Search

Introduction: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods: BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1-2 (early add-on) and ≥ 3 (late add-on) prior antiseizure medications. Results: A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12months was 125 (100-200) mg in the early add-on group and 200 (100-200) in the late add-on group (p

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure‐freedom, seizure response (≥50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45years (33–56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p&nbsp

Background and aims: The present study aims to assess possible qEEG differences between newly diagnosed multiple sclerosis (MS) patients with or without cognitive impairment (CI). Methods: We enrolled 22 patients (18-55-years-old) treated with first-line drugs for

Background and aims: Fatigue is one of the most common, early, and disabling symptom in Multiple Sclerosis (MS). tDCS on Dorso-Lateral Prefrontal Cortex seems to give positive results on MS fatigue. Recently, a new stimulation protocol, transcranial Random Noise Stimulation (tRNS), showed powerful facilitatory effects on motor cortex in healthy subjects and ameliorated pain in MS patients. Here we aimed to explore effects of motor cortex tRNS in MS fatigue.Methods: 13 MS fatigued patients were enrolled in a blind, sham controlled tRNS study. 7 patients received 1.5 mA, 101-640 Hz tRNS stimulation and 6 patient received sham stimulation, both stimulations applied daily over M1 for 15 minutes, for two consecutive weeks. Outcome measures were Modified Fatigue Impact Scale (MFIS) for fatigue, BICAMS for cognitive impact, Purdue Pegboard for manual dexterity, Timed 25 Foot Walking Test (T25FWT) for fatigability, MSQoL-54 for quality of life.Results: ANOVA showed statistically significant improvement in MFIS physical subscale in real stimulation group (Real-p=0.004, Sham-p=0.22). SDMT scores improved only in tRNS subjects (p=0.01). MSQoL-54 scores showed a significative improvement only in tRNS patient (REAL-p=0.02, Sham-p=0.5) Patient Global Impression of Perceived Fatigue was significatively reduced in tRNS group (p=0,005). Conclusion: tRNS on primary motor cortex can decrease MS fatigue. If further studies on larger samples validated and strengthened the results obtained so far, the development of stimulation device suitable for self-managed home based treatment should be strongly pursued to optimize management of such disabling symptom in MS.

Background: Migraine has been associated with increased risk of cardiovascular (CV) accident like angina and myocardial infarction(1) . Vascular changes in migraineur traditionally may prevail in cranial blood district, but more likely it is a generalized vascular phenomenon.(2) Previous studies showed an increased aortic pulse wave velocity (aPWV), a direct measure of aortic stiffness and an independent predictor of stroke and CV disease, in young and middle-aged migraineurs(3) Here we hypothesized that, if associated with the pathogenetic bases of the disease, increased aPWV should be appreciable also in migraineurs children. Materials and Methods: : We studied 10 children with migraine without aura (age 12,9±1,9 years, 7 male and 3 female, blood pressure 123,30±13,6mm Hg) and 6 age-, sex-, and blood pressure–marche healthy control children. In all participants, aortic PWV and aortic augmentation index were measured using an oscillometric technique. Results: Children with migraine without aura had a higher a PWV (5.65 ± 0.60 vs 4.65 ± 0.42 m×s−1, p < 0.002) and aortic augmentation (15.07 ± 13.97 vs 3.00 ± 7,48 p < 0.037) than matched control children. While other variables potentially able to influence aortic distensibility, such as mean brachial arterial pressure and age, are not significantly different between the two groups. Similarly, no significant differences emerged as regards heart rate, diastolic arterial pressure and humeral differential and systolic and aortic pulsation.. Conclusion: The present study showed higher aPWV in children affected by migraine without aura with respect to healthy controls. This result support the data of higher aPWV in migraine(3) and suggest that an increased aortic stiffness is already present in childhood. So, whatever the role played by such vascular alteration, it’s likely to be associated with basic mechanisms of migraine and could represent a new way to shed light on the complex yet unsolved pathophysiological network of the disease.

