An educational campaign about epilepsy among Italian primary school teachers. 2. The results of a focused training program.

A cohort of 582 Italian primary school teachers underwent a questionnaire survey to test their knowledge and attitudes toward epilepsy and verify whether an intensive and focused educational program could result in improvement of knowledge and attitudes. The program consisted of a presentation of the clinical manifestations of epilepsy and the distribution of informative brochures and an educational kit on the disease and its management to be used with their students. After several months, 317 teachers were retested using the same questions. Upon retest, the number of "don't know" answers decreased significantly for almost all questions. This was not the case for negative attitudes. The same holds true for teachers believing that epilepsy is a source of learning disability and social disadvantage. These findings support the beliefs that education on epilepsy is more likely to affect ignorance than prejudice and that stronger interventions are needed to counteract stigmatizing behaviors.

Cortical connections between dorsal and ventral visual streams in humans: Evidence by TMS/EEG co-registration.

Parietal cortex subserves various cognitive tasks, ranging from attention to visuo-motor skills. It is part of a parieto-frontal network involved in attention, and part of the visual dorsal stream, opposed to the visual ventral stream, although increasing evidence suggests interchange of information between them. In this study, co-registration of Transcranial Magnetic Stimulation (TMS) and Electroencephalographic activity (EEG) has been used to investigate the spreading of cortical connections from the parietal cortex in healthy volunteers. TMS on the left parietal cortex activated a network of prefrontal regions in the contra-lateral hemisphere in a time range of 102-167 ms after the stimulus. Moreover, activation in the ipsi-lateral middle temporal and fusiform gyri was observed at 171-177 ms after delivery of TMS. Findings suggest the existence of late driven connections between parietal and prefrontal regions that could partially represent the neural pathway related to attention, even if, in this experiment, no attentional processing was requested. Late connections between dorsal and ventral streams were also evident, confirming previous evidence about interchange of information between them. Conclusively, the present investigation confirms that a great amount of information spreads from parietal cortex to different regions in the brain, supporting the idea that connections are more complex and articulated than those proposed. Present findings also suggest that the simultaneous recording of EEG during the application of TMS is a promising tool for the study of connections in the brain.

Dramatic placebo effect of high frequency repetitive TMS in treatment of chronic migraine and medication overuse headache.

Chronic migraine (CM) is often associated with medication overuse headache (MOH). Few small trials have been conducted on Transcranial Magnetic Stimulation for CM treatment, but results are conflicting. Aim of the study was to investigate the effects of high frequency of repetitive Transcranial Magnetic Stimulation (hf-rTMS) in the dorsolateral prefrontal cortex combined with strongly suggesting to avoid medications overuse in patients suffering with CM and MOH. A six-month single-centre perspective randomized double-blinded study was conducted at the Headache Centre of Trieste. Patients suffering with CM and MOH were randomly enrolled in two groups to receive active hf-rTMS in DLPFC or sham hf-rTMS. Headache days (HD), headache hours (HH) and symptomatic drug intake (SDI) were recorded for 30 days before the beginning of stimulation (T0) and during the three following months (T3). Disability (MIDAS score) was evaluated at T0 and at the three-month follow-up visit. The primary outcome was the evaluation of reduction of HD. Reduction of SDI, HH and disability were considered as secondary outcomes. Out of 26 patients enrolled, 14 completed the study, 7 underwent hf-rTMS and 7 sham-TMS. There were no significant differences between groups at T0 in demographic data and headache measures. Mean number of HD, HH, SDI, and MIDAS similarly reduced in the two groups. Our study failed in demonstrating that hf-rTMS with detoxification advice could be better than detoxification advice alone in CM treatment. hf-rTMS carries a high potential of inducing placebo effect and this can be usefully leveraged to enhance patients' coping strategies.

Memorization Test and Resting State EEG Components in Mild and Subjective Cognitive Impairment.

