Untreated Parkinson's Disease Research Articles

Ophthalmologic features of Parkinson's disease

Patients with Parkinson's disease (PD) commonly complain of impaired visual function and difficulty reading, despite normal visual acuity. Visual problems are particularly important in this population of patients with impaired ambulation and driving safety issues. Although previous studies have evaluated contrast sensitivity, color vision, visuospatial processing, visual hallucinations, and ocular movements, none has systematically evaluated the ocular complaints and ocular findings of PD patients. Thirty patients with early untreated PD and 31 control subjects without neurologic or known ocular diseases were ophthalmologically evaluated for the frequency of visual complaints, dry eyes, blepharitis, visual hallucinations, reduced blink rate, blepharospasm, and convergence insufficiency. Ocular complaints suggesting ocular surface irritation, altered tear film, visual hallucinations, blepharospasm, decreased blink rate, and decreased convergence amplitudes were more common in PD patients than in control subjects. These findings likely account for many of the visual difficulties commonly encountered by PD patients and are directly secondary to PD and not to side-effects of drugs used to treat PD. These ocular abnormalities frequently respond to treatment. A list of practical advices regarding the ocular evaluation of PD patients is provided at the end of the article.—authors’ abstract

Ophthalmologic features of Parkinson’s disease

Patients with Parkinson's disease (PD) commonly complain of impaired visual function and difficulty reading, despite normal visual acuity. Although previous studies have evaluated contrast sensitivity, color vision, visuospatial processing, visual hallucinations, and ocular movements, none has systematically evaluated the ocular complaints and ocular findings of PD patients. Thirty patients with early untreated PD and 31 control subjects without neurologic or known ocular diseases were ophthalmologically evaluated for the frequency of visual complaints, dry eyes, blepharitis, visual hallucinations, reduced blink rate, blepharospasm, and convergence insufficiency. Ocular complaints suggesting ocular surface irritation, altered tear film, visual hallucinations, blepharospasm, decreased blink rate, and decreased convergence amplitudes were more common in PD patients than in control subjects. These findings likely account for many of the visual difficulties commonly encountered by PD patients. These ocular abnormalities frequently respond to treatment.

Análise acústica da prosódia em mulheres com doença de Parkinson: efeito da Levodopa

Untreated Parkinson's disease (PD) patients display speech abnormalities characterized by narrow range of fundamental frequency (Fo) variation and higher amplitude. The role of dopaminergic systems in the pathogenesis of these changes as well as the therapeutic effect of L-dopa have not been clearly determined. The aim of this study is to assess the effect of L-dopa on the prosodic features of the speech of female PD patients. We have studied 8 PD female patients (63.5 +/- 6.8 years). The PD patients (H-Y stage 2, seven subjects; stage 2.5, four patients; stage 1, one patient) were examined when off and on. The fundamental frequency, intensity and duration of five affirmative sentences were analysed with the software WinPitch 1.8 (Philippe Martin). The analysed Fo parameters were: usual Fo (Fo us), maximal Fo (Fo max), minimal Fo (Fo min), Fo max of the prenuclear tonic (Fo max PNT), Fo min of the prenuclear tonic (Fo min PNT), Fo max of the nuclear tonic (Fo max NT), Fo min of the nuclear tonic (Fo min TN), velocity of melodic variation of the PNT (VPNT), velocity of melodic variation of the NT (VNT), amplitude of melodic variation of the PNT (APNT), and amplitude of melodic variation of the NT (ANT). Duration of the statement (D), duration of the PNT (DPNT), duration of the NT (DNT) and number of syllables per second (NSS) were the duration parameters investigated. The following intensity variables were studied: mean intensity (MI), maximal intensity (I max), minimal intensity (I min), intensity of the PNT (IPNT) and intensity of the NT (INT). Differences were statistically significant if p<0.05. When on, PD patients had significantly higher Fo max PNT (201.9 +/- 27.5 Hz), higher APNT (22.1 +/- 18.7 Hz), and smaller MI (32 +/- 6.2 dB) in comparison with off period (respectively: 168.5 +/- 83.5 Hz, 20.4 +/- 12.1 Hz, 32.7 +/- 5.6 dB). Our findings show that L-dopa replacement therapy slightly improves the Fo range and the intensity of speech of Brazilian female PD patients. These results suggest that non-dopaminergic systems are probably involved in the pathogenesis of prosody changes in PD. They also indicate that therapies other than dopaminergic agents are warranted to treat speech abnormalities in PD.

