Rosario Vasta

Metals and neurodegenerative diseases. A systematic review

ABSTRACT Neurodegenerative processes encompass a large variety of diseases with different pathological patterns and clinical presentation such as Amyotrophic Lateral Sclerosis (ALS), Alzheimer Disease (AD) and Parkinsons disease (PD). Genetic mutations have a known causative role, but the majority of cases are likely to be probably caused by a complex gene‐environment interaction. Exposure to metals has been hypothesized to increase oxidative stress in brain cells leading to cell death and neurodegeneration. Neurotoxicity of metals has been demonstrated by several in vitro and in vivo experimental studies and it is likely that each metal could be toxic through specific pathways. The possible pathogenic role of different metals has been supported by some epidemiological evidences coming from occupational and ecological studies. In order to assess the possible association between metals and neurodegenerative disorders, several case‐control studies have also been carried out evaluating the metals concentration in different biological specimens such as blood/serum/plasma, cerebrospinal fluid (CSF), nail and hair, often reporting conflicting results. This review provides an overview of our current knowledge on the possible association between metals and ALS, AD and PD as main neurodegenerative disorders. HighlightsMetals exposure may increase neuronal oxidative stress leading to neurodegeneration.Metals pathogenic role has been suggested by occupational and ecological studies.Results of case‐control studies on metals serum concentration are controversial.The association between metals and neurodegenerative disorders is still unclear.We provide an overview of the available evidences.

Gender effect on non-motor symptoms in Parkinson's disease: are men more at risk?

INTRODUCTION Several gender differences have been reported in Parkinsons Disease (PD). We evaluated the burden of non-motor symptoms (NMS) in PD and the possible gender differences in their occurrence. METHODS The FRAGAMP study is a large multicenter case-control study. PD patients and controls underwent a face-to-face interview and a neurological examination performed by trained neurologists. Presence of NMS was investigated using a standardized questionnaire; cognitive impairment and depression were assessed using the Mini Mental State Examination and the Hamilton Depression Rating Scale respectively. RESULTS 585 PD patients (59.5% men) and 481 controls (34.9% men) were enrolled in the study. All NMS were significantly more frequent among PD patients than controls. PD women showed a significantly higher frequency of depression and urinary disturbances than parkinsonian men; a close frequency among PD women and men was recorded for hallucination, cognitive impairment and sleep disorders. Nonetheless, with respect to the control population, according to logistic regression stratified by sex and adjusted by age, PD men showed a stronger positive significant association with almost all NMS compared to women, excepting for urinary disturbances. The strongest association among PD men was recorded for cognitive impairment (adjusted OR 5.44 for men and 2.82 for women) and depression (adjusted OR 30.88 for men and 12.72 for women). CONCLUSIONS With respect to the general population, presence of NMS was stronger associated with male gender. Our data suggest that the presence of NMS among PD men is more strictly due to the neurodegenerative processes related to PD.

Validity of medico-administrative data related to amyotrophic lateral sclerosis in France: A population-based study

Abstract The accuracy of French medico-administrative data concerning amyotrophic lateral sclerosis (ALS) is to date unknown. We aimed to assess the validity of hospital discharge data (HDD) and health insurance data (HID) related to ALS. A retrospective population-based study was performed. The French register of ALS in Limousin (FRALim) was used as gold standard (2000–2013 period). All patients discharged from the regional hospitals with a ‘G12.2’ code in their HDD (according to the International Classification of Disease-10th version) or having a G12 HID code were considered. In the study period, the register included a total of 322 incident ALS patients. Among 451 subjects identified through HDD, 290 were true incident ALS cases, corresponding to 90.1% (95% CI 86.3–93.1) sensitivity and 64.3% (95% CI 59.7–68.7) positive predictive value (PPV). A total of 184 subjects were identified through HID, 142 of which were true ALS cases. This corresponded to 44.1% (95% CI 38.6–49.7) sensitivity and 75.5% (95% CI 68.7–81.5) PPV. The combination of both HDD and HID led to 93.8% (95% CI 90.6–96.2) sensitivity and 60.8% (95% CI 56.3–65.1) PPV. This study shows that French HDD and HID, even if combined, are not per se suitable for accurate and exhaustive direct identification of ALS cases.

Side effects induced by the acute levodopa challenge in Parkinson's Disease and atypical parkinsonisms.

