Postural stability in Parkinson's disease: the effects of disease severity and acute levodopa dosing

We systematically assessed the potential effects of disease severity and acute levodopa dosing on body balance by a stable force measuring platform in 56 patients with Parkinson's disease, and compared them to 34 healthy volunteers. Postural sway variables were significantly higher in both patient groups without (Hoehn and Yahr 1-2) and with (Hoehn and Yahr 3-4) a clinically evident deficit of postural stability compared to controls. Levodopa dosing significantly increased postural sway 1 and 2 hours post-dose. The standardization of static posturography with respect to the clinical characteristics and drug schedule of patients may improve the sensitivity of the test, disclosing abnormalities of postural stance even at the early stages of the disease and revealing possible acute drug effects.     

^99mTc-TRODAT-1 SPECT多巴胺转运体显像在诊断早期帕金森病中的意义

目的探讨99mTc-TRODAT-1 SPECT多巴胺转运体(DAT)显像在诊断早期帕金森病(PD)中的意义.方法对62例早期PD、12例晚期PD及10名正常人进行99mTc-TRODAT-1 SPECT 基底节DAT显像,选取纹状体区和小脑为感兴趣区,计算两者的放射性比值,比较3组间该比值的差异,并分析早期PD患者DAT放射性结合率与H&Y分级及UPDRS评分之间的相关性.结果PD患者基底节99m Tc-TRODAT-1摄取率显著降低,早期PD患者病变较重肢体对侧纹状体放射性摄取率较同侧纹状体显著下降.PD患者纹状体区放射性摄取率与PD患者的H&Y分级呈负相关,而与UPDRS Ⅱ、Ⅲ评分无相关性.结论99mTc-TRODAT-1 SPECT基底节 DAT显像可用于临床早期PD的诊断.     

Striatal dopamine transporter binding assessed by [I-123]IPT and single photon emission computed tomography in patients with early Parkinson's disease: implications for a preclinical diagnosis

BACKGROUND: Specific binding to dopamine transporters may serve as a tool to detect early loss of nigrostriatal dopaminergic neurons in patients with Parkinson's disease. OBJECTIVE: To determine striatal dopamine transporter binding using the cocaine analogue [I-123]N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chl orophenyl) tropane ([I-123]IPT) and single photon emission computed tomography. PATIENTS AND METHODS: We studied 9 control subjects (mean age, 58 years; range, 41-69 years) and 28 patients with early Parkinson's disease (Hoehn and Yahr stages I [n = 14] and II [n = 14] [symptom duration, <5 years]; mean age, 55.5 years; range, 36-71 years). Single photon emission computed tomography was performed 90 minutes after injection of 120 to 150 MBq of radioactive [I-123]IPT. RESULTS: Specific striatal [I-123] IPT binding (mean +/- SD) was significantly reduced in patients with early Parkinson's disease (ipsilateral striatum: 4.09+/-0.97; range, 2.46-6.40; contralateral striatum: 3.32+/-0.76; range, 1.80-5.13) compared with controls (left striatum: 7.28+/-0.94; range, 5.78-8.81; right striatum: 7.41+/-1.28; range, 5.58-9.44). IPT binding ratios (mean +/- SD) were significantly lower in patients with Hoehn and Yahr stage II (ipsilateral striatum: 3.47+/-0.75; contralateral striatum: 2.96+/-0.73) compared with those with Hoehn and Yahr stage I (ipsilateral striatum: 4.72+/-0.75; contralateral striatum: 3.69+/-0.61) (P<.001). The ipsilateral striatum of patients with Hoehn and Yahr stage I showed a significant mean+/-SD reduction of IPT binding (ipsilateral striatum: 4.72+/-0.75) compared with either right or left striatum of controls (P<.001). Only in 1 patient was IPT binding to the ipsilateral striatum (ratio, 6.40) higher than the lowest value observed in the striatum of a control subject (ratio, 5.58). CONCLUSIONS: Use of [I-123] IPT and single photon emission computed tomography demonstrates a reduction of dopamine transporter binding in patients with early Parkinson's disease. Significantly reduced IPT binding already observed in the ipsilateral striatum of patients with Hoehn and Yahr stage I demonstrates the potential of this method to detect preclinical disease.     

