Brucellar Psychosis

© Springer International Publishing Switzerland 2016
Mehmet Turgut, Fuad Sami Haddad and Oreste de Divitiis (eds.)Neurobrucellosis10.1007/978-3-319-24639-0_10

10. Brucellar Psychosis

Hamid Reza Naderi 

Department of Infectious Diseases, Mashhad University of Medical Sciences, Mashhad, Iran



Hamid Reza Naderi


The cognitive and mood disorders among neurobrucellosis patients are well documented. While neurobrucellosis is typically diagnosed by abnormal cerebrospinal fluid (CSF) analysis and detected specific antibodies in CSF, it is prudent to consider any case with unexplained psychological or mental disorder in the course of an active brucellosis as brucellar psychosis. The psychological manifestations of brucellosis can present in various clinical forms, and prompt antibrucellar antibiotic therapy should be started following the diagnosis of the infection by strong serological tests and/or isolation of the organism. The subject is especially concerning in the endemic areas where brucellosis is prevalent or whenever there is a history of exposure to Brucella species. The psychotic manifestations of a patient with active brucellosis improve by antibrucellar treatment, even without antipsychotic therapy.

NeurobrucellosisPsychosisCerebrospinal fluidAntibrucellar treatment





Twice a day


Cerebrospinal fluid


Central nervous system


Double strength


Criteria Diagnostic and Statistical Manual of Mental Disorders-IV




Enzyme-linked immunosorbent assay


Hamilton Depression Rating Scale




Microagglutination test


Minnesota Multiphasic Personality Inventory


Mini-Mental State Examination


Every night at bedtime


Standard agglutination test



10.1 Introduction

Edward Browne described a curious case in his famous “Arabian Medicine” back in 1920. He wrote: “A certain prince of the House of Buwayh was afflicted with melancholia and suffered from the delusion that he was a cow. Every day he would low like a cow, causing annoyance to everyone and crying ‘Kill me, so that a good stew may be prepared from my flesh’; until matters reached such a pass that he would eat nothing, while the physicians were unable to do him any good. Finally, Avicenna was persuaded to take the case in hand. First of all he sent a message to the patient bidding him be of good cheer because the butcher was coming to slaughter him, whereat, the sick man rejoiced. Some time afterwards Avicenna, holding a knife in his hand, entered the sick-room, saying ‘Where is this cow, that I may kill it?’ The patient lowed like a cow to indicate where he was. By Avicenna’s orders he was laid on the ground bound hand and foot. Avicenna then felt him all over and said: ‘He is too lean, and not ready to be killed; he must be fattened’. Then they offered him suitable food, of which he now partook eagerly, and gradually he gained strength, got rid of his delusion, and was completely cured” [10]. According to the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM)-IV criteria for specification of mental disorders, we shall assume that this case was an acute psychotic disorder not otherwise specified [33]. The diagnosis requires the presence of delusions, false implausible beliefs, hallucinations, or false perceptions that may be visual, auditory, or tactile [9] about which there is inadequate information to make a specific diagnosis or any disorder with psychotic symptoms that does not meet the criteria for any specific psychotic disorder [33]. The patient treated by Avicenna was a nobleman with no recorded preceding event for triggering his sudden bizarre behavior, and he was completely cured within 1 month of feeding and medication. Hence, it is likely that he suffered from a psychotic disorder due to a treatable medical illness, and it would not be farfetched to regard Avicenna’s case as the first possible case of toxic or septic encephalopathy presenting as acute psychosis described in the literature.

It has long been suggested that infection can affect the levels of neurotransmitters which is associated with septic encephalopathy development. During an infectious illness, the central nervous system (CNS) is one of the first organs affected and reciprocal interactions between the immune system and the CNS are considered to be major components of the host response in the process [12]. The evidence proposed immune and inflammatory cascades in conjunction with infection may play a role in the pathology [19]. Theoretically, circulating cytokines synthesized by an infectious trigger can diffuse through the blood–brain barrier, or they can act on their receptors in the CNS to modulate brain function [12]. However, one major limitation is related to the difficulty of proving causality. The interactions between infectious agents and host factors resulting in mental disturbance generally do not follow Koch’s postulates, which require that there be a one-to-one correspondence between the two entities [43]. According to Yolken and Torrey [43], the relationship between infectious agents and chronic diseases often does not follow the straightforward associations defined by Koch’s postulates but rather a number of factors, including the timing of infection, the nature of the infecting strain, and the genetic makeup of the host, can compromise the situation leading the infected subject to diverse clinical outcomes. Recently, Hayes et al. [19] examined molecular changes in the cerebrospinal fluid from patients with schizophrenia and at-risk mental status for psychosis exploring how infectious agents such as Toxoplasma gondii and herpes simplex type 1 affect these molecular changes, and they found the possible relationship of some inflammatory molecular signatures in the CSF to these disease-associated infections.

