The bacteriological characteristics, predisposing factors, routes of infection, clinical manifestations, treatment options and prognosis of multiple brain abscesses and multiatrial brain abscesses are discussed. METHODS: The clinical data of 85 patients with brain abscess (52 cases of monogenic brain abscess, 15 cases of multiple brain abscess and 18 cases of multiatrial brain abscess) over a period of 20 years were retrospectively analyzed. RESULTS: The incidence of multiple brain abscesses and multiatrial brain abscesses was 17.6% and 21.2%, respectively. Bloodstream infection was the common type of infection (73.3% and 50.0%, respectively); elevated temperature, headache, nausea and vomiting were the most common symptoms; positive bacterial culture rate was higher than that of solitary brain abscess and Staphylococcus aureus was the most common causative organism; stereotactic abscess puncture and drainage was the most frequently used treatment, and 30.8% of multiatrial brain abscesses required repeat treatment, which was higher than that of solitary brain abscesses (2.2%). There were 3 cases (20.0%) of multiple brain abscess deaths but all were related to critical condition before treatment or other causes of death. Conclusion: multiple brain abscesses and multiatrial brain abscesses are not uncommon, and their routes of infection and clinical manifestations differ from those of monogenic brain abscesses. stereotactic remains the treatment of choice for all kinds of brain abscesses, but some multiatrial brain abscesses require repeat treatment. The prognosis of brain abscesses is related to the severity of the disease before treatment. Keywords: brain abscess, multiple, multiatrial, clinical features, treatment options Multiple and multiloculated Pyogenic Brain Abscess Xin YU, Rui LIU, Jiangning ZHANG, Yaming WANG, Subin QI, Hongwei WANG. Department of Neurosurgery, Navy General Hospital of PLA, Beijing 100048, CHINA Abstract: OBJECTIVE: To determine whether there are differences in the bacteriology of the there are differences in the bacteriology, predisposing factors, treatment choices and outcomes between single, multiple and multiloculated METHODS: We studied clinical data collected during a 20-year period from 85 patients with pyogenic brain abscess, including 52 cases of single, 15 multiple and 18 multiloculated brain abscess. RESULTS: The incidence of multiple and multiloculated abscess were 17.6% and 21.2%. Hematogenous spread from a remote infectious focus was the most common causes of infection for multiple (73.3%) and 18 multilocutated( 50.0%) abscess. Fever, headache, nausea and vomit were the most common symptoms in patients with multiple and multiloculated abscess. Staphylococci aureus was the most commonly isolated pathogens in patients with multiple and multiloculated abscess. Stereotactic operation was performed for most patients and the rate of recurrent abscess formation after the initial operation and another operation were needed were 2.2% for single, 2.7% for Mortality was 0.0% for single, 20.0% for multiple and 0.0% for multiloculated abscess respectively. COMCLUSIONS: Multiple and multiloculated pyogenic brain abscess are not rare and their clinical characteristics are different from Stereotactic operation is still the first treatment choice, but repeat aspiration maybe needed for some patients with multiloculated abscess. Neurological status and concomitant medical disease at presentation were the most important factors influencing the prognosis. Bacterial brain abscess, multiple, multiloculated, clinical characteristic, treatment choice Bacterial brain abscess is one of the most important emergencies in neurosurgery for many years. Multiple Pyogenic Brain Abscess MPBA and Multiloculated Pyogenic Brain Abscess MCPBA are two special types of brain abscess, which have been less reported in the literature [1-4]. In this paper, we report the treatment experience of 85 cases of brain abscess (52 solitary, 15 MPBA and 18 MCPBA) admitted to the Department of Neurosurgery of the Naval General Hospital during the 20 years from 1991 to 2010, and compare the three different types of brain abscess in terms of etiology, clinical manifestations, bacteriology, predisposing factors, treatment options and prognosis to discuss the clinical characteristics of MPBA and MCPBA . Patients and methods A total of 85 patients with brain abscess were admitted to the Department of Neurosurgery of the Naval General Hospital during the 20 years from 1991 to 2010. Diagnostic criteria for brain abscess: (i) typical clinical manifestations, including fever, headache, and neurological localization signs with or without impaired consciousness; (ii) typical manifestations of brain abscess on CT or/and MRI; (iii) intraoperative findings and histopathological or pathogenic findings. Two or more abscess