Enhancing both motor and cognitive functioning in Parkinson's disease: Aerobic exercise as a rehabilitative intervention.

BACKGROUND: Aerobic exercise training (AET) has been shown to provide health benefits in individuals with Parkinson's disease (PD). However, it is yet unknown to what extent AET also improves cognitive and procedural learning capacities, which ensure an optimal daily functioning. OBJECTIVE: In the current study, we assessed the effects of a 3-month AET program on executive functions (EF), implicit motor sequence learning (MSL) capacity, as well as on different health-related outcome indicators. METHODS: Twenty healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike-training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after AET, EF tests assessed participants' inhibition and flexibility functions, whereas implicit MSL capacity was evaluated using a version of the Serial Reaction Time Task. RESULTS: The AET program was effective as indicated by significant improvement in aerobic capacity in all participants. Most importantly, AET improved inhibition but not flexibility, and motor learning skill, in both groups. CONCLUSION: Our results suggest that AET can be a valuable non-pharmacological intervention to promote physical fitness in early PD, but also better cognitive and procedural functioning.

Referrals, Wait Times and Diagnoses at an Urgent Neurology Clinic over 10 Years.

BACKGROUND: An urgent neurology assessment clinic was created at our institution to improve access to prompt neurological assessment, and has been in operation for over a decade. We assessed its timeliness and impact. METHODS: The clinic database was examined retrospectively for trends in the volume and waiting time to assessments, neurologic diagnoses, and whether neurologic assessment changed patients' diagnoses. Before and after implementation, the frequency of emergency department neurology assessments and hospital admissions for neurological investigation were compared. RESULTS: In the first decade, 25145 referrals were received; 12460 patients were accepted and assessed within an average of 3.8 working days. The most common problems seen included headache and seizure (20.2% each). Overall, 44.6% of assessments resulted in a change to the referring diagnosis; this proportion varied by the type of problem seen (from 10.5% for seizures to 92.5% for psychiatric disturbances). From the pre- to post-opening periods, there were fewer emergency room neurological assessments (35.7% reduction) and fewer hospital admissions for neurological investigation (4.4/week to 2.2/week, 50% reduction). CONCLUSIONS: The urgent neurology clinic model at our institution has provided excellent service, including wait times of a few days, to a catchment of over two million Canadians for over a decade; clinic assessments have affected diagnoses and patient care.

Kernel-based testing for single-cell differential analysis.

Single-cell technologies offer insights into molecular feature distributions, but comparing them poses challenges. We propose a kernel-testing framework for non-linear cell-wise distribution comparison, analyzing gene expression and epigenomic modifications. Our method allows feature-wise and global transcriptome/epigenome comparisons, revealing cell population heterogeneities. Using a classifier based on embedding variability, we identify transitions in cell states, overcoming limitations of traditional single-cell analysis. Applied to single-cell ChIP-Seq data, our approach identifies untreated breast cancer cells with an epigenomic profile resembling persister cells. This demonstrates the effectiveness of kernel testing in uncovering subtle population variations that might be missed by other methods.

Inflammatory markers and BDNF in obstructive sleep apnea (OSA) in Parkinson's disease (PD).

OBJECTIVE: Obstructive sleep apnea (OSA) exacerbates Parkinson's disease (PD) manifestations including cognitive dysfunction. Both OSA and PD have been associated with inflammation. Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive function. We aimed to investigate inflammatory cytokines and BDNF in relation to OSA and PD symptoms. METHODS: In a prospective observational study, patients with PD underwent overnight polysomnography. Morning serum levels of interleukin (IL)-1ß, IL-6, IL-8, TNFα, and BDNF were quantified at baseline (n = 64) and 6 months (n = 38). Outcomes included non-motor and motor standard scores; Montreal Cognitive Assessment (MoCA); and Epworth Sleepiness scale (ESS). Associations were assessed using linear regression, adjusting for age, sex and body mass index. RESULTS: At baseline, IL-6 was associated with the Apnea-Hypopnea Index (ß = 0.013, p = 0.03), and the Oxygen Desaturation Index (ß = 0.028, p = 0.002). No other associations between cytokines and sleep parameters were found. Motor dysfunction was associated with IL-6 (ß = 0.03, p = 0.001). ESS was associated non-significantly with IL-6 (ß = 0.04, p = 0.07) and BDNF (ß = 555, p = 0.06). At follow-up, change in IL-6 was associated with change in non-motor (ß = 0.08, p = 0.007), and motor (ß = 0.03, p = 0.001) symptoms. Change in BDNF was associated with change in ESS (ß = 1450, p = 0.02). INTERPRETATION: We found an association between IL-6 levels and both OSA severity and PD motor dysfunction. At follow-up, increasing IL-6 correlated with deterioration of motor and non-motor PD symptoms. Increasing BDNF correlated with increasing sleepiness. Further work with a larger sample size is needed, but our results support the hypothesis that OSA-related inflammation plays a role in PD manifestations and progression.