Cardiac sympathetic denervation in bradykinesia-dominant Parkinson's disease

Cardiac iodine-123-labeled-metaiodobenzylguanidine uptake is reduced in early-stage Parkinson's disease, suggesting sympathetic nerve degeneration. The scintigraphic findings in patients with Parkinson's disease with different clinical features have, however, not been established. Iodine-123-labeled-metaiodobenzylguanidine myocardial scintigraphy was performed in 143 patients with Parkinson's disease. The early and delayed heart to mediastinum ratios were analyzed according to the dominant motor deficit (tremor, bradykinesia, rigidity, and postural instability), age, sex, age at onset, disease duration, and Hoehn and Yahr stage. Both ratios correlated with bradykinesia, age at disease onset, and disease duration; but not with sex, Hoehn and Yahr stage, tremor, rigidity, and postural instability. Our results suggest a close link between myocardial sympathetic degeneration and bradykinesia, age at onset and disease duration.     

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.     

Cerebrospinal fluid nitrate levels in patients with Parkinson's disease

It has been suggested that nitric oxide could be implicated in the neuronal degeneration of substantia nigra compacta in patients with Parkinson's disease. Recently, it has been reported decreased CSF nitrate levels (oxidation product that provides an indirect estimation of nitric oxide) in Parkinson's disease patients, assessed with a colorimetric method. We studied the CSF and plasma levels of nitrate with a kinetic cadmium-reduction method in 31 Parkinson's disease patients and 38 matched controls. The CSF and plasma nitrate levels were not correlated either in patient or in the control group, and they did not differ significantly between the two study groups. They were not influenced significantly by antiparkinsonian drugs in patients, although there was a trend for CSF nitrate levels to be higher in patients treated with levodopa or with dopamine agonists. CSF and plasma nitrate levels did not correlate with age at onset, duration, scores of the unified Parkinson's disease rating scales and Hoehn & Yahr staging in the patients group. These data suggest that CSF and plasma levels of nitrate are apparently unrelated with the risk for PD.     

[123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease.

OBJECTIVES: The main neuropathological feature in Parkinson's disease is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine (DA) transporters in the striatum. [123I]beta-CIT single photon emission computed tomography (SPECT) studies have demonstrated this loss of striatal DA transporter content in Parkinson's disease in vivo. However, studies with this radioligand also showed that an adequate imaging of the striatal DA transporter content could only be performed on the day after the injection of radioligand, which is not convenient for outpatient evaluations. Recently, a new radioligand [123I]FP-CIT, with faster kinetics than beta-CIT, became available for imaging of the DA transporter with SPECT, and the applicability of this ligand was tested in patients with early and advanced Parkinson's disease, using a one day protocol. METHODS: [123I]FP-CIT SPECT was performed in six patients with early and 12 patients with advanced Parkinson's disease, and in six age matched healthy volunteers. RESULTS: Compared with an age matched control group striatal [123I]FP-CIT uptake in patients with Parkinson's disease was decreased, and this result was measurable three hours after injection of the radioligand. In the Parkinson's disease group the uptake in the putamen was reduced more than in the caudate nucleus. The contralateral striatal uptake of [123I]FP-CIT was significantly lower than the ipsilateral striatal uptake in the Parkinson's disease group. Specific to non-specific striatal uptake ratios correlated with the Hoehn and Yahr stage. A subgroup of patients with early Parkinson's disease also showed significantly lower uptake in the putamen and lower putamen:caudate ratios than controls. CONCLUSION: [123I]FP-CIT SPECT allows a significant discrimination between patients with Parkinson's disease and age matched controls with a one day protocol, which will be to great advantage in outpatient evaluations.     

