Unmasking herpes encephalitis masquerading as acute psychosis via neuroimaging

Abstract

Psychosis is a complex mental health condition that can have a profound impact on individuals and their families. It is characterized by a loss of contact with reality, including delusions, hallucinations, and disorganized thinking. While psychosis is most commonly associated with psychiatric disorders such as schizophrenia, it is crucial to consider other potential causes to ensure accurate diagnosis and appropriate treatment. One such often overlooked condition is herpes encephalitis, a viral infection that affects the brain, like in this case where a 22 year old male presented with acute episodes of psychosis which later turned out to be herpes encephalitis diagnosed on MRI (Magnetic Resonance Imaging) of brain screening followed by CSF (Cerebrospinal Fluid) analysis. In this article, we will also discuss herpes encephalitis and explore its role as a differential diagnosis for psychosis.

Introduction

Herpes encephalitis is a rare but serious infection that occurs when the herpes simplex virus (HSV) enters the brain. It is estimated to affect approximately 1 in 500,000 individuals each year [1]. The virus can be transmitted through direct contact with an infected person or by reactivation of the virus in individuals who have previously been exposed to HSV. Once the virus enters the brain, it can cause inflammation and damage to the brain tissue, leading to a range of neurological symptoms [1].

The symptoms of herpes encephalitis can vary depending on the individual and the specific areas of the brain that are affected. Early symptoms may include fever, headache, and flu-like symptoms, which can easily be mistaken for a common viral illness. However, as the infection progresses, more severe symptoms may develop, including confusion, altered consciousness, seizures, and focal neurological deficits. In some cases, individuals may experience behavioral changes, such as irritability, aggression, and psychosis-like symptoms, like in our case [2].

Due to the overlap in symptoms, herpes encephalitis is often misdiagnosed as psychosis, leading to delayed treatment and potentially life-threatening consequences. The behavioral changes and cognitive impairments seen in herpes encephalitis can mimic the symptoms of psychosis, making it challenging for healthcare professionals to differentiate between the two conditions. This misdiagnosis can have devastating consequences for patients, as the appropriate antiviral treatment for herpes encephalitis must be initiated promptly to prevent further damage to the brain [3].

Case presentation

A 22 year old male was taken to a local primary health care by his mother with chief complains of altered behaviour and hallucinations since 7 days and was started on Tablet Haloperidol 5 mg for his psychotic episode and was sent home. He was again brought to the phc after some days, this time in an acute confused state with agitation. There were no signs of improvement even with antipsychotic medications which was prescribed earlier and the patient was referred to a tertiary care for further evaluation. On further history taking, the patient's mother reported that the patient had been experiencing flu like symptoms, including fever with severe headache and fatigue since the past 1 week. Also, over the past 2 days, the patient's behaviour had become increasingly unusual in the form of incoherent speech, suspiciousness and fearfulness. He showed irritability and aggressiveness which was unprovoked in nature, along with occasional muttering to self was seen as accounted by relative. The patient was prescribed antipsychotic medications by a local physician for his presentation with acute episodes of psychosis, the complaints worsened and showed no signs of improvement even after medications. The patient had no significant past history of any psychiatric disorder and no history of any high risk behaviour such as drug abuse.

The patient was presented in the emergency department, was alert but disoriented to time, place and person and was irritable with psychomotor agitation. He was febrile to touch and a temperature of 102.3 degree fahrenheit was recorded with a pulse rate 130 beats per minute, regular in rhythm with normal volume and blood pressure of 120/80mm of hg in right arm on supine position with a respiratory rate of 22 cycles per minute. On central nervous system examination, patient had an altered mental status with rigidity of neck and difficulty in verbal fluency. Visual and auditory hallucinations were present with a positive Kernig's sign with exaggerated deep tendon reflexes and bilateral extensor plantar response with normal cranial nerve examination and other central nervous system (CNS) examination.

Routine blood investigations of the patient indicated an active infection and inflammation. White blood cell count was elevated at 15,000/µL (normal range: 4000-11,000/µL), and the neutrophil percentage was high at 70% (normal range: 40-60%), both of which were consistent with infection. Inflammatory markers were notably increased, with a C-Reactive Protein (CRP) level of 40 mg/L (normal range: <10 mg/L) and an Erythrocyte Sedimentation Rate (ESR) of 50 mm/hour (normal range: 0-20 mm/hour), suggesting systemic inflammation. Liver function tests revealed mildly elevated levels of ALT at 60 U/L (normal range: 7-56 U/L) and AST at 70 U/L (normal range: 10-40 U/L), indicating potential liver involvement. The viral serology results confirmed the presence of herpes simplex virus (HSV) infection, as they were positive for HSV antibodies. Overall, these findings supported the presence of an active HSV infection with associated systemic inflammation and mild liver involvement.

