Acta Neurochir DOI 10.1007/s00701-016-2741-4
CLINICAL ARTICLE - NEUROSURGICAL TECHNIQUES
Retrospective analysis of 620 cases of brain abscess in Chinese patients in a single center over a 62-year period Zhen Zhang 1,2 & Xinwang Cai 1,2 & Jia Li 3 & Xiaokui Kang 1,2 & Haining Wang 1,2 & Lin Zhang 1,2 & Rong Yan 1,2 & Nannan Gao 1,2 & Shengjie Liu 1,2 & Shuyuan Yue 1,2 & Jianning Zhang 1,2 & Shuyuan Yang 1,2 & Xinyu Yang 1,2
Received: 5 October 2015 / Accepted: 8 February 2016 # Springer-Verlag Wien 2016
Abstract Background Despite advances in laboratory diagnostics, antibiotic regimens, and neurosurgical techniques, brain abscess (BA) remains a potentially fatal infectious disease. This study analyzed clinical and epidemiological aspects of BA in Chinese patients treated at a single center during a 62-year period. Method We retrospectively analyzed 620 BA patients treated at Tianjin Medical University General Hospital, Tianjin, PR China from 1952 to 2014. Because of the initiation of imaging technology use in 1992, and other specific changes, we analyzed data over three study periods: 1952–1972, 1980–1991, and 2002–2014. Information including incidence, sex, age, community distribution, BA size and location, therapeutic method, prognosis and outcome of BA patients was collected and evaluated. Results Our study included 620 BA patients. The percentage mortality significantly decreased from 22.8 % in 1952 to 6.3 % in 2014 (p < 0.001). Although the incidence of BA was higher in males than females, there was no significant change in the male/female incidence ratio over time: 2.5 in Zhen Zhang, Xinwang Cai and Jia Li contributed equally to this work * Xinyu Yang [email protected]
1
Department of Neurosurgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, People’s Republic of China
2
Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, 154 Anshan Road, Heping District, Tianjin 300052, People’s Republic of China
3
Department of Neurosurgery, Baoding No.1 Hospital, Baoding 071000, People’s Republic of China
1952–1972, 2.6 in 1980–1991, and 2.2 in 2002–2014. The cryptogenic infection incidence significantly increased over time (p < 0.001). The number of positive bacterial cultures significantly decreased over the three study periods (p < 0.01). Conclusions The prognosis of patients with BA has gradually improved over the past 62 years in Tianjin, China. This may be because improvements in neurosurgical techniques, cranial imaging, and antimicrobial regimens have facilitated less invasive and more precise neurosurgical procedures. Keywords Brain abscess . Cryptogenic infection . Stereotactic aspiration . Chinese patients
Introduction Brain abscess (BA) is a pyogenic infection of the brain parenchyma surrounded by a capsule with fibroblasts and neovascularization [6]. Historically, BA has been caused by contiguous infection, hematogenous dissemination of bacteria, neurosurgical procedures, head trauma, or unknown mechanisms [6]. The incidence of BA has been estimated at 0.4 per 100, 000 people per year, whereas the true incidence is assumed to be greater in high risk groups such as patients with human immunodeficiency virus (HIV) or a history of treatment with immunosuppressive drugs [15]. Important changes over the past 6 decades (including the introduction of cranial imaging, improved neurosurgical techniques and antimicrobial regimens) have considerably improved the outcome of BA in Western countries [29]; the incidence of BA is approximately 8 % of intracranial masses and only 1–2 % mortality in Western countries [25]. However, because of different socioeconomic conditions over time, BA remains a disease associated with high morbidity and mortality in developing countries.
Acta Neurochir
The rapid development of China’s economy over the past few decades has led to rapid urbanization, accelerated population aging, improved medical insurance, and considerable lifestyle changes. A previous retrospective study in southern China analyzed data from 60 patients with BA in Shanghai [41]; however, a large series study of BA in China over the past 6 decades is still lacking. The Tianjin Medical University General Hospital is a large comprehensive teaching hospital and the birthplace of the Department of Neurosurgery in China. The institution has more than 1,600 beds, and is both a primary and tertiary referral center for most patients. This retrospective study aimed to identify any changes in epidemiological, clinical, diagnostic, therapeutic and prognostic aspects of BA patients treated at the Neurosurgery Department of Tianjin Medical University General Hospital over three study periods: 1952– 1972, 1980–1991, and 2002–2014.
