Anti-NMDAR Encephalitis developing neuroleptic malignant syndrome

Dear Editor, Neuroleptic malignant syndrome (NMS) has an incidence of 0.02–3.23% and affects individuals across all age groups, with a higher incidence in men compared to women. The cardinal symptoms of NMS encompass hyperthermia, rigidity, altered mental status, and autonomic dysfunction, typically manifesting within four weeks of initiating antipsychotic treatment.[1] A 30-year-old female was initially admitted to a civil hospital with a two-week history of fever and a one-week history of headache, vomiting, and altered sensorium and a provisional diagnosis of acute meningoencephalitis was made. After a week of treatment, the patient was transferred to Command Hospital, Pune, where a psychiatry consult was sought on day 3 of admission due to behavioral abnormalities, characterized by agitation, irrelevant talk, and attempts to leave her bed. General examination revealed a thin-built female with stable vitals, pallor, and disoriented to time, place, and person. Neurological examination disclosed no focal deficits, but the Mental State Examination identified an agitated and uncooperative individual with increased motor activity, incoherent speech, perplexed affect, and reduced sleep and appetite. Laboratory investigations revealed leucocytosis with hemoglobin of 9.8 g/dL. Her workup including blood, urine, and bone marrow C/s revealed no growth, infection workup was negative, serum angiotensin-converting enzyme was normal, paraneoplastic panel and autoimmune encephalitis panel was negative, electroencephalography revealed generalized slowing and neuroimaging including contrast-enhanced computed tomography chest, abdomen, and pelvis along with contrast-enhanced magnetic resonance imaging brain revealed no abnormality. 18F-fluorodeoxyglucose positron emission tomography revealed marked medial occipital lobe hypometabolism based on which she was diagnosed as a case of anti-N-methyl-D-aspartate receptor encephalitis.[2] The diagnostic challenge unfolded when the patient, after receiving an injection haloperidol 5 mg IM two doses 12 h apart, rapidly developed features of generalized rigidity, fever, reduced verbal output, and poor oral intake. The patient was moved to the Intensive Care Unit, where NMS diagnosis was confirmed based on the development of hyperthermia, rigidity, altered mental status, and hypermetabolism following exposure to a dopamine antagonist within the 72 h preceding the onset of symptoms along with elevated creatine phosphokinase (CPK) levels (2086 IU/L).[3] Immediate interventions, including intramuscular lorazepam 2 mg IM 8 hourly, intravenous 1 mg/kg bolus of dantrolene, followed by 1 mg/kg intravenously every six hours,[4] discontinuation of haloperidol, hydration, and antipyretics were initiated, leading to a gradual improvement in the patient’s condition. Despite the availability of operational criteria, distinguishing NMS from extrapyramidal side effects and other disorders with similar clinical features remains challenging. Laboratory investigations play a crucial role in ruling out other conditions like CPK levels and rhabdomyolysis leading to myoglobinuric renal failure, although no single investigation modality is specific to NMS. Cerebrospinal fluid analysis reveals no abnormality in 95% of patients.[5] The pathophysiological mechanisms of NMS are likely related to antipsychotic-induced dopamine blockade. The risk of NMS is likely correlated with the dopamine receptor binding affinity of antipsychotic medication. Also, it has been observed in various studies that patients with central dopamine tract lesions resemble NMS-like clinical characteristics.[6] Certain genetic polymorphisms have also been associated with a predisposition to NMS.[7] NMS can be associated with both first-generation and second-generation antipsychotics, and its onset is idiosyncratic, occurring after a single dose or prolonged use. It is also worthwhile to note that NMS is not a dose-dependent phenomenon but is associated with greater risk at higher doses.[8] The presented case suggests potential links between anti-NMDA receptor encephalitis and NMS. First, NMS and anti-NMDA receptor encephalitis can coexist. Second, patients with anti-NMDA receptor encephalitis are more susceptible to neuroleptic medication. Lastly, NMS-like features may develop in the natural course of anti-NMDA receptor encephalitis. Thus, differentiation becomes challenging yet imperative as management for both is different.[9] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the forms, the patient has given her consent for the relevant clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.