First Author: Lothar Burghaus
All Authors: Burghaus L, SchÃ¼tz U, Krempel U, Lindstrom J, SchrÃ¶der H
Journal Title: Parkinsonism & related disorders
Abstract: Cerebral cortical cholinergic deficits, represented by a decrease in choline acetyltransferase activity, severe losses of nicotinic binding sites as well as cell degeneration in the basal forebrain can be observed in neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. The potential role of nicotinic acetylcholine receptor subunits as pharmacological targets for the treatment of cognitive deficits raises the question as to what extent these subunits are affected in neurodegenerative diseases. We here report on a significant decrease of the alpha4 and the alpha7 nicotinic acetylcholine receptor subunit in cortices of Parkinson patients which turns out to be similar to recent findings in Alzheimer patients.
The Role of Brain-Derived Neurotrophic Factor in the Pathophysiology of Psychiatric and Neurological Disorders
Authors: Becker C, Jick SS, Meier CR
Abstract: Large population based studies on the association of Parkinson disease (PD) with stroke are scarce. This study aimed to quantify the risk of a first-time diagnosis of idiopathic PD in patients with a history of stroke, and to assess incidence rates for stroke in PD patients.We used the UK-based General Practice Research Database to compare the prevalence of stroke/TIA in newly diagnosed PD patients and in a matched comparison group without PD between 1994 and 2005. We conducted a follow-up study with a nested case-control analysis to quantify the risk of incident stroke/TIA in relation to a previous PD diagnosis.A history of stroke/TIA was associated with a significantly increased relative risk of being diagnosed with PD compared to patients without such a history (adj. odds ratio [OR] 1.65, 95% confidence intervals [CI] 1.47-2.00). In the cohort study, the crude incidence rate ratios (IRRs) for incident hemorrhagic stroke, ischemic stroke or TIA were 0.66 (95% CI 0.26-1.72), 1.46 (95% CI 1.03-2.07) and 1.86 (95% CI 1.40-2.47), respectively.In this large observational study the risk of a PD diagnosis was significantly increased after a previous stroke event, as was the risk of a first-time ischemic stroke in newly diagnosed PD patients compared to persons free of PD.
Authors: Chin-Chan M, Navarro-Yepes J, Quintanilla-Vega B
Abstract: Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (A?) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as ?-synuclein (?-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase A?, P-Tau, ?-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of A? and ?-syn, and the reduced activity/protein levels of A? degrading enzyme (IDE)s such as neprilysin or insulin IDE. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action.
Authors: Farrer MJ
Abstract: Parkinson disease is a complex, multifactorial neurodegenerative disease. Although a heritable basis was originally thought unlikely, recent studies have implicated several genes in its pathogenesis, and molecular findings now allow accurate diagnosis and challenge past criteria for defining Parkinson disease. Most importantly, genetic insights provide the rationale for new strategies for prevention or therapy, and have led to animal models of disease in which these strategies can be tested. Neuroprotective therapies can now be designed to slow or halt disease progression in affected subjects and asymptomatic carriers.