Influence of aerobic exercise training on the neural correlates of motor learning in Parkinson's disease individuals.

BACKGROUND: Aerobic exercise training (AET) has been shown to provide general health benefits, and to improve motor behaviours in particular, in individuals with Parkinson's disease (PD). However, the influence of AET on their motor learning capacities, as well as the change in neural substrates mediating this effect remains to be explored. OBJECTIVE: In the current study, we employed functional Magnetic Resonance Imaging (fMRI) to assess the effect of a 3-month AET program on the neural correlates of implicit motor sequence learning (MSL). METHODS: 20 healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+ 5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after the AET program, participants' brain was scanned while performing an implicit version of the serial reaction time task. RESULTS: Brain data revealed pre-post MSL-related increases in functional activity in the hippocampus, striatum and cerebellum in PD patients, as well as in the striatum in HC individuals. Importantly, the functional brain changes in PD individuals correlated with changes in aerobic fitness: a positive relationship was found with increased activity in the hippocampus and striatum, while a negative relationship was observed with the cerebellar activity. CONCLUSION: Our results reveal, for the first time, that exercise training produces functional changes in known motor learning related brain structures that are consistent with improved behavioural performance observed in PD patients. As such, AET can be a valuable non-pharmacological intervention to promote, not only physical fitness in early PD, but also better motor learning capacity useful in day-to-day activities through increased plasticity in motor related structures.

Bilateral focal polymicrogyria in Ehlers-Danlos syndrome.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a heterogeneous group of generalized connective tissue disorders that has been described in association with epilepsy and cerebral cortical dysplasia, mostly gray matter heterotopias, in 3 reports. However, to our knowledge, association of EDS with another type of cortical cerebral dysplasia, bilateral focal polymicrogyria, has never previously been described. SETTING: Two research-oriented hospitals. PATIENTS: We describe 2 patients with EDS and bilateral polymicrogyria. The first, a 29-year-old black man, presented with EDS of unspecified type, seizures, and bilateral frontocentral and frontoposterior polymicrogyria with hypoplasia of the inferior part of the cerebellar vermis. The second, a 20-year-old woman, had type III EDS, seizures and congenital bilateral perisylvian syndrome with polymicrogyria. CONCLUSIONS: The association of bilateral focal polymicrogyria and EDS in these 2 patients suggests that extracellular matrix proteins implicated in the pathogenesis of EDS, such as collagen and tenascin, may play an important role in cerebral cortical formation and organization. In a clinical setting, the association of EDS with these cortical structural lesions has implications for diagnosis and management.

Genome-wide scan for Parkinson's disease: the GenePD Study.

A genome-wide scan for idiopathic PD in a sample of 113 PD-affected sibling pairs is reported. Suggestive evidence for linkage was found for chromosomes 1 (214 cM, lod = 1.20), 9 (136 cM, lod = 1.30), 10 (88 cM, lod = 1.07), and 16 (114 cM, lod = 0.93). The chromosome 9 region overlaps the genes for dopamine beta-hydroxylase and torsion dystonia. Although no strong evidence for linkage was found for any locus, these results may be of value in comparison with similar studies by others.

Epidemiologic study of 203 sibling pairs with Parkinson's disease: the GenePD study.

