• C Khouri, S Planès, S Logerot, C Villier, and M Mallaret.
• Service de pharmacie, CHU Grenoble-Alpes, 38000 Grenoble, France; Pôle Santé Publique, Pharmacovigilance, CHU Grenoble-Alpes, 38000 Grenoble, France.
• Encephale. 2016 Jun 1; 42 (3): 277-80.

BackgroundNeuroleptic malignant syndrome (NMS) is an uncommon but potentially fatal adverse effect of neuroleptic drugs. It is commonly characterized by muscular rigidity, fever, altered mental status, and autonomic dysfunction. Emerging of NMS is possible with all neuroleptics, classic and atypical. NMS occurs most often during the first week of treatment or after increasing the dosage of the neuroleptic medication. The frequency of NMS ranges from 0.07 to 2.2%. Its pathophysiology is not clearly understood but the blockade of dopamine receptors appears to be the central mechanism. Issues of NMS are those of diagnosis, treatment and reintroduction of antipsychotic treatment or not.ObjectiveWe here present an interesting case because of its atypical clinical presentation and its slow resolution, illustrating the various problems linked to the NMS.Case ReportA 55-year-old woman with a history of mental retardation and infantile psychosis is hospitalized for worsening of her psychiatric symptoms. She is treated by risperidone long-acting injection every 2weeks, escitalopram 20 mg/d and oxazepam 10 mg/d. Early December 2012, she had fever spikes treated with many antibiotics and neuroleptics were stopped, without improvement. Early January 2013, a pulmonary embolism was diagnosed, and a treatment with loxapine is introduced and her injection of risperidone is done because of the state of agitation of the patient. Two weeks later, a NMS is suspected to hyperthermia, tremor of the limbs, a slight stiffness, and neuroleptics are stopped. Dantrolene is then introduced, but after 7days of treatment the fever is still important. Other assumptions are then discussed: infection, serotonin syndrome, encephalopathy, catatonia, malignant hyperthermia. But diagnosis of NMS is finally retained because of the recurrence of symptoms after introduction of clozapine early February.DiscussionIn this patient, diagnosis was made more difficult by the use of long-acting neuroleptic. NMS was indeed partly rejected because of the lack of improvement despite 7 days of dantrolene treatment, but the release of risperidone lasts 7weeks after the injection. This NMS is also of atypical presentation with a minor muscular rigidity. And this case is particularly interesting because of the recurrence of NMS with clozapine, allowing to finally diagnose it. This atypical neuroleptic is not known to be a major provider of NMS but the very short period before reintroduction and possible persistence of risperidone in the body could explain the recurrence.ConclusionNMS can be hard to diagnose. It is a diagnosis of exclusion, but we should keep in mind that there is great variability of its clinical presentation in order to not exclude too quickly this syndrome in a patient treated by neuroleptic.Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

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