Neuroleptic malignant syndrome in a patient with COVID-19 and the possible role of SARS-CoV-2 in its manifestation. Case report and overview of published cases (preprint)

Background: The manifestationof severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is more complex than that of pulmonary infection, and neuropsychiatric symptoms play a role in this complexity. In this paper, we present the case of a 29-year-old schizophrenic patient who suffered from neuroleptic malignant syndrome (NMS) that developed during coronavirus disease 2019 (COVID-19) infection, with an emphasis on the possible connection between these two conditions. Additionally, we provide an overview of published NMS cases in patients with COVID-19 or after vaccination against SARS-CoV-2. Case presentation: A 29-year-old patient treated for schizophrenia was admitted to the hospital for agitation and aggressivity; shortly after arrival at the hospital, laryngospasm and hypoxia occurred. The patient tested positive for SARS-CoV-2, and later, he developed pneumonia. After continuing restlessness, haloperidol was administered, and a few days later, neuroleptic malignant syndrome occurred. He was treated with bromocriptine and recovered. Conclusions: As SARS-CoV-2 is known to interact with angiotensin-converting enzyme 2 and DOPA-decarboxylase is known to be coexpressed with this receptor, we hypothesized that COVID-19 infection might playa substantial role in the development of NMS.

Neuroleptic Malignant Syndrome with Adrenal Insufficiency After BNT162b2 COVID-19 Vaccination in a Man Taking Valproate: A Case Report.

BACKGROUND Considering the ongoing coronavirus disease 2019 (COVID-19) pandemic, sufficient information about common and serious adverse events is needed to rapidly distribute COVID-19 vaccines worldwide. We report a case of neuroleptic malignant syndrome (NMS) with adrenal insufficiency after initial vaccination with Pfizer/BioNTech BNT162b2. CASE REPORT A 48-year-old man presented to the Emergency Department with fever and an altered mental status 7 days after receiving the first dose of the BNT162b2 COVID-19 vaccine. The patient had a history of end-stage renal disease and epilepsy treated with valproate. He was diagnosed with NMS based on the clinical findings of hyperthermia, muscular rigidity, and an elevated creatine kinase level. Additionally, a reduction in the response of cortisol to adrenocorticotropic hormone (ACTH) stimulation was observed in the rapid ACTH stimulation test. The patient was treated with dantrolene, bromocriptine, and hydrocortisone, and he responded well to treatment. Dantrolene and bromocriptine were tapered off over 4 weeks. Hydrocortisone was also tapered, and the patient was discharged on oral hydrocortisone (30 mg). CONCLUSIONS The present case suggests a possible link between the BNT162b2 COVID-19 vaccine and NMS with adrenal insufficiency based on the temporal relationship between vaccine administration and disease onset, although the patient was taking valproate, a potential cause of NMS. Having a high level of suspicion is important because the diagnosis of NMS with adrenal insufficiency is often challenging due to non-specific clinical manifestations. However, this case does not negate the utility of vaccination because these complications are extremely rare and can be treated with early diagnosis and proper management.

Successful Emergency Treatment of Refractory Neuroleptic Malignant Syndrome With Electroconvulsive Therapy and a Novel Use of Dexmedetomidine: A Case Report From California in the Era of COVID-19.

ABSTRACT: We describe the case of a patient, hospitalized in a California community medical ICU for over a month, with severe neuroleptic malignant syndrome (NMS), unresponsive to medical management, but responsive to electroconvulsive therapy (ECT). We discuss the medical, logistical, and legal challenges in providing ECT in this setting. We also describe a previously unpublished use of dexmedetomidine, which aided in the safe and rapid reduction of benzodiazepines and permitted a successful ECT course. The rapid delivery and efficacy of ECT were essential because of the burgeoning coronavirus pandemic. The patient's treatment required exemplary efforts by providers across multiple disciplines, ongoing medicolegal consultation with the county mental health medical director, as well as consultation with expert members of the International Society for ECT and Neurostimulation. We conclude with a discussion of the unique challenges of providing emergency ECT to patients in California, including during a serious pandemic, when courts are closed. This case illustrates the importance of cultivating and maintaining high-quality ECT expertise in community hospitals and keeping ECT services available even during pandemics. Also, this case demonstrates that ECT is not "merely an elective procedure" but a vital, life-saving treatment, even during the era of COVID-19. To our knowledge, this is the first such published case of emergency ECT performed in California.

