Continuing Education Activity

Kluver-Bucy syndrome (KBS) is a rare neuropsychiatric disorder due to lesions affecting bilateral temporal lobes, especially the hippocampus and amygdala. It is characterized by hyperorality, hypermetamorphosis, hypersexuality, bulimia, placidity, visual agnosia, and amnesia. This activity reviews the evaluation and treatment of KBS and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

• Identify the etiology of Kluver-Bucy syndrome.
• Review the evaluation of Kluver-Bucy syndrome.
• Outline the treatment and management options available for Kluver-Bucy syndrome.
• Summarize interprofessional team strategies for improving care coordination and communication to advance awareness of Kluver-Bucy syndrome and improve outcomes.

Introduction

Kluver-Bucy syndrome (KBS) is a neuropsychiatric disorder due to lesions affecting bilateral temporal lobes, especially the hippocampus and amygdala.[1]

Clinical Features 

1. Hyperorality (A tendency or compulsion to examine objects by mouth)
2. Hypermetamorphosis (Excessive attentiveness to visual stimuli with a tendency to touch every such stimulus regardless of its history or reward value)
3. Hypersexuality 
4. Bulimia
5. Placidity
6. Visual agnosia and
7. Amnesia.

Patients having a combination of three or more different elements listed above are described as having partial KBS.[2][3]

The clinical features of KBS were initially reported by Sanger Brown and Edward Albert Sharpey-Schäfer, two British experimental neurologists, in 1888.[4] They described the behavioral transformations after the removal of bilateral temporal lobes in monkeys. But the complete syndrome was described later by Heinrich Kluver (neuropsychologist) and Paul Clancy Bucy (neurosurgeon) in 1939, unaware of the previous reporting.[5] They described the behavioral syndrome which occurred in a Rhesus monkey (named Aurora) three weeks after bilateral temporal lobectomy. The first description of KBS in humans came from Dr. Hrayr Terzian (1925-1988) and Dr. Giuseppe Ore in 1955 in a 19-year-old man who underwent bilateral temporal lobectomy for seizures.[6][7][6] The first identified and reported case of KBS was in a 22-year-old male patient with bilateral temporal damage due to herpes simplex meningoencephalitis by Marlowe et al.[8]

Etiology

KBS is known to be associated with several pathologies. There are many case reports of several conditions (listed below) ranging from infections like shigellosis to methamphetamine withdrawal. But how KBS occurred in these conditions remains unclear.

1. Herpes simplex encephalitis (HSE)[9]
2. Stroke (temporal lobe infarction - usually bilateral)[10][11]
3. Listeria meningoencephalitis[12]
4. Traumatic brain injury[13]
5. Central nervous system tuberculosis[2]
6. Primary cerebral Whipple disease[14]
7. Alzheimer disease[15]
8. Pick disease [16]
9. Hypoglycemia[17]
10. Acute sporadic porphyria[18]
11. Huntington disease[19]
12. Juvenile neuronal lipofuscinosis[20]
13. Toxoplasmosis
14. Epilepsy[21]
15. Parkinson disease
16. Heat stroke[22]
17. Shigellosis[23]
18. Methamphetamine withdrawal[24]
19. Systemic lupus erythematosus[25]
20. Anoxic-ischemic encephalopathy[26]
21. Neurocysticercosis[26]
22. Non-Hodgkin lymphoma[27]
23. Mycoplasmal bronchitis.[28]
24. Methotrexate leukoencephalopathy[29]
25. Subdural hygroma[30]
26. Susac syndrome[31] - associated with partial KBS
27. Anti-NMDAR encephalitis[32]
28. Exposure to cannabis[33]

The most common pathologies leading to the development of KBS are head injury and stroke in adults and herpes simplex encephalitis in children.

Epidemiology

Human KBS is more or less restricted to case series and reports. Hence the exact prevalence is difficult to estimate.

Pathophysiology

The significant clinical symptoms of KBS are produced by the destruction of either the temporal neocortex or the amygdala bilaterally. The full syndrome is rarely seen in humans because the anterior temporal lobe dysfunction is usually less severe in humans when compared to that following total temporal lobe resection in monkeys.[34]

The exact anatomical basis of KBS is still controversial. KBS is thought to occur due to the disturbances in the temporal portions of limbic networks that connect with multiple cortical and subcortical circuits to modulate emotional behavior and affect.[34] A sine qua non for KBS is the involvement of medial temporal lobe regions along with bilateral lesions of the Ammon horn.[35] Even though KBS is always thought to follow bilateral malfunctions of the temporal lobes, it is important to note that the amygdala, uncus, hippocampus, orbitofrontal and cingulate gyri, and insular cortex have an important role in its pathogenesis. 

