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Year : 2000  |  Volume : 48  |  Issue : 2  |  Page : 170-3

Meningoencephalitis in brucellosis.

Department of Medicine, Neurology Division, S.P. Medical College, Bikaner, 334003, India.

Correspondence Address:
Department of Medicine, Neurology Division, S.P. Medical College, Bikaner, 334003, India.

  »  Abstract

Human brucellosis, more specifically neurobrucellosis, is a less commonly reported disease in India; although, animal brucellosis and seroprevalence in specific areas is well reported. We are reporting 4 cases of neurobrucellosis presenting as meningoencephalitis. Diagnosis was confirmed by serological test and agglutination titre was > 1:320 in all the patients. All these patients had close contact with animals and history of raw milk ingestion was present in 3 cases. The aim of presenting these cases is to create awareness among physicians while treating meningitis in persons, engaged in occupations related to brucellosis or having a history of ingestion of raw milk or milk product.

How to cite this article:
Kochar D K, Kumawat B L, Agarwal N, Shubharakaran, Aseri S, Sharma B V, Rastogi A. Meningoencephalitis in brucellosis. Neurol India 2000;48:170

How to cite this URL:
Kochar D K, Kumawat B L, Agarwal N, Shubharakaran, Aseri S, Sharma B V, Rastogi A. Meningoencephalitis in brucellosis. Neurol India [serial online] 2000 [cited 2021 Feb 26];48:170. Available from:

   »   Introduction Top

Brucellosis is endemic in the regions where animals are raised in large numbers, in the absence of correspondingly high level of hygiene. It is characterised by recurrent attacks of fever, hepatosplenomegaly, lymphadenopathy, joint pain particularly affecting sacroiliac, knees, ankles, elbows and shoulder joints. Less commonly it affects myocardium, lungs, kidney, brain, meninges and gonads.[1] Nervous system involvement can be categorized into central and peripheral forms. The former is commonly acute and is seen in about 5% of cases, resulting in meningoencephalitis, while the latter may either be acute or chronic in presentation.[2] We are reporting 4 cases of neurobrucellosis who presented as meningoencephalitis, during last one and half years, because of relative rarity of the disease in India.

   »   Case report Top

Case 1: A 50 years old woman was admitted in May 1997 with worsening altered consciousness of three days duration. She had moderate fever, backache, headache and vomiting for ten days prior to admission. Fever was moderate, remittent without chills and rigors and with no specific diurnal variation. Headache was global, continuous and pulsatile in nature, associated with vomiting, which was projectile in nature, for about 3 days prior to admission. Pain in the lumbosacral region was mild to moderate in severity, without any radiation and aggravation with movements. There was no history of convulsions. There was history of milking cows and goats daily and consumption of raw milk.
On examination, her pulse was 104/min, regular, blood pressure 110/70 mmHg, respiratory rate 20/ min and temperature of 100oF. She was anaemic but had no icterus, clubbing, lymphadenopathy, skin rash or joint swelling. Neurological examination revealed diminished consciousness with Glasgow coma scale of 5, neck rigidity and positive Kernig's sign. Pupils were equal and reacting to light. Fundus examination showed bilateral flexor plantar response. Cardiovascular and respiratory system were unremarkable. Mild hepatosplenomegaly was present. Blood examination revealed haemoglobin of 8.5 gm%, white cell counts 4500/mm[3] with normal differential count and ESR of 35 mm in 1st hour. Other investigations including renal and liver function tests were within normal limits. Peripheral blood film for malarial parasite was negative. Widal test, rheumatoid factor and LE cells were negative. Chest X-ray was normal. Standard plate agglutination test for brucellosis in serum was strongly positive with antibody titres of > 1:320. The antigen used for the diagnosis of brucellosis was strained, smooth suspension of killed bacterial antigen procured from Division of Biological Products, Indian Veterinary Research Institute, Izzatnagar (UP). This antigen gives positive reaction both for Br. abortus and Br. melitensis. CSF examination revealed 210 cells/cmm with 84% lymphocytes and 16% polymorphs, protein 160 mg%, sugar 48 mg% and raised Brucella agglutination titers (>1:160) [Table II]. Routine gram staining, ZN staining and India Ink staining were negative. VDRL test in CSF was negative. CT scan of head showed old lacunar infarct in left middle cerebral artery territory (not related to the present illness). She was treated with combination therapy of doxycycline 100 mg twice daily, rifampicin 450 mg twice daily orally for eight weeks and streptomycin 1 gm by intramuscular route daily for initial 14 days. She started showing signs of recovery and became fully conscious in 10 days. Serum antibody titers were less than 1:80 four weeks after starting treatment and CSF titers were less than 1:40 after eight weeks. There were no neurological sequelae on follow-up after eight weeks.
Other three cases had also similar clinical features and investigations results with mild variations. [Table I] and II give details of these patients who were aged 30,32 and 30 years respectively.