An MRI brain screening was done which revealed bilateral temporal and parietal lobe abnormalities as explained in Fig. 1, Fig. 2, Fig. 3, Fig. 4 which on further consultation from Neurologist lead to the probable diagnosis of herpes encephalitis owing to the history and radiological findings.

Fig. 1.

T2-weighted axial section MRI scan of the brain in a patient with Herpes Simplex Virus Encephalitis.

This image shows extensive hyperintense lesions with red arrows, primarily involving the temporal lobes, as well as evidence of involvement in the frontal lobes and insular cortex. The diffuse edema and the mass effect along with midline shift is also seen due to the inflammation indicating a severe infection process.

Fig. 2.

T2-weighted FLAIR MRI scan of brain axial section illustrating advanced Herpes Simplex Virus Encephalitis.

The image reveals pronounced hyperintense signal abnormalities within the left temporal lobe, extending into the left frontal lobe and insular region. Notable features include significant edema and mass effect, displacing the midline structures and indicating a severe inflammatory response. This extensive involvement is characteristic of advanced herpes encephalitis, emphasizing the aggressive nature of the infection which correlates with the clinical deterioration observed in neuropsychiatric symptoms.

Fig. 3.

T2 weighted coronal section MRI scan of brain.

The image shows extensive hyperintense (bright) areas shown with red arrow on T2-weighted MRI, particularly visible in the temporal lobes. These areas indicate inflammation and edema. There is also evidence of involvement of adjacent structures, which can be seen as irregularity and swelling, suggesting the spread of inflammation.

Fig. 4.

T2 weighted axial section MRI scan of brain at the level of basal ganglia and thalamic structures.

The MRI brain image in axial section shows significant bilateral hyperintense abnormalities, shown with red arrows, especially notable in the temporal lobes, indicating severe inflammation, typical of herpes encephalitis. The lesions are hyperintense, suggesting the presence of edema and inflammation in close proximity to basal ganglia and thalamus.

The cerebrospinal fluid (CSF) analysis revealed several significant findings indicative of a herpes simplex virus (HSV) infection. The CSF appearance was clear and colourless, and the opening pressure was within the normal range of 10-20 centimetres of water (cm H₂O). However, the total protein level was elevated at 80 milligrams per deciliter (mg/dL), above the normal range of 15-45 mg/dL, suggesting an inflammatory process.

The glucose level was normal at 60 mg/dL, consistent with the normal CSF glucose range of approximately two-thirds of blood glucose levels. The white blood cell (WBC) count was elevated at 100 cells per microliter (cells/µL) (normal range: 0-5 cells/µL), with a differential showing 90% lymphocytes and 10% neutrophils, which is characteristic of viral infections.

The Gram stain, India ink stain, acid-fast bacilli (AFB) stain, and cryptococcal antigen tests were all negative, ruling out bacterial and fungal infections, as well as tuberculosis. The HSV polymerase chain reaction (PCR) test was positive for HSV deoxyribonucleic acid (DNA), confirming the presence of herpes simplex virus in the CSF. These findings collectively supported a diagnosis of HSV infection in the central nervous system (CNS), accompanied by inflammation and an elevated protein level in the CSF.

A diagnosis of herpes encephalitis was made after the above mentioned investigations and the patient was immediately started on injectable acyclovir 500 mg intravenous thrice a day along with other empirical antibiotics and supportive management. Prophylactic antiepileptic medication (intravenous levetiracetam 500 mg twice a day) was also started. Patient's general condition and neurological status was thoroughly monitored throughout the hospital stay. The patient's condition improved eventually after close monitoring of vital signs and neurological status following treatment by injection acyclovir.

Acute psychotic episodes during the hospital stay were treated with consultation of psychiatrist by injection haloperidol 5mg and injection promethazine 25mg intramuscular twice a day followed by sos and eventually the medication was weaned off.

Patient's condition improved gradually following antiviral treatment and psychiatric symptoms also resolved within a few day of treatment initiation and was asked to follow up with neurologist and psychiatrist for further management and monitoring.

Discussion

Herpes encephalitis can lead to psychosis due to its effects on the brain. The herpes simplex virus (HSV) attacks the brain, causing inflammation and tissue damage, particularly in the limbic system, which is involved in regulating emotions and behavior [4]. This disruption can result in various psychiatric symptoms, including hallucinations, delusions, and disorganized thinking, characteristic of psychosis. Additionally, the virus can directly affect neurotransmitter systems, such as dopamine, further contributing to psychotic symptoms [4].