Patterning of globus pallidus local field potentials differs between Parkinson's disease and dystonia.

Here we test the hypothesis that there are distinct temporal patterns of synchronized neuronal activity in the pallidum that characterize untreated and treated parkinsonism and dystonia. To this end we recorded local field potentials (LFPs) from the caudal and rostral contact pairs of macroelectrodes implanted into the pallidum of patients for the treatment of Parkinson's disease (12 cases recorded on and off medication, 17 macroelectrodes) and dystonia (10 cases, 19 macroelectrodes). Percentage LFP power in the 11-30 Hz band was decreased and that in the 4-10 Hz band increased across both contact pairs in treated Parkinson's disease compared with untreated Parkinson's disease. Dystonic patients had even less 11-30 Hz power and greater 4-10 Hz power compared with untreated or treated Parkinson's disease patients. The change in the 4-10 Hz band in patients with dystonia was particularly manifest in the more rostral contact pair, presumed to be within or bridging the globus pallidus externus. We conclude that untreated and treated Parkinson's disease and dystonia are characterized by different spatiotemporal patterns of activity in the human pallidum.

Motor impairment influences Farnsworth-Munsell 100 Hue test error scores in Parkinson's disease patients

Farnsworth-Munsell 100 Hue test (FMT) error scores and peg insertion abilities significantly differ between Parkinson's disease (PD) patients and controls. Both tasks ask for performance of voluntary movements. The objective of this study was to demonstrate a relation between FMT error scores and peg insertion outcomes. We successively performed both tasks in 28 previously untreated PD patients. The FMT error score was significantly ( p=0.016) lower in patients with better peg insertion outcome. A significant (Spearman R=0.47, p=0.012) correlation between peg insertion results and the FMT error scores appeared. Motor impairment influences FMT error scores in PD patients.

A pharmacological analysis elucidating why, in contrast to (-)-deprenyl (selegiline), α-tocopherol was ineffective in the DATATOP study

The Parkinson Study Group who conducted the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial designed their study in the belief that the MAO inhibitor (-)-deprenyl (selegiline), the antioxidant α-tocopherol, and the combination of the two compounds will slow the clinical progression of the disease to the extent that MAO activity and the formation of oxygen radicals contribute to the pathogenesis of nigral degeneration. In fact, (-)-deprenyl only delayed the onset of disability associated with early, otherwise untreated Parkinson's disease, however, in contrast to the expectation of the authors, α-tocopherol proved to be ineffective in the DATATOP study. Enhancer substances, (-)-deprenyl, (-)-1-phenyl-2-propylaminopentane [(-)-PPAP] the (-)-deprenyl analogue free of MAO inhibitory potency, and R-(-)1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] the presently known most potent enhancer substance, are peculiar stimulants. They enhance the impulse propagation mediated release of the catecholamines in the brain. Due to their enhancer effect, the amount of catecholamines released from selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus) is significantly higher in rats treated with an enhancer substance than in saline treated rats. We compared the effect of (-)-deprenyl 0.025 and 0.25 mg/kg, (-)-PPAP 0.1 mg/kg, (-)-BPAP 0.0001 mg/kg, and α-tocopherol 25 and 50 mg/kg, in this test. The doses of (-)-deprenyl and α-tocopherol were selected to be in compliance with the dose given in the DATATOP study. Compared to saline treated rats, the enhancer substances significantly increased the amount of dopamine released from the striatum, substantia nigra and tuberculum olfactorium and the amount of norepinephrine released from the locus coeruleus; α-tocopherol was ineffective. The results indicate that α-tocopherol was ineffective, because, unlike (-)-deprenyl it dose not enhance the activity of the nigrostriatal dopaminergic neurons.

