Severity Of Parkinsonian Symptoms Research Articles

Influence of White Matter Hyperintensities on the Cognition of Patients With Parkinson Disease

White matter hyperintensities (WMH) have been associated with cognitive impairment in elderly persons and in patients with Alzheimer disease. However, the role of WMH in Parkinson disease (PD) dementia remains to be elucidated. The cohort for this study comprised 71 consecutive patients with PD, all of whom completed a clinical assessment, neuropsychologic investigation, and magnetic resonance imaging of brain. WMH were rated using the semiquantitative visual rating system proposed by Scheltens et al. The PD dementia group had significantly more WMH than the PD without dementia group in the evaluated brain regions except for the infratentorial area. The WMH showed a significant correlation with age, Unified Parkinson's Disease Rating Scale, Mini-Mental State Examination, sum of the box of Clinical Dementia Rating, and many of the cognitive domains. The linear regression model showed that the WMH was independently associated with cognitive impairment in patients with PD, regardless of age, sex, duration or severity of PD symptoms, and vascular risk factors. These findings confirm that WMH might be associated with cognitive decline in patients with PD, regardless of age, sex, education status, duration or severity of PD symptoms, and vascular risk factors. This result suggests that other nonvascular factors contribute to the progression of dementia in patients with PD.

SF-36 includes less Parkinson Disease (PD)-targeted content but is more responsive to change than two PD-targeted health-related quality of life measures

ObjectiveTo compare validity including responsiveness, and internal consistency reliability and scaling assumptions of a generic (SF-36) and Parkinson Disease (PD)-targeted (PDQ-39; PDQUALIF) health-related quality of life (HRQOL) measures.MethodsNinety-six PD patients were administered for all HRQOL measures by telephonic interview at baseline and 18 months. Relative efficiency and responsiveness were compared relative to four external criteria (self-ratings of PD’s daily effects, global Quality of Life, PD symptom severity, and a depression screener). We examined whether PD-targeted measures explained unique variance beyond the SF-36 by regressing criterion variables on HRQOL scales/items. Adequacy of PD-targeted measures’ original scaling was explored by item-scale correlations.ResultsRelative efficiency estimates were similar for generic and PD-targeted measures across all criteria. Responsiveness analyses showed that the SF-36 yielded large (>0.8) effect sizes (ES) for three of eight scales for each of two criterion variables, compared to only one large ES for any scale in either PD-targeted measure. Adjusted R2 increased from 14 to 27% in regression models that included PD-targeted items compared to models with only SF-36 scales. Item-scale correlations showed significant cross-loading of items across scales of the PD-targeted measures.ConclusionsSF-36 responsiveness was better than that of two PD-targeted measures, yet those measures had content that significantly explains PD patients’ HRQOL.

Syndrome parkinsonien sous aripiprazole : à propos d’un cas

Aripiprazole is an atypical antipsychotic with a pharmacological profile, different from other atypical antipsychotics. It is a high-affinity partial agonist at the dopamine D2 and serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2 receptors. It is associated with a good safety and tolerability profile including extrapyramidal side-effects. We report on a 37 year-old female patient with paranoid schizophrenia who developed Parkinsonian symptoms after one month of aripiprazole 10mg per day. She had been admitted to our unit for a psychotic episode with delusions of persecution and grandiosity. It was her second hospitalization. During the first hospitalization, seven years earlier, she had been treated with haloperidol. We do not have any information about the tolerability of that treatment. At the start, she received olanzapine with good tolerability but without efficacy on psychotic symptoms. After 4 weeks, we switched from olanzapine to risperidone 6 mg per day. After a few days, the patient developed severe Parkinsonian symptoms. We reduced the dose to 4 mg per day without any effect on the extrapyramidal symptoms.We decided to discontinue risperidone and to introduce aripiprazole 10mg per day. After one month, the patient developed severe Parkinsonian symptoms including hypertonia, akinesia, and shuffling gait. After reduction of the dose of Aripiprazole to 5mg per day, all the Parkinsonian symptoms had disappeared within 5 days without any other medication. Few reports of Parkinsonian symptoms with aripiprazole have been published in the adult population. There is one report of Parkinsonian symptoms, associated with hypersalivation without akathisia, in a patient treated with 30 mg per day of aripiprazole. All the symptoms disappeared after a switch to olanzapine. The other cases have been reported when aripiprazole was associated with anti-depressant serotonin specific reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. One report has been published of a 16 year-old girl who had already developed extrapyramidal symptoms with olanzapine and risperidone. Another has been published concerning a 3 year-old child who had taken a half tablet of aripiprazole 15 mg. We hypothesise that cytochrome P450 2D6 is implicated in this case-report because it is active in metabolizing aripiprazole. This patient could have been deficient in this enzyme, thus failing to metabolize aripiprazole at a normal rate.