One of the earliest researchers who believed that microbial agents might be etiologically linked to psychotic disorders was Emil Kraepelin. In 1896, he addressed the dementia praecox as “a tangible morbid process of the brain caused by an autointoxication” [43]. Since then, numerous reports throughout the world have been published to present cases with infection-related psychoses supporting the infectious theory. Tuberculosis, typhoid fever, syphilis, toxoplasmosis, herpes simplex and cytomegalovirus infection, and cysticercosis are just a few infamous infectious diseases that have been linked to psychiatric disorders [3, 18, 20, 22, 26, 37, 39]. Interestingly, brucellosis caused by different Brucella spp. (B. abortus, B. canis, B. melitensis, and B. suis) is one of these infectious agents in which neuropsychiatric manifestations have raised much attention during the past decades. Neurobrucellosis was first reported by Hughes in 1896 [27]. The psychiatric changes in neurobrucellosis occur rarely, and there are few reports of brucellar psychosis in the literature [2, 4, 14, 23, 28].

10.2 Brucellar Psychosis

Although rarely seen, the spectrum of psychosomatic manifestations of patients with brucellosis is very diverse, and many authors presented cases with mental disabilities that ranged from subtle cognitive dysfunctions detected only by neuropsychological evaluation to apparent psychosis or schizophreniform disorders. The psychiatric manifestations, while rarely reported, were depression, amnesia, agitation, nightmares, personality disorders, euphoria, nervousness, loss of perception, disturbance of spontaneous and voluntary attention, disturbances in process of thinking with poverty of content, hallucination, delirium, convulsion, dysarthria, psychosis, and night raving [14, 17, 23, 30]. In a study by Shehata et al. [35], 38.5 % of patients with brucellosis without apparent neurological symptoms had depression or cerebellar affection, in addition to significant impairments in some cognitive function, as mental control, logical memory, and visual reproduction in comparison with control group. In this study, depression was detected in seven patients (29.2 %); three of them have evident neurobrucellosis, whereas four were apparently without any neuropsychiatric involvement [35]. Depression is significantly more present in patients with brucellosis without marked neurological symptoms than in patients with apparent neurological manifestations. The explanation of that could be relied on the mechanism of depression in these patients whose altered moods point to different mechanisms such as direct effect of the organism or its products on the meninges and brain [1, 35]. Alapin [2], in his extensive review of neurological aspects of brucellosis, wrote that “many papers underline the commonness of neurological and psychotic complications with infection by B. melitensis. There is an option that B. abortus produce a much lower percentages of neuro-psychiatric complications than B. melitensis or B. suis” [2, 38]. Roger and Poursines [31] classified the neuropsychiatric manifestations of brucellosis as “psychotic encephalitis of the pseudo-tumoral form” and “different psychological disorders” with psychasthenia as the most common form for a late course of chronic brucellosis.

According to Alapin [2], multiple cases were diagnosed as neurasthenia, psychasthenia, or depression during the course of chronic brucellosis without an acute period. Evans [15] called this state “a ramshackle feeling” (in French: patraquement) and Janbon and Bertrand “subjective syndrome of chronic brucellosis.” Those subjective symptoms were headaches, tiredness/fatigability both physical and mental, insomnia in the evening as well as early awakening, increased nervous sensibility, sexual troubles, as well as pains and aches without easy explanation. Those symptoms sometimes increased to complete psychic asthenia, incapacity of concentration, troubles of memory, irritability, exaggeration of emotions, and depressive states. Such a state is much more expressed in persons who, even before infection, showed immaturity or inadequacy of personality [2].

