Parkinson''s disease incidence: magnitude, comparability, time trends

In this study, we reviewed incidence surveys of Parkinson's Disease (PD) from all over the world, published during the period 1945-1989, using reported quality criteria. In addition, we compared age-specific PD incidences from selected observations by stratified analysis. Crude incidences were described for 11 populations, and age-specific incidences for three of them: Iceland, Rochester (Minn, USA), and Turku (Finland). Effect modification by age was detected: a) by comparing incidences by age at diagnosis with incidence by age at clinical disease onset; and b) when only data on onset of disease was computed. For disease onsets, the incidences in Rochester for the period 1955-1966, and in Turku (Finland) during the interval 1968-1970, were lower than that in Iceland for the period 1958-1960: RR = 0.58 95% CI (0.41, 0.83), and RR = 0.67 95% CI (0.51, 0.87), respectively. For the Rochester population aged 40-69 years, a statistically significant 56% decrease in the incidences of Parkinsonism onsets during the period 1945-1966 was found. Validity problems in comparing PD incidences and the role of PD underdiagnosis were emphasized. We concluded that: a) stratified analysis is more suitable than standardization when comparing incidences for etiological purposes; b) the incidence of PD was highest in Iceland; and c) in Rochester, PD incidence under the age of 70 decreased with time.     

Parkinson''s disease occurrence in Europe

Parkinson's disease (PD) surveys and death-record studies in European populations were reviewed. Particular attention was given to methodological aspects. Two sets of quality criteria were used. Four door-to-door surveys revealed underdiagnosis of prevalent idiopathic parkinsonism ranging from 30% to 71%. Quality surveys based on medical records were scarce. The analysis of a) the time relationships between the diagnostic process and the study period for measurements, and b) a variation observed in the shape of the curve for age-specific prevalences, suggested that both incidence and prevalence were underestimated by these surveys, especially among the elderly. In the UK, Denmark and Sweden, mortality from parkinsonism increased over time for ages over 70 years, but decreased for the younger age groups. A two-fold variation in mortality was found between countries. It is concluded that PD is widely distributed in Europe, and that most geographical differences in reported disease occurrence can be explained by methodological variations in measurements. The pattern of variation of age-specific figures was similar for mortality and prevalence. This might reflect decreasing prevalences among those aged under 70 years and increasing ascertainment in the elderly. There is a need for research methods for specific purposes in this field to be developed.     

Cost analysis of unilateral and bilateral pallidotomy for Parkinson''s disease

With the rapid increase in provision of deep brain stimulation for Parkinson's disease, the efficacy of pallidotomy in symptom alleviation appears to be increasingly ignored. We demonstrate that lesional surgery is effective with benefit over a significant period of time with very significant societal cost savings. Such studies are essential for future planning of services so that maximum numbers of patients can benefit from surgery, both lesional and neuromodulation, as deemed appropriate.     

The effect of vascular disease on late onset Parkinson''s disease

The clinical severity of late onset Parkinson's disease (PD) varies from patient to patient and it is further complicated by the increasing prevalence of accompanying disorders in the elderly. We set out to study the impact of ischemic heart disease, minor stroke, hypertension and diabetes mellitus in a group of late onset PD patients (age >or=70 years). Consecutive late onset PD patients seen in the Department of Neurology, Medical School of Patras, Greece were included in this study. We used very strict criteria to eliminate the possibility of including patients with vascular parkinsonism. Comparisons were made between groups of patients suffering with idiopathic Parkinson's disease (IPD) and the above-mentioned diseases. One hundred and sixty-seven consecutive late onset PD patients were included in this study. The most common accompanying disorders in our group were hypertension in 31 (18%) of the patients and minor stroke in 20 (12%). The Hoen and Yahr score in late onset IPD patients who suffered from minor stroke, ischemic heart disease or diabetes mellitus was significantly higher when compared with patients without the above disorders. The results clearly suggest that the presence of vascular disease on an IPD patient may aggravate PD severity. In clinical grounds, these findings can be proved significant since early and aggressive prevention of vascular disease and treatment of vascular risk may contribute in controlling symptom severity in PD.     

