Early Recognition of Neuroleptic Malignant Syndrome Without Hyperthermia: A Narrative Review

13/09/2026

AI Summary

Neuroleptic malignant syndrome frequently presents without documented hyperthermia; many patients are afebrile at initial presentation and fever often develops later.
Muscular rigidity and rising creatine kinase are earlier and more consistent markers than measured hyperthermia for early recognition of NMS.
Heightened bedside awareness, structured monitoring of rigidity and CK trajectory, and early exclusion of alternative diagnoses shorten time to recognition despite retrospective evidence.

AI Summary

Primary cohort, case-register, pharmacovigilance, and clinical-feature-frequency data document that a clinically important minority of diagnosed patients are afebrile at presentation, and that rigidity precedes measured hyperthermia in the majority who eventually become febrile.

This review synthesises the evidence bearing on early recognition of NMS in patients who do not yet meet the fever criterion, and asks what earlier markers, clinical patterns, and management steps are supported by primary evidence.

Feature-frequency series show that rigidity and rising creatine kinase (CK) are earlier and more universal markers than measured hyperthermia; pathophysiological modelling is consistent with the view that hyperthermia is a downstream and variable manifestation of the underlying pathophysiological process; and outcome data indicate that delayed recognition tracks with the leading causes of death and disability (respiratory failure, acute kidney injury, rhabdomyolysis).

Basic summary

Cureus. 2026 Aug 13;18(8):e114485. doi: 10.7759/cureus.114485. eCollection 2026 Aug.

ABSTRACT

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal idiosyncratic reaction to dopamine antagonism, traditionally recognised by hyperthermia, muscular rigidity, autonomic instability, and altered mental status. International consensus and DSM-5 research criteria uniformly require documented repeated hyperthermia to establish a diagnosis. Primary cohort, case-register, pharmacovigilance, and clinical-feature-frequency data document that a clinically important minority of diagnosed patients are afebrile at presentation, and that rigidity precedes measured hyperthermia in the majority who eventually become febrile. This review synthesises the evidence bearing on early recognition of NMS in patients who do not yet meet the fever criterion, and asks what earlier markers, clinical patterns, and management steps are supported by primary evidence. Feature-frequency series show that rigidity and rising creatine kinase (CK) are earlier and more universal markers than measured hyperthermia; pathophysiological modelling is consistent with the view that hyperthermia is a downstream and variable manifestation of the underlying pathophysiological process; and outcome data indicate that delayed recognition tracks with the leading causes of death and disability (respiratory failure, acute kidney injury, rhabdomyolysis). Because all available evidence is retrospective, cohort, pharmacovigilance, or observational in design, conclusions are directional rather than definitive. Awareness of the afebrile presentation, structured attention to rigidity and CK trajectory, and early exclusion of alternative diagnoses are supported by the primary literature as low-cost strategies to shorten the time to recognition. Formal criteria are unchanged; the change proposed here is one of clinical awareness at the bedside.

PMID:42732346 | PMC:PMC13570673 | DOI:10.7759/cureus.114485

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