Patients and methods Study design and setting We retrospectively analyzed and compared 620 BA cases treated in the Department of Neurosurgery at our hospital from 1952 to 2014. Since computed tomography (CT) became available in 1980 and stereotactic navigation systems have been used since the early twenty-first century, we analyzed the clinical aspects of BA over three study periods: 1952– 1972, 1980–1991, and 2002–2014. The following data were collected from hospital records: demographic data, neurological status at admission, clinical presentation, predisposing factors, anatomical location, organisms cultured, and treatment. The incidence, sex, BA location and characteristics, therapeutic method, and prognosis was systematically analyzed and compared over the three time periods. Patients meeting the following criteria were included: (1) those diagnosed with BA via angiography and/or A-scan ultrasound examination, CT and/or magnetic resonance imaging (MRI) findings; (2) evidence of BA seen on exploratory aspiration and/or collection of appropriate microbiological specimens; (3) classical clinical manifestations including headache, fever, and/or altered mental status. The following patients were excluded: (1) those with neurological symptoms unrelated to BA; (2) those with other forms of intracranial empyema such as epidural abscess or subdural empyema.
only aerobic culture was done in our laboratory from 1952– 1972. Both aerobic and anaerobic culture was done in 1980– 1991 and 2002–2014. Treatment Treatment consisted of either antimicrobial therapy only, aspiration and/or excision. Antimicrobial therapy only is supposed to be the most appropriate for small BAs or for patients in poor neurologic condition. Empirical treatments consisted of penicillin and chloramphenicol systemically in 1952–1972. Due to lack of bactericidal activity and potential side effects, chloramphenicol was limited. After that, vancomycin plus a third- or fourth-generation cephalosporin (i.e., ceftriaxone) and metronidazole became an effective regimen for empiric coverage since the 1980s. Antibiotic therapy lasted for 4–6 weeks in accordance with the therapeutic response and neuroimaging findings after the 1980s. Aspiration was suitable for BA located near brain areas controlling important bodily functions, deep-seated abscesses and diagnosis, especially with the use of stereotactic navigation systems. In cases of superficial BA, BA recurrence after aspiration, or BA not located near areas controlling important functions, the patients were more likely to be treated via excision. All benefits and risks of surgery were carefully explained to the patients and their relatives. Statistical analysis The chi-squared test was used between two groups for qualitative comparisons. One-way analysis of variance (ANOVA) was performed for comparisons among multiple groups, followed by a post hoc Bonferroni test. Statistical significance was set at p < 0.05. SPSS software version 17.0 (SPSS, Chicago, IL, USA) was used for statistical analysis.
Results Epidemiology Clinical characteristics of the patients in this series are displayed in Table 1. During a 62-year period (1952–2014), 620 BA patients were treated at our hospital. The mean age was under 60 years, there were 440 men (71 %) and 180 women (29 %), and the male-to-female ratio was 2.5 in 1952–1972, 2.6 in 1980–1991, and 2.2 in 2002–2014. Predisposing factors
Microbial findings All materials (pus, cerebrospinal fluid) obtained from the BA by exploratory aspiration, excision, or lumbar puncture were cultured for bacteria. However, owing to technical limitations,
Table 1 lists data available on the predisposing factors. The majority of BA cases were caused by contiguous spread; however, the rate of contiguous spread showed a significant decline over time: 66.3 % in 1952–1972, 37.1 % in 1980–1991,
Acta Neurochir Table 1 Characteristics at admission during different time periods
Characteristics
1952-1972
1980-1991
2002-2014
Number of patients (%)
Number of patients (%)
Number of patients (%)
Total number of patients
400
140
80
Mean age (years) Sex
0.05 p > 0.05
Congenital heart defects
16 (4.0)
—
6 (7.5)
Postoperative infection Unknown mechanisms
— 40 (10.0)
2 (1.4) 57 (40.7)
5 (6.3) 34 (42.5)
49 (12.3)
60 (42.9)
19 (23.8)
Temporal lobe Parietal lobe
168 (42.0) 22 (5.5)
57 (40.7) 19 (13.6)
13 (16.3) 4 (5.0)
Occipital lobe Cerebellum
1 (0.3) 115 (28.8)
4 (2.9) 14 (10.0)
3 (3.8) 5 (6.3)
387 (96.8) 340 (85.0) 223(55.8)
126 (90.0) 92 (65.7) 56 (14.0)
53 (66.3) 29 (36.3) 6 (7.5)
p < 0.001 p < 0.001 p < 0.001
229 (57.3) 74 (18.5) 82 (20.5) 91 (22.8)
87 (62.1) 12 (8.6) 39 (27.9) 10 (7.1)
48 (60.0) 17 (21.3) 14 (17.5) 5 (6.3)
p > 0.05 p > 0.05 p > 0.05 p < 0.001
Abscess location Frontal lobe
Presenting symptoms Headache Vomiting Papilledema Fever Focal neurological deficits Seizures Deaths
p < 0.001
The figures in parentheses are percentages
and 21.3 % in 2002–2014 (p < 0.001, Table 1). Moreover, the rate of infection of unknown origin significantly increased over time: 10 % in 1952–1972, 40.7 % in 1980–1991, and 42.5 % in 2002–2014 (p < 0.001, Table 1). The rates of hematogenous spread (13.0 % in 1952–1972, 16.4 % in 1980– 1991, 5 % in 2002–2014), congenital heart defects (4 % vs 7.5 %), postoperative infection (1.45 % vs 6.3 %), and posttraumatic infection (2.8 % in 1952–1972, 2.1 % in 1980– 1991, 6.3 % in 2002–2014) were not significantly different when compared with the rates of contiguous spread and unknown infection (p > 0.05, Table 1).
by nausea or vomiting (74.4 %, n = 461), and a history of fever (58.7 %, n = 364). Fourteen patients (16.6 %, n = 103) presented with focal neurological deficits (i.e., ataxia). Other presenting complaints included seizures (21.8 %, n = 135) and papilledema (46 %, n = 285). BA patients were significantly less likely to present with headache, vomiting and papilledema consistent with raised intracranial pressure in 1980–1991 and 2002–2014 compared with 1952–1972 (p < 0.001, Table 1).
