s of the A.I.S.F. Annual Meeting 2010 /Digestive and Liver Disease 43S (2011), S65–S108 S75 Conclusions: Adrenal dysfunction is common in nonseptic cirrhotic patients and, according to our preliminary results, is independently associated with reduced survival. These findings highlight the clinical relevance of adrenal dysfunction in nonseptic cirrhotic patients with ascites.

OBJECTIVE:Frontotemporal lobar degeneration (FTLD) includes different heterogeneous conditions mainly characterized by personality changes and cognitive deficits in language and executive functions; movement disorders have also been associated with FTLD. The present study aimed to measure the primary motor cortex (M1) inhibitory and facilitatory functions in patients affected by FTLD.MATERIALS AND METHODS:The study included 17 FTLD patients, 8 age-matched healthy controls and 8 Alzheimer's disease (AD) patients. Transcranial magnetic stimulation (TMS) was used to study intracortical inhibition (ICI) and facilitation (ICF) by using a double-pulse paradigm.RESULTS:FTLD patients were comparable with controls and AD patients for ICI and ICF. Corticobasal degeneration (CBD) patients presented significant reduced inhibition at ISI3; moreover two out of seven CBD patients had only ipsilateral responses.DISCUSSION:The present study reveals a selective impairment of M1 ICI inhibitory response in CBD, which may help in distinguishing among the FTLD clinical spectrum.

We describe a case of a young patient suffering from a rapidly progressive cognitive decline, associated with delusions, myoclonus and seizures and with no family history for dementia. Clinical features, along with skin biopsy findings were overlapping storage disease; the genetic analysis, however, demonstrated a de novo presenilin 1 mutation. The present report suggests the usefulness of genetic determinations in early‐onset cases of dementia, even without an autosomal dominant trait of inheritance; for these cases and their relatives an extensive genetic counselling should be recommended.

Objective: In recent years, a promising tool has been introduced which allows the co-registration of electroencephalographic (EEG) activity during brain transcranial magnetic stimulation (TMS). The aims of the present study are to identify eventual stimulus-related artefacts, and to confirm and extend previous EEG/TMS findings about the possible networks generating EEG responses evoked by TMS.Methods: Focal TMS was delivered to the left primary motor cortex (MI), with different coils (real and sham) and orientations (45 and 135 degrees in respect to the sagittal plane), in six healthy subjects. EEG and motor evoked potentials (MEPs) were simultaneously recorded from 19 scalp electrodes.Results: TMS, with coil oriented at 45 degrees, induced EEG responses characterized by a sequence of positive deflections peaking at approximately 14, 30, 60 and 190 ms and negative deflections peaking at approximately 10, 18, 40 and 100 ms post-TMS. The negative components were recorded at the recording electrode corresponding with the stimulation site (N10, N18), as well as at recording electrodes over the frontal region of the contralateral, unstimulated, hemisphere (N40) and bilaterally over the central hemispheres with its maximal representation at the stimulation site (N100). The positive components were insteaddetected at the frontal region of the right, unstimulated, hemisphere (P14), over the central electrodes Cz, Fz and the frontal region of the right hemisphere (P30), at the stimulation site (P60), and over the frontal regions of both hemispheres. When TMS was delivered with the coil oriented at 135 degrees,no MEPs were recorded from the right target muscle. Nonetheless, all the TMS-induced EEG components were still evoked apart from the N20-P30. Finally, TMS with the sham coil over left MI did not induce either significant EEG responses or MEPs.Conclusions: In conclusion, the TMS evoked components we have obtained by recording in continuous mode strikingly fit with those already described by other authors for both their latencies and the spatio-temporal pattern of scalp distribution.Significance: This experiment is a farther validation of the combined EEG/TMS recording technique as a promising tool for experimental and clinical purposes. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Objective: Repetitive transcranial magnetic stimulation (rTMS) is proposed for the treatment of drug-resistant depression. Studies performed in accordance with evidence-based medicine (EBM) are scarce, particularly in seeking optimal treatment and evaluation parameters. We aimed to test various types of rTMS in a large sample of depressed patients following EBM rules and to investigate treatment-related changes in plasma levels of neurotransmitters involved in depression.Methods: Seventy-one drug-resistant depressed patients were randomly assigned to low (1 Hz) or high (17 Hz) rate TMS, applied for 5 days over the left dorsolateral prefrontal cortex (L-DLPFC). Patients were separated into two study designs. One group (20 patients) received only active treatment, while the other entered a double-blind, placebo-controlled, crossover design. Pre- and post-treatment blood samples were taken for evaluation of plasma levels of dopamine and serotonin.Results: After a week of treatment patients had a measurable benefit. However, overall the placebo stimulation did not differ significantly from real stimulation, nor were differences observed between the two rates of rTMS. The only difference emerged when the real stimulation was applied at 17 Hz following placebo treatment. Plasma levels of neurotransmitters between active and placebo rTMS were similar.Conclusions: Using the treatment schedule of I week, although a clinical improvement after active treatment was indeed observed, this was both clinically and biochemically indistinguishable from that seen in the placebo arm.Significance: This suggests that most of the previous emphasis, for short period of treatment, should be tempered down and that further work is required in order to verify whether optimal stimulation and evaluation parameters for TMS-treatment of depression beyond the placebo effect may be found following EBM rules. (c) 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Cholinergic deafferentation/recovery in rats mainly impinges on the fronto-parietal coupling of brain rhythms [D. P. Holschneider et al. (1999) Exp. Brain Res., 126, 270-280]. Is this reflected by the functional coupling of fronto-parietal cortical rhythms at an early stage of Alzheimer's disease (mild AD)? Resting electroencephalographic (EEG) rhythms were studied in 82 patients with mild AD and in control subjects, such as 41 normal elderly (Nold) subjects and 25 patients with vascular dementia (VaD). Patients with AD and VaD had similar mini-mental state evaluation scores of 17-24. The functional coupling was estimated by means of the synchronization likelihood (SL) of the EEG data at electrode pairs, accounting for linear and non-linear components of that coupling. Cortical rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha (1 8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz) and gamma (30-40 Hz). A preliminary data analysis (Nold) showed that surface Laplacian transformation of the EEG data reduced the values of SL, possibly because of the reduction of influences due to head volume conduction. Therefore, the final analysis was performed on Laplacian-transformed EEG data. The SL was dominant at alpha 1 band in all groups. Compared with the Nold subjects, patients with VaD and mild AD presented a marked reduction of SL at both fronto-parietal (delta-alpha) and inter-hemispherical (delta-beta) electrode pairs. The feature distinguishing the patients with mild AD with respect to patients with VaD groups was a more prominent reduction of fronto-parietal alpha 1 SL. These results suggest that mild AD is characterized by an abnormal fronto-parietal coupling of the dominant human cortical rhythm at 8-10.5 Hz.

