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Background: Therapeutic plasma exchange (TPE) is a highly effective rescue treatment for patients with acute exacerbation of neuroimmunological disease that removes circulating autoantibodies and inflammatory components from the bloodstream. The aims of this study are to explore the safety and the effectiveness of TPE in patients with autoimmune neurological disorders. Methods: We retrospectively evaluated the frequency of adverse events (AEs) and the effectiveness of TPE using the modified Ranking Scale (mRS) in patients with acute neurological flares who underwent TPE at the University Hospital of Palermo. Results: Of 59 patients, the majority underwent TPE due to multiple sclerosis (MS) relapse. In 23.7% of cases, TPE was performed before obtaining a definite diagnosis due to the severity of the clinical presentation. After TPE, the mRS score was globally reduced (p < 0.0001), and this effect was marked in patients with MS, Guillain–Barré syndrome, and myasthenia gravis crisis but not in those with paraneoplastic syndromes. Circulating pathogenetic antibodies, younger age, and the early use of TPE were factors strongly associated with TPE effectiveness. The overall safety profile of TPE was satisfactory with an AE frequency of 15%. Conclusions: These results highlight the early use of TPE in patients with circulating pathogenetic antibodies as well as its favorable safety profile.

Migraine is one of the most prevalent and disabling neurological conditions, presenting episodes of throbbing headache that limit activities of daily living. Several factors may influence migraine frequency, such as lifestyle or alcohol consumption. Among the most recognised ones, sleep plays a biunivocal role, since poor sleep quality may worsen migraine frequency, and a high migraine frequency may affect sleep quality. In this paper, the authors evaluate the relationship between migraine and insomnia by exploring a cohort of patients affected by episodic or chronic migraine. To do so, a phone interview was performed, asking patients about their migraine frequency and mean pain intensity, in addition to the questions of the Insomnia Severity Index. The last one explores several symptoms impairing sleep that focus on insomnia. Patients complaining of insomnia showed an increased migraine frequency, and a weak but significant correlation was found between headache days per month and insomnia scores. Such results were particularly evident in patients affected by chronic migraine. Such results suggest how insomnia, in the presented data, seems to be associated with migraine frequency but not with pain intensity.

Background/Objectives: Increasing evidence shows an involvement of brain plasticity mechanisms in both motor and central manifestations of neuromuscular disorders (NMDs). These mechanisms could be specifically addressed with neuromodulation or rehabilitation protocols. The aim of this scoping review is to summarise the evidence on plasticity mechanisms’ involvement in NMDs to encourage future research. Methods: A scoping review was conducted searching the PubMed and Scopus electronic databases. We selected papers addressing brain plasticity and central nervous system (CNS) studies through non-invasive brain stimulation techniques in myopathies, muscular dystrophies, myositis and spinal muscular atrophy. Results: A total of 49 papers were selected for full-text examination. Regardless of the variety of pathogenetic and clinical characteristics of NMDs, studies show widespread changes in intracortical inhibition mechanisms, as well as disruptions in glutamatergic and GABAergic transmission, resulting in altered brain plasticity. Therapeutic interventions with neurostimulation techniques, despite being conducted only anecdotally or on small samples, show promising results; Conclusions: despite challenges posed by the rarity and heterogeneity of NMDs, recent evidence suggests that synaptic plasticity may play a role in the pathogenesis of various muscular diseases, affecting not only central symptoms but also strength and fatigue. Key questions remain unanswered about the role of plasticity and its potential as a therapeutic target. As disease-modifying therapies advance, understanding CNS involvement in NMDs could lead to more tailored treatments.

IntroductionCharcot–Marie–Tooth disease (CMT) is an inherited neuropathy that affects the sensory and motor nerves. It can be considered the most common neuromuscular disease, with a prevalence of 1/2500.MethodsConsidering the absence of a specific medical treatment and the benefits shown by physical activity in this population, a systematic review was completed using several search engines (Scopus, PubMed, and Web of Science) to analyze the use, effectiveness, and safety of a training program performed in telecoaching (TC). TC is a new training mode that uses mobile devices and digital technology to ensure remote access to training.ResultsOf the 382 studies identified, only 7 met the inclusion criteria. The effects of a TC training program included improvements in strength, cardiovascular ability, and functional abilities, as well as gait and fatigue. However, the quality of the studies was moderate, the size of the participants in each study was small, and the outcome measured was partial.DiscussionAlthough many studies have identified statistically significant changes following the administration of the TC training protocol, further studies are needed, with appropriate study power, better quality, and a higher sample size.

Background: Myasthenia gravis (MG) is an autoimmune disease characterized by fluctuating muscle weakness due to autoantibodies targeting neuromuscular junction proteins. Mycophenolate mofetil (MMF), an immunosuppressive therapy, has shown potential for managing MG with fewer side effects compared to other treatments. This study aims to evaluate the effectiveness and safety of MMF in MG patients in a real-life multicenter setting. Methods: A retrospective cohort study was conducted on generalized MG patients, refractory to azathioprine (AZA) and treated with MMF alone or with steroids, at three Italian centers from January 2011 to February 2024. Patients were assessed using the Myasthenia Gravis Foundation of America (MGFA) classification, MG composite score (MGCS), and MG activity of daily living (MGADL) scores at baseline, 6, 12, 18, and 24 months. Statistical analyses included the Spearman correlation, the Friedman test, and ANOVA. Results: Thirty-two patients were enrolled (13 males, mean age 66.5 ± 11.5 years). Significant improvements in MGADL and MGCS scores were observed at 6 and 12 months (p < 0.001), with continued improvement over 24 months. Side effects were reported in 12% of patients. MMF showed a faster onset of symptom control compared to azathioprine, with a significant improvement noted within 6 months. Conclusions: A recent study found that MMF and AZA were equally effective in improving patients’ quality of life, but because AZA had more serious adverse events than MMF, lower doses of AZA were therefore recommended to reduce the adverse events while maintaining efficacy. Conversely, results showed that MMF is effective and well-tolerated in the long-term management of MG, providing faster symptom control and a favorable safety profile. Future prospective studies with larger cohorts are needed to confirm these findings and explore sex differences in response to MMF treatment.