Microbiological investigations Brain abscess locations and clinical manifestation The common abscess locations were the cerebellum and the temporal lobe, followed by the frontal lobe, parietal lobe, and occipital lobe over the entire study period from 1952 to 2014 (Table 1). The common clinical presentation over the entire study period (1952–2014) was headache (91.3 %, n = 566), followed
Bacterial cultures were performed in 347 patients in 1952– 1972 and 112 patients in 1980–1991. The organism was cultured from pus in 38 cases and cerebrospinal fluid cultures in 47 cases during 2002–2014 (Table 2). The three common p a t h o g e n s c u l t u r e d w e r e P ro t e u s s p p . ( n = 8 0 ) , Staphylococcus spp. (n = 77) and Streptococcus spp. (n = 43). Even though positive cultures were obtained in 332 cases (61 %), there was a significant decline throughout the three
Acta Neurochir Table 2 Microbial findings in 1952–1972, 1980–1991 and 2002-2014
Microbial findings
1952-1972
1980-1991
2002-2014
Number of patients
Number of patients
Number of patients
Staphylococcus aureus Staphylococcus epidermidis
56 0
16 0
3 2
Streptococcus pneumonia
2
1
0
Streptococcus aerobic Streptococcus viridians
41 0
0 0
0 7
Streptococcus hemolyticus Streptococcus mutans
0 0
7 0
0 1
Streptococcus intermadius
0
0
1
Proteus species Enterobacter species
64 12
16 0
0 2
Alcaligenes species Citrobacter freundii
6 0
0 4
0 0
Escherichia coli Gaffkya tetragena
0 10
4 0
0 0
Brazil Nocardia Anaerobic bacteria(14)
0 _
0
1
Peptococcus anaerobicus Bacteroides fragilis Escherichia coli Lactobacillus brevis
_ _ _ _
5 4 2 1
0 0 0 0
Proteus mirabilis Fungus (1) Multiple bacteria (49) Other organisms (12) Negative culture (212)
_ _ 30 10 116
0 _ 18 2 32
2 1 1 0 64
Total
347
112
85
p value
Aerobic bacteria(258)
p > 0.05 p > 0.05 p < 0.001
The figures in parentheses are total number of cases
study periods (p < 0.001, Table 2). There were no significant differences in the incidence of multiple bacterial infections over time, which accounted for 8.6 % of BA cases in 1952– 1972, 16.1 % in 1980–1991, and 1.2 % in 2002–2014 (p > 0.05, Table 2).
Treatment and outcome In 1952–1972, 177 patients (44.3 %) were treated with aspiration and 128 patients (31.3 %) had excision only. Of the patients treated with aspiration, 76 (19 %) then had excision for BA recurrence. In 1980–1991, treatment involved aspiration in 57 patients (40.7 %), excision in 56 patients (40 %), and aspiration then excision in 12 patients (8.6 %). In 2002–2014, we determined the different methods of treatment according to the BA location, size, forming time, and the patient’s condition. Of the 80 included patients from 2002 to 2014, 30 patients (37.5 %) received only a pure drug
treatment; in 90 % of these cases the disease improved, but three patients (3.75 %), who were in poor condition immediately after hospitalization, died. Neurosurgical treatment involved excision of the abscess in 27 patients, stereotactic aspiration in 19 patients, and four patients underwent excision after aspiration for abscess recurrence. There did not appear to be a vast difference between mortality rates in aspiration and excision groups from 1952 to 2014. However, when looking at the groups of data in the different time periods, there was a significantly lower mortality rate over time regardless of whether the patients were treated with aspiration or excision (p < 0.001, Table 3).