BACKGROUND: Mild (MCI) and Subjective Cognitive Impairment (SCI) are conditions at risk of developing Alzheimer's disease (AD). Differential between normal aging at early stages can be really challenging; available biomarkers need to be combined and can be quite invasive and expensive. OBJECTIVE: The aim of this pilot study is to examine possible EEG alterations in MCI and SCI compared to controls, analyzing if a cognitive task could highlight early AD hallmarks. METHOD: We recruited 11 MCI, 8 SCI and 7 healthy subjects as controls (CS), all matched for age and education. Neuropsychological assessment and EEG recording, at resting state and during a mental memory task, were performed. Classical spectral measures and nonlinear parameters were used to characterize EEGs. RESULTS: During cognitive task, α-band power reduction was found predominantly in frontal regions in SCI and CS, diffused to all regions in MCI; moreover, decreased EEG complexity was found in SCI compared to controls. The α -band power attenuation restricted to frontal regions in SCI during a free recall task (involving frontal areas), suggests that MCI patients compensate for encoding deficit by activating different brain networks to perform the same task. Furthermore, EEG complexity reduction - that has been found already in SCI - could be a possible early hallmark of AD. CONCLUSION: This study draws attention on the importance of nonlinear approach in EEG analysis and the potential role of cognitive task in highlighting EEG alterations at very early stages of cognitive impairment; EEG could therefore have a practical impact on dementia diagnosis.

Role of comorbidities and in-hospital complications in short-term status epilepticus outcome.

OBJECTIVE: pre-morbid patient conditions and hospitalization complications possibly play a role in status epilepticus short-term outcome, although evidence is incomplete and non-conclusive. The study's aim was to define whether comorbidities and in-hospital complications arising after status epilepticus affect its prognosis. METHODS: A retrospective single center study was carried out. All selected patients were adults presenting an EEG-proven status epilepticus episode between 2003 and 2014. Medical charts were comprehensively reviewed. In-hospital mortality and length of hospital stay represented study outcomes. RESULTS: One hundred seventy-three subjects met the inclusion criteria. Seventy-one cases (41%) developed infections and 59 (34%) non-infectious complications. Median hospital stay was 16days and overall in-hospital mortality was 44%. Multivariate analysis revealed the association between in-hospital mortality and the following comorbidities: history of diabetes mellitus (Odds ratio=7.89, p=0.002) and evidence of extracranial malignancy (Odds ratio=10.28, p=0.009). Complications were not associated to death after multivariate statistics, which instead displayed systemic inflammatory response syndrome significance (Odds ratio=12.90, p<0.001). Infections and non-infectious complications were associated with longer hospital stay (p=0.025 and p=0.01 respectively). CONCLUSIONS: status epilepticus management is a multifaceted problem. RESULTS: suggest that some pre-morbid patient conditions and in-hospital adverse events play an unfavorable prognostic role. This preliminary information may help clinicians optimize preventive and therapeutic strategies to guarantee patients the best chances of survival.

Patterns of care of brain tumor-related epilepsy. A cohort study done in Italian Epilepsy Center.

Epilepsy is the most common comorbidity in patients with brain tumors. STUDY AIMS: To define characteristics of brain tumor-related epilepsy (BTRE) patients and identify patterns of care. Nationwide, multicenter retrospective cohort study. Medical records of BTRE patients seen from 1/1/2010 to 12/31/2011, followed for at least one month were examined. Information included age, sex, tumor type/treatments, epilepsy characteristics, antiepileptic drugs (AEDs). Time to modify first AED due to inefficacy and/or toxicity was assessed with the Kaplan-Meier method and Cox proportional hazard models were used to identify predictors of treatment outcome. Enrolled were 808 patients (447 men, 361 women) from 26 epilepsy centers. Follow-up ranged 1 to 423 months (median 18 months). 732 patients underwent surgery, 483 chemotherapy (CT), 508 radiotherapy. All patients were treated with AEDs. Levetiracetam was the most common drug. 377 patients (46.7%) were still on first drug at end of follow-up, 338 (41.8%) needed treatment modifications (uncontrolled seizures, 229; side effects, 101; poor compliance, 22). Treatment discontinuation for lack of efficacy was associated with younger age, chemotherapy, and center with <20 cases. Treatment discontinuation for side effects was associated with female sex, enzyme-inducing drugs and center with > 20 cases. About one-half of patients with BTRE were on first AED at end of follow-up. Levetiracetam was the most common drug. A non enzyme-inducing AED was followed by a lower risk of drug discontinuation for SE.

