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Introduction: Postural instability and gait impairments are common in people with PD, both of which have a negative effect on their quality of life. Systematic reviews have demonstrated benefits of using exergaming in enhancing these outcomes. However, there is no consensus over whether exergaming therapy is better than conventional physical therapy for enhancing gait, balance, and quality of life. Objectives: The aim of this overview is to systematically synthesize and evaluate the available evidence found in published systematic reviews and meta-analyses, on the effects of exergaming therapy on balance, gait, and quality of life, compared to conventional physical therapy or no intervention. Methods: This overview was reported in accordance with the statement of Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). A comprehensive search was carried out in nine databases. Two reviewers independently extracted data using a standardized forms and the search strategy included terms related to intervention, population, and study type. The methodological quality of the included systematic reviews/meta-analysis (SRs/Mas) was evaluated using the "A Measurement Tool to Assess Systematic Reviews 2" (AMSTAR-2). The "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) was used to assess the quality of the evidence. The risk of bias assessment was performed using the "Risk Of Bias In Systematic Reviews" (ROBIS). PROSPERO registration number: CRD42021238131. Results: 112 SRs/MAs were found and nine of them were selected. Six reviews were rated as very low methodological quality and three reviews as low methodological quality. Five reviews were classified with low risk of bias and four reviews with high risk of bias. Most of the SR/MAs demonstrated significant effects on balance favoring exergaming therapy over conventional therapy, however those studies had been rated as very low quality of evidence. Inconclusive results were found for the quality of life and gait outcomes. Conclusion: Exergaming therapy shows promise for the rehabilitation of PD. However, this overview was unable to conclude with certainty that exergaming therapy is superior to conventional physical therapy in improving gait, balance, or quality of life in people with PD. The effectiveness of exergaming therapy in the treatment of people with PD still need to be verified by high-quality studies.

Neurodegenerative diseases are inherited diseases of the central nervous system, which cause progressive damage to specific populations of neurons and lead to a deterioration in the quality of life (1,2). Parkinson disease (PD) is a progressive neurodegenerative disease and is the second most common after AD, and is characterized by postural instability, tremor and rigidity. Moreover, physical activity can reduces risk of other geriatric diseases such as diabetes, hypertension, osteoporosis and cardiovascular disease, which may also contribute to PD pathogenesis (3). We enrolled 12 subjects (age: 62.74 ± 4.94; height: 175,5cm ± 7,41 cm; weight: 75,5 ± 17,95 kg) affected by PD. An home-based training program was developed for 12 weeks, 3 times a week, an hour and a half for each session. At the beginning (T0), at the end of the study (T1) physical parameters (strength, balance and eye-hand reactivity) and hematochemicals parameters (glycemia, insulin, bone metabolism markers and neurotrophins) were tested. Statistical analyzes were performed using R version 3.4.3 and IBM SPSS Statistics 22. Changes in anthropometric, physical parameters, and hematochemical measurements between T0,T1 were evaluated using t Student test for paired data. The results obtained have confirmed that this protocol can influence over all bone metabolism markers; in fact parathormone decrease T0 62,250 to T1 35,675 ng/ml, p value

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor impairments and it is correlated with loss of bone mineral density. This study aimed to analyze the effects of resistance training on bone metabolism, systemic homeostasis, body composition, and physical performance in people with PD. Thirteen subjects (age 64.83 ± 5.70) with PD diagnosis were recruited. Participants performed neuromuscular tests, body composition assessment, and blood sample analysis at baseline, and after an 11 weeks-training period. Each training session lasted 90 min, three times a week. The participants had significant improvements in the timed up and go (p < 0.01), sit to stand (p < 0.01), dominant peg-board (p < 0.05), dominant foot-reaction time (p < 0.01), and functional reach tests (p < 0.05). They showed better pressure foot distributions in the left forefoot (p < 0.05) and hindfoot (p < 0.05) and increased cervical right lateral bending angle (p < 0.05). The protocol affects bone metabolism markers osteocalcin (p < 0.05), calcium (p < 0.01), PTH (p < 0.01), the C-terminal telopeptide (CTX) (p < 0.01), and vitamin D (p < 0.05). Eleven weeks of resistance training improved manual dexterity, static and dynamic balance, reaction time, cervical ROM, and reduced bone loss in people with PD.