Treatment of psychosis in Parkinson's disease: safety considerations.

Psychosis only rarely occurs in patients with untreated Parkinson's disease. Much more commonly, psychosis is induced by drug therapy for Parkinson's disease and is the strongest known risk factor for nursing home placement. Delusions are less frequent than hallucinations, but are more concerning as they are often paranoid in nature. Treatment begins with a search for correctable infectious, toxic, and metabolic aetiologies. If symptoms persist, anti-Parkinson's disease medications are slowly reduced. However, withdrawal of these drugs usually worsens parkinsonism and is often not tolerated. Certain atypical antipsychotics can be used to treat psychosis without compromising motor function. The choice of atypical antipsychotic is largely based on ease of use and adverse effect profile as most have comparable efficacy in improving psychosis. Currently, there are five marketed atypical drugs - clozapine, risperidone, olanzapine, quetiapine and ziprasidone. Ziprasidone is the only agent whose adverse effect profile has not been reported in Parkinson's disease. The most common adverse effects of clozapine in Parkinson's disease are sedation, orthostatic hypotension and sialorrhoea. Sedation is generally helpful since these patients are frequently awake at night and tend to have worse behavioural problems then. Clozapine does not induce deterioration of motor function, but it has the potential to cause agranulocytosis, which is idiosyncratic and not dose-related. In risperidone-treated Parkinson's disease patients, reported adverse effects include somnolence, sialorrhoea, dizziness, palpitations, constipation, delirium, fatigue, leg cramps, depression, urinary incontinence and hypotension. Although in some Parkinson's disease studies, risperidone has been well tolerated, others have shown that many patients are unable to tolerate the drug due to deterioration of motor function. While an initial study of olanzapine in Parkinson's disease psychosis showed the drug to be effective without deterioration of motor function, succeeding reports demonstrated a deleterious effect of the drug on motor functioning. The most common adverse effects of quetiapine in Parkinson's disease patients are sedation and orthostatic hypotension. There is a lack of double-blind trials; however, cumulative reports involving >200 Parkinson's disease patients strongly suggest that quetiapine is well tolerated and effective. Unlike clozapine, it does not improve tremor and may induce mild deterioration of motor function. Recently, cholinesterase inhibitors have been reported to alleviate psychosis in Parkinson's disease. Although ondansetron, an antiemetic with antiserotonergic properties, has been reported to relieve psychosis in Parkinson's disease, its prohibitive cost has prevented further study in this population. Electroconvulsive treatment is generally reserved for the patient with psychotic depression who is unable to tolerate any pharmacological therapy.

Neuroprotection in Parkinson's disease: clinical trials.

