Levodopa availability improves with progression of Parkinson’s disease

Background Previous pharmacokinetic trials with standard levodopa formulations showed a different behaviour of levodopa degradation in plasma of patients with Parkinson’s disease (PD) in various stages. Objectives To investigate associations between levodopa plasma levels in relation to the scored intensity of PD. Subjects and Methods We administered water soluble 100 mg levodopa and 25 mg benserazide to 50 PD patients, taken off medication for at least 12 hours, and assessed the levodopa plasma concentrations during an 180 minutes period under standardised conditions. Results The computed area under the curve (AUC) values of levodopa plasma levels were significant higher in advanced PD patients. PD rating scores significantly correlated to the AUC outcomes and the maximum levodopa plasma concentration. Conclusions Levodopa availability improves with progression of PD. This may result from deteriorated peripheral activity of levodopa metabolising enzymes or an increasing enteric dysfunction with subsequent better duodenal levodopa absorption or both. Received in revised form: 12 February 2005     

Drivers with Parkinson’s disease: are the symptoms of PD associated with restricted driving practices?

This study examined whether symptoms (motor, cognitive, vision, sleepiness, depression) of Parkinson’s disease (PD) were associated with restricted driving practices. To quantify driving practices, electronic devices were installed in the vehicles of 27 drivers with PD (78 % men; M = 71.6, SD = 6.6; Unified Parkinson’s Disease Rating Scale (UPDRS) motor score M = 30.1, SD = 8.6; disease duration M = 3.9, SD = 2.8 years) and 20 controls (80 % men; M = 70.6, SD = 7.9) for 2 weeks. Participants completed measures of sleepiness, depression, quality of life, and assessments of motor, cognitive and visual functions. The PD group had significantly slower brake response times (p < 0.05), poorer cognitive and quality of life scores (p < 0.01) and greater depression (p < 0.05) compared to controls. Slower reaction time was significantly related to reduced driving; specifically, fewer trips (r = ?0.46; p < 0.05), distance (r = ?0.54, p < 0.01) and duration at night (r = ?0.58, p < 0.01). Better cognitive scores were associated with driving less often in difficult situations such as bad weather and rush hour (p < 0.05), as well as reduced speed on city streets, but only for the control group. While most drivers with PD rated their overall health as good or excellent, the five PD drivers who rated their health more poorly had significantly worse clinical symptoms (UPDRS motor scores, contrast sensitivity, depression, brake response time) and more restricted driving patterns. These findings show that drivers with PD who perceive their health poorly have greater symptomatology and were more likely to restrict their driving, possibly due to noticeable declines in multiple driving-related abilities.     

Animal models of Parkinson’s disease progression

Parkinson’s disease (PD) is a progressive neurodegenerative disorder whose etiology is not understood. This disease occurs both sporadically and through inheritance of single genes, although the familial types are rare. Over the past decade or so, experimental and clinical data suggest that PD could be a multifactorial, neurodegenerative disease that involves strong interactions between the environment and genetic predisposition. Our understanding of the pathophysiology and motor deficits of the disease relies heavily on fundamental research on animal models and the last few years have seen an explosion of toxin-, inflammation-induced and genetically manipulated models. The insight gained from the use of such models has strongly advanced our understanding of the progression and stages of the disease. The models have also aided the development of novel therapies to improve symptomatic management, and they are critical for the development of neuroprotective strategies. This review critically evaluates these in vivo models and the roles they play in mimicking the progression of PD.     

Early diagnosis and therapy of Parkinson’s disease: can disease progression be curbed?

Parkinson’s disease (PD), the second most common neurodegenerative disorder, is characterized by the loss of dopamine (DA) neurons in the substantia nigra (SN). Currently, there are numerous therapeutic drugs for the treatment of PD; however, they are limited in efficacy and primarily target motor symptoms. Furthermore, these drugs have various adverse effects after long-term use. Usually, PD patients begin to take anti-parkinsonian drugs when they have developed obvious motor symptoms. At that time, a significant portion of the DA neurons in SN has been lost and the biology of the disease may have already been present for over a decade. This stage of PD diagnosis underscores the need for biomarkers that accurately indicate the onset of PD in order to apply disease-modifying therapies at an earlier stage of disease. However, development of disease modifying drugs has faced many setbacks, mostly due to the ways in which clinical trials are planned and executed. In this review paper, we summarize the recent findings of genetic biomarkers such as SNCA, LRRK2, parkin, PINK1, DJ1, etc., as well as evaluate the imaging techniques such as single proton emission computed tomography and positron emission tomography for their potential in diagnosing PD at earlier stages. Clinical trial designs, along with a comprehensive analysis of neuroprotective drugs for future treatment of PD, are also reviewed.     