Naturalistic evaluation of entacapone in patients with signs and symptoms of L-dopa wearing-off

ABSTRACTObjective: To evaluate the effectiveness of entacapone in the management of levodopa wearing-off in Parkinson's disease (PD) in a naturalistic, real-life setting.Research design and methods: This prospective, open-label, observational study included patients with idiopathic PD. Patients were eligible for inclusion if they had been taking 3–5 doses of levodopa per day for ≥2 months and had shown signs of levodopa wearing-off for ≥1 month. Subjects received entacapone (recommended dose: 1 × 200 mg tablet with each levodopa dose) for 28 days. Patients were asked to complete a wearing-off questionnaire and the eight-question Parkinson's Disease Questionnaire Quality of Life assessment (PDQ-8). Activities of daily living (both in the on and off states) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) part II. Clinical Global Impression (CGI) of severity of PD-related symptoms was assessed using a modified CGI tool.Patient global assessment of severity of PD symptoms was also obtained.Results: A total of 341 patients were enrolled by 68 physicians across Canada. At Day 28, 56.9% of the subjects indicated improvement compared to baseline on the modified CGI of change (CGI-C); 21.4% reported no change. Improvements were also observed on the UPDRS II and the PDQ-8. Benefit from entacapone appeared to be relatively uniform across subgroups (e.g., number of daily levodopa doses, use of other anti-PD medications).Study limitations: The results of this study may be biased due to factors inherent in open-label, community-based trials (e.g., compliance). This is, however, reflective of everyday clinical practice.Conclusions: In this naturalistic, real-life study, the addition of entacapone to levodopa therapy provided benefits in quality of life and activities of daily living for a substantial proportion of PD patients experiencing wearing-off.

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123I] FP‐CIT spect study in vascular parkinsonism and Parkinson's disease

There is substantial evidence to support a role for small vessel disease (SVD) as a cause for vascular parkinsonism (VP). Using [(123)I] FP-CIT SPECT (single photon emission computed tomography), we have tried to determine whether VP patients have pre-synaptic dopaminergic function similar to PD patients, and whether the severity of parkinsonian symptoms as well as the levodopa response in VP patients are correlated with pre-synaptic dopaminergic dysfunction. Thirteen patients fulfilling operational clinical criteria for VP had [(123)I] FP-CIT scans. Mean [(123)I] FP-CIT uptake in the basal ganglia was significantly lower in VP patients than in healthy controls, and the asymmetry index was not significantly different between these groups. In contrast, compared with the PD group, only the mean asymmetry index was significantly lower in VP patients. None of the parameters measured was significantly different between VP patients who had an insidious onset of parkinsonism (VPi) and those who had an acute onset (VPa). There was a significant correlation between the bilateral basal ganglia FP-CIT uptake reduction in the VP patients and UPDRS motor scores, but not with the mean % reduction in motor UPDRS after levodopa. We suggest that in the majority of VP patients, pre-synaptic dopaminergic function is reduced. The presence of a rather symmetrical FP-CIT uptake in the basal ganglia may help to distinguish VP from PD and could therefore be used as a criterion for the clinical diagnosis of VP.

Acute parkinsonism with corresponding lesions in the basal ganglia after heroin abuse

Parkinsonian syndromes with encephalopathy after heroin abuse are rare. We report a 41-year-old Caucasian woman presenting with symmetric akinetic-rigidic parkinsonism. Twenty-four hours after snorting heroin, the patient exhibited a generalized dyskinetic syndrome and impaired vision, and severe parkinsonian symptoms developed within 2 weeks. The akinetic-rigid syndrome showed good …

Sporadic rapid‐onset dystonia–parkinsonism presenting as Parkinson's disease

We report on a 38-year-old patient with rapid-onset dystonia-parkinsonism (RDP) with a missense mutation in the Na/K-ATPase alpha3 subunit (ATP1A3). Asymmetrical parkinsonian symptoms evolved over a year. After a stable episode of another 2.5 years, overnight he developed oromandibular dystonia and more severe parkinsonian symptoms. We conclude that RDP should be considered as a rare cause of levodopa-unresponsive parkinsonism even if there is no family history and the classic presentation is lacking.