Objective: spontaneous intracranial hypotension (SIH) can sometime represent a puzzling clinical condition due to missing causal factors and poor response to treatment. Here we describe a SIH case where cerebrospinal fluid (CSF) leaks follow to the uncommon cause of meningeal diverticula[1]. Materials: a 54-years-old-woman who works as a caregiver came to our attention for a symptomatology characterized by heavy headache localized on the vertex that started after long lasting upright position and that improved with rest. During last two months the pain has begun costant, associated with vertigo and non responsive to rest or symptomatic drugs. Methods: the patient was admitted to our Unit and remained for 9 days. During such period she underwent medical therapy with intravenous hydratation, 5% glucose solution and 8 mg of desametasone per day. We performed a cerebral CT scan and cerebral and cervicodorsal contrast-enhanced magnetic resonance imaging (MRI). Moreover, the patient underwent a Neuro-surgical consult. Results: CT scan showed intracranial hypotension suggestive signs and the diagnosis was confirmed by cerebral MRI scan, showing pachimeningeal thickening and contrast enhancement and slight caudal sliding of the cerebellar tonsils and diencephalic structures, associated to smaller ventricles. Cervico-dorsal MRI scan revealed the causal factor, highlighting the presence of 5 meningeal diverticula turning outwards at the level of right D9- D10 and D11-D12 and left D8-D9, D9-D10 and D10-D11 intervertebral foramen (the biggest 12 mm). The patient response to medical therapy was good and led to symptoms regression, making not necessary other therapeutic approaches, such as epidural blood patch or surgical intervention. One month after discharge the patient referred no headache, but sporadic vertigo that she controlled using antivertiginous drugs. Discussion: spontaneous intracranial hypotension has several causes, one of them is represented by cerebrospinal leaks. Meningeal diverticula represent a possible, even if very rare, cause of cerebrospinal leaks and, in our case, such link was probably at the origin of our patient symptoms and imaging signs. Medical treatment succeded in soothing patient’s headache and vertigo, so, in future, it will be useful to reconsider the need for surgical intervention in patients with meningeal diverticula. Conclusions: Meningeal diverticula, even if rare, are possible causes of SIH and medical treatment could be effective in such cases, since surgery is not always needed.

Planning reaching and grasping an object requires selective computation of extrinsic (i.e. distance) and intrinsic (i.e. size) object properties, respectively. However, the mechanism for this selection can be partially effective in this process, and nonrelevant object attributes can be used. An experiment was carried out to test whether linguistic information on object properties, as well as sensorial object information, could be automatically involved in movement planning. Subjects were required to reach and grasp a wooden bar, that could have two sizes and could be placed at two spatial positions. An Italian word, either lungo (long) or corto (short) was written on the external face of the object. No analysis of the word was required to the subjects. Results showed that arm velocity was higher for farther object position. In addition, the word influenced arm velocity. Faster reaching movements were found for stimuli with the word lungo with respect to stimuli with the word corto. In other words, the subjects planned a movement as if the stimuli with the word lungo were positioned farther than the stimuli with the word corto. This finding indicates that high-level coding are automatically involved in the analysis of object attributes, as distance. We conclude that in human behaviour the verbal representation is may be related to pragmatic object representation. This may support the notion of the correspondence between praxic and linguistic functions, shown by neuropsychological studies.

Despite a huge effort of the scientific community, the functioning of Long-Term Memory (LTM) processes is still debated and far from being elucidated. Functional and neurophysiological data point to an involvement of Dorsolateral Prefrontal Cortex (DLPFC) in both encoding and retrieval phases. However, the recently proposed Explicit/Implicit Memory Encoding and Retrieval (EIMER) model proposes that LTM at the encoding phase consists of anatomically and chronologically different sub-phases. On this basis, we aimed to investigate the role of right DLPFC during a late-encoding phase by means of low-frequency rTMS. Thirty right-handed healthy subjects were divided into three experimental groups. Inhibitory rTMS was applied over right-DLPFC immediately after the encoding phase (Late-Encoding Group) or before recognition phase (Pre-Recognition Group), 24 h after, of an LTM task. Both groups also received sham stimulation during the non-target phase, while the third group (Sham Group) received only sham stimulation in both phases. The Late-Encoding Group collected a lower number of correct responses compared with Sham Group (p = 0.00), while Pre-Retrieval Group increased accuracy as compared to the Sham Group (p = 0.0). rTMS-inhibition of the right DLPFC seems able to interfere with LTM memory performances when delivered at a late stage of the encoding phase, with opposite effects at the pre-retrieval phase.

