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Background The integrity of the neural pathways that link genital sensitive areas to the brain and the correlation with subjective sensations in transgender women with gender dysphoria after gender affirming surgery (GAS) have not been explored in detail and remain controversial, so far. Aim To test with electrophysiology the integrity of the nervous paths after GAS, and to explore the relationship between genital sensitivity and self-perceived orgasmic intensity in transgender women after GAS. Methods Six patients who underwent GAS between 2016 and 2019 were enrolled in the study, and the evaluation of genital and pelvic neural pathways was performed. Outcomes Genital sensory thresholds (at clitoral, vaginal, and anal sites) investigated by Somatosensory Evoked Potentials (SEP) and the intensity of orgasm (measured by a psychometric tool, the Orgasmometer) were combined to obtain an objective and subjective evaluation. Results SSEPs confirmed the integrity of the large diameter, dorsal column-lemniscus pathway subserving the genital area after GAS. Perceptual Threshold (PT) values were much lower at the neoclitoris compared to neovagina and anal sites. There was no correlation between Orgasmometer and SEP at anal and neovaginal level, while a trend was found at clitoral level. Clinical Implication These findings could lead clinicians to a better understanding of postsurgical sexual life in transgender women in order to develop surgical techniques that could focus more on functional aspects of neovagina and neoclitoris. Strengths & Limitations Limitations: study very preliminary/exploratory; small number of patients; no long-term follow-up. Strengths: first assessment of sensory pelvic floor innervation in transgender women after GAS; use of objective methods; first attempt at correlating objectives findings to subjective experience of the sexual orgasm. Conclusions Our evaluation showed that SSEPs is a good indicator of neural sensitivity, especially in neoclitoris, and that these measurements were consistent with the analysis of self-perceived orgasmic intensity.

Background and Rationale Hyperkinetic movement disorders represent a heterogeneous group of diseases, different from a genetic and clinical perspective. In the past, neurophysiological approaches provided different, sometimes contradictory findings, pointing to an impaired cortical inhibition as a common electrophysiological marker. Our aim was to evaluate changes in interhemispheric communication in patients with idiopathic cervical dystonia (ICD) and spinocerebellar ataxias (SCAs). Materials and Methods Eleven patients with ICD, 7 with genetically confirmed SCA2 or SCA3, and 10 healthy volunteers were enrolled. The onset latency and duration of the ipsilateral silent period (iSPOL and iSPD, respectively), as well as the so-called transcallosal conduction time (TCT), were then recorded from the abductor pollicis brevis of the right side using an 8-shaped focal coil with wing diameters of 70 mm; all these parameters were evaluated and compared among groups. In SCAs, changes in neurophysiological measures were also correlated to the mutational load. Results iSPD was significantly shorter in patients with SCA2 and SCA3, when compared both to control and ICD ( P < .0001); iSPOL and TCT were prolonged in SCAs patients ( P < .001). Changes in iSPD, iSPOL, and TCT in SCAs are significantly correlated with the mutational load ( P = .01, P = .02, and P = .002, respectively). Discussion This is the first study to assess changes in interhemispheric communication in patients with SCAs and ICD, using a transcranial magnetic stimulation protocol. Together with previous data in Huntington’s disease, we suggest that these changes may underlie, at least in part, a common disease mechanism of polyglutamine disorders.

COVID‐19 is a public health emergency with cases increasing globally. Its clinical manifestations range from asymptomatic and acute respiratory disease to multiple organ dysfunction syndromes and effects of COVID‐19 in the long term. Interestingly, regardless of variant, all COVID‐19 share impairment of the sense of smell and taste. We would like to report, as far as we know, the first comprehensive neurophysiological evaluation of the long‐term effects of SARS‐CoV‐2 on the olfactory system with potential‐related neurological damage. The case report concerns a military doctor, with a monitored health history, infected in April 2020 by the first wave of the epidemic expansion while on military duty in Codogno (Milan). In this subject, we find the electrophysiological signal in the periphery, while its correlate is absent in the olfactory bulb region than in whole brain recordings. In agreement with this result is the lack of metabolic signs of brain activation under olfactory stimulation. Consequently, quantitative and qualitative diagnoses of anosmia were made by means of olfactometric tests. We strongly suggest a comprehensive series of olfactometric tests from the first sign of COVID‐19 and subsequent patient assessments. In conclusion, electrophysiological and metabolic tests of olfactory function have made it possible to study the long‐term effects and the establishment of neurological consequences.

Background Venous percutaneous transluminal angioplasty (vPTA) in patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI) have shown contradictory results. The aim of the study is to evaluate the efficacy of the procedure in a randomized wait list control study. Methods 66 adults with neurologist-confirmed diagnosis of MS and sonographic diagnosis of CCSVI were allocated into vPTA-yes group (n = 31) or vPTA-not group (n = 35, control group). vPTA was performed immediately 15 days after randomization in the PTA-yes group and 6 months later in the control group. Evoked potentials (EPs), clinical-functional measures (CFMs), and upper limb kinematic measures (ULKMs) were measured at baseline (T0) and six months after in both groups, just before the venous angioplasty in the vPTA-not group (T1). Results Comparing the vPTA-yes and vPTA-not group, the CFM-derived composite functional outcome showed 11 (37%) versus 7 (20%) improved, 1 (3%) versus 3 (8%) stable, 0 versus 7 (20%) worsened, and 19 (61%) versus 18 (51%) mixed patients (χ2 = 8.71, df = 3, P = 0.03). Unadjusted and adjusted (for baseline confounding variables) odds ratio at 95% confidence interval were, respectively, 1.93 (1.3-2.8), P value 0.0007, and 1.85 (1.2-1.7), P value 0.002. EP- and ULKM-derived composite functional outcome showed no significant difference between the two groups. Conclusions Venous angioplasty can positively impact a few CFMs especially for the quality of life but achieving disability improvement is unlikely.

