Hrayr Terzian (1925-1988): a life between experimental neurophysiology and clinical neurology.

This article provides a biographic and scientific profile of prof. Hrayr Terzian (Addis Abeba 1925-Verona 1988). In 1966, Terzian was appointed professor of the clinic of nervous and mental diseases in Cagliari, and in 1970 moved to Verona, where until his death he led the Neurology Clinic serving as the first rector of the local university. As a close friend of the psychiatrist Franco Basaglia (1924-1980), Terzian contributed to the reform of the Italian mental health system. His interests and scientific contributions were extremely broad. He was the first to describe the electroencephalographic changes induced by the antipsychotic chlorpromazine and, together with Henri Gastaut (1915-1995) and his wife Yvette, to describe the rolandic arched ("mu") rhythm. He contributed to elucidate the inhibitory mechanisms of the cerebellum on the antigravity postural tone and provided the first description of Klüver-Bucy syndrome in humans. Always attentive to the social and political aspects of medical practice, prof. Terzian achieved outstanding results both in experimental neurophysiology and in clinical neurology. Besides offering a tribute to Hrayr Terzian, this article provides a brief historical overview of the different clinical pictures caused by bilateral temporal lesions: from the first animal observations by Sanger Brown (1852-1928) and sir Edward Albert Sharpey-Schäfer (1850-1935), later confirmed and expanded upon by Heinrich Klüver (1897-1979) and Paul C. Bucy (1904-1992), to the first cases of bitemporal lesions in humans, including that of the famous patient H.M. (Henry Gustav Molaison, 1926-2008).

Klüver & Bucy syndrome: an investigation of social and affective cognition.

Klüver-Bucy syndrome (KBS) leads to important behavioral symptoms and social maladaptation. Rarely described, no previous study has investigated its social and affective cognitive profile. We report the case of ASP, a patient who developed a complete KBS at 9 years that evolved into an incomplete KBS. Orbitofrontal and temporal damages were evidenced. While a classic neuropsychological assessment showed a preserved global functioning, an extensive evaluation of her social and affective cognition (reversal learning, decision-making, emotion recognition, theory of mind, creative thinking) showed remarkable deficits. The relevancy of such findings for the characterization KBS and the field of neuropsychology are discussed.

Prevalence of hyperphagia in Alzheimer's disease: a meta-analysis.

BACKGROUND: Unlike other behavioural and psychological symptoms of dementia, hyperphagia is less recognized among patients with Alzheimer's disease (AD). The prevalence of hyperphagia varies among studies, but there has been no systematic review or meta-analysis. METHODS: An extensive search on the literature on hyperphagia in AD published between 1 January 1980 and 30 October 2017 was conducted. Data on the prevalence were retrieved. Meta-analysis with a random effect model was performed to determine the pooled estimate of prevalence. Meta-regression analysis was performed based on study characteristics, population demographics, or condition information. RESULTS: Results from 20 studies were extracted. Twenty-six reported cases of hyperphagia were identified. The mean age of onset was 70.7 ± 8.9 years, with a male predominance (68.4%). Hyperphagia occurred in all stages of AD. Only eight studies reported the prevalence of hyperphagia. Meta-analysis showed a pooled prevalence of hyperphagia of 18.6%. Publication bias may have been present. Meta-regression showed that ethnicity accounted for the variance among studies (coefficient: -1.247 (95% confidence interval: -1.978 to -0.516), R2 analogue: 0.77, P < 0.001). CONCLUSIONS: Hyperphagia occurs in all stages of AD. In this meta-analysis of eight published studies, the prevalence of hyperphagia was 18.6%. In view of the possible publication bias, a large-scale study on hyperphagia is recommended in the future.

Sanger Brown and Edward Schäfer before Heinrich Klüver and Paul Bucy: their observations on bilateral temporal lobe ablations.

