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Background: Genetic, biologic and clinical data suggest that Parkinson's disease (PD) is an umbrella for multiple disorders with clinical and pathological overlap, yet with different underlying mechanisms. To better understand these and to move towards neuroprotective treatment, we have established the Quebec Parkinson Network (QPN), an open-access patient registry, and data and bio-samples repository., Objective: To present the QPN and to perform preliminary analysis of the QPN data., Methods: A total of 1,070 consecutively recruited PD patients were included in the analysis. Demographic and clinical data were analyzed, including comparisons between males and females, PD patients with and without RBD, and stratified analyses comparing early and late-onset PD and different age groups., Results: QPN patients exhibit a male:female ratio of 1.8:1, an average age-at-onset of 58.6 years, an age-at-diagnosis of 60.4 years, and average disease duration of 8.9 years. REM-sleep behavior disorder (RBD) was more common among men, and RBD was associated with other motor and non-motor symptoms including dyskinesia, fluctuations, postural hypotension and hallucinations. Older patients had significantly higher rates of constipation and cognitive impairment, and longer disease duration was associated with higher rates of dyskinesia, fluctuations, freezing of gait, falls, hallucinations and cognitive impairment. Since QPN's creation, over 60 studies and 30 publications have included patients and data from the QPN., Conclusions: The QPN cohort displays typical PD demographics and clinical features. These data are open-access upon application (http://rpq-qpn.ca/en/), and will soon include genetic, imaging and bio-samples. We encourage clinicians and researchers to perform studies using these resources.

Essential tremor (ET) is a common neurodegenerative disorder that is characterized by a postural or motion tremor. Despite a strong genetic basis, a gene with rare pathogenic mutations that cause ET has not yet been reported. We used exome sequencing to implement a simple approach to control for misdiagnosis of ET, as well as phenocopies involving sporadic and senile ET cases. We studied a large ET-affected family and identified a FUS p.Gln290(∗) mutation as the cause of ET in this family. Further screening of 270 ET cases identified two additional rare missense FUS variants. Functional considerations suggest that the pathogenic effects of ET-specific FUS mutations are different from the effects observed when FUS is mutated in amyotrophic lateral sclerosis cases; we have shown that the ET FUS nonsense mutation is degraded by the nonsense-mediated-decay pathway, whereas amyotrophic lateral sclerosis FUS mutant transcripts are not., (Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: Little is known on the long-term course of early manganese (Mn) neurotoxic effects. Mn alloy workers were examined in a follow-up study 14 years after exposure ceased at a Canadian facility., Methods: The same battery of neurofunctional tests used in the initial examination in 1990 was administered to 77 Mn-workers and 81 referents in 2004., Results: Manganese-workers had poorer scores compared to referents both in the initial and follow-up examinations for several motor tasks of the Luria Motor Scale. At follow-up, older Mn-workers (>45 years at cessation of exposure) had poorer scores than referents for tests of cognitive flexibility. Cumulated exposure was associated with poorer test scores for certain neuromotor and cognitive tests and on a mood scale. Differences on certain tests observed at initial examination were not present at follow-up., Conclusions: Manganese exposure was associated with persistent deficits for certain neuromotor functions, cognitive flexibility, and adVerse mood states, while recovery occurred for other functions., ((c) 2007 Wiley-Liss, Inc.)

Introduction: Psychiatric manifestations have been reported in cases of manganism, and mood disorders are often observed in manganese (Mn) exposed workers. We examined neuropsychiatric symptoms among formerly Mn-exposed workers 14 years after cessation of exposure., Materials and Methods: A study was conducted in 1990 among workers from a ferro- and silico-Mn plant and unexposed working men referents from the same region in South-West Quebec. At follow-up in 2004, 77 former Mn-workers and 81 referents agreed to participate and responded to a neuropsychiatric symptom checklist, the Brief Symptom Inventory (BSI); scores were transformed into T-scores based on a normative population. Cumulated exposure indices (CEI) were computed for each former Mn-worker. Linear and logistic regression analyses were used., Results: Mean T-scores were significantly higher among former Mn-workers than referents on scales of Depression and Anxiety. Mean T-scores of psychological distress increased with the CEI tertiles, with significant associations for the scales Somatization, Depression, Anxiety and Hostility. Former Mn-workers in the two highest tertiles of CEI showed a higher risk for T-scores >or=63 for Hostility (OR, 7.5; 95% CI, 1.5-38.9), Depression (OR, 2.6; 95% CI, 1.1-8.4) and Anxiety (OR, 3.0; 95% CI, 1.1-8.4)., Conclusion: These results suggest that past exposure to Mn may have lasting consequences on neuropsychiatric symptoms.

Pollution of hydrographic basins has affected the flora and fauna that thrive in these aquatic ecosystems, and fish, which constitute an important food resource, often contain a plethora of potentially toxic chemicals. In a major research project on early neurotoxic effects of environmental exposure to manganese among residents in Southwest Quebec, fish consumption from 2 lakes of the Upper St. Lawrence River System, was surveyed as a potential confounding factor. Participants were selected using a random, stratified sampling strategy from lists of the Quebec Health Plan. Following exclusions, 273 men and women between 20-69 years were retained for the present analysis. A total of 103 (37.7%) reported eating fish from the Upper St. Lawrence. Although fisheaters and non-fisheaters were similar for most socio-demographic variables, significantly more fisheaters (65.2%) reported consuming alcoholic beverages as compared to non-fisheaters (42.4%) (Chi Sq. <0.01). To eliminate this possible bias, fisheaters were matched to non-fisheaters for the variables sex, alcohol consumption (never or occasionally vs. regularly), age (+/-5y) and education (+/-2y). A total of 63 matched pairs were thus created. Paired analyses (t-test or Signed Rank) showed that fisheaters had higher levels of blood organic mercury and lead. Analysis of nervous system functions revealed that both groups performed similarly on tests of sensory function, visual memory and recognition, fine motor performance and some motor tests, but fisheaters performed significantly more poorly (p<0.05) on tests requiring cognitive flexibility, word naming, auditory recall, and more complex motor tasks. The profile of deficits is consistent with diminished capacity for information processing. These observations were made within a study that was not specifically designed to examine the effects of fish eating from these two lakes, and the characterization of fish dietary habits has many limitations. Nevertheless, the findings are sufficiently compelling to warrant further studies, since fish from the Upper St. Lawrence Lakes are known to contain multiple neurotoxic substances.