Authors: Gayed I, Joseph U, Fanous M, Wan D, Schiess M, Ondo W, Won KS
Abstract: The aim of this study was to evaluate the impact of DaTscan in a heterogeneous group of patients with movement disorders as well as the degree of confidence in scan findings between different readers.A retrospective evaluation of consecutive patients who underwent DaTscan during 1 year was performed. The patients' demographics, symptoms, duration, clinical diagnosis, and medications were collected. The scan findings were categorized by 2 blinded observers on a semiquantitative scale as follows: 0, normal; 1, mild; 2, moderate; 3, marked; and 4, absent uptake for each of the caudate heads and putamina separately. A correlation of the scan findings with the clinical symptoms and diagnosis as well as interobserver agreement was performed. Disagreement was considered when a difference greater than 2 in more than 1 area of the basal ganglia was recorded. Descriptive statistics and ? test for interobserver agreement were used for data analysis.Fifty-seven patients were included (mean age, 63.4 years; 29 men, 28 women). Clinical diagnosis of Parkinson disease (PD) was certain in 26 and uncertain in 31 patients. DaTscan was markedly abnormal in 24 (92%) of 26 patients with certain clinical diagnosis of PD and normal in the remaining 2 (8%). In 31 patients with uncertain diagnosis, 15 (48%) had markedly abnormal scans, 5 (16%) had mild abnormalities, and 11 (36%) had normal scans. Each of the sensitivity and positive predictive value of DaTscan in patients who had certain clinical diagnosis of PD (26 patients) is 92%. Interobserver agreement occurred in 52 (91%) of 57 scans and disagreement in 5 (9%) of 57 (? = 0.82). There was also a good correlation with laterality of symptoms in 32 (82%) of 39 positive studies.Markedly abnormal DaTscan is confirmed as the diagnostic pattern for PD. This pattern helps confirm the diagnosis in patients with unclear clinical diagnosis. Good interobserver agreement is easily obtained in reading DaTscans.
Authors: Gao J, Huang X, Park Y, Hollenbeck A, Blair A, Schatzkin A, Chen H
Abstract: Preliminary evidence suggests that daytime sleepiness may predate clinical diagnosis of Parkinson disease. The authors examined daytime napping and nighttime sleeping durations, reported in 1996-1997 by 220,934 US NIH-AARP Diet and Health Study participants, in relation to Parkinson disease diagnoses at 3 clinical stages: established (cases diagnosed before 1995, n = 267), recent (1995-1999, n = 396), and prediagnostic (2000 and after, n = 770). Odds ratios and 95% confidence intervals were derived from multivariate logistic regression models. Longer daytime napping was associated with higher odds of Parkinson disease at all 3 clinical stages: the odds ratios comparing long nappers (>1 hour/day) with nonnappers were 3.9 (95% confidence interval: 2.8, 5.6) for established cases, 2.2 (95% confidence interval: 1.7, 3.0) for recent cases, and 1.5 (95% confidence interval: 1.2, 1.9) for prediagnostic cases. Further control for health status or nighttime sleeping duration attenuated the association for established cases but made little difference for recent or prediagnostic cases. In the nighttime sleeping analysis, a clear U-shaped association with Parkinson disease was observed for established cases; however, this association was attenuated markedly for recent cases and disappeared for prediagnostic cases. This study supports the notion that daytime sleepiness, but not nighttime sleeping duration, is one of the early nonmotor symptoms of Parkinson disease.
Authors: Doan JB, de Bruin N, Pellis SM, Suchowersky O, Whishaw IQ, Brown LA
Abstract: We examined whether people with Parkinson disease (PD) have difficulty negotiating a gait obstruction in threatening (gait path and obstacle raised above floor) and nonthreatening (gait path and obstacle at floor level) contexts. Ten PD patients were tested in both Meds OFF and Meds ON states, along with 10 age-matched controls. Participants completed 18 gait trials, walking 4.7?m at a self-selected speed while attempting to cross an obstacle 0.15?m in height placed near the centre point of the walkway. Kinematic and kinetic parameters were measured, and obstacle contact errors were tallied. Results indicated that PD patients made more obstacle contacts than control participants in the threatening context. Successful crossings by PD patients in the threatening condition also exhibited kinematic differences, with Meds OFF PD patients making shorter crossing steps, with decreased initiation and crossing velocities. The findings from this study lend support to the theory that PD patients rely on directed attention to initiate and control movement, while providing indication that the motor improvements provided by current PD pharmacotherapy may be limited by contextual interference. These movement patterns may be placing PD patients at risk of obstacle contact and falling.