Background: Epilepsy and hypertension are common chronic conditions, both showing high prevalence in older age groups. This review outlines current experimental and clinical evidence on both direct and indirect role of hypertension in epileptogenesis and discusses the principles of drug treatment in patients with hypertension and epilepsy. Methods: We selected English-written articles on epilepsy, hypertension, stroke, and cerebrovascular disease until December, 2018. Results: Renin-angiotensin system might play a central role in the direct interaction between hypertension and epilepsy, but other mechanisms may be contemplated. Large-artery stroke, small vessel disease and posterior reversible leukoencephalopathy syndrome are hypertension-related brain lesions able to determine epilepsy by indirect mechanisms. The role of hypertension as an independent risk factor for post-stroke epilepsy has not been demonstrated. The role of hypertension-related small vessel disease in adult-onset epilepsy has been demonstrated. Posterior reversible encephalopathy syndrome is an acute condition, often caused by a hypertensive crisis, associated with the occurrence of acute symptomatic seizures. Chronic antiepileptic treatment should consider the risk of drug-drug interactions with antihypertensives. Conclusions: Current evidence from preclinical and clinical studies supports the vision that hypertension may be a cause of seizures and epilepsy through direct or indirect mechanisms. In both post-stroke epilepsy and small vessel disease-associated epilepsy, chronic antiepileptic treatment is recommended. In posterior reversible encephalopathy syndrome blood pressure must be rapidly lowered and prompt antiepileptic treatment should be initiated.

Event-Related Potentials (ERPs) occurring independently from any stimulus are purely endogenous (emitted potentials) and their neural generators can be unequivocally linked with cognitive processes. In the present study, the subjects performed two similar visual counting tasks: a standard two-stimulus oddball, and an omitted-target oddball task, characterized by the physical absence of the target stimulus. Our investigation aimed at localizing the neural sources of the scalp-recorded endogenous/emitted ERPs. To optimize the source localization, the high temporal resolution of electrophysiology was combined with the fine spatial information provided by the simultaneous recording of functional magnetic resonance (fMRI). Both tasks identified two endogenous ERP components in the 300 to 520 ms interval. An earlier component, pP2, showed a bilateral generator in the anterior Insula. A later P3 component (P3b) was generated bilaterally in the temporal-parietal junction, the premotor and motor area and the anterior intraparietal sulcus (this latter one only in the standard oddball). Anticipatory slow waves (beginning 900 to 500 ms pre-stimulus), also of endogenous nature, were produced by the inferior and middle frontal gyrus and the supplementary and cingulate motor areas. Our protocol disentangled pre- from post-stimulus fMRI activations and provided original clues to the psychophysiological interpretation of emitted/endogenous ERPs.

Background and rationale Histopathological studies revealed degeneration of the dorsal motor nucleus of the vagus nerve (VN) early in the course of idiopathic Parkinson’s disease (IPD). Degeneration of VN axons should be detectable by high-resolution ultrasound (HRUS) as a thinning of the nerve trunk. In order to establish if the VN exhibits sonographic signs of atrophy in IPD, we examined patients with IPD compared with age-matched controls. Material and methods We measured the caliber (cross-sectional area, CSA) and perimeter of the VN in 20 outpatients with IPD (8 females and 12 males; mean age 73.0 + 8.6 years) and in age-matched controls using HRUS. Evaluation was performed by blinded raters using an Esaote MyLab Gamma device in conventional B-Mode with an 8–19 MHz probe. Results In both sides, the VN CSA was significantly smaller in IPD outpatients than in controls (right 2.37 + 0.91, left 1.87 + 1.35 mm2 versus 6.0 + 1.33, 5.6 + 1.26 mm2; p + 0.85, left 4.78 + 1.74 mm versus 8.87 + 0.86, 8.58 + 0.97 mm; p Conclusion Our findings provide evidence of atrophy of the VNs in IPD patients by HRUS. Moreover, HRUS of the VN represent a non-invasive easy imaging modality of screening in IPD patients independent of disease stage and duration and an interesting possible additional index of disease.

Event-related potentials (ERPs) are obtained from the electroencephalogram (EEG) or the magnetoencephalogram (MEG, event-related fields (ERF)), extracting the activity that is time-locked to an event. Despite the potential utility of ERP/ERF in cognitive domain, the clinical standardization of their use is presently undefined for most of procedures. The aim of the present review is to establish limits and reliability of ERP medical application, summarize main methodological issues, and present evidence of clinical application and future improvement. The present section of the review focuses on well-standardized ERP methods, including P300, Contingent Negative Variation (CNV), Mismatch Negativity (MMN), and N400, with a chapter dedicated to laser-evoked potentials (LEPs). One section is dedicated to proactive preparatory brain activity as the Bereitschaftspotential and the prefrontal negativity (BP and pN). The P300 and the MMN potentials have a limited but recognized role in the diagnosis of cognitive impairment and consciousness disorders. LEPs have a well-documented usefulness in the diagnosis of neuropathic pain, with low application in clinical assessment of psychophysiological basis of pain. The other ERP components mentioned here, though largely applied in normal and pathological cases and well standardized, are still confined to the research field. CNV, BP, and pN deserve to be largely tested in movement disorders, just to explain possible functional changes in motor preparation circuits subtending different clinical pictures and responses to treatments.