Advances in our understanding of the cause and pathogenesis of Parkinson's disease (PD) have permitted the rational selection of putative neuroprotective agents for study in PD. However, the list of agents that might provide neuroprotective effects derived from laboratory studies is daunting, and we face the challenge of determining which agents to bring to the clinic and how to find the resources (patients and funds) to properly study so many promising therapeutic opportunities.1 Appropriate outcome variables that are not confounded by any symptomatic effect of the drug and are acceptable to clinicians and regulatory authorities also remain to be defined. The first clinical trials designed to test the capacity of putative neuroprotective agents to alter the natural history of PD have now been performed and illustrate some of these problems. The DATATOP (Deprenyl and Tocopherol Antioxidant Therapy of PD) study used the time to reach a disease milestone in untreated PD patients (ie, need for levodopa) as the primary end point. However, interpretation of results was confounded by the drug's symptomatic effect. The SINDEPAR (Sinemet-Deprenyl-Parlodel) study used the change in motor score between initial visit and final visit after washout of all study medications as the primary end point. However, here too there were concerns about confounding symptomatic effects, because antiparkinsonian medications have now been shown to have a long duration response that can persist for weeks and perhaps even months after withdrawal. More recent studies have used surrogate markers of the integrity of nigrostriatal function such as striatal uptake of fluorodopa on positron emission tomography (PET) or beta-CIT-on single-photon emission computerized tomography (SPECT) as primary outcome measures. However, it has not yet been confirmed that striatal uptake of these isotopes does in fact correlate with the remaining number of dopamine neurons or terminals, and the possibility of a confounding pharmacological effect has not yet been completely excluded. To date, no drug has been established to have a neuroprotective effect in PD, and none has been approved for a neuroprotective indication. Furthermore, regulatory agencies have not yet agreed that any of the outcome measures currently used will be acceptable for approval of a new drug. Resolution of these issues is of critical importance to convince pharmaceutical companies to expend the hundreds of millions of dollars necessary to bring a new drug to market. Drugs that already have been approved in PD for their symptomatic effects, such as dopamine agonists or propargylamines (eg, selegiline), offer the best opportunity for establishing that a drug is neuroprotective in PD in the immediate future, but herein also lies the difficulty of establishing that any benefits observed are not solely because of the drug's symptomatic properties. Currently, this will most likely entail demonstrating that the drug provides benefit for PD patients for both imaging and clinical markers of disease progression.

Review: Selegiline improves symptoms and levodopa is better than pramipexole for motor function in untreated Parkinson disease

Source Citation Miyasaki JM, Martin W, Suchowersky O, Weiner WJ, Lang AE. Practice parameter: initiation of treatment for Parkinson’s disease: an evidence-based review. Report of the Quality Standa...

Psychophysiological approach in Parkinson's disease: L-dopa effects on preprogramming and control activity.

To investigate whether preprogramming (Bereitschaftspotential, BP) and control activity (skilled performance positivity, SPP) in a complex task are sensitive to L-dopa, movement related potentials (MRPs) were recorded in 12 non-demented Parkinson's disease (PD) patients before and after acute L-dopa administration, and in 17 control subjects. After L-dopa administration, the PD patients scored a significantly higher percentage of correct performances ( p<0.05), linked to a decreased BP amplitude ( p<0.001) and an increased SPP amplitude ( p<0.005), than before therapy. Our findings suggest that preprogramming activity is impaired in untreated PD patients. Dopaminergic drug administration seems to restore their ability to use more automatic motor strategies which become more similar to that of normal subjects.

Decreased phasic EMG activity during rapid eye movement sleep in treatment-naïve Parkinson's disease: effects of treatment with levodopa and progression of illness.

Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently associated with Parkinson's disease (PD) and may anticipate its diagnosis by several years. We assessed the presence of motor dyscontrol during REM sleep in treatment-naïve PD patients and investigated the putative effect of levodopa (L-dopa) treatment on motor activity. Overnight sleep studies were performed on 15 previously untreated PD patients and 14 controls at baseline, again after a 3- to 9-month treatment period with a low dose of L-dopa, and 2 to 5 days after treatment discontinuation (in 8 patients). No differences in sleep parameters were observed across groups or treatment conditions. None of the patients met criteria for RBD at baseline, whereas 5 patients were symptomatic at the time of the second sleep study. A quantitative analysis of electromyographic (EMG) activity during REM sleep showed a lower phasic twitching activity in untreated PD than in controls. However, an increase in both phasic twitching and tonic activity was found after treatment with L-dopa. Discontinuation of treatment resulted in a return to pretreatment values of phasic but not of tonic EMG activity. Thus, the increase in phasic activity seems to depend on the effects of L-dopa, whereas the increase in tonic EMG activity during REM sleep might be caused by other factors such as the progression of disease. Potential implications for the understanding of the relationship between RBD and PD are discussed.

