Neurocritical Care

, Volume 10, Issue 1, pp 136–140 | Cite as

The Parkinsonism-Hyperpyrexia Syndrome

  • Edward J. Newman
  • Donald G. Grosset
  • Peter G. E. Kennedy


The parkinsonism-hyperpyrexia syndrome (PHS) is a rare but potentially fatal complication seen in Parkinson’s disease (PD) patients, most commonly following reduction or cessation of antiparkinson medications. Clinically it resembles neuroleptic malignant syndrome with rigidity, pyrexia, and reduced conscious level. There may be features of autonomic instability, and serum creatine kinase (CK) may be elevated. Complications of PHS include acute renal failure, aspiration pneumonia, deep venous thrombosis/pulmonary embolism, and disseminated intravascular coagulation (DIC). Management consists of dopaminergic drug replacement, supportive measures, and treatment of complications. The prognosis is improved with early recognition and management. Mortality of up to 4% has been reported, but an additional one-third of patients have permanent sequelae. Patients and physicians should be warned against sudden reduction in antiparkinson medications. PHS should always be considered in a patient with parkinsonism who presents with an acute deterioration in symptoms.


Parkinsonism Hyperpyrexia Syndrome 


  1. 1.
    Delay J, Pichot P, Lemperiere T, et al. A non-phenothiazine and non-reserpine major neuroleptic, haloperidol, in the treatment of psychoses. Ann Med Psychol (Paris). 1960;118(1):145–52.Google Scholar
  2. 2.
    Caroff SN, Mann SC, Campbell EC, et al. Neuroleptic malignant syndrome. In: Frucht SJ, Fahn S, editors. Movement disorder emergencies diagnosis and treatment. New York: Humana Press; 2005. p. 41–52.Google Scholar
  3. 3.
    Nisijima K, Ishiguro T. Cerebrospinal fluid levels of monoamine metabolites and gamma-aminobutyric acid in neuroleptic malignant syndrome. J Psychiatr Res. 1995;29:233–44. doi: 10.1016/0022-3956(95)00007-R.PubMedCrossRefGoogle Scholar
  4. 4.
    Kipps CM, Fung VS, Grattan-Smith P, et al. Movement disorder emergencies. Mov Disord. 2005;20:322–34. doi: 10.1002/mds.20325.PubMedCrossRefGoogle Scholar
  5. 5.
    Berardi D, Amore M, Keck PE Jr, et al. Clinical and pharmacologic risk factors for neuroleptic malignant syndrome: a case-control study. Biol Psychiatry. 1998;44:748–54. doi: 10.1016/S0006-3223(97)00530-1.PubMedCrossRefGoogle Scholar
  6. 6.
    Keck PE Jr, Pope HG Jr, Cohen BM, et al. Risk factors for neuroleptic malignant syndrome. A case-control study. Arch Gen Psychiatry. 1989;46:914–8.PubMedGoogle Scholar
  7. 7.
    Toru M, Matsuda O, Makiguchi K, et al. Neuroleptic malignant syndrome-like state following a withdrawal of antiparkinsonian drugs. J Nerv Ment Dis. 1981;169:324–7. doi: 10.1097/00005053-198105000-00011.PubMedCrossRefGoogle Scholar
  8. 8.
    Takubo H, Harada T, Hashimoto T, et al. A collaborative study on the malignant syndrome in Parkinson’s disease and related disorders. Parkinsonism Relat Disord. 2003;9(Suppl 1):S31–41. doi: 10.1016/S1353-8020(02)00122-0.PubMedCrossRefGoogle Scholar
  9. 9.
    Konagaya M, Goto Y, Matsuoka Y, et al. Neuroleptic malignant syndrome-like condition in multiple system atrophy. J Neurol Neurosurg Psychiatry. 1997;63:120–1.PubMedCrossRefGoogle Scholar
  10. 10.
    Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991;148:705–13.PubMedGoogle Scholar
  11. 11.
    Mayeux R, Stern Y, Mulvey K, et al. Reappraisal of temporary levodopa withdrawal (“drug holiday”) in Parkinson’s disease. N Engl J Med. 1985;313:724–8.PubMedGoogle Scholar
  12. 12.
    Grosset D, Antonini A, Canesi M, et al. Adherence to antiparkinson medication in a multi-centre European study. Mov Disord. 2008; in press.Google Scholar
  13. 13.
    Douglas A, Morris J. It was not just a heatwave! Neuroleptic malignant-like syndrome in a patient with Parkinson’s disease. Age Ageing. 2006;35:640–1. doi: 10.1093/ageing/afl096.PubMedCrossRefGoogle Scholar
  14. 14.
    Gaig C, Marti MJ, Tolosa E, et al. Parkinsonism-hyperpyrexia syndrome not related to antiparkinsonian treatment withdrawal during the 2003 summer heat wave. J Neurol. 2005;252:1116–9. doi: 10.1007/s00415-005-0798-8.PubMedCrossRefGoogle Scholar
