Pietro Li Voti

A questionnaire study on knowledge of and attitudes toward epilepsy in schoolchildren and university students in Rome, Italy

PURPOSE To estimate the knowledge of and attitudes toward epilepsy in schoolchildren and university students in Rome. METHODS We administered a custom-designed questionnaire in Italian on general knowledge, specific knowledge and social impact of epilepsy to a random sample of upper-middle class pupils and university undergraduate students in Rome. RESULTS The young people we studied have a reasonable knowledge of epilepsy: as many as 91% claimed to know something about the disease. Yet only 16% correctly stated the prevalence as being about 1 in 100. Middle-school pupils and university graduates consider epilepsy as an illness from which patients rarely recover and one that creates problems in finding employment. The largest number of correct answers for nearly all the questionnaire items came from university students. CONCLUSIONS These findings suggest that apart from an encouragingly large number of the subjects we studied claim to know something about epilepsy (91% today versus 73% 22 years ago), Italian students still know little about epilepsy. These preliminary data should provide a starting point for a future in-depth population-based survey and information campaigns at schools in the Rome metropolitan area.

Short-term and long-term plasticity interaction in human primary motor cortex

Repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) elicits changes in motor evoked potential (MEP) size thought to reflect short‐ and long‐term forms of synaptic plasticity, resembling short‐term potentiation (STP) and long‐term potentiation/depression (LTP/LTD) observed in animal experiments. We designed this study in healthy humans to investigate whether STP as elicited by 5‐Hz rTMS interferes with LTP/LTD‐like plasticity induced by intermittent and continuous theta‐burst stimulation (iTBS and cTBS). The effects induced by 5‐Hz rTMS and iTBS/cTBS were indexed as changes in MEP size. We separately evaluated changes induced by 5‐Hz rTMS, iTBS and cTBS applied alone and those induced by iTBS and cTBS delivered after priming 5‐Hz rTMS. Interactions between 5‐Hz rTMS and iTBS/cTBS were investigated under several experimental conditions by delivering 5‐Hz rTMS at suprathreshold and subthreshold intensity, allowing 1 and 5 min intervals to elapse between 5‐Hz rTMS and TBS, and delivering one and ten 5‐Hz rTMS trains. We also investigated whether 5‐Hz rTMS induces changes in intracortical excitability tested with paired‐pulse transcranial magnetic stimulation. When given alone, 5‐Hz rTMS induced short‐lasting and iTBS/cTBS induced long‐lasting changes in MEP amplitudes. When M1 was primed with 10 suprathreshold 5‐Hz rTMS trains at 1 min before iTBS or cTBS, the iTBS/cTBS‐induced after‐effects disappeared. The 5‐Hz rTMS left intracortical excitability unchanged. We suggest that STP elicited by suprathreshold 5‐Hz rTMS abolishes iTBS/cTBS‐induced LTP/LTD‐like plasticity through non‐homeostatic metaplasticity mechanisms. Our study provides new information on interactions between short‐term and long‐term rTMS‐induced plasticity in human M1.

Primary somatosensory cortical plasticity and tactile temporal discrimination in focal hand dystonia

OBJECTIVE To investigate whether theta burst stimulation (TBS) applied over primary somatosensory cortex (S1) modulates somatosensory temporal discrimination threshold (STDT) and writing performances in patients with focal hand dystonia (FHD). METHODS Twelve patients with FHD underwent STDT testing and writing tasks before and after intermittent, continuous, or sham TBS (iTBS, cTBS, sham TBS) over S1 contralateral to the affected hand. Twelve healthy subjects underwent iTBS and cTBS over S1 and STDT values were tested on the right hand before and after TBS. RESULTS Baseline STDT values were higher in patients than in healthy subjects on both the affected and unaffected hand. In patients and healthy subjects iTBS decreased, whereas cTBS increased STDT values and did so to a similar extent in both groups. In patients, although STDT values decreased after iTBS, they did not normalize. S1 modulation did not improve the writing performance. CONCLUSIONS In patients, S1 responds normally to protocols inducing homotopic synaptic plasticity. The inhibitory interneuron activity responsible for STDT is altered. SIGNIFICANCE The pathophysiological mechanisms underlying abnormal temporal discrimination differ from those responsible for motor symptoms in FHD.

