Language-related motor facilitation in Italian Sign Language signers.

Linguistic tasks facilitate corticospinal excitability as revealed by increased motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in the dominant hand. This modulation of the primary motor cortex (M1) excitability may reflect the relationship between speech and gestures. It is conceivable that in healthy individuals who use a sign language this cortical excitability modulation could be rearranged. The aim of this study was to evaluate the effect of spoken language tasks on M1 excitability in a group of hearing signers. Ten hearing Italian Sign Language (LIS) signers and 16 non-signer healthy controls participated. Single-pulse TMS was applied to either M1 hand area at the baseline and during different tasks: (i) reading aloud, (ii) silent reading, (iii) oral movements, (iv) syllabic phonation and (v) looking at meaningless non-letter strings. Overall, M1 excitability during the linguistic and non-linguistic tasks was higher in LIS group compared to the control group. In LIS group, MEPs were significantly larger during reading aloud, silent reading and non-verbal oral movements, regardless the hemisphere. These results suggest that in hearing signers there is a different modulation of the functional connectivity between the speech-related brain network and the motor system.

Impulsivity traits and awareness of motor intention in Parkinson's disease: a proof-of-concept study.

INTRODUCTION: In patients with Parkinson's disease (PD), impulsivity is still a matter of investigation. It has been hypothesized that impulsive personality traits may favour impulse control disorder (ICD) onset during dopaminergic therapy. In healthy subjects, a relationship between the awareness of motor intention and impulsive personality traits assessed by the Barratt impulsivity scale (BIS-11) has been reported. The aim of this study was to evaluate the relationship between the awareness of voluntary action and impulsivity traits in PD. METHODS: Twenty-eight PD patients (stages I-III on the Hoehn and Yahr scale) underwent an impulsivity trait assessment by the BIS-11 scale and a task based on the Libet's clock. Participants were requested to perform a self-initiated movement and report the time they first feel their intention to move (W-judgement) or the time of the actual movement (M-judgement). RESULTS: In patients with higher BIS-11 scores, the time lag between the W-judgement and the actual movement was significantly lower than in patients with lower BIS-11. No difference emerged in the M-judgement. CONCLUSION: Data suggest that also in PD patients, the impulsive personality trait is related to a "delayed" awareness of motor intention and therefore to a shorter interval to allow a conscious "veto" of the impending action. Characterization of the temporal profile of awareness of motor intention could prove useful in identifying PD patients at risk of developing ICDs during dopaminergic treatment.

Timing to Carotid Endarterectomy Affects Early and Long Term Outcomes of Symptomatic Carotid Stenosis.

BACKGROUND: The aim of this study is to evaluate early and long-term outcomes according to the timing to carotid endarterectomy (CEA) of symptomatic carotid stenosis. METHODS: Consecutive CEAs with selective shunting for symptomatic carotid stenosis ≥50% performed between 2009 and 2020. Patients had acute neurological impairment on presentation, defined as <5 points on the National Institutes of Health Stroke Scale (NIHSS). We grouped patients according to time between index event and CEA: the first group was operated between 0 and 2 days, the second group between 3 and 7 days, the third group between 8 and 14 days and the last group after 15 days. Thirty-day neurological status improvement was defined as a decrease (≥1) in the 30-day NIHSS score versus NIHSS score immediately before surgery. RESULTS: Five hundred CEAs were performed. The perioperative combined stroke and mortality rate was 3.6% (18/500), representing a perioperative mortality rate of 0.2 (n = 1) and stroke rate of 3.4% (n = 17). Overall freedom from stroke was 95% at 1 year, 89 % at 6 years, and 88% at 10 years. Annual stroke rate was 0.6% after the 30-day period. Thirty-day improvement in neurologic status occurred in 103 patients (20.6%), while in 380 (76%) neurologic status was unchanged, and 17 (3.4%) experienced worsening of their neurologic status. Patients treated within 7 days from the index event had significant benefit (OR = 2.6) in the 30-day neurological improvement versus those treated after 7 days from the index event. Timing to CEA <2 days increased significantly the risk of late stroke (OR = 9.7). CONCLUSIONS: The ideal timing for performing CEA is between 3 and 7 days from the index event if NIHSS <5 as it is associated with the best rates of improvement in neurological status and durability in the long term. Very early CEA (<48 hrs) was associated with increased late stroke occurrence.

Reallocation of Carotid Surgery Activity with the Support of Telemedicine in a COVID-Free Clinic during COVID-19 Pandemic.