   »   Discussion Top

Brucellosis is an infectious disease, with world wide distribution, transmitted to humans through consumption of raw milk or infected milk products, contact with infected animals or through the respiratory tract, abraded skin or conjunctiva.[3] There are frequent reports of brucellosis from countries like Kuwait, Saudi Arabia and other middle East countries, where animals are raised in large number.[4],[5] Although animal brucellosis is well reported in India, there are only few reports of human brucellosis from India and still fewer of neurobrucellosis.[6],[7] Shakir et al[2] have categorized the neurobrucellosis into central and peripheral forms, the former occurring commonly as acute meningoencephalitis and the latter as polyradiculoneuropathy. Other workers have also reported isolated cases of neurobrucellosis with primary involvement of peripheral nerves causing cauda equina like syndromes and peripheral neuropathy.[2]
We have come across four cases of meningoencephalitis, one of which also had peripheral neuropathy resulting in delayed nerve conduction velocity (case 2 - [Table I], in the last eighteen months. However, many might have been overlooked previously because this disease is usually not considered as a cause of meningitis in this region. All the patients were involved in occupations which helps in the transmission of the disease. Three of them were shepherds and one was keeping animals surrounding the areas of living. The diagnosis of brucellosis depends on the presence of clinical features together with a positive blood culture or tissue culture and/or the detection of raised brucella agglutinins in the patient's serum. Most authorities consider agglutination titre of 1/160 or higher to be significant in a symptomatic patient, living in a non endemic area. However, in endemic areas only titres of 1/320 to 1/640 or higher are considered significant.[8] Diagnosis in patients being reported in this study was confirmed by serological test. However, blood and CSF culture along with ELISA test may be more informative. The risk of spread of infection, difficulty in culture, time period of more than 6 weeks and positivity of blood or bone marrow culture in only 50 to 70% patients, do not make blood culture the investigation of choice for the diagnosis of brucellosis. All patients showed brucella agglutination titers of more than 1:160, the minimum required level for the confirmation of the diagnosis.[9],[10],[11] Other important causes of fever with unconsciousness in this region like cerebral malaria, enteric encephalopathy, pyogenic and tubercular meningitis were ruled out by appropriate investigations. Fungal infection in CSF was ruled out by 'India ink' staining. The criteria necessary for definite diagnosis of neurobrucellosis are i) neurological dysfunction not explained by other neurologic diseases, ii) abnormal CSF indicating lymphocytic pleocytosis and increased protein, iii) positive CSF culture for brucella organisms or positive brucella IgG agglutination titre in the blood and CSF iv), response to specific chemotherapy with a significant drop in the CSF lymphocyte count and protein concentration. Our patients fulfilled all the above mentioned criteria for the diagnosis of neurobrucellosis except that the CSF culture was not performed. Although demonstration of brucella organisms from CSF culture is the confirmatory test for the diagnosis of neurobrucellosis, the positivity is only 30%. Definite clinical and CSF parameters and improvement with antibrucella treatment in our patients confirms the aetiology. Raised antibody titers in CSF decline progressively in response to the treatment. We used doxycycline 100 mg twice daily, rifampicin 450 mg twice daily, both orally for eight weeks and streptomycin one gram per day for initial fourteen days as a common therapeutic regimen.[1] In one case (case 4) the treatment had to be extended for another 4 weeks because of slow recovery. No patient had neurological sequelae at the end of the treatment.
Brucella organisms elaborate no exotoxins but produce a potent endotoxin. An important factor in virulence is their ability to survive intracellularly within polymorphonuclear leucocytes and monocytes.[12] 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 involvement can also be secondary to the bone disease caused by brucella or abscess formation in the brain. Nervous system can be involved in various stages of brucellosis i.e. at the onset of illness, during the course of illness or during convalescence or months after recovery from acute infection.[4] Animal experiments with brucella endotoxin,, have shown that endothelial lining can develop vascular and perivascular inflammatory reaction.
Transient cerebral ischaemia can occur secondary to the vascular spasm. Encephalopathy in brucellosis is always secondary to vascular involvement. Chronic pachymeningitis and leptomeningitis has been described in brucellosis.[13] There is also evidence of intrathecal production of antibodies which might be responsible for neural involvement.[14] Meningoencephalitis is well recognized in brucellosis. The pathololgy is due to a direct effect of the organism or its products on the meninges and brain.[2] Chronic brucella meningitis might be due to persistent intracellular effects of the organism, or perhaps the infection might trigger an immune mechanism leading to demyelination.[2] Myeloradiculopathy has also been described which can result from infectious arachnoiditis of the spinal cord or vasculitis leading to infarcts.[15]
The purpose of reporting these cases is to create awareness and highlight the fact that diagnosis of brucellosis should be kept in mind in case meningitis develops in persons who live with and/or deal in animal products.


