The onset of PAID signs often occurs in the first week after severe brain injury, when differential diagnosis is most difficult, and continues for weeks to months, in some cases for longer than 1 year. We have found that the episodes tend to persist the longest in patients with brain injury due to anoxia. Early diagnosis is challenging because the various constituent parts of the syndrome may be caused by a wide variety of processes that may occur in these very ill patients, including seizures, infection, the effects of drugs, withdrawal from drug therapy, pain, or agitation. PAID signs occur at a time when the patient's mental status is abnormal, and tests such as electroencephalography may be difficult to obtain or coordinate with the intermittent phenomena. These signs invariably include temperature elevation (as high as 41°C), increases in heart and breathing rates, hypertension, diaphoresis, agitation, and extensor posturing. Creatine kinase levels are rarely reported; in one case these values were within the reference range, and in another, elevated.