Fifty years before a report on the complete bitemporal lobectomy syndrome in primates, known as the Klüver-Bucy syndrome, was published, 2 talented investigators working at the University College in London, England-neurologist Sanger Brown and physiologist Edward Schäfer-also made this discovery. The title of their work was "An investigation into the functions of the occipital and temporal lobes of the monkey's brain," and it involved excisional brain surgery in 12 monkeys. They were particularly interested in the then-disputed primary cortical locations relating to vision and hearing. However, following extensive bilateral temporal lobe excisions in 2 monkeys, they noted peculiar behavior including apparent loss of memory and intelligence resembling "idiocy." These investigators recognized most of the behavioral findings that later came to be known as the Klüver-Bucy syndrome. However, they were working within the late-19th-century framework of cerebral cortical localizations of basic motor and sensory functions. Details of the Brown and Schäfer study and a glimpse of the neurological thinking of that period is presented. In the decades following the pivotal work of Klüver and Bucy in the late 1930s, in which they used a more advanced neurosurgical technique, tools of behavioral observations, and analysis of brain sections after euthanasia, investigators have elaborated the full components of the clinical syndrome and the extent of their resections. Other neuroscientists sought to isolate and determine the specific temporal neocortical, medial temporal, and deep limbic structures responsible for various visual and complex behavioral deficits. No doubt, Klüver and Bucy's contribution led to a great expansion in attention given to the limbic system's role in action, perception, emotion, and affect-a tide that continues to the present time.

Partial Klüver-Bucy syndrome in a Paediatric patient: A post-neurosurgical and neuropsychological cases.

A variety of cognitive, behavioural, and emotional impairments have been reported in the literature that are associated with the resection of the temporal cortex. Klüver-Bucy syndrome is one infrequently reported disorder in the paediatric population. This paper describes the neuropsychological findings of a female paediatric patient at 7 and 10 years of age with a diagnosis of partial Klüver-Bucy syndrome (pKBS) following total resection of the amygdala and right hippocampus to resect a glioma. The patient presented emotional problems, aggressiveness, hypermetamorphosis, social indifference, and behavioural dysexecutive syndrome, which was found at both 7 and 10 years, but with a decrease in the severity of alterations in attention, impulsivity, hyperactivity, and aggressive behaviour in a second evaluation after she had a neuropsychological intervention. These findings describe the neuropsychological profile of paediatric case with resection of the amygdala and right temporal lobe.

The 100 Most Cited Kluver-Bucy Research Articles: A Bibliometric Analysis.

Kluver-Bucy Syndrome (KBS) is a rare neuropsychiatric disorder characterized by hyperorality, hypersexuality, bulimia, visual agnosia, and amnesia due to lesions affecting bilateral temporal lobes. It is attributed to a multitude of causes, including stroke, herpes simplex encephalitis, Alzheimer's disease, and head trauma. Current treatments for KBS include symptomatic management with antipsychotics, mood stabilizers, carbamazepine, and selective serotonin reuptake inhibitors. The bibliometric analysis was done to reflect the relevance and understanding of KBS in recent literature. The SCOPUS database was utilized to conduct a search for all articles with the terms "Kluver-Bucy" and "Kluver Bucy" from January 1, 1955 (the first available articles from the search) to February 1, 2023. The parameters included in this analysis were article title, citation numbers, citations per year, authors, institutions, publishing journals, country of origin, Source Normalized Impact per Paper, and Scopus CiteScore. Since 1937, when Kluver-Bucy Syndrome was first defined, the publications on KBS have steadily increased, with up to six publications a year in 2002. The most common institutions were SUNY Upstate Medical University, VA Medical Center, and the State University of New York (SUNY) System. Seven of these papers were published in Neurology. Almost 75% of the articles were published in journals of medicine and neuroscience. This is the first bibliometric analysis to evaluate the most influential publications about Kluver-Bucy Syndrome. A majority of the research is case-based and there is a dearth of clinical trials to identify the exact pathophysiology and physiotherapy management, possibly owing to the rarity of the disease. Our research suggests that there may be a significant overlap between Sanfilippo syndrome and KBS, suggesting that refined guidelines for establishing diagnosis may be required for children. Our study could bring a renewed interest in this field and lead to additional research focused on understanding the pathophysiology of KBS in order to promote the development of novel diagnostics and treatment.

Anti-Ma2 Encephalitis: An Atypical Case Associated With Klüver-Bucy Syndrome and Hypothalamic Dysfunction.