Background. Alzheimer’s cognitive-behavioral syndrome is the result of impaired connectivity between nerve cells, due to misfolded proteins, which accumulate and disrupt specific brain networks. Electroencephalography, because of its excellent temporal resolution, is an optimal approach for assessing the communication between functionally related brain regions. O bjective. To detect and compare EEG resting-state networks (RSNs) in patients with amnesic mild cognitive impairment (aMCI), and healthy elderly (HE). Methods. We recruited 125 aMCI patients and 70 healthy elderly subjects. One hundred and twenty seconds of artifact-free EEG data were selected and compared between patients with aMCI and HE. We applied standard low-resolution brain electromagnetic tomography (sLORETA)-independent component analysis (ICA) to assess resting-state networks. Each network consisted of a set of images, one for each frequency (delta, theta, alpha1/2, beta1/2). Results. The functional ICA analysis revealed 17 networks common to groups. The statistical procedure demonstrated that aMCI used some networks differently than HE. The most relevant findings were as follows. Amnesic-MCI had: i) increased delta/beta activity in the superior frontal gyrus and decreased alpha1 activity in the paracentral lobule (ie, default mode network); ii) greater delta/theta/alpha/beta in the superior frontal gyrus (i.e, attention network); iii) lower alpha in the left superior parietal lobe, as well as a lower delta/theta and beta, respectively in post-central, and in superior frontal gyrus(ie, attention network). Conclusions. Our study confirms sLORETA-ICA method is effective in detecting functional resting-state networks, as well as between-groups connectivity differences. The findings provide support to the Alzheimer’s network disconnection hypothesis.

BACKGROUND: The management of epilepsy in older adults has become part of daily practice because of an aging population. Older patients with epilepsy represent a distinct and more vulnerable clinical group as compared with younger patients, and they are generally under-represented in randomized placebo-controlled trials. Real-world studies can therefore be a useful complement to characterize the drug's profile. Brivaracetam is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A and approved as adjunctive therapy for focal seizures in adults with epilepsy. OBJECTIVE: The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive brivaracetam in older patients (≥65 years of age) with epilepsy treated in a real-world setting. METHODS: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a 12-month retrospective multicenter study including adult patients prescribed adjunctive brivaracetam. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events and the incidence of adverse events. Data were compared for patients aged ≥65 years of age ('older') vs those aged

Objective: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting. Methods: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure‐freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Results: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases. Significance: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE.

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32-56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy.

Objectives. Fibromyalgia (FM) is characterized by spontaneous chronic widespread pain in combination with hyperalgesia to pressure stimuli. Sound-induced flash illusions (SIFIs) reflect cross-modal interactions between senses allowing to assess a visual cortical hoerexcitability (VCH) by evaluating the fission and fusion illusions disruption. The aims of the present study were to explore whether SIFIs are perceived differently in patients with fibromyalgia as compared to healthy controls (HCs) and how migraine affects fission and fusion illusions in fibromyalgia. Methods. A single flash (F) accompanied by 0 to 4 beeps (B) was presented to induce the fission illusion while multiple flash (i.e., 2 to 4) accompanied by 0 or 1 beep was presented to induce fusion illusion. The mean number of perceived flashes in fission and fusion illusion trials was compared between the groups (i.e., FM, FM with migraine, and HCs) using repeated-measures analysis of variance. Medication history was recorded along with the administration of Fibromyalgia Impact Questionnaire and Hospital Anxiety and Depression scales. Results. Twenty-four patients with FM (mean age 51, 2 ± 10, 6 years; 22 females), seventeen patients with FM and migraine without aura (mean age 47.8 ± 11.4 years; 16 females; 13 chronic, 4 episodic migraine), and forty-one age- and sex-matched HCs (mean age 47.3 ± 6.9 years; 34 females) participated in the study. Fission and fusion illusory effects were detected in all the participants. However, in FM patients, the fission illusion was reduced and almost abolished as compared to HCs (1F1B, p = 0.02 ; 1F2B, p < 0.0001 ; 1F3B, p < 0.0001 ; 1F4B, p = 0.0001 ), while there were no differences between groups in fusion trials. Migraine did not affect the fission and the fusion illusions. Conclusion. Results from this study confirm that patients with FM have a VCH suggesting that the pathological changes in cortical excitability might have important roles in the pathophysiology of FM. SIFI represents a noninvasive behavioral tool for the exploration of cross-sensory functional interplay.

