Calogero Edoardo Cicero

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.

Electroencephalographic lateralization, clinical correlates and pharmacological response in untreated Parkinson's disease

BACKGROUND In Parkinsons disease (PD), different topographically defined cortical-subcortical oscillatory networks have been implicated in motor program dysfunction. Few studies have focused on clinical correlates of cortical activity asymmetry using quantitative electroencephalography. METHODS We retrospectively selected N = 34 L-dopa naïve PD subjects who had undergone standardized electroencephalography. We selected N = 18 subjects group-matched by age, sex and hand dominance with normal electroencephalography and no parkinsonism and/or cognitive decline as controls. A Welchs periodogram was applied to electroencephalographic signal epochs recorded from homologous pairs of electrodes over each hemisphere. An index of lateralization was then obtained as the absolute value of the electroencephalographic asymmetry index, computed by subtracting left from right-sided log power spectral density for each homologous site and frequency band. A standardized L-dopa acute challenge test was performed on all PD subjects to compute short-duration response magnitude. RESULTS In mid/lateral frontal regions higher index of lateralization for the beta band (p = 0.015) and lower index of lateralization for the theta band (p = 0.036) were found in PD subjects as compared to controls. Both parameters correlated with Hoehn-Yahr staging (beta: r = 0.428, p = 0.012; theta: r = -0.464, p = 0.006). In occipital region lower index of lateralization for the alpha band was found in PD correlating with L-dopa short-duration response magnitude (r = 0.456; p = 0.007). CONCLUSIONS Lateralization of frontal cortex beta electroencephalographic activity is associated with clinical disability. Occipital cortex alpha activity may relate to L-dopa responsiveness in untreated PD subjects.

Knowledge, attitudes, and practices towards epilepsy among general practitioners in rural Bolivia: Results before and after a training program on epilepsy

INTRODUCTION Epilepsy represents a major health problem in low- and middle-income countries where treatment gap (TG) levels are high. The reduction of epilepsy TG in the rural area of the Chaco region, Plurinational State of Bolivia, has been the aim of many projects based on the reinforcement of the primary care setting. To plan educational campaigns directed to the healthcare professionals, it is necessary to establish their baseline knowledge level. The objective of our study was to assess the baseline level of knowledge, attitudes, and practices (KAP) towards epilepsy among general practitioners (GPs) of the rural communities of the Chaco region. METHODS The study was conducted in three departments of Bolivia. All the GPs living in these areas were invited to participate in the study consisting of two training modules six months apart from each other, each with two-day duration. They answered a validated questionnaire to evaluate the KAP towards epilepsy before and after the courses. RESULTS Fifty GPs [30 men (60%); mean age: 32.1±5.8years] participated in the first training course. After six months, 31 GPs (62%) [19 men (61.3%); mean age: 33±5.0years] participated in the second module. Before the training, the majority of GPs declared a low level of satisfaction about their epilepsy knowledge, which improved after the courses. A change in practices was recorded after the training, with an increased confidence to manage antiepileptic treatment. CONCLUSION Our study showed the significant impact of specific training programs on epilepsy among GPs.

A screening questionnaire for convulsive seizures: A three-stage field-validation in rural Bolivia

Introduction Epilepsy is one of the most common neurological diseases in Latin American Countries (LAC) and epilepsy associated with convulsive seizures is the most frequent type. Therefore, the detection of convulsive seizures is a priority, but a validated Spanish-language screening tool to detect convulsive seizures is not available. We performed a field validation to evaluate the accuracy of a Spanish-language questionnaire to detect convulsive seizures in rural Bolivia using a three-stage design. The questionnaire was also administered face-to-face, using a two-stage design, to evaluate the difference in accuracy. Methods The study was carried out in the rural communities of the Gran Chaco region. The questionnaire consists of a single screening question directed toward the householders and a confirmatory section administered face-to-face to the index case. Positive subjects underwent a neurological examination to detect false positive and true positive subjects. To estimate the proportion of false negative, a random sample of about 20% of the screened negative underwent a neurological evaluation. Results 792 householders have been interviewed representing a population of 3,562 subjects (52.2% men; mean age 24.5 ± 19.7 years). We found a sensitivity of 76.3% (95% CI 59.8–88.6) with a specificity of 99.6% (95% CI 99.4–99.8). The two-stage design showed only a slightly higher sensitivity respect to the three-stage design. Conclusion Our screening tool shows a good accuracy and can be easily used by trained health workers to quickly screen the population of the rural communities of LAC through the householders using a three-stage design.

Knowledge and attitudes towards epilepsy among nonmedical health workers in rural Bolivia: Results after a long-term activity in the Chaco region

INTRODUCTION Epilepsy represents a major global healthcare issue, particularly in low- and middle-income countries (LMIC), where nonmedical health workers play a key role in providing care to people with epilepsy (PWE). Over the last 20 years, many projects have been carried out by our group in the Chaco region, Plurinational State of Bolivia, with the aim of enhancing knowledge about epilepsy. However, the level of knowledge of epilepsy that nonmedical health workers have reached has never been assessed until now. The main objective of our study was to assess the level of knowledge, attitudes, and practices (KAP) towards epilepsy among nonmedical health staff of the rural communities of the Chaco region in Bolivia. METHODS The study was conducted in three departments of Bolivia. The nonmedical health personnel were invited to participate in a training program. They answered a validated questionnaire to evaluate their knowledge and attitudes towards epilepsy before and after the courses. RESULTS One hundred nineteen subjects [42 men (36.2%); mean age 29.3 ± 1.1 years] were interviewed among community health workers and nurses before the courses, demonstrating a very good level of knowledge regarding epilepsy and its causes. Only 55 health workers participated in the second training module, and their answer did not significantly differ from the baseline. CONCLUSION Our study confirms the usefulness of continuous educational campaigns, especially directed to nonspecialist healthcare providers of rural communities of LMIC, as they may be the only persons responsible for providing healthcare to PWE in that setting. Moreover, the importance of the baseline assessment of KAP was highlighted in order to adapt the educational campaigns to the baseline level of knowledge found.