Introduction: In recent years, a growing body of literature has investigated the use of non-invasive brain stimulation (NIBS) techniques as a putative treatment in Huntington's Disease (HD). Our aim was to evaluate the effects of cerebellar transcranial Direct Current Simulation (ctDCS) on the motor outcome in patients affected by HD, encompassing at the same time the current knowledge about the effects of NIBS both on motor and non-motor dysfunctions in HD.Materials and Methods: Four patients (two females) were enrolled and underwent ctDCS (both anodal or sham, elapsed by at least 3 months: 2.0 mA, 20 min per day, 5 days a week). Clinical scores were assessed by using the Unified Huntington's Disease Rating Scale – part I (UHDRS-I), immediately before ctDCS (T0), at the end of the 5-days treatment (T1) and 4 weeks later (T2).Results: Anodal ctDCS improved motor scores compared to baseline (p = 0.0046), whereas sham stimulation left them unchanged (p = 0.33, Friedman test). In particular, following anodal ctDCS, UHDRS-I score significantly improved, especially regarding the subitem “dystonia,” both at T1 and T2 compared to sham condition (p < 0.05; Wilcoxon matched-pairs signed test).Conclusions: ctDCS improved motor scores in HD, with effects lasting for about 4 weeks after tDCS completion. This is the first study discussing the putative role of cerebellar non-invasive simulation for the treatment of HD.

Background Mutations in TGM6 gene, encoding for transglutaminase 6 (TG6), have been implicated in the pathogenesis of spinocerebellar ataxia type 35 (SCA35), a rare autosomal dominant disease marked by cerebellar degeneration and characterized by postural instability, incoordination of gait, features of cerebellar dysfunction and pyramidal signs. Case presentation Here we report the case of an Italian patient with late-onset, slowly progressive cerebellar features, including gait ataxia, scanning speech and ocular dysmetria and pyramidal tract signs. Whole exome sequencing revealed the rare heterozygous c.1024C > T (p.R342W) variant of TGM6, located at a highly evolutionary conserved position and predicted as pathogenic by in silico tools. Expression of TG6-R342W mutant in HEK293T cells led to a significant reduction of transamidase activity compared to wild-type TG6. Conclusion This finding extends SCA35 genetic landscape, highlighting the importance of TGM6 screening in undiagnosed late-onset and slowly progressive cerebellar ataxias.

Event-related potentials (ERPs) are obtained from the electroencephalogram (EEG) or the magnetoencephalogram (MEG, event-related fields (ERF)), extracting the activity that is time-locked to an event. Despite the potential utility of ERP/ERF in cognitive domain, the clinical standardization of their use is presently undefined for most of procedures. The aim of the present review is to establish limits and reliability of ERP medical application, summarize main methodological issues, and present evidence of clinical application and future improvement. The present section of the review focuses on well-standardized ERP methods, including P300, Contingent Negative Variation (CNV), Mismatch Negativity (MMN), and N400, with a chapter dedicated to laser-evoked potentials (LEPs). One section is dedicated to proactive preparatory brain activity as the Bereitschaftspotential and the prefrontal negativity (BP and pN). The P300 and the MMN potentials have a limited but recognized role in the diagnosis of cognitive impairment and consciousness disorders. LEPs have a well-documented usefulness in the diagnosis of neuropathic pain, with low application in clinical assessment of psychophysiological basis of pain. The other ERP components mentioned here, though largely applied in normal and pathological cases and well standardized, are still confined to the research field. CNV, BP, and pN deserve to be largely tested in movement disorders, just to explain possible functional changes in motor preparation circuits subtending different clinical pictures and responses to treatments.

Background: Vagal nerve stimulation (VNS) is an effective palliative therapy in drug-resistant epileptic patients and is also approved as a therapy for treatment-resistant depression. Depression is a frequent comorbidity in epilepsy and it affects the quality of life of patients more than the seizure frequency itself. The aim of this systematic review is to analyze the available literature about the VNS effect on depressive symptoms in epileptic patients. Material and methods: A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to January 2020. All studies concerning depressive symptom assessment in epileptic patients treated with VNS were included. Results: Nine studies were included because they fulfilled inclusion criteria. Six out of nine papers reported a positive effect of VNS on depressive symptoms. Eight out of nine studies did not find any correlation between seizure reduction and depressive symptom amelioration, as induced by VNS. Clinical scales for depression, drug regimens, and age of patients were broadly different among the examined studies. Conclusions: Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response. However, more rigorous studies addressing this issue are encouraged.

Phantom limb pain (PLP) is a disabling and intractable sensation arising in about 80% of patients after amputation. The aim of this study was to evaluate the possibility to modulate nociceptive processing and pain perception with cerebellar transcranial direct current stimulation (ctDCS) in patients suffering from painful and non-painful phantom limb sensations. Fourteen upper limb amputees underwent ctDCS (anodal or sham, 2.0 mA, 20 min per day, 5 days a week). Clinical scores and electrophysiological parameters were assessed before tDCS, at the end of the 5-day treatment, 2 and 4 weeks later. Laser-evoked potentials (LEPs) were obtained from the stump using a Nd:YAP laser by pulses with short duration (5 ms) and small diameter spots (5 mm). Changes in visual analogue scores (VAS) were evaluated (chronic pain, paroxysmal pain, stump pain, phantom movements, phantom sensations). Anodal polarization significantly dampened LEP amplitudes (N1, p = 0.021 and N2/P2, p = 0.0034), whereas sham intervention left them unchanged. Anodal ctDCS significantly reduced paroxysmal pain (p

