New-onset apathy in bipolar disorder: a clinical warning for encephalitis

Introduction

In bipolar disorder, the sudden onset of apathy and psychomotor slowing in euthymic patients may be interpreted as relapse, which can lead to overlooking underlying organic causes. This case highlights the importance of considering infectious encephalitis in the differential diagnosis and the need to distinguish it from neuroleptic malignant syndrome (NMS). Case Presentation: A 31-year-old man with a diagnosis of bipolar disorder presented with a one-week history of apathy, psychomotor slowing, disorganised behaviour and delayed responses. At admission, he was euthymic, adherent to treatment, and was receiving lithium 1800 mg/day and long-acting risperidone 50 mg (every two weeks); his serum lithium level was within the therapeutic range (0.79 mmol/L). The symptoms began approximately one week after the last administration of long-acting risperidone and were preceded by two days of insomnia. During hospitalisation, the patient developed confusion and fever (39°C); laboratory investigations revealed leukocytosis (15.3 ×10⁹/L), elevated C-reactive protein (6.3–18.5 mg/L), and increased creatine kinase levels (peak 1008 U/L). Creatine kinase levels were monitored and it did not show progressive elevation. No muscle rigidity was observed. Neuroimaging findings were unremarkable. Lumbar puncture was performed, and gram-negative coccobacilli were identified in the cerebrospinal fluid culture; antimicrobial treatment was therefore initiated with meropenem. Marked clinical improvement was observed, with resolution of apathy and cognitive symptoms. The patient was discharged in remission on lithium (1800 mg/day) and aripiprazole (15 mg/day). Discussion: This case demonstrates that symptoms such as apathy, insomnia, behavioural disorganisation and psychomotor slowing in bipolar disorder should not always be attributed to a mood episode. The diagnostic process progressed from an initial consideration of a bipolar episode to neuroleptic malignant syndrome following creatine kinase elevation, and ultimately to a diagnosis of infectious encephalitis. While the absence of rigidity and progressive CK elevation weakened the diagnosis of NMS, the presence of fever and inflammatory findings directed further investigations. This highlights the importance of re-evaluating the diagnosis throughout the clinical course. The role of neuroinflammatory processes in the emergence of psychiatric symptoms is increasingly recognised. Central nervous system infections may present in their early stages with non-specific behavioural and cognitive symptoms and may lead to diagnostic delay, particularly in patients with an existing psychiatric disorder. In addition, dopaminergic blockade associated with antipsychotic treatment may create the impression of clinical slowing through motor symptoms and alterations in consciousness, contributing to early diagnostic uncertainty. In this case, the presence of fever and elevated inflammatory markers supported the diagnosis of infectious encephalitis. Current evidence also suggests that bidirectional interactions between the dopaminergic system and the immune response may contribute to the heterogeneity of clinical presentations. Conclusion: Atypical behavioural changes emerging in euthymic patients with bipolar disorder should not be interpreted as relapse without excluding organic causes. In the presence of fever and inflammatory findings, infectious encephalitis should be considered in the differential diagnosis. Early diagnosis is critical for improving clinical outcomes. Keywords: bipolar disorder – apathy – encephalitis – neuroinflammation – neuroleptic malignant syndrome

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