Exploring the Neuropsychological Correlates of Swallowing Disorders in People with Parkinson's Disease: a Cross-Sectional Study.

Around 80% of persons with Parkinson's disease (PD) present symptoms of dysphagia. Although cognitive impairment may contribute to dysphagia, few studies have investigated the association between the PD neuropsychological profile and objective measures of swallowing dysfunction. Since the swallowing function comprises involuntary but also voluntary actions, we hypothesize that specific measures of attention and executive functions can be underlined in PD-related dysphagia. Therefore, the aim of this study was to extensively investigate the correlation and the relationship between attentive and executive functions and safety/efficiency of pharyngeal phase of swallowing in people with PD. All participants received a fiberoptic endoscopic evaluation of swallowing and were evaluated using the Penetration Aspiration Scale (PAS); the Yale Pharyngeal Residue Severity Rating Scale (IT-YPRSRS), and the Functional Oral Intake Scale (FOIS-IT). Participants also underwent a neuropsychological assessment covering global cognitive status, attention, and frontal executive functions. Correlations and associations between neuropsychological measures and swallowing components were calculated. Twenty-one participants with PD (mean age 69.38 ± 6.58 years, mean disease duration 8.38 ± 5.31 years; mean MDS-UPDRS III 43.95 ± 24.18) completed all evaluations. The most significant correlations were found between attentive functions (i.e., Stroop Time), and executive functions (i.e., Raven's Progressive Matrices, Digit Backward and Semantic Fluency), and FOIS-IT, PAS, and IT-YPRSRS sinuses and valleculae. These associations were not influenced by disease duration. These results suggest that a dysfunction to attentional processes and/or to executive functions can contribute to penetration and the presence of pharyngeal residue in participants with middle-stage PD.

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases.

BACKGROUND: The number of deep brain stimulation (DBS) procedures is rapidly rising as well as the novel indications. Reporting adverse events related to surgery and to the hardware used is essential to define the risk-to-benefit ratio and develop novel strategies to improve it. OBJECTIVE: To analyze DBS complications (both procedure-related and hardware-related) and further assess potential predictive factors. METHODS: Five hundred seventeen cases of DBS for Parkinson's disease were performed between 2006 and 2021 in a single center (mean follow-up: 4.68 ± 2.86 years). Spearman's Rho coefficient was calculated to search for a correlation between the occurrence of intracerebral hemorrhage (ICH) and the number of recording tracks. Multiple logistic regression analyzed the probability of developing seizures and ICH given potential risk factors. Kaplan-Meier curves were performed to analyze the cumulative proportions of hardware-related complications. RESULTS: Mortality rate was 0.2%, while permanent morbidity 0.6%. 2.5% of cases suffered from ICH which were not influenced by the number of tracks used for recordings. 3.3% reported seizures that were significantly affected by perielectrode brain edema and age. The rate of perielectrode brain edema was significantly higher for Medtronic's leads compared to Boston Scientific's (Χ2(1)= 5.927, P= 0.015). 12.2% of implants reported Hardware-related complications, the most common of which were wound revisions (7.2%). Internal pulse generator models with smaller profiles displayed more favorable hardware-related complication survival curves compared to larger designs (X2(1)= 8.139, P= 0.004). CONCLUSION: Overall DBS has to be considered a safe procedure, but future research is needed to decrease the rate of hardware-related complications which may be related to both the surgical technique and to the specific hardware's design. The increased incidence of perielectrode brain edema associated with certain lead models may likewise deserve future investigation.

Access, referral, service provision and management of individuals with primary progressive aphasia: A survey of speech-language therapists in Italy.