  »   References Top

1.Solera J, Elisa MA, Espinosa A: Recognition and optimum treatment of brucellosis. Drugs 1997; 53(2): 245-256.   Back to cited text no. 1    
2.Shakir Ra, Al-Din ASN, Araj GF et al: Clinical categories of neurobrucellosis. A report of 19 cases. Brain 1987; 118: 213-223.   Back to cited text no. 2    
3.Al-Deeb SM, Phadeke J, Yaqub BA: Neurobrucellosis. Neurology 1988; 38: 354.   Back to cited text no. 3    
4.Bashir R, Zuheir AK, Edward JH et al: Nervous system brucellosis: Diagnosis and treatment. Neurology 1985; 35: 1576-1581.   Back to cited text no. 4    
5.Lulu AR, Araj GF, Khateeb MI et al: Human brucellosis in Kuwait: A prospective study of 400 cases. New Series QJM 1988; 66: 249: 39-54.   Back to cited text no. 5    
6.Ghosh D, Gupta P, Prabhakar S: Systemic brucellosis with chronic rneningitis. A case report. Neurol India 1999; 47: 58-60.   Back to cited text no. 6    
7.Banerjee TK, Pal AK, Das S: Neurobrucellosis presenting as acute meningoencephalitis. Neurol India 1999; 47: 160.   Back to cited text no. 7    
8.Madkour MM: Brucellosis. Oxford Text Book of medicine, In Dshealtherall, JGG Leadingnon and DA Warrell (Edi), oxford medical publication, London: 619-623.   Back to cited text no. 8    
9.Cernyseva M, Knjazeva EN, Egorova LS: Study of plate agglutination test with rose Bengal antigen for the diagnosis of human brucellosis. WHO 1977; 55(6): 669-674.   Back to cited text no. 9    
10.Elberg SS: A guide to the diagnosis, treatment and prevention of human brucellosis. Geneva: World health Organization WHO Document No. VPH/S1: 1983; 31: 5-36.   Back to cited text no. 10    
11.Malik GM: A clinical study of brucellosis in adults in the Asir region of southern Saudi Arabia. Am J Trop Med Hyg 1997; 56(4): 375-377.   Back to cited text no. 11    
12.John M Kissane: Bacterial disease. Brucellosis. Anderson's Pathology 8th Edition 1985; 307.   Back to cited text no. 12    
13.Joglekar MD Nagalotimath SJ: Neurobrucellosis. J Assoc Physicians India 1926; 24: 183-186.   Back to cited text no. 13    
14.Bucasa KS, Sindic CJ, Limet JN et al: Antibody activity of CSF oligoclonal IgG in infectious neurological diseases. Detection using immunoblotting. Acta Neurol Belg 1988; 88: 203-220.   Back to cited text no. 14    
15.Pascual G, Gombarros O, Palo JM at al: Localized CNS brucellosis. Acta Neurol Scand 1988; 78: 282-289.   Back to cited text no. 15    


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