Clinical Study And Risk Factors Analysis Of Neurobrucellosis

Objectives This study aims to systematically summarize the clinical characteristics of neurobrucellosis, to conduct dynamic analysis of its radiographic, laboratory, and neuro-electro-physiological characteristics, to analyze its risk factors and the efficacy of treatment.Methods A total of 557 cases of neurobrucellosis were collected, who had been treated at outpatient and inpatient departments of the Affiliated Hospital of Inner Mongolia Medical University, Disease Prevention and Control Center of Inner Mongolia Autonomous Region during September 2012- November 2014. Cross-sectional investigation was carried out by specialized personnel(neurological clinicians)trained for epidemiological survey. An analysis of risk factors of neurobrucellosis was performed based on the detailed recorded data of patients, such as age at the onset, gender, nationality, course of disease, SAT, contact history, season at the onset,place of residence etc. Patients who had been diagnosed with neurobrucellosis were classified as central type and peripheral type. Among the 35 patients with lesions to their central nervous system, cerebrospinal fluid(CSF) and radiographic examinations, plus four tests for neurobrucellosis were carried out at hospitalization,after two and six weeks of treatment respectively. Meanwhile neuro-electro-physiological examination was performed among the 31 patients with lesions to their peripheral nervous system, and in comparison with 28 healthy subjects in the control group, the related characteristics of neuro-electro-physiology were analized. 66 patients with neurobrucellosis were subjected to fundamental medication of doxycycline(100 mg bid for six weeks), rifampicin(600 mg qd for six weeks), and ceftriaxone sodium(2.0 bid iv for 4-6 weeks), or levofloxacin(0.4qd iv for 4-6 weeks)if allergic to cephalosporins. For those with cerebrovascular damages, NHISS and m RS scores were taken at hospitalization, then NIHSS scores after two weeks of treatment, and m RS scores after three months of treatment respectively. The efficacy of treatment was assessed through clinical symptoms, signs, and radiographicvariations among those with inflammatory changes of central nervous system and demyelination, while the efficacy among those with peripheral nervous system lesions was evaluated via neuro-electro-physiological examination after two and six weeks of treatment.Results1. Clinical manifestations of neurobrucellosis were diverse and complicated,including 35 cases of fever, 38 cases of hidrosis, 18 cases of headache, 35 cases of dyskinesia, 10 cases of nausea and vomiting, 34 cases of sensory disturbance, 26 cases of arthralgia as well as pains in the neck and back, 6 cases of lalopathy, 5 cases of convulsion, 5 cases of unconsciousness, 4 cases of psychosis, 4 cases of bowel and bladder disturbances, 3 cases of dizziness, 2 cases of dysphagia with choking and coughing, 1 case of diplopia, 1 case of prosopoplegia with dyspnea; 10 cases of cerebrovascular damages, 22 cases of inflammatory changes of central nervous system and demyelination, 3 cases of intraspinal abscess, and 31 cases of peripheral nervous system damages.2. Radiology of neurobrucellosis. 16 out of 35 cases undergoing radiographic examination proved abnormal( 4 with encephalorrhagia, 5 with cerebral infarction, 1with subdural hematoma, 3 with inflammatory changes and demyelination, and 3with intraspinal abscess), while the other 19 were normal.3. CSF examination. There were 9 with increased CSF pressure, 8 with decreased glucose level, 9 with decreased chlorides, 12 with increased proteins, 20 with increased LDH and AST, 1 with ADA>15U/L. Early stage changes were similar to those of viral meningitis, while manifestations at advanced or severe stage were like those of tubercular or bacterial meningitis. Blood routines of 59 patients were normal.5 cases with increased lymphocyte count and 1 case with decreased lymphocyte count were reported respectively, and 30 with abnormal hepatic function.4. Preferred fundamental treatment consisted of doxycycline(100 mg bid po),rifampicin(600 mg qd), and ceftriaxone sodium(2.0 bid iv), with symptomatic therapy. Patients’ conditions improved after six weeks, which proved a favorable efficacy.5. Cross-sectional epidemiological survey. The proportion of complicated nervous system lesions detected among brucellosis patients was 11.8%, and the proportion of central nervous system lesions to peripheral nervous system lesions was close to 1:1.Single- and multi-factor analysis suggested that gender, nationality and regional distribution were not related to nervous system lesions in brucellosis patients(P>0.05), while age, course of disease and SAT grading were related factors.Increased age and SAT grading, as well as prolonged course of disease were the risk factors of nervous system lesions in brucellosis patients(P<0.05).6. Neuro-electro-physiological manifestation of early stage neurobrucellosis was peripheral sensory nerve damage of limbs, while severe stage damages were mainly to sensory and motor nerves at the same time. The abnormality rates of Finger I and III median sensory nerve amplitude and conduction velocity among PNSNB group were higher than those among the control group; abnormality rates of ulnar sensory nerve amplitude were also higher than those among the control group, but conduction velocity was not much different. The abnormality rate of wrist median motor nerve amplitude among PNSNB group was higher than that among the control group, while the abnormality rates of ulnar, common peroneal, and tibial motor nerve amplitudes between the two groups showed no difference. The abnormality rates of common peroneal and tibial motor nerve conduction velocities among PNSNB group were higher than those among the control group, while those of median and ulna motor nerves between the two groups were of no difference. F wave latentcies extension of ulna and tibial nerves among PNSNB group were longer than those among the control group.Conclusion1. Clinical manifestations of neurobrucellosis are diverse and complicated. Nervous system lesions have been detected among 11.8% of brucellosis patients, and the proportion of central nervous system lesions to peripheral nervous system lesions is close to 1:1. For patients with nervous system lesions that worsen, or cannot be remarkably alleviated after symptomatic treatment(or without rational clinical explanation), the possibility of neurobrucellosis should be considered if with positive contact history.2. Early stage changes of neurobrucellosis are similar to those of viral meningitis,while manifestations at the advanced or severe stage are like those of tubercular or bacterial meningitis.3. Most radiographic changes of neurobrucellosis are nonspecific, showing inflammatory feature(granuloma; abnormal enhancement of meninges, peripheralvascular interstitials and lumbar nerve roots), white matter and vascular changes.MRA or CTA indicates diffuse vasculitis. And inflammatory demyelination presents itself mostly in the form of multifocal sclerotic or disseminated encephalomyelitis that doesn’t involve cingulate gyrus, and without enhancement. SWI of encephalorrhagia manifests small multifocal intracerebral hemorrhages.4. Peripheral nerve damages in most cases are related to the spinal nerves(median,tibial and superficial peroneal nerves). Cranial nerves are less involved, and facial nerves the least involved in comparison to other cranial ones that are more likely to be injured, such as abducent, auditory and vestibular nerves. By means of clinical neuro-electromyography and other neuro-electro-physiological examinations, early stage detection rate could be elevated for the purpose of early diagnosis and treatment.5. Age, course of disease and SAT grading are the risk factors of neurobrucellosis,while gender, nationality and regional distribution are not. Older patients with prolonged course of disease and higher SAT grading are more likely to develop neurobrucellosis.6. Doxycycline, rifampicin and cephalosporins(esp. ceftriaxone sodium, or quinolones for those allergic to cephalosporins) are both fundamental and first-choice medication for neurobrucellosis. The treatment should last for at least six weeks.Standardized, sufficient and combined medication is recommended for better efficacy and prognosis.