Discussion BA is a serious, life-threatening clinical disease and the management is complicated. Previous research showed that the
Acta Neurochir Table 3 Operation and results of 552 cases of brain abscess
Operation
Number of patients
Number of deaths
19521972
19801991
20022014
19521972
19801991
20022014
Aspiration Excision
177 128
57 56
19a 27
39 (22) 22 (17.2)
2 (3.5) 5 (8.9)
1 (5.9)a 1 (4)
Aspiration, then excision
76
12
4
25 (25)
2 (16.6)
0 (0)
The figures in parentheses are percentages a
Stereotactic navigation systems has been used in 2002–2014
incidence of BA has decreased from 2.7 % in 1935–1944 to 0.9 % in 1965–1981 in the USA [27]. Consistent with these findings, the incidence of BA decreased in the present study from 1952 to 2014. There were more male than female patients, with the male:female ratio ranging from 2.2:1 to 2.6:1, in accordance with previous research [5, 29]. There was a significant variance in mean age, ranging from 24 to 60 years, similar to the findings of other series [5, 11, 15, 22, 26, 38]. In contrast, Roche et al. [33] reported that BAs occurred in the first 2 decades of life; however, this may reflect the fact that their observations were based on research conducted during the past several decades, when childhood infections were seen more evidently [20, 24, 34]. Over the past 2 decades, wide use of CT and MRI has enhanced the diagnosis of BAs. Overall, mortality from BA has recently decreased from 40 to 60 % before the introduction of CT to 0–10 % afterward [7, 21, 23, 37]. In our study, the mortality associated with BA declined from 22.8 % in the pre-CT era during 1952–1972 to 7.1 % in 1980–1991and to 6.3 % in 2002–2014. The rate of BA patients with a good outcome increased from 33 to 70 %, with no or minimal neurologic sequelae [5]. A previous retrospective study reported that outcome was favorable in 78.33 % of Southern Chinese BA patients [41]. The clinical manifestations of BA were variable and nonspecific, as this is influenced by the size and location of the BA. In our previous work, fever and altered mental status were the common symptoms [5], but another previous study indicated that the triad of symptoms of BA occurred in a minority of cases (15–30 %) [39]. Some series have reported that fever was not helpful diagnostically and occurred in only 29 % [13] and 43 % [7] of cases; however, this is not in accordance with the results of our current study, in which headache, fever, and altered mental status were the frequent presenting symptoms, occurring in 91.3 %, 58.7 % and 16.6 % of BA patients, respectively. Seizures are a presenting sign in up to 25 % of BA patients, and may have either focal or generalized presentation [6, 7, 13, 39]. Similarly, in the present study, 20.5 %, 27.9 % and 17.5 % of BA patients showed different degrees of epileptic seizures in 1952–1972, 1980– 1991, and 2002–2014, respectively. Other important
symptoms identified in our current study were vomiting and papilledema, occurring in 74.4 % and 46 % of BA patients, respectively; this was similar to a previous study [5]. The common source of BA has previously been reported to be development from contiguous spread, arising from the frontal sinus, middle ear/mastoid, and dental infection [24, 28]; frontal sinus infection tends to lead to frontal lobe abscess, and temporal lobe and cerebellar abscess is associated with middle ear/mastoid infection [24, 28]. In contrast, the current study found a decline in the incidence of contiguous spread; this was similar to another study [12]. This decline in contiguous spread may be due to aggressive and widespread treatment of chronic otitis and sinusitis. Antibiotic management policies in China are relatively loose, and the preventative use of antibiotics is very common. In addition, with an increasing number of patients with HIV and those undergoing immunosuppressive therapy, cryptogenic infection has become an important predisposing factor for BA. A few recent case reports have detailed cryptogenic BA related to patent foramen ovale [9, 16, 18]. In contrast with previous reports [12, 19, 32], the rate of head trauma in the present study was not significantly different during the different time periods. Among the 480 patients with BA in 1952–1972 and 2002– 2014, 4.6 % of cases were associated with congenital heart disease, which was similar to our previous findings [40]; the most commonly reported form of congenital heart disease is tetralogy of Fallot [35, 40]. Although there was a trend toward a lower proportion of the Proteus spp. among the aerobic bacteria, Staphylococcus spp., Streptococcus spp. and Proteus spp. remained the most commonly identified pathogens over the three time periods studied; this was consistent with previous studies [5, 7, 20]. There was a significantly increased proportion of negative cultures in 1952–2014, which was likely due to aggressive and widespread use of antimicrobial therapy. When culture results are negative, PCR-amplified 16S ribosomal DNA sequencing can potentially overcome this limitation and provide a more sensitive and precise diagnosis [1, 2]. Cerebral nocardiosis accounts for only 2 % of all cerebral abscesses [23]. There was only one case of nocardia infection in the current series; this patient was cured after SMZ treatment,
Acta Neurochir