Theories Regarding the Etiology

1. Norman Geschwind's theory: Interruption of visual input to limbic circuit leading to disconnection syndrome produces KBS.[36]
2. Muller theory: Disconnection of the pathways connecting the dorsomedial thalamus with the prefrontal cortex and other limbic areas leads to KBS. These pathways are essential for memory and emotional regulation.[37]

The Origin of Various Symptoms

• Rage is produced by the involvement of the ventromedian nucleus of the thalamus and amygdala.[38]
• A permanent "hypersexed state," is produced by discrete bilateral lesions of the lateral amygdaloid nucleus. Temporal lobe seizures may produce a transient state.
• Visual agnosia results from bilateral ventral temporal ablations and temporal lobectomies.

History and Physical

In Adults

1. Hyperorality - Socially inappropriate lickings and a strong compulsion to place objects inside the mouth
2. Hypersexuality - Lack of social restraint in terms of sexuality, with inappropriate sexual activity and attempted copulation with inanimate objects
3. Eating disorder - Objects are placed in the mouth and explored with the tongue to counteract visual agnosia. Bulimia, which is an eating disorder characterized by binge eating, followed by purging, is also markedly seen and may cause weight gain.
4. Placidity - Flat affect and reduced response to emotional stimuli
5. Visual agnosia (Psychic blindness) - Inability to recognize familiar objects or faces presented visually

Placidity, hyperorality, and dietary changes are the most commonly occurring symptoms of KBS.

In Children

KBS in children usually occurs secondary to HSE with classic features occurring only in a few.

1. Marked indifference
2. Bulimia and hyperorality
3. Lack of emotional attachment towards the family
4. Hypersexuality:
   • The frequent holding of genitals
   • Intermittent pelvic thrusts
   • Rubbing of genitals to the bed after lying prone

Evaluation

The diagnosis of KBS is mainly clinical. Once diagnosed, proper evaluation to find out the underlying pathology will be helpful in the overall management.

Magnetic resonance imaging of the brain is useful in identifying the extent of temporal lobe damage.

An electroencephalogram is also useful to identify seizures originating especially from the temporal lobe.

In head injury and other conditions producing a long duration of loss of consciousness, the appropriate staging of the consciousness is possible with the Modified Innsbruck Remission Scale, which includes the Kluver Bucy phase as well.[39]

Treatment / Management

The treatment of KBS can be challenging due to the fact that there is no specific treatment for the condition, and the clinical course will vary from patient to patient. Most of the treatment focuses on managing the symptoms. The main drugs used in the management are:

1. Mood stabilizers
2. Antidepressants (selective serotonin reuptake inhibitors)
3. Antipsychotic drugs
4. Carbamazepine
5. Leuprolide

Carbamazepine and leuprolide are used to reduce sexual behavioral abnormality, whereas haloperidol and anticholinergics are useful in treating behavioral abnormalities associated with KBS.[40] Carbamazepine has been found to improve outcomes in patients with KBS secondary to traumatic brain injury.[41]

Differential Diagnosis

KBS requires differentiation from the following conditions:

1. Alzheimer disease - Memory loss, personality changes
2. Conditions causing hyperphagia - Prader-Willi syndrome and Kleine-Levin syndrome
3. Frontotemporal degeneration - Progressive deterioration of intellect associated with behavioral and personality changes.
4. Korsakoff syndrome - Poor memory, irritation, personality changes

Prognosis

Some KBS features (i.e., hyperorality, placidity, hypermetamorphosis) persist indefinitely, whereas others gradually resolve over several years.

The clinical course of the disease varies among the case reports.

KBS occurring secondary to epileptic seizures, infections, and traumatic brain injuries may have a better prognosis as many of the damages would be reversible if recognized early and managed appropriately.

Complications

Due to hyperorality and hypermetamorphosis, the patient may try to put whatever objects he comes across into his mouth, which can be dangerous.

Due to hypersexuality, he may try to engage in sex with others whom he does not even know, leading to criminal procedures against the patient if there is no awareness of the diagnosis.

Bulimia can cause weight gain, electrolyte disturbance, and poor oral hygiene.

Deterrence and Patient Education

Patients' relatives should be educated about the condition and counseled that treatment may not always be successful. They should receive information that situations may arise, which require physical patient restraint.

Pearls and Other Issues

KBS is not a life-threatening condition. But it can profoundly affect the quality of life of the patient and the carers to a great extent. Any behavioral change following lesions of temporal lobes should be watched with suspicion for the development of KBS. More research is needed into the pathophysiology of the symptoms of KBS as well as the pharmacological and nonpharmacological management methods.

Enhancing Healthcare Team Outcomes

A close interaction between the treating neurologist, psychiatrist, neurosurgeon, and radiologist is necessary for coming to the final diagnosis of KBS. Careful monitoring of diet is required if they have symptoms consistent with eating disorders. Staff members, including nurses, should be cognizant of hypersexual behaviors in these patients.

The outcomes for these patients are poor; they often require medications to suppress abnormal behavior, and often, physical restraints are needed. Many end up in psychiatric institutions where they remain for life.