Transcranial magnetic stimulation (TMS) has been effective in the treatment of psychiatric and movement disorders.1 Tardive dyskinesia (TD) is a persistent motor adverse event due to long-term neuroleptic exposure with a prevalence of about 30% among psychiatric patients. We describe a patient with resistant depression who underwent TMS of dorsolateral prefrontal cortex (DLPFC), a main target for stimulation in depression.1 This resulted in a complete yet transient improvement of the TD symptomatology. A 65-year-old woman had recurrent major depression of 30 years’ duration resulting in multiple hospitalizations and poor response to pharmacotherapy. During her last hospitalization, due to a depressive episode with psychotic symptoms, the patient was admitted with a therapy of amitriptyline 120 mg/day, lamotrigine 200 mg/day, and thioridazine 75 mg/day, to which she had not responded in the prior 5 months. Amitriptyline was increased up to 200 mg/day with …

Activity-dependent modulation of cortical synaptic transmission is a fundamental mechanism involved in learning and memory storage. This modulation has been widely studied in in vitro brain slices and in vivo animal models. More recently, transcranial magnetic stimulation has allowed detection of activity-dependent excitability modulation occurring in the intact human primary motor cortex (MI) after execution of different kinds of motor tasks. Both increased and decreased MI excitability have been described after exercise. While increased MI excitability is generally considered direct expression of cortical synaptic plasticity, a controversy still exists as to whether decreased MI excitability reflects fatigue of central nervous system (CNS) structures or cortical neuronal reorganization taking place after exercise. Here, we extend previous findings in order to provide further support for the latter hypothesis. Abduction- adduction movements of the thumb performed for 1 min at 2 Hz frequency rate produce a 55% decrease in MI excitability of mean 30 min duration. Similar decrements in amplitude and duration of motor evoked potentials (MEPs) are not reached if the same task is performed once again during the maximal inhibition phase (10 min post-exercise) produced by a previous activation. Moreover, the same task performed at a lower (1 Hz) frequency rate produces no significant MEP changes but can transiently reverse activity-dependent depression obtained after previous 2 Hz movements. Repeated execution of the same task (2 Hz), each being performed after recovery from a previously induced MEP depression, ceases to produce an MEP decrement, suggesting adaptation in MI excitability modulation. This adaptation is long lasting and task-specific, since a different motor task (1 min circular movement of the thumb) restores activity-dependent modulation. Overall, these findings suggest that the dynamic modulation of MEPs occurring after execution of different kinds of simple motor skills reflects some form of activity-dependent, plastic neuronal reorganization instead of CNS fatigue. Possible anatomo-functional mechanisms involved in this activity-dependent modulation of MI excitability are discussed.

