Genetic and Epidemiological Study of Adult Ataxia and Spastic Paraplegia in Eastern Quebec.

OBJECTIVE: To estimate the minimum prevalence of adult hereditary ataxias (HA) and spastic paraplegias (HSP) in Eastern Quebec and to evaluate the proportion of associated mutations in identified genes. METHODS: We conducted a descriptive cross-sectional study of patients who met clinical criteria for the diagnosis of HA (n = 241) and HSP (n = 115) in the East of the Quebec province between January 2007 and July 2019. The primary outcome was the prevalence per 100,000 persons with a 95% confidence interval (CI). The secondary outcome was the frequency of mutations identified by targeted next-generation sequencing (NGS) approach. Minimum carrier frequency for identified variants was calculated based on allele frequency values and the Hardy-Weinberg (HW) equation. RESULTS: The minimum prevalence of HA in Eastern Quebec was estimated at 6.47/100 000 [95% CI; 6.44-6.51]; divided into 3.73/100 000 for autosomal recessive (AR) ataxias and 2.67/100 000 for autosomal dominant (AD) ataxias. The minimum prevalence of HSP was 4.17/100 000 [95% CI; 4.14-4.2]; with 2.05/100 000 for AD-HSP and 2.12/100 000 for AR-HSP. In total, 52.4% of patients had a confirmed genetic diagnosis. AR cerebellar ataxia type 1 (2.67/100 000) and AD spastic paraplegia SPG4 (1.18/100 000) were the most prevalent disorders identified. Mutations were identified in 23 genes and molecular alterations in 7 trinucleotides repeats expansion; the most common mutations were c.15705-12 A > G in SYNE1 and c.1529C > T (p.A510V) in SPG7. CONCLUSIONS: We described the minimum prevalence of genetically defined adult HA and HSP in Eastern Quebec. This study provides a framework for international comparisons and service planning.

Exposure to Pesticides and Welding Hastens the Age-at-Onset of Parkinson's Disease.

BACKGROUND: The age-at-onset (AAO) of Parkinson's disease (PD) is thought to be influenced by environmental factors and polygenic predispositions. Professional exposures to pesticides and toxic metals were shown to be associated with an earlier onset in small sample studies. AIM OF STUDY: The aim of this study was to confirm the association between professional exposures to pesticides and toxic metals and the AAO of PD, on a larger cohort of patients, defined with a clinic-based ascertainment scheme. METHODS: We used an incident cohort of 290 patients recruited through three designated movement disorder clinics in the province of Quebec, Canada. Patients completed a detailed questionnaire regarding professional exposures to pesticides and toxic metals. We compared the AAO in patients without prior professional exposure (N = 170) and those with exposure to pesticides (N = 53) or toxic metals through welding (N = 30). We further subdivided patients exposed to pesticides according to the frequency and proximity of their contacts. RESULTS: Patients with prior exposure to pesticides (AAO = 54.74 years) or toxic metals (54.27 years) had a significantly earlier AAO compared to the control group (59.26 years) (p = 0.003). In those exposed to pesticides, closer (p = 0.03) and more frequent (p = 0.02) contacts were negatively correlated with AAO. CONCLUSION: Exposure to pesticides and toxic metals were both associated with an earlier onset of PD, an effect that was greater with higher levels of exposure, both in terms of frequency and proximity.

