Brucellosis is a global burden causing 500,000 infections per year worldwide [1]. Brucellosis is an emerging zoonotic infection and has widespread geographical distribution [2]. Since brucellosis is a systemic infection, Neurobrucellosis is a rare but important presentation of brucellosis [3]. Neurological manifestations can present as meningoencephalitis, polyradiculopathy, peripheral and cranial neuropathies (Abducens, facial and vestibulocochlear cranial nerve involvement being more common), demyelinating syndromes, psychiatric disturbances [4,5]. In most of the cases, diagnosis of neuro brucellosis is usually made after 2-12 months of symptom onset [6]. In our case 2 days duration of fever which is followed by bilateral hearing loss on 4^th day, proximal muscle weakness on 5^th day and gradually during the course of hospital stay patient was diagnosed to have coagulase negative staphylococcus species positive native valve infective endocarditis.

A 48-year-old female from rural Karnataka (INDIA) presented to medicine OPD with complaints of history of fever 2 days back, currently afebrile, occasional headache, nausea, vomiting, giddiness with mild swaying and no neurological deficits. She was treated for the same from local doctor near her home. 

On examination, blood pressure was 144/80 mm Hg and pulse rate 104/min, temperature 98°F, Dixhalpike’s maneuver negative, Rhomberg’s positive, tandem gait positive, no nystagmus and rest of the neurological examination was normal. 

After admission on 2^nd day patient developed decreased hearing, severe headache, high degree fever, and developed exanthematous rashes on both legs after 4 days of fever followed by on both forearms sparing palms and soles, focal neurological examination was normal. 

On 3^rd day  high degree fever 102°F, 103° F, spikes associated with headache, decreased hearing, difficulty in going to bathroom, power in both proximal lower limbs muscles was +3/5, neck stiffness was present other systems were normal. On investigating, OX-2 came positive, doxycycline 100 mg BD was started in view of rickettsia infection.

MRI brain showed evidence of demyelinating plaques in right dentate nucleus, subcortical white matter of left parietal region and the right posterior limb of internal capsule, non-enhancing lesion on contrast. 

Figure 1: Erythematous rashes on both legs vegetations on mitral valve

Investigations showed evidence of brucellosis (Latex agglutination test positive). Retrospectively history of intake of unpasteurized cow milk was found. Rifampicin 600 mg OD was added. Intravenous amikacin and meropenem 1gm TID and doxycycline 100 mg BID were started. CSF analysis showed high protein, normal glucose, normal ADA levels, cell count-170 with 95% lymphocytes. 

Figure 2: Temperature chart showing fever spikes

Fundoscopy showed Roth’s spot. 2D ECHO was done and was found to be normal. Both ear examination, rhinne’s showed AC>BC, weber was lateralized to left ear, Absolute Bone Conduction (ABC) was decreased in both the ears and intact tympanic membrane. MRI SPINE was found to be normal. 

Repeat 2D ECHO was done on day 06 to rule out endocarditis, as fever spikes were still there, it came out to be normal.

Figure 3: Temperature normalized after treatment

On 7^th day patient generalized condition started improving, power of lower limb improved to 4/5, hearing improved by 50%, neck stiffness also reduced. Tb PCR and CSF CBNAAT came negative, ANA PROFILE was negative.

On 9^th day patient 2^nd blood culture report came out as coagulase negative staphylococcus species (CoNS) positive. As there was growth of CoNS, with high index suspicion of infective endocarditis, repeat 3^rd  echo  was  done,  and  it  showed  1-2  mm  multiple vegetations on mitral valve and few vegetations on aortic valve (RCC).

Figure 4: Demyelinating lesion in right dentate nucleus

Injection Teicoplanin was added as per culture sensitivity. Three different samples from different venipuncture sites were sent for blood culture. No evidence of immune or vascular MHA-microcytic hypochromic anemia, TG: toxic granules, CONs: coagulase negative staphylococcus phenomena noted on examination. Over course of the hospital, patient developed urinary tract infection as patient had urinary retention and self-catheterization was done and was discharged in a state of good health.

As per culture, injection Teicoplanin was given intravenously for 30 days gentamycin for 21 days for infective endocarditis and rifampicin and doxycycline for brucellosis was given with monitoring for renal function. A repeat CSF analysis was done after 45 days of antibiotics and showed normal picture.