We studied six patients suffering from benign rolandic epilepsy of childhood with central temporal spikes who presented so-called 'extreme somatosensory evoked potentials (SEPs)' following peripheral somatosensory stimulation. Stimuli were delivered to the fingers of one hand using both a triggered tendon hammer and low-intensity electrical stimulation. The electrical stimulation was delivered in sequences in different conditions (i.e. random order, 1, 3 and 10 Hz). Both tapping and electrical stimulation produced scalp evoked potentials in all subjects, characterized by a spike followed by a slow wave, similar in morphology and scalp distribution to the spontaneously occurring spikes. This paroxysmal activity was sensitive to stimulus rate; the number of evoked spikes was inversely related to the frequency of stimulation, being maximal at 1 Hz and disappearing at high frequencies (10 Hz). Spontaneous spikes disappeared during high-frequency stimulation but were present during low-frequency stimulation. Averaged SEPs at 3-Hz stimulation showed a late high-amplitude component, identical in morphology and distribution to the single evoked spike. We therefore conclude that, in these subjects, the so-called 'extreme SEPs' are evoked spikes and that evoked and spontaneous spikes share common cortical sensorimotor generators. The evidence that these generators can be influenced by afferent input provides important information regarding the functional mechanisms involved in modulating cortical excitability in benign rolandic epilepsy. Moreover, we suggest that peripheral electrical stimulation can be used as an additional activation test in this kind of epilepsy.

Objectives: We report the analysis of scalp topography and dipole modeling of the rolandic spikes in 6 patients suffering of benign rolandic epilepsy of childhood with extremely high amplitude SEP by tapping stimulation of the finger of the hand. Methods: EEG and BESA analysis were performed for both rolandic spontaneous interictal spikes and high amplitude scalp activity evoked by tapping and electrical stimulation of the first finger of the right hand. Results: The evoked responses showed a morphology characterized by a rapid phase (spike) followed by a slow phase (slow wave). The spike presented an early small positive component followed by a main negative component. Similar morphology, dipole configuration and source localization were observed for both rolandic spikes and evoked high amplitude scalp responses. Dipole localization showed an overlap of spatial coordinates between rolandic and evoked spikes. Conclusions: These findings suggest that the extremely high amplitude SEPs could be evoked spikes which probably had the same cortical generators of the spontaneous rolandic spikes.

We evaluated vertex-parietal P37, N50, and contralateral N37 somatosensory evoked potentials (SEPs) to posterior tibial nerve stimulation during weak (20 to 30%) and strong (80 to 90%) ipsilateral gastrocnemius-soleus contraction. The results were compared with data obtained during full relaxation. P37 and N50 were attenuated significantly during weak contraction and then abolished during strong contraction, whereas the contralateral N37 was not. The N37 potential spreads over the vertex and over the ipsilateral parietal region during strong contraction. The Cz'-F3 montage was not appropriate for detecting these SEP patterns. These findings suggest that thalamic or cortical gating mechanisms affect specific cortical responses. P37 and N50 could reflect the arrival of the afferent volley into the motor areas from thalamic and cortical (subareas 1 and 2 of S1) projections. N37 could be generated in subarea 3b. Differential analysis of N37 and P37 is required in clinical practice, mainly in those conditions that involve the motor system and in those conditions in which tonic muscular activity is increased.

The human somatosensory cortex (S1) is capable of modification after partial peripheral deafferentation, but it is not known whether spinal and brainstem changes contribute to this process. We recorded spinal, brainstem and cortical somatosensory evoked potentials following ulnar nerve stimulation in patients affected by unilateral carpal tunnel syndrome with EMG evidence of chronic alterations in median nerve sensorimotor conduction at the wrist lasting at least 4 weeks, and compared them with those from the unaffected hand and with those obtained in a control group. Amplitudes of spinal N13 and brainstem P14 potentials following stimulation of the ulnar nerve ipsilateral to the deafferented median nerve were greater than those following stimulation of the contralateral ulnar nerve. Side-to-side amplitude differences in N13 and P14 were greater in patients than in the control group. Parietal N20 and P27 potentials, supposedly generated in S1, were also significantly increased. The present results suggest that a chronic pathological modification of peripheral sensorimotor inputs is associated with changes in neural activity at multiple sites of the somatosensory system. Changes in spinal and brainstem structures could contribute to the mechanisms subserving changes in the S1. Changes in synaptic strength and unmasking inputs secondary to disconnection of the normally dominant inputs to the 'median nerve' cortex may be the mechanisms underlying ulnar nerve SEP changes.