Background The incidence of stroke in high-income countries has been on the decline; however, few epidemiological surveys have been conducted in recent years to specifically estimate the incidence along with outcome of stroke, in Italy. This study aimed to examine the incidence and case fatality rates of stroke in an elderly Italian population. Methods A cohort of 2200 people > 65 years was randomly stratified from the total elderly population of Bagheria, Italy. A 9-year prospective population-based study was performed (19,800 person/years). Results We identified 112 first-ever strokes, 53 females and 59 males: 82 (73.1%) ischemic, 13(11.6%) intracerebral haemorrhages, 6 (5.35%) subarachnoid haemorrhages, while 11(9.8%) were classified as undetermined strokes. The crude overall annual incidence was 5.65 per 1000 (95%CI: 4.61 to 6.70) for first-ever stroke. The overall crude incidence rates were 4.74 per 1000 (5.08 for males and 4.46 for females) for ischemic stroke, 0.65 (0.99 for males and 0.37 for females) for intracerebral haemorrhage, and 0.03 for subarachnoid haemorrhage. The incidence rate for first-ever stroke was 5.4 per 1000 (95% CI: 5.36 to 5.45) after adjustment for the 2015 World population and 5.56 (95% CI: 5.52 to 5.61), compared to the 2015 European population. Overall case fatality rates for first-ever stroke was 8.19% at 28 days and 24.1% at 1 year. Conclusion Our study shows that in the elderly population investigated, stroke incidence and case fatality rates resulted being lower, compared to those from Italian and most European populations. Similar to previous studies, these rates increased linearly with age and were higher in males.

The prevalence and impact of imaging findings detected during screening procedures in patients undergoing transcranial MR-guided Focused Ultrasound (tcMRgFUS) thalamotomy for functional neurological disorders has not been assessed yet. This study included 90 patients who fully completed clinical and neuroradiological screenings for tcMRgFUS in a single-center. The presence and location of preoperative imaging findings that could impact the treatment were recorded and classified in three different groups according to their relevance for the eligibility and treatment planning. Furthermore, tcMRgFUS treatments were reviewed to evaluate the number of transducer elements turned off after marking as no pass regions the depicted imaging finding. A total of 146 preoperative imaging findings in 79 (87.8%) patients were detected in the screening population, with a significant correlation with patients’ age (rho = 483, p

Recently, the LRP10 gene has been associated with Parkinson's disease (PD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB). The aim of the present study was to evaluate the presence of mutations of the LRP10 gene in patients with PD or DLB from Southern Italy. Sequencing analysis revealed only 2 missense and 3 synonymous variants in patients and control subjects and a rare variant p.L622F in a PD case. These results suggest that LRP10 mutations are not a frequent cause of PD and DLB in Southern Italy.

Background Heart rate variability (HRV) decreases in Parkinson’s disease (PD) and it can be considered a marker for cardiovascular dysautonomia. The purpose of this pilot study is to evaluate long-term time-domain analysis of HRV of PD patients and compare the results with those of matched healthy individuals. Methods Idiopathic PD patients without comorbidity impairing HRV, and age-matched healthy individuals were recruited in a pilot study. A long-term time domain analysis of HRV using 24-h ambulatory ECG was performed. Results Overall, 18 PD patients fulfilling inclusion criteria completed the evaluation (mean age was 55.6 ± 8.8, disease duration: 5.0 ± 4.7). Mean SCOPA-AUT score was 10.1 ± 7.3. Patients were on Hoehn & Yahr stage 1–2 and mean Levodopa Equivalent Dose (LED) was 311 ± 239.9. Mean of the 5-min standard deviation (SD) of R-R intervals distribution (SDNN) for all 5 min segments of the entire recording (ISDNN) was significantly lower in patients compared to controls. ISDNN was significantly different between Parkinson’s disease patients and healthy controls. Conclusions In our population characterized by mild to moderate disease severity, time-domain assessment of HRV seemed to be a potential tool to characterize cardiovascular dysautonomia. Decrease of ISDNN in PD may reflect an autonomic derangement extending all day and night long.

Transcranial magnetic resonance-guided focused ultrasound is a recently introduced incisionless treating option for essential tremor and tremor-dominant idiopathic Parkinson disease. There is preliminary evidence that it may result in a promising effective treatment option for other movement disorders too. Here, we report on two patients with multiple sclerosis with medication refractory debilitating essential tremor comorbidity who successfully underwent unilateral Vim tcMRgFUS thalamotomy for tremor control. Patients' clinical condition and expanded disability status scale scores showed no changes during the 1-year follow-up period with no evidence of multiple sclerosis activity or progression.

