Keywords
brain abscess - chronic suppurative otitis media (CSOM) - prevention
Introduction
Brain abscess is a focal collection of pus in the brain parenchyma surrounded by a
well-vascularized collagenous capsule.[1] It is life-threatening condition with long-term neurological sequelae in 9 to 36%
of patients.[2] With the advancements in imaging and microbiological techniques, neurosurgical procedures,
and effective antibiotic treatments, brain abscess mortality has decreased in recent
years.[3] However, the incidence of brain abscess remains unchanged in developing countries,
particularly among populations of lower socioeconomic status due to chronic suppurative
otitis media (CSOM) and immunosuppression.[4]
[5] We searched PubMed and Google Scholar for references using the key words “brain
abscess” and “India” and reviewed both retrospective and prospective studies published
in peer-reviewed journals in this decade to understand the current status. There were
eight brain abscess ([Table 1]) and six otogenic brain abscess ([Table 2]) journal articles. The number of years of study from various institutions in [Table 1] ranges from 1.5 to 28 years and the number of patients in these studies ranges from
8 to 89 per year with an average of 24 brain abscess cases per year. Lakshmi et al
reported the average number of brain abscess specimens received for microbiological
analysis was 21 per year.[6]
Table 1
Publications on brain abscess in India in the current decade (2010–2019)
|
Reference and place of study
|
Duration and (y)
|
No. of patients
|
Age range (average)
|
Gender (%)
|
No. of culture positive (%) and organisms
|
Predisposing factors (%)
|
Location (%)
|
No. of died patients (%)
|
|
Male
|
Fe-male
|
|
Abbreviations: CSOM, chronic suppurative otitis media; CHD, congenital heart disease;
GNB, gram negative bacteria; No., number.
|
|
Tomar et al, 20117
Chhatrapati Sahuji Maharaj Medical University, Lucknow, Uttar Pradesh
|
Aug 2009–Dec 2010 (1.5)
|
30
|
9–47 (25)
|
24
(69)
|
11
(31)
|
22 (73). Pyogenic: 18 (82)
Streptococci: 10 (33)
Staphylococci: 1 (3)
Bacteroides sp.: 2 (6)
Nocardia: 1(3); Fungal:1 (3)
Mycobacteria: 3 (10)
Mixed infection 4: (13)
|
CSOM: 15 (50) CHD: 3 (10)
Postoperative/traumatic: 2(6)
Pulmonary tuberculosis: 2 (6)
|
Temporal: 10 (33)
Cerebellar: 9 (30)
Frontal: 3 (10)
Parietal: 4 (13)
Temporoparietal: 4 (13)
|
|
|
Lakshmi et al, 20116
Nizam’s Institute of Medical Sciences, Hyderabad, Telangana
|
1987–2010 (24)
|
352
|
2–80 (28)
|
|
|
247 (70); Pyogenic:232 (94)
S
taphylococcus
aureus: 68 (28)
Streptococcus: 35(14)
Enterococcus: 34 (14)
GNB:62(25) parasitic 2(0.5)
Anaerobes: 39 (16)
Mixed infections: 30 (12)
Fungal: 5 (1) Nocardia: 3(0.8)
Mycobacteria: 9 (5)
|
CSOM: 135 (38)
CHD: 32 (9)
Post-traumatic/operative: 42(12)
Pulmonary: 9 (3)
Sepsis: 33 (9)
Sinusitis: 8 (2)
|
Temporal: 81 (23)
Cerebellar: 26 (7)
Frontal: 81 (23)
Parietal: 102 (29)
Occipital: 12 (3)
Others: 11 (3)
Multiple: 39 (11)
|
|
|
Muzumdar et al, 20118
Seth GS Medical College & King Edward Memorial Hospital, Mumbai, Maharashtra
|
1999–2006 (7)
|
289
|
1.5–62 (32)
|
204 (71)
|
86 (29)
|
76 (26)
Streptococcus:19 (25)
Staphylococcus: 18 (24)
Klebsiella: 17 (22)
P
revotella
aeruginosa:16(21)
|
CSOM: 120 (42)
Pulmonary/CHD: 17 (6)
Post-traumatic/operative: 12 (4)
Sinusitis: 15 (5)
|
Temporal: 111 (38)
Cerebellar: 74 (25)
Frontal: 61 (21)
Parietal: 19 (7)