We evaluated the effects of transcranial random noise stimulation (tRNS) on fatigue in 17 subjects with relapsing–remitting multiple sclerosis with low physical disability. Two different patient groups underwent real or sham stimulation for 10days, targeting the primary motor cortex of the dominant side or contralateral to the most compromised limb. In the ‘real group’, beneficial effects were observed using the Modified Fatigue Impact Scale (p = 0.04; physical subscale: p = 0.03), the subscales ‘change in health’ (p = 0.006) and ‘role limitations due to physical problems’ (p = 0.001) of the Multiple Sclerosis Quality of Life-54, and by assessing the patient impression of perceived fatigue (p = 0.005).

Inherited neuromuscular disorders (INMD) are a heterogeneous group of rare diseases that involve muscles, motor neurons, peripheral nerves or the neuromuscular junction. Several different lab abnormalities have been linked to INMD: sometimes they are typical of the disorder, but they usually appear to be less specific. Sometimes serum biomarkers can point out abnormalities in presymtomatic or otherwise asymptomatic patients (e.g., carriers). More often a biomarker of INMD is evaluated by multiple clinicians other than expert in NMD before the diagnosis, because of the multisystemic involvement in INMD. The authors performed a literature search on biomarkers in inherited neuromuscular disorders to provide a practical approach to the diagnosis and the correct management of INMD. A considerable number of biomarkers have been reported that support the diagnosis of INMD, but the role of an expert clinician is crucial. Hence, the complete knowledge of such abnormalities can accelerate the diagnostic workup supporting the referral to specialists in neuromuscular disorders.

Gambling disorder (GD) is a psychiatric disease that has been recently classified as a behavioural addiction. So far, a very few studies have investigated the alteration of functional connectivity in GD patients, thus the concrete interplay between relevant function-dependent circuitries in such disease has not been comprehensively assessed. The aim of this research was to investigate resting-state functional connectivity in GD patients, searching for a correlation with GD symptoms severity. GD patients were assessed for gambling behaviour, impulsivity, cognitive distortions, anxiety and depression, in comparison with healthy controls (HC). Afterwards, they were assessed for resting-state functional magnetic resonance imaging; functional connectivity was assessed through a data-driven approach, by using independent component analysis. The correlation between gambling severity and the strength of specific resting-state networks was also investigated. Our results show that GD patients displayed higher emotional and behavioural impairment than HC, together with an increased resting state functional connectivity in the network including anterior cingulate cortex, the caudate nucleus and nucleus accumbens, and within the cerebellum, in comparison with the control group. Moreover, a significant correlation between behavioural parameters and the strength of the resting-state cerebellar network was found. Overall, the functional alterations in brain connectivity involving the cerebellum observed in this study underpin the emotional and behavioural impairment recorded in GD patients. This evidence suggests the employment of novel neuromodulatory therapeutic approaches involving specific and salient targets such as the cerebellum in addictive disorders.