帕金森病多巴胺能神经元模型的建立

帕金森病是一种常见的中枢神经系统进行性退行性病变，其病因机制尚未明确，且缺乏令人满意的治疗方法。因此，建立有效的帕金森病模型对其病凶机制的进一步探讨有着重要的意义。Berger等人于1982年建立腹侧中脑原代细胞培养方法，通常应用小鼠或大鼠胚胎(13～15d胎龄)中脑组织进行培养。多巴胺能神经元可存体外存活长达数月，因此，可为多巴胺能神经元急性或慢性损伤的病因机制的研究提供实验手段。多巴胺能神经元在体外可通过免疫化学、放射自显影及荧光组织化学等方法确认。故其形态学及数量上的改变在体外较容易被检测，凶而这种实验模型的建立对于帕金森病病凶机制及新的治疗方法的探讨将起着重要的作用。     

Clinical characteristics of the alpha-synuclein mutation (G209A)-associated Parkinson''s disease in comparison with other forms of familial Parkinson''s disease in Greece

An Ala53Thr mutation of the alpha-synuclein has been recently identified as a rare cause of familial Parkinson's disease (fPD). In the present study, the clinical characteristics of Parkinson's disease (PD) patients with Ala53Thr alpha-synuclein mutation (alpha-synPD) were compared with fPD patients without any known mutation. An investigator blinded to the results of the genetic analysis examined 15 alpha-synPD patients and 43 consecutive fPD patients. Demographic data, age at onset of the illness, duration of the disease and modality of presentation were collected. Segregation ratios for both sexes in individuals at risk of developing alpha-synPD were estimated. The Unified Parkinson's disease rating scale (UPDRS) was also completed. The 15 alpha-synPD patients were matched for duration of the disease and age at onset with 15 of the 43 fPD patients (MfPD). Comparisons were also made between 14 patients belonging to three multicase families with patterns of inheritance similar to alpha-synPD. The alpha-synPD patients were significantly younger (mean difference 11.8 years) and showed the first sign of the disease earlier in life (mean difference 12.7 years) as compared with the fPD patients. Tremor at onset was present in only one (6.7%) of the alpha -synPD patients compared with 18 (41.9%) of the fPD patients (P = 0.01). At the time of examination rigidity, postural instability, orthostatic hypotension and the overall clinical severity did not differ significantly either between alpha-synPD and fPD or between alpha-synPD and MfPD groups. Nevertheless, some clinically relevant trends concerning the psychiatric symptoms and complications of therapy were recognized. The overall clinical severity and the progression of the disease in patients with alpha-synPD did not differ from that of the fPD patients. The alpha-synPD patients presented the illness at a younger age and also had lower prevalence of tremor when compared with the fPD patients.     

The adverse effect of benzhexol on memory in Parkinson''s disease

Seventy-eight subjects suffering from idiopathic Parkinson's disease were studied in 2 separate groups to test the hypothesis that benzhexol affects memory. In study A, 54 subjects were tested by means of a free recall technique; in study B, 24 subjects were given a signal detection memory task. Both studies yielded significant correlations between memory impairment and dosage levels of benzhexol. No correlation was found between memory status and dosage of levodopa, duration of illness or Hamilton depression scores. The implications of these findings are discussed.     

卡麦角林治疗帕金森病的临床研究

目的探讨卡麦角林结合左旋多巴治疗帕金森病的效果。方法将80例帕金森患者随机分为2组：治疗组和对照组，两组均予以左旋多巴治疗，其中治疗组加有卡麦角林治疗，治疗3年后评价疗效，观察不良反应。结果治疗组疗效与对照组疗效相当，但治疗组左旋多巴用量明显小于对照组，治疗组运动波动症状的发生率明显小于对照组。结论卡麦角林结合左旋多巴治疗帕金森病可明显降低左旋多巴的用量，减少运动波动症状的发生。     