similarly to a previous report of nocardiosis treated with similar therapeutic drugs that achieved similar results [30]. Nocardial infections reportedly occur more frequently in immunocompromised hosts [36], but in our case there was no relevant medical history to suggest this. The management of patients with BA is complex, even though cranial imaging techniques and minimally invasive surgical techniques have greatly improved. After BA was confirmed in our hospital, infectious diseases doctors would participate in and offer beneficial consultative advice, promoting the appropriate and rational use of antimicrobial agents during the treatment. Under certain conditions, a purely medical treatment may be the only choice. For the choice of antimicrobial therapy, infectious diseases doctors play a significant, even primary, role in the medical care of BA patients. According to previous studies, if the BA is small (
CLINICAL ARTICLE - NEUROSURGICAL TECHNIQUES
Retrospective analysis of 620 cases of brain abscess in Chinese patients in a single center over a 62-year period Zhen Zhang 1,2 & Xinwang Cai 1,2 & Jia Li 3 & Xiaokui Kang 1,2 & Haining Wang 1,2 & Lin Zhang 1,2 & Rong Yan 1,2 & Nannan Gao 1,2 & Shengjie Liu 1,2 & Shuyuan Yue 1,2 & Jianning Zhang 1,2 & Shuyuan Yang 1,2 & Xinyu Yang 1,2
Received: 5 October 2015 / Accepted: 8 February 2016 # Springer-Verlag Wien 2016
Abstract Background Despite advances in laboratory diagnostics, antibiotic regimens, and neurosurgical techniques, brain abscess (BA) remains a potentially fatal infectious disease. This study analyzed clinical and epidemiological aspects of BA in Chinese patients treated at a single center during a 62-year period. Method We retrospectively analyzed 620 BA patients treated at Tianjin Medical University General Hospital, Tianjin, PR China from 1952 to 2014. Because of the initiation of imaging technology use in 1992, and other specific changes, we analyzed data over three study periods: 1952–1972, 1980–1991, and 2002–2014. Information including incidence, sex, age, community distribution, BA size and location, therapeutic method, prognosis and outcome of BA patients was collected and evaluated. Results Our study included 620 BA patients. The percentage mortality significantly decreased from 22.8 % in 1952 to 6.3 % in 2014 (p < 0.001). Although the incidence of BA was higher in males than females, there was no significant change in the male/female incidence ratio over time: 2.5 in Zhen Zhang, Xinwang Cai and Jia Li contributed equally to this work * Xinyu Yang [email protected]
1
Department of Neurosurgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, People’s Republic of China
2
Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, 154 Anshan Road, Heping District, Tianjin 300052, People’s Republic of China
3
Department of Neurosurgery, Baoding No.1 Hospital, Baoding 071000, People’s Republic of China
1952–1972, 2.6 in 1980–1991, and 2.2 in 2002–2014. The cryptogenic infection incidence significantly increased over time (p < 0.001). The number of positive bacterial cultures significantly decreased over the three study periods (p < 0.01). Conclusions The prognosis of patients with BA has gradually improved over the past 62 years in Tianjin, China. This may be because improvements in neurosurgical techniques, cranial imaging, and antimicrobial regimens have facilitated less invasive and more precise neurosurgical procedures. Keywords Brain abscess . Cryptogenic infection . Stereotactic aspiration . Chinese patients
Introduction Brain abscess (BA) is a pyogenic infection of the brain parenchyma surrounded by a capsule with fibroblasts and neovascularization [6]. Historically, BA has been caused by contiguous infection, hematogenous dissemination of bacteria, neurosurgical procedures, head trauma, or unknown mechanisms [6]. The incidence of BA has been estimated at 0.4 per 100, 000 people per year, whereas the true incidence is assumed to be greater in high risk groups such as patients with human immunodeficiency virus (HIV) or a history of treatment with immunosuppressive drugs [15]. Important changes over the past 6 decades (including the introduction of cranial imaging, improved neurosurgical techniques and antimicrobial regimens) have considerably improved the outcome of BA in Western countries [29]; the incidence of BA is approximately 8 % of intracranial masses and only 1–2 % mortality in Western countries [25]. However, because of different socioeconomic conditions over time, BA remains a disease associated with high morbidity and mortality in developing countries.
Acta Neurochir
The rapid development of China’s economy over the past few decades has led to rapid urbanization, accelerated population aging, improved medical insurance, and considerable lifestyle changes. A previous retrospective study in southern China analyzed data from 60 patients with BA in Shanghai [41]; however, a large series study of BA in China over the past 6 decades is still lacking. The Tianjin Medical University General Hospital is a large comprehensive teaching hospital and the birthplace of the Department of Neurosurgery in China. The institution has more than 1,600 beds, and is both a primary and tertiary referral center for most patients. This retrospective study aimed to identify any changes in epidemiological, clinical, diagnostic, therapeutic and prognostic aspects of BA patients treated at the Neurosurgery Department of Tianjin Medical University General Hospital over three study periods: 1952– 1972, 1980–1991, and 2002–2014.