Background: Patients with age-related white matter changes (ARWMC) frequently present a gait disorder, depression and cognitive impairment. Our aims are to define which alterations in the gait parameters are associated with motor or neuro-psychological impairment and to assess the role of motor, mood or cognitive dysfunction in explaining the variance of the gait parameters. Methods: Patients with gait disorders admitted to a Neuro-rehabilitation Department, affected by vascular leukoencephalopathy who had ARWMC confirmed by a brain MRI, were consecutively enrolled, classified by a neuroradiological scale (Fazekas 1987) and compared to healthy controls. We excluded subjects unable to walk independently, subjects with hydrocephalus or severe aphasia, with orthopaedic and other neurological pathologies conditioning the walking pattern. Patients and controls were assessed by clinical and functional scales (Mini Mental State Examination, Geriatric Depression Scale, Nevitt Motor Performance Scale, Berg Balance Scale, Functional Independence Measure), and computerised gait analysis was performed to assess the spatial and temporal gait parameters in a cross-sectional study. Results: We recruited 76 patients (48 males, aged 78.3 ± 6.2 years) and 14 controls (6 males, aged 75.8 ± 5 years). In the multiple regression analysis, the gait parameter with overall best model summary values, associated with the ARWMC severity, was the stride length even after correction for age, sex, weight and height (R2 = 0.327). The motor performances justified at least in part of the gait disorder (R2 change = 0.220), but the mood state accounted independently for gait alterations (R2 change = 0.039). The increase in ARWMC severity, the reduction of motor performance and a depressed mood state were associated with a reduction of stride length (R = 0.766, R2 = 0.587), reduction of gait speed (R2 = 0.573) and an increase in double support time (R2 = 0.421). Conclusion: The gait disorders in patients with ARWMC are related to motor impairment, but the presence of depression is an independent factor for determining gait alterations and functional status. These data pave the way for longitudinal studies, including gait parameters, to quantitatively assess gait changes after treatment or to monitor the natural progression of the gait disorders.

The cluster headache is a primary headache characterized by attacks of unilateral pain associated with ipsilateral cranial autonomic features. These attacks recur in clusters during the years alternating with periods of complete remission, and their onset is often during the night. This annual and nocturnal periodicity hides a strong and mysterious link among CH, sleep, chronobiology and circadian rhythm. Behind this relationship, there may be the influence of genetic components or of anatomical structures such as the hypothalamus, which are both involved in regulating the biological clock and contributing even to the periodicity of cluster headaches. The bidirectional relationship manifests itself also with the presence of sleep disturbances in patients affected by cluster headaches. What if the key to studying the physiopathology of such disease could rely on the mechanisms of chronobiology? The purpose of this review is to analyze this link in order to interpret the pathophysiology of cluster headaches and the possible therapeutic implications.

Hereditary transthyretin amyloidosis (hATTR) is a multisystemic, rare, inherited, progressive and adult-onset disease, affecting the sensory-motor nerves, heart, autonomic function, and other organs. There are over 130 mutations known in the TTR gene. The His90Asn mutation has been previously reported in several reports, but its pathogenetic role is still debated. We report two sporadic cases of adult women with a heterozygous His90Asn mutation in TTR gene and neurological involvement extensively investigated. A typical Congo red-positive pathologic deposition of amyloid fibrils in the salivary glands was documented in one subject. Patients were successfully treated with patisiran with a good clinical outcome. These data support a pathogenetic role of His90Asn mutation in hATTR, and suggest early treatment in symptomatic carriers of His90Asn mutation.

Chronic migraine is a disease with a high burden on patients from both a working and quality of life point of view. The pathophysiology of this subtype of migraine is due to several factors, such as medication overuse. Nevertheless, the detrimental recurring of headache attacks with central and peripheral sensitization plays a central role and explains some additional symptoms complained about by these patients even in the interictal phase. OnabotulinumtoxinA is a therapy indicated for chronic migraine since it has proven to reduce peripheral sensitization, showing even efficacy on central symptoms. The aim of this narrative review is to present the current evidence regarding the effect of OnabotulinumtoxinA on sensitization and interictal symptoms.

The pathophysiological mechanisms underlying migraine are more difficult to investigate in children than in the adult population. Abnormal cortical excitability turns out to be one of the most peculiar aspects of migraine, accounting for the manifestations of migraine attacks. Recently, visual cortical excitability has been explored effectively in adult migraineurs with a technique based on cross-modal audio-visual illusions (with sound-induced flash illusions (SIFIs) being reduced in migraineurs compared to non-migraineur subjects). On such a basis, in this study, we investigated visual cortical excitability in children with migraine using SIFIs using combinations of visual and sound stimuli presented randomly. We evaluated 26 children with migraine without aura and 16 healthy children. Migraineurs did not differ from the age-matched healthy subjects regarding fission or fusion illusions but perceived more flashes in trials of multiple flashes with or without beeps. The higher number of SIFIs in migraineur children compared to adults may be due to a greater propensity of visual stimulation to be driven by auditory stimuli (i.e., acoustic dominance). The increased ability to perceive flashes reveals a hyperfunctional visual cortex, demonstrating that the use of SIFIs is a valid tool for assessing visual cortical responsiveness even in pediatric migraine.

In recent years, our knowledge rapidly increased with respect to the immunology and immunological aspects of neuromuscular disorders [...].

Migraine is a burdensome neurological disorder that still lacks clear and easily accessible diagnostic biomarkers. Furthermore, a straightforward pathway is hard to find for migraineurs’ management, so the search for response predictors has become urgent. Nowadays, artificial intelligence (AI) has pervaded almost every aspect of our lives, and medicine has not been missed. Its applications are nearly limitless, and the ability to use machine learning approaches has given researchers a chance to give huge amounts of data new insights. When it comes to migraine, AI may play a fundamental role, helping clinicians and patients in many ways. For example, AI-based models can increase diagnostic accuracy, especially for non-headache specialists, and may help in correctly classifying the different groups of patients. Moreover, AI models analysing brain imaging studies reveal promising results in identifying disease biomarkers. Regarding migraine management, AI applications showed value in identifying outcome measures, the best treatment choices, and therapy response prediction. In the present review, the authors introduce the various and most recent clinical applications of AI regarding migraine.

