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.

Our search yielded 285 relevant articles.The top 100 are listed below (Table 1).The publication dates for this topic range from 1955 to 2022 (Figure 1).The greatest number of publications occurred between 2000 and 2009 (70 publications, 24.6%).The year with the greatest number of publications was 2001 (12 publications), followed by 2011 (10 publications) and 2014 (9 publications).The average number of citations was 89.1 (standard error (SE) ± 18.0).The range was 1,230, and the median was 36 (interquartile range, 35.5).Analysis of the citations per year yielded a mean of 3.4 and a median of 2.0.The 10 most cited articles were published between 1992 and 2006, ranging from 183 to 1,321 total citations.The most cited article was "Semantic dementia: Progressive fluent aphasia with temporal lobe atrophy," with 1,578 total citations to date, including 51 self-citations.The article was published in 1992 (Table 1    Our analysis indicates that there was a significant association between Scientific Journal Rank (SJR) 2021 and the total number of citations (Table 2).For every 1-point increase in SJR, there were 56.4 additional citations (p<0.01).A similar trend was noted in Scopus' CiteScore (2022) value which indicated that for every 1-point increase in CiteScore, there were 11.4 additional citations (p<0.05).A similar association was appreciated when analyzing average citation per year.For every 1-point increase in SJR, there were 1.9 more average citations per year (p<0.05) and for every 1-point increase in CiteScore, there were 0.4 more average citations per year (p<0.05).*Three article anomalies were excluded from this analysis due to a low number of citations in an impactful journal: Klüver-Bucy Syndrome: Successful Treatment With Carbamazepine [61], Amygdalectomy impairs crossmodal association in monkeys [14], Visual discrimination impaired by cutting temporal lobe connections [58].

Journal of Publication
The top 100 cited articles were published in 10 journals (Table 3).The Journal of Neurology published 7% of the articles, followed by Brain (4%).The 2021 SJR for these two journals was 2.6 and 4.6, respectively, while the 2020 Impact factors were 9.9 and 13.5, respectively.

Discussion
KBS is a rare neuropsychiatric disorder in which destruction of bilateral temporal lobes and amygdala causes hypersexuality, amnesia, visual agnosia, bulimia, hyperorality, hypermetamorphosis, and placidity [1,4].Partial KBS is defined as having at least three of these symptoms.

Pathophysiology
Multiple papers have described the pathophysiology of KBS, including Alzheimer's disease, herpes simplex encephalitis, stroke, and head trauma [2,3].Herpes simplex virus is known to cause dysfunction of the temporal lobes.Costa et al. [2] wrote a case report of a 21-year-old man who developed KBS.This patient presented to the emergency department with seizures.The patient's MRI revealed bilateral temporal lobe lesions and the patient had positive herpes simplex 1 IgG and IgM antibodies.Once the patient's neurologic deficits had resolved, he developed the symptoms of KBS.Al-Attas et al. [104] reported a case of a male who developed KBS after a non-dominant middle cerebral artery stroke.The middle cerebral artery feeds the temporal lobes; therefore, the lesion resulted in behaviors consistent with KBS.Alzheimer's disease is known to cause cortical atrophy.When the amygdala and temporal lobes are affected, KBS can occur [74].
The first reported patient that was described to have KBS had a bilateral temporal lobectomy for the treatment of epileptic seizures [105].

Presentation in Adults vs Children
In 1998, Pradhan et al. [46] described the presentation of KBS in young children who had no previous exposure or educational teachings about sex.The study focused on seven pre-pubertal patients, ages 2.5 to 6 years, who developed KBS as a sequela of herpes simplex encephalitis.The presentations ranged from 10 months to 5.5 years after infection.Incomplete KBS was more likely than complete syndrome, although patients displayed a majority of the symptoms of complete syndrome.All patients displayed alterations in emotions, exemplified by a loss of attachment to family members as well as a range of dispositions from abnormally cheerful to irritable.Dietary changes were also noted with cases of bulimia.Hyperorality was described through a strong propensity to place non-food objects in their mouth.Children displayed hypersexuality in a different way than adults; these manifestations included intermittent pelvic thrusting and fixation on their genitals through frequent holding and rubbing of genitals when in a prone position.Hypermetamorphosis, or easy distractibility through visual stimulation, was found in three of the seven patients.Patients also had abnormal sporadic sharp or spike waves arising from the temporal lobe in sleep electroencephalogram findings.In all patients, the manifestations of the syndrome declined over time [46].
In their 2015 study, Shapiro et al. [77] described Sanfilippo syndrome Type A as a variant of KBS.Sanfilippo syndrome is caused by deficient activity of lysosomal enzymes that result in a degradation of heparan sulfate with symptoms such as progressive dementia, aggressive behavior, hyperactivity, and seizures.Of the four variants of Sanfilippo syndrome, Type A was considered to be the most prevalent.Aggression and a lack of regard for dangerous situations distinguished Type A from other forms of Sanfilippo syndrome that also included cognitive impairment.Measurable volume loss in cortical and subcortical gray matter, particularly in the amygdala, was also seen in these children.The findings suggest that KBS can manifest through different pathophysiological mechanisms and with different presenting symptoms than those previously reported in adults.