Anti-Ma2 encephalitis is a rare form of autoimmune encephalitis that has classically been described as a paraneoplastic neurobehavioral disorder due to its association with underlying malignancies. We discuss the case of a 30-year-old female with an exceptionally aggressive presentation of anti-Ma2 encephalitis accompanied by Klüver-Bucy syndrome and hypothalamic dysfunction. Her course was complicated by repeated aspiration events secondary to severe hyperphagia and delays in immunosuppressive treatment due to concerns of infection. The patient's encephalitis was refractory to multiple immunosuppressive therapies and she ultimately expired before a primary malignancy could be detected and treated.

Herpes Simplex Encephalitis: Detection, Management, and Outcomes.

The pathophysiology of herpes simplex encephalitis (HSE) is incompletely understood and proposed to be secondary to the retrograde transport of the herpes simplex virus type 1 (HSV-1) via the trigeminal and/or olfactory nerves to the central nervous system (CNS). In this case report, we present a 68-year-old female who presents to our emergency department after a fall. Upon initial admission, her neurological examination was benign, and a computer tomography (CT) scan of her brain showed a subdural hematoma for which she was treated conservatively. Day 4 of her hospitalization marked a rapid decline in her course of illness, beginning with confusion and hallucinations, progressing to subclinical seizures, and culminating in irreversible brain damage and palliative extubation on day 16 of hospitalization. This case report discusses our insight into the challenges of early diagnosis and treatment of herpes encephalitis and their impact on improving patient outcomes.

Transient Kluver-Bucy Syndrome as a Manifestation of Post-temporal Lobe Seizure: A Rare Case Entity.

Following epileptic seizures, patients can subsequently experience a post-ictal state characterized by disorienting symptoms, such as confusion, drowsiness, hypertension, headache, and nausea, rather than neurobehavioral sequelae. We report the case of a 64-year-old male with unilateral left temporal lobe injury, who presented with post-ictal transient Kluver-Bucy Syndrome symptomatology following a complex partial seizure. Brain magnetic resonance imaging revealed encephalomalacia of the left temporo-parieto-occipital region from a previous infarct, and his symptoms resolved following the administration of antiepileptic medications. Therefore, transient Kluver-Bucy Syndrome can follow unilateral temporal lobe injury and should be suspected in patients who fit the clinical criteria, even in the absence of classic bilateral temporal lobe damage on imaging.

Successful Combination Therapy of Trazodone and Fluvoxamine for Pica in Alzheimer's Disease: A Case Report.

Pica in Alzheimer's disease (AD) makes it difficult for caregivers to provide care. However, few effective medications have been reported for pica in AD. We report a case of AD with pica that was successfully improved by trazodone and fluvoxamine. An 80-year-old woman with AD was admitted to our hospital due to aggravated pica, including eating weeds in the facility's garden and eating a dishwashing sponge. Her pica was accompanied by oral tendency, prosopagnosia, and placidity. She took rivastigmine and memantine, but these were ineffective for her pica. She was given olanzapine and perospirone, but both were discontinued due to over-sedation and severe extrapyramidal symptoms, respectively. We then administered trazodone and fluvoxamine, both of which have demonstrated effectiveness for pica in frontotemporal dementia (FTD). Her pica behaviors then disappeared without daytime sleepiness. In this case, pica with oral tendency, which was accompanied by prosopagnosia and placidity, may be interpreted as a partial symptom of Klüver-Bucy syndrome (KBS). KBS is often seen in FTD, but also occurs in late-stage AD. Our case together with previous reports showing that trazodone and fluvoxamine were effective for pica in FTD suggest that the same common drug therapy may be successful in pica with oral tendency, regardless of the subtype of dementia.

Klüver-Bucy syndrome secondary to a nondominant middle cerebral artery ischemic stroke: a case report and review of the literature.