// Andrea Mazzatenta 1 , Alessandro Cellerino 2 , Nicola Origlia 3 , Davide Barloscio 3,4 , Ferdinando Sartucci 4 , Camillo Di Giulio 1 and Luciano Domenici 3,5 1 Department of Neuroscience, Imaging and Clinical Science, ‘G. d’Annunzio’ University of Chieti-Pescara, Chieti, Italy 2 Scuola Normale Superiore, Pisa, Italy 3 Neuroscience Institute, CNR-Pisa, Pisa, Italy 4 Department di Medicina Clinica e Sperimentale, Sezione di Neurologia, e Dai di Neuroscienze, Pisa, Italy 5 Department of Applied Clinical Science and Biotechnology (DISCAB), School of Medicine, l’Aquila University, L’Aquila, Italy Correspondence to: Andrea Mazzatenta, email: // Keywords : aging, olfaction, olfactometry, absolute threshold, olfactory phenotype, Gerotarget Received : January 27, 2016 Accepted : March 18, 2016 Published : March 26, 2016 Abstract The mechanism of the natural aging of olfaction and its declinein the absence of any overt disease conditions remains unclear. Here, we investigated this mechanism through measurement of one of the parameters of olfactory function, the absolute threshold, in a healthy population from childhood to old age. The absolute olfactory threshold data were collected from an Italian observational study with 622 participants aged 5-105 years. A subjective testing procedure of constant stimuli was used, which was also compared to the ‘staircase’ method, with the calculation of the reliability. The n-butanol stimulus was used as an ascending series of nine molar concentrations that were monitored using an electronic nose. The data were analyzed using nonparametric statistics because of the multimodal distribution. We show that the age-related variations in the absolute olfactory threshold are not continuous; instead, there are multiple olfactory phenotypes. Three distinct age-related phenotypes were defined, termed as ‘juvenile’, ‘mature’ and ‘elder’. The frequency of these three phenotypes depends on age. Our data suggest that the sense of smell does not decrease linearly with aging. Our findings provide the basis for further understanding of olfactory loss as an anticipatory sign of aging and neurodegenerative processes.

Respiratory failure represents an unavoidable step in patients with amyotrophic lateral sclerosis (ALS) and other motor neuron diseases (MND). The development of diaphragm ultrasonography (DUS) provides an alternative useful and risk-free tool to supply clinical, functional, and neurophysiological assessment of respiratory muscle weakness. Our aim was to evaluate if sonographic changes (thickness and echogenicity in the costal portion of the diaphragm, at rest and during respiratory movements) may be used in ALS patients to assess disease severity over time, to rule out any risk or discomfort due to traditional neurophysiological investigations. Twenty ALS patients (mean age, 64.6 ± 10.5 years) were enrolled and data were compared with age-matched healthy volunteers; DUS data were correlated with respiratory function and disease severity scale. Examinations were performed using Telemed Echo-wave II or Esaote MyLabGamma devices in conventional B-Mode. Mean resting thickness was reduced in all cases; changes in thickness during inspiration and expiration were also reduced (p

Rationale: Spinal cord stimulation (SCS) is an effective option for neuropathic pain treatment. New technological developments, as high-frequency (HF) and theta burst stimulation (TBS), have shown promising results, although putative mechanisms of action still remain debated. Methods: thirty patients with lower back pain were enrolled and underwent LF, HF, and TBS. Laser evoked potentials (LEPs) were recorded by using a Nd:YAG laser. Amplitudes and latencies of the main two components (N1, N2/P2) were compared among different experimental sessions. Changes in resting motor threshold (RMT), cortical silent period (cSP), short intracortical inhibition (SICI), and intracortical facilitation (ICF) were also evaluated. Results: TBS dampened LEP amplitudes compared with LF (N1: p = 0.032; N2/P2: p < 0.0001) and HF stimulation (N1: p = 0.029; N2/P2: p < 0.0001, Holm-Sidak post-hoc test). Concurrently, TBS increased N1 latency, when compared with baseline and LF stimulation (p = 0.009 and 0.0033). Whereas RMT and SICI did not change among experimental conditions, TBS significantly prolonged cSP duration compared with baseline (p = 0.002), LF (p = 0.048), and HF-SCS (p = 0.016); finally, both HF (p = 0.004) and TBS (p = 0.0039) increased ICF. Conclusion: TBS modulates medial and lateral pain pathways through distinct mechanisms, possibly involving both GABA(a)ergic and Glutamatergic networks at an intracortical level. These results may have implications for therapy and for the choice of best stimulation protocol.

Background Several methods have been proposed to diagnose and score disease severity in Amyotrophic Lateral Sclerosis (ALS) patients (pt.). Traditionally neurophysiological tests have been employed. The development of neuromuscular ultrasound (US) have provided a further useful tool. Our aim was to evaluate sonographic changes of muscles and nerve trunks to define diagnosis and assess ALS severity. Materials and methods 20 ALS pt. (15 m e 5 f, mean age: 63.9 + 9.5 yrs) were enrolled. All investigations were performed using an Esaote MyLabGamma device in conventional B-Mode. We evaluated the following muscles: sternocleidomastoid, diaphragm, biceps brachii/brachialis, forearm flexors, rectus femoris and anterior tibial; among the nerve, vagus, median, ulnar and sural. Results We found in all cases increased echogenicity with decreased muscle thickness and fasciculations; mean diaphragm rest thickness was reduced; changes in thickness during inspiration and expiration were also reduced and loss in the most severe cases. Median and Ulnar nerve cross-sectional area (CSA) resulted smaller; sural and vagal nerve resulted spared. ALS disease severity, measured using Functional Rating Scale (ALSFRS), correlated with quantitative ultrasound data. Conclusions neuromuscular ultrasound resulted a simple, fast and easy method, painless and risk-free, able to provide useful functional and structural information in ALS pt. Furthermore, diaphragm US may allow to point out concomitant respiratory failure. Moreover is desirable that US become an indispensable tool of the diagnostic armamentarium of the neuromuscular physician in pt. with ALS.

