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March 01, 1999; 52 (4) Article

Susceptibility to neuroleptic malignant syndrome in Parkinson’s disease

M. Ueda, M. Hamamoto, H. Nagayama, K. Otsubo, C. Nito, T. Miyazaki, A. Terashi, Y. Katayama
First published March 1, 1999, DOI: https://doi.org/10.1212/WNL.52.4.777
M. Ueda
From the Department of Neurology (Drs. UedaHamamoto, Nagayama, and Miyazaki), Tokyo Metropolitan Tama Geriatric Hospital, Higashimurayama-city; and the Division of Neurology (Drs. Ueda, Otsubo, Nito, Terashi, and Katayama), Second Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
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M. Hamamoto
From the Department of Neurology (Drs. UedaHamamoto, Nagayama, and Miyazaki), Tokyo Metropolitan Tama Geriatric Hospital, Higashimurayama-city; and the Division of Neurology (Drs. Ueda, Otsubo, Nito, Terashi, and Katayama), Second Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
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H. Nagayama
From the Department of Neurology (Drs. UedaHamamoto, Nagayama, and Miyazaki), Tokyo Metropolitan Tama Geriatric Hospital, Higashimurayama-city; and the Division of Neurology (Drs. Ueda, Otsubo, Nito, Terashi, and Katayama), Second Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
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K. Otsubo
From the Department of Neurology (Drs. UedaHamamoto, Nagayama, and Miyazaki), Tokyo Metropolitan Tama Geriatric Hospital, Higashimurayama-city; and the Division of Neurology (Drs. Ueda, Otsubo, Nito, Terashi, and Katayama), Second Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
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C. Nito
From the Department of Neurology (Drs. UedaHamamoto, Nagayama, and Miyazaki), Tokyo Metropolitan Tama Geriatric Hospital, Higashimurayama-city; and the Division of Neurology (Drs. Ueda, Otsubo, Nito, Terashi, and Katayama), Second Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
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T. Miyazaki
From the Department of Neurology (Drs. UedaHamamoto, Nagayama, and Miyazaki), Tokyo Metropolitan Tama Geriatric Hospital, Higashimurayama-city; and the Division of Neurology (Drs. Ueda, Otsubo, Nito, Terashi, and Katayama), Second Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
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A. Terashi
From the Department of Neurology (Drs. UedaHamamoto, Nagayama, and Miyazaki), Tokyo Metropolitan Tama Geriatric Hospital, Higashimurayama-city; and the Division of Neurology (Drs. Ueda, Otsubo, Nito, Terashi, and Katayama), Second Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
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Y. Katayama
From the Department of Neurology (Drs. UedaHamamoto, Nagayama, and Miyazaki), Tokyo Metropolitan Tama Geriatric Hospital, Higashimurayama-city; and the Division of Neurology (Drs. Ueda, Otsubo, Nito, Terashi, and Katayama), Second Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
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Citation
Susceptibility to neuroleptic malignant syndrome in Parkinson’s disease
M. Ueda, M. Hamamoto, H. Nagayama, K. Otsubo, C. Nito, T. Miyazaki, A. Terashi, Y. Katayama
Neurology Mar 1999, 52 (4) 777; DOI: 10.1212/WNL.52.4.777

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Abstract

Objective: To determine susceptibility to neuroleptic malignant syndrome (NMS) in patients with PD in relation to central monoamine metabolism.

Methods: CSF levels of homovanillic acid (HVA), 3-methoxy-4-hydroxy phenyletilene glycol (MHPG), and 5-hydroxyindole acetic acid (5-HIAA) were assayed in 98 PD patients (mean age, 77.2 years), including 11 patients with a prior NMS-like episode, by high-performance liquid chromatography with electrochemical detection.

Results: Patients with a previous NMS-like episode had worse parkinsonian disability as measured by Hoehn & Yahr scale (3.7 ± 0.8 versus 3.0 ± 1.1; p = 0.038) and lower CSF HVA levels (20.9 ± 17.3 versus 44.7 ± 22.2 ng/mL; p = 0.001) compared to those without, despite similar age, disease duration, and daily dosages of antiparkinsonian drugs between groups. Logistic regression analysis showed that the CSF HVA level (p = 0.008), but not 5-HIAA level (p = 0.621), was significantly and independently related to NMS, and that the MHPG level (p = 0.070) was tendentially associated with the disorder. Odds ratios (95% confidence intervals) corresponding to 10 ng/mL increment in CSF HVA, MHPG, and 5-HIAA levels were 0.30 (0.13 to 0.73), 4.03 (0.89 to 18.2) and 1.29 (0.47 to 3.58), respectively.

Conclusions: Central dopaminergic and possible noradrenergic activity contributes to NMS development in an elderly population of PD patients. Measuring CSF levels of monoamine metabolites may provide a means for identifying NMS susceptibility in PD patients.

  • Received July 1, 1998.
  • Accepted in final form November 24, 1998.
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