BACKGROUND: Klüver-Bucy syndrome is a rare and complex neurobehavioral cluster that occurs in humans and results from a temporal lobe lesion. It can be associated with a variety of causes. Stroke is a rarely reported cause of this syndrome. CASE PRESENTATION: In this report, we present the case of a 68-year-old Saudi male who developed Klüver-Bucy syndrome subsequent to a nondominant middle cerebral artery ischemic stroke involving right temporal lobe. The patient manifested most of the Klüver-Bucy syndrome clinical features, including hypersexuality, hyperphagia, hyperorality, and visual hypermetamorphosis (excessive tendency to react to every visual stimulation with a tendency to touch every such stimulus). These neurobehavioral manifestations improved after he was started on treatment. CONCLUSIONS: The clinical course, anatomical association relying on pathophysiology, and potential treatment have all been deliberated in regard to the rare occurrence of Klüver-Bucy syndrome resulting from temporal lobe pathology.

Sexual Behavioral Disinhibition Associated with Nucleus Lentiformis Lesion: A Forensic Neuroscience Perspective Through a Case.

Organic brain disturbances particularly related to frontal cortex structures and subcortical areas including the basal ganglia may play a role in behavioral disinhibition disorders. Kluver-Bucy syndrome (KBS), which is one of the better knowns of these syndromes, includes hyperorality, visual agnosia, and hypersexuality, has been reported to occur after temporal lobe and amygdala lesions; however, several patients who had focal lesions in areas other than the temporal cortex and amygdala have been reported to present partial KBS symptoms. Nucleus lentiformis refers to a large portion of the basal ganglia including the putamen and globus pallidus, and specific structures within this broad area are known to be important for reward and value-based decision making. To date, KBS symptoms including hypersexual behavior associated with nucleus lentiformis lesions have never been reported. Here, we present a 38-year-old male patient who developed increased sexual interest and hyperorality after infarctions in the right lenticular nucleus and right occipitotemporal region and committed a first-degree sexual assault. He was sent to our institution for the assessment of criminal responsibility to the index sexual crime. According to a comprehensive and thorough forensic psychiatric evaluation, he was diagnosed as having an organic personality disorder with partial KBS symptoms. To the best of our knowledge, this is the first reported case of deviant sexual behavior and hyperorality developing after nucleus lentiformis infarction. We aimed to discuss possible neurobiologic explanations of late-onset deviant sexual behavior, which resulted in sexual criminal behavior following a cerebrovascular infarction.

James Wenceslaus Papez, His Circuit, and Emotion.

James Papez worked on the anatomical substrates of emotion and described a circuit, mainly composed of the hippocampus, thalamus and cingulum, and published his observations in 1937. However, such an idea existed before him, as evidenced by the rudimentary indications from Paul Broca, and Paul MacLean added some other structures like, septum, amygdala, and hypothalamus in its ambit and called it the limbic system. Paul Ivan Yakovlev, proposed a circuit which also referred to orbitofrontal, insular, anterior temporal lobe, and other nuclei of thalamus. Further works hinted at cerebellar projections into this system and the clinical picture of aggression, arousal and positive feeding responses with stimulation of cerebellar nuclei, attests its possible role. Finally, the work of Heinrich Klüver and Paul Bucy of the United States of America on ablating the temporal lobes and amygdala and the resultant behaviour of the animals, almost incontrovertibly adduced evidence for the operation of a neural circuitry in the genesis of emotion. Additionally, Papez circuit may also be concerned with memory and damage to its various components in Parkinson's disease, Alzheimer's disease, Korsakoff's syndrome, semantic dementia, and global amnesia, where cognitive disturbance is almost universal, lends credence to its putative role.

Bilateral Anterior Opercular Syndrome With Partial Kluver-Bucy Syndrome in a Stroke Patient: A Case Report.

Bilateral anterior opercular syndrome and partial Kluver-Bucy syndrome are associated with bilateral middle cerebral artery lesions. The combination of these two syndromes has only been reported in a child with limbic encephalitis. In this case, a 44-year-old woman with bilateral middle cerebral artery infarction, which occurred 2 years prior, could walk independently. However, she showed automatic-voluntary dissociation and anarthria with preserved writing skills. She also presented hypersexuality, hypermetamorphosis, and memory disturbances. Here, we report a case of an adult stroke patient who suffered from bilateral anterior opercular syndrome accompanied by partial Kluver-Bucy syndrome.

A case with probable herpes simplex encephalitis characterized by specific emotional and behavioral disorders and Gogi (word-meaning) aphasia-like syndrome with neologism and neologistic kanji processing.

