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Neuroleptic malignant syndrome following BMT

Bone Marrow Transplantation volume 29, pages 803–804 (2002)Cite this article

Neuroleptic malignant syndrome (NMS), a severe adverse effect of psychotropic drugs, is characterized by hyperthermia, extrapyramidal symptoms, autonomic instability, alterations in consciousness, elevated creatine phosphokinase in serum, and leukocytosis.1 Mental disturbances such as adjustment disorder, mood disorder, and delirium, are frequent in BMT patients because of physical and psychological stress from pretransplant irradiation, chemotherapy, GVHD, and pathogen-free protective isolation rooms.2 Psychotropic drugs are used commonly to treat psychiatric symptoms in these patients. The reported occurrence of NMS in patients receiving neuroleptic and related medications is 0.1 to 12.2%.3 Mortality in NMS is about 10%.4 Transplant recipients represent a group at high risk for NMS since exhaustion and multiple medical illnesses, frequently seen in post-transplantation patients, are considered to be risk factors for NMS.5 However, NMS is relatively difficult to identify in this setting because of the agranulocytosis and fever that follow BMT, and also the neurologic symptoms that occasionally occur as adverse effects of immunosuppressants.6 Here, we describe a patient with NMS following BMT successfully treated after early diagnosis.

A 52-year-old woman with acute myeloid leukemia (FAB M0) underwent HLA–matched BMT. Before transplantation she had been treated with six courses of cytarabine and aclarubicin hydrochloride. She had no history of central nervous system disease except for depressive symptoms first noted a few months before BMT. BMT was carried out following conditioning with cyclophosphamide (60 mg/kg), thiotepa (200 μg/m2) on 2 consecutive days and total body irradiation (12 Gy in four 3 Gy doses on 4 consecutive days). Tacrolimus hydrate (1.2 mg/day) was given as prophylaxis against GVHD beginning on the day before transplantation. The patient had been depressed for 4 months before BMT and was diagnosed as adjustment disorder with mixed anxiety and depressed mood according to the forth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).7 Amitriptyline hydrochloride (50 mg/day) was started 16 days before transplantation. At the time of transplantation neurologic examination was normal, although anxiety and depression were still present. Amitriptyline hydrochloride was continued for 4 days after transplantation. When she became delirious, haloperidol (10 mg/day) was added. Within 48 h the patient became febrile (39.5°C) and developed tremors, rigidity in the upper extremities and fluctuating consciousness levels. On post-transplant day 6, in addition to the continuing fever, she developed generalized rigidity, tachycardia, hypertension, and rhabdomyolysis (creatine phosphokinase, 538 U/l; normal, <160). The serum creatinine concentration was 1.73 mg/dl. We diagnosed the patient as probable NMS according to the criteria of Pope et al,1 although following BMT granulocytes were too few to be counted. Haloperidol and tacrolimus hydrate were discontinued. Cyclosporine (100 mg/day) and methylprednisolone (125 to 500 mg/day) were initiated as GVHD prophylaxis. Within the next 4 days the fever, tremor, hypertension, and tachycardia all improved. Within the next 12 days the disturbed consciousness and rigidity resolved, but low-grade fever continued. Subsequently, the creatine phosphokinase gradually rose to reach 2088 U/l on post-transplant day 19, returning to normal on day 25. No evidence of infections, endocrinopathies, or cerebrovascular events was noted during the febrile episode.

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References

  1. Pope HG Jr, Keck PE, McElroy SL . Frequency and presentation of neuroleptic syndrome in a large psychiatric hospital Am J Psychiatr 1986 143: 1227 1233

    Article  Google Scholar 

  2. Sasaki T, Akaho R, Sakamaki H et al. Mental disturbances during isolation in bone marrow transplant patients with leukemia Bone Marrow Transplant 2000 25: 315 318

    Article  CAS  Google Scholar 

  3. Naganuma H, Fujii L . Incidence and risk factors in neuroleptic malignant syndrome Acta Psychiatr Scand 1994 90: 424 426

    Article  CAS  Google Scholar 

  4. Shalev A, Hermesh H, Munitz H . Mortality from neuroleptic malignant syndrome J Clin Psych 1989 50: 18 25

    CAS  Google Scholar 

  5. Caroff SN, Mann SC . Neuroleptic malignant syndrome Med Clin N Am 1993 77: 185 202

    Article  CAS  Google Scholar 

  6. Woo M, Przepiorka D, Ippoliti C et al. Toxicities of tacrolimus and cyclosporin A after allogeneic blood stem cell transplantation Bone Marrow Transplant 1997 20: 1095 1098

    Article  CAS  Google Scholar 

  7. Allen F . Diagnostic and Statistical Manual of Mental Disorders, 4 edn (DSM-IV) American Psychiatric Press: Washington, DC 1994 pp 739 742

    Google Scholar 

  8. Garrido SM, Chauncy TR . Neuroleptic malignant syndrome following autologous peripheral blood stem cell transplantation Bone Marrow Transplant 1998 21: 427 428

    Article  CAS  Google Scholar 

  9. Levinson DF, Simpson GM . Neuroleptic-induced extrapyramidal symptoms with fever Arch Gen Psych 1986 43: 839 848

    Article  CAS  Google Scholar 

  10. Heimann-Patterson TD . Neuroleptic malignant syndrome and malignant hyperthymia Med Clin N Am 1993 77: 477 492

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, Yokohama City University, School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan

    M Onose, C Kawanishi, H Onishi, T Yamada, M Itoh & K Kosaka

  2. Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan

    J Taguchi, S Fujisawa & H Kanamori

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  1. M Onose
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  2. C Kawanishi
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  3. H Onishi
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  4. T Yamada
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  5. M Itoh
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  6. K Kosaka
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  7. J Taguchi
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  8. S Fujisawa
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  9. H Kanamori
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Onose, M., Kawanishi, C., Onishi, H. et al. Neuroleptic malignant syndrome following BMT. Bone Marrow Transplant 29, 803–804 (2002). https://doi.org/10.1038/sj.bmt.1703532

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