To assess the intraoperative neuroimaging findings in patients treated with transcranial MR-guided focused ultrasound (tcMRgFUS) thalamotomy using 1.5T equipment in comparison with the 48-h follow-up.Fifty prospectively enrolled patients undergoing unilateral tcMRgFUS thalamotomy for either medication-refractory essential tremor (n = 39) or Parkinson tremor (n = 11) were included. Two radiologists evaluated the presence and size of concentric lesional zones (zone I, zone II, and zone III) on 2D T2-weighted sequences acquired intraoperatively after the last high-energy sonication and at 48 h. Sonication parameters including number of sonications, delivered energy, and treatment temperatures were also recorded. Differences in lesion pattern and size were assessed using the McNemar test and paired t test, respectively.Zones I, II, and III were visualized in 34 (68%), 50 (100%), and 44 (88%) patients, and 31 (62%), 50 (100%), and 45 (90%) patients after the last high-energy sonication for R1 and R2, respectively. All three concentric zones were visualized intraoperatively in 56-58% of cases. Zone I was significantly more commonly visualized at 48 h (p 0.001). Diameter of zones I and II and the thickness of zone III significantly increased at 48 h (p 0.001). Diameters of zones I and II measured intraoperatively demonstrated significant correlation with thermal map temperatures (p ≤ 0.001). Maximum temperature significantly correlated with zone III thickness at 48 h. A threshold of 60.5° had a sensitivity of 56.5-66.7% and a specificity of 70.5-75.5% for thickness 6 mm at 48 h.Intraoperative imaging may accurately detect typical lesional findings, before completing the treatment. These imaging characteristics significantly correlate with sonication parameters and 48-h follow-up.• Intraoperative T2-weighted images allow the visualization of the zone I (coagulation necrosis) in most of the treated patients, while zone II (cytotoxic edema) is always detected. • Lesion size depicted with intraoperative transcranial MRgFUS imaging correlates well with procedure parameters. • Intraoperative transcranial MRgFUS imaging may have a significant added value for treating physicians.

Introduzione La tcMRgFUS consente di effettuare una vera e propria esplorazione neurofunzionale per confermare ed ottimizzare il target lesionale prima di indurre una lesione cerebrale permanete. La scelta del target di trattamento si basa tuttavia su coordinate stereotassiche che non tengono conto delle diversità anatomiche di ciascun individuo. L'ottimizzazione del target di trattamento viene effettuata sulla base del feedback del paziente durante la procedura stessa. Materiali e metodi È’ stato utilizzato uno scanner RM da 1.5T per acquisire sequenze morfologiche 3D e ultrastrutturali (DTI) in pazienti successivamente sottoposti a tcMRgFUS. È stata effettuata una segmentazione delle aree eloquenti cerebrali poi utilizzate come seed per un algoritmo di trattografia probabilistica mirato a rappresentare le proiezioni corticali da e verso il talamo con particolare riferimento alle aree motoria primaria e supplementaria e alla corteccia premotoria. Le mappe di parcellizzazione talamica ottenute sono state confrontate con le lesioni indotte mediante tcMRgFUS. Obiettivi Scopo di questo lavoro è valutare retrospettivamente il possibile ruolo della parcellizzazione talamica per l'identificazione del nucleo ventrale intermedio (VIM) in pazienti sottoposti a tcMRgFUS. Risultati In tutti i casi è stato possibile rappresentare i maggiori gruppi di nuclei talamici che ricevono da o proiettano verso la corteccia. È stato possibile identificare un’ottima sovrapposizione tra le mappe di parcellizzazione talamica così ottenute (con particolare riferimento al nucleo VIM) e le lesioni indotte mediante tcMRgFUS. Conclusioni Questi risultati preliminari lasciano ipotizzare la possibilità di utilizzare questa tecnica durante la pianificazione di trattamenti tcMRgFUS e ottimizzare i tempi di trattamento specie nei casi in cui il target di trattamento si discosti dalle coordinate stereotassiche.

Background Heart rate variability (HRV) decreases in Parkinson’s disease (PD) and it can be considered a marker for cardiovascular dysautonomia.Purpose To evaluate long-term time-domain analysis of HRV of PD patients and compare the results with those of matched healthy individuals.Method Idiopathic PD patients without comorbidity impairing HRV, and age-matched healthy individuals were recruited in a pilot study. A long-term time domain analysis of HRV using 24-hour ambulatory ECG was performed.Results 18 PD patients fulfilling inclusion criteria completed the evaluation (mean age was 55.6 ±8.8, disease duration: 5.0±4.7). Mean SCOPA-AUT score was 10.1±7.3. Patients were on Hoehn & Yahr stage 1-2 and mean Levodopa Equivalent Dose (LED) was 311 ± 239.9. Mean of the 5-minute standard deviation (SD) of R-R intervals distribution (SDNN) for all 5 min segments of the entire recording (ISDNN) was significantly lower in patients compared to controls. ISDNN significantly correlated with age, LED, levodopa and SCOPA-AUT scores.Conclusion In our population characterized by mild to moderate disease severity, time-domain assessment of HRV seemed to be a potential tool to characterize cardiovascular dysautonomia. Decrease of ISDNN in PD may reflect a circadian overall sympathetic and parasympathetic disarrangement.

