Neuroleptic malignant syndrome (or malignant extrapyramidal autonomic syndrome): Time to revisit diagnostic criteria and terminology?

To the Editor

Neuroleptic malignant syndrome (NMS) is an uncommon but potentially life-threatening adverse reaction to medications having dopamine receptor–blocking properties, also referred to as ‘neuroleptics’. Although most reported cases of NMS implicate antipsychotics as the offending agent, there have also been many reports about its occurrence with agents traditionally considered to be non-neuroleptics (Berman, 2011). In this scenario, we feel that continued retention of the term NMS may not only be scientifically inaccurate but also detrimental to clinical practice as clinicians may lower their guard against this serious complication when initiating non-neuroleptic agents. A new term with less implications for presumed etiology of such a condition may have better clinical utility.

Furthermore, standard diagnostic criteria mention elevated temperature (>39°C) as a core diagnostic criteria of NMS while also recognizing the heterogeneous nature of its presentation (American Psychiatric Association [APA], 2013). However, there have been prior reports highlighting atypical presentations of NMS, wherein the patients remained afebrile throughout the course of this reaction (Menon et al., 2016). Such presentations not only challenge the theoretical underpinnings of NMS but also question the wisdom of having separate core and additional criteria. Although a couple of aberrant observations may not necessarily invalidate diagnostic criteria for NMS, or for that matter, any medical condition, the serious and potentially life-threatening nature of NMS demand that criteria be carefully recalibrated so as to minimize medical errors. There is a need to re-conceptualize NMS as a spectrum of clinical manifestations with no presentation being a sine qua non for diagnosing the syndrome.

Considering these issues, we propose an alternate term ‘Malignant Extrapyramidal Autonomic Syndrome’ (MEAS), which may better capture the underlying myriad manifestations of this condition while remaining non-committal about the nature of the offending agent. The latter will encourage clinicians to remain watchful for this adverse reaction when initiating a wide variety of agents and not just antipsychotics. This will, doubtless, facilitate early and accurate diagnosis of the condition which is of paramount importance to avoid potentially lethal sequelae including death. We hope that our observations trigger a debate on the terminology and criteria of NMS so as to make its diagnosis faster and easier thereby facilitating prompt intervention to hasten its resolution.