The aim of this study is to report the reallocation of carotid surgery activity with the support of telemedicine in a COVID-free clinic during COVID-19 pandemic. Patients with symptomatic carotid stenosis or asymptomatic vulnerable plaques were reallocated to a COVID-free private clinic which began to cooperate with the National Health System during the emergency. Quick training of staff nurses was performed. Surgeons moved to the COVID-19 free clinic. Remote cerebral monitoring was performed with the support of telemedicine. Twenty-four patients underwent standard carotid endarterectomy with eversion technique. Five patients (20.8%) had recently symptomatic stenosis, and the remaining 19 patients (79.2%) had a risky asymptomatic carotid stenosis. No technical issue with remote cerebral monitoring was detected. In the early postoperative period, no neurological/systemic complication was observed. Three patients under dual antiplatelet therapy (12.5%) had neck hematoma. All patients were discharged the day after surgery. In our preliminary experience, reallocation in a COVID-free clinic allowed us to maintain a functioning carotid surgery activity during COVID-19 pandemic. A multidisciplinary approach and support of telemedicine were crucial. Training of unskilled nurse staff was necessary.

Drug treatments in patients with cardiac diseases and epilepsy.

OBJECTIVE: Comorbidity between epilepsy and heart diseases is frequent. METHODS: All drugs classified within the group of drugs for cardiovascular system according to the Anatomical Therapeutic Chemical (ATC) classification system were reviewed for their effects on seizures or epilepsy. RESULTS: Several agents showed antiseizure properties in animal models of seizures and/or in patients with epilepsy and only few were proconvulsant. Drugs with anticonvulsant effects include mecamylamine and guanfacine (antihypertensive drugs), indapamide, amiloride, furosemide and bumetanide (diuretics), fasudil (peripheral vasodilator), bioflavonoids (vasoprotective drug), propranolol (beta blocking agent), isradipine, nimodipine, verapamil and diltiazem (calcium channel blockers: CCBs), fosinopril and zofenopril (agents acting on the renin-angiotensin system), several statins, and fenofibrate (lipid-modifying agents). Drugs with proconvulsant properties in experimental models or in patients include reserpine, buflomedil, naftidrofuryl, and clonidine and propranolol at high doses. Drug-drug interactions (DDI) between antiseizure medications (ASMs) and drugs for cardiovascular system were also searched in two leading publicly accessible drug compendia. The most important DDIs occur between enzyme-inducing (EI) ASMs and ivabradine, ranolazine, macitenan and between EI-ASMs and the CCBs felodipine, nicardipine, nisoldipine, and verapamil. Simvastatin and atorvastatin are the lipid-modifying agents with more DDIs with EI-ASMs. Several pharmacodynamic interactions have been also documented. DISCUSSION AND CONCLUSIONS: Available data show that the treatment of patients with epilepsy and vascular comorbidities is challenging and requires the appropriate knowledge of pharmacological properties of drugs and drug interactions.

RAD51 haploinsufficiency causes congenital mirror movements in humans.

Congenital mirror movements (CMM) are characterized by involuntary movements of one side of the body that mirror intentional movements on the opposite side. CMM reflect dysfunctions and structural abnormalities of the motor network and are mainly inherited in an autosomal-dominant fashion. Recently, heterozygous mutations in DCC, the gene encoding the receptor for netrin 1 and involved in the guidance of developing axons toward the midline, have been identified but CMM are genetically heterogeneous. By combining genome-wide linkage analysis and exome sequencing, we identified heterozygous mutations introducing premature termination codons in RAD51 in two families with CMM. RAD51 mRNA was significantly downregulated in individuals with CMM resulting from the degradation of the mutated mRNA by nonsense-mediated decay. RAD51 was specifically present in the developing mouse cortex and, more particularly, in a subpopulation of corticospinal axons at the pyramidal decussation. The identification of mutations in RAD51, known for its key role in the repair of DNA double-strand breaks through homologous recombination, in individuals with CMM reveals a totally unexpected role of RAD51 in neurodevelopment. These findings open a new field of investigation for researchers attempting to unravel the molecular pathways underlying bimanual motor control in humans.

Role of the dorsal premotor cortex in rhythmic auditory-motor entrainment: a perturbational approach by rTMS.