帕金森病脑深部电刺激术治疗的术后药物调整与程控配合

目的分析丘脑底核-脑深部电刺激术(STN-DBS)治疗帕金森病患者的术后程控工作及相关情况,为STN-DBS术后刺激参数的设置、药物的调整提供参考依据。方法病例选自2005年3月至2006年12月在北京天坛医院接受双侧STN-DBS植入术治疗的57例帕金森病患者。分析手术前后药物的用量和调整情况,评估不同刺激参数对震颤、运动徐缓和僵直等PD运动症状的改善作用。结果与术前相比PD患者DBS术后服用多巴胺类药物的剂量明显减少,术前平均707.59mg,术后平均253.62mg,平均减少63%,其中8例不再服用左旋多巴类药物。刺激频率为10Hz时无治疗作用,130Hz以上时症状可得到显著改善。除3例发生对侧肢体痉挛性收缩外,频率达到185Hz时能够获得最佳治疗效果。电压为2V-3V时可较好的改善运动,并随着电压值的增加治疗作用逐渐增强。结论本研究证实STN-DBS是一种安全、有效的治疗帕金森病的方法,STN-DBS能够显著减少左旋多巴类药物用量及药物引起的异动症、运动波动等并发症的发生。刺激电压是术后程控的主要调节参数。     

Evaluation of olfactory function by topographic EEG analysis in patients with Parkinson''s disease

Olfactory function impairment has been observed in patients with idiopathic Parkinson's disease (PD) using psychophysical procedures. In this study, an electrophysiological technique based on spectral analysis and topographic EEG mapping was used to evaluate EEG arousal response to olfactory stimulation in ten normal subjects and ten PD patients in stage II according to Hoehn and Yahr's scale, all of whom had akinetic-rigid syndrome and were receiving chronic L-Dopa therapy. Olfactory function was stimulated using diluted benzaldehyde by means of an apparatus set up in our laboratory. Spontaneous and post-olfactory stimulus EEGs were recorded from 20 electrodes placed upon the scalp according to the Int. 10–20 System. Total EEG power (from 0.5 to 19.5 Hz) was evaluated over 10 sec. artefact-free epochs. An olfactory arousal reaction was detected in nine of the ten PD patients and was characterised by a significant decrease in total power similar to that observed in all of the 10 normal subjects; these variations in EEG were found in all but the anterior regions of the scalp. The use of this technique does not seem to reveal any clear alteration in the olfactory function of PD patients.

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Sommario Una alterazione della funzione olfattiva è stata osservata in pazienti affetti da morbo di Parkinson idiopatico (MP) impiegando metodiche psicofisiche. In questo studio è stata utilizzata una tecnica elettrofisiologica, basata sull'impiego dell'analisi spettrale e sulla rappresentazione in mappe del segnale EEG, al fine di valutare la reazione di arousal prodotta dalla stimulazione olfattiva in 10 soggetti normali di controllo ed in 10 pazienti affetti da MP, in stadio II secondo la scale di Hoehn e Yahr, con forma acinetico-ipertonica ed in terapia cronica con L-Dopa. La stimolazione olfattiva veniva condotta, utilizzando Benzaldeide diluita in olio di paraffina, mediante un'apparecchiatura messa a punto nel nostro laboratorio. L'EEG basale e dopo stimolo veniva registrato da 20 elettrodi disposti secondo il Sistema Internazionale 10–20; su epoche di 10 sec. prive di artefatti è stata calcolata la potenza totale (da 0.5 a 19.5 Hz) in corrispondenza di tutti gli electtrodi. Una reazione di arousal veniva rilevata in 9 su 10 pazienti con MP ed era caratterizzata da un decremento di potenza totale analogo a quello verificato nel gruppo di controllo; tali variazioni interessavano tutte le regioni dello scalpo tranne le anteriori. L'impiego di questa metadica oggettiva non sembra pertanto mettere in evidenza una chiara alterazione della funzione olfattiva in pazienti affetti da MP.