Patients and methods Study design and setting We retrospectively analyzed and compared 620 BA cases treated in the Department of Neurosurgery at our hospital from 1952 to 2014. Since computed tomography (CT) became available in 1980 and stereotactic navigation systems have been used since the early twenty-first century, we analyzed the clinical aspects of BA over three study periods: 1952– 1972, 1980–1991, and 2002–2014. The following data were collected from hospital records: demographic data, neurological status at admission, clinical presentation, predisposing factors, anatomical location, organisms cultured, and treatment. The incidence, sex, BA location and characteristics, therapeutic method, and prognosis was systematically analyzed and compared over the three time periods. Patients meeting the following criteria were included: (1) those diagnosed with BA via angiography and/or A-scan ultrasound examination, CT and/or magnetic resonance imaging (MRI) findings; (2) evidence of BA seen on exploratory aspiration and/or collection of appropriate microbiological specimens; (3) classical clinical manifestations including headache, fever, and/or altered mental status. The following patients were excluded: (1) those with neurological symptoms unrelated to BA; (2) those with other forms of intracranial empyema such as epidural abscess or subdural empyema.
only aerobic culture was done in our laboratory from 1952– 1972. Both aerobic and anaerobic culture was done in 1980– 1991 and 2002–2014. Treatment Treatment consisted of either antimicrobial therapy only, aspiration and/or excision. Antimicrobial therapy only is supposed to be the most appropriate for small BAs or for patients in poor neurologic condition. Empirical treatments consisted of penicillin and chloramphenicol systemically in 1952–1972. Due to lack of bactericidal activity and potential side effects, chloramphenicol was limited. After that, vancomycin plus a third- or fourth-generation cephalosporin (i.e., ceftriaxone) and metronidazole became an effective regimen for empiric coverage since the 1980s. Antibiotic therapy lasted for 4–6 weeks in accordance with the therapeutic response and neuroimaging findings after the 1980s. Aspiration was suitable for BA located near brain areas controlling important bodily functions, deep-seated abscesses and diagnosis, especially with the use of stereotactic navigation systems. In cases of superficial BA, BA recurrence after aspiration, or BA not located near areas controlling important functions, the patients were more likely to be treated via excision. All benefits and risks of surgery were carefully explained to the patients and their relatives. Statistical analysis The chi-squared test was used between two groups for qualitative comparisons. One-way analysis of variance (ANOVA) was performed for comparisons among multiple groups, followed by a post hoc Bonferroni test. Statistical significance was set at p < 0.05. SPSS software version 17.0 (SPSS, Chicago, IL, USA) was used for statistical analysis.
Results Epidemiology Clinical characteristics of the patients in this series are displayed in Table 1. During a 62-year period (1952–2014), 620 BA patients were treated at our hospital. The mean age was under 60 years, there were 440 men (71 %) and 180 women (29 %), and the male-to-female ratio was 2.5 in 1952–1972, 2.6 in 1980–1991, and 2.2 in 2002–2014. Predisposing factors
Microbial findings All materials (pus, cerebrospinal fluid) obtained from the BA by exploratory aspiration, excision, or lumbar puncture were cultured for bacteria. However, owing to technical limitations,
Table 1 lists data available on the predisposing factors. The majority of BA cases were caused by contiguous spread; however, the rate of contiguous spread showed a significant decline over time: 66.3 % in 1952–1972, 37.1 % in 1980–1991,
Acta Neurochir Table 1 Characteristics at admission during different time periods
Characteristics
1952-1972
1980-1991
2002-2014
Number of patients (%)
Number of patients (%)
Number of patients (%)
Total number of patients
400
140
80
Mean age (years) Sex
0.05 p > 0.05
Congenital heart defects
16 (4.0)
—
6 (7.5)
Postoperative infection Unknown mechanisms
— 40 (10.0)
2 (1.4) 57 (40.7)
5 (6.3) 34 (42.5)
49 (12.3)
60 (42.9)
19 (23.8)
Temporal lobe Parietal lobe
168 (42.0) 22 (5.5)
57 (40.7) 19 (13.6)
13 (16.3) 4 (5.0)
Occipital lobe Cerebellum
1 (0.3) 115 (28.8)
4 (2.9) 14 (10.0)
3 (3.8) 5 (6.3)
387 (96.8) 340 (85.0) 223(55.8)
126 (90.0) 92 (65.7) 56 (14.0)
53 (66.3) 29 (36.3) 6 (7.5)
p < 0.001 p < 0.001 p < 0.001
229 (57.3) 74 (18.5) 82 (20.5) 91 (22.8)
87 (62.1) 12 (8.6) 39 (27.9) 10 (7.1)
48 (60.0) 17 (21.3) 14 (17.5) 5 (6.3)
p > 0.05 p > 0.05 p > 0.05 p < 0.001
Abscess location Frontal lobe
Presenting symptoms Headache Vomiting Papilledema Fever Focal neurological deficits Seizures Deaths
p < 0.001
The figures in parentheses are percentages
and 21.3 % in 2002–2014 (p < 0.001, Table 1). Moreover, the rate of infection of unknown origin significantly increased over time: 10 % in 1952–1972, 40.7 % in 1980–1991, and 42.5 % in 2002–2014 (p < 0.001, Table 1). The rates of hematogenous spread (13.0 % in 1952–1972, 16.4 % in 1980– 1991, 5 % in 2002–2014), congenital heart defects (4 % vs 7.5 %), postoperative infection (1.45 % vs 6.3 %), and posttraumatic infection (2.8 % in 1952–1972, 2.1 % in 1980– 1991, 6.3 % in 2002–2014) were not significantly different when compared with the rates of contiguous spread and unknown infection (p > 0.05, Table 1).
by nausea or vomiting (74.4 %, n = 461), and a history of fever (58.7 %, n = 364). Fourteen patients (16.6 %, n = 103) presented with focal neurological deficits (i.e., ataxia). Other presenting complaints included seizures (21.8 %, n = 135) and papilledema (46 %, n = 285). BA patients were significantly less likely to present with headache, vomiting and papilledema consistent with raised intracranial pressure in 1980–1991 and 2002–2014 compared with 1952–1972 (p < 0.001, Table 1).