Synchronization of body movements to an external beat is a universal human ability, which has also been recently documented in nonhuman species. The neural substrates of this rhythmic motor entrainment are still under investigation. Correlational neuroimaging data suggest an involvement of the dorsal premotor cortex (dPMC) and the supplementary motor area (SMA). In 14 healthy volunteers, we more specifically investigated the neural network underlying this phenomenon using a causal approach by an established 1-Hz repetitive transcranial magnetic stimulation (rTMS) protocol, which produces a focal suppression of cortical excitability outlasting the stimulation period. Synchronization accuracy between rhythmic cues and right index finger tapping, as measured by the mean time lag (asynchrony) between motor and auditory events, was significantly affected when the right dPMC function was transiently perturbed by "off-line" focal rTMS, whereas the reproduction of the rhythmic sequence per se (inter-tap-interval) was spared. This approach affected metrical rhythms of different complexity, but not non-metrical or isochronous sequences. Conversely, no change in auditory-motor synchronization was observed with rTMS of the SMA, of the left dPMC or over a control site (midline occipital area). Our data strongly support the view that the right dPMC is crucial for rhythmic auditory-motor synchronization in humans.

Reliability of administrative data for the identification of Parkinson's disease cohorts.

Parkinson's disease (PD) is a major worldwide public health problem with a prevalence that is expected to increase dramatically in the coming decades. Because administrative data are useful for epidemiologic and health service studies, we aimed to define procedural algorithms to identify PD patients (on a regional basis) using these data. We built two a priori algorithms, respecting privacy laws, with increasing theoretical specificity for PD including: (1) a hospital discharge diagnosis of PD; (2) PD-specific exemption; (3) a minimum of two separate prescriptions of an antiparkinsonian drug. The two algorithms differed for drugs included. Sensitivities were tested on an opportunistic sample of 319 PD patients from the databases of 5 regional movement disorders clinics. The estimated prevalence of PD in the sample population from Tuscany was 0.49 % for algorithm 1 and 0.28 % for algorithm 2. Algorithm 1 correctly identified 291 PD patients (sensitivity 91.2 %), and algorithm 2 identified 242 PD patients (sensitivity 75.9 %). We developed two reproducible algorithms demonstrating increasing theoretical specificity with good sensitivity in identifying PD patients based on an evaluation of administrative data. This may represent a low-cost strategy to reliably follow up a large number of PD patients as a whole for evaluating the effects of therapies, disease progression and prevalence.

"Thirty-day neurologic improvement associated with early versus delayed carotid endarterectomy in symptomatic patients".

BACKGROUND: Neurologic outcome after early or delayed carotid endarterectomy (CEA) has yet to be fully elucidated. The aim of this study was to determine 30-day neurologic improvement with respect to the timing of CEA in symptomatic patients. METHODS: Single-institution review of consecutive patients who underwent CEA for symptomatic carotid stenosis ≥60% in the period between January 2009 and November 2013. Patients recruited had acute neurologic impairment on presentation, defined as <5 points on the National Institutes of Health Stroke Scale (NIHSS). Patients were grouped according to time between the qualifying event and surgery (0-14 days, early CEA and 15-30 days, delayed CEA). Thirty-day neurologic status improvement was defined as a decrease (≥1) in the 30-day NIHSS score versus NIHSS score immediately before surgery. RESULTS: There were 100 and 222 patients in the early and delayed CEA groups, respectively. The type of qualifying symptoms (stroke versus transient ischemic attack rate) was similar and there were no significant differences in 30-day adverse outcome rates between the 2 cohorts. There were no deaths, 4 strokes (1.2%, 3 vs. 1; P = 0.091), and 4 myocardial infarcts (1.2%, 0 vs. 4; P = 0.315). Thirty-day improvement in neurologic status was associated with early CEA, very early CEA (48 hours), and NIHSS >2 before surgery, with an odds ratio of 4.9 (confidence interval [CI], 0.9-25.7; P = 0.03), 12.9 (CI, 1.4-115.7; P = 0.02), and 2.6 (CI, 1.7-4.1; P < 0.001), respectively. CONCLUSIONS: Our results suggest that reducing the time to intervention in selected (NIHSS <5) symptomatic patients is safe and associated with improved neurologic status.

Neurophysiological Correlates of Central Fatigue in Healthy Subjects and Multiple Sclerosis Patients before and after Treatment with Amantadine.