BACKGROUND AND OBJECTIVES: In Italy, approximately 650 individuals receive a diagnosis of primary progressive aphasia (PPA) every year. Unfortunately, the frequency with which patients are referred to speech-language services is suboptimal, likely due to skepticism regarding the value of speech-language therapy in the context of neurodegeneration. MATERIALS AND METHODS: We conducted a virtual survey of speech and language therapists (SLTs) across Italy, to collect information about the assessment, intervention and management of patients with PPA. To ensure that as many SLTs as possible received the survey, the Italian Federation of SLTs (Federazione Logopedisti Italiani, FLI) aided in disseminating the survey. RESULTS: In total, 336 respondents participated in the online survey, 140 of whom had previous experience with PPA patients. Respondents indicated having seen a total of 428 PPA patients in the previous 24 months (three patients on average, range: 0-40). SLTs who reported never working with PPA identified underdiagnoses, low referral rates and the rarity of the clinical syndrome as major reasons for their lack of experience with PPA. SLTs with experience working with PPA indicated that patients may not have accessed services because of service dysfunction and geographical barriers. Respondents reported using informal interviews during assessments and tests developed for post-stroke aphasia, while impairment-based/restitutive interventions were utilised most often. CONCLUSION: Findings may serve to inform health policy organisations regarding the current shortcomings and needed recommendations for improving the care of individuals with PPA in Italy. Improving awareness of the utility of rehabilitation among SLTs and other clinical service providers may serve to facilitate access to intervention, which in turn will serve to better support individuals living with PPA. WHAT THIS PAPER ADDS: What is already known on the subject Speech and language therapists (SLTs) play a crucial role in the assessment, diagnosis and treatment of people with primary progressive aphasia (PPA). However, the frequency with which individuals with PPA are referred for speech and language services is suboptimal due to skepticism regarding the value of speech and language therapy in the context of neurodegeneration, the scarcity of SLTs with expertise in the treatment of PPA and the lack of awareness of the SLT role amongst referrers. What this paper adds to existing knowledge In recognition of the lack of published information on the provision of speech and language therapy services and clinicians' approaches to the assessment and treatment of individuals with PPA in Italy, we conducted an online survey to evaluate the current referral patterns for speech and language therapy services and to examine the current barriers to access these services for individuals with PPA in Italy. What are the potential or actual clinical implications of this work? The data presented here support that SLTs view treatment as useful for individuals with PPA and other professional figures and may serve to improve access to intervention, which in turn will serve to better support individuals living with PPA. The results highlight the need to inform health policy organisations about current gaps and aid in developing recommendations for improving the care of individuals with PPA, in order to understand how SLTs can best support individuals with PPA and their families.

Striatal Dopamine Deficit and Motor Impairment in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Idiopathic normal pressure hydrocephalus can present with parkinsonism. However, abnormalities of the striatal dopamine reuptake transporter are unclear. OBJECTIVES: To explore presence and features of striatal dopaminergic deficit in subjects with idiopathic normal pressure hydrocephalus as compared to Parkinson's disease (PD) patients and healthy controls. METHODS: We investigated 50 subjects with idiopathic normal pressure hydrocephalus, 25 with PD, and 40 healthy controls. All participants underwent [123 I]-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane and single-photon emission computed tomography to quantify the striatal dopamine reuptake transporter binding. All subjects with idiopathic normal pressure hydrocephalus underwent a levodopa (l-dopa) challenge test and magnetic resonance imaging to evaluate ventriculomegaly and white matter changes. Gait, cognition, balance, and continence were assessed with the Idiopathic Normal Pressure Hydrocephalus Rating Scale, and parkinsonism with the motor section of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale. All patients completed a 2-year follow-up. RESULTS: A total of 62% of patients with idiopathic normal pressure hydrocephalus featured a reduced striatal dopamine reuptake transporter binding, which correlated with the severity of parkinsonism but not with features of ventriculomegaly or white matter changes. Unlike PD, this dopaminergic deficit in idiopathic normal pressure hydrocephalus was more symmetric and prominent in the caudate nucleus. CONCLUSIONS: Subjects with idiopathic normal pressure hydrocephalus can present a reduction of striatal dopamine reuptake transporter binding, which is consistent with the severity of parkinsonism and qualitatively differs from that found in PD patients. Longitudinal interventional studies are needed to prove a role for striatal dopamine reuptake transporter deficit in the pathophysiology of idiopathic normal pressure hydrocephalus. © 2020 International Parkinson and Movement Disorder Society.

PSEN1 Compound Heterozygous Mutations Associated with Cerebral Amyloid Angiopathy and Cognitive Decline Phenotype.

