- Email: [email protected]
Silent Brain Abscess in Patients With Infective Endocarditis
MAYO CLINIC PROCEEDINGS
large prospectively collected database of Danish patients who had bacterial meningitis. Specifically, Bijlsma and associates evaluated our risk score in a cohort of 218 patients who had bacterial meningitis and a negative Gram stain. They discovered that our model had a high sensitivity (98.5%) but a very low specificity (9.2%) for identifying patients with meningitis and a negative Gram stain at risk for an adverse clinical outcome. We derived and validated our prognostic model in a very large and heterogeneous patient population from the Houston, Texas, area that included meningitis caused by viruses, bacteria, fungi, and mycobacteria and in which only 22 of 567 patients (3.7%) had culture-proven bacterial meningitis. In contrast, the analysis by Bijlsma and colleagues included only bacterial meningitis cases, which are associated with higher adverse clinical outcomes. In the United States, the use of conjugate vaccines has reduced the incidence of bacterial meningitis from 5.5 cases per 100,000 persons in 1986 to 1.38 per 100,000 persons in 2007.1 Thus, although the fraction of bacterial meningitis cases we reported differs considerably from that of Bijlsma and associates, our data accurately reflect the current epidemiology of community-acquired meningitis with a negative Gram stain in US hospitals.2 It is reassuring to see that 203 of 218 patients (93%) with bacterial meningitis and a negative Gram stain in the Dutch Meningitis Cohort Study were identified by our high-risk score and that their adverse clinical outcome rate was 30%. The low-risk score in that study was seen in only 15 of the 218 patients (7%), and only 1 of the 15 (7% of the patients with a low-risk score; 0.5% of the 218 patients with bacterial meningitis with a negative Gram stain) had an adverse clinical outcome. The single low-risk patient who had an adverse outcome had nosocomial meningitis and would have been excluded from 422
our community-acquired meningitis study; hence, applying our calculations to this adverse clinical outcome in the analysis by Bijlsma and colleagues yielded a 0% adverse outcome rate. Despite these reassuring findings, we agree with Bijlsma and associates that a risk score specifically derived and validated in patients with bacterial meningitis is preferred in predicting outcomes in this patient population.3,4 Nabil T. Koury, MD University of Texas Health Science Center Houston, TX
Monir Hossain, PhD Cincinnati Children’s Hospital Medical Center Cincinnatti, OH
Susan H. Wootton, MD Lucrecia Salazar, MD Rodrigo Hasbun, MD University of Texas Health Science Center Houston, TX 1. McIntyre PB, O’Brien KL, Greenwood B, van de Beek D. Effect of vaccines on bacterial meningitis worldwide. Lancet. 2012;380(9854): 1703-1711. 2. Khoury NT, Hossain MM, Wootton SH, Salazar L, Hasbun R. Meningitis with a negative cerebrospinal fluid gram stain in adults: risk classification for an adverse clinical outcome. Mayo Clinic Proc. 2012; 87(12):1181-1188. 3. Aronin SI, Peduzzi P, Quagliarello VJ. Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing. Ann Intern Med. 1998;129(11): 862-869. 4. Weisfelt M, van de Beek D, Spanjaard L, Reitsma JB, de Gans J. A risk score for unfavorable outcome in adults with bacterial meningitis. Ann Neurol. 2008; 63(1):90-97. http://dx.doi.org/10.1016/j.mayocp.2013.01.017
Silent Brain Abscess in Patients With Infective Endocarditis To the Editor: There are few reports in the literature describing central nervous system abscess in asymptomatic patients with infective endocarditis (IE). In a report by Snygg-Martin et al,1 silent brain lesions were detected in 30% of patients with left-sided IE. However, findings consistent with abscesses were