While these authors represented depression as the most common manifestation of brucella mental disturbances, some like Imboden believed that depressive mood is part of a fatigue syndrome accompanied by any chronic illness rather than a specific representation of neurobrucellosis, which manifests significantly more often in cases who suffer from other psychological traumatic experiences and personality or mood disorders. In one study, he compared eight patients with brucellosis who had recovered in 2 or 3 months, with 16 who were still symptomatic after 1 year with such complaints as fatigue, headache, nervousness, and vague aches and pains. All, but one, were males. There were no differences between the two groups in medical findings at onset or at time of reexamination. The 16 who were still ill, however, differed significantly from the eight who had recovered with respect to incidence of psychologically traumatic events in early life (69 % vs. 25 %), a seriously disturbed life situation within 1 year before or after the acute infection (69 % vs. 0 %), and significantly higher scores on an index of morale loss derived from the Minnesota Multiphasic Personality Inventory (MMPI) [21]. He described a patient who was visited 2 years after a treated acute brucellosis. He was an emigrant who suffered from depression, extreme fatigue, headaches, introversion, and asociality. His younger siblings were dead, and his parents left him alone and returned to their homeland before his illness. Another patient with the diagnosis of chronic brucellosis and symptoms of depression and lassitude was a heavy drinker who became a member of a religious order after his father died. His mood disorder did not improve even after the successful treatment of brucellosis. The authors debated whether these disturbed life-associated mood disorders were related to the diagnosis of brucellosis [25]. Conversely, Eren et al. [14] studied 34 neurobrucellosis cases and 30 patients with brucellosis without neurological involvement. The patients were evaluated by two psychiatrists, and the Hamilton Depression Rating Scale (HDRS) and Mini-Mental State Examination (MMSE) or Folstein tests were performed before the therapy and 1 and 2 weeks after the therapy. The psychiatrists interviewed the neurobrucellosis patients and diagnosed mild depression due to a general medical condition (neurobrucellosis) according to DSM-IV criteria in all of the cases. The mean score of MMSE among neurobrucellosis patients was 21.7 before the therapy. The improvement began in the first week of the therapy and reached a mean score of 24.3 at the end of the second week (p ≤ 0.001). The mean HDRS test score among neurobrucellosis patients was ten before the therapy and improved to 8.2 1 week later (p = 0.006) and to 5.2 2 weeks later (p = 0.001). On the other hand, among the brucellosis patients without neurological involvement, no significant changes of MMSE and HDRS test scores were observed. The test scores of neurobrucellosis patients were also compared with the scores of the patients without neurological involvement before the therapy. Test scores of HDRS were significantly different in two groups (p = 0.035), whereas test scores of MMSE were not (p = 0.351). They also found that the improvement in the MMSE scores in neurobrucellosis was significant (p ≤ 0.001), whereas in control group, it was not. The mild depression that was detected in neurobrucellosis patients after the psychiatric examination was improved at the end of 2 weeks (p = 0.001). On the other hand, among the brucellosis patients without neurological involvement, depression was not detected as HDRS test scores were within normal ranges. The significant difference between the HDRS scores in two groups (p = 0.035) supports the depression seen in neurobrucellosis. While no improvement of the scores was noticed among the patients without neurological involvement, the authors concluded that the cognitive and emotional disturbances among neurobrucellosis improve by antibiotic therapy, without any antidepressive or antipsychotic therapy [14]. Finally, it seems that although previous traumatic stress disorders during childhood as well as the current life-disturbing events can affect the extent and severity of the mood swings in brucella patients, the deleterious impact of the infection itself on their psychological symptoms and mental disabilities is a matter of serious concern.

10.3 Case Records

A wide variety of psychiatric symptoms ranging from memory deficits and mild personality changes to severe depression and frank psychosis have been described in patients with brucellosis. Alapin [2] claimed that the difference in severity of cases is due to such pathogenetic factors as extreme virulence of Brucella spp., constitutional somatopsychic predisposition of individuals, and the time of exposure to infectious process.

Almost all authors have pointed out that neuropsychiatric manifestations of brucellosis can display in every stage of the disease: as a presenting symptom in acute brucellosis [32], during the exacerbations mostly with febrile course [32, 38], or in chronic course, mainly many years after infection [2].

Alapin [2] presented two interesting cases with active brucellosis and paranoid personality disorder, which had persecutory delusions:

“He showed confusional state, was agitated, expressed multiple persecutory delusions and several ideas of reference (“they think that I am a Nazi … I am followed . . . trains were stopped to prevent my being on time”, etc.). During further observation he became lucid and then he was able to explain that during the acute phase he had visual and auditory illusions and hallucinations. The delusional syndrome slowly receded when treated with chlorpromazine but returned later … The CSF was normal and the electroencephalogram (EEG) showed rather a normal trace. The diagnosis of brucella encephalopathy with chronic paranoid psychosis and brucella peripheral poly-neuropathy was made.”

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Dec 11, 2016 | Posted by in NEUROLOGY | Comments Off on Brucellar Psychosis

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