Introduction Acute levodopa challenge may be performed to predict levodopa chronic responsiveness. The aim of the study was to investigate frequency of side effects during the acute levodopa challenge in PD and atypical parkinsonisms. Methods We enrolled 34 de novo PD patients and 29 patients affected by atypical parkinsonisms (Multiple System Atrophy, MSA, n = 10; Progressive Supranuclear Palsy, PSP, n = 12 and Corticobasal Degeneration, CBD, n = 7) who underwent an acute levodopa challenge. Side effects occurring during test were recorded. Results Side effects were more frequent among atypical parkinsonisms as unique group when compared to PD patients (64.3% versus 23.5%; p-value 0.002) with an adjusted OR of 4.36 (95%CI 1.40–13.5). Each atypical parkinsonisms showed almost double occurrence of side effects (MSA 90%, PSP 41.7% and CBD 57%). Conclusions Side effects during acute levodopa challenge may be frequent in atypical parkinsonisms. This information could be useful in order to better prepare the patient for the test. Furthermore, it could represent a useful cue in differential diagnosis with PD.

Head trauma and Parkinson’s disease: results from an Italian case-control study

We evaluated the possible association between head trauma and Parkinson’s disease (PD). The FRAGAMP (Fattori di Rischio Ambientali e Genetici Associati alla Malattia di Parkinson) study is a large Italian multicenter case-control study carried out to evaluate the possible role of environmental and genetic factors in PD. Cases and controls were enrolled from six movement disorders centers located in the Central-Southern Italy. A standardized questionnaire was administered to record demographic, epidemiological, and clinical data. Positive history of head trauma was considered only if the head trauma preceded the onset of PD. All cases and controls underwent a standard neurological examination. Adjusted ORs and 95% CI were estimated using multivariate analysis (logistic regression). Four hundred ninety-two PD patients (292 men and 200 women) and 459 controls (160 men and 299 women) were enrolled in the study. A positive history for head trauma was reported by 106 (21.5%) PD patients and by 62 (13.5%) healthy controls. Multivariate analysis (OR adjusted by age, sex, family history, coffee smoking, and alcohol consumption) showed a significant positive association between PD and head trauma with an adjusted OR of 1.50 (95%CI 1.04–2.17; p value 0.03). In agreement with literature data, our study supports the positive association between head trauma and PD.

Switching L-dopa Therapy from Pulsatile to Pulse Administration Reduces Motor Complications in Parkinsonʼs Disease

Objective To evaluate the severity of wearing-off and dyskinesia in patients with complicated Parkinson disease (PD) after switching L-dopa oral therapy from a “pulsatile” administration, consisting in intermittent multiple daily small doses of the drug, to a “pulse” administration, consisting in standard oral doses given at specific interdose intervals. Methods Thirty-four PD patients with motor complications were monitored twice with standardized waking day motor status evaluations using the Unified Parkinson Disease Rating Scale-Motor Examination (UPDRS-ME) and the Abnormal Involuntary Movement Scale (AIMS) after switching L-dopa administration modality from “pulsatile” to “pulse.” To quantify predictable motor fluctuations, a Wearing Off Index was computed based on changes in treatment response magnitude. Results On the whole, after switching from “pulsatile” to “pulse” administration, there was a reduction in number of L-dopa daily doses and an increase in the amount of the dosage of the single doses, AIMS maximum score decreased without increasing motor disability. More specifically, in predominant fluctuating patients, there was a significant reduction in UPDRS-ME average score as well as in Wearing Off Index. In predominant dyskinetic patients, there was a significant reduction in average and maximum AIMS scores with no changes in average and maximum UPDRS-ME scores. Conclusions Switching L-dopa therapy from “pulsatile” to “pulse” modality may reduce the severity of wearing-off and dyskinesia in complicated PD.

Dopaminergic and non-dopaminergic gait components assessed by instrumented timed up and go test in Parkinson’s disease

The timed up and go test (TUG) is a widely used clinical test for the evaluation of balance and mobility. An instrumented version of TUG (iTUG) has been proposed to provide quantitative information on TUG performances. Here, we hypothesized that l-dopa may differently influence gait parameters recorded by a portable inertial sensor. To test this idea, we evaluated iTUG test in patients with Parkinson’s disease (PD), both in l-dopa OFF and ON state. Twenty-eight PD patients performed the iTUG. Subjects were instructed to perform the task both in practical “OFF” and “ON” state. The system differentiated the test in six phases, recording phase durations, three-axial accelerations, average and peak angular speeds during turning. In all patients, sit-to-stand vertical and medio-lateral accelerations together with turning phase duration and angular speeds improved after l-dopa administration, while sit-to-stand and stand-to-sit phases antero-posterior accelerations were less responsive. In PD, l-dopa modulates iTUG in different ways, mostly improving the turning phases and less acting on postural controls during the sit-to-stand and stand-to-sit phases. Our results suggest different involvement of dopaminergic mechanisms on gait as assessed by iTUG. This is important for those aspects which are not improved by pharmacological therapy.