Transcutaneous spinal Direct Current Stimulation (tsDCS) is a noninvasive technique based on the application of weak electrical currents over spinal cord.We studied the effects of tsDCS on interhemispheric motor connectivity and visual processing by evaluating changes in ipsilateral Silent Period (iSP), Transcallosal Conduction Time (TCT) and hemifield Visual Evoked Potentials (hVEPs), before (T0) and at a different intervals following sham, anodal and cathodal tsDCS (T9-T11 level, 2.0 mA, 20'). Motor Evoked Potentials (MEPs) were recorded from abductor pollicis brevis (APB), abductor hallucis (AH) and deltoid muscles. hVEPs were recorded bilaterally by reversal of a horizontal square wave grating with the display positioned in the right hemifield.Anodal tsDCS increased TCT (p0.001) and the interhemispheric delay for both the main VEP components (N1: p = 0.0003; P1: p0.0001), dampening at the same time iSP duration (APB: p0.0001; AH: p = 0.0005; deltoid: p0.0001), while cathodal stimulation elicited opposite effects (p0.0001).tsDCS modulates interhemispheric processing in a polarity-specific manner, with anodal stimulation leading to a functional disconnection between hemispheres. tsDCS would be a new promising therapeutic tool in managing a number of human diseases characterized by an impaired interhemispheric balance, or an early rehabilitation strategy in patients with acute brain lesions, when other non-invasive brain stimulation techniques (NIBS) are not indicated due to safety concerns.

The introduction of three-dimensional echography (3D echo) in vascular field is not recent, but it still remains a seldom-used technique because of the costs of ultrasound probe and the need of dedicated laboratories. Therefore, despite significant prognostic implications, the high diagnostic accuracy in plaque definition, and the relative ease of use, 3D echo in vascular field is a niche technique. The purpose of this review is mainly clinical and intends to demonstrate the potential strength of a 3D approach, including technical aspects, in order to present to clinicians and imagers the appealing aspects of a noninvasive and radiation-free methodology with relevant diagnostic and prognostic correlates in the assessment of carotid atherosclerosis. A comprehensive literature search (since 1990s to date) using the PubMed, MEDLINE, and Cochrane libraries databases has been conducted. Articles written in English have been assessed, including reviews, clinical trials, meta-analyses, and interventional/observational studies. Manual cross-referencing was also performed, and relevant references from selected articles were reviewed. The search was limited to studies conducted in humans. Search terms, retrieved also with PubMed Advanced search and AND/OR Boolean operators (mainly in title and abstract), included three-dimensional, echo, stroke/transient ischemic attack, predictors, carotid, imaging, and biomarkers.

The cerebellum is involved in a wide number of integrative functions. We evaluated the role of cerebellum in peripersonal defensive behavior, as assessed by the so‐called hand blink reflex (HBR), modulating cerebellar activity with transcranial direct current stimulation (tDCS). Healthy subjects underwent cerebellar (sham, anodal, and cathodal tcDCS) and motor cortex tDCS (anodal or cathodal; 20′, 2 mA). For the recording of HBR, electrical stimuli were delivered using a surface bipolar electrode placed on the median nerve at the wrist and EMG activity recorded from the orbicularis oculi muscle bilaterally. Depending on the hand position respective to the face, HBR was assessed in four different conditions: “hand‐far,” “hand‐near” (eyes open), “side hand,” and “hand‐patched” (eyes closed). While sham and cathodal cerebellar stimulation had no significant effect, anodal tcDCS dramatically dampened the magnitude of the HBR, as measured by the area under the curve (AUC), in the “hand‐patched” and “side hand” conditions only, for ipsilateral (F (4,171) = 15.08, P

BACKGROUND AND PURPOSE Cerebral vasomotor reserve (VMR) is the capability of cerebral arterioles to change their diameter in response to various stimuli, such hypercapnia. Changes of VMR due to transcranial direct current stimulation (tDCS) have been poorly studied. METHODS Twenty-five healthy subjects underwent anodal/cathodal and sham tDCS on right primary motor area. Before and after tDCS, we assessed VMR by Transcranial Color-Coded Sonography (TCCS) calculating trought Breath Holding Index (BHI) and Heart Rate Variability (HRV), in particular after Valsalva manouver. RESULTS A-tDCS decreased VMR and BHI (p 0.05). CONCLUSIONS Our study confirms that tDCS induces a modification of bilateral VMR with a polarity-specific effect; based on this bilateral MFV and BHI modifications, we can speculate an involvement of the SNS in the VMR regulation.

Introduction Several methods have been proposed to diagnose and quantify disease severity in patients (pt.) with Amyotrophic Lateral Sclerosis (ALS). Traditionally neurophysiological tests have been employed. The development of neuromuscular ultrasound (US) have provided a further useful tool to supplement clinical and neurophysiological assessment of ALS. Our aim was to evaluate sonographic changes of muscles and nerve trunks in an attempt to define diagnosis and assess severity of the disease. Methods 35 consecutive ALS pt. (20 males e 15 females, mean age: 64.6 ± 10.5 yrs) were enrolled; in four cases the diagnosis was not previously established. All investigations were performed using an Esaote MyLabGamma or a Telemed Echo-wave II device in conventional B-Mode. We evaluated the following muscles: tongue, sternocleidomastoid, diaphragm, biceps brachii/brachialis, forearm flexors, rectus femoris and anterior tibial; among the nerve, brachial plexus, vagus, median, ulnar and sural. Results We found in all cases increased echogenicity with decreased muscle thickness and fasciculations; these findings allowed us to diagnose an ALS in the 4 cases not previously identified and later confirmed. Mean diaphragm rest thickness was reduced; changes in thickness during inspiration and expiration were also reduced and loss in the most severe cases (3 pt.). Brachial plexus, Median and Ulnar nerve cross-sectional area (CSA) resulted smaller in ALS; vagus and sural nerve resulted spared. ALS disease severity, measured using Functional Rating Scale (ALSFRS), correlated with quantitative ultrasound data. Conclusion Neuromuscular ultrasound resulted a simple, fast and easy method, painless and risk-free, able to provide useful functional and structural informations in ALS pt. Furthermore diaphragm US may allow to point out concomitant respiratory failure. Moreover is desirable that US become an indispensable tool of the diagnostic armamentarium of the neuromuscular physician in pt. with ALS.