Occipital: 7 (2)
Multiple: 17 (6)
|
8 (3)
|
|
Sarmast et al., 20129
Sher I Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir (SKIMS)
|
Oct 2001–2011 (10)
|
114
|
0.5–70 (31)
|
83 (73)
|
31
(27)
|
93 (82)
S. pneumoniae: 22(24)
Staphylococcus:29(31)
Streptococcus: 16(17)
P. aeruginosa:11(12)
Enterobacter 4: (4)
K
lebsiella
pneumoniae: 3 (3)
Haemophilus
influenzae:6 (6)
B
acteroides
fragilis: 1 (1)
Peptostreptococcus: 1 (1)
Mixed infection: 4 (3)
|
CSOM: 57 (50)
CHD: 4 (4)
Post-traumatic/operative: 21(18)
Pulmonary: 8 (7)
Sinusitis: 6 (5)
Adjacent local infection: 3(2)
|
Temporal: 33 (29)
Cerebellar: 16(14)
Frontal: 17 (15)
Parietal: 12 (10)
Occipital: 6 (5)
Temporoparietal: 28(24)
Parieto-occipital: 9 (7)
|
8 (7)
|
|
Bajpai et al, 201410
Sanjay Gandhi Post Graduate Institute of Medical Sciences& King George Medical University
Lucknow, Uttar Pradesh
|
|
90
|
(24)
|
67
(74)
|
23
(26)
|
64 (71)
S. aureus:13 (20)
S. intermedius:8 (12)
Enterococcus sp.:4 (7)
Escherichia coli:7 (11)
P. aeruginosa: 4 (7)
P. mirabilis:2 (3)
B. fragilis:8 (12)
Fusobacterium sp.: 6 (10)
Peptostreptococcus sp.:5 (9)
Mixed infection: 7(8)
|
CSOM: 34 (49)
CHD: 3 (4)
Head trauma: 8(11)
Dental infection: 5(7)
Sinusitis: 6(6)
Pulmonary tuberculosis: 4 (5)
HIV: 2 (2)
Diabetes: 1(1)
|
Temporal: 11 (12)
Cerebellar: 12 (13)
Frontal: 23 (25)
Parietal: 21 (23)
Occipital: 3(3)
Temporoparietal: 6 (6)
Frontoparietal: 5 (5)
Temporo-occipital: 1 (1)
|
|
|
Kothari et al, 201511 King Edward Memorial Hospital & Seth Gordhandas Sunderdas Medical College, Mumbai,
Maharashtra
|
1998–2006 (8)
|
715
|
|
|
|
Tuberculosis: 426 (60)
Pyogenic: 280 (39)
Fungal: 9 (1)
|
CSOM: 189 (67)
CHD: 50 (18)
Post-traumatic: 14 (5)
Miscellaneous: 27(10)
|
Temporal: 111(39)
Cerebellar: 72 (26)
Frontal: 54(19)
Parietal: 19 (7)
Occipital: 7 (2)
Multiple: 17 (6)
|
39 (5)
|
|
Naik et al 201512
Osmania Hospital, Hyderabad, Telangana
|
June 2009–2012 (3)
|
24
|
2–70
|
20
83
|
4
17
|
11 (46)
Staphylococcus: 4 (17)
Streptococcus: 3 (13)
Klebsiella: 2 (9)
Mixed infection: 2 (9)
|
CSOM:10 (42)
CHD: 5 (20)
Post-traumatic/operative: 5 (20)
|
Temporal: 3 (13)
Cerebellar: 7(29)
Parietal: 6 (25)
Frontal: 3(13)
Occipital: 1 (4)
Temporoparietal: 2 (8)
Multiple: 2 (8)
|
|
|
Sudhaharan et al, 201613
Nizam's Institute of Medical Sciences, Hyderabad, Telangana
|
1987–2014 (28)
|
430
|
|
35
(73)
|
13
(27)
|
116:(27); anaerobes: 48 (41)
Peptostreptococcus: 26(54)
Bacteroides: 18 (37)
Peptococcus: 5 (10)
Veillonella: 3 (6)
P. melaninogenicus: 1(2)
Mixed 14: (3)
|
CSOM: 36(75)
CHD: 5 (10)
Trauma: 4 (8)
Pulmonary:1 (2)
|
Temporal: 13(27)
Cerebellar: 10(21)
Frontal: 12 (25)
Parietal: 4 (8)
Occipital: 2(4)
Frontoparietal: 6 (12)
|
1 (2)
|
Table 2
Publications on otogenic brain abscess in India in the current decade (2010–2019)
|
Reference and place of study
|
Duration (y)
|
No. of patients/samples
|
Age range in years
(average)
|
Gender (%)
|
Symptoms and predisposing factors
|
No. of culture positive and isolated organisms (%)
|
Location (%)
|
No. of died patients (%)
|
|
Male
|
Female
|
Temporal
|
Cerebellar
|
|
Abbreviations: NA, not available; No., Number; T-P, temporoparietal.
|
|
Borade et al, 201114
Dr. Vaishampayan Memorial Govt. Medical College, Solapur, Maharashtra
|
Jan 1997–Dec 2010 (4)
|
72
|
6–54 (16 y)
|
40 (55)
|
32 (45)
|
Cholesteatoma: 62 (86)
Granulations: 10 (14)
|
(20)
Escherichia coli,
Pseudomonas
Proteus spp.