L'exposition à des pesticides et à des métaux toxiques associés à la soudure diminue l'âge d'apparition de la maladie de Parkinson. Contexte: Il est courant de penser que l'âge d'apparition de la maladie de Parkinson (MP) est influencé par des facteurs environnementaux et des prédispositions polygéniques. À cet égard, on a montré, dans des études portant sur des échantillons plus restreints, que l'exposition à des pesticides et à des métaux toxiques lors d'une activité professionnelle était associée à un âge d'apparition de cette maladie plus précoce. Objectif de l'étude: Confirmer cette association à l'aide d'une cohorte de patients plus nombreux, cohorte établie en fonction d'un plan clinique de définition des cas (clinic-based ascertainment scheme). Méthodes: Notre étude a donc reposé sur une cohorte de 290 patients recrutés au Québec au sein de trois cliniques des troubles du mouvement préalablement désignées. Les patients choisis ont alors répondu à un questionnaire complet en ce qui concerne leur exposition à des pesticides et à des métaux toxiques dans le cadre de leur travail. Nous avons ensuite comparé l'âge d'apparition de la MP chez des patients n'ayant pas été exposés à ces éléments (n = 170) à l'âge d'apparition de la MP chez ceux ayant été exposés à des pesticides (n = 53) ou à des métaux toxiques associés à la soudure (n = 30). Plus encore, nous avons subdivisé les patients exposés à des pesticides selon la fréquence et le niveau de proximité de leurs contacts avec ces éléments. Résultats: L'âge d'apparition de la MP chez les patients préalablement exposés à des pesticides (54,74 ans) ou à des métaux toxiques (54,27 ans) s'est révélé notablement plus précoce en comparaison avec l'âge d'apparition de notre groupe témoin (59,26 ans ; p = 0,003). Chez ceux ayant été exposés à des pesticides, des contacts plus étroits (p = 0,03) et plus fréquents (p = 0,02) ont été corrélés négativement à l'âge d'apparition de la MP. Conclusion: En somme, l'exposition à des pesticides et à des métaux toxiques a été associée à un âge d'apparition de la MP plus précoce, corrélation qui s'est avérée plus importante avec un accroissement des niveaux d'exposition, qu'il s'agisse de fréquence ou de proximité.

Pulvinar sign in a case of anti-HU paraneoplastic encephalitis.

This article reports the case of a 68-year-old patient with anti-HU antibodies paraneoplastic encephalitis. The clinical manifestations were atypical and the paraclinical work-up, notably the magnetic resonance imaging (MRI) showing bilateral posterior thalamic hyperintensities (pulvinar sign), misleadingly pointed towards a variant Creutzfeld-Jakob disease. After presenting the case, the differential diagnosis of the pulvinar sign is discussed along with other important diagnostic considerations.

Foreperiod and range effects on time interval categorization.

One factor influencing the perceived duration of a brief interval is the length of the period preceding it, namely the foreperiod (FP). When multiple FPs are varied randomly within a testing session, longer FPs result in longer perceived duration. The purpose of this study was to identify what characteristics modulate this effect. In a task where participants were asked to categorize the duration of target intervals with respect to a 100-ms standard, the FPs were distributed over a 150-, 300-, or 900-ms range with the midpoint (1000 ms) of these distributions being kept constant. The results indicate that the effect of the length of variable FPs on perceived duration was much stronger in the 900-ms range condition. More specifically, this effect is due to the differences between the shortest FPs. The results also reveal that, overall, there are more short responses in the 300-ms condition than in the other range conditions. Moreover, the data reveal that the narrower the distribution, the better the discrimination. One interpretation of the main result (range effect) is that a wider distribution leads to an increased prior uncertainty towards the foreperiod length.

In-simulator training of driving abilities in a person with a traumatic brain injury.

AIM: This study reports the case of a 23-year-old woman (MC) who sustained a severe traumatic brain injury in 2004. After her accident, her driving license was revoked. Despite recovering normal neuropsychological functions in the following years, MC was unable to renew her license, failing four on-road evaluations assessing her fitness to drive. METHOD: In hope of an eventual license renewal, MC went through an in-simulator training programme in the laboratory in 2009. The training programme aimed at improving features of MC's driving behaviour that were identified as being problematic in prior on-road evaluations. To do so, proper driving behaviour was reinforced via driving-specific feedback provided during the training sessions. RESULTS: After 25 sessions in the simulator (over a period of 4 months), MC significantly improved various components of her driving. Notably, compared to early sessions, later ones were associated with a reduced cognitive load, less jerky speed profiles when stopping at intersections and better vehicle control and positioning. A 1-year retention test showed most of these improvements were consistent. CONCLUSIONS: The learning principles underlying well conducted simulator-based education programmes have a strong scientific basis. A simulator training programme like this one represents a promising avenue for driving rehabilitation. It allows individuals without a driving license to practice and improve their skills in a safe and realistic environment.

