Parkinson's Scale Research Articles

Influence of cell preparation and target location on the behavioral recovery after striatal transplantation of fetal dopaminergic neurons in a primate model of Parkinson’s disease

Surgeries involving transplantation of fetal dopamine (DA) neurons into the caudate-putamen of patients with Parkinson's disease (PD) have been performed in various clinical trials to examine a potential restoration of motor function. The absence of studies in non-human primates to define the best transplantation protocols have lead to the use of a broad variety of techniques that potentially could have a major impact on the clinical outcome. The effects of using different cell and tissue preparation, and surgical targets, remain unknown. For this purpose, 20 St. Kitts African Green Monkeys (AFG) rendered parkinsonian by i.m. injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were balanced into 4 groups and unilaterally grafted in the (a) caudate or (b) putamen with fetal ventral mesencephalic (VM) tissue as (c) solid pieces or as a (d) cell suspension. By 9 months post-transplantation all animals showed significant and similar behavioral improvement as determined by a UPDRS based PD scale. Postmortem analyses showed that VM transplants survived in all animals. They were located in both surgical target sites, producing a broad DA reinnervation of the targeted nuclei that could also extend to the non-grafted nucleus on the ipsilateral side. Although no differences between groups were found in survival of DA neurons or degree of DA reinnervation, there was a significant correlation between striatal reinnervation and behavioral recovery only in animals transplanted in the putamen surgical target. Additionally, there was in general a stronger glial reaction to solid grafts than to cell suspensions. These studies provide data for the optimal time course, cell preparation and surgical targets for systematic examinations of both potential benefits and side effects of dopamine neuron cell transplantation in primate models of PD.

Metric attributes of the unified Parkinson's disease rating scale 3.0 battery: Part II, construct and content validity

This article is the second of a two-part series concerning the metric properties of the following three Parkinson's disease (PD) scales: modified Hoehn and Yahr staging (H&Y), Schwab and England (S&E), and Unified Parkinson's Disease Rating Scale (UPDRS) 3.0. Part II focuses on construct and content validity. To assess construct validity, a sample of 1,136 PD patients completed the above-mentioned PD scales. Correlation coefficients between measures of disability and dysfunction [S&E, UPDRS Activities of Daily Living (ADL), and UPDRS Motor Examination] were |r| = 0.69-0.77, indicating good convergent validity. Results showed that the S&E (F(5,945) = 193.47; P < 0.0001) and UPDRS subscales discriminated between modified H&Y stages (F(20,2784) = 25.28; P < 0.001). A panel of 12 to 13 international experts rated the relevance of the scales and items. This enabled the scales' content validity index to be calculated, which ranged from 41.7% (UPDRS Mentation) to 83.3% (UPDRS Motor Examination). In conclusion, while the modified H&Y, S&E, and UPDRS displayed satisfactory construct validity, the content validity of all scales except UPDRS Motor Examination failed to attain adequate standards.

Positron Emission Tomography of Monoaminergic Vesicular Binding in Aging and Parkinson Disease

The type-2 vesicular monoamine transporter (VMAT2) might serve as an objective biomarker of Parkinson disease (PD) severity. Thirty-one subjects with early-stage PD and 75 normal subjects underwent continuous intravenous infusion of (+)-[(11)C]dihydrotetrabenazine (DTBZ) and positron emission tomography (PET) imaging to estimate the striatal VMAT2 binding site density with equilibrium tracer modeling. Parkinson disease patients were evaluated clinically in the practically defined 'off' state with the Unified Parkinson Disease Rating Scale (UPDRS), the Hoehn and Yahr Scale (HY), and the Schwab and England Activities of Daily Living Scale (SE). In normal subjects there was age-related decline in striatal DTBZ binding, approximating 0.5% per year. In PD subjects, specific DTBZ binding was reduced in the caudate nucleus (CD; -44%), anterior putamen (-68%), and posterior putamen (PP; -77%). The PP-to-CD ratio of binding was reduced significantly in PD subjects. Dihydrotetrabenazine binding was also reduced by approximately 50% in the PD substantia nigra. Striatal binding reductions correlated significantly with PD duration and SE scores, but not with HY stage or with UPDRS motor subscale (UPDRS(III)) scores. Striatal and midbrain DTBZ binding was asymmetric in PD subjects, with greatest reductions contralateral to the most clinically affected limbs. There was significant correlation between asymmetry of DTBZ binding and clinical asymmetry measured with the UPDRS(III). In HY stage 1 and 1.5 subjects (n=16), PP DTBZ binding contralateral to the clinically unaffected body side was reduced by 73%, indicating substantial preclinical nigrostriatal pathology in PD. We conclude that (+)-[(11)C]DTBZ-PET imaging displays many properties necessary of a PD biomarker.

