Unusual complication of Herpes simplex encephalitis: complete Klüver-Bucy syndrome

Abstract

Klüver-Bucy syndrome is a rare neurobehavioral disorder caused by a bilateral temporal lobe lesion affecting the hippocampus and amygdala; clinically characterised by hyperorality, hypermetamorphosis, placidity, altered sexual behaviour, eating, disorders and visual impairment, agnosia and amnesia. However, the complete syndrome is rarely seen, and diagnosis does not require all the symptoms to be manifested simultaneously.

We describe a patient who developed a complete Klüver-Bucy syndrome secondary to bilateral temporal involvement due to herpetic encephalitis.

Background

Klüver-Bucy syndrome (KBS) was described in 1937 by psychologist Heinrich Klüver and neurosurgeon–neuropathologist Paul Clancy Bucy as a behavioural syndrome in Rhesus monkeys that had undergone bilateral temporal lobectomy.¹ Transient and permanent KBS have been observed in humans, clinically characterised by hyperorality, hyper metamorphosis, placidity, altered sexual behaviour, eating disorders, visual agnosia and memory disorders.² The complete syndrome is rarely seen, and diagnosis does not require all the symptoms to be manifested simultaneously, being hyperorality and emotional changes the most common manifestations of partial KBS.¹

KBS is a rare disease; there are no epidemiological studies to estimate the prevalence, and information on humans is restricted to case series and reports.³ Those case reports have been associated with KBS with several aetiologies. Still, the common pathology of these causes is bilateral destruction or dysfunction of mesial temporal lobes, although there are case reports where unilateral damage can also cause the syndrome.⁴

We report the case of a woman in her 50s who presented with a complete KBS following Herpes simplex encephalitis.

Case presentation

A previously healthy woman in her 50s, right-handed, was admitted to the neurology service with a 3-day history of headache, fever and drowsiness. She could follow simple but not complex commands, orientation was impaired and language content was meaningless; there were no other features on physical examination. A CT scan showed bilateral hypodensity of the temporal lobes (figure 1A). Routine blood tests were normal. CSF showed mild lymphocytic pleocytosis (30 monocytes), glucose 60.3 mg/dL and hyperproteinorrhachia (75.4 mg/dL), with positive detection of herpes simplex virus DNA in cerebrospinal fluid using PCR assay. Cranial MRI showed hyperintense signal changes in both temporal lobes in T2 (figure 1B) and fluid-attenuated inversion recovery-weighted imaging along with diffusion restriction (figure 1C). EEG showed diffuse slowing. She was diagnosed with herpes simplex virus encephalitis and successfully treated with acyclovir and discharged. A month later, she displayed aggressive behaviour, abulia and impulsiveness, hyper metamorphosis, prosopagnosia, hyperorality with hyperphagia and a high compulsion to place objects inside the mouth, insomnia and hypersexuality. A neuropsychological evaluation was performed, which showed alterations in the maintenance of attention alternating with periods of hyperprosexia, impulsiveness, low tolerance for frustration and irritability, disorientation in time, reduction of the informative content of language and alterations in episodic and semantic memory. As well as in the processing of static and sequential visual memory, alterations in visual perception and memory, and alterations in executive functions corresponding to planning, organisation, verification and mental flexibility.

Figure 1.

(A) CT scan of the skull shows bilateral temporal hypodensity, right predominant. (B) T2-weighted axial magnetic resonance image showing hyperintense signal changes in both temporal lobes. (C) Diffusion-weighted MRI reveals restriction of diffusion in bilateral temporal lobes.

Given the history of herpetic encephalitis confirmed by positive PCR for herpes simplex in cerebrospinal fluid, the bilateral involvement of the temporal lobes demonstrated by MRI, and the compatible neuropsychological characteristics, we concluded that complete Klüver-Bucy syndrome secondary to bilateral temporal involvement due to herpetic encephalitis. In addition, the MRI showed necrotic scars in both temporal lobes with significant affection on the right side (figure 2A, B).

Figure 2.

