Virus-Induced Voracity: Uncovering Hyperphagia Post-Herpes Simplex Virus Type 1

In human beings, leading cause of sporadic encephalitis is herpes simplex virus type 1 (HSV-l) [1]. Herpes simplex virus type 2 is also able to cause encephalitis (especially in the immuno-compromised host and neonates), but HSV-1 is accountable for almost 90% of herpes simplex virus (HSV) encephalitis in adults and children. Clinical features of encephalitis include fever, headache, seizure, irritability, lethargy, confusion, aphasia, and focal deficit [2]. As an alternative, it can lead to encephalopathy (manifesting as altered sensorium, confusion, behavioural abnormalities, agitation, or disturbance of the sleep-wake cycle) devoid of inflammation of brain tissue or direct central nervous system infection [3]. Clinicians need to be familiar with acute complications like progressive temporal lobe oedema, which can lead to uncal herniation, and status epilepticus, moreover chronic complications like anti-NMDAR encephalitis [2, 4]. MRI brain is usually abnormal, showing asymmetric changes in the mesotemporal lobe, insular cortex, and orbitofrontal lobe with associated oedema, possibly restricted diffusion, or haemorrhage [3]. CSF PCR confirms diagnosis for HSV-1 and herpes simplex virus type 2, which has replaced viral cultures and other studies as the test of choice, and has impressive sensitivity (96%) and specificity (99%). False-negative PCR can take place in the initial stage of the disease, and if the clinical suspicion is high, acyclovir should be started empirically and CSF HSV PCR should be repeated within 3–7 days [5]. HSV encephalitis is treated with acyclovir 10 mg/kg intravenously every 8 h for 14–21 days. Dosage should be modified in patients with impaired renal function [2]. Intravenous acyclovir is a salvage therapy for HSV encephalitis and has decreased mortality from above 70% to around 10–20% [6]. Here, we are presenting a unique case of HSV-1 encephalitis that developed hyperphagia as a sole complication of encephalitis, a rare presentation.

A 25-year-old woman was brought to the hospital with a complaint of acute-onset high-grade fever for 10 days, associated with headache and vomiting. Three days later, she developed irrelevant talk, was unable to recognize family members, and was experiencing visual hallucinations, seeing imaginary objects, and subsequently within next 8 days she had become drowsy with altered sensorium. There was no history of new seizure episodes, but she had a history of meningoencephalitis at the age of 8 years, following which she developed left focal seizures with impaired awareness, well controlled with anti-seizure medications. The last seizure episode was 4 years ago. There was no history of substance abuse or any other prior comorbidity. On examination, her GCS was 11 (E3M5V3). No other focal neurological deficits were found. All required investigations including routine blood investigations, MRI brain, video EEG, and CSF analysis were done. MRI (Fig. 1) unveiled hyperintensity in both temporal lobes in T2 and FLAIR imaging along with diffusion restriction. EEG showed diffuse 6–6.5 Hz theta activity suggestive of generalized slowing. Routine blood analysis was normal with borderline raised C-reactive protein and ESR (Tables 1, 2). CSF analysis showed lymphocytic pleocytosis and elevated protein (Table 3). Autoimmune and paraneoplastic encephalitis panel and other relevant investigations were sent (Table 4). Based on clinical features, MRI and CSF findings, the possibility of viral encephalitis was considered, and treatment started with injectable acyclovir 500 mg 8 hourly and other supportive therapies. Later on, the diagnosis was confirmed by CSF neurotropic viral panel report, which showed positive PCR for HSV-1. At the end of first week of treatment, the patient became afebrile, and her neurological status improved in terms of awareness, but she began to show behavioural abnormalities in the form of hyperphagia (online suppl. Video 1; for all online suppl. material, see https://doi.org/10.1159/000541698). She developed hyperphagia for both edible and non-edible items. Quetiapine was initiated for the same. The patient received 21 days of intravenous acyclovir, and at the time of discharge, she scored 24/30 in the Mini-Mental State Examination (MMSE). Although there was significant improvement in her consciousness, only partial improvement was noticed in the hyperphagia at the end of 3 weeks of treatment. After 1 month of her follow-up, the hyperphagia significantly reduced (online suppl. Video 2).