In ten healthy subjects and in ten patients suffering from Multiple Sclerosis (MS), we investigated the cortical functional changes induced by a standard fatiguing repetitive tapping task. The Cortical Silent Period (CSP), an intracortical, mainly GABAB-mediated inhibitory phenomenon, was recorded by two different hand muscles, one acting as prime mover of the fatiguing index-thumb tapping task (First Dorsal Interosseous, FDI) and the other one not involved in the task but sharing largely overlapping central, spinal, and peripheral innervation (Abductor Digiti Minimi, ADM). At baseline, the CSP was shorter in patients than in controls. As fatigue developed, CSP changes involved both the "fatigued" FDI and the "unfatigued" ADM muscles, suggesting a cortical spread of central fatigue mechanisms. Chronic therapy with amantadine annulled differences in CSP duration between controls and patients, possibly through restoration of more physiological levels of intracortical inhibition in the motor cortex. These inhibitory changes correlated with the improvement of fatigue scales. The CSP may represent a suitable marker of neurophysiological mechanisms accounting for central fatigue generation either in controls or in MS patients, involving corticospinal neural pools supplying not only the fatigued muscle but also adjacent muscles sharing an overlapping cortical representation.

RAD51 deficiency disrupts the corticospinal lateralization of motor control.

Mirror movements are involuntary symmetrical movements of one side of the body that mirror voluntary movements of the other side. Congenital mirror movement disorder is a rare condition characterized by mirror movements that persist throughout adulthood in subjects with no other clinical abnormalities. The affected individuals have mirror movements predominating in the muscles that control the fingers and are unable to perform purely unimanual movements. Congenital mirror movement disorder thus provides a unique paradigm for studying the lateralization of motor control. We conducted a multimodal, controlled study of patients with congenital mirror movements associated with RAD51 haploinsufficiency (n = 7, mean age 33.3 ± 16.8 years) by comparison with age- and gender-matched healthy volunteers (n = 14, mean age 33.9 ± 16.1 years). We showed that patients with congenital mirror movements induced by RAD51 deficiency had: (i) an abnormal decussation of the corticospinal tract; (ii) abnormal interhemispheric inhibition and bilateral cortical activation of primary motor areas during intended unimanual movements; and (iii) an abnormal involvement of the supplementary motor area during both unimanual and bimanual movements. The lateralization of motor control thus requires a fine interplay between interhemispheric communication and corticospinal wiring. This fine interplay determines: (i) the delivery of appropriate motor plans from the supplementary motor area to the primary motor cortex; (ii) the lateralized activation of the primary motor cortex; and (iii) the unilateral transmission of the motor command to the limb involved in the intended movement. Our results also unveil an unexpected function of RAD51 in corticospinal development of the motor system.

TMS interference with primacy and recency mechanisms reveals bimodal episodic encoding in the human brain.

A classic finding of the psychology of memory is the "serial position effect." Immediate free recall of a word list is more efficient for items presented early (primacy effect) or late (recency effect), with respect to those in the middle. In an event-related, randomized block design, we interfered with the encoding of unrelated words lists with brief trains of repetitive TMS (rTMS), applied coincidently with the acoustic presentation of each word to the left dorsolateral pFC, the left intraparietal lobe, and a control site (vertex). Interference of rTMS with encoding produced a clear-cut double dissociation on accuracy during immediate free recall. The primacy effect was selectively worsened by rTMS of the dorsolateral pFC, whereas recency was selectively worsened by rTMS of the intraparietal lobe. These results are in agreement with the double dissociation between short-term and long-term memory observed in neuropsychological patients and provide direct evidence of distinct cortical mechanisms of encoding in the human brain.

Impulsivity Traits in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Background: In Parkinson's disease (PD), impulsivity as a personality trait may be linked to the risk of developing impulse control disorders (ICDs) during dopaminergic therapy. However, studies evaluating differences in trait impulsivity between patients with PD and healthy controls or between patients with PD with and without ICDs reported partly inconsistent findings. Objectives: We conducted a systematic review and meta-analysis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) of studies comparing Barratt Impulsiveness Scale (BIS-11) scores between patients with PD and healthy controls and between patients with PD with and without ICDs. Methods: Eligible studies were identified through a systematic search in 3 databases. Mean differences with 95% confidence intervals (CIs) for BIS-11 total and subscale scores were separately calculated for studies comparing patients with PD and healthy controls and patients with PD with and without ICDs. Meta-regressions were performed to explore sources of heterogeneity (percentage of men, age, disease duration, and levodopa equivalent daily dose). Results: A total of 40 studies were included in the quantitative analyses. BIS-11 total scores were significantly higher in patients with PD compared with healthy controls (mean difference 2.43; 95% CI, 1.03, 3.83), and in patients with PD with active ICDs compared with patients without ICDs (6.62; 95% CI, 5.01, 8.23). No significant moderators emerged by meta-regression analyses. Conclusions: The present meta-analysis supports that impulsivity, as a personality trait, may characterize patients with PD, even in the absence of ICDs. Moreover, these data corroborate findings of clinical studies reporting higher levels of trait impulsivity in PD patients with ICDs compared with patients without ICDs.

