All three major, or two major and four minor criteria suggest a high probability of NMS.
Major Criteria:
Hyperthermia Rigidity Elevated CPK (usually > 1000 UI/L)
Minor Criteria:
Altered consciousness level Tachycardia Labile arterial pressure Tachypnea Diaphoresis Leukocytosis
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Allows for prospective and retrospective diagnoses.
Prospective diagnoses (all three required):
Hyperthermia (oral temperature >37.5°C) EPS with at least two of the following: lead-pipe muscular rigidity, cogwheeling, sialorrhea, oculogyric crisis, retrocollis, opisthotonos, trismus, dysphagia, choreiform movements, dyskinetic movements, festinating gait, flexor-extensor posturing Autonomic dysfunction with two or more of the following: hypertension (>20mmHg rise in diastolic above baseline), tachycardia (>30 beats/min above baseline), tachypnea (>25 respirations/min), prominent diaphoresis, incontinence
Retrospective diagnoses (if one of the three criteria above are not documented, a probable diagnosis is still permitted if both
of the following criteria are met):
Clouded consciousness
(e.g., delirium, mutism, stupor, coma) Leukocytosis (>15,000 WBC/mm3)
CPK >300 U/mL |
Hyperthermia Rigidity Dystonia Blood pressure elevation (>140mmHg systolic, >90mmHg diastolic, or both) Tachycardia Diaphoresis Elevated CPK Leukocytosis |
Requires all three major criteria, plus three minor criteria.
Major Criteria:
Neuroleptic administration in past 7 days Hyperthermia Rigidity
Minor Criteria:
Altered consciousness Tachycardia Labile arterial pressure Tachypnea Elevated CPK or myoglobinuria Leukocytosis
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Classifies diagnoses according to Type I, II, III, and IV subclasses of NMS. Also indicates use of rating scales to measure symptom severity for research purposes. |
Hyperthermia (oral temperature >38.0°C on at least 2 occasions) Rigidity CPK >4-times the upper limit Changes in mental status (delirium, altered consciousness) Autonomic activation, including: tachycardia (>25% above baseline), diaphoresis, blood pressure elevation (systolic or diastolic ≥25% above baseline), or fluctuation (≥20mmHg diastolic change or ≥25mmHg systolic change), urinary incontinence, pallor, tachypnea (>50% above baseline) |
Type I (Classical NMS):
Must be induced by oral or parental ingestion of typical or atypical neuroleptic, dopamine depleter/ antagonist, or a psychoactive agent in past 2 weeks, or by intramuscular administration of a neuroleptic in past 8 weeks; may also be induced by withdrawal of antiparkinsonian or anticholinergic agent in the past 1 week Altered consciousness (rated on the Glasgow Coma Scale) EPS (rated on the Simpson-Angus Rating Scale) Hyperthermia (oral temperature >38.5°C for at least 48 hours) Autonomic dysfunction, with at least two of the following: tachycardia (>100 beats/min), tachypnea (>25 respirations/min), blood pressure fluctuations (at least 30mmHg change in systolic, or 15mmHg change in diastolic) Diaphoresis Incontinence Any two of the following: elevation in CPK, leukocytosis, low serum iron levels, elevation of liver enzymes, myoglobinuria
Type II (Atypical NMS):
Must be induced by the same agents as Type I NMS (above) Altered consciousness Hyperthermia Autonomic dysfunction Any one of the following: elevation in CPK, leukocytosis, low serum iron levels, elevation of liver enzymes, myoglobinuria
Note that EPS is not necessary for Type II NMS.
Type III (Impending/threatened/
incipient/aborted NMS):
Induced by exposure to either typical or atypical neuroleptic, but condition does not meet criteria for either Type I or II; otherwise strongly suspected to be NMS.
Type IV (miscellaneous conditions as NMS):
Includes miscellaneous conditions resulting from withdrawal of antiparkinsonian agents, or exposure to psychostimulants, or dopamine depleters/antagonists |