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder caused by the deposition of amyloid beta-peptide (Aß) aggregates. Aß aggregates lead to vessel rupture and intracerebral hemorrhages, detected by magnetic resonance imaging (MRI). Presenile CAA is usually genetically determined by mutations in the amyloid precursor protein (APP) gene. However, mutations after codon 200 in the presenilin 1 (PSEN1) gene have been reported to facilitate CAA onset. Here, we analyzed the genetic bases in a patient of 55 years old affected by CAA and cognitive decline. DNA was isolated and genetic analysis was performed by Next-Generation Sequencing (NGS). RNA was extracted and retro-transcribed to perform segregation analysis by TOPO-TA cloning. WB analysis was carried out to check the impact of the mutations on protein. Two compound heterozygous mutations in PSEN1 exon 10, such as a novel stop-gain mutation (c.1070C > G) and a pathogenic splice variant (c.1129A > T), were found by NGS. Both mutations altered the presenilin 1 protein, truncating its C-terminal portion. This is the first case of CAA and cognitive decline caused by two compound mutations in PSEN1. With this report, we suggest extending the genetic analysis to PSEN1 when cerebral microbleeds are observed by MRI investigation in a patient affected by presenile cognitive decline.

Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases.

Identifying biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different miRNA signatures in plasma derived LEVs and SEVs of Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD) patients. LEVs and SEVs were isolated from plasma of patients and healthy volunteers (CTR) by filtration and differential centrifugation and RNA was extracted. Small RNAs libraries were carried out by Next Generation Sequencing (NGS). MiRNAs discriminate all NDs diseases from CTRs and they can provide a signature for each NDs. Common enriched pathways for SEVs were instead linked to ubiquitin mediated proteolysis and Toll-like receptor signaling pathways and for LEVs to neurotrophin signaling and Glycosphingolipid biosynthesis pathway. LEVs and SEVs are involved in different pathways and this might give a specificity to their role in the spreading of the disease. The study of common and different miRNAs transported by LEVs and SEVs can be of great interest for biomarker discovery and for pathogenesis studies in neurodegeneration.

Substantia Nigra Volumetry with 3-T MRI in De Novo and Advanced Parkinson Disease.

Background Magnetization transfer-prepared T1-weighted MRI can depict a hyperintense subregion of the substantia nigra involved in the degeneration process of Parkinson disease. Purpose To evaluate quantitative measurement of substantia nigra volume by using MRI to support clinical diagnosis and staging of Parkinson disease. Materials and Methods In this prospective study, a high-spatial-resolution magnetization transfer-prepared T1-weighted volumetric sequence was performed with a 3-T MRI machine between January 2014 and October 2015 for participants with de novo Parkinson disease, advanced Parkinson disease, and healthy control participants. A reproducible semiautomatic quantification analysis method that entailed mesencephalic intensity as an internal reference was used for hyperintense substantia nigra volumetry normalized to intracranial volume. A general linear model with age and sex as covariates was used to compare the three groups. Results Eighty participants were evaluated: 20 healthy control participants (mean age ± standard deviation, 56 years ± 11; 11 women), 29 participants with de novo Parkinson disease (64 years ± 10; 19 men), and 31 participants with advanced Parkinson disease (60 years ± 9; 16 women). Volumetric measurement of hyperintense substantia nigra from magnetization transfer-prepared T1-weighted MRI helped differentiate healthy control participants from participants with advanced Parkinson disease (mean difference for ipsilateral side, 64 mm3 ± 14, P < .001; mean difference for contralateral side, 109 mm3 ± 14, P < .001) and helped distinguish healthy control participants from participants with de novo Parkinson disease (mean difference for ipsilateral side, 45 mm3 ± 15, P < .01; mean difference for contralateral side, 66 mm3 ± 15, P < .001) and participants with de novo Parkinson disease from those with advanced Parkinson disease (mean difference for ipsilateral side, 20 mm3 ± 13, P = .40; mean difference for contralateral side, 43 mm3 ± 13, P = .004). Conclusion Magnetization transfer-prepared T1-weighted MRI volumetry of the substantia nigra helped differentiate the stages of Parkinson disease. © RSNA, 2020 Online supplemental material is available for this article.

Should We Consider Deep Brain Stimulation Discontinuation in Late-Stage Parkinson's Disease?