Background: Hereditary transthyretin amyloidosis is a rare disease caused by transthyretin (TTR) gene mutations. The aim of our study was to identify early signs of cardiac involvement in patients with a TTR gene mutation in order to differentiate carriers from patients with neurological or cardiac disease. Methods: A case–control study was carried out on 31 subjects with the TTR mutation. Patients were divided into three groups: 23% with cardiac amyloidosis and polyneuropathy (group A), 42% with only polyneuropathy (group B) and 35% carriers (group C). Speckle-tracking echocardiography (left-ventricular global longitudinal strain—GLS, atrial stiffness) was performed in all patients. The apical/basal longitudinal strain ratio (SAB) and relative apical sparing (RAS) were assessed in all subjects. Results: Analyzing groups C and B, we only found a significant difference in the SAB (p-value 0.001) and RAS (p-value 0.039). These parameters were significantly more impaired in group A compared to group B (SAB p-value 0.008; RAS p-value 0.002). Also, atrial stiffness was significantly impaired in groups A and B compared to group C. Conclusions: Our study suggests the diagnostic role of the SAB and RAS in cardiac amyloidosis. The SAB and RAS showed a gradual increase from carriers to patients with neurological and cardiac diseases. Thus, these parameters, in addition to atrial stiffness, could be used to monitor carriers. More extensive data are needed.

Abstract Neurological vertigo is a common symptom in children and adults presenting to the emergency department (ED) and its evaluation may be challenging, requiring often the intervention of different medical specialties. When vertigo is associated with other specific symptoms or signs, a differential diagnosis may be easier. Conversely, if the patient exhibits isolated vertigo, the diagnostic approach becomes complex and only through a detailed history, a complete physical examination and specific tests the clinician can reach the correct diagnosis. Approach to vertigo in ED is considerably different in children and adults due to the differences in incidence and prevalence of the various causes. The aim of this systematic review is to describe the etiopathologies of neurological vertigo in childhood and adulthood, highlighting the characteristics and the investigations that may lead clinicians to a proper diagnosis. Finally, this review aims to develop an algorithm that could represent a valid diagnostic support for emergency physicians in approaching patients with isolated vertigo, both in pediatric and adult age.

Background and aims. Patients with Myasthenia gravis (MG) are considered vulnerable as they may present with respiratory muscle weakness and because they are on immunosuppressive treatment; thereby, COVID-19 may have a detrimental effect on these patients. Vaccines against COVID-19 are currently available and it has been shown as they can prevent severe COVID-19 in vulnerable patients. Notwithstanding their efficacy, vaccine hesitancy has not been completely dispelled in the general population. Unfortunately, there is limited data about the safety of these vaccines in MG patients. The aims of this study are to evaluate the impact of COVID-19 in a MG cohort, the adherence to COVID-19 vaccination in Italy and vaccine safety in MG patients. Methods. A retrospective cohort study of MG patients attending the Neuromuscular Clinic of the University Hospital “Paolo Giaccone” of Palermo, Italy, was performed. Patients underwent telephone interviews with a dedicated questionnaire on SARS-CoV-2 vaccination and infection. Vaccine safety was assessed though the evaluation of vaccine-related adverse events (AEs) and comparisons of MG-ADL scores before and after vaccination. Patient worsening was defined as two or more point increases in MG-ADL scores. Results. From a total of 90 participants, 75 answered the questionnaire and 70.5% of them (n = 53) received the vaccine; ten patients did not receive vaccination and 3 patients were partially vaccinated. Among the vaccinated patients, about 45% (n = 24) experienced at least one AE, with a complete resolution within one week. No serious AEs and life-threatening conditions were observed. Globally, MG-ADL scores did not worsen after vaccination. Nine unvaccinated patients experienced SARS-CoV2 infection and four of them (44%) died—one patient required respiratory support, whereas three patients were asymptomatic. Conclusions. COVID-19 significantly impacted MG patients with an increase in mortality due to respiratory sequelae. Vaccines against SARS-CoV-2 showed good short-term safety in MG patients, who may take advantage of vaccination to avoiding life-threatening complications such as COVID-19 pneumonia.

Autoimmune neuromuscular diseases are a group of heterogenous pathologies secondary to the activation of the immune system that damage the structures of the peripheric nerve, the neuromuscular junction, or the skeleton muscle. The diagnosis of autoimmune neuromuscular disorders comprises a combination of data from clinical, laboratory, electromyography, imaging exam, and biopsy. Particularly, the whole-body MRI examination in the last two decades has been of great use in the assessment of neuromuscular disorders. MRI provides information about the structures involved and the status of activity of the disease. It can also be used as a biomarker, detect the pattern of specific muscle involvement, and is a useful tool for targeting the optimal muscle site for biopsy. In this work, we summarized the most used technical protocol of whole-body MRI and the role of this imaging technique in autoimmune neuromuscular disorders.

Myasthenia gravis (MG) is an antibody-mediated neuromuscular disease affecting the neuromuscular junction. In most cases, autoantibodies can be detected in the sera of MG patients, thus aiding in diagnosis and allowing for early screening. However, there is a small proportion of patients who have no detectable auto-antibodies, a condition termed “seronegative MG” (SnMG). Several factors contribute to this, including laboratory test inaccuracies, decreased antibody production, immunosuppressive therapy, immunodeficiencies, antigen depletion, and immune-senescence. The diagnosis of SnMG is more challenging and is based on clinical features and neurophysiological tests. The early identification of these patients is needed in order to ensure early treatment and prevent complications. This narrative review aims to examine the latest updates on SnMG, defining the clinical characteristics of affected patients, diagnostic methods, management, and therapeutic scenarios.

Chronic migraine is a burdensome condition, and onabotulinumtoxinA is revealed to be an effective therapy. Migraine shows a bidirectional relationship with sleep, but the effects of preventive therapies on sleep quality are poorly studied. This study aims to evaluate the effects of a single session of onabotulinumtoxinA on patients’ sleep quality and correlates the results with measures of comorbid anxiety/depression. Patients completed self-administrable questionnaires about sleep quality (Pittsburgh Sleep Quality Index—PSQI) and psychological symptoms (Beck Depression Inventory, 2nd edition—BDI-II—and Hospital Anxiety and Depression Scale—HADS—subscales “a” and “d” for anxiety and depression, respectively), and reported migraine frequency at baseline and after 12 weeks. The 42 included patients showed a significant reduction in migraine days (from 20.6 ± 6.0 to 13.6 ± 6.2, p < 0.001), while no changes were observed in sleep quality (PSQI score from 11.0 ± 5.0 to 9.8 ± 4.6, p = 0.277) or psychological measures (BDI-II from 16.7 ± 10.2 to 15.7 ± 10.3, p = 0.678; HADS-a from 10.3 ± 4.8 to 9.3 ± 5.5, p = 0.492; and HADS-d from 7.2 ± 3.9 to 7.1 ± 5.0, p = 0.901). On the other hand, a strong correlation among PSQI, BDI-II, HADS-a, and HADS-d scores (p < 0.001, rho > 0.7) was found. Despite its efficacy in migraine prevention, a single session of onabotulinumtoxinA was not able to affect patients’ sleep quality or their psychological symptoms.