  15. 15.
    Grace JB, Thompson P. Neuroleptic malignant like syndrome in two patients on cholinesterase inhibitors. Int J Geriatr Psychiatry. 2006;21:193–4. doi: 10.1002/gps.1441.PubMedCrossRefGoogle Scholar
  16. 16.
    Gordon PH, Frucht SJ. Neuroleptic malignant syndrome in advanced Parkinson’s disease. Mov Disord. 2001;16:960–2. doi: 10.1002/mds.1166.PubMedCrossRefGoogle Scholar
  17. 17.
    Mizuta E, Yamasaki S, Nakatake M, et al. Neuroleptic malignant syndrome in a parkinsonian woman during the premenstrual period. Neurology. 1993;43:1048–9.PubMedGoogle Scholar
  18. 18.
    Shimada J, Sakakibara R, Uchiyama T, et al. Intestinal pseudo-obstruction and neuroleptic malignant syndrome in a chronically constipated parkinsonian patient. Eur J Neurol. 2006;13:306–7. doi: 10.1111/j.1468-1331.2006.01151.x.PubMedCrossRefGoogle Scholar
  19. 19.
    Factor SA. Fatal Parkinsonism-hyperpyrexia syndrome in a Parkinson’s disease patient while actively treated with deep brain stimulation. Mov Disord. 2007;22:148–9. doi: 10.1002/mds.21172.PubMedCrossRefGoogle Scholar
  20. 20.
    Factor SA, Santiago A. Parkinsonism-hyperpyrexia syndrome in Parkinson’s disease. In: Movement disorder emergencies: Diagnosis and treatment . New York: Humana Press; 2005. p. 29–41.Google Scholar
  21. 21.
    Ueda M, Hamamoto M, Nagayama H, et al. Susceptibility to neuroleptic malignant syndrome in Parkinson’s disease. Neurology. 1999;52:777–81.PubMedGoogle Scholar
  22. 22.
    Ueda M, Hamamoto M, Nagayama H, et al. Biochemical alterations during medication withdrawal in Parkinson’s disease with and without neuroleptic malignant-like syndrome. J Neurol Neurosurg Psychiatry. 2001;71:111–3. doi: 10.1136/jnnp.71.1.111.PubMedCrossRefGoogle Scholar
  23. 23.
    Shalev A, Hermesh H, Munitz H. Mortality from neuroleptic malignant syndrome. J Clin Psychiatry. 1989;50:18–25.PubMedGoogle Scholar
  24. 24.
    Serrano-Duenas M. Neuroleptic malignant syndrome-like, or—dopaminergic malignant syndrome—due to levodopa therapy withdrawal. Clinical features in 11 patients. Parkinsonism Relat Disord. 2003;9:175–8. doi: 10.1016/S1353-8020(02)00035-4.PubMedCrossRefGoogle Scholar
  25. 25.
    Hashimoto T, Tokuda T, Hanyu N, et al. Withdrawal of levodopa and other risk factors for malignant syndrome in Parkinson’s disease. Parkinsonism Relat Disord. 2003;9 Suppl 1:S25–30. doi: 10.1016/S1353-8020(02)00119-0.PubMedCrossRefGoogle Scholar
  26. 26.
    Ikebe S, Harada T, Hashimoto T, et al. Prevention and treatment of malignant syndrome in Parkinson’s disease: a consensus statement of the malignant syndrome research group. Parkinsonism Relat Disord. 2003;9 Suppl 1:S47–9. doi: 10.1016/S1353-8020(02)00123-2.PubMedCrossRefGoogle Scholar
  27. 27.
    Rosenberg H, Davis M, James D, et al. Malignant hyperthermia. Orphanet J Rare Dis. 2007;2:21. doi: 10.1186/1750-1172-2-21.PubMedCrossRefGoogle Scholar
  28. 28.
    Mueller PS, Vester JW, Fermaglich J. Neuroleptic malignant syndrome. Successful treatment with bromocriptine. J Am Med Assoc. 1983;249:386–8. doi: 10.1001/jama.249.3.386.CrossRefGoogle Scholar
  29. 29.
    Sato Y, Asoh T, Metoki N, et al. Efficacy of methylprednisolone pulse therapy on neuroleptic malignant syndrome in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2003;74:574–6. doi: 10.1136/jnnp.74.5.574.PubMedCrossRefGoogle Scholar
  30. 30.
    Magdalinou KN, Martin A, Kessel B. Prescribing medications in Parkinson’s disease (PD) patients during acute admissions to a District General Hospital. Parkinsonism Relat Disord. 2007;13:539–40. doi: 10.1016/j.parkreldis.2006.11.006.PubMedCrossRefGoogle Scholar
  31. 31.
    Grosset K, Needleman F, MacPhee G, et al. Switching from ergot to nonergot dopamine agonists in Parkinson’s disease: a clinical series and five-drug dose conversion table. Mov Disord. 2004;19:1370–4. doi: 10.1002/mds.20210.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Edward J. Newman
    • 1
  • Donald G. Grosset
    • 1
  • Peter G. E. Kennedy
    • 1
  1. 1.Department of NeurologyInstitute of Neurological Sciences, Southern General HospitalGlasgowUK

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