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) effects may decrease with Parkinson's disease (PD) progression. There is no indication if, when, and how to consider the interruption of DBS treatment in late-stage PD. The objective of the current study was to investigate the percentage of "poor stimulation responders" among late-stage PD patients for elaborating an algorithm to decide whether and when DBS discontinuation may be considered. METHODS: Late-stage PD patients (Hoehn Yahr stage ≥4 and Schwab and England Scale <50 in medication on/stimulation on condition) treated with STN-DBS for at least 5 years underwent a crossover, double-blind, randomized evaluation of acute effects of stimulation. Physicians, caregivers, and patients were blinded to stimulation conditions. Poor stimulation responders (MDS-UPDRS part III change <10% between stimulation on/medication off and stimulation off/medication off) maintained the stimulation off/medication on condition for 1 month for open-label assessment. RESULTS: Thirty-six patients were included. The acute effect of stimulation was significant (17% MDS-UPDRS part III), with 80% of patients classified as "good responders." Seven patients were classified as "poor stimulation responders," and the stimulation was switched off, but in 4 cases the stimulation was switched back "on" because of worsening of parkinsonism and dysphagia with a variable time delay (up to 10 days). No serious adverse effects occurred. CONCLUSIONS: The vast majority of late-stage PD patients (92%) show a meaningful response to STN-DBS. Effects of stimulation may take days to disappear after its discontinuation. We present a safe and effective decisional algorithm that could guide physicians and caregivers in making challenging therapeutic decisions in late-stage PD. © 2020 International Parkinson and Movement Disorder Society.

GBA-Related Parkinson's Disease: Dissection of Genotype-Phenotype Correlates in a Large Italian Cohort.

BACKGROUND: Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. OBJECTIVES: We determined the frequency of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. METHODS: Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. ß-glucocerebrosidase activity was measured. The Kaplan-Meier method and Cox proportional hazard regression models were performed. RESULTS: Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA-PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA-PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA-PD had the lowest ß-glucocerebrosidase activity. CONCLUSIONS: GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles. © 2020 International Parkinson and Movement Disorder Society.

The TANDEM investigation: efficacy and tolerability of levodopa-carbidopa intestinal gel in (LCIG) advanced Parkinson's disease patients.

The TANDEM investigation was carried out in 17 Italian Movement Disorder centers on behalf of a joint initiative of neurologist members of the Italian Academy for Parkinson's disease and Movement Disorders (LIMPE-DISMOV Academy) and gastroenterologist members of the Italian Society of Digestive Endoscopy (SIED) to evaluate the efficacy and tolerability of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced Parkinson's disease (PD) in routine medical care. Motor scores in "ON" and OFF" state (UPDRS-III), complications of therapy (UPDRS-IV), activities of daily living, sleep disorders and quality of life were evaluated at baseline and at two follow-up assessments (FUV1 and FUV2) within the initial 12-month LCIG treatment. In 159 patients (55% males) with a mean age of 69.1 ± 6.6 years and a diagnosis of PD since 13.6 ± 5.5 years, the UPDRS-III total score (in "OFF") decreased from baseline (45.8 ± 13.2) to FUV1 (41.0 ± 17.4; p < 0.001) and FUV2 (40.5 ± 15.5; p < 0.001), the UPDRS-IV total score decreased from baseline (8.8 ± 2.9) to FUV1 (5.1 ± 3.4; p < 0.001) and FUV2 (5.5 ± 3.2; p < 0.001). The percentage of patients exhibiting freezing, dystonia, gait/walking disturbances, falls, pain and sleep disorders was significantly reduced. Twenty-eight device complications were reported and 11 (6.9%) patients prematurely terminated the study. LCIG after 12-month treatment led to sustained improvement of time spent in "OFF", complications of therapy, PD-associated symptoms and sleep disorders. LCIG tolerability was consistent with the established safety profile of LCIG.

Demographic and clinical determinants of neck pain in idiopathic cervical dystonia.

Cervical dystonia is associated with neck pain in a significant proportion of cases, but the mechanisms underlying pain are largely unknown. In this exploratory study, we compared demographic and clinical variables in cervical dystonia patients with and without neck pain from the Italian Dystonia Registry. Univariable and multivariable logistic regression analysis indicated a higher frequency of sensory trick and a lower educational level among patients with pain.

Freezing of gait in Parkinson's disease reflects a sudden derangement of locomotor network dynamics.