The personality associated with Parkinson’s disease

Since at least 1913 reports have suggested there are personality traits and behaviors that are found premorbidly in those who go on to develop Parkinson’s disease (PD). This premorbid personality consists of traits such as industriousness, punctuality, inflexibility, cautiousness, and lack of novelty seeking and persists after the onset of the motor illness. The existence of this personality remains controversial but is supported by case-based anecdotes, twin studies, and comparison of patients with PD with medical control patients on standardized instruments. In addition a large number of epidemiologic studies show that people who develop PD have low lifetime risks for cigarette smoking, coffee drinking, and alcohol consumption, again suggesting that there is a behavior pattern that predates PD. Despite the retrospective nature of much of these data, the use of nonstandardized instruments, and diffuse concepts of personality, the great majority of studies show striking similarity in identifying these traits. An integrating hypothesis, involving damage to dopaminergic systems, known to predate the onset of the motor illness, is discussed.     

The progression of pathology in longitudinally followed patients with Parkinson’s disease

The present study describes the pathological progression of longitudinally followed cases with levodopa-responsive Parkinson’s disease who came to autopsy during the Sydney Multicenter Study of Parkinson’s disease. Standardised clinical and neuropathological assessments over five epochs of time verified three different clinicopathological groups. A group of younger onset patients with a typical long duration clinical course of Parkinson’s disease. This group of cases had Lewy body distributions consistent with the Braak staging of disease. In this group, brainstem Lewy bodies dominate in those surviving to 5 years; by 13 years, 50% of cases have a limbic distribution of Lewy bodies; and by 18 years, all will have at least this pathological phenotype. Approximately 25% of cases had an early malignant, dementia-dominant syndrome and severe neocortical disease consistent with dementia with Lewy bodies. The last group had an older onset, shorter survival, and a more complex disease course with higher Lewy body loads and a higher proportion with additional neuropathologies. These cases with higher loads of Lewy bodies and shorter survivals suggest that widespread Lewy body pathology either occurs at the onset of clinical disease or rapidly infiltrates the brain. In these cases with shorter survivals, there was more plaque pathology, supporting a more aggressive and linked phenotype. Our data suggest that the selection of similar study cohorts by pathology alone would not be able to differentiate the three different phenotypes identified. The data are also not consistent with a unitary concept of the pathogenesis of Lewy body disease.     

Fear of falling is independently associated with recurrent falls in patients with Parkinson’s disease: a 1-year prospective study

The present study aimed to examine whether fear of falling (FoF) could independently predict recurrent falls in people with Parkinson’s disease (PD). Seventy patients with PD completed the study. Thirty-two patients had fallen at least once in the previous 12 months. Most of patients with PD had moderate disease severity (Hoehn and Yahr stage III). FoF was assessed by the activities-specific balance confidence (ABC) scale. PD specific motor and balance impairment was determined by Unified PD rating scale (UPDRS). Functional mobility was measured by timed-up-and-go (TUG) test. All patients were followed for 12 months by phone interview to register monthly fall incidence. Results of stepwise discriminant analysis showed that after adjusting for the fall history (F = 32.57, P < 0.001) and UPDRS motor score (F = 25.23, P < 0.001), ABC score (F = 18.84, P < 0.001) remained as a significant predictor of recurrent falls. We further established that a cut-off ABC score of 69 (i.e. 0–100, 0 indicates no confidence and 100 indicates full confidence) demonstrated the best sensitivity (93%) in predicting future falls in PD patients. The results indicate that those with an ABC score <69 at baseline had significantly higher risk of sustaining recurrent falls in the next 12 months. Findings of the present study highlight the importance of considering FoF during fall risk assessment in patients with PD.     

Neurocysticercosis associated with hypoparathyroidism and Fahr's disease (?): report of a case

The author reports a case of neurocysticercosis and hypoparathyroidism in a 28 year-old female with bilateral symmetric basal ganglia calcification demonstrable by C.A.T.-Scan. A brief review of the literature is made in order to show why the eponym "Fahr's disease" should not be applied to this case.     

Occurrence of Crohn's disease with Parkinson’s disease

We retrospectively investigated the co-occurrence of Crohn's disease in a cohort of 876 patients with Parkinson’s disease, based on the observation that LRRK2 is a shared genetic risk factor. We identified 2 patients with Crohn's disease; this number was consistent with the number of cases expected in the general population.     

Comparison of Botulinum neurotoxin efficiency in dystonia associated with Parkinson’s disease and atypical parkinsonism: a retrospective study with a self-reported improvement scale

Journal of Neurology - Botulinum neurotoxin (BoNT) is a useful therapeutic option to treat dystonic manifestations. Data on its efficiency on dystonia associated with Parkinson’s disease (PD)...     

Hyposmia: a possible biomarker of Parkinson’s disease

Hyposmia, identified as reduced sensitivity to odor, is a common non-motor symptom of Parkinson’s disease (PD) that antedates the typical motor symptoms by several years. It occurs in ～90% of early-stage cases of PD. In addition to the high prevalence, the occurrence of hyposmia may also predict a higher risk of PD. Investigations into hyposmia and its relationship with PD may help elucidate the underlying pathogenic mechanisms. This review provides an update of olfactory dysfunction in PD and its potential as a biomarker for this devastating disease.