Neuroleptic Malignant Syndrome

Dr. Scholer presented the interesting case of a female who developed significant altered mental status secondary to neuroleptic malignant syndrome (NMS).

What is Neuroleptic Malignant Syndrome?

NMS is a life-threatening neurologic emergency characterized by the triad of altered mental status, elevated temperature, and rigidity: it is also often associated with dysautonomia. NMS is associated with medications, classically antipsychotics and these symptoms typically develop within two weeks of initiation of therapy. The most commonly associated medications are high potency first generation neuroleptics (i.e.haloperidol, fluphenazine) but it can occur with essentially every neuroleptic class. Other medications (antiemetics, lithium) have also been implicated. The exact mechanism behind this process is unclear but it is presumed to be associated with dopamine receptor blockade.

Risk can increase in the setting of sepsis, which is problematic because NMS can look very similar to sepsis. It can also occur with withdrawal of medications used to treat Parkinson, comorbid neurologic disease, trauma, or surgery.

OK: But how do I diagnosis it?

The diagnosis of NMS is clinical. Generally, you want to rule out other etiologies of altered mental status and hyperthermia: most importantly, this means ruling out sepsis. Patients often get brain imaging as well. LP is typically obtained although results are non-specific: ~1/3 of patients may have a non-specific protein elevation.

How do I treat my patient?

The most important piece in management is to STOP THE OFFENDING AGENTS. If you are unsure which medication caused it, stop everything that can be associated. These patients are generally admitted to the ICU for aggressive supportive care, including temperature management and benzos for agitation.

If you need to restart antipsychotic medication, wait at least two weeks before resuming therapy and even then start low and go slow.

Does anything else look like NMS?

Yes! NMS can easily be confused with sepsis (as mentioned above) but it also can be confused with serotonin syndrome, the anticholinergic toxidrome, and malignant hyperthermia. While the meds a patient is exposed to can help differentiate, the clinical syndromes also present differently. Use the table below to help determine the difference between these clinical entities.