- Email: [email protected]
Brucellar spondylitis and meningoencephalitis: a case report
The Netherlands Journal of Medicine 2001;59:158–160
Letter to the Editor
Brucellar spondylitis and meningoencephalitis: a case report ´ ´ J.C. Arevalo Lorido*, J. Carretero Gomez, J. Romero Requena, J.C. Bureo Dacal, ´ P. Bureo Dacal A. Vera Tome, Department of Internal Medicine, University Hospital Infanta Cristina, 06011 Badajoz, Spain Received 22 February 2001; received in revised form 1 May 2001; accepted 29 May 2001
Abstract Brucellosis, a zoonosis with a worldwide distribution, is a systemic infection that can present with involvement of both nervous and musculoskeletal systems. We report a case of spondylitis and meningoencephalitis and describe the clinical features, and difficulties in treatment. Osteoarticular complications of brucellosis are common but involvement of the nervous system is rare and it should be included in the differential diagnosis of any obscure neurologic disorder. 2001 Elsevier Science B.V. All rights reserved. Keywords: Brucellosis; Spondylitis; Neurobrucellosis
Introduction Brucellosis remains a major zoonosis worldwide. It is a systemic infection caused by facultative intracellular bacteria of the genus Brucella that manifests most commonly as fever of unknown origin. However, the disease can involve many organs and tissues. Among focal forms, those affecting the musculoskeletal system are the most common [1]. Spondylitis is the most prevalent and important clinical form of osteoarticular involvement in adults with infection due to Brucella species, and may be difficult to diagnose.
* Corresponding author. Alonso Nunez ˜ 6, 7C, 06011 Badajoz, Spain. ´ Lorido). E-mail address: [email protected] (J.C. Arevalo
Involvement of the central or peripheral nervous system occurs in about 2–5% of patients [2]. Our case presented both spondylitis and meningoencephalitis, but meningoencephalitis several days after spondylitis.
Case report A 62-year-old woman was admitted because of fever, anorexia, weight loss of at least 10 kg and back pain. Four years before admission she underwent removal of papilloma in her left breast. Three months before admission she had a severe back pain irradiating to her left arm, and a persistent temperature from 37 to 388C. Two months before admission she developed severe anorexia with weight loss of at least 10 kg. The temperature was 37.88C, the pulse was 68 and the blood pressure was 120 / 80 mmHg.
0300-2977 / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved. PII: S0300-2977( 01 )00143-7
´ Lorido et al. / Brucellar spondylitis and meningoencephalitis J.C. Arevalo
On examination, there was no rash or lymphadenopathy. The lungs were clear. The heart was normal. The breasts were normal. The abdomen were also normal. Neurologic examination was normal. She did not have a history of occupational exposure or ingestion of unpasteurized dairy products. She lived in a rural area. Laboratory tests were normal, erythrocyte sedimentation rate was 15 mm / s. A radiograph of the chest showed a increased kyphosis with narrowing of Th7–Th8 disc, and an increased intensity in vertebral bodies Th7 and Th8, compatible with spondylitis. A MRI was performed (Fig. 1) which confirmed the diagnosis. Blood culture were negative. Agglutination test was positive for antibodies to Brucella (titer 1:2560). The Coombs’ test revealed titers of antibodies to Brucella of 1:2560. Treatment with a combination of oral doxycycline (100 mg every 12 h) and rifampin (900 mg / day orally) was started, but the patient worsened, developing weakness in their both legs, confusion, headache drowsiness and dizziness. On examination there was not clinical signs of meningeal irritation. The cranial nerves were intact, but she had spastic weakness in her legs, with an increased deep tendon reflexes and a bilateral Babinski sign. A CT scan of the brain was normal. The CSF opening pressure was 150 mmH 2 O with 40 lymphocytes / mm 3 , 237 mg / dl
Fig. 1. MRI showing focal decrease signal intensity in Th7–Th8 vertebrae.
159
proteins and 28 mg / dl glucose. Brucella agglutinations titers in CSF were 1:128. Trimethroprim–sulfamethoxazole (TMP–SMZ) and streptomycin were added to the treatment with improvement of fever, but weakness worsened; a surgical management (descompressive laminectomy) was performed with a favorable response.