Altered Modulation of Silent Period in Tongue Motor Cortex of Persistent Developmental Stuttering in Relation to Stuttering Severity.

Motor balance in developmental stuttering (DS) was investigated with Transcranial Magnetic Stimulation (TMS), with the aim to define novel neural markers of persistent DS in adulthood. Eleven DS adult males were evaluated with TMS on tongue primary motor cortex, compared to 15 matched fluent speakers, in a "state" condition (i.e. stutterers vs. fluent speakers, no overt stuttering). Motor and silent period thresholds (SPT), recruitment curves, and silent period durations were acquired by recording tongue motor evoked potentials. Tongue silent period duration was increased in DS, especially in the left hemisphere (P<0.05; Hedge's g or Cohen's dunbiased = 1.054, i.e. large effect size), suggesting a "state" condition of higher intracortical inhibition in left motor cortex networks. Differences in motor thresholds (different excitatory/inhibitory ratios in DS) were evident, as well as significant differences in SPT. In fluent speakers, the left hemisphere may be marginally more excitable than the right one in motor thresholds at lower muscular activation, while active motor thresholds and SPT were higher in the left hemisphere of DS with respect to the right one, resulting also in a positive correlation with stuttering severity. Pre-TMS electromyography data gave overlapping evidence. Findings suggest the existence of a complex intracortical balance in DS tongue primary motor cortex, with a particular interplay between excitatory and inhibitory mechanisms, also in neural substrates related to silent periods. Findings are discussed with respect to functional and structural impairments in stuttering, and are also proposed as novel neural markers of a stuttering "state" in persistent DS, helping to define more focused treatments (e.g. neuro-modulation).

Sexual dysfunction in multiple sclerosis: a MRI, neurophysiological and urodynamic study.

We studied 31 patients with relapsing-remitting (RR) multiple sclerosis (MS) in which we performed an urodynamic study, the pudendal cortical evoked potentials, the tibial cortical evoked potentials and the cranial and cervical spinal cord magnetic resonance imaging (MRI). We calculated the T(1) and T(2) lesion load (LL) and brain parenchymal fraction (BPF) of whole brain, frontal lobes, pons and cervical spinal cord. We also estimated the cross-sectional area at C(2) level. Spearman's rank correlation analysis showed a relationship between symptoms of sexual dysfunction and age (r=0.73, p<0.0001), cognitive performances (r=-0.63, p<0.0001), level of independence (r=-0.63, p<0.0001), disability (r=0.56, p<0.001), symptoms of anxiety (r=0.55, p<0.001) and depression (r=0.50, p<0.005), disease duration (r=0.42, p<0.02) and parenchymal atrophy in the pons (r=-0.38, p=0.031). Sexual dysfunction was not correlated with any other MRI measure, urodynamic patterns or cortical evoked potentials. In multiple regression analysis, sexual dysfunction was predicted only by T(1) lesion load of the pons. In conclusion, we confirmed previous correlations of sexual dysfunction with various clinical variables and demonstrated an association between sexual dysfunction and destructive lesions in the pons, as detected by MRI, in patients with relapsing-remitting multiple sclerosis.

Motor excitability evaluation in developmental stuttering: a transcranial magnetic stimulation study.

INTRODUCTION: Developmental stuttering (DS) is viewed as a motor speech-specific disorder, although several lines of research suggest that DS is a symptom of a broader motor disorder. We investigated corticospinal excitability in adult DS and normal speakers. METHODS: Transcranial magnetic stimulation (TMS) was administered over left/right hand representation of the motor cortex while recording motor evoked potentials (MEPs) from the contralateral first dorsal interosseous (FDI) muscle. Resting, active motor thresholds, silent period threshold and duration were measured. A stimulus-response curve at resting was also obtained to evaluate MEP amplitudes. RESULTS: Lower corticospinal responses in the left hemisphere of DS were found, as indicated by a reduction of peak-to-peak MEP amplitudes compared to normal speakers. CONCLUSIONS: This provides further evidence that DS may be a general motor deficit that also involves motor non-speech-related structures. Moreover, our results confirm that DS may be related to left hemisphere hypoactivation and/or lower left hemisphere dominance. The present data and protocol may be useful for diagnosis of subtypes of DS that may benefit from pharmacological treatment by targeting the general level of cortical excitability.