The median-to-ulnar communicating branch (MUC) is an asymptomatic variant of the upper limb innervation that can lead to interpretation errors in routine nerve conduction studies. The diagnosis of carpal tunnel syndrome (CTS) or ulnar nerve lesions can be complicated by the presence of MUC. In this study, we describe electrophysiological features of MUC in CTS patients presenting to our clinic. We enrolled MUB cases from consecutive CTS patients referred to our laboratory between the years 2014 and 2019. MUC was present in 53 limbs (36 patients) from the studied population. MUC was bilateral in 53% of patients. MUC type II was the most common subtype (74%), followed by types III and I; more coexisting MUC types were found in the majority of tested limbs. A positive correlation was demonstrated between the severity of CTS and the presence of positive onset, faster CV, or a double component of the compound muscle action potentials. We emphasize the importance of suspecting the presence of MUC in CTS in the presence of a positive onset or a double component in routine motor conduction studies.

Pseudoneglect phenomenon refers to a condition in which healthy subjects tend to perceive the left side of exactly bisected lines as being slightly longer than the right one. However, behavioural data showed that athletes practising an open-skill sport display less pseudoneglect than the general population. Given the fact that so-called exergames (also known as active video games) are platforms designed to fully mimic sport activity, this work intends to investigate whether and how a one-week training period of exergame open-skill sport can determine a similar decrease in pseudoneglect. Fifteen healthy participants (non-athletes) responded to a visuospatial attention task and a control memory task in basal conditions (t0: Pre-game) and after a short period (one week, one hour/day) of tennis exergaming (t1: Post-game). In the Post-game condition, subjects from this experimental group (ExerGame group: EG) reduced leftward space overestimation and made significantly fewer leftward errors compared to the Pre-game condition. Additionally, two other experimental groups were employed: one evaluated within the same conditions of the main experiment but using a non-exergame (Non-Exergame groups: NEG) and the other one without any video game stimulus (Sedentary group: SE). Our findings suggest that daily training of a tennis exergame seems to be able to improve visuospatial attention isotropy by reducing leftward space overestimation, whereas outcomes from non-exergaming and sedentary activity do not modify subjects’ performance.

Background: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is an adult-onset multisystemic disease, affecting the peripheral nerves, heart, gastrointestinal tract, eyes, and kidneys. Nowadays, several treatment options are available; thus, avoiding misdiagnosis is crucial to starting therapy in early disease stages. However, clinical diagnosis may be difficult, as the disease may present with unspecific symptoms and signs. We hypothesize that the diagnostic process may benefit from the use of machine learning (ML). Methods: 397 patients referring to neuromuscular clinics in 4 centers from the south of Italy with neuropathy and at least 1 more red flag, as well as undergoing genetic testing for ATTRv, were considered. Then, only probands were considered for analysis. Hence, a cohort of 184 patients, 93 with positive and 91 (age- and sex-matched) with negative genetics, was considered for the classification task. The XGBoost (XGB) algorithm was trained to classify positive and negative TTR mutation patients. The SHAP method was used as an explainable artificial intelligence algorithm to interpret the model findings. Results: diabetes, gender, unexplained weight loss, cardiomyopathy, bilateral carpal tunnel syndrome (CTS), ocular symptoms, autonomic symptoms, ataxia, renal dysfunction, lumbar canal stenosis, and history of autoimmunity were used for the model training. The XGB model showed an accuracy of 0.707 ± 0.101, a sensitivity of 0.712 ± 0.147, a specificity of 0.704 ± 0.150, and an AUC-ROC of 0.752 ± 0.107. Using the SHAP explanation, it was confirmed that unexplained weight loss, gastrointestinal symptoms, and cardiomyopathy showed a significant association with the genetic diagnosis of ATTRv, while bilateral CTS, diabetes, autoimmunity, and ocular and renal involvement were associated with a negative genetic test. Conclusions: Our data show that ML might potentially be a useful instrument to identify patients with neuropathy that should undergo genetic testing for ATTRv. Unexplained weight loss and cardiomyopathy are relevant red flags in ATTRv in the south of Italy. Further studies are needed to confirm these findings.

Abstract Background To investigate the genetic and environmental factors responsible for phenotype variability in a family carrying a novel CACNA1A missense mutation. Mutations in the CACNA1A gene were identified as responsible for at least three autosomal dominant disorders: FHM1 (Familial Hemiplegic Migraine), EA2 (Episodic Ataxia type 2), and SCA6 (Spinocerebellar Ataxia type 6). Overlapping clinical features within individuals of some families sharing the same CACNA1A mutation are not infrequent. Conversely, reports with distinct phenotypes within the same family associated with a common CACNA1A mutation are very rare. Case presentation A clinical, molecular, neuroradiological, neuropsychological, and neurophysiological study was carried out in proband and his carrier mother. The new heterozygous missense variant c.4262G > A (p.Arg1421Gln) in the CACNA1A gene was detected in the two affected family members. The proband showed a complex clinical presentation characterized by developmental delay, poor motor coordination, hemiplegic migraine attacks, behavioral dysregulation, and EEG abnormalities. The mother showed typical episodic ataxia attacks during infancy with no other comorbidities and mild cerebellar signs at present neurological evaluation. Conclusions The proband and his mother exhibit two distinct clinical phenotypes. It can be hypothesized that other unknown modifying genes and/or environmental factors may cooperate to generate the wide intrafamilial variability.

PurposeHereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils. The clinical phenotype is heterogeneous, and characterized by a multisystemic disease affecting the sensorimotor and autonomic functions along with other organs.Materials and MethodsAll the patients were assessed by complete neurological assessment, neurophysiological evaluation, of the median nerve, and handgrip analysis. The data are presented as means and standard deviations. Parametric and non-parametric assessments have been performed to identify differences between groups. Pearson's correlation has been carried out when appropriate.ResultsTwenty patients with ATTRv (66.1 ± 8.4 years; eight females) and 30 controls (61.1 ± 11.6 years; 16 females) were enrolled. Handgrip strength was reduced in patients with ATTR in both right and left hands compared to the controls. Significant differences were found between patients and controls in the right (handgrip right, HGSR TTR 21.1 ± 13 kg vs. HGSR Control 29.4 ± 11.3 kg, p = 0.017) and left (handgrip left, HGSL TTR 22.2 ± 10.7 kg. vs. HGSL Control 31 ± 11.3 kg, p = 0.007). NIS and CMAP amplitude of the median nerve were related to HGS measures for both hands in patients with ATTRv.ConclusionsThe progression of bilateral carpal tunnel syndrome is related to neurophysiological data in the median nerve in ATTRv. Also, handgrip measures might represent an important tool for the assessment of disease progression in ATTRv. We propose using a combination of CMAP amplitude and HGS for the assessment of hand motor strength in ATTRv.

