Neuroleptic malignant syndrome in a COVID-19 patient.

It is recognized by now that COVID-19 can have a wide variety of neurologic and psychiatric manifestations. Patients with confirmed COVID-19 infections are presenting with various central and peripheral nervous system symptoms, including acute cerebrovascular disease, impaired consciousness, dizziness, and loss of taste and smell (Mao, 2020). Given that COVID-19 appears to affect central nervous system function, it is likely that some of these patients will start to show neuropsychiatric symptoms. We present a case of a COVID-19 patient with neuroleptic malignant syndrome (NMS). The possibility that COVID-19 infection could make patients more susceptible to the development of NMS warrants further study.

Case

A middle age male with a past medical history of Schizophrenia, Hepatitis C and multiple previous suicide attempts presented to the Emergency Department via EMS for altered mental status. In the ED, he was noted to be febrile (101.2F), tachycardic (122) and normotensive (109/71). He was hypoxic (93%) and tachypneic (40 s). On exam, the patient did not open eyes or make any motor or verbal response to painful stimuli and sternal rub. He had a rigid posture. His blood sugar was normal, Chest X-ray revealed bilateral peripheral infiltrates concerning for COVID-19 infection. He was emergently intubated. Review of medical records showed that the patient had received a haloperidol decanoate injection approximately 3 weeks prior.

Labs revealed a mild leukocytosis (12.3 K/mm3) with a neutrophilic predominance (87.2%) and lymphopenia (5.1%). He was also noted to be in acute kidney failure (Cr = 5.8 mg/dL) with a creatinine kinase of 120,000 IntUnit/L. Multiple inflammatory markers were elevated including CRP (14.1 mg/dL), Ferritin (505.2 ng/dL) and LDH (1421 units/L). COVID-19 test by PCR was positive. The patient was admitted to the ICU for ventilator management and treatment of his altered mental status with associated rhabdomyolysis and acute kidney failure. Broad-spectrum antibiotic and antiviral coverage (cefepime, linezolid, ampicillin, and acyclovir) as well as hydroxychloroquine were initiated for empiric treatment of COVID-19 and meningitis. Head CT was negative, and EEG showed slow background and occasional right hemispheric discharge associated with some left-hand tremor. Cerebral spinal fluid (CSF) analysis revealed 0 WBC, 0 RBC and normal protein.

Maximum accumulated dose of dantrolene of 10 mg/kg IV was administered over a two-day period followed by bromocriptine 5 mg loading dose then 2.5 mg three times daily. He was also placed on levetiracetam for seizure prophylaxis and initiated on hemodialysis for acute renal failure. All antibiotics were discontinued after negative CSF results. Hydroxychloroquine treatment was continued for a planned duration of five days. His CK began to downtrend on hospital day 4, and rigidity also improved at around the same time. He remained intubated and sedated, with no improvement in mentation. A junctional cardiac rhythm has developed preventing the patient from getting an MRI of the head.

Conclusion

NMS during the acute infectious phase of COVID-19 has not been previously described. Typically, NMS is associated with the use of antipsychotics or antiemetics, especially when used in high doses or depot formulations. However, some studies suggest that acute medical illnesses including organic brain disease are risk factors for developing NMS (Pelonero, 1998). It is proposed that in COVID-19 infected patients, the SARS-CoV-2 virus uses ACE2 receptors found in the nervous system to cause neurological symptoms. Autopsy reports of some COVID-19 patients have shown hyperemic and edematous brain tissue with evidence of neuronal degeneration (Mao, 2020). The full neuropsychiatric manifestations of COVID-19 have yet to be observed and studied. While these symptoms are typically found in patients with severe COVID-19 infection, some patients are presenting without the typical symptoms of fever and cough and only with neurological manifestations (Mao, 2020). Besides the risk factor of haloperidol decanoate use three weeks prior to admission, it is possible that the COVID-19 infection made the patient more susceptible to the development of NMS. The link between COVID-19 and NMS needs to be further studied.

Statement regarding consent issue

We are not able to obtain a consent from the patient himself secondary to his altered mental status. No family has been identified. We presented the situation to the hospital administration as well as hospital’s Research and Publication Committee. After removing all identifying information, we have the approval from the Chief Operating Officer (COO) and Human Research Protection Officer Mara Bryant (who chairs the committee) to proceed with the publication. The COO is the second highest-ranking officer of our hospital (after the President). The Human Research Protection Officer oversees all matters related to patient research and publication. Together with the Research and Publication Committee, they ensure all patient privacy has been observed and that all the ethical standards regarding clinical research are upheld. If a research project is approved for publication, an IRB approval letter is usually issued. If a project, a case report/correspondence like ours, is deemed to have no patient experimentation, an exemption/wavier letter will be issued. We have here an IRB exemption/wavier letter to indicate this report is purely observational with no human experimentation involved. Being signed off by the COO also indicates that all privacy has been observed and no unethical issue is detected.