We evaluated the combined use of transcranial random noise stimulation (tRNS) with the Graded Repetitive Arm Supplementary Program (GRASP) in sub-acute ischemic stroke patients suffering from arm impairment. Eighteen ischemic stroke patients with upper limb disability were randomly assigned to either the GRASP + tRNS or GRASP + Sham stimulation group. Fugl-Meyer Assessment-Upper extremity (FMA-UE) was performed to evaluate upper limb impairment before treatment (T0), after the last stimulation (T1) and after 30 days (T2). At T1 and T2, beneficial effects in the tRNS group correlated with better FMA-UE score than sham stimulation group (p

Migraine is a highly disabling disease characterized by recurrent pain. Despite an intensive effort, mechanisms of migraine pathophysiology still represent an unsolved issue. Evidence from both animal and human studies suggests that migraine is characterized by hyperresponsivity or hyperexcitability of sensory cortices, especially the visual cortex. This phenomenon, in turn, may affect multisensory processing. Indeed, migraineurs present with an abnormal, reduced, perception of the Sound-induced Flash Illusion (SiFI), a crossmodal illusion that relies on optimal integration of visual and auditory stimuli by the occipital visual cortex. Decreasing visual cortical excitability with transcranial direct current stimulation (tDCS) can increase the SiFI in healthy subjects. Moving away from these issues, we applied cathodal tDCS over the visual cortex of migraineurs, with and without aura, in order to decrease cortical excitability and thus physiologically restoring the perception of a reliable SiFI. Differently from our expectations, tDCS was unable to reliably modulate SiFI in migraine. The chronic, relatively excessive, visual cortex hyperexcitability, featuring the migraineur brain, may render tDCS ineffective for restoring multisensory processing in this disease.

We evaluated the relationship between motor and neuropsychological deficits in subjects affected by amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer’s Disease (AD). Kinematics of goal-directed movement of aMCI and AD subjects were compared to those of age-matched control subjects. AD showed a slowing down of motor performance compared to aMCI and controls. No relationships were found between motor and cognitive performances in both AD and aMCI. Our results suggest that the different motor behaviour between AD and aMCI cannot be related to memory deficits, probably reflecting the initial degeneration of parietal-frontal circuits for movement planning. The onset of motor dysfunction in early AD could represent the transition from aMCI to AD.

A number of researchers have proposed that the premotor and motor areas are critical for the representation of words that refer to actions, but not objects. Recent evidence against this hypothesis indicates that the left premotor cortex is more sensitive to grammatical differences than to conceptual differences between words. However, it may still be the case that other anterior motor regions are engaged in processing a word's sensorimotor features. In the present study, we used singleand paired-pulse transcranial magnetic stimulation to test the hypothesis that left primary motor cortex is activated during the retrieval of words (nouns and verbs) associated with specific actions. We found that activation in the motor cortex increased for action words compared with non-action words, but was not sensitive to the grammatical category of the word being produced. These results complement previous findings and support the notion that producing a word activates some brain regions relevant to the sensorimotor properties associated with that word regardless of its grammatical category.

Objective: To investigate the modulatory effect of a subthreshold low frequency repetitive transcranial magnetic stimulation (rTMS) train on motor cortex excitability. Methods: The study consisted of two separate experiments. Subjects received a 10 min long subthreshold 1Hz rTMS train. In the first experiment, (single pulse paradigm), cortical excitability was assessed by measuring the amplitude of motor evoked potentials (MEPs) before and after the rTMS train. In the second experiment, a paired pulse paradigm was employed. Results: Corticospinal excitability, as measured by the MEP amplitude, was reduced by the rTMS train (experiment 1), with a significant effect lasting for about 10 min after the train completion. There was notable inter-individual as well as intra-individual variability in the effect. rTMS produced a significant decrease in intra-cortical facilitation as measured by the paired pulse paradigm (experiment 2). This effect lasted for up to 15 min following the train. Intra-cortical inhibition was not significantly affected. Conclusions: Subthreshold low frequency rTMS depresses cortical excitability beyond the duration of the train. This effect seems primarily due to cortical dysfacilitation. These results have implications on the therapeutic use of rTMS. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Background: Patients affected by Multiple Sclerosis (MS) can show a tremor of their upper limbs, mostly during the performing of finalised action (action tremor) or at the maintaining of a position against gravity (postural tremor), as key clinical feature of their disease. Objectives: In order to reduce the tremor, patients underwent to repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex of left hemisphere. Methods: Eight patients affected by a middle form of MS were enrolled into the study. A standard neurological examination was carried out and the individual degree of disability was established employing the Expanded Disability Status Score (EDSS). At EDSS patients scored from 1.5 to 6.5, mean 4.6 ±1.9 SD. Tremor was rated according to the Fahn-Tolosa Marin Rating Scale. rTMS was delivered at 1 Hz frequency, along ten subsequent, separate sessions lasting ten minutes each one (i.e. 600 pulses). All subjects were aware about the aim of the study and fulfilled a formal consent. They were free to interrupt the study at any time. Before the first session, at the fifth day and at the last day of stimulation, kinematics of upper limb movements were recorded. Patients were asked to perform a continuous pointing, moving back and forth, as fast as possible, their right index finger between two black spots depicted on a working table, placed 15 cm apart. Task lasted six minutes divided in six parts, lasting one minute each one, divided by a resting period of 30 sec. Movements were recorded by means of a optoelectronic device (ELITE system) working at the sampling rate of 100 Hz. At the end of the last session a new clinical assessment was carried out. Results: Movement time, peak of velocity and acceleration and deceleration were analysed. Number of peaks of deceleration during the targeting phase was considered as the key marker of the tremor. Results of kinematics showed an overall improvement of symptoms including a decrease of time of movement execution and time of the deceleration phase as consequence of the reduction of number of peak of deceleration (i.e. tremor). Conclusions: Reduction of tremor became apparent at the clinical evaluation. Moreover, tremor was effectively influenced by rTMS and patients reported a subjective improvement of their symptoms. We concluded that this technique could be useful in order to reduce disability in MS patients.