Figure 5: Demyelinating lesion in posterior limb of right internal capsule

Brucellosis is a zoonotic infection caused by bacterial genus Brucella. It is a major public health problem worldwide and is the most common zoonotic infection [1]. Brucellae are aerobic gram-negative coccobacilli that has unique ability to invade both phagocytic and nonphagocytic cells and to survive in intracellular environment.

Brucella bacteria may affect the nervous system directly or indirectly, as a result of cytokine or endotoxin on the neural tissue. Cytotoxic T lymphocytes and microglia activation play an immunopathologic role in this disease. Infection triggers the immune mechanism leading to a demyelinating state of cerebral and spinal cord [7]. Hearing loss due to vestibulocochlear nerve involvement, deep grey matter involvement, and extensive white matter lesions on neuroimaging mimicking demyelinating disorders seems to be unique for brucellosis [8].

Figure 6: Normal appearance of MRI Spine 

Figure 7: 2D ECHO showing multiple vegetations on mitral valve

In our case a 48-years-old lady presented with history of fever, nausea, giddiness and erythematous rashes with OX-2 positive, but no history of tick bite or eschar mark. And further even after starting doxycycline, deafness, proximal myopathy, meningitis and high degree fever did not subside. ENT examination pointed towards central cause of hearing loss. Audiometry could not be performed due to technical reasons. As patient had fever, headache, elevated protein and lymphocytosis on CSF analysis, similar picture can be seen with tubercular meningitis. Since brucella was positive and natural history was not suggestive of TB and patient responded to treatment without starting antitubercular treatment and steroids, clinical diagnosis of neurobrucellosis was made. Further MRI brain showed demyelinating changes. 

Since demyelinating changes in brain white matter and hearing loss were not explainable with tuberculosis (Tb PCR and CBNAAT negative) or rickettsia infection. 

Considering her serology for brucella, clinical presentation, brain imaging and response to chemotherapy, a diagnosis of neurobrucellosis was made. The criteria to diagnose neurobrucellosis includes 

• neurological dysfunction not explained by other neurological disease, 

• abnormal CSF indicating lymphocytic pleocytosis and increased protein, 

• positive CSF culture for Brucella organisms or positive Brucella IgG agglutination titre in the blood and 

• CSF, response to specific chemotherapy with a significant drop in the CSF lymphocyte count and protein concentration [9] 

Our patient fulfilled the above mentioned criteria. Although Brucella titre in this patient was 1:80 in this patient but it was considered significant because of patient’s clinical presentation which got improved after therapeutic treatment for Brucella. 

Patient’s continuous spikes of fever and second blood culture being positive for coagulase negative staphylococcus species, prompted us to look for ongoing active source of infection and, a repeat 2D ECHO showed vegetations     on      heart     valves.     So,      diagnosis       of  neurobrucellosis with coagulase negative staphylococcus species septicemia was made and infective endocarditis based on the modified Duke’s criteria [10].

Patient was then treated aggressively with antibiotic teicoplanin as per sensitivity to CoNS for 3 weeks  and improved drastically with this treatment. Repeat 2D ECHO was done after 2 weeks of treatment, vegetations were decreased and no valvular abnormality seen. Patient was discharged with no fever, normal muscle power and normal hearing. Treatment for neurobrucellosis was continued for 6 weeks.A repeat CSF analysis which was done after 45 days showed normal picture.

Clinical Significance

A high clinical suspicion can lead to diagnose a case of neurobrucellosis with atypical features and hunt for persistent high degree fever lead to diagnosis of infective endocarditis. Meticulous use of timely antibiotics saved the life of the patient and prevented all complications of infective endocarditis which could have endangered patient’s life.

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3. McLean, D.R., et al. “Neurobrucellosis: Clinical and Therapeutic Features.” Clinical Infectious Diseases, vol. 15, no. 4, 1992, pp. 582–590.

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8. Rajan, R., et al. “Teaching NeuroImages: Deep Gray Matter Involvement in Neurobrucellosis.” Neurology, vol. 80, no. 3, 2013, pp. e28–e29.

9. Kochar, D.K., et al. “Meningoencephalitis in Brucellosis.” Neurology India, vol. 48, no. 2, 2000, p. 170.

10. Li, J.S., et al. “Proposed Modifications to the Duke Criteria for the Diagnosis of Infective Endocarditis.” Clinical Infectious Diseases, vol. 30, no. 4, 2000, pp. 633–638, https://doi.org/10.1086/313753.