not described. Ruttmann et al2 studied patients undergoing cardiac surgery for IE. They found cerebral abscesses in 5 of 65 patients (7.7%), but they did not mention any clinical findings observed before surgery. In a study by Thuny et al,3 the incidence of silent emboli was 3.8%, but not all patients included were critically ill. We conducted a cross-sectional study to determine the prevalence of silent brain abscesses among patients with IE. The medical records of 47 consecutive patients with IE admitted to our cardiology service were reviewed. Three were excluded for having right-sided IE. The remaining 44 patients had indications for valve replacement surgery. They were evaluated for motor or sensory deficits and changes in mental status, according to the modified Rankin Scale (mRS). Fifteen of the 44 patients were excluded because they had some degree of encephalopathy and/or motor deficit. Of the remaining 29 patients who were asymptomatic, 27 underwent cranial magnetic resonance imaging and 2 underwent computed tomography before they had surgery. The median SD age of the patients was 5414.8 years, and 33 patients (75%) were males. An abscess was considered early stage (cerebritis) when an area of hypointensity was observed on T1- and T2weighted magnetic resonance imaging; the abscess was considered a mature brain abscess when it exhibited low intensity on a T1-weighted image, with a smooth marginated capsule that enhanced with gadolinium contrast medium. Of the 29 asymptomatic patients (mRS, 0) with left-sided IE, 6 (21%) had a brain abscess, and 23 of them did not. These abscesses ranged from 6 to 35 mm in diameter, and most were located in the frontal and temporal lobes. The prevalence of silent brain abscess was 21%.The most frequently involved valve in both groups (those with and without Mayo Clin Proc. n April 2013;88(4):420-424 www.mayoclinicproceedings.org
LETTERS TO THE EDITOR
TABLE. Characteristics and Findings in 29 Asymptomatic Patients With Infective Endocarditis With and Without Brain Abscessa,b
Characteristic/finding Female Age (y) Vegetationc Days from fever onset In-hospital mortality Valve involved Mitral NV Aortic NV MAo NV Mitral PV Aortic PV MAo PV Positive blood culture Blood culture microorganism Streptococcus Enterococci Staphylococcus aureus Staphylococci, coagulase-negative Streptococcus pneumoniae GNB Valve Gram stain Positive cocci GNB Valve culture Streptococcus viridans Enterococcus faecalis S aureus PCM Surgery indication: HF
Patients with brain abscess (n¼6) 44 6 25 1
0 (36-76) (100) (20-40) (17)
0 4 (67) 1 (17) 0 1 (17) 0 2 (33) 1 (17) 1 (17) 0 0 0 0 1/5 (20) 0 0 0 0 3 (50) 3 (50)
Patients without brain abscess (n¼23) 7 55 21 12 5
(30) (17-84) (91) (2-150) (22)
8 6 4 3 2
(35) (26) (17) (13) (9) 0 15 (65) 3 2 6 1 1 1
P value .64 .75 .45 .98 .78 .08 .06 .96 .35 .56 .33 .15
(13) (9) (26) (4) (4) (4)
.81 .56 .16 .60 .60 .60
9/18 (50) 2/18 (11)
.23 .43
1/18 1/18 2/18 19 20
.59 .59 .43 .09 .04
(5) (5) (11) (83) (87)
GNB ¼ aerobic gram-negative bacilli; HF ¼ heart failure; MAo ¼ mitral and aortic; NV ¼ native valve; PCM ¼ previous cardiomyopathy; PV ¼ prosthetic valve. b Data are presented as No. (percentage) or mean (range). c Diagnosed by echocardiography. a
brain abscess) was a native aortic valve. The most common reason for valve replacement was heart failure in the group of patients without brain abscess. As shown in the Table, there were no significant differences between the groups in blood culture findings, valve Gram stain and culture, and previous heart pathology. None of the patients with IE and brain abscesses had diabetes, multiple organ dysfunction, septic shock, or thrombocytopenia. One patient had acute renal failure,
Mayo Clin Proc. n April 2013;88(4):420-424 www.mayoclinicproceedings.org
and one had hepatic dysfunction. No patients in this group died. Among the patients with IE and no brain abscess, 1 presented with septic shock, 7 had thrombocytopenia, almost half (48%) had acute renal failure, 7 had multiple organ dysfunction, and 5 had spleen abscesses. Of the 5 patients who died in this group, all had heart failure. There were no significant differences between groups in terms of clinical findings, type of valve affected, or microorganism producing the endocarditis.