Subregional prefrontal cortex recruitment as a function of inhibitory demand: an fMRI metanalysis.

Convergent studies corroborated the idea that the right prefrontal cortex is the crucial brain region responsible for inhibiting our actions. However, which sub-regions of the right prefrontal cortex are involved is still a matter of debate. To map the inhibitory function of the sub-regions of the right prefrontal cortex, we performed Activation Likelihood Estimation (ALE) meta-analyses and meta-regressions (ES-SDM) of fMRI studies exploring inhibitory control. Sixty-eight studies (1684 subjects, 912 foci) were identified and divided in three groups depending on the incremental demand. Overall, our results showed that higher was the inhibitory demand based on the individual differences in performances, more the upper portion of the right prefrontal cortex was activated to achieve a successful inhibition. Conversely, a lower demand of the inhibitory function, was associated with the inferior portions of the right prefrontal cortex recruitment. Notably, in the latter case, we also observed activation of areas associated with working memory and responsible for cognitive strategies.

Epidemiology of amyotrophic lateral sclerosis in the north east Tuscany in the 2018-2021 period.

Background: The incidence of Amyotrophic Lateral Sclerosis (ALS) varies among different geographical areas and seems to increase over time. This study aimed to examine the epidemiologic data of ALS in the north-east Tuscany and compare the results with those of similar surveys. Methods: Data from ALS cases diagnosed in Florence and Prato Hospitals were prospectively collected from 1st June 2018 to 31st May 2021. Results: The age- and sex-adjusted incidence rate of ALS in cases per 100,000 population was 2.71 (M/F ratio: 1.21), significantly higher as compared to that reported in the 1967-1976 decade in the same geographical area (0.714). The age- and sex-adjusted incidence rate among resident strangers was similar to that of the general population (2.69). A slightly higher incidence rate (4.36) was observed in the north-east area of Florence province, which includes the Mugello valley. The mean prevalence was of 7.17/100,00. The mean age at diagnosis was 69.7 years, with a peak between 70 and 79 years among men and a smoother age curve among women. Conclusions: ALS epidemiological features in north-east Tuscany are in line with other Italian and European Centers. The dramatic increase of the local disease burden over the last decades probably reflects better ascertainment methods and health system.

Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines.

This article is based on a consensus conference, promoted and supported by the International Federation of Clinical Neurophysiology (IFCN), which took place in Siena (Italy) in October 2018. The meeting intended to update the ten-year-old safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings (Rossi et al., 2009). Therefore, only emerging and new issues are covered in detail, leaving still valid the 2009 recommendations regarding the description of conventional or patterned TMS protocols, the screening of subjects/patients, the need of neurophysiological monitoring for new protocols, the utilization of reference thresholds of stimulation, the managing of seizures and the list of minor side effects. New issues discussed in detail from the meeting up to April 2020 are safety issues of recently developed stimulation devices and pulse configurations; duties and responsibility of device makers; novel scenarios of TMS applications such as in the neuroimaging context or imaging-guided and robot-guided TMS; TMS interleaved with transcranial electrical stimulation; safety during paired associative stimulation interventions; and risks of using TMS to induce therapeutic seizures (magnetic seizure therapy). An update on the possible induction of seizures, theoretically the most serious risk of TMS, is provided. It has become apparent that such a risk is low, even in patients taking drugs acting on the central nervous system, at least with the use of traditional stimulation parameters and focal coils for which large data sets are available. Finally, new operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement.

Event-related rTMS at encoding affects differently deep and shallow memory traces.