Microbiological investigations Brain abscess locations and clinical manifestation The common abscess locations were the cerebellum and the temporal lobe, followed by the frontal lobe, parietal lobe, and occipital lobe over the entire study period from 1952 to 2014 (Table 1). The common clinical presentation over the entire study period (1952–2014) was headache (91.3 %, n = 566), followed
Bacterial cultures were performed in 347 patients in 1952– 1972 and 112 patients in 1980–1991. The organism was cultured from pus in 38 cases and cerebrospinal fluid cultures in 47 cases during 2002–2014 (Table 2). The three common p a t h o g e n s c u l t u r e d w e r e P ro t e u s s p p . ( n = 8 0 ) , Staphylococcus spp. (n = 77) and Streptococcus spp. (n = 43). Even though positive cultures were obtained in 332 cases (61 %), there was a significant decline throughout the three
Acta Neurochir Table 2 Microbial findings in 1952–1972, 1980–1991 and 2002-2014
Microbial findings
1952-1972
1980-1991
2002-2014
Number of patients
Number of patients
Number of patients
Staphylococcus aureus Staphylococcus epidermidis
56 0
16 0
3 2
Streptococcus pneumonia
2
1
0
Streptococcus aerobic Streptococcus viridians
41 0
0 0
0 7
Streptococcus hemolyticus Streptococcus mutans
0 0
7 0
0 1
Streptococcus intermadius
0
0
1
Proteus species Enterobacter species
64 12
16 0
0 2
Alcaligenes species Citrobacter freundii
6 0
0 4
0 0
Escherichia coli Gaffkya tetragena
0 10
4 0
0 0
Brazil Nocardia Anaerobic bacteria(14)
0 _
0
1
Peptococcus anaerobicus Bacteroides fragilis Escherichia coli Lactobacillus brevis
_ _ _ _
5 4 2 1
0 0 0 0
Proteus mirabilis Fungus (1) Multiple bacteria (49) Other organisms (12) Negative culture (212)
_ _ 30 10 116
0 _ 18 2 32
2 1 1 0 64
Total
347
112
85
p value
Aerobic bacteria(258)
p > 0.05 p > 0.05 p < 0.001
The figures in parentheses are total number of cases
study periods (p < 0.001, Table 2). There were no significant differences in the incidence of multiple bacterial infections over time, which accounted for 8.6 % of BA cases in 1952– 1972, 16.1 % in 1980–1991, and 1.2 % in 2002–2014 (p > 0.05, Table 2).
Treatment and outcome In 1952–1972, 177 patients (44.3 %) were treated with aspiration and 128 patients (31.3 %) had excision only. Of the patients treated with aspiration, 76 (19 %) then had excision for BA recurrence. In 1980–1991, treatment involved aspiration in 57 patients (40.7 %), excision in 56 patients (40 %), and aspiration then excision in 12 patients (8.6 %). In 2002–2014, we determined the different methods of treatment according to the BA location, size, forming time, and the patient’s condition. Of the 80 included patients from 2002 to 2014, 30 patients (37.5 %) received only a pure drug
treatment; in 90 % of these cases the disease improved, but three patients (3.75 %), who were in poor condition immediately after hospitalization, died. Neurosurgical treatment involved excision of the abscess in 27 patients, stereotactic aspiration in 19 patients, and four patients underwent excision after aspiration for abscess recurrence. There did not appear to be a vast difference between mortality rates in aspiration and excision groups from 1952 to 2014. However, when looking at the groups of data in the different time periods, there was a significantly lower mortality rate over time regardless of whether the patients were treated with aspiration or excision (p < 0.001, Table 3).