The high prevalence of silent brain abscess in this study could be explained by the fact that all of the patients were critically ill and required valve replacement surgery. In patients with IE, the presence of a brain abscess is an important consideration in decisions regarding medical vs surgical treatment.4,5 Because of the lack of typical clinical findings in patients with IE and silent brain abscesses, routine brain imaging assessment could be cost-effective and provide opportunities to recognize and treat this entity early, particularly in patients who are severely ill. María C. Ferreyra, MD Esther R. Chavarría, PhD Fundación Médica de Río Negro y Neuquén Cipolletti, Río Negro, Argentina
Diego A. Ponieman, MD, MPH Mount Sinai Medical Center New York, NY
Pablo A. Olavegogeascoechea, MD, MPH Universidad Nacional del Comahue Cipolletti, Río Negro, Argentina 1. Snygg-Martin U, Gustafsson L, Rosengren L, et al. Cerebrovascular complications in patients with left-sided infective endocarditis are common: a prospective study using magnetic resonance imaging and neurochemical brain damage markers. Clin Infect Dis. 2008;47(1):23-30. 2. Ruttmann E, Willeit J, Ulmer H, et al. Neurological outcome of septic cardioembolic stroke after infective endocarditis. Stroke. 2006;37(8): 2094-2099. 3. Thuny F, Avierinos JF, Tribouilloy CH, et al. Impact of cerebrovascular complications on mortality and neurologic outcome during infective endocarditis: a prospective multicentre study. Eur Heart J. 2007; 28(9):1155-1161. 4. Arlotti M, Grossi P, Pea F, et al; GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) Working Group on Brain Abscesses. Consensus document on controversial issues for the treatment of infections of the central nervous system: bacterial brain abscesses. Int J Infect Dis. 2010;14(suppl 4):S79-S92. 5. Tunkel AR, Wispelwey B, Scheld WM. Brain abscess. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 5th ed., Vol 1. Philadelphia, PA: Churchill Livingstone; 2000: 1016-1028. http://dx.doi.org/10.1016/j.mayocp.2013.02.001
423
large prospectively collected database of Danish patients who had bacterial meningitis. Specifically, Bijlsma and associates evaluated our risk score in a cohort of 218 patients who had bacterial meningitis and a negative Gram stain. They discovered that our model had a high sensitivity (98.5%) but a very low specificity (9.2%) for identifying patients with meningitis and a negative Gram stain at risk for an adverse clinical outcome. We derived and validated our prognostic model in a very large and heterogeneous patient population from the Houston, Texas, area that included meningitis caused by viruses, bacteria, fungi, and mycobacteria and in which only 22 of 567 patients (3.7%) had culture-proven bacterial meningitis. In contrast, the analysis by Bijlsma and colleagues included only bacterial meningitis cases, which are associated with higher adverse clinical outcomes. In the United States, the use of conjugate vaccines has reduced the incidence of bacterial meningitis from 5.5 cases per 100,000 persons in 1986 to 1.38 per 100,000 persons in 2007.1 Thus, although the fraction of bacterial meningitis cases we reported differs considerably from that of Bijlsma and associates, our data accurately reflect the current epidemiology of community-acquired meningitis with a negative Gram stain in US hospitals.2 It is reassuring to see that 203 of 218 patients (93%) with bacterial meningitis and a negative Gram stain in the Dutch Meningitis Cohort Study were identified by our high-risk score and that their adverse clinical outcome rate was 30%. The low-risk score in that study was seen in only 15 of the 218 patients (7%), and only 1 of the 15 (7% of the patients with a low-risk score; 0.5% of the 218 patients with bacterial meningitis with a negative Gram stain) had an adverse clinical outcome. The single low-risk patient who had an adverse outcome had nosocomial meningitis and would have been excluded from 422