Comparación farmacocinética de Sinemet&lt;FONT FACE=Symbol&gt;â&lt;/FONT&gt;y Grifoparkin&lt;FONT FACE=Symbol&gt;â&lt;/FONT&gt; (levodopa/carbidopa 250/25 mg) en pacientes con enfermedad de Parkinson avanzada: un estudio con dosis única

There are doubts wether generic medications have the same bioavailability and efficacy compared with the original drugs developed by pharmaceutical companies with research capabilities. To compare the pharmacokinetics and clinical (motor) responses of Sinemet and Grifoparkin (generic carbidopa/levodopa 250/25 mg) in patients with advanced Parkinson's disease. Patients were randomly assigned to Sinemet (15 patients 62 +/- 12 years old; mean disease duration 11 +/- 7 years) or Grifoparkin (15 patients, 64 +/- 11 years old; mean disease duration 12 +/- 4 years) groups. Medication and food were withheld 12 h before the study. Fifteen blood samples were collected (starting 9 AM) immediately before (sample 1, t = 0 min) and after (samples 2-15, t = 20-360 min) oral administration of a single dose of Sinemet or Grifoparkin, and plasmatic L-DOPA was quantified using HPLC with electrochemical detection. Additionally, each patient was clinically evaluated every 20 minutes, using the tapping test and the unified Parkinson's disease scale Hoehn & Yarh. Tmax (time at which the maximal L-DOPA concentration was reached) were 69 +/- 12 min and 64 +/- 11 min for Sinemet and Grifoparkin respectively (NS). Cmax (maximal L-DOPA concentration reached) was 3161 +/- 345 ng/ml for Sinemet and 3274 +/- 520 ng/ml for Grifoparkin (NS). The t1/2 (half life time), CL (clearance) and volume of distribution (Vd) values calculated were 159 +/- 32 min, 51.7 +/- 5.1 1/h and 3.6 +/- 1.2 l/kg for Sinemet and 161 +/- 48 min, 58.7 +/- 8 l/h and 3.0 +/- 0.7 l/kg for Grifoparkin (NS). UPDRS-III value for the best "on state" and for the worst "off state" were 23 +/- 11 and 50 +/- 19 for Sinemet and 20 +/- 7 and 46 +/- 13 for Grifoparkin respectively (NS). The results obtained showed that both drugs are bioequivalent in patients with advanced Parkinson's disease.

Electrical stimulation of the prelemniscal radiation in the treatment of Parkinson's disease: an old target revised with new techniques.

In the treatment of tremor and rigidity in patients with Parkinson's disease (PD), the prelemniscal radiation (RAPRL), a subthalamic bundle of fibers, is an exquisite target that can be visualized easily on ventriculograms. We sought to evaluate the effect of electrical stimulation of the RAPRL on symptoms and signs of PD in a long-term trial and to determine the localization of the stimulated area by means of stereotactic magnetic resonance imaging studies. Ten patients with PD predominantly on one side had tetrapolar electrodes stereotactically oriented through a frontal parasagittal approach to the RAPRL contralateral to the most prominent symptoms. Preoperative and postoperative evaluations at 3, 6, 9, and 12 months after surgery were performed using conventional PD scales and quantitative evaluations of tremor amplitude and reaction time. Stereotactic high-resolution magnetic resonance imaging studies with the electrodes in place were used for anatomic localization. In all patients, temporary suppression of tremor occurred when the electrodes reached the target. The most effective stimulation was obtained when the pair of contacts was placed in the RAPRL. Long-term stimulation at 130 Hz, 0.09 to 0.450 milliseconds, and 1.5 to 3.0 V produced significant improvement in tremor and rigidity and mild improvement in bradykinesia. The RAPRL is an effective target for the alleviation of tremor and rigidity in patients with PD by either lesioning or neuromodulation; however, neuromodulation has the advantage of not inducing an increase in bradykinesia. The stimulated area seems to be independent of the subthalamic nucleus.

Extrapyramidal signs in patients with probable Alzheimer disease.

To examine whether extrapyramidal signs (EPSs) were associated with more rapid progression of Alzheimer disease (AD). Cross-sectional with longitudinal follow-up and the likelihood of arriving at 4 end points: Mini-Mental State Examination score of less than 9, Blessed Dementia Rating Scale score for activities of daily living of 15 or more, institutionalization, and death using a proportional hazard model with 6 variables: overall EPSs, bradykinesia, tremors, abnormal gait, cogwheel rigidity, and postural instability. Multidisciplinary behavioral neurology research clinic. We examined the individual EPS characteristics of 164 patients with mild-moderately probable AD, free of neuroleptic medication, participating in a longitudinal study of dementia. Patients with AD with EPSs (n= 51 [31%]) were older (P>.001) and had lower Mini-Mental State Examination scores (P=.003) than those without EPSs at study entry. Bradykinesia was present in 35 (69%) of the 51 patients with EPSs, abnormal gait in 18 (35%), rigidity in 10 (20%), postural instability in 10 (20%), tremors in 7 (14%), and oral-mandibular dyskinesia in 2 (4%). Using proportional hazard analysis with time-dependent covariates for overall EPSs and individual EPSs, adjusted by age at study entry, education, Mini-Mental State Examination score, and Blessed Dementia Rating Scale score for activities of daily living, the development of EPSs was associated with time to institutionalization (P<.001) but not with cognitive (eg, Mini-Mental State Examination score <9) or functional (eg, Blessed Dementia Rating Scale score > or = 15) decline or death. However, when we examined severity of the EPSs, as measured by the New York University Parkinson's Disease Scale, the development of EPSs was associated with functional decline (P=.005). Of the individual EPSs, rigidity predicted death (P<.001) and institutionalization (P=.03), whereas tremors predicted functional decline (P=.02). In this cohort, the presence or absence of EPSs is related to time to institutionalization, but not to severe cognitive or functional impairment or death. However, when severity of the extrapyramidal phenomenon is taken into account, EPSs are related to functional decline. Further, it appears that a subgroup of patients with AD with EPSs, where cogwheel rigidity and tremors are the core signs, can have a worse outcome.

