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I was astonished to find that Sato and colleagues were able to identify 40 cases of neuroleptic malignant syndrome (NMS) in patients with Parkinson’s disease from a single institution over three years.1 At a recent neurosciences grand round in Birmingham, UK, which has an interest in Parkinson’s disease research, we could only recall two such cases in living memory.
There are two possible explanations for this high incidence of NMS. Firstly, in Japan the Parkinson’s disease population may be more prone to developing NMS when their anti-parkinsonian medication is reduced. This could be due to genotypic differences between Japanese and Western populations. Whereas a higher prevalence of the Parkin mutation has been noted in Japan,2 judging from the age range and duration of disease given in table 1 of Sato’s report,1 these were not all young onset patients as one would expect with the Parkin gene. Nevertheless, it would be of interest to know if this high incidence of NMS has been seen in other Japanese centres and whether any genotypic reason can be found.
The second possible explanation is that the reductions in anti-parkinsonian medication that precipitated NMS were substantial. NMS has been recorded in Parkinson’s disease in the past in association with so-called ‘drug holidays’, which have now been abandoned in most countries owing to the high fatality rate. Against this explanation is the fact that three patients had no change in their medication in Sato’s study.1
The interest of this paper lies not so much with the proven benefits of methylprednisolone therapy in NMS in Parkinson’s disease, as in the high incidence of NMS in the Japanese patients treated in this unit. I would value the author’s further comments.
We greatly appreciate Dr Clark’s comments about our work on the efficacy of methylprednisolone pulse therapy in neuroleptic malignant syndrome (NMS) in Parkinson’s disease.1 We agree with him that 40 cases of this syndrome identified from a single institute over three years in patients with Parkinson’s disease is a large number. The study institution—the Futase Social Insurance Hospital—is a specialised centre for neurological diseases, particularly among elderly patients, and we have treated several hundred patients with Parkinson’s disease. Furthermore, half the NMS patients were transferred from other non-specialised hospitals and private offices in the area. The large number of patients and inappropriate treatment in some patients resulted in an accumulation of NMS cases in our hospital. Physicians from other non-specialised hospitals and private clinics in the area are not always aware the risk of NMS on withdrawal of antiparkinsonian drugs. Indeed, in 30 cases of Parkinson’s disease, physicians stopped antiparkinsonian drugs because of psychiatric symptoms, dyskinesia, and the on-off phenomenon. These factors may have resulted in the accumulation of NMS cases in our hospital.
We were not aware that Japanese patients with Parkinson’s disease are more prone to developing NMS when antiparkinsonian drugs are reduced. However, the possibility of genotypic differences between Western and Japanese populations is interesting,2 and comparisons could usefully be made on the prevalence of mutations in parkin or other genes between these populations.