our community-acquired meningitis study; hence, applying our calculations to this adverse clinical outcome in the analysis by Bijlsma and colleagues yielded a 0% adverse outcome rate. Despite these reassuring findings, we agree with Bijlsma and associates that a risk score specifically derived and validated in patients with bacterial meningitis is preferred in predicting outcomes in this patient population.3,4 Nabil T. Koury, MD University of Texas Health Science Center Houston, TX
Monir Hossain, PhD Cincinnati Children’s Hospital Medical Center Cincinnatti, OH
Susan H. Wootton, MD Lucrecia Salazar, MD Rodrigo Hasbun, MD University of Texas Health Science Center Houston, TX 1. McIntyre PB, O’Brien KL, Greenwood B, van de Beek D. Effect of vaccines on bacterial meningitis worldwide. Lancet. 2012;380(9854): 1703-1711. 2. Khoury NT, Hossain MM, Wootton SH, Salazar L, Hasbun R. Meningitis with a negative cerebrospinal fluid gram stain in adults: risk classification for an adverse clinical outcome. Mayo Clinic Proc. 2012; 87(12):1181-1188. 3. Aronin SI, Peduzzi P, Quagliarello VJ. Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing. Ann Intern Med. 1998;129(11): 862-869. 4. Weisfelt M, van de Beek D, Spanjaard L, Reitsma JB, de Gans J. A risk score for unfavorable outcome in adults with bacterial meningitis. Ann Neurol. 2008; 63(1):90-97. http://dx.doi.org/10.1016/j.mayocp.2013.01.017
Silent Brain Abscess in Patients With Infective Endocarditis To the Editor: There are few reports in the literature describing central nervous system abscess in asymptomatic patients with infective endocarditis (IE). In a report by Snygg-Martin et al,1 silent brain lesions were detected in 30% of patients with left-sided IE. However, findings consistent with abscesses were
not described. Ruttmann et al2 studied patients undergoing cardiac surgery for IE. They found cerebral abscesses in 5 of 65 patients (7.7%), but they did not mention any clinical findings observed before surgery. In a study by Thuny et al,3 the incidence of silent emboli was 3.8%, but not all patients included were critically ill. We conducted a cross-sectional study to determine the prevalence of silent brain abscesses among patients with IE. The medical records of 47 consecutive patients with IE admitted to our cardiology service were reviewed. Three were excluded for having right-sided IE. The remaining 44 patients had indications for valve replacement surgery. They were evaluated for motor or sensory deficits and changes in mental status, according to the modified Rankin Scale (mRS). Fifteen of the 44 patients were excluded because they had some degree of encephalopathy and/or motor deficit. Of the remaining 29 patients who were asymptomatic, 27 underwent cranial magnetic resonance imaging and 2 underwent computed tomography before they had surgery. The median SD age of the patients was 5414.8 years, and 33 patients (75%) were males. An abscess was considered early stage (cerebritis) when an area of hypointensity was observed on T1- and T2weighted magnetic resonance imaging; the abscess was considered a mature brain abscess when it exhibited low intensity on a T1-weighted image, with a smooth marginated capsule that enhanced with gadolinium contrast medium. Of the 29 asymptomatic patients (mRS, 0) with left-sided IE, 6 (21%) had a brain abscess, and 23 of them did not. These abscesses ranged from 6 to 35 mm in diameter, and most were located in the frontal and temporal lobes. The prevalence of silent brain abscess was 21%.The most frequently involved valve in both groups (those with and without Mayo Clin Proc. n April 2013;88(4):420-424 www.mayoclinicproceedings.org
LETTERS TO THE EDITOR
TABLE. Characteristics and Findings in 29 Asymptomatic Patients With Infective Endocarditis With and Without Brain Abscessa,b
Characteristic/finding Female Age (y) Vegetationc Days from fever onset In-hospital mortality Valve involved Mitral NV Aortic NV MAo NV Mitral PV Aortic PV MAo PV Positive blood culture Blood culture microorganism Streptococcus Enterococci Staphylococcus aureus Staphylococci, coagulase-negative Streptococcus pneumoniae GNB Valve Gram stain Positive cocci GNB Valve culture Streptococcus viridans Enterococcus faecalis S aureus PCM Surgery indication: HF