L-dopa effects on preprogramming and control activity in a skilled motor act in Parkinson's disease

Objectives: The authors investigated whether preprogramming (Bereitschaftspotential, BP) and control activity (skilled performance positivity, SPP) in a bimanual, sequential skilled performance task (SPT) is sensitive to l-dopa administration in non-demented Parkinson's disease (PD) patients. Methods: Movement related potentials (MRPs) were recorded in 12 non-demented parkinsonian patients before and after acute l-dopa administration, and in 17 control subjects, all of whom were performing SPT for the first time. BP, SPP and correct performances were evaluated both as a grand average and in sequential blocks in order to verify the learning effect. Results: After l-dopa administration the PD patients scored a significantly higher percentage of correct performances ( P<0.05), linked to a decreased BP amplitude ( P<0.001) and an increased SPP amplitude ( P<0.005), than before therapy. Dynamic evaluation through the block analysis did not show any learning effect in off-therapy patients but showed that l-dopa intake improved learning, linked to a BP amplitude decrease ( P<0.005) and a SPP amplitude increase ( P<0.05). Furthermore, l-dopa minimized differences in the learning trend between off-therapy PD patients and controls. Conclusions: Our findings suggest that skilled motor learning is impaired in non-demented untreated PD patients. Dopaminergic drug administration seems to restore the ability of PD patients to use more automatic motor strategies, as demonstrated by the electrophysiological and behavioural pattern, which became more similar to that of normal subjects.

Plasma Homocysteine and l-DOPA Metabolism in Patients with Parkinson Disease

Homocysteine is formed by demethylation of methionine and is involved in transmethylation mechanisms. Hyperhomocysteinemia is associated with a wide range of clinical manifestations, mostly affecting the central nervous system (e.g., mental retardation, cerebral atrophy, and epileptic seizures) (1)(2). Hyperhomocysteinemia has also been associated with an increased risk for atherosclerotic and thrombotic vascular diseases (3)(4)(5). Although various mechanisms have been proposed, mostly involving endothelial damage related to increased oxidative stress (6), the exact cellular and molecular bases for the adverse effects of homocysteine are still elusive. Alterations in transmethylation reactions that lead to hyperhomocysteinemia have been suggested in the pathophysiology of neurodegenerative disorders such as Alzheimer disease and Parkinson disease (PD) (7)(8). Furthermore, the potential role of homocysteine in neurodegeneration has recently been pointed out by a study showing that the amino acid induces apoptosis in cultures of hippocampal neurons (9). The processes of methyl-group transfer are involved in the metabolism of l-3,4-dihydroxyphenylalanine (l-DOPA), the most effective drug used for the therapy of PD (10). The main metabolism of l-DOPA is its O-methylation to form 3- O -methyldopa (3-OMD). The reaction involves the enzyme catechol- O -methyl-transferase, with S -adenosylmethionine as methyl-group donor. Demethylation of S -adenosylmethionine forms S -adenosylhomocysteine, which is hydrolyzed to homocysteine. Homocysteine is then metabolized via a transsulfuration pathway, forming cystathionine, or a remethylation cycle, which leads back to methionine (11). The catabolism of l-DOPA might therefore interfere, at various steps, with homocysteine metabolism. Indeed, there is experimental evidence that l-DOPA administration increases concentrations of plasma homocysteine (12) and cerebral S -adenosylhomocysteine (12)(13). In PD patients treated with l-DOPA, plasma homocysteine is higher than in controls and untreated PD patients (14)(15)(16)(17). This further supports …

Proton magnetic resonance spectroscopy (1H-MRS) of motor cortex and basal ganglia in de novo Parkinson's disease patients.

Proton MR spectroscopy (1H-MRS) has been previously performed in Parkinson's disease (PD) and parkinsonian syndromes to evaluate in vivo concentrations of basal ganglia and cerebral cortex metabolites such as N-acetylaspartate (NAA), choline (Cho), and creatine (Cr). However, this technique has never been used to evaluate motor cortex in untreated PD patients. In this study, single-voxel 1H-MRS of basal ganglia and motor cortex was carried out in 10 de novo patients with PD and 10 age-matched healthy controls. A significant reduction in the NAA/Cr ratio was observed in the motor cortex of PD patients compared with controls (p)<(0.01). Basal ganglia spectra did not allow any evaluation due to the presence of artefacts related to inorganic paramagnetic substances. The motor cortex reduction of the NAA/Cr ratio in de novo PD patients may reflect an altered neuronal functioning due to a loss of thalamocortical excitatory inputs and may represent an in vivo marker for the diagnosis of PD.