     

Comparison of lisuride and bromocriptine in the treatment of advanced Parkinson''s disease

Twenty patients with advanced idiopathic Parkinson's disease were studied, all having a deteriorating response to levodopa and suffering from daily fluctuations in disability. A double-blind randomized cross-over study was conducted. Basic levodopa and anticholinergic treatment was continued unchanged in all patients. The dose increment period of 4-8 weeks was followed by a 4 week treatment period on a fixed optimal dose. In both treatment groups the mean optimal daily dose of lisuride was 1.3 mg (range 0.2-2.4 mg) and that of bromocriptine about 15 mg (range 3.75-30.0), without any significant differences between the treatment groups. The addition of lisuride or bromocriptine to levodopa treatment resulted in a significant and equal further improvement of parkinsonian disability. The therapeutic profiles of both lisuride and bromocriptine were similar. There was significantly more improvement in tremor than in other parkinsonian symptoms. Both lisuride and bromocriptine elicited a significant improvement in fluctuations of disability. No significant differences between the treatments were observed. The occurrence of clinical side effects seemed to be similar with both treatment regimens. In advanced parkinsonian patients the therapeutic efficacy of lisuride seems to be equal to that of bromocriptine as far as parkinsonian disability and fluctuations in disability are concerned.     

Lisuride plus selegiline in the treatment of early Parkinson''s disease

We treated 20 early Parkinson's disease subjects with the dopamine agonist lisuride in combination with the MAO-B inhibitor selegiline (L-deprenyl). We started with lisuride alone for one month, then we added selegiline versus placebo to lisuride in double-blind conditions for 3 months; finally all patients received lisuride and selegiline for another 3 months. Lisuride alone (1.43 +/- 0.10 mg) significantly improved PD. When selegiline (10 mg/day) was added in the double-blind phase the mean lisuride dosage could be reduced by 22.8% without deterioration of the clinical effects, and the same occurred in the former placebo group when selegiline was added. The combination of both drugs was well tolerated. These data are of interest for the interpretation of the effects of selegiline.     

帕金森病核团毁损术疗效与并发症的关系

目的：进一步总结帕金森病的微电极导向苍白球腹后部毁损术和丘脑腹中间核毁损术疗效。方法：微电极导向立体定向核团毁损术治疗帕金森病患者300例。对近期进行的100例患者在手术靶点选择、手术方法、手术疗效和并发症等方面进行总结，并与早期进行的100例手术患者比较。结果：近期进行的100例患者手术效果较好，并发症发生率低。结论：根据患者症状选择合适的毁损术能提高手术疗效；对靶点采用磁共振成像（MRI）图像和座标相结合的定位方法,可减少个体差异引起的误差；适当减少微电极记录针道数，降低毁损温度，能减轻电极与脑组织粘连，减少脑出血等并发症。     

The effect of onset age on the clinical features of Parkinson's disease

Many clinicians view age at onset as an important determinant of clinical phenotype in Parkinson's disease (PD) and this has been reinforced by the identification of Mendelian genes that account for some cases of younger onset PD. A systematic review of OVID Medline for articles relevant to the relationship between clinical features and age at onset in PD published in English between 1950–2007 was performed. There are very few prospective community based studies which focus on the relationship between age at onset and the features of PD and a variety of case definitions are used in the literature. Most studies of young onset PD are based on specialist clinic referral series. The available evidence suggests that PD patients with a younger age at onset have: (i) a slower disease progression, (ii) an increased rate of dystonia at onset and during treatment, (iii) a lower rate of dementia and (iv) an increased rate of dyskinesias in response to l -DOPA treatment. The majority of the available studies do not report patient genotype data, but it is probably that the clinical heterogeneity of PD will be further refined with detailed clinico-genetic studies.     

如何提高帕金森病中脑细胞移植中的细胞存活率？

虽然胚胎中脑细胞移植对帕金森病的疗效已得到广泛证实,但在这项技术广泛应用于临床之前仍有一些问题亟待解决。其中主要是移植物存活率低和宿主纹状体神经支配恢复有限。迄今为止,人们尝试了很多方法来解决这些问题,包括神经营养因子的广泛应用,以及神经和(或)非神经来源组织的联合移植。本文将对目前的胚胎中脑细胞移植术中所用的神经保护手段及其局限性进行简要的介绍。     

