Motor fluctuations in Parkinson’s disease
Introduction
Fluctuations in the severity of symptoms has been a well recognised feature of Parkinson’s disease (PD). However, it was with the advent of levodopa treatment that fluctuations became common and disabling. Approximately 10% of all patients treated with levodopa develop motor fluctuations (MF) per treatment year so that with long term treatment MF eventually affect most of the patients [1]. After initial smooth and stable therapeutic response, the duration of action of levodopa seems to decrease, i.e. end-of-dose deterioration. This is due to a reduction in the dopamine synthesising and storage capabilities of the nigro-striatal system and relates to the extent of its degeneration [2]. The same mechanism contributes partly to the ‘off’ periods. In addition, long term levodopa treatment leads to development of abnormal involuntary movements in 24–89% of patients [3], [4]. While some of these are frequently associated with peak plasma levels of levodopa (e.g. peak dose dyskinesias), not all of these phenomena can be explained (e.g. on–off phenomenon). Whether these motor fluctuations occur as a result of the progression of the disease or as a result of chronic levodopa (LD) treatment is yet to be ascertained. While longer duration of LD treatment has been implicated with increased frequency of MF [5], this view is not shared by others [6]. Progression of disease has been considered as the factor responsible for worsening in PD patients along with development of MF [6].
The risk factors incriminated in development of MF include age at onset of disease [7], duration of levodopa treatment [3], [8], duration of illness, severity of disease at the time of starting levodopa therapy and duration of disease prior to levodopa therapy [9]. MF were less in PD patients who had tremor as the predominant symptom as compared to those who had rigidity or bradykinesia. Young onset PD patients seem to develop MF earlier as compared to older PD patients [10]. Identification of risk factors is important from therapeutic point of view especially as regards the time of initiation of LD therapy.
We conducted a study to answer the following questions: (1) What are the prevalence and patterns of MF in Parkinson’s disease? (2) What are the risk factors for development of motor fluctuations?
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Materials and methods
This study was conducted at the All India Institute of Medical Sciences (AIIMS), New Delhi, a tertiary referral centre catering to a population of more than 10 million people. Eighty consecutive patients of PD both new and those on follow up attending the Movement Disorder Clinic from January 1996 to December 1996 were studied.
The diagnosis of Parkinson’s disease was based on the presence of bradykinesia associated with at least one of the following symptoms: muscular rigidity, 4–6 Hz rest
Results
The clinical and demographic features of the 80 patients are shown in Table 1, Table 2. Of the 80 patients included in the study, 59 (73.8%) were males and 21 (26.2%) females. Mean age of the patients was 60.1±9.7 years (range 28–78 years), with the mean age at onset of illness being 55.1±11.00 years (range 13–75 years) and the mean duration of illness 5.0±4.3 years (range 1 month–25 years). Tremor and bradykinesia were the commonest symptoms at onset of illness and were seen in 70% (n=56) and
Discussion
MF were seen in 50% (n=40) of the patients examined. Similar observations have been made by others. Dyskinesia was seen in 24–89.5% of patients after 3 years of sustained LD therapy [3], [5].
A shorter interval from the disease onset to levodopa treatment and longer duration of levodopa therapy were seen to be significantly associated with the risk of development of MF. The role of LD in causing motor fluctuations has been a matter of contention. While some workers believe that MF are caused by
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