OBJECTIVE: To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with PD. METHODS: Sibling pairs (n = 203) with PD were collected as part of the GenePD study. Standardized family history, medical history, and risk factor data were collected and analyzed. RESULTS: The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset (p = 0.03) and multivitamin use with later onset (p = 0.007). Age at onset correlation between sibling pairs was significant (r = 0.56, p = 0.001) and was larger than the correlation in year of onset (r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with PD. The frequency of affected parents (7.0%) and siblings (5.1%) was increased when compared with frequency in spouses (2.0%). CONCLUSIONS: The greater similarity for age at onset than for year of onset in sibling pairs with PD, together with increased risk for biological relatives over spouses of cases, supports a genetic component for PD. Risk to siblings in this series is increased over that seen in random series of PD cases; however, patients in this sample have similar ages at onset and sex distribution as seen for PD generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease.

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Longitudinal study of asymptomatic meningococcal carriage in two Belgian populations of schoolchildren.

In Brussels, a 15-month longitudinal survey was conducted in two primary schools, from March 1975 to May 1976, in order to analyse the dynamic of asymptomatic meningococcal carriage, during an epidemic mainly caused by serogroup B, serotype 2 Neisseria meningitidis. In the first school, which is situated in a suburban area with upper-middle socio-economic status of residents, a mean prevalence of carriers of 10 per cent, an acquisition rate of eight per 1000 months, and a mean duration of carriage of 12.4 months were observed among 158 schoolchildren aged six to 11 years old. In the second school, which is situated in a densely populated area with low socio-economic status of residents, a mean prevalence of carriers of 33 per cent, an acquisition rate of 28 per 1000 months, and a mean duration of carriage of 11.7 months were observed among 203 schoolchildren aged three to 14 years old. For both schools, the median duration of carriage was estimated at 9.4 months. The differences of prevalence and incidence of acquisition between the two schools cannot be explained by age, sex or ethnic factors and are probably related to socio familial variables. The theoretical relationship between prevalence, incidence and duration of meningococcal carriage was for the first time demonstrated in this study. The results also suggest that populations of low socio-economic status and living in densely populated areas constitute a target population for meningococcal disease prevention.

Impact of air pollution by lead on the heme biosynthetic pathway in school-age children.

Blood-lead level (Pb-B), erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity, free erythrocyte porphyrin (FEP) concentration, delta-aminolevulinic acid concentration in urine (ALAU), hematocrit value, and hemoglobin concentration were compared for groups of children 10-13 years old from areas differently polluted by lead (rural area and lead smelter area). The biological responses of the children were also compared with those observed in adults similarly exposed to lead (Pb-B: 10-40 mug/100 ml). Compared with the rural children, children living less than 1 km from the smelter exhibited a significant increase of Pb-B and FEP, a significant inhibition of ALAD, and a slight positive correlation of ALAU with Pb-B; however, they showed no biological signs of anemia. In children living approximately 1.5 km from the smelter, there was still a significant increase of Pb-B and a concomitant inhibition of ALAD, but no change in FEP concentration. Comparison of the dose-response curves between Pb-B and FEP in adult males, adult females, and children indicates that the sensitivity to lead is in the order of children larger than or equal to women greater than men. Based on the FEP response, it is proposed that 25 mug Pb/100 ml blood be regarded as the maximum biologically allowable concentration of lead in blood of school-age children.

[Epidemiology of "stress" and the problems it poses in the medical and social fields. The special case of acute psychic reactions to psychologic trauma]. / L"épidémiologie du "stress" et les problèmes qu'il pose sur le plan médical et social. Le cas particulier des réactions psychiques aiguës à un psychotraumatisme.

It is important to distinguish clearly between the terms "stress" and the "breakdown in adaptation" which can result therefrom. Stress may be defined as the alert response of the organism to physical and psychological aggression. We need to expand our knowledge about the physiological and pathological reactions which occur at the onset of stress and study the importance of disturbances thus engendered. The direct and indirect consequences of stress and breakdown in adaptation also require evaluation not only from the general and occupational medicine viewpoint, but also sociologically. At the same time, research should be carried out on ways of avoiding--or at least limiting--the damaging consequences of exposure to stress-inducing situations, and on establishing effective preventive or corrective treatment. Special attention should be given to acute psychotraumatism.