Sleep and Periodic Leg Movement Patterns in Drug-Free Patients with Parkinson's Disease and Multiple System Atrophy

To assess and compare polygraphic sleep measures and periodic leg movement (PLM) patterns in untreated patients with mild to moderate Parkinson's disease (PD), multiple system atrophy (MSA) and healthy age-matched controls. Polysomnographic recordings of 2 consecutive nights were performed in 10 patients with PD (mean age 65 years, mean Hoehn and Yahr stage 2.2), 10 patients with MSA (mean age 61 years) and in a control group of 10 healthy subjects (mean age 64 years). All patients and controls were free of antiparkinsonian medication and other centrally active drugs for 2 weeks prior to polysomnography. NA. NA. NA. Sleep measures for the second night showed a significantly lower total sleep time, sleep efficiency and sleep period time in PD and MSA patients compared to healthy controls. PLM-indices during sleep and wakefulness were significantly higher in PD, but not in MSA patients compared to controls. Five patients with PD and 7 patients with MSA, but no control subject, showed abnormal rapid eye movement (REM) sleep features (i.e., REM sleep without atonia or behavioral manifestations typical for REM sleep behavior disorder). Sleep disruption and increased motor activity during REM and non REM sleep are a frequent finding in PD and MSA. An increased PLM index in untreated PD patients may be due to a dopaminergic deficit and is probably not associated with dopaminergic treatment.

Respiratory chain enzyme activities in spermatozoa from untreated Parkinson's disease patients.

We studied respiratory chain enzyme activities in spermatozoa homogenates from 12 untreated Parkinson's disease (PD) male patients and from 23 age matched healthy male controls. When compared with controls, PD patients showed significantly lower specific activities for complexes I+ III, II+III, and IV. However, citrate synthase corrected activities were similar in patients and controls. Values for enzyme activities in the PD group did not correlate with age at onset, duration, scores of the Unified Parkinson's Disease Rating Scales and Hoehn and Yahr staging. These results suggest that this tissue cannot be used to develop a diagnostic test for PD.

In vivo magnetic resonance spectroscopy of human fetal neural transplants.

To better define the survival and cellular composition of human fetal neurotransplants in vivo, we performed quantitative 1H MRS to determine the concentration of the neuronal amino acid [N-acetylaspartate] within MRI-visible grafts. In all, 71 grafts in 38 patients [24 Parkinson's disease (PD), 14 Huntington's disease (HD)] were examined, as well as 24 untreated PD and HD patients and 13 age-matched normal controls. MRI appearances of edema were present in three out of 71 grafts, the remainder being consistent with histologically identified viable neural transplant tissue. N-acetylaspartate (NAA), creatine, choline, myoinositol and glutamine plus glutamate (Glx) were identified in all post-transplant putamens, with abnormal metabolites, lactate and/or lipid detectable in only three patients. Of 71 grafts, 19 occupied more than 60% of the MRS-examined volume (VOI) (mean 84.2 +/- 3%; range 61-100%). In those, [NAA] was 8.50 +/- 0.99 mM in eight PD spectra and 6.59 +/- 0.81 mM in 11 HD spectra, and was not significantly different from controls. In contrast, transplanted fetal neurones contain less than 0.4 mM of the neuronal amino acid NAA. This suggests that established fetal neurotransplants in the human putamen of both PD and HD patients are populated by adult neurones, axons and dendrites.