Treatment and Management
Current treatments for KBS include symptomatic management with antipsychotics, mood stabilizers, carbamazepine, and SSRIs [1].Multiple papers have described successful treatment of the symptoms with carbamazepine [61,72].Lanska [106] described treatment of KBS as "difficult and unsatisfactory", given that there is no specific medication that can fully resolve the symptoms of KBS.
Management of Kluver-Bucy syndrome revolves around symptomatic management.
Ott [42] found that the sequelae of temporal lobe lesions may vary in both their severity and presentation, presenting an opportunity for specialized treatment modalities.For example, the use of beta-blocker Propranolol was found to be effective in quelling verbal and physical aggression, while gonadotropinreleasing hormone antagonist Leuprolide effectively controlled hypersexual and inappropriate behaviors.Stewart [72] and Hooshmand et al. [61] highlighted the effectiveness of the anti-seizure medication carbamazepine in symptoms and demonstrated a dramatic reduction in unprovoked episodes of rage.The effect of SSRIs was also investigated and found to have a positive effect on the overall constellation of symptoms [42,76].
Documented cases vary in the etiologies of temporal lobe lesions, which could play a role in the varied outcomes of various treatment modalities.Larger sample sizes with more standardized treatment protocols are indicated to assess the efficacy of individual treatment options and which symptoms they best target, if not all.

Publication Trends
Since 1937, the publications on KBS have steadily increased, with up to six publications a year in 2002.This study is the first bibliometric providing a detailed analysis on the top 100 most cited articles in the study of KBS.The analysis included the most cited publications, authors, countries, and institutions contributing to the field of KBS research.The analysis also included average citations per year to account for the effects of earlier publications on total number of citations.Currently, there are no NIH grants funding research on KBS.The Genetic and Rare Disease Information Center has minimal information about the disorder [107].
In 1937, Heinrich Klüver and Paul Bucy [108] expanded on experiments from 1881, noting that the removal of temporal lobes in the Macacus rhesus yielded dramatic behavioral changes, including visual agnosia, oral fixation, hypersensitivity to visual stimuli, increased sexual activity, and changes in dietary habits.In 1955, Dr. Hrayr Tersian and Dr. Giuseppe D. Ore [11] first documented similar findings in humans who had a temporal lobectomy.Since that time, research on KBS has steadily increased, with peak research activity between 2000 and 2009 (Figure 1), suggesting that a majority of impactful research on KBS has occurred in the last two decades.

Top Cited Publications
The top cited article, "Semantic Dementia: Progressive fluent aphasia with temporal lobe atrophy" by Hodges et al. [4] was published in Brain in 1992.The paper had 1,578 total citations and 1,321 non-selfcitations, with 51 citations per year.The study described the progression of language decline in patients with anterior inferior temporal lobe conditions, discussing KBS as symptoms that developed after suspected Alzheimer's disease or Pick's disease.The second most cited article in this analysis was "Visual neurones responsive to faces in the monkey temporal cortex" [5], published in 1982 in Experimental Brain Research.The article had 872 non-self-citations with an average of 23 citations per year.The study discussed that 48 neurons in the superior temporal sulcus were most important in arousal, emotional and motor reactions, which can explain how temporal lobe damage can lead to KBS [5].The next paper discussed how the "social brain", including the amygdala, can show that deficits such as KBS can be a model of autism [6].
The bibliometric analysis reflected that most articles came out of the United States, showing that there

Limitations
Inherent limitations to bibliometric analyses include limited availability, exclusion of certain formats of publications such as conferences or textbooks, and difficulty in parsing apart authorships.Moreover, newer articles may not have had adequate time to garner enough citations for inclusion in the "top 100" analyses.Focusing our search through Scopus has its limitations of being a singular database to collect the data.KBS is a rare condition, mainly discussed in case reports and series, another limitation of our study.

Conclusions
In conclusion, we demonstrated the relevance and understanding of KBS in recent literature through our bibliometric analysis of the 100 most cited research articles on KBS.Further research on KBS is warranted, especially with the purpose to find more effective, therapeutic options.

FIGURE 1 :
FIGURE 1: Chart detailing the trends of the number of publications per year from 1955 to 2015

FIGURE 2 :
FIGURE 2: Map detailing the distribution of Top Cited Articles by Country of Origin.The United States has published 58% of the top cited articles.Created on Excel Powermap, Excel, 2023

FIGURE 5 :
FIGURE 5: Chart detailing the authors with the most papers published on Kluver-Bucy Syndrome.James A. Horel had the most publications on the subject with six articles. ).

TABLE 3 : Table listing the top journals publishing papers on Kluver-Bucy Syndrome.
higher incidence of KBS in the US with more research done on the disorder.VA Medical Centers and SUNY Upstate Medical University published the greatest number of articles, furthering our knowledge of this rare disease.