Objective Purpose of this study is to evaluate the effects of training with six commercial Xbox KinectTM games on cognitive and motor aspects in Parkinson's disease (PD) patients and to compare the effects with a group of paired healthy subjects. Methods This study was a quasi-experimental, controlled trial. Eight individuals with PD (mean age 68.9 ± 7.9) and eight older adults without PD, matched by age (mean age 67.6 ± 7.3) were enrolled in the study. Ten sessions of six Xbox 360 KinectTM commercial games were performed for 5 weeks. Subjects were evaluated before and 7 and 30 days after intervention. They were assessed using Montreal Cognitive Assessment, Frontal Assessment Battery (FAB), Timed Up and Go test, Ten Meters Walking test, and Balance Berg Scale. The Freezing of Gait Questionnaire, the Movement Disorder Society Unified Parkinson Disease Rating Scale, and the Parkinson's disease Questionnaire were also applied to PD group. Results Significant improvement was found for cognitive aspects measured by Montreal Cognitive Assessment and FAB in both groups but without retention on FAB in PD group. No significant improvements were found for motor aspects in none group. Conclusion Motor-cognitive training using Xbox KinectTM games is a feasible resource to improve executive functions in PD patients and in older healthy people.

We evaluated the combined use of transcranial random noise stimulation (tRNS) with the Graded Repetitive Arm Supplementary Program (GRASP) in sub-acute ischemic stroke patients suffering from arm impairment. Eighteen ischemic stroke patients with upper limb disability were randomly assigned to either the GRASP + tRNS or GRASP + Sham stimulation group. Fugl-Meyer Assessment-Upper extremity (FMA-UE) was performed to evaluate upper limb impairment before treatment (T0), after the last stimulation (T1) and after 30 days (T2). At T1 and T2, beneficial effects in the tRNS group correlated with better FMA-UE score than sham stimulation group (p

no abstract available

Background: High-quality intraoperative imaging is needed for optimal monitoring of patients undergoing transcranial MR-guided Focused Ultrasound (tcMRgFUS) thalamotomy. In this paper, we compare the intraoperative imaging obtained with dedicated FUS-Head coil and standard body radiofrequency coil in tcMRgFUS thalamotomy using 1.5-T MR scanner. Methods: This prospective study included adult patients undergoing tcMRgFUS for treatment of essential tremor. Intraoperative T2-weighted FRFSE sequences were acquired after the last high-energy sonication using a dedicated two-channel FUS-Head (2ch-FUS) coil and body radiofrequency (body-RF) coil. Postoperative follow-ups were performed at 48 h using an eight-channel phased-array (8ch-HEAD) coil. Two readers independently assessed the signal-to-noise ratio (SNR) and evaluated the presence of concentric lesional zones (zone I, II and III). Intraindividual differences in SNR and lesional findings were compared using the Wilcoxon signed rank sum test and McNemar test. Results: Eight patients underwent tcMRgFUS thalamotomy. Intraoperative T2-weighted FRFSE images acquired using the 2ch-FUS coil demonstrated significantly higher SNR (R1 median SNR: 10.54, R2: 9.52) compared to the body-RF coil (R1: 2.96, p &lt, 0.001, R2: 2.99, p &lt, 0.001). The SNR was lower compared to the 48-h follow-up (p &lt, 0.001 for both readers). Intraoperative zone I and zone II were more commonly visualized using the 2ch-FUS coil (R1, p = 0.031 and p = 0.008, R2, p = 0.016, p = 0.008), without significant differences with 48-h follow-up (p &ge, 0.063). The inter-reader agreement was almost perfect for both SNR (ICC: 0.85) and lesional findings (k: 0.82&ndash, 0.91). Conclusions: In the study population, the dedicated 2ch-FUS coil significantly improved the SNR and visualization of lesional zones on intraoperative imaging during tcMRgFUS performed with a 1.5-T MR scanner.

Background Mitoxantrone (MX) has been used as second line therapy for aggressive multiple sclerosis (MS). Potential cardiotoxic effects of MX limit its use; a cumulative dose of up to 100 mg/m2, has been long considered relatively safe. We calculated the frequency of cardiac side effects in MS patients treated with MX. Methods We performed a cohort study including all MS patients treated with MX at the Neurological Department of the University Hospital of Palermo, Italy. Two hundred-sixty-four MS patients diagnosed according to validated criteria were included and followed-up until the end of September 2010. Patients were treated with MX as a second line therapy if they had no previous heart diseases determined by clinical evaluation, electrocardiography, and echocardiography. Treatment administration was made at a monthly dose of 8 mg/m2 for the first three months and at a dose of 12 mg/m2 every three months. Echocardiography was routinely performed every six months. Treatment was stopped before reaching the final dose if signs had appeared of impaired heart function, confirmed left ventricular ejection fraction reduction lower to 50%, or a confirmed reduction of more than 10% with respect to the first examination. Results Heart involvement was observed in 12.4% of treated individuals, and symptomatic congestive heart failure occurred in 2.7% of the cohort. A patient had a myocardial infarction, and 3.1% showed electrocardiographic anomalies not present at baseline. Conclusion Our study confirms that cardiac adverse events associated with MX are more common than previously reported.

