along central motor pathways: noninvasive evaluation in healthy subjects and in patients with neurological disease.

Motor evoked potentials (MEPs) to scalp stimulation have been obtained in 45 control patients and in 70 patients with neurological diseases. Optimal responses were obtained through a pericranial cathode consisting of 6 to 12 regularly spaced, interconnected pericranial cathodal discs whose resistance was carefully balanced with that of a stimulating anodal disc placed on the appropriate scalp region. The foci of maximal response for proximal and distal upper limb muscles as well as for lower limb muscles were localized. The scalp to cervical cord central conduction time (CCT) along motor tracts governing the hand muscles was 5.21 +/- 0.42 ms. This index was highly correlated with the subject's height and stable in time when repeatedly tested. Collision between orthodromically and antidromically propagated motor impulses was obtained. Response facilitation was achieved by means of prestimulus voluntary contraction of the target muscle, continuous vibration of its tendon, or scalp stimulation with paired shocks. The presence of a premovement facilitation of MEPs was also demonstrated, as was the presumed presence of transcallosal facilitation. An efferent volley secondary to scalp stimulation was recorded from the nerve trunk. Abnormalities in MEP characteristics as well as in CCTs were found in patients with multiple sclerosis, amyotrophic lateral sclerosis, cord compression, and degenerative diseases of the central nervous system.

The treatment of severe forms of myasthenia gravis.

In this study we introduced and tested the clinical efficacy of a combined treatment based on the association of plasma exchange (PE) with high daily doses of prednisone in 18 patients with severe forms of myasthenia gravis (MG). A myasthenic score based on strength and resistance was evaluated in each patient in basal condition and during the treatment. The study design included 5 sessions of PE, performed within a period of 15 days, 1 session every 3 days, associated with administration of oral prednisone (1 mg/kg of body weight), which began at the same time as the first session and was continued following a daily schedule for at least three months. A significant improvement was obtained from the start of the therapy, with a reduction of the myasthenic score from 26.56 to 11.44 by day 10 and with further reduction after PE interruption. An early improvement, recorded within 24-48 hours of the beginning of the study design, was observed in 11/18. The administration of steroid therapy was never followed by a worsening of myasthenic symptoms (as reported when it is administered in the absence of concomitant PE). No recurrence of symptoms was reported after 29 months' follow-up. This type of therapeutic association was generally well tolerated and no unwanted side effects were observed. According to our results we can conclude that medium-high doses of oral prednisone in simultaneous association with PE lead to a successful control of severe forms of MG and may be considered a valid therapeutic strategy.