Introduction High resolution ultrasonography (HRUS) of peripheral nerves is an emerging tool in investigating peripheral nerves, complementary to electrodiagnostic tests, and it is commonly performed using a linear array transducer with upper frequencies between 12 and 19 MHz. Since 2016 a very-high-resolution US (VHRUS) device is available for clinical use (Vevo-MD) that incorporates transducers with upper frequencies of 48 MHz (pixel resolution 50 μ m, depth 2.3 cm) and 70 MHz (pixel resolution 30 μ m, depth 1 cm). Our aim was to investigate the potential role of VHRUS in the assessment of the posterior tibial nerve (PTN) and sural nerve (SN) healthy echographic features being both commonly involved in peripheral neuropathies. Methods We studied these nerves (at the ankle) in 10 healthy subjects, comparing images obtained with VHRUS to those usually obtained with a 19 MHz HRUS. In particular, we compared 19 vs 48 MHz for PNT and 19 vs 70 MHz for SN. We measured nerves’ areas, perimeters and fascicular pattern obtained from the images acquired with both devices by using dedicated offline post-processing tools, and we compared the respective values. Results Our data show significant agreement in the measurements of area and perimeter obtained with both devices. However, using VHRUS we experienced a much higher degree of confidence in visualizing both nerves and their internal structure thanks to its superior spatial resolution. We also noticed that scanning depth was always sufficient for this diagnostic task. Conclusion VHRUS shows promising advantages compared with HRUS although further studies are needed to validate its use also in subjects with well-established peripheral neuropathies.

Introduction Amblyopia is a neurodevelopmental disorder characterized by visual acuity and contrast sensitivity loss, refractory to pharmacological and mechanical treatments in adulthood. In animal models, the corpus callosum (CC) plays a critical role in the development of the ocular dominance, thus strengthening the hypothesis of an involvement of both striate and extrastriate areas in the pathogenesis of amblyopia. To investigate the role of interhemispheric pathways in amblyopia, we studied the response of the visual cortex to transcranial Direct Current Stimulation (tDCS) applied over the primary visual area (V1) contralateral to the amblyopic eye. Methods Visual evoked potentials (VEPs) triggered by grating stimuli of different contrasts (K90%, K50%, K20%) were recorded in both hemispheres before and after inactivation of the occipital cortex of one side via cathodal tDCS (2.0 mA, 20′). VEPs were recorded before (T0), immediately after (T1) and 60′ following tDCS (T2). The display was either centered on the vertical meridian (central stimulation) or positioned in the right hemifield (with its inner edge at a distance of 1 degree from the fixation point). Visual acuity was tested at each time interval, to assess behavioral changes between active and sham stimulation. Results Cathodal tDCS improved visual acuity respect to baseline (recovery of 8.4 ± 3.3 letters, Holm-Sidak post hoc method p Conclusion tDCS is a promising treatment for amblyopia in adults. The rapid recovery of excitability and the persistent transcallosal disinhibition following perturbation of cortical activity strongly supports a critical role of interhemispheric balance in the pathophysiology of amblyopia.

Introduction Only few studies have explored the pathophysiology of PSE; some Authors have suggested a defective visual inhibition as a contributing factor to photoparoxysmal response, pointing to an overactive visuomotor connectivity thus inducing abnormal motor responses. In order to investigate functional changes underlying photosensitivity, we studied the response of the visual cortex to low-frequency, inhibitory repetitive transcranial magnetic stimulation (rTMS) in drug-free patients with photosensitive seizures and healthy volunteers. Methods Visual evoked potentials (VEPs) triggered by grating stimuli of different luminance contrasts (K20%, K50% and K90%) were recorded in both hemispheres before and after transient functional inactivation of the occipital cortex of one side via low-frequency rTMS (0.5 Hz, at 120 % of resting motor threshold, for 20’). VEPs were recorded before (T0), immediately after (T1) and 45’ following the completion of rTMS (T2). The display was either centered on the vertical meridian (central stimulation) or positioned in the right hemifield (with its inner edge at a distance of 1 degree from the fixation point). Results Baseline amplitudes of the VEP components (N1 and P1) were enhanced in photosensitive patients. At T1, rTMS produced an inhibitory effect on VEPs amplitudes at all contrasts in the targeted side and a concurrent facilitation of responses in the contralateral hemisphere. Compared with PSE subjects, VEP amplitudes remained persistently dampened in the stimulated hemisphere of controls (Holm–Sidak post hoc method, p Conclusion The rapid recovery of excitability and the persistent transcallosal disinhibition following perturbation of cortical activity may play a role in the pathophysiology of photosensitive epilepsy. Beyond the stereotyped dichotomy between generalized and focal epilepsies, our data seem to indicate PSE as a “system disease”.

Background ERPs occurring independently of any specific sensory event are purely endogenous (emitted potentials) and their neural generators univocally linked with cognitive components. Aim of the study was to localize and compare the sources of the scalp-recorded ERPs from two visual tasks: a standard two-stimulus oddball and an omitted-target oddball task, combining the high temporal resolution of electrophysiology with the fine spatial information provided by fMRI. Material and methods Thirteen healthy right-handed volunteers (5 females; mean age 26 years, range 22–29), were enrolled. The source modelling (dipole analysis) of ERPs was seeded to the clusters of fMRI activations. The simultaneous EEG-fMRI recording guaranteed the same cognitive states during the experimental session. Results Data depicted an antero-to-posterior neural circuitry for the rare, task–relevant events. P300 (P3b) was generated in frontal, temporo-parietal and parietal areas (these latter only in the standard oddball), namely the temporo-parietal junction (TPj), the premotor and motor area (M1) and the anterior intraparietal sulcus (aIPs). Anterior Insula contributed to the pP2, a recently described prefrontal component (different from the P3a) associated with the stimulus–response mapping. The anticipatory prefrontal negativity (pN) and Bereitschaftspotential (BP) were produced by anterior areas, namely the inferior and middle frontal gyrus over the lateral brain surface and the SMA-CMA areas over the medial cortex. Conclusions Recording emitted ERPs from omission of target stimuli in a simultaneous EEG-fMRI event-related paradigm allows a detailed spatio-temporal modeling of the neural generators of purely endogenous late potentials and provide useful insight to the interpretation of emitted/endogenous ERPs.

