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IntroductionSubthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for patients with Parkinson’s disease (PD) with motor complications; the contribution of sex in determining the outcome is still not understood.MethodsWe included 107 patients (71 males) with PD consecutively implanted with STN-DBS at our center. We reviewed patient charts from our database and retrospectively collected demographical and clinical data at baseline and at three follow-up visits (1, 5 and 10 years).ResultsWe found a long-lasting effect of DBS on motor complications, despite a progressive worsening of motor performances in the ON medication condition. Bradykinesia and non-dopaminergic features seem to be the major determinant of this progression. Conversely to males, females showed a trend towards worsening in bradykinesia already at 1-year follow-up and poorer scores in non-dopaminergic features at 10-year follow-up. Levodopa Equivalent Daily Dose (LEDD) was significantly reduced after surgery compared to baseline values; however, while in males LEDD remained significantly lower than baseline even 10 years after surgery, in females LEDD returned at baseline values. Males showed a sustained effect on dyskinesias, but this benefit was less clear in females; the total electrical energy delivered was consistently lower in females compared to males. The profile of adverse events did not appear to be influenced by sex.ConclusionOur data suggest that there are no major differences on the motor effect of STN-DBS between males and females. However, there may be some slight differences that should be specifically investigated in the future and that may influence therapeutic decisions in the chronic follow-up.

Osmotic demyelination syndrome (ODS) is caused by damage to the pons myelin sheath and nerve cells. Although the pathophysiological mechanism responsible for the damage is not yet fully understood, it is currently believed that osmotic-type changes (especially if they are massive and too rapid) cause oedema that leads to compression and, subsequently, demyelination of white matter fibres. It generally manifests with acute paraparesis/tetraparesis, dysphagia, dysarthria, diplopia, and loss of consciousness, as well as hallucinations, spasms, and other neurological symptoms related to brainstem damage. In extreme cases, the locked-in syndrome may also appear. Of note, in some cases an association between osmotic demyelinating damage and the onset of movement disorders has been documented and, although the pathophysiology is still unknown, a correlation has been postulated between ODS and movement disorders. Here, we present a patient with ODS who developed parkinsonism, thus supporting the hypothesis of a correlation between these pathological events.

BackgroundHeterozygous mutations in the GBA gene, encoding the lysosomal enzyme β-glucocerebrosidase (GCase), are the most frequent genetic risk factor for Parkinson’s disease (PD). GBA-related PD (GBA-PD) patients have higher risk of dementia and reduced survival than non-carriers. Preclinical studies and one open-label trial in humans demonstrated that the chaperone ambroxol (ABX) increases GCase levels and modulates α-synuclein levels in the blood and cerebrospinal fluid (CSF).Methods and analysisIn this multicentre, double-blind, placebo-controlled, phase II clinical trial, we randomise patients with GBA-PD in a 1:1 ratio to either oral ABX 1.2 g/day or placebo. The duration of treatment is 52 weeks. Each participant is assessed at baseline and weeks 12, 26, 38, 52 and 78. Changes in the Montreal Cognitive Assessment score and the frequency of mild cognitive impairment and dementia between baseline and weeks 52 are the primary outcome measures. Secondary outcome measures include changes in validated scales/questionnaires assessing motor and non-motor symptoms. Neuroimaging features and CSF neurodegeneration markers are used as surrogate markers of disease progression. GCase activity, ABX and α-synuclein levels are also analysed in blood and CSF. A repeated-measures analysis of variance will be used for elaborating results. The primary analysis will be by intention to treat.Ethics and disseminationThe study and protocols have been approved by the ethics committee of centres. The study is conducted according to good clinical practice and the Declaration of Helsinki. The trial findings will be published in peer-reviewed journals and presented at conferences.Trial registration numbersNCT05287503, EudraCT 2021-004565-13.

ABSTRACT Background Elevated low‐frequency activity (4–12 Hz) within the globus pallidus internus (GPi) has been consistently associated with dystonia. However, the impacts of the genetic etiology of dystonia on low‐frequency GPi activity remain unclear; yet it holds importance for adaptive deep brain stimulation (DBS) treatment. Methods We compared the properties of GPi electrophysiology acquired from 70 microelectrode recordings (MER) trajectories of DYT‐GNAL, DYT‐KMT2B, DYT‐SGCE, DYT‐THAP1, DYT‐TOR1A, DYT‐VPS16, and idiopathic dystonia (iDYT) patients who underwent GPi‐DBS surgery across standard frequency bands. Results DYT‐SGCE patients exhibited significantly lower alpha band activity (2.97%) compared to iDYT (4.44%, p = 0.006) and DYT‐THAP1 (4.51%, p = 0.011). Additionally, theta band power was also significantly reduced in DYT‐SGCE (4.42%) compared to iDYT and DYT‐THAP1 (7.91% and 7.00%, p < 0.05). Instead, the genetic etiology of dystonia did not affect the spatial characteristics of GPi electrophysiology along MER trajectories. Conclusion Considering the genetic etiology of dystonia in closed‐loop DBS treatments and utilizing theta and alpha activity for GPi stimulation may optimize clinical outcomes. MER‐based DBS lead placement can proceed independently of the underlying genetic cause.