Objectives. Fibromyalgia (FM) is characterized by spontaneous chronic widespread pain in combination with hyperalgesia to pressure stimuli. Sound-induced flash illusions (SIFIs) reflect cross-modal interactions between senses allowing to assess a visual cortical hoerexcitability (VCH) by evaluating the fission and fusion illusions disruption. The aims of the present study were to explore whether SIFIs are perceived differently in patients with fibromyalgia as compared to healthy controls (HCs) and how migraine affects fission and fusion illusions in fibromyalgia. Methods. A single flash (F) accompanied by 0 to 4 beeps (B) was presented to induce the fission illusion while multiple flash (i.e., 2 to 4) accompanied by 0 or 1 beep was presented to induce fusion illusion. The mean number of perceived flashes in fission and fusion illusion trials was compared between the groups (i.e., FM, FM with migraine, and HCs) using repeated-measures analysis of variance. Medication history was recorded along with the administration of Fibromyalgia Impact Questionnaire and Hospital Anxiety and Depression scales. Results. Twenty-four patients with FM (mean age 51, 2 ± 10, 6 years; 22 females), seventeen patients with FM and migraine without aura (mean age 47.8 ± 11.4 years; 16 females; 13 chronic, 4 episodic migraine), and forty-one age- and sex-matched HCs (mean age 47.3 ± 6.9 years; 34 females) participated in the study. Fission and fusion illusory effects were detected in all the participants. However, in FM patients, the fission illusion was reduced and almost abolished as compared to HCs (1F1B, p=0.02; 1F2B, p

Mitochondrial tRNASer(UCN) is considered a hot-spot for non-syndromic and aminoglycoside-induced hearing loss. However, many patients have been described with more extensive neurological diseases, mainly including epilepsy, myoclonus, ataxia, and myopathy. We describe a novel homoplasmic m.7484A>G mutation in the tRNASer(UCN) gene affecting the third base of the anticodon triplet in a girl with profound intellectual disability, spastic tetraplegia, sensorineural hearing loss, a clinical history of epilepsia partialis continua and vomiting, typical of MELAS syndrome, leading to a myoclonic epilepticus status, and myopathy with severe COX deficiency at muscle biopsy. The mutation was also found in the homoplasmic condition in the mother who presented with mild cognitive deficit, cerebellar ataxia, myoclonic epilepsy, sensorineural hearing loss and myopathy with COX deficient ragged-red fibers consistent with MERRF syndrome. This is the first anticodon mutation in the tRNASer(UCN) and the second homoplasmic mutation in the anticodon triplet reported to date.

Background: Antibodies against acetylcholine receptors (AChRs) can also target nicotinic AChRs that are present throughout the central nervous system, thus leading to cognitive dysfunctions in patients with myasthenia gravis (MG). However, the presence of cognitive impairment in MG is controversial, and the factors that may influence this risk are almost completely unknown. In this study, the frequency of mild cognitive impairment (MCI) in MG, as well as the clinical, immunological, and behavioral correlates of MCI in MG were evaluated. Methods: A total of 52 patients with MG underwent a comprehensive assessment including motor and functional scales, serological testing, and neuropsychological and behavioral evaluation. Results: The frequency of MCI was 53.8%, and the most impaired cognitive domains were, in order, visuoconstructive/visuospatial skills, memory, and attention. After multivariate analysis, only pyridostigmine use was inversely associated with the presence of MCI, while a trend toward a positive association between MCI and disease severity and arms/legs hyposthenia was found. Correlation analyses showed that daily doses of prednisone and azathioprine significantly correlated with depressive symptomatology, while disease severity significantly correlated with depressive symptomatology and sleep disturbance. Conclusions: The presence of MCI is rather frequent in MG and is characterized by multidomain amnestic impairment. Such preliminary data need further confirmation on larger case series.

Von Hippel-Lindau (VHL) disease is an autosomal dominant condition that predisposes affected individuals to a variety of malignant and benign neoplasms. The pathogenetic turning point of this illness is the accumulation of hypoxia-inducible factor (HIF)-1α, a transcription factor of several genes involved in oncogenesis, angiogenesis, tissue regeneration, metabolic regulation, hematopoiesis, and inflammatory responses. From an oncological perspective, increased awareness of the molecular pathways underlying this disease is bringing us closer to the development of specific and targeted therapies. Meanwhile, on the surgical side, improved understanding can help to better identify the patients to be treated and the surgical timing. Overall, pathogenesis research is crucial for developing patient-tailored therapies. One of the actual key topics of interest is the link between the VHL/HIF axis and inflammation. The present study aims to outline the fundamental mechanisms that link VHL disease and immune disorders, as well as to explore the details of the overlap between VHL disease and myasthenia gravis (MG) pathogenetic pathways. As a result, MG becomes a paradigm for autoimmune disorders that might be related with VHL disease.

Chronic migraine is a burdensome disease presenting with episodic pain and several symptoms that may persist even among headache attacks. Multisensory integration is modified in migraine, as assessed by the level of the perception of sound-induced flash illusions, a simple paradigm reflecting changes in cortical excitability which reveals to be altered in migraineurs. OnabotulinumtoxinA is an effective preventive therapy for chronic migraineurs, reducing peripheral and central sensitization, and may influence cortical excitability. Patients affected by chronic migraine who started onabotulinumtoxinA preventive therapy were included. Clinical effects (headache diaries and migraine related questionnaires) were assessed at the beginning of the therapy and after 12 weeks. Contextually, patients underwent the evaluation of multisensory perception by means of the sound-induced flash illusions. OnabotulinumtoxinA showed effectiveness both in migraine prevention and in reducing headache burden. Even one session of therapy was able to restore, at least partially, multisensory processing, as shown by patients’ susceptibility to the sound-induced flash illusion. OnabotulinumtoxinA could influence migraineurs cortical excitability concurrently to the beneficial effects in headache prevention.