Discussion BA is a serious, life-threatening clinical disease and the management is complicated. Previous research showed that the
Acta Neurochir Table 3 Operation and results of 552 cases of brain abscess
Operation
Number of patients
Number of deaths
19521972
19801991
20022014
19521972
19801991
20022014
Aspiration Excision
177 128
57 56
19a 27
39 (22) 22 (17.2)
2 (3.5) 5 (8.9)
1 (5.9)a 1 (4)
Aspiration, then excision
76
12
4
25 (25)
2 (16.6)
0 (0)
The figures in parentheses are percentages a
Stereotactic navigation systems has been used in 2002–2014
incidence of BA has decreased from 2.7 % in 1935–1944 to 0.9 % in 1965–1981 in the USA [27]. Consistent with these findings, the incidence of BA decreased in the present study from 1952 to 2014. There were more male than female patients, with the male:female ratio ranging from 2.2:1 to 2.6:1, in accordance with previous research [5, 29]. There was a significant variance in mean age, ranging from 24 to 60 years, similar to the findings of other series [5, 11, 15, 22, 26, 38]. In contrast, Roche et al. [33] reported that BAs occurred in the first 2 decades of life; however, this may reflect the fact that their observations were based on research conducted during the past several decades, when childhood infections were seen more evidently [20, 24, 34]. Over the past 2 decades, wide use of CT and MRI has enhanced the diagnosis of BAs. Overall, mortality from BA has recently decreased from 40 to 60 % before the introduction of CT to 0–10 % afterward [7, 21, 23, 37]. In our study, the mortality associated with BA declined from 22.8 % in the pre-CT era during 1952–1972 to 7.1 % in 1980–1991and to 6.3 % in 2002–2014. The rate of BA patients with a good outcome increased from 33 to 70 %, with no or minimal neurologic sequelae [5]. A previous retrospective study reported that outcome was favorable in 78.33 % of Southern Chinese BA patients [41]. The clinical manifestations of BA were variable and nonspecific, as this is influenced by the size and location of the BA. In our previous work, fever and altered mental status were the common symptoms [5], but another previous study indicated that the triad of symptoms of BA occurred in a minority of cases (15–30 %) [39]. Some series have reported that fever was not helpful diagnostically and occurred in only 29 % [13] and 43 % [7] of cases; however, this is not in accordance with the results of our current study, in which headache, fever, and altered mental status were the frequent presenting symptoms, occurring in 91.3 %, 58.7 % and 16.6 % of BA patients, respectively. Seizures are a presenting sign in up to 25 % of BA patients, and may have either focal or generalized presentation [6, 7, 13, 39]. Similarly, in the present study, 20.5 %, 27.9 % and 17.5 % of BA patients showed different degrees of epileptic seizures in 1952–1972, 1980– 1991, and 2002–2014, respectively. Other important
symptoms identified in our current study were vomiting and papilledema, occurring in 74.4 % and 46 % of BA patients, respectively; this was similar to a previous study [5]. The common source of BA has previously been reported to be development from contiguous spread, arising from the frontal sinus, middle ear/mastoid, and dental infection [24, 28]; frontal sinus infection tends to lead to frontal lobe abscess, and temporal lobe and cerebellar abscess is associated with middle ear/mastoid infection [24, 28]. In contrast, the current study found a decline in the incidence of contiguous spread; this was similar to another study [12]. This decline in contiguous spread may be due to aggressive and widespread treatment of chronic otitis and sinusitis. Antibiotic management policies in China are relatively loose, and the preventative use of antibiotics is very common. In addition, with an increasing number of patients with HIV and those undergoing immunosuppressive therapy, cryptogenic infection has become an important predisposing factor for BA. A few recent case reports have detailed cryptogenic BA related to patent foramen ovale [9, 16, 18]. In contrast with previous reports [12, 19, 32], the rate of head trauma in the present study was not significantly different during the different time periods. Among the 480 patients with BA in 1952–1972 and 2002– 2014, 4.6 % of cases were associated with congenital heart disease, which was similar to our previous findings [40]; the most commonly reported form of congenital heart disease is tetralogy of Fallot [35, 40]. Although there was a trend toward a lower proportion of the Proteus spp. among the aerobic bacteria, Staphylococcus spp., Streptococcus spp. and Proteus spp. remained the most commonly identified pathogens over the three time periods studied; this was consistent with previous studies [5, 7, 20]. There was a significantly increased proportion of negative cultures in 1952–2014, which was likely due to aggressive and widespread use of antimicrobial therapy. When culture results are negative, PCR-amplified 16S ribosomal DNA sequencing can potentially overcome this limitation and provide a more sensitive and precise diagnosis [1, 2]. Cerebral nocardiosis accounts for only 2 % of all cerebral abscesses [23]. There was only one case of nocardia infection in the current series; this patient was cured after SMZ treatment,
Acta Neurochir
similarly to a previous report of nocardiosis treated with similar therapeutic drugs that achieved similar results [30]. Nocardial infections reportedly occur more frequently in immunocompromised hosts [36], but in our case there was no relevant medical history to suggest this. The management of patients with BA is complex, even though cranial imaging techniques and minimally invasive surgical techniques have greatly improved. After BA was confirmed in our hospital, infectious diseases doctors would participate in and offer beneficial consultative advice, promoting the appropriate and rational use of antimicrobial agents during the treatment. Under certain conditions, a purely medical treatment may be the only choice. For the choice of antimicrobial therapy, infectious diseases doctors play a significant, even primary, role in the medical care of BA patients. According to previous studies, if the BA is small (
