Association of Herpes Simplex Virus Type 1 Encephalitis with Manic Symptoms

Highlights

Temporal lobe involvement: Damage to the temporal lobes and limbic system, regions crucial for mood regulation and impulse control, likely contributed to the patient’s manic symptoms.

Delayed onset: The manic symptoms emerged weeks after neurological recovery, emphasizing the need for long-term psychiatric monitoring in encephalitis survivors.

Neurochemical mechanisms: Post-encephalitic dopaminergic and serotonergic dysregulation may play a role in mood disturbances.

Diagnostic challenges: Distinguishing secondary mania from primary psychiatric disorders is crucial for appropriate management and prognosis.

Successful management: The patient responded well to divalproex, olanzapine, and clonazepam, with full remission of symptoms at follow-up.

Clinical implications: Highlights the importance of multidisciplinary care, including neurology, psychiatry, and neurorehabilitation, in Central Nervous System (CNS) infection survivors.

Need for awareness: Increased recognition of HSV-1 encephalitis-related psychiatric complications can lead to timely diagnosis and better patient outcomes.

Dear Editor,

Herpes simplex virus type 1 (HSV-1) encephalitis is a life-threatening viral infection of the central nervous system, primarily affecting the temporal lobes and limbic structures. It is associated with significant neurological morbidity and mortality. ¹ While cognitive and behavioral disturbances are common sequelae, emerging literature highlights the potential for post-encephalitic mood disorders, including mania.^2–4 These psychiatric manifestations may mimic primary mood disorders, complicate diagnosis, and delay treatment. Herein, we report a rare case of mania following HSV-1 encephalitis and discuss its neuropsychiatric implications. Written informed consent was obtained from the patient and caregiver for the publication of this report.

Case Report

A 67-year-old man with no prior psychiatric history had been hospitalized with high-grade fever, confusion, and altered sensorium lasting five days. Cerebrospinal fluid analysis revealed elevated protein levels, and HSV-1 DNA was confirmed by polymerase chain reaction. Magnetic resonance imaging of the brain revealed swelling with long Repetition Time (TR) hyperintensity and restricted diffusion, involving the right hippocampus, para-hippocampal gyrus, amygdala, anterior temporal lobe, and insular cortex. He was treated with intravenous acyclovir (3 g/day) for 14 days, leading to improvement in his level of consciousness. Approximately two weeks after completion of the acyclovir course, a psychiatric opinion was obtained for decreased sleep and behavioral changes. During the mental status examination, the patient was pleasant, overfamiliar, and very cooperative during the interview. He greeted the examiner spontaneously. He was authoritative, singing devotional songs, and explaining. Eye-to-eye contact was maintained, and rapport was easily established. Psychomotor activity increased, as evidenced by elevated speech tone, tempo, and volume, while he recalled humorous anecdotes from his past. Reaction time decreased, speech was relevant and coherent, with a euphoric mood, and he sang. No delusions or abnormal perceptions were reported. These symptoms were suggestive of mania. Given the sub-acute onset of manic symptoms after viral encephalitis, and in the absence of any psychiatric history, he was diagnosed with mania secondary to a general medical condition (HSV-1 encephalitis), per Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. ⁵ The Young Mania Rating Scale (YMRS), ⁶ severity score was 30. He was started on tablet divalproex sodium (1,000 mg/day), tablet olanzapine (10 mg/day), and tablet clonazepam (1 mg/day). After two weeks, the manic symptoms improved significantly. At one-month follow-up, he was asymptomatic and had returned to his baseline level of functioning (YMRS score 6).

Discussion

Neuropsychiatric sequelae are common after HSV-1 encephalitis, with depressive and cognitive symptoms more frequently reported than mania. In this case, manic features emerged two weeks after the resolution of encephalitis, providing temporal support for a causal link. Magnetic Resonance Imaging (MRI) showed swelling with long TR hyperintensity and restricted diffusion involving the right hippocampus, parahippocampal gyrus, amygdala, anterior temporal lobe, and insular cortex, structures central to mood regulation, which may have contributed to manic symptoms. These observations are consistent with the description of secondary mania following HSV-1 encephalitis, as described by Vasconcelos-Moreno et al.²

The use of YMRS ensured standardized quantification of symptoms. ⁵ While an autoimmune encephalitis panel (including anti-N-Methyl-D-Aspartate (NMDA) receptor antibodies) was not performed due to resource limitations, the clinical course and full remission with psychotropics suggest a direct post-encephalitic cause rather than autoimmune etiology. Nevertheless, emerging evidence indicates that neuronal surface antibodies, including anti-NMDA receptor antibodies, may play a role in post-infectious psychiatric syndromes.^7,8 Case evidence supports mood stabilizers and antipsychotics in managing HSV-related psychiatric sequelae. ² In this case, divalproex and olanzapine were effective, highlighting the importance of early psychiatric recognition and treatment.

Conclusions

Mania can be a neuropsychiatric manifestation of HSV-1 encephalitis, with symptoms emerging two weeks after recovery. Awareness of this possibility is crucial for early diagnosis and intervention. Clinicians should maintain a high index of suspicion for organic mood disorders in any patient presenting with acute behavioral changes and consider neuro-psychiatric manifestations of encephalitis, either infective or autoimmune.

Supplemental Material

Supplemental material for this article is available online.