Staphylococcus
Streptococcus
|
12(17)
|
60 (83)
|
5 (7)
|
|
Suligavi et al, 201515
SN Medical College, Agra, Uttar Pradesh
|
2008–2013 (6)
|
8
|
8–51 (21 y)
|
5 (63)
|
3 (37)
|
Headache: (100)
Vomiting: (63) Seizures: (38)
|
Pseudomonas sp.: 1
B
acteroides
fragilis:1
|
6 (75)
|
2 (25)
|
0
|
|
Borgohain et al, 201516
Gauhati Medical College & Hospital, Guwahati, Assam
|
July 2013–Dec 2014 (1.5)
|
17
|
5–20 (14 y)
|
12 (75)
|
4 (25)
|
Headache, nausea, and vomiting: (100)
|
12 (71)
Klebsiella: 5 (38)
Pseudomonas: 7 (54)
|
1 (6)
|
16 (94)
|
NA
|
|
Bhattacharjee et al, 2016.17
Silchar Medical College, Silchar, Assam
|
Sept 2014–2015 (1)
|
33
|
9–65 (21 y)
|
18 (54)
|
15 (46)
|
Headache: (90)
Fever: 25 (76)
Seizures: 55
Cholesteatoma: (76)
|
Proteus mirabilis and
Enterococcus: 17 (52)
P. aeruginosa: 16 (48)
|
25 (76)
|
8 (24)
|
0
|
|
Mukherjee et al, 201618
KPC Medical College & Hospital, Kolkata, West Bengal
|
May 2009–April 2014 (5)
|
22
|
8–58 (26 y)
|
17 (77)
|
5 (23)
|
Headache: (100)
Fever: 13 (59)
Altered sensorium: 9 (41)
|
NA
|
7 (32)
|
15 (68)
|
0
|
|
Melkundi and Melkundi, 201719 MR Medical College and Gulbarga Institute of Medical Sciences, Gulbarga, Karnataka
|
2006–2015 (10)
|
20
|
4–32 (18 y)
|
16 (80)
|
4 (20)
|
NA
|
NA
|
6 (30)
T-P 5 (25)
|
8 (40)
|
2 (10)
|
Common Symptoms
As shown in [Table 1], the majority of brain abscess patients in India was males, which is in line with
findings of studies across the globe.[20]
[21]
[22] The average age of the patients was 20 to 30 years, which is similar or a decade
lower compared with studies in other countries.[2]
[5]
[23] Headache was found to be the most common symptom. Other symptoms include fever,
focal neurologic deficit, seizure, nausea, and vomiting.[8]
[9]
[10]
[11] Studies in other countries have reported similar symptoms.[24] The classic triad of fever, headache, and focal neurologic deficit was observed
in half of the patients, and the mean duration of the symptoms before diagnosis was
approximately 8 days.[25]
[26]
[27]
Neuropathology
Brain abscess begin as localized areas of cerebritis in the brain parenchyma in response
to an infection. The computed tomography (CT) or magnetic resonance imaging (MRI)
studies show that the brain abscess development can be divided into four stages: early
cerebritis (Days 1–3), late cerebritis (Days 4–9), early capsule formation (Days 10–13),
and late capsule formation (after Day 14). A well-developed abscess consists of five
distinct histological zones: a necrotic center, a peripheral zone of inflammatory
cells, a dense collagenous capsule, a layer of neovascularization, and cerebral edema
external to the capsule.[27]
More than 90% of the brain abscesses reported in [Tables 1] and 2 were single and were located in the frontal and temporal lobes and the cerebellum,
and occasionally in the parietal and occipital lobes. The most common predisposing
condition was middle ear infection (8–75%), as shown in [Table 1]. Other common predisposing conditions were congenital heart disease (CHD; 4–20%),
post-traumatic, and neurosurgical procedures (4–20%). Other studies have reported
CSOM as the main predisposing factor, followed by post-traumatic and CHD.[5]
[24]
[28] Middle ear infections are associated with abscess formation in the temporal or cerebellar
lobes ([Table 2]). In addition, intraventricular rupture of brain abscess has been reported, resulting
in acute deterioration and death.[29]
[30] Other factors that contribute to intracranial complications are the virulence of
organisms and the host’s immunity status.[15] Whole genome sequencing of Streptococcus intermedius TYG1620 isolated from a human brain abscess showed the presence of the type VII secretion
system, which might be associated with strain-specific pathogenicity, including abscess
formation.[31] The host inflammatory response, which increases with bacterial cell lysis following
the administration of antibiotics, can cause damage to the surrounding normal brain
parenchyma, which exceeds the brain area occupied by the infecting organism.[32] It has been shown that several inflammatory cytokine (tumor necrosis factor-α [TNF-α],
interferon-γ, interleukin-1β [IL-1β], IL-10, IL-17, IL-23) levels are significantly
higher in a brain abscess than in blood, and their expression in the abscess is influenced
by the bacterial pathogen and the duration of symptoms.[10]
Etiology
This review found that 26 to 82% of the brain abscess samples were culture-positive
