Brucella meningoencephalitis with hydrocephalus masquerading as tuberculosis
ABSTRACT Neurobrucellosis is a rare form of localized brucellosis usually with no systemic manifestations. We report a rare case of brucellosis presenting as meningoencephalitis associated with hydrocephalus. This patient had a lymphocytic predominant CSF and was initially treated with empirical anti tubercular therapy and steroids. A week later, when his CSF culture grew Brucella species, the treatment was changed to a combination of streptomycin, doxycycline and rifampicin and the patient improved with this therapy. This case illustrates the need to consider neurobrucellosis as a close differential diagnosis of neurotuberculosis in endemic areas when the patient presents with meningo encephalitis with lymphocytic CSF
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ABSTRACT: A new designed Autonomous Underwater Vehicle r2D4 for operation to 4,000 meters was built for the purpose of seafloor mapping on the oceanic ridge having hydrothermal activity in July 2003. An expanded interferometry sonar with operating frequencies of 100 kHz was installed on the AUV for high resolve bathymetry mapping, not to mention the backscatter imaging. In effect, the interferometry sonar is simply composed of three hydrophones, which are arranged at intervals of three and thirteen wavelengths in the L-shape at each side, in addition, to a side scanning sonar Klein System 2000 with operating frequencies of 100 kHZ and 500 kHz. It explains features of low cost and low power consumption. An initial survey test of the AUV was carried out up to 500 meters deep off Ryotsu port of Sado Island in July 2003. In advance of the sea test of the AUV, a test of the interferometry sonar with the barge had been carried out. L-shape array of hydrophones enables us to make a phase difference measurement successfully with high resolution. It follows that a detailed swath bathymetry was brought about. Consequently, a seafloor mapping was carried out to reveal the detail topography on the top of Kuroshima knoll in the vicinity of Okinawa islands in December 2003. The AUV is installed with the PHotonic Inertial Navigation System (PHINS), which provides inertial navigation and motion measurements of the AUV. Furthermore, since the AUV is able to move underwater very stably along planed courses, it is a proper platform in materializing the synthetic aperture of the side scanning transducers. We have been devoting ourselves to process the observation data. As a result, the synthetic aperture technique was very useful for the improvement of the seafloor bathymetry mapping as expected.Underwater Technology, 2004. UT '04. 2004 International Symposium on; 05/2004
Asian Pacific Journal of Tropical Medicine (2010)835-837
Brucella meningoencephalitis with hydrocephalus masquerading as
*, Bekur Ragini, Abdul Razak, M Mukhya prana Prabhu
Department of Internal Medicine, Kasturba Medical College, Manipal, Karnataka, India
Contents lists available at ScienceDirect
Asian Pacific Journal of Tropical Medicine
ARTICLE INFO ABSTRACT
Received 12 July 2010
Received in revised form 17 August 2010
Accepted 15 September 2010
Available online 20 October 2010
*Corresponding author: Dr.Vishwanath Sathyanarayanan, #1, OPD Block, Department
of Internal Medicine, Kasturba Medical College, Manipal-576104, Karnataka, India.
Brucellosis rarely presents with involvement restricted
to nervous system. Human brucellosis especially
neurobrucellosis is rarely reported in India, where animals
are raised in large numbers with low hygiene and hence
the disease is expectedly endemic. Clinical spectrum of
neurobrucellosis is varied, several areas of the nervous
system, both central and peripheral can be involved.
Identification of the specific neurologic syndromes is
important as the response to treatment is better in the acute
form when compared to the chronic form, which is more
indolent and requires longer duration of therapy. No clear
cut classification system exist till date for the spectrum of
clinical syndromes is quite varied. In this rare case report
of neurobrucellosis, we also discuss regarding the existing
classification systems and a short review of treatment
recommendations existing till today. Awareness of the
conditition and performance of appropriate serological and
microbiological tests will differentiate neurobrucellosis from
chronic infections especially tuberculosis.
2. Case report
A 29 year old shop-keeper with post-polio flaccid
paralysis of both lower limbs was brought to the emergency
department with altered sensorium for the past 1 day.
There was history of intermittent fever since 2 months.
Fever used to be there for 1-2 days, followed by afebrile
period for 4-5 days only to recur again. History of loss
of appetite, night sweats and loss of weight were also
present. No history of headache, vomiting or joint pain.