The "level of processing" effect is a classical finding of the experimental psychology of memory. Actually, the depth of information processing at encoding predicts the accuracy of the subsequent episodic memory performance. When the incoming stimuli are analyzed in terms of their meaning (semantic, or deep, encoding), the memory performance is superior with respect to the case in which the same stimuli are analyzed in terms of their perceptual features (shallow encoding). As suggested by previous neuroimaging studies and by some preliminary findings with transcranial magnetic stimulation (TMS), the left prefrontal cortex may play a role in semantic processing requiring the allocation of working memory resources. However, it still remains unclear whether deep and shallow encoding share or not the same cortical networks, as well as how these networks contribute to the "level of processing" effect. To investigate the brain areas casually involved in this phenomenon, we applied event-related repetitive TMS (rTMS) during deep (semantic) and shallow (perceptual) encoding of words. Retrieval was subsequently tested without rTMS interference. RTMS applied to the left dorsolateral prefrontal cortex (DLPFC) abolished the beneficial effect of deep encoding on memory performance, both in terms of accuracy (decrease) and reaction times (increase). Neither accuracy nor reaction times were instead affected by rTMS to the right DLPFC or to an additional control site excluded by the memory process (vertex). The fact that online measures of semantic processing at encoding were unaffected suggests that the detrimental effect on memory performance for semantically encoded items took place in the subsequent consolidation phase. These results highlight the specific causal role of the left DLPFC among the wide left-lateralized cortical network engaged by long-term memory, suggesting that it probably represents a crucial node responsible for the improved memory performance induced by semantic processing.

Mouse Tracking to Explore Motor Inhibition Processes in Go/No-Go and Stop Signal Tasks.

Response inhibition relies on both proactive and reactive mechanisms that exert a synergic control on goal-directed actions. It is typically evaluated by the go/no-go (GNG) and the stop signal task (SST) with response recording based on the key-press method. However, the analysis of discrete variables (i.e., present or absent responses) registered by key-press could be insufficient to capture dynamic aspects of inhibitory control. Trying to overcome this limitation, in the present study we used a mouse tracking procedure to characterize movement profiles related to proactive and reactive inhibition. A total of fifty-three participants performed a cued GNG and an SST. The cued GNG mainly involves proactive control whereas the reactive component is mainly engaged in the SST. We evaluated the velocity profile from mouse trajectories both for responses obtained in the Go conditions and for inhibitory failures. Movements were classified as one-shot when no corrections were observed. Multi-peaked velocity profiles were classified as non-one-shot. A higher proportion of one-shot movements was found in the SST compared to the cued GNG when subjects failed to inhibit responses. This result suggests that proactive control may be responsible for unsmooth profiles in inhibition failures, supporting a differentiation between these tasks.

Efficacy of Tocilizumab in Limbic Encephalitis with Anti-CASPR2 Antibodies.

We report the case of a 64-year-old man who presented with subacute memory, balance impairment, behavioral and mood changes, and epileptic seizures. Magnetic resonance imaging (MRI) showed bilateral hippocampal abnormalities. Brain [18F]-FDG fluorodeoxyglucose positron emission tomography (PET) revealed hypometabolism in both the temporal lobe as well as in the left insular and parietal regions. The clinical and neuroradiological picture and the detection of anti-CASPR2 antibodies in serum oriented the diagnosis towards autoimmune limbic encephalitis. Intravenous high-dose steroid and immunoglobulin treatments were ineffective. We did not use rituximab for the presence of antibodies to HbcAg positivity. Tocilizumab given intravenously 8 mg/kg once a month for six months and then subcutaneously 162 mg every week for six months resulted in clinical and neuroradiological improvement. These data support the efficacy of tocilizumab in autoimmune limbic encephalitis associated with anti-CASPR2 antibodies, which has been sporadically reported in the literature.

Effects of Music Reading on Motor Cortex Excitability in Pianists: A Transcranial Magnetic Stimulation Study.

Neurophysiological studies suggest that music reading facilitates sensorimotor cortex. The aim of this study was to evaluate (1) whether in pianists, reading notes in bass and treble clef selectively enhances right and left primary motor cortex (M1) excitability; and (2) whether reading notes played with the thumb or little finger selectively modulates the excitability of specific muscles. Twenty musicians (11 pianists, 9 non-pianists) participated. Transcranial magnetic stimulation (TMS) was applied while subjects read the bass or the treble clef of sheets music and during the observation of a blank staff (baseline). When pianists read the treble clef, the excitability of the left M1 was higher compared to that recorded in the right M1. Moreover, in the treble clef condition motor evoked potentials (MEPs) induced by TMS of the left M1 were higher when pianists read notes to be played with the 5° finger (little finger) with respect to 1° finger (thumb) notes, whereas in the bass clef condition TMS of the right M1 induced higher MEPs for 1° finger note compared to 5° finger notes. No significant modulation was observed in non-pianists. These data support the view that music reading may induce specific inter- and intra-hemispheric modulation of the motor cortex excitability.