Fas gets protective

A deadly receptor reveals a benevolent side in a study on page 575. Landau and colleagues show that the cell death–inducing receptor Fas is required for protection against neurodegeneration in a mouse model of Parkinson's disease (PD). Figure Loss of dopamine-containing neurons (red) is accelerated in the brains of Fas-deficient mice (bottom). The Fas receptor (Fas), best known for its apoptotic role in the immune system, is widely expressed in nonimmune tissues, including the central nervous system. In the brains of patients with PD, the expression of both Fas and Fas ligand (FasL) is reduced, whereas the expression of soluble Fas is elevated. Soluble Fas is a decoy receptor that impairs Fas signaling by competing for free ligand. Apoptosis has been implicated in PD neurodegeneration, but this occurs independently of caspase-8, an upstream activator in Fas-mediated apoptosis, suggesting that Fas may not be the predominant death inducer in PD.Using mice with Fas/FasL mutations, the authors showed that decreased Fas expression increased susceptibility to a PD-causing neurotoxin. Neuronal cell loss was markedly increased in Fas-deficient mice, and these mice developed severe PD symptoms within days of toxin exposure. In contrast, two strains of mice that express Fas but have mutations in the Fas death domain, a region responsible for apoptotic signaling, were resistant to PD. Fas defects might also underlie PD in humans, as circulating T cells from patients with PD failed to up-regulate Fas expression in response to mitogenic stimulation. Although the Fas-induced signals that protect the brain have yet to be identified, these findings suggest that, in this model of PD, Fas-induced neuroprotection trumps Fas-induced cell death.

Is there a relationship between Parkinson's disease and obsessive-compulsive disorder?

Obsessive-compulsive (OC) symptoms and obsessive-compulsive disorder (OCD) have been reported in Parkinson's disease (PD). This is interpreted as an indirect evidence for the involvement of frontobasal ganglia circuitry in OCD. However, the evidence for relationship between the OC symptoms and PD is inconsistent. This study systematically assessed OC symptoms and OCD in non-demented idiopathic PD patients ( n=69) and matched medically ill controls ( n=69). The cases did not differ from controls with respect to OC symptoms, clinical and subclinical OCD, tics and other psychiatric diagnoses. There was no relationship between severity of PD and OC symptoms. The findings do not support relationship between OCD and PD. While the findings of this study do not in any way rule out the involvement of frontobasal ganglia circuitry in OCD, it is speculated that the involvement of different circuitry in the pathophysiology of OCD and PD explain the lack of association between PD and OCD.

Factors of importance for weight loss in elderly patients with Parkinson's disease.

Weight loss is reported frequently in patients with Parkinson's disease (PD). The objective of this study was to find the underlying factors of this phenomenon. Twenty-six L-dopa-treated patients with PD and 26 age- and sex-matched healthy controls were assessed twice within a 1-year interval. Body weight, body fat mass, resting energy expenditure, physical activity, energy intake, thyroid hormones and cognitive function were investigated. Nineteen (73%) of the PD patients lost body weight, although energy intake and the time for rest increased. Weight loss was most marked in patients with more severe PD symptoms and in whom cognitive function had decreased. Multiple regression analyses showed that determinants for weight loss were female gender, age and low physical activity. Weight loss was common in PD patients, in spite of the increased energy intake and was most obvious in patients with increased PD symptoms and decreased cognitive function.

Relationship of substantia nigra echogenicity and motor function in elderly subjects.

Patients with Parkinson's disease (PD) exhibit an increased echogenicity of the substantia nigra (SN) on transcranial sonography. Some healthy adults with the same echo characteristics showed a reduced 18fluorodopa uptake on PET, indicating a subclinical alteration of the nigrostriatal system. To determine whether the sonographic phenotype of hyperechogenic SN has any relevance for motor function in elderly subjects and whether an increased echogenicity of the SN is associated with an impaired motor function. In a population-based, cross-sectional study, 93 subjects older then 60 years without history of extrapyramidal disorder underwent sonographic and neurologic examinations, with a quantitative motor assessment. Elderly healthy subjects without prediagnosed extrapyramidal disorder but with SN hyperechogenicity had more frequent and more severe parkinsonian symptoms and a slower finger tapping than those with a regular echogenicity of the SN (p < 0.05, U test). With increasing age, subjects with SN hyperechogenicity develop a more substantial slowing of movements than subjects without this echo pattern, stressing the functional relevance of this sonographic finding. The authors speculate that hyperechogenicity of the SN may be detected by transcranial sonography early in life and may serve as a risk marker for nigral injury, although only a minority of these subjects will develop the full clinical picture of PD.