There was history of cattle rearing but no consumption of
raw milk from cows. On examination he was conscious,
febrile (100ºF), not verbalizing or obeying commands,
pulse was 70/min, respiratory rate was 18/min, SpO2 98%
on room air and BP was 140/80 mmHg. Head was turned
to right side with clenched teeth and tonically flexed
upper limbs noted. Pupils were 3 mm symmetrical in
size but not reacting to light and marked neck stiffness
was present. Cardiovascular, respiratory and abdomen
examination were normal. Bystanders claimed this state
since the last night. The clinical condition was suspected
to be status epilepticus secondary to meningoencephalitis.
With intravenous diazepam seizure aborted and he was
Neurobrucellosis is a rare form of localized brucellosis usually with no systemic manifestations.
We report a rare case of brucellosis presenting as meningoencephalitis associated with
hydrocephalus. This patient had a lymphocytic predominant CSF and was initially treated
with empirical anti tubercular therapy and steroids. A week later, when his CSF culture grew
Brucella species, the treatment was changed to a combination of streptomycin, doxycycline and
rifampicin and the patient improved with this therapy. This case illustrates the need to consider
neurobrucellosis as a close differential diagnosis of neurotuberculosis in endemic areas when the
patient presents with meningo encephalitis with lymphocytic CSF.
Vishwanath Sathyanarayanan et al./Asian Pacific Journal of Tropical Medicine (2010)835-837
Full blood count revealed WBC count 15 400/cumm, 80%
neutrophils.The blood biochemistry, urine routine, chest
X-ray and ECG were normal.A CT head (Figure 1) showed
mild hydrocephalus with meningeal enhancement. A
guarded lumbar puncture was done. CSF analysis showed
160 WBCs with 99% lymphocytes. CSF-glucose was low (29
mg/dL), protein was high (157 mg/dL). Cerebrospinal fluid-
adenosine deaminase activity (CSF-ADA) was 21 IU/L. CSF-
PCR for Mycobacterium tuberculosis was negative. Patient
was started on empirical antitubercular therapy in view
of 2 months history of fever, meningitis, communicating
hydrocephalus and lymphocytic predominance of CSF, with
four drugs [Isoniazid (H), Rifampicin(R), Pyrazinamide (Z)
and Ethambutol (E)] and dexamethasone and Ceftriaxone.
Serum was tested for Brucella agglutinins by standard tube
agglutination test (STAT) and the titer was 320. A week
later, Brucella species was isolated from CSF by BacT/Alert
automated blood culture system.
Figure 1. Computed tomography of brain.
It shows meningeal enhancement and mild hydrocephalus.
Following the laboratory confirmation, case was re-
evaluated as neurobrucellosis and HZE stopped and
dexamethasone continued in view of hydrocephalus and
tapered. Streptomycin(S) 750 mg/day i.m was started along
with oral doxycycline 200 mg/day. The dose of rifampicin
was increased to 600 mg/day and ceftriaxone was continued.
Fever subsided, disorientation improved and he started
obeying commands from the second day. Seizures did not
recur during the recovery period that extended to four weeks.
Streptomycin was stopped after two weeks and ceftriaxone
stopped after four weeks and then he was discharged
symptom free after four weeks. Rifampicin and doxycycline
were continued. He was reviewed after one month as an
out-patient and found to be symptom free. He was advised
to continue rifampicin and doxycycline for 4 more months.
Lumbar puncture was repeated after 6 months and CSF sent
for culture was reported as sterile. Hence treatment was
Brucellosis is a well known zoonosis endemic in
Mediterranean, Middle east, Africa Latin America and
South west Asia. Humans acquire infection commonly
through consumption of unpastuerised dairy products and
rarely via cuts and aerosols. Majority of human disease has
been due to Brucella melitensis. Localized involvement of
nervous system (neurobrucellosis) has been observed in only
wide. Nervous system can be involved in various stages
of brucellosis i.e. at the onset, during the course of illness,
convalescence or months after recovery from acute infection.
The effect on nervous system can be due to direct effect
of bacilli, cytokines or endotoxins on peripheral nerves,
spinal cord, meninges and brain. The whole spectrum of
neurological manifestations include meningitis(M)/meningo-
encephalitis(ME) as the most common manifestations and
rarely cranial neuropathies, peripheral neuropathies, chorea,
demyelination, transient ischemic attacks, and psychiatric
In 2009, pooled analysis of 187 neurobrucellosis cases with
varied presentation of neurobrucellosis mimicking various
pathologies hence a thorough evaluation of patients is
crucial. Neurobrucellosis presenting as acute psychosis,
thalamic infarction, and spastic paraparesis have been
reported. First case of neurobrucellosis associated with
hydrocephalus was described by Guney F et al in 2008 after
consumption of fresh sheep cheese, stressing the need to
consider neurobrucellosis in any case of hydrocephalus
especially from endemic areas of brucellosis. In 2006,
Turkish experience based on 452 cases of spinal brucellosis
found that the clinical and radiological features are atypical
and non specific hence difficulty in identifying them, CT/
up. Epidemiological, clinical and imaging findings in
brucellosis with osteoarticular involvement by Poubagher
et al found that MRI is the method of choice for diagnosing
osteoarticular and spinal complications of human brucellosis
and the closest differential diagnosis for tubercular
spondylodiskitis is brucellosis.