Sensory-specific clock components and memory mechanisms: investigation with parallel timing.

A challenge for researchers in the time-perception field is to determine whether temporal processing is governed by a central mechanism or by multiple mechanisms working in concert. Behavioral studies of parallel timing offer interesting insights into the question, although the conclusions fail to converge. Most of these studies focus on the number-of-clocks issue, but the commonality of memory mechanisms involved in time processing is often neglected. The present experiment aims to address a straightforward question: do signals from different modalities marking time intervals share the same clock and/or the same memory resources? To this end, an interval reproduction task involving the parallel timing of two sensory signals presented either in the same modality or in different modalities was conducted. The memory component was tested by manipulating the delay separating the presentation of the target intervals and the moment when the reproduction of one of these began. Results show that there is more variance when only visually marked intervals are presented, and this effect is exacerbated with longer retention delays. Finally, when there is only one interval to process, encoding the interval with signals delivered from two modalities helps to reduce variance. Taken together, these results suggest that the hypothesis stating that there are sensory-specific clock components and memory mechanisms is viable.

The lifespan of time intervals in reference memory.

To further explore how memory influences time judgments, we conducted two experiments on the lifespan of temporal representations in memory. Penney et al (2000, Journal of Experimental Psychology Human Perception and Performance 26 1770-1787) reported that the perceived duration of auditorily and visually marked intervals differs only when both marker-type intervals are compared directly. This finding can be explained by a 'memory-mixing' process, whereby the memory trace of previous intervals influences the perception of upcoming ones, which are then added to the memory content. In the experiments discussed here, we manipulated the mixing mode of auditory/visual signal presentations. In experiment 1, signals from the same modality were either grouped by blocks or randomised within blocks. The results showed that the auditory/visual difference decreased but remained present when modalities were grouped by blocks. In experiment 2, we used a line-segmentation task. The results showed that, after a training block was performed in one modality, the perceived duration of signals from the other modality was distorted for at least 30 trials and that the magnitude of the difference decreased as the block went on. The results of both experiments highlight the influence of memory on time judgments, providing empirical support to, and quantitative portrayal of, the memory-mixing process.

The structure of sensory events and the accuracy of time judgments.

We investigated how does the structure of empty time intervals influence temporal processing. In experiment 1, the intervals to be discriminated were the silent durations marked by two sensory signals, both lasting 10 or 500 ms; these signals were two identical flashes (intramodal: VV), or one visual flash (V) followed by an auditory tone (A) (intermodal: VA). For the range of duration under investigation (standards = 0.2, 0.6, 1, or 1.4 s), the results indicated that both the marker length and sensory mode influenced discrimination, but no interaction between these variables or between one of these variables and standard duration was significant. In experiment 2, we compared, for each of four marker-type conditions (VV, AA, VA, AV; and standard = 1 s), intervals marked by two 10 ms signals with intervals marked by unequal signal length (markers 1 and 2 lasting 10 and 500 ms, or 500 and 10 ms). As in experiment 1, the results revealed significant marker-mode and marker-length effects, but no significant interaction between these variables. Experiment 3 showed that, for the same conditions as in experiment 2, perceived duration is not influenced by marker length and that the variability of interval reproductions does not depend on the perceived duration of intervals. The results are discussed in the light of a single-clock hypothesis: marker-length and marker-mode effects are presented as being non-temporal sources of variability associated mainly with sensory and memory processes.