Fall risk factors in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, gait disturbance, and postural instability. Patients with PD suffer frequent falls, yet little research has been done to identify risks specific to PD patients. The objective of this study was to identify the risk factors associated with falls for PD patients through the collection of demographic, environmental, and medical information as well as fall diaries completed during a 3-month period. Patients with a diagnosis of idiopathic PD, with and without falls, were included in the study provided they could stand and walk and had no other condition that could predispose them to falls. Of the 118 participants, 59% reported one or more falls. A total of 237 falls were reported. Duration and severity of PD symptoms, particularly freezing, involuntary movements, and walking and postural difficulties, were significantly associated with an increased risk of falls. Other factors associated with falls were postural hypotension and daily intake of alcohol. Forty percent of falls resulted in injury, but serious injury was rare. The findings have implications for reducing the risk of falls through patient education.

The influence of white matter hyperintensities on the clinical features of Parkinson's disease.

This study was designed to investigate the influence of white matter hyperintensities (WMH) on clinical features of Parkinson's disease (PD) patients. The study subjects were 44 patients with PD who took a brain MRI. The severity of Parkinsonian symptoms was assessed in both 'on' and 'off' states, using the UPDRS-motor score. Thirteen patients (30%) showed WMH. The patients with WMH were significantly older than those without WMH (67 +/- 5.7 vs 60 +/- 6.4 years). In both 'off' and 'on' states, the gait scores were significantly higher in patients with WMH than in those without WMH (1.6 +/- 0.18 vs 1.1 +/- 0.12, P < 0.05), but other motor symptom (tremor, bradykinesia, rigidity) scores between the two patient groups were not statistically different. After taking a single dose of oral levodopa/benserazide (200mg/50mg), the patients with WMH showed significantly less improvement in bradykinesia score than those without WMH (25 +/- 4.1% vs 40 +/- 4.0%, P < 0.05), but the improvements in other symptoms were comparable between the two groups. These results suggest that WMH on MRI may influence Parkinsonian motor symptoms, particularly gait symptom and levodopa-responsiveness to bradykinesia symptom.

Movement-related potentials in Parkinson's disease. Motor imagery and movement preparation.

Movement-related potentials (MRPs) associated with voluntary movements reflect cortical activity associated with processes of movement preparation and movement execution. Early-stage pre-movement activity is reduced in amplitude in Parkinson's disease. However, it is unclear whether this neurophysiological deficit relates to preparatory or execution-related activity, since previous studies have not been able to separate different functional components of MRPs. Motor imagery is thought to involve mainly processes of movement preparation, with reduced involvement of end-stage movement execution-related processes. Therefore, MRP components relating to movement preparation and execution may be examined separately by comparing MRPs associated with imagined and actual movements. In this study, MRPs were recorded from 14 subjects with Parkinson's disease and 10 age-matched control subjects while they performed a sequential button-pressing task, and while they imagined performance of the same task. Early-stage pre-movement activity was present in both Parkinson's disease patients and control subjects when they imagined movement, but was reduced in amplitude compared with that for actual movement. Movement execution-related components, arising predominantly from the primary motor cortex, were relatively unaffected in Parkinson's disease subjects. However, motor preparatory processes, probably involving the supplementary motor area, were reduced in amplitude overall and abnormally prolonged, indicating impaired termination following the motor response. Further, this impaired termination of preparatory-phase activity was observed only in patients with more severe parkinsonian symptoms, and not in early-stage Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in non-human primates is antagonized by pretreatment with nimodipine at the nigral, but not at the striatal level