Authors: Evatt ML, DeLong MR, Kumari M, Auinger P, McDermott MP, Tangpricha V,
Abstract: Vitamin D insufficiency has been reported to be more common in patients with Parkinson disease (PD) than in healthy control subjects, but it is not clear whether having a chronic disease causing reduced mobility contributes to this relatively high prevalence.To examine the prevalence of vitamin D insufficiency in a cohort of untreated patients with early PD (diagnosed within 5 years of study entry). DESIGN, SETTING, AND PATIENTS The Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) cohort is a well-characterized cohort of subjects with early, nondisabling PD. The cohort is well suited for examining the prevalence of vitamin D insufficiency early in the course of the disease. We conducted a survey study of vitamin D status in stored blood samples from patients with PD enrolled in the placebo group of the DATATOP trial. Samples from baseline visits and end point/final visits (mean [SD], 18.9 [13.1] months) were analyzed for 25-hydroxyvitamin D (25[OH]D) concentration in blinded fashion.The mean vitamin D concentration and the prevalence of vitamin D insufficiency at baseline and end point/final visits.Among 199 subjects, 170 (85.4%) had samples from the baseline and end point visits available for analysis; 13 were excluded (10 with low probability of having PD and 3 with 25[OH]D concentrations>3 SDs above the mean). In the remaining 157 subjects, the mean (SD) 25(OH)D concentrations at the baseline and end point visits were 26.3 (8.6) ng/mL and 31.3 (9.0) ng/mL, respectively (to convert to nanomoles per liter, multiply by 2.496). The prevalence of vitamin D insufficiency (25[OH]D concentration<30.0 ng/mL) was 69.4% at baseline and 51.6% at the end point.The prevalence of vitamin D insufficiency in patients with early PD was similar to or higher than those reported in previous studies. Vitamin D concentrations did not decline during progression of PD. Further studies are needed to elucidate the natural history and significance of vitamin D insufficiency in PD.
Authors: Knobel D, Aybek S, Pollo C, Vingerhoets FJ, Berney A
Abstract: To describe how subthalamic deep brain stimulation (STN-DBS) and reduction in dopamine replacement therapy (DRT) allowed rapid resolution of dopamine dysregulation syndrome (DDS) with severe behavioral disorder in a patient with late stage Parkinson disease (PD).DDS was recently defined as compulsive use of dopaminergic drugs, associated with severe behavioral symptoms, and impaired social functioning, occurring in about 4% of PD patients under DRT. STN-DBS is an effective treatment for late stage PD with treatment resistant motor fluctuations, which frequently allows also to reduce DRT.A late stage PD patient referred to our center for STN-DBS, suffering from severe DDS necessitating in-ward psychiatric management, was comprehensively assessed preoperatively and postoperatively for motor, cognitive, and psychiatric status.Following subthalamic DBS procedure and medication reduction, we observed a rapid and dramatic resolution of DDS and associated psychiatric symptoms, allowing discharge from a 2-year stay in a psychiatric institution.DDS occurring in late stage PD patients may be dramatically improved by STN-DBS, possibly in relation with the reduction of dopaminergic medication. In contrast to other psychiatric symptoms, DDS should not be considered as an obstacle to DBS procedure in late stage PD patients.
Authors: Rogano LA, Assis M, Teixeira MJ
Abstract: We present ten patients with Parkinson's disease who underwent stereotactic ablative radiofrequency procedures. Seven patients underwent pallidotomy, two subthalamotomy and VIM, and one subthalamotomy. Seven developed miosis and all semiptosis ipsilateral immediately after the procedure. The occurrence of Horner's syndrome is probably due to the lesion of sympathetic fibers among hypothalamus, Forel's field and thalamus after the stereotactic procedure.
Authors: Bonnet AM, Houeto JL
Abstract: The efficiency of pergolide has been confirmed by the study of a group 29 parkinsonian patients. They were relatively young, and the duration of evolution of their Parkinson's disease was more then ten years, with levodopa-induced dyskinesia and fluctuations. In this group of patients with most serious motor disability, it has been possible to improve dyskinesia and fluctuations with a relatively important dosage of pergolide and without increase of levodopa dosage.