The role of tactile information of the hand in the control of reaching to grasp movements was investigated. The kinematics of both reaching (or transport) and grasp components were studied in healthy subjects in two experimental conditions. In one condition (control condition) subjects were required to reach and grasp an object that could have two sizes and that could be located at two distances from the viewer. In the other condition (anaesthesia condition) the same movements were executed, but anaesthesia was provided to the subjects' fingertips. In both conditions vision of the hand was prevented during movement. Anaesthesia affected mainly the kinematics of the first phase of grasping, that is, the finger-opening phase. This phase was lengthened and maximal finger aperture increased. In contrast, the duration of the successive phase (finger-closure) was poorly modified. The reaching component was also impaired by anaesthesia. Although the total extent of hand path and the spatial relations between the finger aperture and closure phases did not change between the two conditions, hand path variability increased. This occurred during transport deceleration phase and after the increase in variability of finger path. In addition, the whole movement was slowed down. The results of the present experiment suggest that tactile signals at the beginning and at the end of movement can be used to compute grasp time and to optimise grasp temporal parameters. Alternatively, signals from tactile receptors can be involved in encoding the position sense of the fingers. When this input is lacking, the control of grasp and in particular that of finger-opening phase can be impaired. Finally, the effect of the grasp impairment on the reaching component supports the notion that the coordination between reaching and grasping involves the whole temporal course of the two components.

mild cogntiive impairment

The observation of an action modulates motor cortical outputs in specific ways, in part through mediation of the mirror neuron system. Sometimes we infer a meaning to an observed action based on integration of the actual percept with memories. Here, we conducted a series of experiments in healthy adults to investigate whether such inferred meanings can also modulate motor cortical outputs in specific ways. We show that brief observation of a neutral stimulus mimicking a hand does not significantly modulate motor cortical excitability (Study 1) although, after prolonged exposure, it can lead to a relatively nonspecific modulation (Study 2). However, when such a neutral stimulus is preceded by exposure to a hand stimulus, the latter appears to serve as a prime, perhaps enabling meaning to the neutral stimulus, which then modulates motor cortical excitability in accordance with mirror neuron-driving properties (Studies 2 and 3). Overall results suggest that a symbolic value ascribed to an otherwise neutral stimulus can modulate motor cortical outputs, revealing the influence of top-down inputs on the mirror neuron system. These findings indicate a novel aspect of the human mirror neuron system: an otherwise neutral stimulus can acquire specific mirror neuron-driving properties in the absence of a direct association between motor practice and perception. This significant malleability in the way that the mirror neuron system can code otherwise meaningless (i.e. arbitrarily associated) stimuli may contribute to coding communicative signals such as language. This may represent a mirror neuron system feature that is unique to humans.