In the general population, transcranial anodal direct current stimulation of the cerebellum (ctDCS) reduces pain intensity and the amplitude of nociceptive laser evoked potentials (LEPs), whereas cathodal ctDCS elicits opposite effects. Since behavioral findings suggest that the cerebellar activity of highly hypnotizable individuals (highs) differs from the general population, we investigated whether hypnotizability-related differences occur in the modulation of pain by ctDCS. Sixteen healthy highs (according to the Stanford Hypnotic Susceptibility Scale, form A) and 16 participants not selected according to hypnotizability (controls) volunteered to undergo laser nociceptive stimulation of the dorsum of the left hand before and after anodal or cathodal ctDCS. LEPs amplitudes and latencies and the subjective pain experience (Numerical Rating Scale) were analyzed. Smaller LEP amplitudes and longer latencies were observed in highs with respect to controls independently of stimulation. After anodal and cathodal cerebellar stimulation, controls reported lower and higher pain than before it, respectively. In contrast, highs did not report significant changes in the perceived pain after both stimulations. They increased significantly their N2/P2 amplitude after anodal ctDCS and did not exhibit any significant change after cathodal tDCS, whereas controls decreased the N1 and N2P2 amplitude and increased their latency after anodal cerebellar stimulation and did the opposite after cathodal ctDCS. In conclusion, the study showed impaired cerebellar pain modulation and suggested altered cerebral cortical representation of pain in subjects with high hypnotizability scores.

Purpose As well as obtaining confirmation of the magnocellular system involvement in developmental dyslexia (DD); the aim was primarily to search for a possible involvement of the parvocellular system; and, furthermore, to complete the assessment of the visual chromatic axis by also analysing the koniocellular system. Methods Visual evoked potentials (VEPs) in response to achromatic stimuli with low luminance contrast and low spatial frequency, and isoluminant red/green and blue/yellow stimuli with high spatial frequency were recorded in 10 dyslexic children and 10 age- and sex-matched, healthy subjects. Results Dyslexic children showed delayed VEPs to both achromatic stimuli (magnocellular-dorsal stream) and isoluminant red/green and blue/yellow stimuli (parvocellular-ventral and koniocellular streams). To our knowledge, this is the first time that a dysfunction of colour vision has been brought to light in an objective way (i.e., by means of electrophysiological methods) in children with DD. Conclusion These results give rise to speculation concerning the need for a putative approach for promoting both learning how to read and/or improving existing reading skills of children with or at risk of DD. The working hypothesis would be to combine two integrated interventions in a single programme aimed at fostering the function of both the magnocellular and the parvocellular streams.

Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of the motor system. About 10% of cases are familial and 20% of these families have point mutations in the Cu/Zn superoxide dismutase 1 (SOD-1) gene. SOD-1 catalyses the superoxide radical (O−2) into hydrogen peroxide and molecular oxygen. The clinical neurophysiology in ALS plays a fundamental role in differential diagnosis between the familial and sporadic forms and in the assessment of its severity and progression. Sixty ALS patients (34 males; 26 females) were enrolled in the study and examined basally (T0) and every 4 months (T1, T2, and T3). Fifteen of these patients are SOD-1 symptomatic mutation carriers (nine males, six females). We used Macro-EMG and Motor Unit Number Estimation (MUNE) in order to evaluate the neuronal loss and the re-innervation process at the onset of disease and during follow-up period. Results and Discussion: SOD-1 mutation carriers have a higher number of motor units at the moment of diagnosis when compared with the sporadic form, despite a more dramatic drop in later stages. Moreover, in familiar SOD-1 ALS there is not a specific time interval in which the axonal regeneration can balance the neuronal damage. Taken together, these results strengthen the idea of a different pathogenetic mechanism at the base of sALS and fALS.

Introduction Non-invasive brain stimulation techniques, as repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), have recently emerged as promising tools for modulating pain experience in humans. In previous studies, we have proved that cerebellar tDCS modulates nociceptive processing and pain perception, suggesting that cerebellum is strongly engaged in the sensory-discriminative, as well as in the affective/emotional and cognitive dimensions of pain. The primary aim of this study is to evaluate the possibility to modulate nociceptive processing and pain perception with cerebellar tDCS in patients suffering from phantom limb pain (PLP). Methods Eight patients underwent cerebellar tDCS (anodal or sham, 2.0 mA, 20’ per day, five days a week). Inclusion criteria are: (1) age older than 18 years; (2) unilateral lower limb amputation; (3) average pain of at least 4 on a numeric rating scale; and (4) any medications dosages stable for at least two weeks prior the study. Clinical scores and electrophysiological parameters were assessed before tDCS, at the end of 5-days treatment, two weeks and one month after tDCS completion. Changes in Visual Analogue Scores (VAS) was evaluated (chronic pain, paroxysmal pain, stump pain, telescoping, phantom movements). LEPs were obtained using a Nd:YAP laser (wavelength 1.04 μ m, pulse 164 duration 2–20 ms, maximum energy 7 J). The amputated limb was stimulated by laser pulses with short duration (5 ms) and small diameter spots (5 mm). HADS, SF-36 and BPI were administered to each patient, in order to evaluate the effect of PLP on psychological well-being, daily living and the efficacy of the treatment to improve quality of life and reduce pain perception. Results Anodal tcDCS significantly reduced non painful phantom limb sensations (p Conclusion Anodal tcDCS significantly improves both painful and non painful phantom limb sensations, which are induced by maladaptive changes in the sensorimotor network and posterior parietal cortex respectively. Cerebellar polarization may ultimately restore this connectivity, as tcDCS may act not only on spinal nociceptive neurons, but also on wide-range cortical networks of the pain matrix, thus influencing LEPs and pain experience through top-down and bottom-up mechanisms.

