Symptom Frequencies and Correlations with Temperature Variations in Suspected Cases of Neuroleptic Malignant Syndrome (NMS)

Background: The incidence of NMS is rare. Relative frequencies of symptoms that are most valuable in making a diagnosis of NMS can be assessed statistically only if a large sample of suspected NMS cases is available. Similarly, the relationship of such NMS symptoms to temperature (a cardinal symptom of NMS) can be meaningfully evaluated only by studying large samples.

Method: De-identified archival data on 212 suspected NMS cases were obtained from professionals across the USA and Canada or were extracted from studies published in medical journals. We recorded the symptoms frequencies. The patients’ temperature ranged from 37.20C to 43.00C, with the mean at 39.50 (SD=1.3). All cases were caused by older first-generation antipsychotics (FGAs). We evaluated the frequencies of symptoms reported in these cases. These included symptoms in the realm of mental status, rigidity, and autonomic symptoms. We calculated the frequency of abnormal blood pressure, respiration and heart rate, symptoms such as Dysarthria, Dysphagia, Rigidity, Focal Dystonia, Waxy Flexibility, Myoclonus, Masked Facies, Bradykinesia, Akinesia, Cogwheeling, Stupor, Coma, Obtundation, Mutism, Decrease in Consciousness, Disorientation, Diaphoresis, Sialorrhea, and Seizures. We also calculated their correlations with temperature elevations, the most spectacular symptom of this dangerous syndrome.

Results: The highest symptom frequencies (those > 10%) were found for Rigidity (91.0% of patients), Autonomic Instability (66.5%), Diaphoresis (45.8%), Mutism (34.4%), Tremor (31.6%), Stupor (20.3%), Confusion (15.6%), Incontinence (15.6%), Sialorrhea (14.6%), Coma (13.2%), and Dysphagia (11.3%). Other symptoms were too rare within the sample of the 212 suspected NMS cases to calculate the statistical significances of their relationships to temperature. The only significant correlations found of temperature were to increased heart rate and to the severe cases of coma.

Discussion and Conclusion: Besides the elevated temperature, the most frequently reported symptoms in this sample of suspected NMS caused by FGAs were Rigidity, Autonomic Instability, Diaphoresis, Mutism, and Tremor. Higher temperature was associated with tachycardia as well as profound impairment of consciousness or coma. Reviews and database studies of second generation antipsychotics (SGAs), also referred to as atypical antipsychotics, suggest a lower incidence of NMS and milder severity of symptoms such as hyperthermia and rigidity. It would be of clinical interest to generate similar de-identified files of archival data for suspected cases of NMS in patients treated with SGAs. Furthermore, a similar profile derived from archival data on milder or prodromal NMS cases could enhance our understanding of this syndrome from a spectrum perspective.