DCTN1 encodes the largest subunit of dynactin complex essential in the retrograde axonal transport and cytoplasmic transport of vesicles; mutations in DCTN1 have been reported predominantly in individuals with Perry syndrome and, recently, in patients with progressive supranuclear palsy. Our genetic screening of DCTN1 in 79 patients with progressive supranuclear palsy, 100 patients with multiple system atrophy, and 28 patients with dementia with Lewy bodies from Italy revealed only synonymous and intronic variants, suggesting that DCTN1 mutations do not have a key role in the development of atypical parkinsonism in the Italian population.

Background Autonomic nervous system dysfunction, common in patients with Parkinson’s disease (PD), causes significant morbidity and it is correlated with poor quality of life. To assess frequency of urinary symptoms in patients with PD, without conditions known to interfere with urinary function. Methods Non-demented PD patients were consecutively enrolled from the outpatients clinic of our department. Scales investigating motor and non-motor symptoms were carried out. Evaluation of urinary dysfunctions was carried out using the AUTonomic Scale for Outcomes in Parkinson’s disease (SCOPA-AUT) questionnaire. Patients underwent noninvasive urological studies (nUS), including uroflowmetry and ultrasound of the urinary tract. Results Forty-eight (20 women, 42%) out of 187 PD patients met the inclusion criteria and were enrolled in the study. Mean SCOPA-AUT score was 14.1 ± 6.9 (urinary symptoms subscore 5.2 ± 3.8). Among those evaluated by the SCOPA-AUT scale, the urinary symptoms were among the most common complaints (93.8%). At nUS mean maximum flow rate (Qmax) was 17.9 ± 9.1 ml/s, and mean postvoid residual (PVR) urine volume was 24.4 ± 44.1 ml. Ultrasound investigation documented prostate hypertrophy in 12 male patients (42.8%). Urinary items of the SCOPA-AUT (SCOPA-U subscore) correlated with measures of disease severity only in female patients. Conclusion Urinary symptoms and abnormal findings in nUS are common in PD. Though nigrostriatal degeneration might be responsible for urinary symptoms also in the early-intermediate stage of the disease, when urinary dysfunction occurs other medical conditions need to be excluded.

OBJECTIVETranscranial magnetic resonance–guided focused ultrasound surgery (tcMRgFUS) is one of the emerging noninvasive technologies for the treatment of neurological disorders such as essential tremor (ET), idiopathic asymmetrical tremor-dominant Parkinson’s disease (PD), and neuropathic pain. In this clinical series the authors present the preliminary results achieved with the world’s first tcMRgFUS system integrated with a 1.5-T MRI unit.METHODSThe authors describe the results of tcMRgFUS in a sample of patients with ET and with PD who underwent the procedure during the period from January 2015 to September 2017. A monolateral ventralis intermedius nucleus (VIM) thalamic ablation was performed in both ET and PD patients. In all the tcMRgFUS treatments, a 1.5-T MRI scanner was used for both planning and monitoring the procedure.RESULTSDuring the study period, a total of 26 patients underwent tcMRgFUS thalamic ablation for different movement disorders. Among these patients, 18 were diagnosed with ET and 4 were affected by PD. All patients with PD were treated using tcMRgFUS thalamic ablation and all completed the procedure. Among the 18 patients with ET, 13 successfully underwent tcMRgFUS, 4 aborted the procedure during ultrasound delivery, and 1 did not undergo the tcMRgFUS procedure after stereotactic frame placement. Two patients with ET were not included in the results because of the short follow-up duration at the time of this study. A monolateral VIM thalamic ablation in both ET and PD patients was performed. All the enrolled patients were evaluated before the treatment and 2 days after, with a clinical control of the treatment effectiveness using the graphic items of the Fahn-Tolosa-Marin tremor rating scale. A global reevaluation was performed 3 months (17/22 patients) and 6 months (11/22 patients) after the treatment; the reevaluation consisted of clinical questionnaires, neurological tests, and video recordings of the tests. All the ET and PD treated patients who completed the procedure showed an immediate amelioration of tremor severity, with no intra- or posttreatment severe permanent side effects.CONCLUSIONSAlthough this study reports on a small number of patients with a short follow-up duration, the tcMRgFUS procedure using a 1.5-T MRI unit resulted in a safe and effective treatment option for motor symptoms in patients with ET and PD. To the best of the authors’ knowledge, this is the first clinical series in which thalamotomy was performed using tcMRgFUS integrated with a 1.5-T magnet.

Background The association between multiple sclerosis (MS) and cancer has long been investigated with conflicting results. Several reports suggest an increased cancer risk among MS patients treated with immunosuppressant (IS) drugs. Methods We performed a cohort study including MS patients recruited at the Neurological Department of the University of Palermo. Mean follow-up period was ten years for the whole cohort. We calculated cancer incidence among patients treated with IS. Incidence rates were compared in the cohort by calculating the relative risk according to length and dose of exposure to IS. Cancer incidence among MS patients was compared to cancer incidence in the general population of Sicily in similar age groups. Results On an overall cohort of 531 MS patients (346 women and 185 men) exposed to IS, we estimated a crude incidence rate for cancer of 2.26% (2.02% in women, 2.7% in men). Cancer risk was higher compared to rates observed among an equal number of patients not exposed to IS, and to the risk in the general population in Sicily at similar age groups (adjusted HR: 11.05; CI 1.67–73.3; p = 0.013). Conclusion The present study showed a higher cancer risk in MS patients associated only to previous IS exposure. Studies on long-term outcomes are essential to evaluate the possibility that treatment options that need to be considered for a long time-period may modify risk for life threatening diseases.