TH基因修饰的神经干细胞移植治疗帕金森病的实验研究

目的 探讨TH基因修饰的神经干细胞脑内移植对帕金森病(PD)的治疗作用。方法 构建pN：ATH逆转录病毒载体质粒，用PA317细胞包装，G418筛选阳性克隆，病毒上清感染神经干细胞，将表达TH的神经干细胞植入：PD大鼠纹状体内，测定：PD大鼠旋转行为改善，DA和DOPAC含量变化，以及TH在纹状体的表达。结果 TH基因修饰的神经干细胞移植8周时能显著降低PD大鼠旋转行为，增加纹状体DA和DOPAC含量，TH在纹状体内的表达增加，疗效好于单纯神经干细胞移植组。结论 TH基因修饰的神经干细胞移植对PD大鼠有明显的治疗作用，可望为PD治疗提供新的途径。     

Deprenyl (selegiline) in the treatment of Parkinson''s disease

ABSTRACT — The effects of deprenyl were investigated in 45 parkinsonian patients suffering from fluctuations in disability under long-term levodopa treatment. During a 1 to 3 month period of treatment, 5–10 mg of deprenyl caused a significant reduction in response fluctuations in 26 out of 45 patients (58 %). This improvement was only moderate (58 %) or minimal (42 %). Of 11 parkinsonian patients taking deprenyl with levodopa and benserazide for up to 4 years, 6 patients (55 %) showed moderate and 5 patients (45 %) minimal improvement initially. The improvement in response fluctuations was maintained during the follow-up period, although there was a clear decline in the degree of improvement. The addition of deprenyl to levodopa treatment also caused a further improvement in parkinsonian disability, which, however, decreased during the treatment period. Deprenyl appears to be a useful adjuvant to levodopa in patients with daily fluctuations in disability.     

Effects of levodopa on finger and orofacial movements in Parkinson''s disease

1. 1. The objective of this study is to compare the efficacy of levodopa on finger and orofacial movements in Parkinson's disease. The sensitivity of the orofacial and finger systems to levodopa would suggest the involvement of dopaminergic lesions.

2. 2. The production of isometric force was estimated in both conditions, without and with levodopa, in 14 patients with idiopathic Parkinson's disease (mean duration of symptoms: 9 ± 3 years).

3. 3. Forces generated by the upper and lower lips, tongue, right and left forefingers in the presence of visual feedback were measured by means of force transducers.

4. 4. The target force levels used in the present study included 0.25, 0.5, 1 and 2 newtons corresponding to fine forces presumably involved in speech production. Moreover, motor disability of patients was assessed in each condition, using the motor examination of the Unified Parkinson's disease rating scale and a hand-tapping test.

5. 5. Fourteen control subjects also participated in this study.

6. 6. The beneficial effect of levodopa on finger movements was observed as indicated by an improvement in motor scores and production of forces. In contrast, the production of orofacial forces was either not improved, or aggravated by levodopa.

7. 7. These results suggest that cerebral non dopaminergic lesions participate to the impairments of parkinsonian speech.

     

帕金森病猴丘脑底核神经元的电生理特性

目的探讨帕金森病(PD)猴模型丘脑底核(STN)神经元的电生理特性,为研究帕金森病的病理生理过程提供动物实验依据。方法应用颈内动脉注射MPTP建立PD猴模型。在立体定向仪引导下应用细胞外记录的方法记录"造模"前后猴病理及正常生理状态下STN神经元的放电活动,并对其放电模式进行分析。结果电生理记录显示STN神经元放电频率在生理状态下为2.03±1.12Hz;在病理状态下为9.58±0.85 Hz(P<0.01)。在生理状态下有20个(20/35,57.14%)神经元呈现簇发放电,有15个(15/35,42.86%)神经元呈现连续放电;在PD病理状态下有10个(10/12,85.71%)神经元呈现簇发放电,有2个(2/12,14.29%)神经元呈现连续放电(P<0.05)。生理状态下STN神经元的ISI序列散在分布于30～980ms之间;在PD病理状态下当STN神经元呈连续放电时,ISI分布于50～360ms之间,在150ms以下有一个分布密集条带,当STN神经元呈簇发放电时,ISI分布于30～470ms之间,在40ms以下有一个分布密集条带。结论PD猴模型STN神经元较生理状态下放电频率明显增加,其放电模式也有明显变化,簇状放电模式比例增大,ISI序列发生明显变化。