Background and aims. Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils. The clinical phenotype is heterogeneous, characterized by a multisystemic disease affecting the sensorimotor, autonomic functions along with other organs. Patisiran is a small interfering RNA acting as a TTR silencer approved for the treatment of ATTRv. Punctual and detailed instrumental biomarkers are on demand for ATTRv to measure the severity of the disease and monitor progression and response to treatment. Methods. Fifteen patients affected by ATTRv amyloidosis (66.4 ± 7.8 years, six males) were evaluated before the start of therapy with patisiran and after 9-months of follow-up. The clinical and instrumental evaluation included body weight and height; Coutinho stage; Neuropathy Impairment Score (NIS); Karnofsky performance status (KPS); Norfolk QOL Questionnaire; Six-minute walking test (6 MWT); nerve conduction studies; handgrip strength (HGS); and bioimpedance analysis (BIA). Results. Body composition significantly changed following the 9-months pharmacological treatment. In particular, the patients exhibited an increase in fat free mass, body cell mass, and body weight with a decrease in fat mass. A significant increase after 9 months of treatment was observed for the 6 MWT. Coutinho stage, KPS, NIS, NIS-W, nerve conduction studies, Norfolk, COMPASS-31 scale, and HGS remained unchanged. Conclusions. BIA might represent a useful tool to assess the effects of multiorgan damage in ATTRv and to monitor disease progression and response to treatments. More evidence is still needed for HGS. Patisiran stabilizes polyneuropathy and preserves motor strength by increasing muscle mass after 9 months of treatment.

Background: chronic idiopathic demyelinating polyneuropathy (CIDP) is an acquired, immune-mediated neuropathy characterized by weakness, sensory symptoms and significant reduction or loss of deep tendon reflexes evolving over 2 months at least, associated with electrophysiological evidence of peripheral nerve demyelination. Recently, subcutaneous immunoglobulins (SCIg) have been introduced in clinical practice as a maintenance therapy for CIDP; nevertheless, electrophysiological and efficacy data are limited. Methods: to evaluate SCIg treatment efficacy, we retrospectively reviewed data from 15 CIDP patients referring to our clinic, receiving SCIg treatment and who performed electrophysiological studies (NCS) and clinical scores (MRC sumscore, INCAT disability score and ISS) before starting the treatment and at least one year after. Results: NCS showed no significant changes before and during treatment for all the nerves explored. Clinical scores did not significantly change between evaluations. Correlation analysis evidenced a positive correlation of cMAPs distal amplitude with MRC sumscore and a trend of negative correlation with the INCAT disability score. Conclusions: SCIg maintenance therapy preserves nerve function in CIDP with a good efficacy and safety. Treatment effectiveness can be assessed with ENG, which represents a useful instrument in the follow-up and prognostic assessment of CIDP.

Indicaxanthin (IX) from Opuntia Ficus Indica (OFI) has been shown to exert numerous biological effects both in vitro and in vivo, such as antioxidant, anti-inflammatory, neuro-modulatory activity in rodent models. Our goal was to investigate the eventual neuro-active role of orally assumed fruits containing high levels of IX at nutritionally-relevant amounts in healthy subjects, exploring cortical excitability and plasticity in the human motor cortex (M1). To this purpose, we applied paired-pulse transcranial magnetic stimulation and anodal transcranial direct current stimulation (a-tDCS) in basal conditions and followed the consumption of yellow cactus pear fruits containing IX or white cactus pear fruits devoid of IX (placebo). Furthermore, resting state-functional MRI (rs-fMRI) preliminary acquisitions were performed before and after consumption of the same number of yellow fruits. Our data revealed that the consumption of IX-containing fruits could specifically activate intracortical excitatory circuits, differently from the placebo-controlled group. Furthermore, we found that following the ingestion of IX-containing fruits, elevated network activity of glutamatergic intracortical circuits can homeostatically be restored to baseline levels following a-tDCS stimulation. No significant differences were observed through rs-fMRI acquisitions. These outcomes suggest that IX from OFI increases intracortical excitability of M1 and leads to homeostatic cortical plasticity responses.

Introduction: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have recently been proposed as promising biomarkers in different immune-mediated disorders. We evaluated the plasma levels of MMP-9 and MMP-2 and their tissue inhibitors TIMP-1 and TIMP-2 in a patients’ cohort with generalized myasthenia gravis (MG). Methods: Plasma concentrations of MMP-9, MMP-2, TIMP-1 and TIMP-2 were evaluated in 14 patients with generalized MG and 13 age- and sex-matched healthy controls. The severity of disease was assessed by the modified Osserman classification. Results: Compared to the healthy subjects, MG patients had increased plasma concentrations of MMP-9, but reduced plasma levels of MMP-2 and TIMP-1. MG patients also showed a positive correlation between MMP-2 concentrations and disease severity. An increase in MMP-9 levels and MMP-9/TIMP-1 ratio and a decrease in MMP-2 levels and MMP-2/TIMP-2 ratio were detected in patients with generalized MG. Higher levels of MMP-2 correlated with greater disease severity. Discussion: Our preliminary findings suggest that MMPs and TIMPs could play a role in the pathogenesis of MG and might be associated with the risk of clinical deterioration.

Background: The safety of the new vaccines against SARS-CoV-2 have already been shown, although data on patients with polyneuropathy are still lacking. The aim of this study is to evaluate the adherence to SARS-CoV-2 vaccination, as well as the reactogenicity to those vaccines in patients affected by neuropathy. Methods: A multicentric and web-based cross-sectional survey was conducted among patients affected by neuropathy from part of South Italy. Results: Out of 285 responders, n = 268 were included in the final analysis and n = 258 of them (96.3%) were fully vaccinated. Adherence to vaccination was higher in patients with hereditary neuropathies compared to others, while it was lower in patients with anti-MAG neuropathy (all p < 0.05). The overall prevalence of adverse events (AEs) was 61.2% and its occurrence was not associated with neuropathy type. Being female and of younger age were factors associated with higher risk of AEs, while having an inflammatory neuropathy and steroids assumption were associated with a lower risk (all p < 0.05). Younger age, having had an AE, and COVID-19 before vaccination were factors associated with symptoms worsening after vaccination (all p < 0.05). (4) Conclusions: Patients with neuropathy showed a high level of adherence to COVID-19 vaccination. Safety of vaccines in patients with neuropathies was comparable to the general population and it was more favorable in those with inflammatory neuropathy.