Background Visuo-spatial disturbances could represent a clinical feature of early stage Alzheimer's disease (AD). The magnocellular (M) pathway has anatomo-physiological characteristic which make it more suitable for detecting form, motion and depth compared with parvocellular one (P). Objective Aim of our study was to evaluate specific visual subsystem involvement in a group of AD patients, recording isoluminant chromatic and luminance pattern electroretinograms and pattern visual evoked potentials. Material and methods data were obtained from 15 AD patients (9 females and 6 males, mean age ± 1SD: 77.6 ± 4.01 years) not yet undergoing any treatment, and from 10 age-matched healthy controls. Diagnosis of probable AD was clinically and neuroradiologically established. PERGs were recorded monocularly in response to equiluminant red-green (R-G), blue-yellow (B-Y) and luminance yellow-black (Y-Bk) horizontal square gratings of 0.3 c/deg and 90% contrast, reversed at 1 Hz. VEPs were recorded in response to full-field (14 deg) equiluminant chromatic R-G, B-Y and luminance Y-Bk sinusoidal gratings of 2 c/deg, presented in onset (300 ms)–offset (700 ms) mode, at the contrast levels of 90%. Results All data were retrieved in terms of peak-amplitude and latency and assessed using the Student's t -test for paired data. Temporal differences of PERGs and VEPs, evoked by Y-Bk grating in AD patients compared with controls, suggest a specific impairment of the magnocellular stream. Conclusions Our study support the hypothesis that the impairment of the PERGs and VEPs arising from the magnocellular streams of visual processing may indicate a primary dysfunction of the M-pathways in AD.

Blood oxygenation level dependent (BOLD) response related to interictal activity was evaluated in a patient with post-traumatic focal epilepsy at repeated continuous electroencephalogram (EEG)-functional magnetic resonance imaging examinations. Lateralized interictal EEG activity induced a main cluster of activation co-localized with the anatomical lesion. Spreading of EEG interictal activity to both frontal lobes evoked bilateral clusters of activation indicating that topography of BOLD response might depend on the spatial distribution of epileptiform activity.

Voxel-based morphometry (VBM) enables an unbiased in-vivo whole-brain quantitative analysis of differences in gray matter (GM), white matter (WM) and cerebro-spinal fluid (CSF) volumes. We assessed with VBM 20 spinocerebellar ataxia Type 2 (SCA2) patients with mild or moderate cerebellar deficit and 20 age and sex-matched healthy controls. SCA2 patients showed a significant (P 0.01) correlation was observed between the GM and WM loss and severity of the neurological deficit. In SCA2 patients with mild to moderate cerebellar deficit, GM and WM volume loss and CSF volume increase are confined to the posterior cranial fossa.

The aim of our study was to evaluate Motor Evoked Potentials (MEPs) and cortical excitability, using Transcranial Magnetic Stimulation (TMS) as well as short latency Somatosensory Evoked Potentials (SEPs) in Autosomal Dominant Hereditary Spastic Paraparesis (ADHSP) patients. MEPs were recorded from upper and lower limb muscles in 12 patients (7 m and 5f) affected by ADHSP with spastin mutation (SPG4). We measured: (i) motor threshold (MTh); (ii) total motor conduction time (TMCT); (iii) direct and indirect central motor conduction time (d-CMCT and i-CMCT) calculated by subtracting from the cortical latency those obtained on magnetic spinal stimulation (d-PMCT) and via the F-wave method (i-PMCT); (iv) MEP amplitude (MEP/Mmax ratio%) and (v) duration of the cortical silent period (CSP). Latency, amplitude and persistence of the F-wave obtained with electrical nerve stimulation were also considered; H reflex was also tested from lower extremities. SEPs were recorded from spine and scalp sites following median and posterior tibial nerve stimulation; conventional latency and amplitude measurements were performed. In a comparison with the control group, the MTh recording from lower limbs was significantly higher (67.5 +/- 7.7% versus 52.5 +/- 6.9%), MEPs were absent in one case and showed reduced amplitude in the remainders (22.9 +/- 12.6% versus 66.3 +/- 25.9% of M wave); TMCT resulted to be abnormal (36.5 +/- 3.9 ms versus 27.1 +/- 1.4 ms) and d-CMCT as well as i-CMCT were significantly prolonged (23.1 +/- 3.5 ms versus 13.8 +/- 1.3 ms; and 20.1 +/- 3.4 ms versus 10.6 +/- 1.3 ms, respectively). The CSP, which was normal from the hands, was significantly shortened from the legs and correlated with spasticity scoring (Ashworth scale). Cortical SEPs from lower limbs were abnormal in all cases, whereas SEPs by stimulation of median nerves were normal; F-wave parameters from upper limbs showed no abnormalities, whereas an increased persistence was detected from lower limbs; H reflex amplitudes resulted larger compared with controls. Moreover, shortening of the CSP, being correlated with the Ashworth scale, can be considered an electrophysiological marker of spasticity that seems to arise from impairment of the supraspinal or intracortical inhibitory pathways with an additional contribution of increased segmental motor neuron excitability. These data prove the existence of comparable neurophysiological abnormalities in ADHSP with spastin mutation (SPG4) when long ascending and descending pathways are involved.