(A) T1-weighted axial control resonance image showing the damage in both temporal areas. (B) T2-weighted coronal MRI showing the necrotic scars in temporal areas that explain the behavioural changes in the patient.

Treatment

Medical treatment with oxcarbazepine 1050 mg/day, risperidone 2 mg/day, clonazepam 1 mg/day was indicated.

Outcome and follow-up

At the 3 month follow-up, the patient showed a remarkable improvement in irritability, aggressiveness, impulsivity and hypersexuality, but the other symptoms persist unchanged.

Discussion

Klüver-Bucy syndrome is a rare neurobehavioral disorder caused by bilateral temporal lobes lesion and characterised by hyperorality, placidity, hyper metamorphosis, dietary changes, altered sexual behaviour and visual agnosia. The complete syndrome is not often seen in humans,¹ and diagnosis does not require all the symptoms to be manifested simultaneously. The patients with three or more features are described as having a partial Klüver-Bucy syndrome.⁵ Also, some of these characteristics have been reported to be permanent, such as hyperorality (to explore everything with the mouth), placidity and hyper metamorphosis (excessive visual attentiveness), while the others tend to resolve gradually over the years.³

Klüver-Bucy syndrome has been associated with several pathologies, and herpes simplex encephalitis is one of the most reported aetiologies.^{1 6–10} The Herpes simplex virus type 1 is the most common cause of sporadic encephalitis,¹¹ typically with involvement of bilateral medial temporal lobe, insular cortex and cingulate gyrus¹² and an abnormal MRI in 90% of the cases,¹³ being cerebrospinal fluid analysis for Herpes PCR the most sensitive and specific test for its diagnosis.

The exact pathophysiology of Klüver-Bucy syndrome is not entirely understood. Still, the syndrome is thought to occur due to the disruptions in the temporal regions of limbic connections with multiple cortical and subcortical circuits to modulate emotional behaviour and affect.¹

Two principal theories have been proposed regarding the pathophysiology of the syndrome. The Geschwind theory, based on the interruption of visual input to the limbic circuit leading to disconnection syndrome,¹⁴ and the Muller theory, the interruption of the networks connecting the thalamus dorsomedial with the cortex prefrontal and other limbic areas leads to the syndrome.¹⁵

Other aetiologies include neurosurgical for psychosurgery,¹ neurocysticercosis, tuberculosis, cranial trauma,¹⁶ Shigella-associated encephalopathy,¹⁷ neurotoxicity associated with methotrexate use,¹⁸ Bilateral postanoxic and epileptic temporal damage,¹⁹ due to bilateral anterior temporal infarcts associated with cardioembolism,²⁰ use of illicit drugs as amphetamines,²¹ among other causal possibilities. However, it is still an infrequent problem.

There is no specific treatment for Klüver-Bucy syndrome, focusing on symptomatic management.³ Carbamazepine and leuprolide reduce sexual behavioural abnormality, whereas haloperidol and anticholinergics are used for behavioural abnormalities.³ In a systematic review of pharmacological treatment from cases of Klüver-Bucy syndrome secondary to traumatic brain injury, 50% of the patients improved with carbamazepine in 400–1000 mg/day, mainly in the affective component.²

The clinical course of this problem varies among the case reports, from a chronic condition to transient symptoms, and relatives of patients should be informed that treatment is not always successful.³

Patient's perspective.

As the patient’s family, we are grateful for the improvement demonstrated by medical treatment after the very severe encephalitis. We face behavioural changes to improve the initial problem and actual situation, and we understand the prognosis.

Learning points.

• Kluver-Bucy syndrome is a rare disorder due to bitemporal injury or dysfunction.

• The clinical features of the syndrome are hyperorality, hyper metamorphosis, placidity, altered sexual behaviour, eating disorders, visual agnosia and amnesia.

• The complete syndrome is rarely seen, and the presence of three or more of the clinical features is classified as partial Klüver-Bucy syndrome.

• Herpes simplex encephalitis is one of the principal clinical reported aetiologies of Kluver-Bucy syndrome.

• There is no specific treatment, but carbamazepine and leuprolide are reported to reduce sexual behavioural abnormality.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s)