A right-handed male patient with probable herpes simplex encephalitis is presented because of the rarity of the clinicial picture. Brain X-ray CT scans showed lesions located in the bilateral fronto-temporal regions primarily involving the left lower temporal lobe. The clinical picture following the acute phase of the disease was characterized by specific emotional and behavioral disorders, i.e. oral tendency, hyperactivity, thoughtless talkativeness, random speech and exhilaration, which were partly compatible with the Klüver-Bucy syndrome. Furthermore, this case was characterized by Gogi (word-meaning) aphasia-like transcortical sensory aphasia and neologism produced saliently when naming objects and peculiar neologistic kanji processing in writing to dictation and oral reading. Both the neologism and neologistic kanji processing varied in quantity in parallel with the specific emotional and behavioral disorders. The relationships of these clinical features to lesional sites demonstrated by X-ray CT are discussed.

Unilateral temporal lobe damage and the partial Kluver-Bucy syndrome.

The characteristic behavioural constellation of Kluver-Bucy syndrome is believed to be diagnostic of bilateral temporal lobe damage, even in the partial syndrome. The case described is that of a 54 year old woman with gross atrophy of her right temporal lobe following neurosurgery who developed hyperphagia (with driven food-seeking behaviour), placidity and hyposexuality. Her case thereby meets criteria for the partial syndrome but without evidence of bilateral damage. The discussion covers the various presentations of hyperphagia, the significance of the symptom cluster of Kluver-Bucy syndrome and the management difficulties presented by hyperphagia.

Klüver-bucy syndrome with isolated bilateral hippocampal atrophy following status epilepticus.

Klüver-Bucy syndrome may result from affection of various location of brain. We report a case of Klüver-Bucy syndrome associated with isolated bilateral hippocampal atrophy without any abnormal lesion in other areas following status epilepticus. A 31-year-old man who had no significant medical history presented with status epilepticus after encephalitis of unknown etiology. He had been recovered from status epilepticus three weeks later, but afterwards he developed Klüver-Bucy syndrome: hyperphagia, hypersexuality, hypermetamorphosis, anterograde amnesia and dysosmia. Initial brain MRI showed T2 hyperintensity and swelling of isolated bilateral hippocampus, especially CA1 region without any abnormal lesion in other areas. One month later, follow-up brain MRI showed isolated bilateral hippocampal atrophy. This is a meaningful case report because this case differs from other reports of Klüver-Bucy syndrome in humans in that the anatomic abnormalities revealed by MRI were very selective. We report this case because this case is very educative for above reason. Moreover, this report would give us additional information of the relationship between human behavior and limbic system.

Temporal and pontine involvement in a case of herpes simplex encephalitis, presenting as kluver bucy syndrome - a case report.

Bilateral temporal and frontal lobe involvement is a common characteristic of herpes simplex encephalitis (HSE). Clinical sequelae of herpes simplex encephalitis may manifest sometimes as Kluver Bucy syndrome (KBS). In herpes simplex encephalitis, apart from frontal lobe, extra temporal involvement is rare and uncommon. We report a case of HSE manifesting clinically as KBS with a rare radiological finding of temporal and extratemporal involvement of pons.

Partial Kluver-Bucy syndrome as a delayed manifestation of head injury.

After traumatic brain injury (TBI), the most disabling problems are generally related to neuropsychiatric sequelae, including personality change and cognitive impairment, rather than neurophysical sequelae. Kluver-Bucy syndrome (KBS) is a rare neurobehavioral condition, first described in 1937 as an experimental neurobehavioral syndrome in monkeys with bitemporal brain lesions. The syndrome in man was subsequently observed to be transient or permanent in a variety of neurodegenerative disorders and after traumatic, nontraumatic and infectious brain injury. However, partial KBS may occur in the absence of the classic bilateral temporal lesion, though rare. Pharmacological treatment of post-TBI neuropsychiatric sequelae consists of symptomatic, functional and hypothetical approaches. Specific pharmacological treatment consists of antipsychotics, anti-kindling anticonvulsants or a combination thereof. A case of partial KBS presenting as delayed manifestation of traumatic brain injury that improved with carbamazapine and antipsychotics is presented.