Levodopa prolongs life expectancy and is non-toxic to substantia nigra

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Abstract

The primary objective of the study was to determine the effect of levodopa (LD) on human substantia nigra. The study included patients seen at the Movement Disorder Clinic, Saskatoon over a 32 year period. The evidence provided is based on epidemiological observations of 934 consecutive Parkinson syndrome (PS) patients assessed during 22 years and detailed studies of six patients including two autopsies. Life expectancy increased significantly with LD therapy. The prolonged survival was evident when the patients were treated during early stage of the illness. One parkinsonian patient with substantia nigra (SN) pathology who was extensively studied for 30 years, revealed significant slowing of the disease progression while on LD. Three essential tremor patients who received 24 kg (26 years), 22 kg (21.5 years), and 8.5 kg (12.5 years) LD respectively, had no evidence of PS and one autopsy revealed normal SN. Two dopa-responsive dystonia patients who received LD 3 kg (11 years) and 17 kg (29 years) each had no evidence of PS and one autopsy revealed normal number of SN neurons.These observations indicate that LD is not toxic to human SN and are consistent with salutary effect of the drug on the SN in Parkinson's disease.

Section snippets

Introduction and background

Parkinson's disease (PD) is characterized by marked loss of substantia nigra (SN) pigmented neurons. Whether it is single event or a prolonged process which produces the pathological changes is unknown [1]. It is a progressive disease but the rate of decline varies among patients. The rate of worsening after Stage 2 Hoehn & Yahr [2] however is distinctive for each patient [3]. Although PD is concentrated in older age the aging process does not produce subregional SN neuronal loss characteristic

Material and patients

All patients included in this study were seen by the author personally.

We studied life expectancy in 934 consecutive PS patients assessed at the Movement Disorder Clinic Saskatoon (MDCS) over a 22 year period (1968–1990) [20]. The survival was measured from the date of first MDCS visit. Patients were then divided into those who had onset and MDCS visit before 1st January 1974—highly restricted access to LD and those who had an unrestricted LD access. Survival in each group was compared with sex

Results

Fig. 1 shows that life expectancy in the entire group of 934 PS patients compared to that expected in the matched general population was significantly shorter (P<0.0001). Prior to 1st January 1974, 215 of these patients were assessed at MDCS (had onset). The access to LD in this subgroup was extremely restricted as the patients often needed to attend MDCS to obtain LD prescription. Survival in these 215 patients compared with that expected is seen in Fig. 2. There was markedly reduced life

Discussion

The impact of LD on life expectancy has been a topic of many studies [26]. Our 22 year study of 934 patients is, to my knowledge, the largest such report, and the only report from one centre which assessed survival in patients prior to and subsequent to the widespread use of LD. As expected, the survival in this chronic illness is compromised and even today, remains significantly shorter than expected (Fig. 3). The benefit of LD to survival is evident when the shortened life expectancy in those

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