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease, characterized by the progressive degeneration of the upper and lower motor neurons in the cortex and spinal cord. Although the pathogenesis of ALS remains unclear, evidence concerning the role of the clonotypic immune system is growing. Adaptive immunity cells often appear changed in number, or in terms of their activation profiles, both peripherally and centrally; however, their role in ALS appears conflictive. Data from human and animal model studies, which are currently reported in the literature, show that each subset of lymphocytes and their mediators may mediate a protective or toxic mechanism in ALS, affecting both its progression and risk of death. In the present review, an attempt is made to shed light on the actual role of cellular clonotypic immunity in ALS by integrating recent clinical studies and experimental observations.

The aims of this paper was to determine the effect of self-myofascial release (SMFR) on postural stability and to analyze if it can influence migraine condition. Twenty-five subjects (age 49.7± 12.5) affected by migraine were enrolled. Assessments included a stabilometric analysis in order to evaluate balance and plantar support, with eyes open (OE) and closed (CE); cervical ROM measurement; evaluation of upper limb strength through handgrip. All the analysis were carried out before and after the administration of a single SMFR protocol, using medium density small balls laid in the three most painful trigger points in migraine patients: trapezius, sternocleidomastoids and suboccipital muscles. Performing a T test for paired samples, there was a significant increase in two ranges of the stabilometric analysis: ellipse surface, both with open and closed eyes (p value EO = 0.05; p value EC = 0.04) and length of the sway path, but just with closed eyes (p value = 0.05). SMFR might have a positive impact on postural stability in subjects with migraine. Further investigation should be conducted to confirm the hypothesis.

Abstract Introduction Connectivity within the primary motor cortex can be measured using the paired-pulse transcranial magnetic stimulation (TMS) paradigm. This evaluates the effect of a first conditioning stimulus on the motor evoked potential (MEP) elicited by a second test stimulus when different interstimulus intervals are used. Aim of the present study was to provide, in patients suffering from migraine without aura (MwoA), additional information on intracortical facilitation (ICF), short intracortical inhibition (SICI), and long intracortical inhibition (LICI), using different intensities of the test stimulus (TS). Methods We enrolled 24 patients with episodic MwoA and 24 age- and sex-matched healthy volunteers. Both patients and controls were randomly assigned to two different experimental groups: the first group underwent evaluation of ICF, while in the second group we assessed SICI and LICI. All these measures were assessed by using three different suprathreshold intensities of the TS (110%, 130% and 150% of the resting motor threshold, RMT). Interstimulus intervals (ISIs) of 10 ms were used for testing ICF, while SICI and LICI were carried out by using 2 ms and 100 ms ISIs respectively. All migraine patients underwent the experimental protocol while in the interictal pain-free state. Results A main finding of the study was that an increased ICF could be seen in migraineurs as compared to the healthy subjects only by using a 110% intensity of the TS. Instead, no significant differences were observed between patients and controls as regards both measures of intracortical inhibition. Conclusion We show that hyperresponsivity of the glutamatergic intracortical circuits can be detected in the migraine motor cortex only by applying a low suprathreshold intensity of stimulation. Our results strengthen the notion that, to be reliable, the assessment of cortical excitability in migraine should always include evaluation of the cortical response to different stimulation intensities.

Evidence derived from functional imaging and brain-lesion studies has shown a strong left lateralization for language, and a complementary right hemisphere dominance for visuospatial abilities. Nevertheless, the symmetrical functional division of the two hemispheres gives no reason for the complexity of the cognitive operations involved in carrying out a linguistic task. In fact, a growing number of neuroimaging and neurostimulation studies suggest a possible right hemisphere involvement in language processing. The objective of this work was to verify the contribution of the left and right parietal areas in a phonological task. We applied anodal transcranial direct current stimulation (tDCS) to the right or left inferior parietal lobe, during a syllabic reordering task. After having learnt a combination of images of real objects and trisyllabic pseudowords with a simple consonant–vowel (CV) syllabic structure (e.g., tu-ru-cu), participants were shown the same images paired to two different pseudowords: one correct but with transposed syllables, and one alternative, never before seen. The participant’s task was to orally produce the chosen pseudoword, after having rearranged the order of its syllables. Two types of error were considered: transposition (correct pseudoword but incorrectly reordered) and identity (incorrect pseudoword). The results showed that right anodal stimulation significantly reduced the number of transposition errors, whereas left anodal stimulation significantly reduced the number of identity errors. These results suggested that both left and right inferior parietal areas were differentially involved in a syllabic reordering task, and, crucially, they demonstrated that visuospatial processes served by the right inferior parietal area could be competent for establishing the correct syllabic order within a word.

Background: The detection of anti-acetylcholine receptor (AChR) and anti-muscle-specific tyrosine kinase (MuSK) antibodies is useful in myasthenia gravis (MG) diagnosis and management. BIOCHIP mosaic-based indirect immunofluorescence is a novel analytical method, which employs the simultaneous detection of anti-AChR and anti-MuSK antibodies in a single miniature incubation field. In this study, we compare, for the first time, the BIOCHIP MG mosaic with conventional enzyme-linked immunosorbent assay (ELISA) in the diagnosis of MG. Methods: A total of 71 patients with MG diagnosis were included in the study. Anti-AChR and anti-MuSK antibodies were measured separately by two different ELISA and simultaneously by BIOCHIP. The results were then compared. Results: The overall concordance between ELISA and BIOCHIP for anti-AChR reactivity was 74%. Cohen’s kappa was 0.51 (95% CI 0.32–0.71), which corresponds to 90% of the maximum possible kappa (0.57), given the observed marginal frequencies. The overall concordance for anti-MuSK reactivity was 84%. Cohen’s kappa was 0.11 (95% CI 0.00–0.36), which corresponds to 41% of the maximum possible kappa (0.27). Conclusion: The overall concordance among assays is not optimal.

Studies on the role of nutritional factors and physical activity (PA) in the pathogenesis of multiple sclerosis (MS) go back a long time. Despite the intrinsic difficulty of studying their positive or negative role in MS, the interest of researchers on these topics increased during the last few decades, since the role of diet has been investigated with the perspective of the association with disease-modifying drugs (DMD). The association of DMD, diets, and PA might have an additive effect in modifying disease severity. Among the various diets investigated (low-carbohydrate, gluten-free, Mediterranean, low-fat, fasting-mimicking, and Western diets) only low-carbohydrate, Mediterranean, and fast-mimicking diets have shown both in animal models and in humans a positive effect on MS course and in patient-reported outcomes (PROs). However, the Mediterranean diet is easier to be maintained compared to fast-mimicking and low-carbohydrate diets, which may lead to detrimental side effects requiring careful clinical monitoring. Conversely, the Western diet, which is characterized by a high intake of highly saturated fats and carbohydrates, may lead to the activation of pro-inflammatory immune pathways and is therefore not recommended. PA showed a positive effect both in animal models as well as on disease course and PROs in humans. Training with combined exercises is considered the more effective approach.