([Table 1]). The most frequently identified bacteria were Streptococci (12–42%), Staphylococci (3–31%), Enterococci (7–14%), and gram-negative bacteria (9–23%), including Escherichia coli, Klebsiella, Enterobacter, Citrobacter, Proteus, and Pseudomonas. Anaerobic bacteria (2–41%) such as Peptostreptococcus, Bacteroides, Peptococcus, Fusobacterium, and Veillonella were also isolated in some studies. Nocardia and fungi were seen in 1 to 3% of samples.
Mycobacterium tuberculosis was isolated from 5% (9 cases) and 10% (3 cases) of brain abscess samples in two
studies.[6]
[7] Only one study showed 60% tubercular abscess outnumbering pyogenic abscesses probably
due to endemicity of tuberculosis in India.[11] Mixed infections were observed in 3 to 13% of samples. A retrospective analysis
of 317 brain abscess samples collected over a 3-year period (January 2012 to December
2014) at the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore,
found rare pathogens in 19 samples (12%), including Cryptococcus neoformans, Aspergillus flavus, Mucor, Salmonella, and Pantoea.[33] Molecular characterization of methicillin-resistant S. aureus (MRSA) showed community-acquired (CA-MRSA), hospital-acquired (HA-MRSA), and livestock-associated
(LA-MRSA) strains in brain abscess samples.[34] CSOM was mostly caused by gram-negative bacteria, including E. coli, Klebsiella, Pseudomonas, and Proteus ([Table 2]). The distribution of bacterial pathogens identified in brain abscesses has been
shown to be relatively similar in different continents and to have remained stable
over the past 60 years.[2]
Diagnosis
Imaging techniques such as cranial CT and MRI were used in most studies to confirm
the clinical diagnosis and for follow ups. In some cases, imaging techniques enabled
safe and successful medical treatment without surgical intervention.[8]
[9] MRI, when combined with diffusion-weighted images (DWI) and apparent diffusion coefficients
(ADC) images, differentiates pyogenic brain abscess from nonpyogenic abscesses, neoplasm,
cystic, or necrotic tumors.[7]
[8] Magnetic resonance spectroscopy (MRS) analysis differentiated between brain abscesses
and tumors, as well as between anaerobes and aerobes.[35]
Comprehensive microbiological investigations of brain abscesses were conducted in
most studies, including wet mounts, Gram’s staining, Ziehl–Neelsen staining, and conventional
aerobic and anaerobic cultures. BACTEC aerobic and anaerobic media were used in some
studies to isolate bacterial pathogens.[7]
[10] In other studies, anaerobic incubation was performed in jars using commercial GasPak
systems.[6]
[13]The isolates were identified by standard biochemical tests. Smears and cultures were
also performed for mycobacteria, nocardia, and fungi when requested. This review shows
that the incidence of negative cultures was 18 to 73% ([Tables 1] and [2 ]), which is similar to other reports.[21]
[36] Polymerase chain reaction(PCR) was not performed routinely, but PCR amplification
and sequencing of 16S ribosomal RNA (rRNA) in one study showed the presence of bacterial
DNA in 37% of the culture-negative samples.[35] Other reports demonstrated the usefulness of 16S rRNA PCR sequencing in bacterial
identification in culture-negative samples and samples containing fastidious bacteria.[37]
[38] Multiple sequencing by metagenomics increases the number of identified bacteria
in brain abscess samples, and next-generation sequencing (NGS) identifies infectious
agents with higher confidence where microbiology fails to detect the presence of microbes.[39]
[40]
Management
Patients were managed with combined medical (e.g., antibiotic, steroid, and anticonvulsant)
and surgical (aspiration and excision) treatments and monitored with weekly CT or
MRI scans until the abscess completely disappeared. Empirical intravenous broad-spectrum
antibiotic treatments were immediately initiated upon diagnosis and were further modified
according to microbiological isolation and antibiotic sensitivity. Antibiotics that
are active against both aerobes and anaerobes such as a third-generation cephalosporin,
metronidazole and vancomycin to cover streptococci, staphylococci, strict anaerobes,
and Enterobacteriaceae were used. Aminoglycosides were used for Pseudomonas infection. Long-term therapy with cotrimoxazole or sulfadiazine was used for nocardia
abscesses and antituberculosis drugs were used for treating tuberculous abscesses.