Freezing of gait is a disabling symptom of Parkinson's disease that causes a paroxysmal inability to generate effective stepping. The underlying pathophysiology has recently migrated towards a dysfunctional supraspinal locomotor network, but the actual network derangements during ongoing gait freezing are unknown. We investigated the communication between the cortex and the subthalamic nucleus, two main nodes of the locomotor network, in seven freely-moving subjects with Parkinson's disease with a novel deep brain stimulation device, which allows on-demand recording of subthalamic neural activity from the chronically-implanted electrodes months after the surgical procedure. Multisite neurophysiological recordings during (effective) walking and ongoing gait freezing were combined with kinematic measurements and individual molecular brain imaging studies. Patients walked in a supervised environment closely resembling everyday life challenges. We found that during (effective) walking, the cortex and subthalamic nucleus were synchronized in a low frequency band (4-13 Hz). In contrast, gait freezing was characterized in every patient by low frequency cortical-subthalamic decoupling in the hemisphere with less striatal dopaminergic innervation. Of relevance, this decoupling was already evident at the transition from normal (effective) walking into gait freezing, was maintained during the freezing episode, and resolved with recovery of the effective walking pattern. This is the first evidence for a decoding of the networked processing of locomotion in Parkinson's disease and suggests that freezing of gait is a 'circuitopathy' related to a dysfunctional cortical-subcortical communication. A successful therapeutic approach for gait freezing in Parkinson's disease should aim at directly targeting derangements of neural network dynamics.

Alzheimer's, Parkinson's Disease and Amyotrophic Lateral Sclerosis Gene Expression Patterns Divergence Reveals Different Grade of RNA Metabolism Involvement.

Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by a progressive degeneration of the central or peripheral nervous systems. A central role of the RNA metabolism has emerged in these diseases, concerning mRNAs processing and non-coding RNAs biogenesis. We aimed to identify possible common grounds or differences in the dysregulated pathways of AD, PD, and ALS. To do so, we performed RNA-seq analysis to investigate the deregulation of both coding and long non-coding RNAs (lncRNAs) in ALS, AD, and PD patients and controls (CTRL) in peripheral blood mononuclear cells (PBMCs). A total of 293 differentially expressed (DE) lncRNAs and 87 mRNAs were found in ALS patients. In AD patients a total of 23 DE genes emerged, 19 protein coding genes and four lncRNAs. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses, we found common affected pathways and biological processes in ALS and AD. In PD patients only five genes were found to be DE. Our data brought to light the importance of lncRNAs and mRNAs regulation in three principal neurodegenerative disorders, offering starting points for new investigations on deregulated pathogenic mechanisms.

Validation of the Italian version of carers' quality-of-life questionnaire for parkinsonism (PQoL Carer) in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a rare, rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. Caring for a partner or relative who suffers from PSP entails a strenuous and demanding task, usually lasting for years that affects carers' everyday life routines and emotional and social well-being. The 26-item Parkinsonism Carers QoL (PQoL Carer) is a self-administered, concise instrument evaluating the quality of life of caregivers of patients with atypical parkinsonism (both PSP and multiple system atrophy). Here, the PQoL Carer was translated into Italian and validated in 162 carers of PSP patients (54.3% women; mean age (standard deviation), 62.4 (15.4)) diagnosed according to the Movement Disorder Society criteria and recruited in 16 third-level movement disorders centers participating in the Neurecanet project. The mean PQoL total score was 40.66 ± 19.46. The internal consistency was excellent (Cronbach's alpha = 0.941); corrected item-total correlation was > 0.40 for all the items. A correlation with other health-related quality of life measures as well as with behavioral assessments was shown suggesting adequate convergent validity of the scale. PQoL also correlated with patients' severity of disease. The discriminant validity of the scale was evidenced by its capacity to differentiate between carers with varying levels of self-reported health (p < 0.001). In conclusion, the Italian version of the PQoL Carer is an easy, consistent, and valid tool for the assessment of the quality of life in carers of PSP patients.