Beneficial Effects of Dantrolene in the Treatment of Rhabdomyolysis as a Potential Late Complication Associated With COVID-19: A Case Report (preprint)

Background: Patients with severe COVID-19 have disorders of the respiratory, cardiovascular, coagulation, skeletal muscle and central nervous systems. These system failures may be associated with cytokine release syndrome, characterized by hyperpyrexia, thrombocytopenia, hyperferritinemia, and the elevation of other inflammatory markers. Rhabdomyolysis with high fever is a complication that is rarely found in COVID-19. The exact relations of these clinical conditions in patients with COVID-19 are still unknown. Case presentation: We present the case of a 36-year-old man with severe COVID-19 complicated by rhabdomyolysis and high fever. After admission, his condition continued to deteriorate, with a high body temperature. After 9 days, in his laboratory examination, creatine kinase and myoglobin levels were noted to increase (to 26046 U/L, 3668 ng/mL). In addition to viral therapy, he was immediately treated with hydration. However, high fever and levels of rhabdomyolysis continued. The patient had been diagnosed with malignant hyperthermia associated with a late complication of COVID-19, although he had no hereditary predisposition to malignant hyperthermia or neuroleptic malignant syndrome. The administration of dantrolene with muscle relaxation and anti-inflammatory function showed potential efficacy for rhabdomyolysis, high fever and increased plasma inflammatory markers. Conclusions: : Malignant hyperthermia is triggered by not only anesthetic agents but also viral infections. A possible mechanism of malignant hyperthermia is a hypersensitivity of calcium release from the sarcoplasmic reticulum. These include mutations in or the activation of the skeletal muscle ryanodine receptor calcium release channel. Dantrolene is a ryanodine receptor antagonist and is used as an anti-inflammatory agent. The administration of dantrolene showed potential efficacy for rhabdomyolysis, high body temperature due to inflammation, and increased inflammatory markers. The underlying mechanism of the association of rhabdomyolysis and high fever in COVID-19 might be a similar pathogenesis in malignant hyperthermia.

Neuroleptic malignant syndrome in patients with COVID-19.

We report the first two cases of Coronavirus Disease 2019 (COVID-19) who were receiving intensive care including favipiravir, and were clinically diagnosed with neuroleptic malignant syndrome (NMS) to focus attention on NMS in COVID-19 management. Case 1: A 46-year-old-man with acute respiratory distress syndrome (ARDS) caused by COVID-19 infection was being administered favipiravir. Fentanyl, propofol, and rocuronium were also given. On day 3, midazolam administration was initiated for deep sedation. On day 5, his high body temperature increased to 41.2 °C, creatine kinase level elevated, and he developed tachycardia, tachypnea, altered consciousness, and diaphoresis. NMS was suspected, and supportive therapy was initiated. High-grade fever persisted for 4 days and subsided on day 9. Case 2: A 44-year-old-man with ARDS caused by COVID-19 infection was being treated with favipiravir. On day 5, risperidone was started for delirium. On day 7, his body temperature suddenly increased to 40.8 °C, his CK level elevated, and he developed tachycardia, tachypnea, altered consciousness, and diaphoresis. NMS diagnosis was confirmed, and both, favipiravir and risperidone were discontinued on day 8. On the same day, his CK levels decreased, and his body temperature normalized on day 9. Patients with COVID-19 infection frequently require deep sedation and develop delirium; therefore, more attention should be paid to the development of NMS in patients who are being administered such causative agents. The mechanism underlying the occurrence of NMS in COVID-19 patients treated with favipiravir remains unknown. Therefore, careful consideration of NMS development is necessary in the management of COVID-19 patients.