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.

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.

Updated evidence of the association between toxocariasis and epilepsy: Systematic review and meta-analysis.

Objective To gain further insight on the association between human toxocariasis and epilepsy in light of the new evidence in the last years. Methods A systematic review was conducted without date and language restriction in the following electronic databases: MEDLINE (PubMed), Ingenta Connect, Science Direct (Elsevier), RefDoc, Scopus, HighWire, Scielo and the database of the Institute of Neuroepidemiology and Tropical Neurology of the Limoges University (IENT). Two investigators independently conducted the search up to November 2017. A pooled odds ratio (OR) was estimated using a random effects model. Meta-regression was conducted to investigate potential sources of heterogeneity. Results Database search produced 204 publications. Eleven case-control studies were included that were carried out in 13 countries worldwide. A total number of 4740 subjects were considered (2159 people with epilepsy and 2581 people without epilepsy). The overall pooled OR was 1.69 (95% CI 1.42–2.01) for the association between epilepsy and Toxocara spp. seropositivity. A positive association was constantly reported in the restricted analysis (WB as confirmatory or diagnostic test, younger population, and population–based studies). Meta-regression showed no statistically significant association between covariates and outcome. Conclusion The updated meta-analysis provides epidemiological evidence of a positive association between Toxocara seropositivity and epilepsy. New surveys supported the association, mainly population-based studies. On this basis, health strategies to reduce the impact of Toxocara spp are strongly advised. Further research should be performed to understand the physiopathological mechanisms of toxocara-associated epileptogenesis.

Temperament Traits And Executive Functions In Parkinson's Disease.

INTRODUCTION Aim of the study was to evaluate the possible relationship between Temperament traits and executive dysfunction in patients with Parkinsons disease (PD). METHODS Patients affected by PD diagnosed according to the UK Parkinsons disease Society Brain Bank criteria were enrolled in the study. Patients with a Mini Mental State Examination <24 were excluded from the study. The Temperament and Character Inventory (TCI), a self-report questionnaire assessing the Harm Avoidance (HA), Novelty Seeking (NS) and Reward Dependence (RD) temperamental traits, has been performed. The executive functions were assessed with the Frontal Assessment Battery (FAB). RESULTS Fifty PD patients (28 men and 22 women; mean age 59.1 ± 10.1 years) were enrolled. High HA (mean score 73.3 ± 24.7) and a low NS score (24.2 ± 18.7) were recorded. Fifteen (30%) patients presented a pathological FAB score (≤13.5). Patients with a pathological FAB score presented an HA score significantly higher than patients with normal FAB score (respectively 84.9 ± 13.7 versus 69.8 ± 26.9; p = 0.045). At the univariate analysis an association between high HA score and pathological FAB score was found (OR 3.85, 95%CI 1.06-13.9; p-value 0.040). CONCLUSION Our study confirmed an association between executive disturbances and HA in PD patients, possibly related to a common impairment of the frontostriatal circuits.

Treating People With Epilepsy in Rural Low-Income Countries Is Feasible. Observations and Reflections From a “Real Life Experience” After a Long Lasting Intervention in the Rural Chaco

Introduction: Epilepsy represents an important public health issue, in particular in low and middle-income countries where significant disparities are present in the care available for patients with epilepsy. Treatment cost and unavailability of drugs represent important barriers in treating people with epilepsy especially in rural setting. Aim of the study was to evaluate, by means of routine data, the current real-life clinical practice in epilepsy in the rural communities of the Plurinational State of Bolivia. Treatment activity followed educational campaigns and an anthropological fieldwork over more than 20 years. Material and Methods: Medical records of people with epilepsy (PWE) living in the rural communities of the Bolivian Chaco who received antiepileptic drugs (AEDs), from 2012 to 2016, and were followed-up for at least 1 year were analyzed. Treatment delivery and follow up visits were managed by a neurologist with the support of rural health care workers. Results: From 2012 to 2016, 157 PWE (76 men with a mean age of 24.2 ± 15.7) have been included in the study. Structural epilepsy was the most common type, recorded in 54 cases (34.4%) and the most common reported causes were perinatal factors, present in 11 subjects (20.0%). Almost all patients presented epilepsy with generalized tonic-clonic seizures (91.4%). The most common AED prescribed was phenobarbital followed by carbamazepine. During the follow-up, a dramatic seizures reduction was observed, with 31 subjects (19.7%) being seizures-free at the last follow-up. However, 48 subjects (30.6%) did not assume the medication regularly and 10 interrupted the drug intake. More than 20% of PWE did not receive any financial supports for AEDs. During the follow-up period 10 patients died but only in one case the death was probably caused by epilepsy. Conclusion: Our study demonstrated that PWE in rural areas of the Bolivian Chaco are willing to seek medical attention and to receive antiepileptic treatment. However, improvement in care is needed to assure compliance to AED treatment, including activity to increase awareness toward epilepsy among community members and health staff of the rural communities and to guarantee the coverage of treatment costs and drug supply.