Morphological and functional imaging studies on the diagnosis and progression of Parkinson’s disease

This paper reviews the relative abilities of magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission tomography (SPECT), and proton magnetic resonance spectroscopy (MRS) to detect Parkinson’s disease and monitor its progression. Currently, the main role of MRI lies in its ability to discriminate atypical syndromes from Parkinson’s disease; however, new volumetric approaches may soon allow progression of nigral degeneration to be followed. Proton MRS can also detect reduced levels of putamen N-acetyl aspartate (NAA) in many patients with atypical parkinsonian syndromes. PET and SPECT are both sensitive means of detecting the presence of impaired dopamine terminal function in the striatum and following its progression. PET currently has the greater spatial resolution and provides the added advantages that it also allows extra-striatal dopaminergic function to be monitored.

     

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.     

Recognition and diagnosis of sleep disorders in Parkinson’s disease

Sleep disturbances are among the most frequent and incapacitating non-motor symptoms of Parkinson’s disease (PD), and are increasingly recognized as an important determinant of impaired quality of life. Here we review several recent developments regarding the recognition and diagnosis of sleep disorders in PD. In addition, we provide a practical and easily applicable approach to the diagnostic process as a basis for tailored therapeutic interventions. This includes a stepwise scheme that guides the clinical interview and subsequent ancillary investigations. In this scheme, the various possible sleep disorders are arranged not in order of prevalence, but in a ‘differential diagnostic’ order. We also provide recommendations for the use of sleep registrations such as polysomnography. Furthermore, we point out when a sleep specialist could be consulted to provide additional diagnostic and therapeutic input. This structured approach facilitates early detection of sleep disturbances in PD, so treatment can be initiated promptly.     

Early diagnosis and the clinical genetics of Alzheimer’s disease

Alzheimer’s disease (AD) has a significant genetic background manifested as autosomal dominant inheritance in some early-onset families and as familial risk in late-onset cases. Three genes responsible for early-onset autosomal dominant AD have been identified, and one gene, apolipoprotein E, has been confirmed as a susceptibility gene for late-onset forms of the disorder. These findings raise the possibility of genetic testing, either for early diagnosis or prediction. For early-onset autosomal dominant AD genetic testing will have a limited but useful role in confirming diagnosis in established cases and in predictive counselling for relatives; a situation analogous to that for Huntington’s disease. For late-onset AD significant problems remain to be overcome before the advances in molecular genetics have a direct clinical application Received: 24 August 1997 Accepted: 23 July 1988     

Determinants of delayed diagnosis in Parkinson’s disease

The early and accurate diagnosis of Parkinson’s disease (PD) is the first step towards optimal patient management. The aim of this study was to investigate the major determinants of delayed diagnosis in PD. We recruited a population-representative cohort of 239 newly-diagnosed PD patients who underwent clinical and neuropsychological evaluation. Non-parametric methods were used to define the factors associated with diagnostic delay. The median time from motor symptom onset to primary care physician (PCP) presentation was considerably longer than the time from PCP presentation to PD diagnosis (11 vs. 1 months). Male sex and presenting motor phenotype were independently associated with delayed PCP presentation on Cox regression analysis. Patients presenting with gait disturbance experienced the longest delay, whilst those presenting with tremor had the shortest. In summary, male sex and presenting motor phenotype are key determinants of delayed diagnosis in PD.     

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     

Non-dopaminergic therapy in Parkinson’s disease

Parkinson’s disease no longer seems to be a disease entity caused by only one pathogenetic factor. The facile characterization of Parkinson’s disease as a more or less isolated disorder of the dopaminergic system proves to be an unacceptable oversimplification of the pathology of the disease. Characteristically, not all dopaminergic systems of the central nervous system are involved in the degenerative process. In addition to the nigrostriatal dopaminergic pathway, parts of the glutamatergic, cholinergic, tryptaminergic, noradrenergic, adrenergic, serotonergic, and peptidergic neurons show serious cytoskeletal damage. In the light of these findings, drugs influencing these transmitter systems should be useful in the treatment of parkinsonian symptoms. For this reason, non-dopaminergic drugs are gaining more and more importance. Besides the theoretically interesting adenosine A2 receptor antagonists, budipine, a polyvalent potent new antiparkinsonian drug, has been tested in clinical studies. Budipine is a potent non-dopaminergic antiparkinsonian drug with pharmacological effects that are not comparable to those of conventional drugs applied in Parkinsonian pharmacotherapy. Budipine experimentally increased the brain content of noradrenaline, dopamine, serotonin, and histamine. The dopamine, serotonin, noradrenaline, gamma aminobutyric acid (GABA), and endorphine receptor affinities were not altered, but N-methyl-D-aspartate (NMDA) and sigma receptor affinities were increased as shown by in vivo and in vitro trials with budipine. MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP⁺ antagonistic effects have also been demonstrated. Budipine also shows neuroprotective as well as symptomatic antiparkinsonian effects. In two randomized, double-blind, multicenter, placebo-controlled studies, relevant therapeutic effects have been observed in previously untreated, so-called “de-novo” parkinsonian patients and in subjects in later stages of the disease. Budipine significantly reduces akinesia, rigidity, and tremor. Optimal effects of budipine can be seen 4–6 weeks after starting treatment with this substance. Budipine can be added to all available antiparkinsonian drugs. An open, prospective, long-term study of 2532 patients with Parkinson’s disease (Study BY701/01A) confirmed the favorable safety and tolerability profiles of budipine.