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

The aim of this study was to determine the blood lactate levels in healthy and pathological subjects, particularly with migraine and fibromyalgia. Moreover we investigated the possible correlation between lactate concentration, postural stability and balance disorders; the composition of the groups were: migraine (n = 25; age 49.7 ± 12.5), fibromyalgia (n = 10; age 43.7 ± 21.2), control group (n = 16 age 28.52 ± 2.4). The results showed that patients with fibromyalgia (FG) had higher lactate levels compared to migraine (MG) and control group (CG) (mean ± sd: FG = 1.78 ± 0.9 mmol/L; MG = 1.45±1 mmol/L; CG = 0,85 ± 0,07 mmol/L). The same situation was highlighted about the sway path length with eyes closed (FG = 518 ± 195 mm; MG = 465 ± 165 mm; CG = 405 ± 94,72 mm) and with eyes open (FG = 430 ± 220 mm; MG = 411 ± 143 mm; CG = 389 ± 107 mm). This can be explained by the fact that energy-intensive postural strategies must be used to optimize both static and dynamic coordination, in particular with repeated contractions of tonic oxidative muscle cells responsible for postural control.

Pediatric migraine remains still a challenge for the headache specialists as concerns both diagnostic and therapeutic aspects. The less ability of children to describe the exact features of their migraines and the lack of reliable biomarker for migraine contribute to complicate the diagnostic process. Therefore, there's need for new effective tools for supporting diagnostic and therapeutic approach in children with migraine. Recently, promising results have been obtained in adult headache by means of application of neurostimulation techniques both for investigating pathophysiological mechanisms and also for therapeutical applications. Non-invasive brain stimulation (NIBS) techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) indeed proved to be generally safe and showing also some evidence of efficacy particularly for the symptomatic treatment. On such basis, in the last years increasing interest is rising in scientific pediatric community to evaluate the potential of such approaches for treatment pediatric headaches, particularly in migraine, even if the evidence provided is still very poor. Here we present a perspective for application of TMS and tDCS technique in children migraine principally based on evidence coming by studies in adults.

Fibromyalgia syndrome (FMS) is a complex disorder where widespread musculoskeletal pain is associated with many heterogenous symptoms ranging from affective disturbances to cognitive dysfunction and central fatigue. FMS is currently underdiagnosed and often very poorly responsive to pharmacological treatment. Pathophysiology of the disease remains still obscure even if in the last years fine structural and functional cerebral abnormalities have been identified, principally by neurophysiological and imaging studies delineating disfunctions in pain perception, processing and control systems. On such basis, recently, neurostimulation of brain areas involved in mechanism of pain processing and control (primary motor cortex: M1 and dorsolateral prefrontal cortex: DLPFC) has been explored by means of different approaches and particularly through non-invasive brain stimulation techniques (transcranial magnetic and electric stimulation: TMS and tES). Here we summarize studies on tES application in FMS. The great majority of reports, based on direct currents (transcranial direct currents stimulation: tDCS) and targeting M1, showed efficacy on pain measures and less on cognitive and affective symptoms, even if several aspects as maintenance of therapeutical effects and optimal stimulation parameters remain to be established. Differently, stimulation of DLPFC, explored in a few studies, was ineffective on pain and showed limited effects on cognitive and affective symptoms. Very recently new tES techniques as high-density tDCS (HD-tDCS), transcranial random noise stimulation (tRNS) and tDCS devices for home-based treatment have been explored in FMS with interesting even if very preliminary results opening interesting perspectives for more effective, well tolerated, cheap and easy therapeutic approaches.

Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life.

Background: Over the past decade, three new drugs have been approved for the treatment of hereditary amyloid transthyretin (ATTRv) polyneuropathy. The aim of this work was to analyze whether current therapies prolong survival for patients affected by ATTRv amyloidosis. Methods: The study was conducted retrospectively, analyzing the medical records of 105 patients with genetic diagnoses of familial amyloidotic polyneuropathy followed at the two referral centers for the disease in Sicily, Italy. Of these, 71 received disease-modifying therapy, while 34 received only symptomatic treatment or no therapy. Results: The most used treatment in our patient cohort was tafamidis, followed by liver transplantation, patisiran, inotersen, and diflunisal. The median survival was significantly longer for treated vs. untreated patients (12 years vs. 8 years). In the 71 patients who received disease-modifying treatment, the presence of cardiac involvement, weight loss, or autonomic dysfunction at diagnosis was not related to survival. Conversely, patients diagnosed in the early stage of the disease (PND 1) had significantly longer survival than those diagnosed in the late stage (PND 2–4).

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

Objective: To evaluate therapeutic potential of different montages of transcranial direct current stimulation (tDCS) in Parkinson’s Disease (PD) patients with asymmetric motor symptoms.Materials and Methods: Fourteen patients with asymmetric PD underwent, while on treatment, seven separate sessions including electrophysiological and clinical evaluation at baseline and after anodal, cathodal and sham tDCS of the primary motor cortex (M1) of the two hemispheres. Changes in motor cortical excitability were evaluated by transcranial magnetic stimulation (TMS). Effects on motor symptoms were assessed by testing finger tapping (FT) and upper limb bradykinesia, and by using the Italian validated Movement Disorder Society revision of the Unified PD Rating Scale (MDS-UPDRS).Results: Only anodal tDCS of the more-affected M1 (contralateral to the more-affected body side) and cathodal tDCS of the less-affected M1 (contralateral to the less-affected body side) were able to induce significant changes in cortical excitability, i.e., facilitation and inhibition of the motor evoked potentials respectively. The motor performances of both hands significantly improved after anodal tDCS of the more-affected M1, as well as after cathodal tDCS of the less-affected one.Conclusion: Our findings support the potential usefulness of tDCS as add-on treatment for asymmetric PD, also providing interesting clues on the possible pathophysiological role played by an asymmetric activation of homologous motor cortical areas in PD.