ABSTRACT Background The outcome of levodopa/carbidopa intestinal gel (LCIG) in Parkinson's disease carriers of GBA1 mutations (GBA‐PD) remains uncertain. Objective To evaluate the safety and efficacy of LCIG in a large PD cohort, focusing on GBA1 variants. Methods This multicenter, retrospective, longitudinal “real‐world” study included consecutive patients with advanced PD treated with LCIG at 31 Italian centers; data were collected at baseline, 1‐, 5‐year, and last‐available follow‐up. Results Data from 512 PD patients (59% male, mean age and disease duration at LCIG initiation 67.0 ± 8.0 and 12.9 ± 5.0 years, respectively) were analyzed. GBA1 genotyping was available for 306 patients (60%), of whom 40 (13%) had GBA1 mutations or risk variants. Mean follow‐up on LCIG was 3.9 ± 2.9 years; 5‐year follow‐up data were available for 159 subjects. At baseline, GBA‐PD had a younger age, shorter PD duration, worse cognition, and more hallucinations than noncarriers. At 1‐ and 5‐year follow‐up, LCIG improved motor and non‐motor symptoms, OFF‐time, and dyskinesias in the entire population. In GBA‐PD, MDS‐UPDRS parts I, II, and III scores did not change, while part IV score improved significantly less than in noncarriers; cognition and orthostatic hypotension symptoms worsened more rapidly. Multivariate analysis of predictors for adverse events and LCIG discontinuation found no significant contribution from GBA1 mutation status. Conclusions GBA1 status does not increase the risk of adverse events or LCIG discontinuation. LCIG is a safe option for advanced GBA‐PD, even in patients with cognitive impairment at baseline. However, GBA‐PD experiences lower efficacy on motor disability and complications and faster cognitive decline than noncarriers.

BackgroundGuillain-Barré syndrome (GBS) is an acute/subacute autoimmune inflammatory polyradiculoneuropathy. Previous epidemiological studies carried out in the province of Ferrara, Italy, from 1981 to 2002 indicated that GBS incidence had tendency of increase in the period considered.ObjectivesWe aimed at updating the epidemiology of GBS in the years 2003–2017 and carrying on the work started in the 1980s.MethodsWe conducted an incidence study, by adopting a complete enumeration approach. Cases were identified from administrative, medical records, and database of the Ferrara Hospital and other provincial structures of the study area. Case ascertainment and definition are analogous to those adopted in previous surveys.ResultsIn the period 1 January 2003 to 31 December 2017, 73 patients living in the province of Ferrara (mean population 353,142) were found to be new cases of GBS fulfilling the NINCDS criteria. Male/female ratio 1.15. The mean incidence rate was 1.38 per 100,000 (95% CI 1.08–1.74), 1.54 per 100,000 for men and 1.23 per 100,000 for women, a nonsignificant difference. During the period considered, the rates had slow increase or mild decrease, without nonsignificant difference. The highest rates were observed for the age groups 70–79 years for both sexes. A half of patients reported infectious events in the weeks before the onset of symptoms.ConclusionIn line with many epidemiological data, in the whole period 2003–2017, we observed a trend towards increase or decrease in incidence and periods of relative stability. Similar temporal heterogeneity with the comparison to our previous works was found.

In 1979, Gibson first advanced the idea that the sight of graspable objects automatically activates in the observer the repertoire of actions necessary to interact with them, even in the absence of any intention to act (\"affordance effect\"). The neurophysiological substrate of this effect was later identified in a class of bimodal neurons, the so-called \"canonical\" neurons, located within monkey premotor cortex. In humans, even if different behavioral studies supported the existence of affordance effect, neurophysiological investigations exploring its neural substrates showed contradictory results. Here, by means of Transcranial Magnetic Stimulation (TMS), we explored the time-course of the \"affordance effect\" elicited by the observation of everyday-life graspable objects on motor cortex of resting observers. We recorded motor evoked potentials (MEP) from three intrinsic hand muscles (two \"synergic\" for grasping, OP and FDI and one \"neutral\", ADM). We found that objects' vision determined an increased excitability at 120 milliseconds after their presentation. Moreover, this modulation was proved to be specific to the cortical representations of synergic muscles. From an evolutionary perspective, this timing perfectly fits with a fast recruitment of the motor system aimed at rapidly and accurately choosing the appropriate motor plans in a competitive environment filled with different opportunities.

ABSTRACT Objective Bilateral globus pallidus pars interna deep brain stimulation (GPi‐DBS) is a recognized and effective treatment option for drug‐resistant dystonia patients. However, the clinical GPi‐DBS outcomes vary significantly. Herein, we explored the pre‐implant factors affecting GPi‐DBS effectiveness. Methods Genetic profiles, symptom distribution, age at onset, disease duration, and severity of a cohort of 31 GPi‐DBS dystonia patients were collected. Dystonia motor severity was evaluated before and after GPi‐DBS using the Burke–Fahn–Marsden Dystonia‐Rating‐Scale (BFMDRS‐M). We assessed the interplay of the aforementioned factors in determining the BFMDRS‐M improvement through a multilinear regression analysis. Results BFMDRS‐M score showed a significant improvement (47.8%) since the first year, remaining stable at 5 years (54.3%). Lower limb (0.20), upper limb (0.16) and trunk (0.24) symptoms showed a significantly larger improvement compared to cranial symptoms (0.07, p < 0.05). Consequently, patients with more pronounced lower limb motor symptoms displayed a greater GPi‐DBS effect (p < 0.01). However, pre‐treatment localization of motor symptoms accounted only for 31% of the Inter‐Patient Variability (IPV) in post‐GPi‐DBS improvement. Amelioration varied also across genetic profiles, with the largest improvement reported for DYT‐TOR1A patients (n = 9, 64.2% in the first year), predicting 36% of IPV. Interestingly, combining motor and genetic profiles predicted 73% of the IPV. Including the clinical profile of the patient (age at onset, disease severity and duration) increased prediction accuracy to 81%. Interpretation Our results suggest that motor and genetic profiles contribute independently to the efficacy of the GPi‐DBS treatment. These results may support a personalized prediction of DBS outcomes in dystonia patients.

BackgroundLombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced.MethodsAt the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children.ResultsAfter a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March–September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high.ConclusionsDuring the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.