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. Effects on motor symptoms were assessed by testing finger tapping and upper limb bradykinesia, and by using the Italian validated Movement Disorder Society revision of the Unified Parkinson’s Disease 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. Conclusions. 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.

Background Both motor and non-motor symptoms could contribute to significant deterioration of psychological well-being in patients with Parkinson's disease (PD). However, its assessment has been only indirectly evaluated using tools based on health-related quality of life (HRQoL), such as the PDQ-39 scale. Objectives To evaluate psychological well-being in PD using a specific tool of assessment, the Psychological Well-being Scale (PWS), and its clinical correlates. Methods This article reports data of patients' perception of health state, as measured by means of the PWS, from an epidemiological, cross-sectional study conducted in Italian PD patients (FORTE Study). We tested possible relationship between well-being and clinical characteristics including fatigue, depression, sleep disruption and HRQoL. Results 272 patients completed the PWS questionnaire. Significant and clinically-relevant correlations were found between PWS total score and Parkinson's Fatigue Scale, Beck Depression Inventory, UPDRS Section I, PD Sleep Scale and PDQ-39 for HRQoL scores. Only clinically negligible correlations were found between PWS and motor scores. Conclusions Non-motor symptoms have a significant impact on psychological well-being in PD patients.

Background and objective Progression of Parkinson's disease (PD) is frequently characterized by the occurrence of freezing of gait (FOG) representing a disabling motor complication. We aim to investigate safety and efficacy of transcranial direct current stimulation of the primary motor cortex of PD patients with FOG. Methods In this cross-over, double-blind, sham-controlled study, 10 PD patients with FOG persisting in “on” state underwent anodal and sham direct current stimulation for 5 consecutive days. Clinical assessment over a 1-month period was performed. Results A significant improvement of gait, as assessed by the Stand Walk Sit test, with reduction in number and duration of FOG episodes, along with a significant reduction in the Unified Parkinson's Disease Rating Scale score, were observed after anodal stimulation. Beneficial effects were more evident after the entire 5-day stimulation session, and persisted until the end of the observation period. Conclusions Anodal transcranial direct current stimulation of the motor cortex is safe and has therapeutic potential in PD patients with FOG. © 2014 International Parkinson and Movement Disorder Society

The Red Ear syndrome (RES) is an intriguing syndrome originally described for the first time nearly 20 years ago. RES is characterized by unilateral/bilateral episodes of pain and burning sensation of the ear, associated with ipsilateral erythema. RES episodes are indeed isolated in some patients, but they can occur in association with primary headaches, including in particular migraine in the developmental age. Although the underlying pathophysiological mechanisms are still uncertain, in the recent years the described comorbidities have aroused increasing interest because of possible clinical implications. Moreover, RES seems to be more often associated with clinical features of migraine partially provoked by the involvement of the parasympathetic system. This clinical association has shed new light on the pathophysiology of RES, supporting the hypothesis of a shared pathophysiological background, for example, through the activation of the trigeminal autonomic reflex. Current therapies of RES will be also discussed. Finally, we will resume the more controversial aspects of this relatively new and probably underestimated neurological syndrome.

Our objective was to investigate incidence of amyotrophic lateral sclerosis (ALS) in Sicily, southern Italy, by means of a population based study. We included people with ALS resident in fi ve Sicilian provinces, whose onset occurred in the two-year period 2005 2006 (population at 31 December 2006: 3,481,096 inhabitants). A multisource case-fi nding procedure was adopted and patients were classifi ed as affected by ALS according to revised El Escorial criteria. During the two-year surveillance period, 97 patients meeting eligibility criteria included 57 males (58.8%) and 40 females (41.2%). Crude annual incidence rate was 1.4/100,000 person years (95% CI 1.33 1.47). The incidence rate was higher in males (1.71/100,000; CI 1.61 1.81) than in females (1.11/100,000; CI 1.01 1.21). Standardized incidence rate for the total population in the 45 74-years-old age group was 3.22 (CI 3.11 3.33). Prevalence rate was 6.0/100,000 (CI 5.97 6.03), higher in males (7.1/100,000; CI 7.02 7.18) than females (4.9/100,000; CI 4.86 4.94). In conclusion, ALS rates observed in the present study are higher in males than females, with a peak of incidence at 70 years of age in both genders. These fi ndings are consistent with those of other population based European studies

