Atypical Neuroleptic Malignant Syndrome: Diagnostic Controversies and Considerations

Abstract

Neuroleptic malignant syndrome (NMS) is a serious and potentially fatal adverse effect of antipsychotic drugs. The diagnosis of NMS commonly requires core symptoms of hyperthermia and muscle rigidity. Although diagnostic criteria for NMS have been established and are widely accepted and used, it should be recognized that atypical presentations pose a diagnostic dilemma, as hyperthermia and/or muscle rigidity may be absent or develop slowly over several days, leading to impairment or a significant delay in diagnosis and treatment. Evidence from case reports and retrospective evaluations supports a concept of atypical NMS, particularly with regard to treatment with atypical antipsychotics. However, it remains unclear whether these atypical presentations represent early or impending NMS. Furthermore, it is unclear whether dysfunction in other neurotransmitter systems, in addition to dopamine, may be involved in the pathogenesis of NMS induced by atypical antipsychotics. In patients receiving any antipsychotic, clinicians should carefully evaluate any features of NMS and should not prematurely exclude a diagnosis of NMS in cases where severe rigidity or hyperthermia is not initially apparent.

Psychotropic discontinuation leading to an NMS‐like condition

“…[11][12][13][14] However, there are several case reports in which patients have not presented with all the core symptoms, leading to such cases being termed 'atypical NMS'. The diagnosis and the uncertainly of the nature and course of this condition have been discussed by Picard et al, 15 Odagaki 16 and Trollor et al 17 Our patient had altered consciousness, fever, sweating, elevated CPK and WBC, tachycardia, tachypnoea and incontinence but no documented reports of rigidity, as this was not checked due to his aggression. This case could be described as atypical NMS as the patient had most of the core criteria of NMS other than extrapyramidal symptoms.…”

Antipsychotic Drugs Rechallenge in Multi-antipsychotic Drug Induced Atypical Neuroleptic Malignant Syndrome: A Case of Cotard’s Syndrome

“…The first step of the treatment is discontinuation of the anti-psychotic agent. After that, supportive therapy must be initiated (e.g., aggressive rehydration and restoring electrolyte balance, alkaline fluids, physical cooling, careful monitoring of complications, including aspiration pneumonia, acute renal failure, cardiac arrest, pulmonary embolism, disseminated intravascular coagulation) and specific agents such as amantadine, bromocriptine and dantrolene must be used in order to reduce the mortality rate (6,12,13).…”

“…Due to the high possibility of NMS recurrence, at least 2 weeks should elapse after recovery; low doses of lowpotency anti-psychotics should be titrated gradually after a test dose; and patients should be carefully monitored for early signs of NMS when psychotic symptoms persist (6). We initiated low dosage quetiapine treatment after recovery from NMS and titrated it very slowly.…”

Encephalopathy Associated with Psychotropic Drug Therapy

“…At the same time, great interest has also been taken in the concept of "atypical NMS", which is often presumed to be more associated with atypical antipsychotics than with conventional drugs (Picard et al, 2008). Though still controversial, the review of Trollor et al (2009) suggests that NMS associated with atypical antipsychotics manifests in a typical manner, with one notable exception of clozapineinduced NMS which appears to be less associated with EPS.…”