We mapped the cortical representations of the abductor pollicis brevis, flexor carpi radialis, biceps and deltoid muscles in six subjects with unilateral wrist fractures, immediately after the removal of the splint. This was repeated 1 month later in three out of the six subjects. Duration of immobilization was 1 month. Muscle maps were obtained by delivering four focal magnetic pulses for each scalp position (1 cm apart with reference to Cz) over the contralateral hemisphere. Motor evoked potentials (MEPs) were averaged off-line and expressed as a percentage of the motor action potential evoked by supramaximal peripheral nerve stimulation. Volume, area and threshold of the motor maps showed no significant hemispheric differences within each muscle in 10 control subjects. In the first recording session the volume of each immobilized muscle was distinctly higher when compared to that of controls in terms of absolute value and side-to-side ratio. This finding disappeared 1 month later. Moreover, MEP amplitude difference recorded from hand muscle could be reversed during a small tonic voluntary contraction. Immobilization had no significant effect on the threshold for activation of the target muscles and on the area of the motor map. The increase in MEP amplitudes occurred without changes in spinal excitability as tested by the F wave. These findings suggest that immobilization of the upper limb induces a reversible enhancement of the excitability of structures along the corticomotoneuronal pathway. Sustained restriction of volitional movements and reduction in somatic sensory inputs might promote this functional modulation of the motor system.

We performed topographical mapping of somatosensory evoked potentials (SEPs) to the posterior tibial nerve using earlobe references both ipsilateral and contralateral to the stimulation side. The voltage of the frontal contralateral N37 and P50 components was enhanced, while the voltage of the parietal ipsilateral P37 and N50 components was reduced when the contralateral earlobe was substituted by the ipsilateral earlobe reference. Maps of the same data documented concomitant changes in negative and positive potential fields, showing an expansion of the pre-Rolandic N37 toward the centrotemporal contralateral regions, and a tendency of the parietal ipsilateral P37, N50 components to be more focally distributed at the vertex. SEPs recorded at each earlobe (Cv6 reference) provided an explanation of these results: The contralateral earlobe detected a negative potential corresponding to the N37 potential recorded over the scalp, followed by a P50 potential that attenuated the contralateral responses and enhanced the ipsilateral ones. The ipsilateral earlobe had no significant effects on scalp SEPs, since it detected only a large N33 negativity. Current source density (CSD) maps were, of course, not influenced by the ear used as reference. Our results suggest that the ipsilateral ear reference is better than the contralateral one for recording "genuine" cortical SEPs. Therefore, it can be recommended in the clinical domain for mapping studies of lower-limb cortical SEPs.

We studied the influence of contralateral and ipsilateral cutaneous digital nerve stimulation on motor evoked potentials (MEPs) elicited in hand muscles by transcranial magnetic stimulation (TMS). We tested the effect of different magnetic stimulus intensities on MEPs recorded from the thenar eminence (TE) muscles of the right hand while an electrical conditioning stimulus was delivered to the second finger of the same hand with an intensity four times above the sensory threshold. Amplitude decrement of conditioned MEPs as a function of magnetic stimulus intensity was observed. The lowest TMS stimulus intensity produced the largest decrease in conditioned MEPs. Moreover, we investigated the effects of ipsilateral and contralateral electrical digital stimulation on MEPs elicited in the right TE and biceps muscle using an intensity 10% above the threshold. Marked MEP inhibition in TE muscles following both ipsilateral and contralateral digital stimulation is the main finding of this study. The decrease in conditioned MEP amplitude to ipsilateral stimulation reached a level of 50% of unconditioned MEP amplitude with the circular coil and 30% with the focal coil. The amplitude of conditioned MEPs to contralateral digital stimulation showed a decrease of 60% with the circular coil and more than 50% with the focal coil. The onset of the inhibitory effect of contralateral stimulation using the focal coil occurred at a mean of 15 ms later than that of ipsilateral stimulation. No MEP inhibition was observed when recording from proximal muscles. Ipsilateral and contralateral digital stimulation had no effect on F wave at appropriate interstimulus intervals, where the main MEP suppression was noted. We stress the importance of selecting an appropriate test stimulus intensity to evaluate MEP inhibition by digital nerves stimulation. Spinal and cortical sites of sensorimotor integration are adduced to explain the direct and crossed MEP inhibition following digital nerves stimulation.