HSV-1 particularly affects the bilateral temporal lobe, cingulate gyrus, and insular cortex [7]. In our patient also, similar findings were seen in the MRI of the brain (Fig. 1). Abnormalities on MRI are reported in 90% of cases. CSF PCR is the most sensitive and specific test for diagnosing HSV encephalitis [8]. Our patient’s CSF PCR for HSV-1 was positive, confirming the diagnosis. In 1937, Heinrich Kluver along with Paul Bucy described significant behavioural abnormalities in monkeys following temporal lobectomy. Subsequently, almost identical findings were noticed in humans with diseases affecting bilateral temporal lobe, named as Kluver-Bucy syndrome (KBS) [9]. The aetiology of KBS includes infectious and autoimmune encephalitis, temporal lobe epilepsy, Alzheimer’s disease, bilateral post-anoxic temporal damage, head trauma, neurotoxicity associated with methotrexate use, toxoplasmosis, neurocysticercosis, tuberculosis, pick’s disease, use of illicit drugs such as amphetamines, and cerebrovascular disease [10‒12]. KBS is described by a group of cognitive dysfunctions that include hypersexuality, emotional and behavioural abnormalities like placidity, hyperorality, hypermetamorphosis, visual agnosia, and memory impairment [13, 14]. KBS is believed to happen due to disruptions in the temporal portions of the limbic network that link with various cortical and subcortical circuits to regulate emotional behaviour and effect. Lesions in the medial temporal lobe regions along with involvement of the bilateral hippocampus are the sine qua non for KBS [15]. Though HSV encephalitis has been reported as one of the most common aetiologies of KBS, it is still a rare complication of HSV encephalitis [1, 16]. The complete syndrome is seldom reported and the diagnosis does not require all the symptoms to be existing together. Hyperorality, dietary changes, and placidity are the partial KBS’s most prevalent symptoms [9, 15]. Patients with three or more features are labelled as partial KBS [10]. Particularly, hyperorality is a feature of almost all reported human cases of KBS, and some experts recommended it to be a prerequisite for diagnosis. Rapid weight gain and bulimia occur in few patients, and some eat inedible objects [9]. Our patient developed isolated hyperphagia and also started eating inedible items like paper, pen (online suppl. Video 1) without any other components of KBS.

For HSV encephalitis, acyclovir is the recommended therapy given for 14–21 days, and for the best result it should be initiated prior to the patient becoming unresponsive [11, 15, 17]. We started intravenous acyclovir on day 2 of hospital admission, and the patient received this antiviral for a total of 21 days. There was a significant improvement in her sensorium, with a partial improvement in hyperphagia (online suppl. Video 2). A patient with isolated hyperphagia following HSV encephalitis has not been reported so far, making our case distinctive and exceptional. Treating new-onset hyperphagia is difficult and as yet there is no targeted therapy for this presentation. The illness trajectory differs from patient to patient. Most of the medication focuses on symptomatic treatment. Antipsychotics like haloperidol and others may be helpful in symptom relief and antidepressants can also be used [15, 18]. This patient was treated with quetiapine with moderate improvement. The delayed initiation of treatment could have been the cause of this unfavourable outcome as acyclovir was started after the temporal lobes already had experienced considerable destruction. On follow-up, our patient showed significant weight gain with partial improvement in hyperphagia. The “CARE Checklist” has been completed by the authors for this case report, attached as online supplementary material.

This case report enlightens that acute-onset hyperphagia may be the sole complication of HSV encephalitis, and early initiation of therapy can be the difference between a favourable and an adverse outcome.

Ethical approval is not required for this study (case report) in accordance with local or national guidelines. Written informed consent was obtained from the patient’s husband for publication of the details of their medical case, accompanying images and videos (consent form enclosed).

The authors have no conflicts of interest to declare.

No funding required in this study.

Arpan Mitra and Ankur Vivek: data collection and writing and editing manuscript; Nayana Bhuyan: data collection and writing manuscript; Akansha Jain: writing and editing manuscript; Vijaya Nath Mishra: data interpretation; and Abhishek Pathak: data analysis.

Arpan Mitra and Nayana Bhuyan should be considered as first authors.

All data generated or analysed during this study are included in this article and its online supplementary material files. Further enquiries can be directed to the corresponding author. Data are available in the MRD section of our institute.