cavities were found in the brain, and those with brain parenchyma between the cavities were defined as MPBA (Figure 1), and those without brain parenchyma between the cavities were defined as MCPBA (Figure 2). ④ The lesions shrank or disappeared after anti-inflammatory treatment. Specimens obtained intraoperatively were cultured for aerobic bacteria, anaerobic bacteria, Mycobacterium tuberculosis and fungi. The first specimen cultured for 2 or more positive bacterial organisms was considered to be a mixed infection. Predisposing factors include factors that can lead to a decrease in the patient’s body resistance such as severe congenital heart disease, long-term use of hormones or immunosuppressive agents, and a history of recent severe trauma or surgery. The source of brain abscess was classified according to the medical history and clinical manifestations as blood-borne transmission from distant infected foci, direct transmission from adjacent infected foci, post-neurosurgical infection and those of unknown origin. Treatment selection: In this group of patients, one single microscopic abscess was cured by antimicrobial therapy, one multiple abscess was abandoned for family reasons, and the other 83 patients underwent surgical treatment, which consisted of craniotomy for complete removal of the abscess wall and stereotactic surgery. The latter was divided into stereotactic pus cavity puncture and irrigation and stereotactic pus cavity placement and drainage according to the size of the abscess. For abscesses with a volume of 10 ml, abscess puncture is performed, antibiotic saline is repeatedly flushed until the flushing fluid is clear, and high concentrations of antimicrobial agents are injected at once (usually 1/8 to 1/4 of the daily systemic dosage), while for abscesses with a volume of 10 ml, abscess puncture and tube placement is performed, antibiotic saline is flushed daily, and after 3-5 days, high concentrations of antimicrobial agents are injected and the tube is removed. The number of death cases within one month after surgery was counted. Statistical analysis Quantitative data were described by means and standard deviations, ANOVA for comparison between three groups with normally distributed and chi-square data, and bonferroni test for comparison between two groups, and Kruskal-Wallis test for comparison between three groups with non-normally distributed or chi-square data, and Nemnyi test for comparison between two groups. Qualitative data were described using the number of cases and composition ratios, and comparisons between the three groups of composition ratios were made using the c2 test, and two comparisons were corrected for test levels using the bonferroni method. Results The clinical characteristics of patients with solitary, MPBA and MCPBA are shown in Table 1. bacteriological examination, predisposing factors, treatment and death are shown in Table 2. Table 1 Clinical characteristics of patients with solitary, MPBA and MCPBA Solitary brain abscess Multiple brain abscesses Multi-compartmental brain abscesses (52 cases) (15 cases*) (18 cases) Sex Male 32 (61.5%) 9 (60.0%) 11 (61.1%) Female 20(38.5%) 6(40.0%) 7(38.9%) Age (years) Mean 37.7±21.3 33.1±21.9 33.4±18.1 <14 9(17.3%) 3(20.0%) 4(22.2%) Duration of illness (days) 21.7±17.7 14.8±12.9 23.4±16.0 Clinical manifestations Elevated body temperature 15( 28.8%) 12(80.0%)# 8(44.4%) ☆ Headache 12 9# 8 Nausea and vomiting 14 12# 10# Meningeal irritation symptoms 6 6# 4 Disorders of consciousness 4 2 3 Neurological deficit symptoms 20 7 8 Seizures 2 1 2 Lesion site Frontal lobe 23 15# 7☆ Parietal lobe 3 5# 4# Temporal lobe 8 8# 3☆ Occipital lobe 5 3 2 Basal ganglia area 6 5 1 Cerebellum 2 4# 1 Other 5 0 0 *2 cases were multiple cornu-like abscesses in the whole brain, the remaining 13 patients had a total of 40 lesions, 2 6 cases, 3 4 cases, 4 4 4 cases #: vs. single brain abscess, P<0.05; ☆: vs. multiple brain abscess, P<0.05. Table 2 Infection characteristics, treatment outcome and death in patients with single, MPBA and MCPBA Single brain abscess Multiple brain abscess Multi-compartmental brain abscess 52 cases ( 61.2%) 15 cases (21.2%) 18 cases (17.6%) Predisposing factors 20 (38.5%) 6 (40.0%) 9 (50.0%) Route of infection Blood-borne infection 14 (26.9%) 11 (73.3%)# 9 (50.0%) Adjacent spread 5 0 2 Surgical procedure 7 1 2 Unexplained 26 3# 4# Bacteriological examination Adjunctive anaerobic bacteria 9 (17.3 %)* 5(33.3%)** 7(38.9%)*** Breaking into the ventricle 1 3# 3# Treatment Stereotactic (number of recurrences/treatment) 1/46(2.2%) 1/37 4/13(30.8%) Craniotomy (number of recurrences/treatment) 0/5 0 0/5 Drug or untreated 1 1 0 Re-operation Stereotactic 1 0 3# Craniotomy 0 1 1 Mortality 0 3(20.0 %) ****# 0 1. 