     

Patient experiences of receiving a diagnosis of Parkinson’s disease

Journal of Neurology - To report patients’ own experiences of receiving a diagnosis of Parkinson’s disease (PD) and to identify factors influencing this experience. A survey by the...     

Onset and progression factors in Parkinson’s disease: A systematic review

Current research has identified several factors thought to be associated with the onset and progression of Parkinson’s Disease (PD); however, whether certain factors contribute to or are protective against PD remains unclear. As such, a systematic search of the literature was performed using variations of MeSH and keyword search terms to identify and summarize systematic reviews and primary studies pertaining to factors associated with the onset and progression of PD. Factors referred to both traditional risk factors and prodromal markers. The following databases were searched: MEDLINE, MEDLINE In-Process, EMBASE, PsycINFO, Scopus, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ProQuest Dissertations & Theses, AARP AgeLine, and PDGene. A quality assessment of included systematic reviews was completed using the validated Assessment of the Methodological Quality of Systematic Reviews (AMSTAR) tool. Data extraction targeted reported factors, risk estimates, and 95% confidence intervals (CI). Findings identified 11 systematic reviews of sufficient quality reporting factors for PD onset, and no systematic reviews reporting factors for PD progression. In addition, 93 primary articles were identified, of which, 89 articles addressed factors related to PD onset and 4 articles addressed factors related to the PD progression. Pesticide exposure, rural living, well-water drinking, and farming occupation were consistently found to be positively associated with the onset of PD. Moreover, family history and polymorphisms to key genes were also found to be positively associated with the onset of PD. Conversely, coffee consumption, cigarette smoking, and some polymorphisms were consistently found to be negatively associated with the onset of PD. Urate was the only identified factor linked to the progression of PD; it was mostly found to be negatively associated with PD. In sum, the evidence was systematically found and summarized in the literature pertaining to factors related to the onset and progression of PD.     

Influence of neurotoxins and oxidative stress on the onset and progression of Parkinson’s disease

It is generally accepted that progressive, irreversible and regionally specific neurodegeneration and the presence of Lewy bodies are the essential pathological hallmarks of idiopathic parkinsonism. The causes of these phenomena, however, remain to be elucidated. One of the leading hypotheses is that oxidative stress induced by reactive oxygen species (ROS), such as the hydroxyl radical, damages essential components of the neuron, resulting ultimately in cell death. Observations in the parkinsonian brain at post-mortem support this hypothesis; for example, widespread oxidative protein modification is evident. There are several potential sources of increased oxidative stress in Parkinson’s disease, including mitochondrial dysfunction, increased free iron levels and impaired free radical defence mechanisms. Further, it is possible that glial, rather than neuronal, elements are primarily responsible for the initial increase in oxidative stress in the substantia nigra. It is likely that parkinsonism is the result of aberrations at multiple levels of neuronal function. Oxidative stress is no doubt one of the events involved in neurodegeneration, but is unlikely to be the initiating event. It is to be expected that the search for this event will continue for many years.

     

Potential role of biofeedback therapy for Parkinson’s disease

Parkinson’s disease(PD)is a neurological disorder characterized by rigidity,tremor,bradykinesia,and postural instability.Gait disturbance is one of cardinal symptoms of PD and affects the activities of daily living and quality of life.This symptom in advanced PD patients is usually refractory to medication and surgical intervention such as deep brain stimulation(Morishita et al.,2016).     

Early ophthalmologic features of Parkinson’s disease: a review of preceding clinical and diagnostic markers

Journal of Neurology - Non-motor symptoms in Parkinson’s disease are an important cause of morbidity and may even precede the onset of the motor features of the disease. Visual abnormalities...