Cerebellar continuous theta-burst stimulation affects motor learning of voluntary arm movements in humans

In this study we investigated in healthy subjects whether continuous theta‐burst stimulation (cTBS) over the lateral cerebellum alters motor practice and retention phases during ipsilateral index finger and arm reaching movements. In 12 healthy subjects we delivered cTBS before repeated index finger abductions or arm reaching movements differing in complexity (reaching‐to‐grasp and reaching‐to‐point). We evaluated kinematic variables for index finger and arm reaching movements and changes in primary motor cortex (M1) activity tested with transcranial magnetic stimulation. Peak acceleration increased during motor practice for index finger abductions and reaching‐to‐grasp movements and persisted during motor retention. Peak acceleration decreased during motor practice for reaching‐to‐point movements and the decrease remained during motor retention. Cerebellar cTBS left the changes in peak acceleration during motor practice for index finger abductions and reaching‐to‐grasp arm movements unchanged but reduced peak acceleration at motor retention. Cerebellar cTBS prevented the decrease in peak acceleration for reaching‐to‐point movements during motor practice and at motor retention. Index finger abductions and arm reaching movements increased M1 excitability. Cerebellar cTBS decreased the motor evoked potential (MEP) facilitation induced by index finger movements, but increased the MEP facilitation after reaching‐to‐grasp and reaching‐to‐point movements. Cerebellar stimulation prevents motor retention for index finger abductions, reaching‐to‐grasp and reaching‐to‐point movements and degrades motor practice only for reaching‐to‐point movements. Cerebellar cTBS alters practice‐related changes in M1 excitability depending on how intensely the cerebellum contributes to the task. Changes in M1 excitability reflect mechanisms of homeostatic plasticity elicited by the interaction of an ‘exogenous’ (cTBS‐induced) and an ‘endogenous’ (motor practice‐induced) plasticity‐inducing protocol.

Saliva and serum levetiracetam concentrations in patients with epilepsy

Abstract: Although antiepileptic drug (AED) monitoring in saliva may have some clinical applicability, it has not yet come into routine use. The correlation between levetiracetam (LEV) saliva and serum concentrations also remains unclear. To confirm LEV saliva assay as a useful, noninvasive alternative to serum measurement, we investigated the possible correlation between saliva and serum LEV concentrations. Samples of saliva and blood were collected from 30 patients with epilepsy receiving chronic therapy with LEV as monotherapy or add-on therapy, and LEV concentrations were assayed in saliva and serum. Linear regression analyses showed a close correlation between saliva and serum LEV concentrations (r2 = 0.90; P < 0.001). LEV blood and saliva concentrations were linearly related to daily drug doses (r2 = 0.78 and 0.70; P < 0.01). When data were analyzed for subgroups (patients receiving LEV in monotherapy, as add-on therapy with enzyme-inducer AEDs, and as add-on therapy with noninducer or moderate-inducer AEDs), no significant difference was found between saliva and serum LEV concentrations among groups. These preliminary results indicate that LEV, like other AEDs, can be measured in saliva as an alternative to blood-based assays. Saliva LEV collection and assay is a valid noninvasive, more convenient alternative to serum measurement.

Transcranial direct current stimulation modulates motor responses evoked by repetitive transcranial magnetic stimulation.

INTRODUCTION Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive techniques able to induce changes in corticospinal excitability. In this study, we combined rTMS and tDCS to understand possible interactions between the two techniques, and investigate whether they are polarity dependent. MATERIALS AND METHODS Eleven healthy subjects participated in the study. Each patient underwent both anodal and cathodal conditioning tDCS in two separate sessions; brief 5 Hz-rTMS trains were delivered over the primary motor cortex at an intensity of 120% the resting motor threshold (RMT) before tDCS (T0), immediately after (T1) and 10 min after current offset (T2). We then analysed changes induced by cathodal and anodal tDCS on TMS variables. RESULTS Our results showed that in both anodal and cathodal sessions, the motor evoked potential (MEP) amplitude increased significantly in size before stimulation (T0). Conversely, after anodal tDCS, the MEP facilitation measured at T1 and T2 was absent, whereas after cathodal tDCS it was preserved. CONCLUSIONS Our findings provide new direct neurophysiological evidence that tDCS influences primary motor cortex excitability.

Effects of levetiracetam on generalized discharges monitored with ambulatory EEG in epileptic patients