Normal cerebrospinal fluid levels of insulin in patients with Parkinson's disease

Summary. We compared CSF levels insulin, measured by a Radioimmunoanalysis method, in 24 patients with Parkinson's disease (PD) and 21 matched controls. The CSF insulin levels did not differ significantly between PD patients and controls. CSF insulin levels were not correlated with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the PD group. Antiparkinsonian therapy did not influence significantly and CSF levels of insulin. These results suggest that CSF insulin concentrations are not a biological marker of PD and its severity. Received July 14, 1999; accepted September 16, 1999     

Body composition in Parkinson's disease: a study with dual-energy X-ray absorptiometry

Some investigators have reported that patients with Parkinson's disease (PD) tend to lose weight, and have a low body mass index. For this reason, it was suggested that PD patients have an increased metabolic rate. Using dual-energy X-ray absorptiometry (DXA) we determined, the body composition in 52 unselected PD patients (28 males, 24 females) and in 80 age and sex-matched healthy controls (40 males, 40 females). The mean+/-SD duration of PD was 5.9+/-4.8 years. PD severity was assesed with the Unified PD Rating Scale (UPDRS) and Hoehn & Yahr staging. PD patients and controls did not differ significantly in height, weight and body mass index. The total fat and percentage of fat were significantly higher (p<0.01) and the lean body mass and water content were lower (p<0.001 for each) in male PD patients when compared with male controls. All these values were similar in female PD patients and female controls. Fat mass, lean body mass and water content did not correlate with the UPDRS scores and Hoehn &Yahr staging, although PD patients with higher UPDRS scores had higher percentage of fat.     

Disordered axial movement in Parkinson's disease.

Axial motor impairments are a common cause of disability in patients with Parkinson's disease, become more prominent with longer disease duration, and have been said to be less responsive to levodopa replacement therapy. The ability to turn in bed while lying supine before and after dopaminergic stimulation was studied in a group of 36 patients with Parkinson's disease; 23 were in Hoehn and Yahr stages 3-5 when "off", and 13 were in stages 1-2. Turning was also compared with postural stability and gait before ("off") and after ("on") dopaminergic stimulation. Failure to turn in bed was noted in 19 of the 36 patients in the "off" state, with significant associations between disturbances of gait, postural stability, rising from a chair, whole body bradykinesia, and axial rigidity. Gait, postural stability, rising from a chair, whole body bradykinesia, and axial rigidity were significantly correlated in the "off" state. Disorder of axial movement, gait, and postural stability were not dependent on age at onset of Parkinson's disease, but did relate to duration of disease. After a levodopa challenge, turning in bed returned to normal in all but one patient, and gait, postural stability, rising from a chair, whole body bradykinesia, and axial rigidity also improved in nearly all. It is concluded that in the later stages of Parkinson's disease at least some aspects of axial motor control can remain dopamine responsive.     

What contributes to quality of life in patients with Parkinson's disease?

OBJECTIVE: To identify the factors that determine quality of life (QoL) in patients with idiopathic Parkinson's disease in a population based sample. Quality of life (QoL) is increasingly recognised as a critical measure in health care as it incorporates the patients' own perspective of their health. METHODS: All patients with Parkinson's disease seen in a population based study on the prevalence of parkinsonism were asked to complete a disease-specific QoL questionnaire (PDQ-39) and the Beck depression inventory. A structured questionnaire interview and a complete neurological examination, including the Hoehn and Yahr scale, the Schwab and England disability scale, the motor part of the unified Parkinson's disease rating scale (UPDRS part III), and the mini mental state examination were performed by a neurologist on the same day. RESULTS: The response rate was 78%. The factor most closely associated with QoL was the presence of depression, but disability, as measured by the Schwab and England scale, postural instability, and cognitive impairment additionally contributed to poor QoL. Although the UPDRS part III correlated significantly with QoL scores, it did not contribute substantially to predicting their variance once depression, disability, and postural instability had been taken into account. In addition, patients with akinetic rigid Parkinson's disease had worse QoL scores than those with tremor dominant disease, mainly due to impairment of axial features. CONCLUSION: Depression, disability, postural instability, and cognitive impairment have the greatest influence on QoL in Parkinson's disease. The improvement of these features should therefore become an important target in the treatment of the disease.     