Objective To assess the association between diabetes preceding Parkinson's disease (PD) and PD. Methods PD individuals were matched to PD free individuals randomly selected from people in the same municipality as the cases. Occurrence of diabetes preceding PD onset among cases and controls was assessed through a structured questionnaire. Information regarding current and past medical treatment and other variables was also collected. We used univariate and multivariate logistic models to calculate crude and adjusted odds ratios (OR). Covariates are adjusted for included education, smoking habit, alcohol and coffee consumption. Results 318 PD individuals (165 women, 153 men) and 318 matched controls were included in the study. PD patients had a mean age at interview of 66.7 years. Mean age at PD onset was 60.8 years and mean PD duration 5.9 years. We found an inverse association between PD and diabetes preceding PD onset in all groups stratified by gender, age at PD onset, body mass index (BMI), smoking habit, alcohol and coffee consumption. Multivariate analysis yielded the same findings after controlling for the variables (adjusted OR 0.4; 95% CI, 0.2–0.8). Conclusions Our findings provide additional support for a potential link between diabetes and PD.

Background and purpose: There are few population-based surveys on multiple sclerosis (MS) survival. To investigate MS survival in MS patients recruited during surveys conducted in Sicily. Methods: Multiple sclerosis patients identified during previous surveys were randomly matched to two referent subjects by residence, year of birth, and gender. Living status was obtained by municipality records (end of follow-up June, 30th 2007) and, for the deceased, date and causes of death were searched. Kaplan-Meier plots were used to calculate differences in mortality between MS patients and referent subjects. MS risks for mortality with 95% confidence intervals (CI) were also calculated. Results: We included 194 MS patients and 388 matched persons. Thirty MS patients (15.5%) and 28 referents (7.2%) had died until the end of follow-up. Mean survival from onset of the disease to death was 20.6 years. Mean age at death was 55.5 for MS patients and 64.8 for the referents. Adjusted Hazard Ratios for mortality in MS was 1.81 (95% CI 1.36–2.40). Kaplan-Meier estimates showed a higher mortality amongst patients compared to referent subjects (P

Aim of this study was to determine the predictors of caregiver burden among spouse caregivers of patients with Parkinson's disease (PD). Forty consecutive PD patients and their spouse caregivers were included. Patients were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr scale (HY), the Mini-Mental State Examination (MMSE), the Neuropsychiatric Inventory (NPI), and the Geriatric Depression Scale (GDS). Stress and depressive symptoms among caregivers were evaluated using the Caregiver Burden Inventory (CBI) scale and the GDS. Only PD severity (HY) and mental symptoms (NPI) were significantly associated to caregiver distress. A major attention must be given to the early identification of factors generating stress in caregivers in order to improve caregiver quality of life and patient's care.

Herein we first describe a novel homozygous single nucleotide deletion in PINK1 exon 4 (889delG) which results in a loss of kinase domain on the PINK1 protein (D297fsX318). This mutation was identified in two brothers with early-onset Parkinson disease (EOPD) from a Sicilian consanguineous family. Of note, while one of the two patients developed mental deterioration and psychiatric problems, the other showed no cognitive decline. The present study supports the view that PINK1 is a pathogenic gene in some Italian families with EOPD and contributes to define the PINK1-associated phenotype. Herein we first describe a novel homozygous single nucleotide deletion in PINK1 exon 4 (889delG) which results in a loss of kinase domain on the PINK1 protein (D297fsX318). This mutation was identified in two brothers with early-onset Parkinson disease (EOPD) from a Sicilian consanguineous family. Of note, while one of the two patients developed mental deterioration and psychiatric problems, the other showed no cognitive decline. The present study supports the view that PINK1 is a pathogenic gene in some Italian families with EOPD and contributes to define the PINK1-associated phenotype.

This work was undertaken to evaluate studies on mortality caused by multiple sclerosis (MS), to evaluate if useful inferences can be drawn from survival studies that can be applied to clinical practice. A literature search was carried out to find epidemiological studies on MS prognosis, survival, mortality and causes of death relevant to our aim. The World Health Organization (WHO) reports on worldwide cause-specific mortality were also considered. Studies were evaluated according to the duration of the follow-up study, the year of publication and the methodology used. We evaluated MS survival from a methodological point of view and considered if time trends could be drawn from study results. We conclude that mortality is only slightly higher in MS patients when compared with that in the general population. Mortality is higher particularly for older patients and those with longer disease duration.