The incidence and prevalence of psychosis in herpes encephalitis are relatively low compared to other neurological manifestations of the disease. However, psychosis can occur as a rare complication of herpes encephalitis, particularly in severe cases or when there is involvement of specific brain regions [5]

Studies suggest that psychosis occurs in a minority of patients with herpes encephalitis, with estimates ranging from 2% to 20% [6].

Pathophysiology

Herpes Simplex Virus (HSV) infection begins when the virus enters the body through mucous membranes or breaks in the skin. From there, HSV can spread to the central nervous system (CNS), including the brain. Once it crosses the blood-brain barrier, the virus particularly targets cells within the limbic system, a critical area involved in regulating emotions and memory. Key structures within the limbic system, such as the hippocampus and amygdala, are especially vulnerable to HSV infection, leading to inflammation and tissue damage in these regions [7]. As the infection progresses, it triggers a significant immune response, leading to neuroinflammation. This immune activity involves the release of proinflammatory cytokines and chemokines, which can exacerbate tissue damage. In addition, HSV infection impacts neurotransmitter systems, including dopamine, serotonin, and glutamate, which are essential for mood regulation and cognitive functions. Disruptions in these systems can contribute to psychiatric symptoms, including psychosis.

One major consequence of HSV infection is dopamine dysregulation, as inflammation interferes with dopamine signalling pathways [7]. This disruption can lead to excessive dopamine activity in certain brain regions, a feature often associated with psychosis. Additionally, HSV infection can cause glutamate excitotoxicity, wherein the overactivation of glutamate receptors leads to neuronal damage. This dysregulation of glutamate is implicated in psychosis and other neuropsychiatric symptoms. Over time, the prolonged inflammation and damage to neurons from HSV infection can result in structural changes in the brain. These alterations may underlie some of the lasting neurological and psychiatric effects associated with HSV infection [7]. These sequential events and mechanisms underlying psychosis in herpes encephalitis, emphasises the complex interplay between viral infection, neuroinflammation, and neurotransmitter dysregulation [8].

Recognizing herpes encephalitis as a potential cause of psychosis is crucial for ensuring accurate diagnosis and appropriate treatment. Misdiagnosis can lead to unnecessary psychiatric interventions and prolonged suffering for the patient. By considering herpes encephalitis as a differential diagnosis, healthcare professionals can initiate the necessary investigations, such as brain imaging and cerebrospinal fluid analysis, to confirm or rule out the presence of the virus in the brain. Early diagnosis and treatment can significantly improve outcomes and prevent long-term neurological sequelae [9].

Differentiating between herpes encephalitis and psychosis can be challenging, as the symptoms can overlap. However, several diagnostic methods can aid in the accurate identification of herpes encephalitis. Brain imaging, such as magnetic resonance imaging (MRI), can reveal characteristic abnormalities in the temporal lobes, which are often affected by herpes encephalitis. Additionally, cerebrospinal fluid analysis can detect the presence of herpes simplex virus- deoxyribonucleic acid (HSV DNA) and antibodies, providing further evidence of the infection [10].

Few cases have been reported before where herpes encephalitis had presented with recurrent episodes of psychosis and misdiagnosed as psychosis. Prompt initiation of antiviral therapy resulted in a significant improvement in symptoms and a complete resolution of psychosis.

Early treatment of herpes encephalitis is essential for improving patient outcomes. The primary treatment for herpes encephalitis is antiviral medication, such as acyclovir, which aims to reduce viral replication and limit brain damage [11]. In severe cases, additional supportive care, including management of seizures and other neurological symptoms, may be required. Timely initiation of treatment can help prevent complications and reduce the risk of long-term neurological deficits [12].

Conclusion

To prevent the misdiagnosis of herpes encephalitis as psychosis, healthcare professionals should maintain a high index of suspicion in individuals presenting with new-onset psychosis symptoms. Comprehensive clinical evaluations, including detailed medical history and neurological examinations, should be conducted to identify any potential underlying causes. Collaboration between psychiatrists, neurologists, and infectious disease specialists can facilitate a multidisciplinary approach to diagnosis and treatment, ensuring that all possible causes are thoroughly explored.

Patient consent

A written informed consent was taken from the patient.

Disclosure

The authors hereby certify that the work shown here is genuine, original and not submitted anywhere, either in part or full.