Case Presentation: A 58-year-old male with a history of chronic anemia and schizophrenia presented to the emergency department (ED) from home for seven days of worsening COVID-19 respiratory disease. He was admitted for hypovolemic shock and non-ST-segment elevation myocardial infarction (NSTEMI). His home dose of haloperidol 5 mg daily and 20 mg nightly was continued. His hospital course was complicated by polymicrobial gram-negative bacteremia and respiratory failure due to viral pneumonia. On hospital day number nine he began to deteriorate further despite appropriate antibiotic therapy at which time infectious disease (ID) was consulted. On evaluation by ID, the patient was noted to have muscular rigidity, tremulousness, altered mental status (AMS), tachycardia, and fever of 103.1 degrees Fahrenheit. Pertinent labs included creatine phosphokinase (CPK) 370 IU/L, white blood cell count (WBC) 8.99 k/uL, infectious and metabolic panels were negative or non-contributory. ID recommended a psychiatry consult for possible neuroleptic malignant syndrome (NMS). Antipsychotics were stopped and he was transferred to the intensive care unit (ICU). Neurologic work-up to rule-out organic causes for his symptoms included MRI brain which was negative for intracranial hemorrhage or brain mass, continuous electroencephalography which was without epileptiform activity, and lumbar puncture that was negative for meningitis or encephalitis. Psychiatry recommended scheduled lorazepam for possible NMS versus malignant catatonia (MC). He had marked clinical improvement on lorazepam 2 mg every 6 hours and he had eventual recovery 13-days from the last dose of haloperidol. He was restarted on a lower-dose of haloperidol 14-days after recovery and without relapse.
Discussion: NMS is associated with antipsychotic medications and characterized by mental status changes, muscular rigidity, hyperpyrexia, and dysautonomia. MC is most often associated with schizophrenia and presents with catalepsy, stupor, mutism, waxy flexibility, negativism, posturing, autonomic dysfunction, rigidity, fever, and muscle injury. The pathophysiology of NMS has been attributed to a reduction in dopaminergic activity, either due to withdrawal of dopaminergic medication or reduction in dose; or to dopamine receptor antagonism by antipsychotics. NMS symptoms typically develop over the course of one to three days. MC and NMS share many features including elevated CPK, leukocytosis, altered mental status (AMS), tremors, fever, and autonomic instability; however, lead-pipe rigidity and recent antipsychotic use favor NMS. In one review of 292 cases of suspected NMS versus MC the two diagnosis were indistinguishable in 20% of cases. CPK elevation greater than 1000 international units/L (IU/L) is widely accepted as a cutoff for NMS to be considered, however in one study of thirty psychiatric inpatients with NMS 40% had CPK levels below 1000 IU/L. A retrospective analysis found that the mortality rate in NMS is 5-20% despite early diagnosis and treatment, this rises to 70% if complications are also present. MC has a mortality rate of 9-10% irrespective of effective treatment and earlier diagnosis in one retrospective study.
Conclusions: NMS and MC both require inpatient medical care and pose diagnostic challenges when complicated by co-occurring acute medical conditions. This case highlights the importance of considering both NMS and MC despite non-elevated CPK, in medically complex patients with psychiatric co-morbidities.