Discussion Brucellosis has been widely reported in the central and mediterranean regions of Spain [3]. In these regions brucellosis has been primarily caused by Brucella melitensis, which is carried by sheep and goats. In our case, serovar was not performed but we think Brucella melitensis was the bacteria that involved the bone and CNS from epidemiologic aspect of the patient. Spondylitis is a frequent complication of brucellar infection. The lumbar segment is the most frequently involved followed by the thoracic (as in our patient) and finally the cervical segment. The incidence of neurologic complication is about 2% and they are of marked clinical importance due to their severity and important sequelae [4]. The presentation of neurobrucellosis is diverse and both central and peripheral nervous systems can be involved. Meningoencephalitis is most likely due to the direct effect of the Brucella organism or its endotoxins on the meninges and brain, in this case probably produced by spreading of bacteria from adjacent area of spondylitis. The CSF findings were those of chronic lymphocytic meningitis, normal or low glucose and high protein. Isolation of Brucella from CSF is difficult but serological test usually show a significant titre, as in our case. The culture after surgery was negative in our case because of the previous course of antimicrobial therapy. In this case, the response to a doxycycline / rifampin combination was partial. Failures of antimicrobial treatment rarely represent actual resistance of bacteria to antibiotics; a lack of response is usually encountered when the effect on the spine is great. Since neurobrucellosis was a complication in this
The Netherlands Journal of Medicine 2001;59:158 – 160
160
´ Lorido et al. / Brucellar spondylitis and meningoencephalitis J.C. Arevalo
patient, streptomycin and TMP–SMZ were added. Streptomycin is recommended in cases of systemic brucellosis and TMP–SMZ and rifampin are agents that cross the blood–brain barrier and achieve high levels in the CSF. A 2–4-month course of antimicrobial therapy is required for the treatment of neurobrucellosis. To avoid toxicity, patients should limit their use of streptomycin to 2–3 weeks.
[2] Al Deeb SM, Yaqub BA, Sharif HS, Phadke IG. Neurobrucellosis: clinical characteristics, diagnosis, and outcome. Neurology 1989;39:498–501. [3] Colmenero JD, Reguera JM, Fernandez-Nebro A, CabreraFranquelo F. Osteoarticular complications of brucellosis. Ann Rheum Dis 1991;50:23–6. [4] Shakir RA, Al-Din ASN, Arag GF, Lula´ Mousa AR, Saadah WA. Clinical categories of neurobrucellosis. A report of 19 cases. Brain 1987;110:213–23.
References [1] Mousa ARM, Muhtaseb SA, Almudallal DS, Khodeir SM, Marafie AA. Osteoarticular complications of brucellosis: a study of 169 cases. Rev Infect Dis 1987;9:531–43.
The Netherlands Journal of Medicine 2001;59:158 – 160
Letter to the Editor
Brucellar spondylitis and meningoencephalitis: a case report ´ ´ J.C. Arevalo Lorido*, J. Carretero Gomez, J. Romero Requena, J.C. Bureo Dacal, ´ P. Bureo Dacal A. Vera Tome, Department of Internal Medicine, University Hospital Infanta Cristina, 06011 Badajoz, Spain Received 22 February 2001; received in revised form 1 May 2001; accepted 29 May 2001
Abstract Brucellosis, a zoonosis with a worldwide distribution, is a systemic infection that can present with involvement of both nervous and musculoskeletal systems. We report a case of spondylitis and meningoencephalitis and describe the clinical features, and difficulties in treatment. Osteoarticular complications of brucellosis are common but involvement of the nervous system is rare and it should be included in the differential diagnosis of any obscure neurologic disorder. 2001 Elsevier Science B.V. All rights reserved. Keywords: Brucellosis; Spondylitis; Neurobrucellosis
Introduction Brucellosis remains a major zoonosis worldwide. It is a systemic infection caused by facultative intracellular bacteria of the genus Brucella that manifests most commonly as fever of unknown origin. However, the disease can involve many organs and tissues. Among focal forms, those affecting the musculoskeletal system are the most common [1]. Spondylitis is the most prevalent and important clinical form of osteoarticular involvement in adults with infection due to Brucella species, and may be difficult to diagnose.
* Corresponding author. Alonso Nunez ˜ 6, 7C, 06011 Badajoz, Spain. ´ Lorido). E-mail address: [email protected] (J.C. Arevalo
Involvement of the central or peripheral nervous system occurs in about 2–5% of patients [2]. Our case presented both spondylitis and meningoencephalitis, but meningoencephalitis several days after spondylitis.
Case report A 62-year-old woman was admitted because of fever, anorexia, weight loss of at least 10 kg and back pain. Four years before admission she underwent removal of papilloma in her left breast. Three months before admission she had a severe back pain irradiating to her left arm, and a persistent temperature from 37 to 388C. Two months before admission she developed severe anorexia with weight loss of at least 10 kg. The temperature was 37.88C, the pulse was 68 and the blood pressure was 120 / 80 mmHg.