Striatal dopamine transporter in different disability stages of Parkinson's disease studied with [(123)I]beta-CIT SPECT

Six healthy controls and eighteen patients with Parkinson's disease in different disability stages were studied with SPECT using [(123)I]beta-CIT to label the striatal dopamine transporter. The mean uptake of [(123)I]beta-CIT in the putamen was reduced to 54% of the control mean and to 65% of the average control value in the caudate nucleus. In patients with totally, or predominantly unilateral symptoms the reduction was greater on the side opposite to the predominant symptoms (to 56% of the control mean in the contralateral putamen and to 77% in the ipsilateral putamen). There was a significant negative correlation between [(123)I]beta-CIT uptake in the putamen and the Hoehn and Yahr stage (r = -0.81, p < 0.0001). An analysis of covariance was performed using age and disease duration as covarianes, and the correlation between putaminal [(123)I]beta-CIT uptake and parkinsonian disability according to the Hoehn and Yahr stage remained significant (r = -0.75, p = 0.02). A similar correlation was seen in the caudate nucleus (r = -0.79, p < 0.0001) between the uptake of [(123)I]beta-CIT and the Hoehn and Yahr stage. The correlation also remained significant after correction for the duration of disease and age of the patients (r= -0.76, p = 0.02). The present results show that [1231],Q-CIT SPECT is a useful method to study the function of presynaptic dopaminergic terminals in PD, and might be used in the early diagnosis and follow-up of the disease.     

Effects of deep brain stimulation and levodopa on postural sway in Parkinson's disease

OBJECTIVE: To quantify postural sway in subjects with Parkinson's disease and elderly controls, and determine the effects of Parkinson's disease, deep brain stimulation, levodopa, and their interactions on postural control during quiet stance. METHODS: Centre of foot pressure (CoP) displacement under each foot was measured during three 60 s trials of quiet stance with eyes open in 11 controls and six patients with Parkinson's disease. Subjects with Parkinson's disease were tested in four treatment conditions: off both deep brain stimulation and levodopa (off condition); on deep brain stimulation; on levodopa; and on both deep brain stimulation and levodopa. The variables extracted from CoP included: root mean square distance (rms), mean velocity, 95% power frequency (f(95%)), area of the 95% confidence ellipse (ellipse area), direction of its major axis (mdir), and postural asymmetry between the feet. RESULTS: rms and area of postural sway were larger than normal in subjects with Parkinson's disease in the off condition, increased further with levodopa, and significantly decreased with deep brain stimulation. Mean velocity and f(95%) were also larger than normal but were restored to normal by all treatments, especially by deep brain stimulation. The combined effect of deep brain stimulation and levodopa resulted in a postural sway that was an average of the effect of each treatment individually. Levodopa increased sway more in the mediolateral than in the anterior-posterior direction. Subjects with Parkinson's disease had asymmetrical mean velocity and f(95%) between the feet, and this asymmetry increased with levodopa but decreased with deep brain stimulation. The f(95%) of the CoP correlated with tremor, posture, and gait subcomponents of the unified Parkinson's disease rating scale. CONCLUSIONS: Subjects with Parkinson's disease have abnormal postural sway in stance. Treatment with levodopa increases postural sway abnormalities, whereas treatment with deep brain stimulation improves postural sway. Quantitative evaluation of static posturography may be a useful adjunct to clinical measures in patients with Parkinson's disease.     

Observational study of sleep-related disorders in Italian patients with Parkinson’s disease: usefulness of the Italian version of Parkinson’s disease sleep scale

Sleep disturbances are common in patients with Parkinson's disease (PD). We aimed to evaluate prevalence and severity of nighttime sleep disturbances in Italian PD patients and to validate the Italian version of the Parkinson's disease sleep scale. A total of 221 PD patients and 57 healthy controls participated in a cross-sectional study with retest. PDSS, Epworth Sleepiness Scale (ESS), Hamilton Depression Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehn and Yahr staging were applied. PDSS total and individual items scores from patients were significantly lower than those in controls. Internal consistency of PDSS scale was satisfactory and intraclass correlation coefficient for test-retest reliability was 0.96 for total PDSS score. A significant negative correlation was found between total PDSS and ESS scores, and between total PDSS and HDRS scores. PDSS scores were also related to UPDRS sections II, III and IV, and H&Y stage. PDSS and ESS scores were not related to levodopa equivalent dose. Daytime sleepiness, depressive symptoms and disease severity correlate with sleep disturbances in Italian PD patients. The PDSS is a valid and reliable tool to evaluate sleep disturbances in Italian patients.     