Can Cocaine Abuse Cause Parkinsonism?

Dopamine deficiency is found in both chronic cocaine abusers and Parkinson's disease. The authors sought to determine whether parkinsonian signs occur in chronic cocaine abusers. Fifty male patients with a history of chronic heavy cocaine abuse were examined on the Unified Parkinson Disease Scale (UPDS) and compared with 20 non-cocaine-abusing, age- and sex-matched control subjects. UPDS scores of cocaine abusers ranged from 0 to 1 (mean: 0.08 +/- 0.28) and, in control subjects, from 0 to 3 (mean: 0.15 +/- 0.49; P = 0.5; NS). This study suggests that chronic heavy cocaine abuse does not cause parkinsonism.

Absence of parkinsonism among patients in long-term neuroleptic therapy who abuse cocaine.

The study used the United Parkinson's Disease Scale to compare parkinsonian signs and symptoms among 19 patients in long-term neuroleptic therapy who had a history of cocaine abuse with those among 24 similar patients with no history of cocaine use. There was no significant difference between the two groups' scores. The results suggest that chronic cocaine abuse is not a risk factor for parkinsonism among subjects in long-term neuroleptic therapy.

Airway dysfunction in patients with Parkinson's disease.

To investigate pulmonary function abnormalities in Parkinson's disease (PD), we obtained maximal inspiratory and expiratory flow-volume curves in 63 patients (59 under treatment) with different stages of the disease, not filtered for respiratory symptoms. PD severity was evaluated by the Unified PD Rating Scale, the Webster's scale, and Hoehn and Yahr staging. Patients with more severe PD had lower percentage forced vital capacity (FVC%), and peak inspiratory and expiratory flows. Those with fluctuations and/or dyskinesias had lower FVC% and percentage forced expiratory flow volume in 1 sec (FEV1%). There were a number of weak but significant correlations between PD scales and spirographic parameters. Thirty one patients (49.2%) had pathological flow-volume curves. The clinical profile and the duration of the disease did not influence the pattern of the curve. Physiologic evidence of upper airway obstruction was observed in 3 cases. A spirometric restrictive ventilatory defect (FEV1/FVC higher than or equal to 80%) was observed in 54 patients (85%), while generalized airway obstruction was present only in one nonsmoker. We conclude that abnormal flow-volume loop contour is a frequent finding in PD. This probably reflects involvement of the upper airway musculature, that in some patients can produce upper airway obstruction. Generalized airflow limitation is not an important characteristic of PD. By contrast, a restrictive spirometric defect, probably due to incoordinated expiratory effort or abnormally low chest wall compliance, is the main spirometric finding in these patients.

Long-Term Effects of Medical and Surgical Treatments on Parkinson's Disease

Three groups of patients with Parkinson's disease (PD) were studied: (1) PD patients treated medically with L-Dopa and anticholinergics, (2) PD patients treated with thalamo-subthalamotomies plus medical treatment, and (3) PD patients treated with autologous adrenal medullary transplantation to right caudate nucleus plus medical treatment. Evaluations prior and 1, 6 and 12 months after treatment were accomplished with PD scales (NYPDS, UPDS, Schwab and England and Hoehn and Yahr scales). No attempt was made to compare one PD after treatment in each group. Statistical analysis was performed with the Friedman-Anova test. Group 1 did not show significant improvement at any time but deterioration at 12 months. Group 2 showed significant improvement at 1 month but at 12 months deterioration occurred mainly in the mental condition and akinesia. Group 3 did not show significant improvement at any time but at 12 months there was a tendency of improvement in self-sufficiency.

Clozapine prevents recurrence of psychosis in Parkinson's disease.

Psychosis secondary to dopaminergic therapy can limit the ability to manage motor symptoms of advanced Parkinson's disease (PD). We report the results of an open label 3-month trial that evaluated the antipsychotic effects of clozapine in eight PD patients with drug-induced psychosis. Response was quantified using a simplified brief psychiatric rating scale and two PD scales. Clozapine significantly improved psychiatric scores at low doses. The use of every other day regimens (not previously utilized) led to good control of symptoms and minimized side effects. Clozapine also had a positive sleep effect in four patients and improved dyskinesia in one. Finally, this treatment prevented recurrence of psychosis while levodopa doses were significantly increased and while other antiparkinsonian medications were added. Motor disability related to PD improved as a result of these treatment adjustments. We conclude that clozapine is effective in treating drug-induced psychosis in PD and allows for safe optimization of antiparkinsonian therapy.