0300-2977 / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved. PII: S0300-2977( 01 )00143-7
´ Lorido et al. / Brucellar spondylitis and meningoencephalitis J.C. Arevalo
On examination, there was no rash or lymphadenopathy. The lungs were clear. The heart was normal. The breasts were normal. The abdomen were also normal. Neurologic examination was normal. She did not have a history of occupational exposure or ingestion of unpasteurized dairy products. She lived in a rural area. Laboratory tests were normal, erythrocyte sedimentation rate was 15 mm / s. A radiograph of the chest showed a increased kyphosis with narrowing of Th7–Th8 disc, and an increased intensity in vertebral bodies Th7 and Th8, compatible with spondylitis. A MRI was performed (Fig. 1) which confirmed the diagnosis. Blood culture were negative. Agglutination test was positive for antibodies to Brucella (titer 1:2560). The Coombs’ test revealed titers of antibodies to Brucella of 1:2560. Treatment with a combination of oral doxycycline (100 mg every 12 h) and rifampin (900 mg / day orally) was started, but the patient worsened, developing weakness in their both legs, confusion, headache drowsiness and dizziness. On examination there was not clinical signs of meningeal irritation. The cranial nerves were intact, but she had spastic weakness in her legs, with an increased deep tendon reflexes and a bilateral Babinski sign. A CT scan of the brain was normal. The CSF opening pressure was 150 mmH 2 O with 40 lymphocytes / mm 3 , 237 mg / dl
Fig. 1. MRI showing focal decrease signal intensity in Th7–Th8 vertebrae.
159
proteins and 28 mg / dl glucose. Brucella agglutinations titers in CSF were 1:128. Trimethroprim–sulfamethoxazole (TMP–SMZ) and streptomycin were added to the treatment with improvement of fever, but weakness worsened; a surgical management (descompressive laminectomy) was performed with a favorable response.
Discussion Brucellosis has been widely reported in the central and mediterranean regions of Spain [3]. In these regions brucellosis has been primarily caused by Brucella melitensis, which is carried by sheep and goats. In our case, serovar was not performed but we think Brucella melitensis was the bacteria that involved the bone and CNS from epidemiologic aspect of the patient. Spondylitis is a frequent complication of brucellar infection. The lumbar segment is the most frequently involved followed by the thoracic (as in our patient) and finally the cervical segment. The incidence of neurologic complication is about 2% and they are of marked clinical importance due to their severity and important sequelae [4]. The presentation of neurobrucellosis is diverse and both central and peripheral nervous systems can be involved. Meningoencephalitis is most likely due to the direct effect of the Brucella organism or its endotoxins on the meninges and brain, in this case probably produced by spreading of bacteria from adjacent area of spondylitis. The CSF findings were those of chronic lymphocytic meningitis, normal or low glucose and high protein. Isolation of Brucella from CSF is difficult but serological test usually show a significant titre, as in our case. The culture after surgery was negative in our case because of the previous course of antimicrobial therapy. In this case, the response to a doxycycline / rifampin combination was partial. Failures of antimicrobial treatment rarely represent actual resistance of bacteria to antibiotics; a lack of response is usually encountered when the effect on the spine is great. Since neurobrucellosis was a complication in this
The Netherlands Journal of Medicine 2001;59:158 – 160
160
´ Lorido et al. / Brucellar spondylitis and meningoencephalitis J.C. Arevalo
patient, streptomycin and TMP–SMZ were added. Streptomycin is recommended in cases of systemic brucellosis and TMP–SMZ and rifampin are agents that cross the blood–brain barrier and achieve high levels in the CSF. A 2–4-month course of antimicrobial therapy is required for the treatment of neurobrucellosis. To avoid toxicity, patients should limit their use of streptomycin to 2–3 weeks.
[2] Al Deeb SM, Yaqub BA, Sharif HS, Phadke IG. Neurobrucellosis: clinical characteristics, diagnosis, and outcome. Neurology 1989;39:498–501. [3] Colmenero JD, Reguera JM, Fernandez-Nebro A, CabreraFranquelo F. Osteoarticular complications of brucellosis. Ann Rheum Dis 1991;50:23–6. [4] Shakir RA, Al-Din ASN, Arag GF, Lula´ Mousa AR, Saadah WA. Clinical categories of neurobrucellosis. A report of 19 cases. Brain 1987;110:213–23.
References [1] Mousa ARM, Muhtaseb SA, Almudallal DS, Khodeir SM, Marafie AA. Osteoarticular complications of brucellosis: a study of 169 cases. Rev Infect Dis 1987;9:531–43.
The Netherlands Journal of Medicine 2001;59:158 – 160