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to induce parkinsonism in man and non-human primates. Hypotheses concerning the mechanism of action of MPTP have been related to the pathogenesis of nigral cell death in Parkinson's disease. For instance, alterations of calcium influxes have been reported to be implicated in both MPTP-induced parkinsonism and Parkinson's disease. Recently, we reported that nimodipine, a blocker of L-type calcium channels, prevents dopaminergic MPTP-induced neurotoxicity in C57B1/6 black mice. The present study extended these rodent findings to the non-human primate model of Parkinson's disease and assessed the effects of nimodipine, continuously applied by pellet for 18 days, on behavioural, biochemical and histological parameters, following systemic application of MPTP in common marmosets ( Callithrix jacchus). The experimental design involved five groups of common marmosets and a total of 24 animals. Monkeys assigned to group I ( n = 4) received subcutaneously implanted vehicle pellets 7 days prior to subcutaneous saline injections (control). Monkeys of group II ( n = 4) were treated with nimodipine pellets (80 mg) and saline injections. Marmosets in group III ( n = 8) were treated with vehicle pellets and received 4 times MPTP (MPTP-HCI, 2 mg/kg body weight subcutaneously, separated by an interval of 24 h for a total of 4 days). Monkeys in group IV ( n = 4) and V ( n = 4) were treated as group-III animals except for the implantation of nimodipine pellets (80 mg and 120 mg, respectively) 7 days prior to toxin exposure. In common marmosets MPTP induced severe parkinsonian symptoms, a pronounced dopamine depletion in the caudate-putamen (more than 99% of control) and a loss of tyrosine hydroxylase immunoreactive cells in the substantia nigra (50% percent of control) 7 days after MPTP-administration. Pretreatment with nimodipine (120 mg pellets) did neither attenuate the behavioural impairments in MPTP-treated animals nor antagonize the striatal neurotoxin-induced dopamine depletion, but almost completely prevented (in a dose-dependent manner) the MPTP-induced decrease of nigral tyrosine hydroxylase immunoreactive cells. These data suggest that application of nimodipine, during the observation period of 7 days, protects against MPTP-induced neurotoxicity in common marmosets at the cellular nigral level, but not at the synaptic striatal level, implicating differential mechanisms of actions of MPTP-induced neurotoxicity at the nigral versus the striatal level.

Executive functions and disease characteristics in Parkinson's disease

In the present study, we investigated the association of two executive functions with disease characteristics in Parkinson's disease (PD), especially with severity of motor symptoms. We operationalized two executive functions, viz. fluency and cognitive shifting, each in a number of tests with heterogeneous materials, but with an identical format. We calculated the correlations between test performance and disease characteristics, including the factor scores of the Unified Parkinson's Disease Rating Scale (UPDRS). The results of this study show that only cognitive shifting was consistently associated with the severity of motor symptoms in PD, in particular with rigidity. None of the fluency tests had a significant association with severity of motor symptoms. The present study indicates that PD, as reflected by the severity of motor symptoms, is not associated with a general decrease in executive function. In spite of the fact that both are executive functions and both require generation of items, fluency and cognitive shifting are differentially related to PD.

Clinical features predicting dementia in idiopathic Parkinson's disease

We followed up, after 3 1/2 years, a whole population cohort of 249 patients with Parkinson's disease (PD) 1st examined in 1983 to 1984. Of the survivors, 23.6% qualified for a DSM III-R diagnosis of dementia. In univariate tests, age, certain items of the Webster scale, the Hoehn and Yahr scale, a 10-question mental status questionnaire, and a history of smoking were associated with a diagnosis of dementia 3 1/2 years later. Logistic regression with DSM III-R diagnosis (demented versus nondemented) as the dependent variable, and age and symptom scales for PD as predictor variables, revealed that PD symptoms predicted dementia even after controlling for age. We conclude that dementia is probably more common in PD patients than would be expected in the general population and is associated with the severity of PD symptoms and signs independently of age.

Sequelae of Attempted Suicide by Cyanide Ingestion: A Case Report

A twenty-eight-year-old man presented emergently after ingesting 800 mg of potassium cyanide in a suicide attempt. He survived only with intensive medical and psychiatric intervention, and went on to develop severe parkinsonian symptoms, including profound micrographia and hypersalivation. Bilateral, symmetrical basal ganglial abnormalities were demonstrated with magnetic resonance imaging. Survival following cyanide poisoning is rare; the clinical, radiologic, and neuropathologic sequelae in other documented cases are reviewed.

Anxiety disorders in patients with Parkinson's disease

To study the prevalence and importance of anxiety disorders in patients with idiopathic Parkinson's disease, the authors systematically evaluated 24 parkinsonian patients for the presence of DSM-III-R axis I syndromes. Nine subjects (38%) had a clinically significant current anxiety disorder. Severity of anxiety was not correlated with severity of parkinsonian symptoms, cumulative duration of L-dopa exposure, or current dose of L-dopa. These findings suggest that anxiety disorders should be considered in the medical evaluation and treatment of parkinsonian patients and that further attention should be paid to the role of the dopaminergic system in anxiety and phobic disorders.