2 cases of Staphylococcus epidermidis, 1 case each of Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus griseus, Enterococcus faecalis, Streptococcus griseus, Streptococcus β-hemolyticus, and Streptococcus multivorans. 2, 3 cases of Staphylococcus aureus, 1 case each of Streptococcus β-hemolyticus and Streptococcus constellatus. 3, 3 cases of Staphylococcus aureus, 1 case each of Streptococcus straw green, Streptococcus equinovirus, Streptococcus constellatus and Streptococcus β-hemolyticus. 4. 2 cases died of high cranial pressure brain herniation, and 1 case died of cardiogenic shock the day after surgery. #: vs single brain abscess, P<0.05; ☆: vs multiple brain abscesses, P<0.05. Discussion MPBA accounts for 10% to 50% of bacterial brain abscesses [1,2]. Reports on MCPBA are rare [3,4], and its incidence is about 10% to 43% of brain abscesses [4-8], similar to MPBA. In our group, the incidence of MPBA was 17.6% and the incidence of MCPBA was 21.2%, indicating that MPBA and MCPBA are not uncommon. Kratimenos et al. reported [9] that there was no age difference in the incidence of MPBA, and the incidence of MPBA and MCPBA in children in this group was 20.0% (3/15) and 22.2% (4/18), respectively, similar to the incidence of monogenic brain abscess in children (17.3%, 9/52). All series reported with this group of MPBA were predominantly male[1,9-12] . The most common route of infection in MPBA is the intracranial spread of distant infection via the hematologic route, while direct spread of adjacent foci of infection to the brain parenchyma is rare. In contrast, the route of infection in MCPBA is similar to that of monogenic brain abscesses[4] .The results reported by Stephanov showed that parietal infection was the most common source of infection in MCPBA[7] . In our group, 38.5%, 40.0% and 50.0% of the three groups had predisposing factors before the onset of brain abscess, respectively, and there was no statistical difference, but 26.9%, 73.3% and 50.0% had bloodstream infections, respectively, indicating that the proportion of bloodstream infections in MPBA was significantly higher than that in monogenic and MCPBA, and none of the MPBA cases were spread by adjacent infections, which is basically consistent with the previously reported results. The causative organisms of brain abscesses are influenced by many factors (e.g., different periods of infection, geographic distribution, patient age, underlying medical and surgical disorders, and mode of infection), and therefore the reported differences are large. The bacterial strains isolated in our group were all partly anaerobic Gram-positive cocci and no Gram-negative rods were found, with Staphylococcus aureus as the main causative organism in multiple and MCPBA, which is consistent with the results reported by Sharma et al [12]. And although we immediately cultured all pus specimens for aerobic and anaerobic bacteria, the total positive rate of bacterial culture was only 26.6%, which indicates that not all bacteria survived in the pus and may also be related to the fact that antibiotics had been administered before the surgical taking of the pus specimen. Factors influencing the formation of abscess cyst wall include the type of causative organism, the source of infection as direct bacterial invasion or blood-borne transmission, the immune function of the patient, the application of glucocorticoids and the application of antimicrobials. It has been reported that Bacteroides fragilis can produce a variety of toxins and enzymes, among which trypsin can dissolve the formed abscess wall and hyaluronidase can aggravate pus formation and surrounding brain tissue edema, thus most likely to cause MPBA [14]. The clinical manifestations of brain abscesses are closely related to the precipitating cause, the type of bacteria infected, the route of infection, the size and location of the abscess, and the stage of pathology at the time of admission. stephanov [7] found that 80% of patients with MCPBA had elevated body temperature, while Su found that the clinical features of MCPBA were not different from those of solitary brain abscesses, except that headache and hemiparesis were more common in multiple brain abscesses. The percentage of elevated temperature in the three groups was 28.8%, 80.0%, and 44.4%, respectively, which was highly consistent with the percentage of bloodstream infection, suggesting a definite association between the two. meningoencephalitis manifested significantly more in the MPBA group than in the single brain abscess group. Other clinical symptoms were similar to those of most patients with brain abscesses and did not suggest a specific presentation of multiple and multifocal lesions. Headache, nausea and vomiting remained the most common symptoms in all patients. Although several reports state that altered consciousness is a common symptom of MPBA [12,15], it was rarely found in our group. The presence of focal neurological signs (e.g., hemiparesis, hemianesthesia, and aphasia) depends on the site of the abscess. From the statistics of our group, the chance of MPBA and MCPBA breaking into the ventricles is significantly higher than that of solitary brain abscesses. It is now generally accepted that abscesses >2.5 cm in diameter or those causing significant occupational effects should be treated surgically [1]. The surgical treatment of solitary brain abscesses includes abscess excision and stereotactic abscess puncture and drainage combined with antimicrobial agents, and some authors have also reported on the drainage of abscess cavities by craniotomy under direct vision without stereotactic surgical techniques, instead of excision to treat functional areas or abscesses located deep in the location, which is considered to reduce the impact of surgical trauma on neurological function and to achieve the healing of abscesses purpose [16]. Recent reports almost unanimously agree that stereotactic surgery is a very effective measure for the treatment of both solitary and MPBA and should be the first choice [17-21]. The choice of treatment for MCPBA is still controversial, with some authors recommending surgical resection as the first option and others considering stereotactic as the first treatment option, with repeated puncture and drainage in some patients until the abscess disappears [7], Su reported the incidence of recurrence and reoperation after stereotactic abscess puncture treatment for solitary brain abscess and MCPBA as 13.1% and 38%, respectively, arguing that simple abscess The inability of puncture to completely drain all the pus due to abscess segregation is the cause of recurrence [4]. Among our patients, 45 (90%) of 50 solitary brain abscesses underwent stereotactic surgery, of which 1 (2.2%) recurred and underwent stereotactic surgery again and 5 (10%) underwent craniotomy for resection; among 15 MPBAs, 14 patients underwent stereotactic puncture for a total of 37 abscesses, of which 1 abscess recurred and was surgically resected; among 18 MCPBAs Stereotactic surgery was performed in 13 of the 18 patients with MCPBA, in which a stereotactic surgical planning system was used to design one puncture tract to treat 2-3 pus chambers, or to extract and flush all pus chambers and inject antimicrobial agents as much as possible by intraoperatively changing the position and direction of the puncture needle or repeating the puncture, in which 4 abscesses recurred, 3 were cured after re-steotactic surgery and 1 after surgical resection, and the other 5 patients underwent direct craniotomy resection. We appreciate that although some MCPBAs cannot achieve a one-time cure by stereotactic surgery, satisfactory results can still be achieved by repeated punctures. The reason may be that repeated antimicrobial saline flushing after abscess puncture and high dose of antimicrobial injected into the abscess cavity when the drainage tube was removed made the local antimicrobial reach a high concentration, which was more effective in killing local bacteria that were difficult to be completely killed by systemic drugs. All the patients in this group achieved clinical cure except for those who died. Su reported a mortality rate of 16% in patients with MCPBA, similar to that of single or multiple brain abscesses in the literature [4], and Ersahin et al. noted no statistical difference in mortality between MPBA and MCPBA either. suggesting that if treated promptly MPBAMCPBA and solitary brain abscesses have the same good prognosis [21]. Most reports in the literature consider patient prognosis to be related to the patient’s GSC score on admission and other comorbidities. In our group, only three patients (20.0%) died in the multiple abscess group, one was admitted with high cranial pressure and impaired consciousness and progressive deterioration and died of uncontrollable severe diffuse cerebral edema on the third postoperative day despite stereotactic abscess puncture, one died one week after discharge as an abandoned patient, and another died of cardiac causes.There were no deaths in the MCPBA group. The above results also verified that death was closely related to the severity of the disease at the time of admission. Summary: 1. The incidence of MCPBA in this group was 21.2% and that of MPBA was 17.6%; 2. The most common route of infection in MPBA was distant infection via the hematogenous route to the intracranial area (73.3%), whereas the route of infection in MCPBA was similar to that in monogenic brain abscess. Stereotactic surgery is a very effective measure for the treatment of monogenic and multiple and MCPBA, and should be the first choice; 4. The main factor affecting the patient’s prognosis is the severity of the disease before treatment, and there is no significant relationship with whether it is multiple or multiroom.