25 mmHg systolic change within 24 hours), urinary incontinence, and pallor—may be
seen at any time but provide an early clue to the diagnosis. Tachypnea (rate 50% above
baseline) is common, and respiratory distress —resulting from metabolic acidosis, hyper-
metabolism, chest wall restriction, aspiration pneumonia, or pulmonary emboli—can oc-
cur and lead to sudden respiratory arrest.
A workup, including laboratory investigation,  to exclude other infectious, toxic, met-
abolic, and neuropsychiatric et iologies or complications is essential (see the section “Dif-
ferential Diagnosis” later in this discussion ). Although several laboratory abnormalities
are associated with neuroleptic malignant synd rome, no single abnormality is specific to
the diagnosis. Individuals with neuroleptic malignant syndrome may have leukocytosis,
metabolic acidosis, hypoxia, decreased serum iron concentrations, and elevations in se-
rum muscle enzymes and catecholamines. Findings from cerebrospinal fluid analysis and
neuroimaging studies are generally normal, whereas electroencephalography shows gen-
eralized slowing. Autopsy findings in fatal ca ses have been nonspecific and variable, de-
pending on complications.
Development and Course
Evidence from database studies suggests in cidence rates for neuroleptic malignant syn-
drome of 0.01%–0.02% among indi viduals treated with antips ychotics. The temporal pro-
gression of signs and symptoms provides important clues to the diagnosis and prognosis
of neuroleptic malignant syndrome. Alteration  in mental status and other neurological
signs typically precede systemic signs. The on set of symptoms varies from hours to days
after drug initiation. Some cases develop with in 24 hours after drug initiation, most within