Aim of this study was to investigate the relationship between height in young adult age and Parkinson's disease (PD) risk. We included 266 persons affected by idiopathic PD. Patients were matched by age and sex to 266 controls by a random selection from the municipality of residence. We collected information about height preceding PD from official documents where these characteristics referred to young adult age (nearly 30 years). We compared height in cases and controls by calculating differences in mean distribution and by χ2 analyses. Crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression models. Mean height was significantly lower in persons affected by PD compared to controls (P = 0.03). Difference was significant only in men (P = 0.001). Logistic regression models showed an inverse association between height and PD (OR 0.35; CI 0.16, 0.79; P < 0.01 comparing individuals in the highest percentiles of height with those in the lowest). Our results indicate an association between height and PD in men. Considering that dopamine sensitivity in the hypothalamic-pituitary axis is related to adult height, our findings suggest a relationship between PD and factors modulating somatic growth early in life. © 2007 Movement Disorder Society

Dopaminergic drugs and deep brain stimulation restore cortical inhibition in Parkinson disease (PD) patients. High-frequency rTMS was also found to increase cortical inhibition in PD but its therapeutic effect is still controversial. Here we hypothesize that, if dopaminergic drugs reverse to normal cortical excitability in M1, the effect of high-frequency (hf)-rTMS in PD patients could depend on whether they are in a medicated or unmedicated state. The present study aims to explore the lasting effects of sub-threshold hf rTMS trains over M1 on cortical inhibition in patients with "on" and without "off" L-DOPA treatment. Fourteen PD patients were examined twice while "on" and "off" medication. In both conditions, a paired-pulse paradigm was used to evaluate short intracortical inhibition (SICI) and long intracortical inhibition (LICI) that were evaluated before and after hf rTMS trains applied on the motor cortex. The results were compared with those obtained from normal controls. In baseline condition, SICI and LICI were significantly reduced in "off" compared to "on" patients and controls. hf-rTMS over the motor cortex significantly increased SICI and LICI in "off" medication PD patients. Magnetic stimulation proved to be ineffective when the same patients were in "on" state. The results showed that hf-rTMS affected intracortical inhibition (ICI) only in unmedicated patients. By restoring cortical inhibitory circuits dopaminergic drugs, normalize the excitability changes in M1 subsequent to motor rTMS. Whether patients are in a medicated or an unmedicated state would therefore appear to be critical for rTMS effects in PD patients. If a positive correlation exists between increased cortical inhibition and clinical improvement, hf-rTMS during the "off" state could be regarded as a potential add-on treatment to reduce the need of L-dopa and thus delay the adverse effects of its chronic use.

Background: Autonomic symptoms and sleep disorders are common non-motor symptoms of Parkinson disease (PD), which are correlated with poor quality of life for patients. Purpose: To assess the frequency of autonomic symptoms in a consecutive series of PD patients and to correlate them with other motor and non-motor symptoms. Methods: All consecutive non-demented PD patients who underwent an extensive evaluation including Hoehn and Yahr staging, Unified Parkinson’s Disease Rating Scale, Beck’s Depression Inventory, Neuropsychiatric Inventory, PDQ-39 Scale, the Parkinson’s diseases Sleep Scale, the Epworth Sleepiness Scale and SCOPA-AUT scale were enrolled. Comorbidity has been also considered. Supine to standing position blood pressure and cardiac frequency changes were also measured. Results: 135 PD patients were included (mean age at interview 67.7; mean disease duration: 5.3 years). Patients were stratified according to mean SCOPA-AUT scale score (13.1). Those with higher SCOPA-AUT scale score were significantly older, had longer disease duration, worse disease stage, worse quality of sleep, were more severely affected, and were also taking a higher dosage of levodopa. At multivariate analysis, older age, longer disease duration, and worse quality of sleep were independently associated with higher SCOPA-AUT scale scores. Conclusions: Our results remark the role of autonomic symptoms in PD. In our patient population, characterized by mild to moderate disease severity, most of the patients complained of autonomic nervous system involvement (84 %). A significant association between autonomic symptoms and sleep disorders was also observed.

Dear Editor, We have read with interest comments by Solla et al. [1] regarding our Letter to the Editor published in NeurologicalSciences titled ‘‘Insidious onset of Pisa Syndrome afterrasagiline therapy in a patient with Parkinson’s Disease’’[2]. We thank the authors for their interest in our paper, but we think it is necessary to make some clarifications regarding the temporal relationship between the onset of Pisa Syndrome (PS) and rasagiline therapy. PS occurred in fact after and not before rasagiline treatment as stated by Solla et al. In particular, PS occurred after a time interval of 6–12 months and anyway after rasagiline was added to patient’s therapy. This long time interval is one of the elements that makes the case interesting (time period longer than previously described). Temporal relationship is fundamental for the interpretation of clinical and electrophysiological findings in our case. Rasagiline is an inhibitor of monoamine oxidase type B, and although different mechanisms of action have been advocated, its effect is primarily dopamine mediated [3]. This means that occurrence of Pisa syndrome in our case was likely related not only to the specific mechanisms of action of the drug but also to increased dopamine extracellular levels at the striatal synapses, and thus to the total dopamine agonism load. To conclude, though it is likely that concomitant use of other antiparkinsonian drugs could have contributed to the onset of PS in our patient, it is noteworthy that PS was not evident before rasagiline was started, it became evident after rasagiline was initiated, and it was not anymore evident after rasagiline was stopped.