Fig. 4.1
Brucella organisms on gram stain of colonies from blood culture of a patient with brucellosis, × 1000 (Courtesy of G.F. Araj, M.D.)
Laboratory confirmation of neurobrucellosis should be made by the presence of any 1 of the following criteria: (1) isolation of microorganism from CSF; (2) presence of anti-Brucella antibodies in CSF; (3) detection of lymphocytosis, increased protein, and decreased glucose levels of the CSF; and (4) findings associated with neurobrucellosis in CT or MRI [4]. Lumbar puncture can be a dangerous procedure in intracranial space-occupying lesions such as subdural or epidural empyemas and should not be performed [27]. Serological tests of CSF can be negative in empyemas, and mild nonspecific inflammatory changes in CSF may be detected only [4]. Furthermore, the culture of surgical specimens may reveal a localized infection caused by Brucella species [42]. Polymerase chain reaction (PCR) method is being studied for diagnosis of brucellosis as a promising test due to its sensitivity and specificity and can be a diagnostic modality of choice in brucellosis [19, 20]. PCR is not a routine test, but can be helpful after 10 days of infection, and it can be performed in any tissue [22].
4.6 Differential Diagnosis
Intracranial space-occupying lesions such as hematomas, effusions, calcification or metastatic dural involvement, and other infectious and inflammatory conditions such as tuberculosis, Leptospira species, Borrelia burgdorferi, syphilis, poliomyelitis, and fungal infections should be considered in differential diagnosis of epidural and subdural empyemas. In particular, the differential diagnosis should be that of the epidural and subdural spaces brucellosis. Contrast enhancement may help to distinguish infectious lesions [15, 27]. Neurobrucellosis may mimic many different central and peripheral nervous system pathologies, and a combination of neuroimaging techniques and microbiological diagnostic tests is useful for the detection of neurobrucellosis and evaluation of complications for the prevention of morbidity and mortality.
4.7 Treatment
Treatment is essential, because untreated neurobrucellosis has a high mortality and morbidity [15]. There are uncertainties and difficulties in treatment due to intracellular localization of microorganism, the requirement for a sufficient antibiotic dose level in the CSF, the lack of a treatment guideline entered into practice, and applicability of surgical intervention [25, 42].
4.7.1 Surgical Treatment
Presence of the neurological symptoms and deficits determines the indication of surgical intervention. A combination of surgical and medical therapy is appropriate in patients with neurological deficit [32, 33, 38]. Follow-up only with medical therapy may be an appropriate approach in some cases without neurological deficit [38]. Intracranial epidural and subdural empyemas must be evacuated surgically, and positive culture of the specimens can establish the diagnosis [29, 30].
4.7.2 Antibiotic Therapy
There is no consensus in the literature regarding optimal antimicrobial regimen and appropriate duration of treatment of neurobrucellosis [25, 42]. The medical treatment regimens must include the antibiotics that have penetration feature to the hematoencephalic barrier and sufficient concentrations in the CSF and maintain intracellular activity [3]. Dual-triple combination therapies are recommended including rifampin, tetracyclines, trimethoprim-sulfamethoxazole, ceftriaxone, and aminoglycosides [6, 7, 13, 22]. Single-agent regimens are contraindicated in the treatment of brucellosis [7, 13]. Although there is no certainty about the duration of treatment, the regimens including a combination therapy are advised for no less than 3 months [3, 6, 13]. While the recommended mean duration of neurobrucellosis treatment is 6 months, elongated treatment durations to 1–2 years have been reported in various studies, with individualized treatment in many cases according to signs and symptoms [6, 10].
4.7.3 Corticosteroid Treatment
Corticosteroids can be helpful in some conditions like papilledema, myelopathy, polyneuropathy, and cranial nerve palsies [27]. There is not established clinical trial about steroid use in neurobrucellosis, especially in epidural and subdural empyemas.
4.7.4 Antiepileptic Therapy
In acute stage, if the seizure attacks are frequent, a potent antiepileptic drug such as phenytoin (with landing dose) should be initiated to control the attacks [22]. Also levetiracetam, lamotrigine, or sodium valproate may be suitable alternative options for this purpose [21]. Rifampin can diminish the level of valproic acid, and this should be considered in therapeutic use of valproate. Rifampin also can increase metabolism of lamotrigine and diminish the level of drug in serum. After the termination of the seizure episodes, antiepileptics can be stopped within a short period [25, 29].
4.8 Follow-Up
Follow-up of patients with clinical symptoms and serial neuroimaging is necessary for monitoring of relapse and complications [17]. Relapse or reinfection occurs in 3–9 % of treated patients, and serial follow-ups are recommended [29, 35]. The 2-mercaptoethanol (2-ME) agglutination test measures IgG antibodies and is a good biomarker for relapsed brucellosis. High IgG levels in 2-ME test indicate relapse [35].
Conclusion
Brucellar epidural and subdural empyemas are less common than the other forms of neurobrucellosis and present with nonspecific signs and symptoms.
Brucellar epidural and subdural empyemas should be kept in mind in patients presenting with related symptoms, and required microbiological and neuroimaging tests should be performed in suspected cases.
Treatment should be scheduled as soon as possible to decrease the mortality and morbidity.
Presence of the neurological symptoms and deficits determines the indication of surgery.
Follow-up of patients is necessary for monitoring of relapse and complications of neurobrucellosis.
References
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American Academy of Pediatrics (2009) Brucellosis. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS (eds) Red book: 2009 report of the Committee of Infectious Diseases, 28th edn. American Academy of Pediatrics, Elk Grove Village, pp 237–239
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Araj GF (2010) Update on laboratory diagnosis of human brucellosis. Int J Antimicrob Agents 36:12–17CrossRef