Decreased phagocytic function in patients with Parkinson's disease

To determine the phagocytic function of the peripheral blood polymorphonuclears from patients with treated and untreated Parkinson's disease (PD), these cells were incubated with latex particles and the number of phagocytes, as well as the number of particles engulfed by each individual cell, were counted. Cells of untreated PD patients were significantly less phagocytotic than those of matched subjects without neurological or immune disorders (24% vs. 45%, P < 0.001). In addition, phagocytes from PD patients engulfed less particles per cell than those of the controls (8.4 +/- 0.7 vs. 16.5 +/- 1.3, P < 0.001). There was no significant difference in both functions in untreated and treated PD. The results indicate that in addition to the known immune alterations in patients with PD, the ability of their peripheral blood phagocytic cells to engulf latex particles is impaired.

Reduced ferroxidase activity in the cerebrospinal fluid from patients with Parkinson's disease

Recent evidence suggest the implication of transition metals leading to overproduction of free radicals as a possible causal factor in the death of nigral cells associated to Parkinson's disease (PD). Iron depots in the basal ganglia of PD patients have been described; in addition, contents of nigral copper have been found decreased, while its concentration in cerebrospinal fluid (CSF) is raised, particularly the free form of the metal. To search for a possible link between altered copper concentrations and PD, we advanced the hypothesis that ferroxidase activity of ceruloplasmin is decreased in the CSF of PD patients. We studied 35 untreated PD patients, 14 L-3,4-dihydroxyphenylalanine ( l-DOPA)-treated PD patients and 26 controls. Both CSF ferroxidase activity and CSF copper content were measured and correlated with the clinical stage of the disease. We found that untreated PD patients had a significant reduction of 40% in CSF ferroxidase while CSF copper was slightly increased as compared with both the values in l-DOPA-treated PD patients and controls. We also found that the fraction of copper linked to ferroxidase in untreated PD is inversely related to the clinical stage of the disease.

Gastric myoelectrical activity in patients with Parkinson's disease: evidence of a primary gastric abnormality.

Parkinson's disease patients may experience various gastrointestinal symptoms; however, the exact pathophysiology of these symptoms is not fully understood. Therefore, the aim of this study was to investigate the pattern of gastric myoelectrical activity in patients with Parkinson's disease. Eleven patients with Parkinson's disease and 10 healthy subjects participated in the study. Patients were stratified as "receiving dopaminergic therapy" (N = 5) and "off therapy" (N = 6). Gastric myoelectrical activity was measured by means of surface electrogastrography (EGG) for 30 min before and for 90 min after a standardized meal. The dominant frequency, postprandial EGG power change, and the percentage of normal 2-4 cycles/min (cpm) slow-wave activity in the three groups were calculated and compared. The mean postprandial EGG power increase in the untreated patients was smaller than in the treated patients (-3.11 +/- 1.01 and 1.17 +/- 1.96 dB; P = 0.072). Moreover, both of these values were significantly decreased when compared to the control group (untreated vs control: -3.11 +/- 1.01 vs 8.01 +/- 1.86 dB; P = 0.04 and treated vs control: 1.17 +/- 1.96 vs 8.01 +/- 1.86 dB; P = 0.02). The percentage of normal 2-4 cpm slow waves in untreated patients was not different from the treated patients (82.6 +/- 6.6% vs 75.8 +/- 13.6%, P = NS) or from the control group (88.2 +/- 5.4%, P = NS). The dominant frequency after the meal was similar to that in the fasting state both in the untreated (3.3 +/- 0.1 vs 3.2 +/- 0.2 cpm; P = NS) and treated patients (3.2 +/- 0.1 vs 3.1 +/- 0.1 cpm, P = NS), whereas the dominant frequency significantly increased postprandially in the control group (2.88 +/- 0.12 vs 3.05 +/- 0.16; P < 0.05). Abnormalities in gastric myoelectrical activity in untreated Parkinson's disease patients reflect direct involvement of the gastrointestinal tract by the primary disease process. EGG can be regarded as a useful diagnostic tool in evaluating gastrointestinal involvement in neurodegenerative diseases.