Transcranial magnetic stimulation and preparation of visually-guided reaching movements.

To better define the neural networks related to preparation of reaching, we applied transcranial magnetic stimulation (TMS) to the lateral parietal and frontal cortex. TMS did not evoke effects closely related to preparation of reaching, suggesting that neural networks already identified by our group are not larger than previously thought. We also replicated previous TMS/EEG data by applying TMS to the parietal cortex: new analyses were performed to better support reliability of already reported findings (Zanon et al., 2010; Brain Topography 22, 307-317). We showed the existence of neural circuits ranging from posterior to frontal regions of the brain after the stimulation of parietal cortex, supporting the idea of strong connections among these areas and suggesting their possible temporal dynamic. Connection with ventral stream was confirmed. The present work helps to define those areas which are involved in preparation of natural reaching in humans. They correspond to parieto-occipital, parietal and premotor medial regions of the left hemisphere, i.e., the contralateral one with respect to the moving hand, as suggested by previous studies. Behavioral data support the existence of a discrete stream involved in reaching. Besides the serial flow of activation from posterior to anterior direction, a parallel elaboration of information among parietal and premotor areas seems also to exist. Present cortico-cortical interactions (TMS/EEG experiment) show propagation of activity to frontal, temporal, parietal and more posterior regions, exhibiting distributed communication among various areas in the brain. The neural system highlighted by TMS/EEG experiments is wider with respect to the one disclosed by the TMS behavioral approach. Further studies are needed to unravel this paucity of overlap. Moreover, the understanding of these mechanisms is crucial for the comprehension of response inhibition and changes in prepared actions, which are common behaviors in everyday life.

Linear and non-linear effects of gradient artifact filtering methods in simultaneous EEG-FMRI - biomed 2010.

Simultaneous EEG-fMRI is a powerful emerging tool in functional neuroimaging that exploits the relationship between neuronal electrophysiological activity and its hemodynamic response. It has found application in the study of both spontaneous and evoked brain activity. Combining the complementary advantages of the two techniques it provides a measurement with high temporal and spatial resolution, allowing a reliable localization of event generators. However, EEG data recorded inside MRI scanner are heavily corrupted by different types of artifacts due to the interactions between the patient, EEG electrodes wires and the magnetic fields inside the scanner. In particular, gradient switching and RF pulses, necessary to acquire fMRI data, generate large artifacts that can completely obscure EEG signals. Many methods have been proposed to eliminate or at least reduce gradient artifact. In this paper both a qualitative and a quantitative evaluation of two different algorithms used for gradient artifact removal are presented. Linear and non-linear characteristics of EEG, such as power spectra, fractal dimension and beta scaling exponent, are evaluated for EEGs recorded outside and inside the scanner, in MR static and dynamic conditions. The study highlights how residual artifacts after correction and artifacts induced by correction itself could still considerably affect EEG signals. The results suggest that the quality of both these gradient artifact filtering methods is not yet sufficient to preserve EEG characteristics and thus it must be further improved. The aim of this study is to make neurophysiologists aware of the filtering effects that can compromise linear and non-linear analysis of EEG recorded during functional MRI.

Linear and non-linear parameterization of EEG during monitoring of carotid endarterectomy.

In this paper, new quantitative linear (HLF ratio: high frequency/low frequency spectral power ratio) and non-linear parameters (ZC: zero crossing and FD: fractal dimension) which can assist the physician in real-time decision whether a shunt is required or not during intra-operative EEG monitoring of carotid endarterectomy are presented. The results obtained with the new parameters are compared with those achieved by other indexes proposed in the literature. The HLF ratio and ZC parameters yielded the best results with a 100% of correct identification of both shunt and no-shunt situations. The ZC can be also easily implemented in the real-time monitoring of EEG.

Parieto-occipital cortex and planning of reaching movements: a transcranial magnetic stimulation study.