FP-CIT and MIBG scintigraphy in early Parkinson's disease.

Methods provided by nuclear medicine may be helpful in diagnosis of Parkinson's disease (PD). For that purpose, the sensitivity of iodine-123 metaiodobenzylguanidine ([123I]MIBG) scintigraphy and [123I]FP-CIT single photon emission computed tomography (SPECT) was studied in patients with PD onset (Hoehn and Yahr Stage 1). Cerebral [123I]FP-CIT and cardiac [123I]MIBG scintigraphy were carried out in 18 patients with idiopathic Parkinson's disease, according to Hoehn and Yahr Stage 1. For quantification purposes, we calculated the striatum/posterior lobe binding of FP-CIT and the heart-to-mediastinum (H/M) count ratio regarding MIBG scintigraphy. In 15 of 18 patients, we observed markedly reduced or asymmetric striatal FP-CIT tracer accumulation. FP-CIT binding of the affected striatum was significantly lower as compared with that of the unaffected side. Striatal FP-CIT binding correlated significantly with the motor part of the Unified Parkinson's disease rating scale (UPDRS) but not with age, disease duration, or gender. MIBG scintigraphy delivered significant pathological results in 13 of 18 patients. There was no significant correlation between the H/M ratio relating to MIBG scintigraphy and the motor part of UPDRS, age, disease duration, or gender; however, binding of striatal FP-CIT correlated significantly with cardiac MIBG accumulation. According to the clinical criteria, it might be difficult to prove the diagnosis of PD in patients with slight symptoms and in these cases, FP-CIT SPECT and MIBG scintigraphy may contribute to the early diagnosis of PD. In addition, the functional loss of nigrostriatal and cardiac sympathetic neurons seems to be coupled closely.     

Minimal clinically important change on the unified Parkinson's disease rating scale.

The Unified Parkinson's Disease Rating Scale (UPDRS) is the main outcome measure in clinical trials of Parkinson's disease (PD). The minimal change that represents a clinically meaningful improvement is unknown. The objective of this study was to determine the minimal change on the UPDRS that represents a clinically meaningful improvement in early PD after 6 months of treatment. Data from two independent randomized treatment trials over 6 months involving 603 patients with de novo PD were analyzed to determine the minimal clinically important change (MCIC), referred to the status before treatment, for the UPDRS motor, activities of daily living (ADL), and total scores. An anchor-based method using ratings on a seven-point global clinical improvement was used. A change of five points on the UPDRS motor part was found to be the most appropriate cutoff score for all Hoehn and Yahr stages I to III, and a change of eight points for the UDPRS total score. For the UDPRS ADL score, an MCIC of two points for Hoehn and Yahr stages I/I.5 and II and of three points for Hoehn and Yahr stage II.5/III was the most appropriate cutoff score. These data give the first estimate for cutoffs defining clinically important changes in UPDRS ADL and motor scores. Further studies using larger databases from more diverse study populations are encouraged to better define and solidify the MCIC for the UPDRS.     

Reliability and validity of a scale for measurement of trunk mobility in Parkinson's disease: Trunk Mobility Scale

Axial rigidity is an important motor manifestation in Parkinson's disease (PD). Trunk mobility impairment can cause gait, balance and postural problems. However, only few instruments analyze the trunk mobility in PD patients. The aim of this study is to present a new Trunk Mobility Scale (TMS) and its validation in PD. The TMS constituted of dynamic tests involving trunk movements in sagittal, transversal and coronal planes. Ninety eight PD patients and 31 normal controls were analyzed. A strong correlation was found between the TMS scores and the Hoehn & Yahr staging scale (r: 0.72; p<0.01), motor Unified Parkinson's Disease Rating Scale (r: 0.84; p<0.01) and Schwab and England Activities of Daily Living (r: -0.72; p<0.01). The scale showed a satisfactory reliability rate (αCronbach: 0.85, ICC: 099). TMS is a simple and reliable instrument to evaluate trunk mobility impairment in patients with PD.     