Neurobrucellosis is less commonly reported disease
in India although animal brucellosis and seroprevalence
in specific areas is well reported. Extensive
meningoencephalitis, retrobulbar neuritis and pulmonary
involvement was reported from Lucknow. In 2007,
hospital based case series of 175 cases of serologically,
confirmed cases of brucellosis in Bikaner, Northwest India,
the incidence of neurobrucellosis was 18.86%. Recently
there are no much reports of cases of neurobrucellosis
although incidence of brucellosis is on rise. Majority of
people with cattle rearing profession reside in rural India
have decreased access to tertiary care centre and lack of
awareness among primary care physicians where no specific
data regarding incidence and prevalence in humans exist,
though theoretically expected to be endemic. Brucellosis
closely mimics tuberculosis in its presentation including
neurobrucellosis. It is confused for tuberculosis.
Diagnosis of neurobrucellosis rests in neurological
symptoms usually unaccompanied by systemic
manifestations, positive CSF culture or blood serology and/or
positive CSF culture, and CT/MRI abnormalities are variable.
3-5% of cases in most of the case-series reported world-
35 publications from Turkish medical practice revealed
MRI of spine may be sensitive for diagnosis and follow
Vishwanath Sathyanarayanan et al./Asian Pacific Journal of Tropical Medicine (2010)835-837
Al Sous MW et al found three types of imaging abnormalities
in central nervous system in case of neurobrucellosis-
inflammation, white matter changes and vascular insult.
The white matter changes may mimic other inflammatory/
infectious disease such as multiple sclerosis, acute
disseminated encephalomyelitis/Lyme disease. Only one
case of neurobrucellosis associated with hydrocephalus as a
radiological feature of neurobrucellosis has been reported.
Patients with unexplained neurological and psychiatric
symptoms from endemic areas should raise suspicion of
neurobrucellosis. For rapid diagnosis of neurobrucellosis
light cycler based real time polymerase chain reaction
based assay in CSF samples is more rapid and sensitive than
conventional microbiological tests.
Treatment of brucellosis is complex requiring
protracted administration of more than one antibiotic.
Recommendations in 2006 suggested that treatment of
uncomplicated brucellosis in non-pregnant adults should
be based on a six week regimen of doxycycline combined
with either streptomycin for two to three weeks or rifampicin
for six weeks. Systematic review and meta analysis of
randomized controlled trials in 2008, found that the preferred
treatment in brucellosis should be with dual/triple regimens
including an aminoglycoside. Doxycycline and rifampicin
readily penetrate the blood-brain-barrier (BBB) and
achieve good CSF concentrations. Concentrations of amino-
glycosides in CSF are therapeutic only when meninges
are inflamed. In a new case, when the initial presentation
is M/ME, it is wise to consider other common causes and
challenge them empirically, until the results of diagnostic
work-up arrive. Thus ceftriaxone remains an important
initial drug[1,17]. Ceftriaxone is active against brucella in
vitro, but results of in vivo studies have not been compelling.
Given the benefit of doubt, it becomes necessary to include
ceftriaxone in the initial treatment regimen as it achieves
good concentration in CSF.
Neurobrucellosis generally needs prolonged therapy for
case-series on neurobrucellosis have still suggested that
treatment duration has to be individualized, which seems
reasonable as the spectrum of neurological manifestations
is diverse. Steroids are warranted in special circumstances
like our case where there was hydrocephalus. Other
manifestations requiring steroids include papilledema,
cranial neuropathies, myeloradiculitis, raised intracranial
pressure and optic neuropathy.
This case presented as pyrexia of unknown origin, with
sudden involvement of central nervous system proved to be
due to brucellosis can be easily confused with tuberculosis
with fever, loss of appetite, weight loss, meningeal signs,
clinical suspicion coupled with appropriate microbiological
investigations will improve level of case detection. It will
be reasonable to consider neurobrucellosis as differential
diagnosis in such circumstances.