Validation of the Italian version of the PSP Quality of Life questionnaire.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. The use of health-related quality of life (HR-QoL) measures allows assessing changes in health status induced by therapeutic interventions or disease progress in neurodegenerative diseases. The PSP-QoL is a 45-item, self-administered questionnaire designed to evaluate HR-QoL in PSP. METHODS AND RESULTS: Here, the PSP-QoL was translated into Italian and validated in 190 PSP (96 women and 94 men; mean age ± standard deviation, 72 ± 6.5; mean disease duration, 4.2 ± 2.3) patients diagnosed according to the Movement Disorder Society criteria and recruited in 16 third level movement disorders centers participating in the Neurecanet project. The mean PSP-QoL total score was 77.8 ± 37 (physical subscore, 46.5 ± 18.7; mental subscore, 33.6 ± 19.2). The internal consistency was high (Cronbach's alpha = 0.954); corrected item-total correlation was > 0.40 for the majority of items. The significant and moderate correlation of the PSP-QoL with other HR-QoL measures as well as with motor and disability assessments indicated adequate convergent validity of the scale. Gender and geographic location presented a significant impact on the PSP-QoL in our sample with women and patients from the South of Italy scoring higher than their counterparts. CONCLUSION: In conclusion, the Italian version of the PSP-QoL is an easy, reliable and valid tool for assessment of HR-QoL in PSP.

Parkinson's disease patients have a complex phenotypic and functional Th1 bias: cross-sectional studies of CD4+ Th1/Th2/T17 and Treg in drug-naïve and drug-treated patients.

BACKGROUND: Parkinson's disease (PD) affects an estimated 7 to 10 million people worldwide, and only symptomatic treatments are presently available to relieve the consequences of brain dopaminergic neurons loss. Neuronal degeneration in PD is the consequence of neuroinflammation in turn influenced by peripheral adaptive immunity, with CD4+ T lymphocytes playing a key role. CD4+ T cells may however acquire proinflammatory phenotypes, such as T helper (Th) 1 and Th17, as well as anti-inflammatory phenotypes, such as Th2 and the T regulatory (Treg) one, and to what extent the different CD4+ T cell subsets are imbalanced and their functions dysregulated in PD remains largely an unresolved issue. METHODS: We performed two cross-sectional studies in antiparkinson drug-treated and drug-naïve PD patients, and in age- and sex-matched healthy subjects. In the first one, we examined circulating Th1, Th2, Th17, and in the second one circulating Treg. Number and frequency of CD4+ T cell subsets in peripheral blood were assessed by flow cytometry and their functions were studied in ex vivo assays. In both studies, complete clinical assessment, blood count and lineage-specific transcription factors mRNA levels in CD4+ T cells were independently assessed and thereafter compared for their consistency. RESULTS: PD patients have reduced circulating CD4+ T lymphocytes, due to reduced Th2, Th17, and Treg. Naïve CD4+ T cells from peripheral blood of PD patients preferentially differentiate towards the Th1 lineage. Production of interferon-γ and tumor necrosis factor-α by CD4+ T cells from PD patients is increased and maintained in the presence of homologous Treg. This Th1-biased immune signature occurs in both drug-naïve patients and in patients on dopaminergic drugs, suggesting that current antiparkinson drugs do not affect peripheral adaptive immunity. CONCLUSIONS: The complex phenotypic and functional profile of CD4+ T cell subsets in PD patients strengthen the evidence that peripheral adaptive immunity is involved in PD, and represents a target for the preclinical and clinical assessment of novel immunomodulating therapeutics.

Transcranial direct current stimulation (tDCS) of the cortical motor areas in three cases of cerebellar ataxia.

The excitability of the motor areas of the cerebral cortex is reduced in ataxia. Since transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique able to increase the cortical excitability, we assessed the effect of anodal tDCS over the motor cortex in three patients with ataxia. A clinical evaluation, a video-taped SARA rating scale and a gait analysis with cinematic parameters, were performed pre- and post-sham and anodal tDCS cycle. The full cycle was composed by five consecutive constant current sessions of stimulation. Anodal tDCS (2.0 mA, 20 min,max current density: 0.0278 mA/cm2, max total charge:0.033 C/cm2) was performed on the M1 area of the most affected side. The contralateral primary motor cortex underwent cathodal stimulation (2.0 mA, 20 min, max current density:0.0278 mA/cm2, max total charge: 0.033 C/cm2). After anodal tDCS, gait analysis revealed an improvement of the symmetry of step execution and reduction of base-width lasting 30 days associated to patients' perception of amelioration. No relevant changes were found after sham stimulation. Our results suggest tDCS can improve gait symmetry in patients with ataxia for a short-term period. Future researches are needed in order to standardize time, amplitude, and area of stimulation in order to reach a long lasting effect on cerebellar ataxia.