Colour discrimination impairment is not a reliable early marker of Parkinson's disease

Disturbances of colour visual discrimination have been shown to occur frequently in Parkinson's disease (PD). To verify the potential utility of reduced colour sensitivity as a diagnostic marker of early PD, we examined 14 PD patients, mean age 55.4 years, disease duration 2.3 years, in Hoehn and Yahr stages 1, 1.5, or 2, previously untreated with levodopa. Colour discrimination was measured with the Farnsworth-Munsell 100-hue test in patients who were compared with age-matched controls. The examinations were performed under standard conditions in a room illuminated by a daylight lamp Biolux Osram 6500 K. The mean total error score (MTES) and partial error scores (green-yellow and red-green axis) were calculated for every person examined. No significant differences were found between PD patients (MTES 49.1 ± SD 37) and controls (MTES 37.9 ± SD 25). Similarly, the mean partial scores were not significantly elevated in PD patients. We found an elevation of error scores exceeding the upper limit of normality (control mean + 2SD) only in three patients. We conclude that colour visual discrimination is not consistently impaired in early stages of PD and does not appear as a reliable early marker of Parkinson's disease. Received: 26 September 2000, Received in revised form: 20 March 2001, Accepted: 28 March 2001     

Serum levels of alpha-tocopherol (vitamin E) in Parkinson's disease.

To elucidate the possible role of vitamin E in the pathogenesis of Parkinson's disease (PD), we compared serum levels of alpha-tocopherol (vitamin E), measured by high-performance liquid chromatography, and the vitamin E/cholesterol ratio of 42 Parkinson's disease (PD) patients using their spouses as the control group. The serum levels of vitamin E did not differ significantly between the groups (13.84 +/- 0.56 micrograms/ml for PD and 14.80 +/- 0.57 micrograms/ml for controls), nor did the vitamin E/cholesterol ratio (0.64 +/- 0.03 for both groups). There was no influence of antiparkinsonian therapy on vitamin E or the vitamin E/cholesterol ratio. Serum levels of the vitamin E and vitamin E/cholesterol ratio did not correlate with age, age at onset, scores of the Unified Parkinson's Disease Rating Scale or the Hoehn and Yahr staging in the PD group. These results suggest that serum vitamin E concentrations do not play a role in the pathogenesis of PD.     

Methods of H-reflex evaluation in the early stages of Parkinson's disease.

Differentiating the early stages of Parkinson's disease from the normal consequences of aging or from other common neurologic conditions can be diagnostically problematic. The purpose of this study was to compare methodologies for measuring motor neuron excitability of Parkinson's disease patients with a control group. H-reflexes were monitored in 16 patients diagnosed in the early stages of Parkinson's disease (Hoehn & Yahr stages I and II) compared with 30 subjects who were disease free. Methods of measurement included H-reflex latencies, the relative values of maximum H-reflexes to maximum direct motor responses (H-to-M ratio), the relative values of H-reflex amplitudes during vibration compared with control H-reflex amplitudes (Hv-to-Hc ratio), and double-stimulation H-reflex recovery curves using different interstimulus interval parameters. No significant differences were observed for the H-to-M or Hv-to-Hc ratios, or for the H-reflex latencies. The H-reflex recovery curves for the patients with Parkinson's disease demonstrated significantly greater ratio amplitudes than the control group during the double-stimulus responses between the 150-msec and 700-msec interstimulus intervals. Although comparisons of simple H-reflexes and H-reflexes during vibration did not differentiate the patients in the early stages of Parkinson's disease from the control group, the double-stimulation paradigm was a sensitive method for detecting early diagnoses of this disease.