A large amount of evidence supports a role for the parietal and frontal cortex in the planning of reaching movements. Nevertheless, neither the timing of involvement of these areas nor if and how their activity can be influenced by external stimuli has been clarified. The parieto-occipital cortex has been investigated by applying transcranial magnetic stimulation (TMS) at 25% (Time 1), 50% (Time 2) and 75% (Time 3) of the reaction time from a go signal to hand movement. No local effect was found with Time 1, since pulses were administered before subjects opened their eyes. Reduction of reaction time was observed at Time 2 when stimuli were applied over the anterior occipital lobe, parieto-occipital cortex and posterior parietal cortex. The effect on the posterior parietal cortex reverted when Time 3 was used. The present data confirm the existence, in humans, of a dorso-medial set of areas involved in on-line planning of reaching movements. Moreover, they provide novel evidence on the time course of this involvement. Finally, present data show that it is possible to interact with the flow of activity along this stream by appropriately delivering TMS pulses.

Effect of transcranial magnetic stimulation (TMS) on parietal and premotor cortex during planning of reaching movements.

BACKGROUND: Cerebral activation during planning of reaching movements occurs both in the superior parietal lobule (SPL) and premotor cortex (PM), and their activation seems to take place in parallel. METHODOLOGY: The activation of the SPL and PM has been investigated using transcranial magnetic stimulation (TMS) during planning of reaching movements under visual guidance. PRINCIPAL FINDINGS: A facilitory effect was found when TMS was delivered on the parietal cortex at about half of the time from sight of the target to hand movement, independently of target location in space. Furthermore, at the same stimulation time, a similar facilitory effect was found in PM, which is probably related to movement preparation. CONCLUSIONS: This data contributes to the understanding of cortical dynamics in the parieto-frontal network, and suggests that it is possible to interfere with the planning of reaching movements at different cortical points within a particular time window. Since similar effects may be produced at similar times on both the SPL and PM, parallel processing of visuomotor information is likely to take place in these regions.

Involvement of ipsilateral parieto-occipital cortex in the planning of reaching movements: evidence by TMS.

Involvement of the ipsilateral hemisphere during planning of reaching movements is still matter of debate. While it has been demonstrated that the contralateral hemisphere is dominant in visuo-motor integration, involvement of the ipsilateral hemisphere has also been proposed. Furthermore, a dominant role for left posterior parietal cortex has been shown in this process, independently of the hand and visual field involved. In this study, the possible involvement of ipsilateral parieto-occipital cortex in planning of reaching movements was investigated by transcranial magnetic stimulation (TMS). TMS was applied on four points of the parietal and occipital cortex at 50% (Time 1), 75% (Time 2) and 90% (Time 3) of reaction time from a go-signal to hand movement. The only effect observed was an increase in reaction time when a region around the parieto-occipital junction was stimulated at Time 2. These results provide further support to the hypothesis that, in the posterior parietal cortex, planning of reaching movements also relies on the ipsilateral hemisphere, in addition to the contralateral or dominant one.

Investigating the efficacy of paroxetine in developmental stuttering.

OBJECTIVES: Paroxetine has been reported to be useful for management of stuttering symptoms, but only a few reports have examined its effects. We have investigated the efficacy of paroxetine in a randomized, placebo-controlled study. METHODS: Five stuttering subjects received paroxetine at 20 mg once daily at night for 12 weeks, and 5 received placebo. The percentages of stuttered words and stuttering-associated movements during speech were measured at baseline and after 6 and 12 weeks of treatment. Moreover, left primary motor cortex excitability was measured using transcranial magnetic stimulation. Specifically, resting and active motor thresholds and the cortical silent period (CSP) were obtained at the same periods in both groups. RESULTS: Paroxetine did not affect the percentage of stuttered words between groups. Stuttering-associated movements, however, during speech in facial muscular districts were significantly reduced in subjects treated with paroxetine. Finally, paroxetine administration shortened the CSP with no effect on motor thresholds. CONCLUSION: Paroxetine may be useful in qualitative management of stuttering symptoms and may act on the stuttering brain by diminution of intracortical inhibition, as revealed by the shortening of the CSP after paroxetine administration.