Flucytosine, amphotericin B, and voriconazole were used for fungal infections.[8] Antibiotic therapy was continued for 6 weeks or longer, depending on the therapeutic
response and the neuroimaging findings.[8]
[9]
[11] Abscesses in the cerebritis stage measuring less than 2 cm in diameter and multiple
deep-seated abscesses were treated with medical regimens alone.[9] Surgery was performed for large abscesses and in patients with a poor response to
medical treatment. Most patients underwent abscess aspiration through a single burrhole.[11] If the size of the abscess shown in CT or MR images after the first aspiration increased
or was not reduced despite antibiotic therapy, the aspiration was repeated. Patients
with a poor response to repeated aspirations and post-traumatic abscesses underwent
complete abscess excision through craniotomy.[1]
[8] Stereotactic aspiration is associated with few complications compared with excision
that involves hemorrhage, cerebrospinal fluid (CSF) leakage, seizure, and stroke.[41] When the efficacies of aspiration and excision were compared for the management
of pyogenic brain abscesses, excision was found to be better with respect to duration
of antibiotic use, length of hospital stay, and overall cost of treatment.[42] However, excision is said to have a poor outcome when the abscess is deep-seated
and in the cerebritis stage.[41] In CSOM cases, patients underwent craniotomy for abscess removal followed by radical
mastoidectomy under single anesthesia in the same session or mastoidectomy was done
after the patient’s general and neurological conditions were stabilized.[17]
[19] High-dose corticosteroid treatment was administered to patients with life-threatening
cerebral edema or cerebral herniation and tapered over a period of 4 weeks.[8] Anticonvulsants were administered as prophylactics, and the duration of therapy
was individualized and guided by electroencephalographic (EEG) reports.[9]
[11] The mortality rate in brain abscess patients was 2 to 7%, and up to 10% in patients
with middle ear infection ([Tables 1] and [2 ]).
Prevention
Eradication of potential sources of infection before the abscess fully develops is
a reasonable preventive strategy. Middle ear infection, which is often neglected and
not treated aggressively, remains the most frequent predisposing condition in India
([Tables 1] and [2]) and other Asian countries.[43]
[44]
[45]
[46] Multidisciplinary treatment strategies to address the primary source have helped
to improve outcomes in otogenic brain abscesses.[19] Congenital cyanotic heart disease (CCHD) in the majority of children in Asia remains
either uncorrected or only partially palliated. Uncured CCHD is a high-risk factor
for the occurrence, persistence, and recurrence of a brain abscess.[47]
[48] Prompt diagnosis of CCHD and corrective surgery might help to reduce the development
of brain abscesses in children.[49] Head trauma has become an important predisposing factor with the increasing incidence
of traffic accidents, which requires safety measures.[23] Tooth extraction and treatment for sinusitis may also help to remove the focus of
infection and prevent further spread of bacteria.[50] The duration of hospitalization increases the risk of nosocomial infections concomitant
with higher mortality.[36] Infection control strategies in intensive care units (ICUs) may help to improve
brain abscess outcomes.[20] Health awareness in terms of ear and oral hygiene may help to reduce the overall
incidence of brain abscess.[51]
[52]
Conclusion
The incidence of brain abscess continues to be high in India due to CSOM, particularly
among socioeconomically vulnerable populations with poor health consciousness ([Tables 1] and [2]). New developments include hyperbaric oxygen therapy, which improves brain abscess
outcomes.[53] Gene therapy is another prospect, as there is an association between single nucleotide
polymorphisms in TNF-α, IL-1β, Intercellular Adhesion Molecule 1 (ICAM-1), and monocyte
chemoattractant protein-1 (MCP-1) genes and increased risk of brain abscess development.[54]
[55] Identifying pathogens associated with brain abscess using NGS might contribute to
early detection and appropriate treatment.