PURPOSE Quantitative analysis of epileptiform discharges (EDs) before and after the initiation of an antiepileptic treatment is a useful tool to objectively documentate the efficacy of an antiepileptic drug (AED). Aim of this study was to evaluate the effect of levetiracetam (LEV) on EDs, monitored with ambulatory EEG (A/EEG), in a limited series of patients with generalized epilepsy. METHODS We performed 24h A/EEG recording in basal condition and at follow-up after LEV therapy in 21 adult epileptic patients. Eleven received LEV as monotherapy and 10 as add-on. For each patient we quantified total epileptic activity considering the following parameters: total number, total duration, maximal duration and median duration of EDs. Self-reported information on the effect of LEV on clinical seizures was also collected, to determine the electro-clinical correlation. RESULTS A high variability of the response to LEV was observed in the monotherapy group, without statistical differences for all the parameters investigated. A significant reduction of the total number of seizures (113.6 vs. 41.2; p=.01) was observed in patients in add-on therapy. The modifications of epileptiform EEG abnormalities did not necessarily correlate with the self-reported clinical impressions. DISCUSSION The quantification of EDs monitored by A/EEG provides a useful objective support for evaluating the neurophysiologic profile and the real efficacy of an antiepileptic treatment. In our patients LEV was able to significantly reduce the EDs only in add-on therapy. Further larger studies are necessary to clarify the effects of LEV on electro-clinical features of generalized epilepsy.

Attention-related changes in short-term cortical plasticity help to explain fatigue in multiple sclerosis.

Background: In multiple sclerosis (MS), pathophysiology of fatigue is only partially known. Objective: The aim of this study was to investigate whether the attention-induced modulation on short- and long-term cortical plasticity mechanisms in primary motor area (M1) is abnormal in patients with MS-related fatigue. Methods: All participants underwent 5-Hz repetitive transcranial magnetic stimulation (rTMS), reflecting short-term plasticity, and paired associative stimulation (PAS), reflecting long-term plasticity, and were asked to focus their attention on the hand contralateral to the M1 stimulated. A group of age-matched healthy subjects acted as control. Results: In patients with MS, 5-Hz rTMS and PAS failed to induce the normal increase in motor-evoked potential (MEP). During the attention-demanding condition, 5-Hz rTMS- and PAS-induced responses differed in patients with MS with and without fatigue. Whereas in patients with fatigue neither technique induced the attention-induced MEP increase, in patients without fatigue they both increased the MEP response, although they did so less efficiently than in healthy subjects. Attention-induced changes in short-term cortical plasticity inversely correlated with fatigue severity. Conclusion: Short-term and long-term plasticity mechanisms are abnormal in MS possibly owing to widespread changes in ion-channel expression. Fatigue in MS reflects disrupted cortical attentional networks related to movement control.

Voluntary Movement Takes Shape: The Link Between Movement Focusing and Sensory Input Gating

The aim of the study was to investigate the relationship between motor surround inhibition (mSI) and the modulation of somatosensory temporal discrimination threshold (STDT) induced by voluntary movement. Seventeen healthy volunteers participated in the study. To assess mSI, we delivered transcranial magnetic stimulation (TMS) single pulses to record motor evoked potentials (MEPs) from the right abductor digiti minimi (ADM; “surround muscle”) during brief right little finger flexion. mSI was expressed as the ratio of ADM MEP amplitude during movement to MEP amplitude at rest. We preliminarily measured STDT values by assessing the shortest interval at which subjects were able to recognize a pair of electric stimuli, delivered over the volar surface of the right little finger, as separate in time. We then evaluated the STDT by using the same motor task used for mSI. mSI and STDT modulation were evaluated at the same time points during movement. mSI and STDT modulation displayed similar time-dependent changes during index finger movement. In both cases, the modulation was maximally present at the onset of the movement and gradually vanished over about 200 ms. Our study provides the first neurophysiological evidence about the relationship between mSI and tactile-motor integration during movement execution.

Somatosensory temporal discrimination in Parkinson’s disease, dystonia and essential tremor: Pathophysiological and clinical implications

OBJECTIVE To investigate whether changes in the somatosensory temporal discrimination threshold (STDT) in Parkinsons disease (PD) and dystonia reflect the involvement of specific neural structures or mechanisms related to tremor, and whether the STDT can discriminate patients with PD, dystonia or essential tremor (ET). METHODS We tested STDT in 223 patients with PD, dystonia and ET and compared STDT values in patients with PD and dystonia with tremor with those of PD and CD without tremor. Data were compared with those of age-matched healthy subjects. RESULTS STDT values were high in patients with dystonia and PD but normal in ET. In PD, STDT values were similar in patients with resting or postural/action tremor and in those without tremor. In dystonia, STDT values were higher in patients with tremor than in those without tremor. The ROC curve showed that STDT discriminates tremor in dystonia from ET. CONCLUSIONS In PD, STDT changes likely reflect basal ganglia abnormalities and are unrelated to tremor mechanisms. In dystonia, the primary somatosensory cortex and cerebellum play an additional role. SIGNIFICANCE STDT provides information on the pathophysiological mechanisms of patients with movement disorders and may be used to differentiate patients with dystonia and tremor from those with tremor due to ET.