Patients with brain abscess (n¼6) 44 6 25 1
0 (36-76) (100) (20-40) (17)
0 4 (67) 1 (17) 0 1 (17) 0 2 (33) 1 (17) 1 (17) 0 0 0 0 1/5 (20) 0 0 0 0 3 (50) 3 (50)
Patients without brain abscess (n¼23) 7 55 21 12 5
(30) (17-84) (91) (2-150) (22)
8 6 4 3 2
(35) (26) (17) (13) (9) 0 15 (65) 3 2 6 1 1 1
P value .64 .75 .45 .98 .78 .08 .06 .96 .35 .56 .33 .15
(13) (9) (26) (4) (4) (4)
.81 .56 .16 .60 .60 .60
9/18 (50) 2/18 (11)
.23 .43
1/18 1/18 2/18 19 20
.59 .59 .43 .09 .04
(5) (5) (11) (83) (87)
GNB ¼ aerobic gram-negative bacilli; HF ¼ heart failure; MAo ¼ mitral and aortic; NV ¼ native valve; PCM ¼ previous cardiomyopathy; PV ¼ prosthetic valve. b Data are presented as No. (percentage) or mean (range). c Diagnosed by echocardiography. a
brain abscess) was a native aortic valve. The most common reason for valve replacement was heart failure in the group of patients without brain abscess. As shown in the Table, there were no significant differences between the groups in blood culture findings, valve Gram stain and culture, and previous heart pathology. None of the patients with IE and brain abscesses had diabetes, multiple organ dysfunction, septic shock, or thrombocytopenia. One patient had acute renal failure,
Mayo Clin Proc. n April 2013;88(4):420-424 www.mayoclinicproceedings.org
and one had hepatic dysfunction. No patients in this group died. Among the patients with IE and no brain abscess, 1 presented with septic shock, 7 had thrombocytopenia, almost half (48%) had acute renal failure, 7 had multiple organ dysfunction, and 5 had spleen abscesses. Of the 5 patients who died in this group, all had heart failure. There were no significant differences between groups in terms of clinical findings, type of valve affected, or microorganism producing the endocarditis.
The high prevalence of silent brain abscess in this study could be explained by the fact that all of the patients were critically ill and required valve replacement surgery. In patients with IE, the presence of a brain abscess is an important consideration in decisions regarding medical vs surgical treatment.4,5 Because of the lack of typical clinical findings in patients with IE and silent brain abscesses, routine brain imaging assessment could be cost-effective and provide opportunities to recognize and treat this entity early, particularly in patients who are severely ill. María C. Ferreyra, MD Esther R. Chavarría, PhD Fundación Médica de Río Negro y Neuquén Cipolletti, Río Negro, Argentina
Diego A. Ponieman, MD, MPH Mount Sinai Medical Center New York, NY
Pablo A. Olavegogeascoechea, MD, MPH Universidad Nacional del Comahue Cipolletti, Río Negro, Argentina 1. Snygg-Martin U, Gustafsson L, Rosengren L, et al. Cerebrovascular complications in patients with left-sided infective endocarditis are common: a prospective study using magnetic resonance imaging and neurochemical brain damage markers. Clin Infect Dis. 2008;47(1):23-30. 2. Ruttmann E, Willeit J, Ulmer H, et al. Neurological outcome of septic cardioembolic stroke after infective endocarditis. Stroke. 2006;37(8): 2094-2099. 3. Thuny F, Avierinos JF, Tribouilloy CH, et al. Impact of cerebrovascular complications on mortality and neurologic outcome during infective endocarditis: a prospective multicentre study. Eur Heart J. 2007; 28(9):1155-1161. 4. Arlotti M, Grossi P, Pea F, et al; GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) Working Group on Brain Abscesses. Consensus document on controversial issues for the treatment of infections of the central nervous system: bacterial brain abscesses. Int J Infect Dis. 2010;14(suppl 4):S79-S92. 5. Tunkel AR, Wispelwey B, Scheld WM. Brain abscess. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 5th ed., Vol 1. Philadelphia, PA: Churchill Livingstone; 2000: 1016-1028. http://dx.doi.org/10.1016/j.mayocp.2013.02.001
423