In conclusion, in any case of meningitis or meningoencephalitis
with lymphocytic predominance in CSF neurobrucellosis is an
important close differential diagnosis to neurotuberculosis
in endemic places. Though antitubercular drugs are
active against Brucella, diagnosis becomes important as
neurobrucellosis needs prolonged therapy with those specific
drugs that attain good CSF concentration to exert their
bactericidal activity. And high index of clinical suspicion
3-6 months, but no large trials exist. A recent review of most
CSF picture and CT feature of hydrocephalus. High index of
coupled with appropriate microbiological investigations will
improve level of case detection.
Conflict of interest statement
We declare that we have no conflict of interest.
 Pappas G, Akritidis N, Christou L. Treatment of neurobrucellosis
what is known and what remains to be answered. Expert Rev Anti
Infect Ther 2007; 5(6): 983-90.
 Haji AM, Rasooli NM, Jafari S, Hasibi M, Soudabakhsh A.
Clinical and laboratory findings in neurobrucellosis: review of 31
cases. Arch Iran Med 2008; 11(1): 21-5.
 Gul HC, Erdem H, Bek S. Overview of neurobrucellosis: a pooled
analysis of 187 cases Int J Infect Dis 2009; 13(6): e339-43.
 Ates MA. Acute psychosis due to neurobrucellosis: a case report.
Anatolian J Psychiatry(Anadolu psikiyatri Dergisi) 2008; 9(3):
 Thomas J, Uta K, Reinhard B, Jochen L, Karl JB. Neurobrucellosis
with thalamic infarction: a case report. Neurol Sci 2008; 29(6):
 Sibel K, Yousuf ZD, Mehmet K, Meliha T. Acquired progressive
spastic paraparesis due to neurobrucellosis: a case report. Acta
Neurol Belg 2007; 107: 118-21.
 Guney F, Gumus H, Ogmegul A, Kandemir B, Emlik D, Arslan
U, et al. First case report of neurobrucellosis associated with
hydrocephalus. Clin Neurol Neurosurg 2008; 110(7): 739-42.
 Turgut M, Turgut AT, Kosar U. Spinal brucellosis: Turkish
experience based on 452 cases published during the last century.
Acta Neurochir(Wien) 2006; 148(10): 1033-44.
 Pourbagher A, Pourbagher MA, Savas L, Turunc T, Demiroglu
YZ, Erol I, et al. Epidemiological, clinical and imaging findings
in brucellosis patients with osteoarticular involvement. AJR Am J
Roentgenol 2006; 187(4): 873-80.
 Priyanka V, Maneesh KS, Ravindra KG, Atul A. Extensive
meningoencephalitis, retrobulbar neuritis and pulmonary
involvement in a patient of neurobrucellosis. Neurology India
2007; 55(2): 157-9.
 Kochar DK, Gupta BK, Gupta A, Kalla A, Nayak KC, Purohit SK.
Hospital-based case series of 175 cases of serologically confirmed
brucellosis in Bikaner. J Assoc Physician India 2007; 55: 271-5.
 Al Sous MW, Bohlega S, Al-Kawi MZ, Alwatban J, Mc Lean DR.
Neurobrucellosis: Clinical and neurological correlation. AJNR Am
J Neuroradiol 2004; 25; 395-401.
 Yetkin MA, Bulut C, Erdine FS, Oral B, Tulek N. Evaluation of
the clinical presentation in neurobrucellosis. Int J Infect Dis 2006;
 Colmenero JD, Queipo-ortuno MI, Reguera JM, Baeza G,
Salazar JA, Morata P. Real time polymerase chain reaction:a
new powerful tool for the diagnosis of neurobrucellosis. J Neurol
Neurosurg Psychiatry 2005; 76(7):1025-7.
 Ariza J, Bosilkovski M, Cascio A, Colmenero JD, Corbel MJ,
Falagas ME, et al. Perspectives for the treatment of brucellosis in
the 21st century: the Ioannina recommendations. PLoS Med 2007;
 Skalsky K,Yahav D, Bishara J, Pitlik S, Leibovici L, Paul M.
Treatment of human brucellosis: Systematic review and meta
analysis of randomized controlled trials. BMJ 2008; 336(7646):
 Gul HC, Erdem H, Gorenek L, Ozdag MF, Kalpakci Y, Avci IY,et
al. Management of neurobrucellosis;an assessment of 11 cases.
Intern Med 2008; 47(11): 995-1001.