|
Introduction
Bacterial meningitis is one of the most serious infections in children with high mortality and morbidity1. The incidence of bacterial meningitis in Thailand is 24.6 per 100,000 for children under five years2, which is similar to other countries3. Amongst the pediatric population, neonates and young infants have the highest incidence, particularly at the age of fewer than 2 months4.
Early diagnosis of primary infection and its complications leads to prompt treatment which is essential for a favorable outcome5. Identifying intracranial infection in neonates and infants could be a clinical challenge due to atypical manifestations, and non-specific signs and symptoms1,6. Therefore, a combination of physical examination, laboratory test, and imaging examination is helpful for the diagnosis.
Cranial sonography (CRS) is usually used as the initial imaging examination for intracranial evaluation in neonates and infants because of its portability, no need for sedation, real-time, non-ionizing radiation, and reproducibility. Abnormalities in CRS are depicted in approximately 65% of infants with acute bacterial meningitis and could be up to 100% in patients with severe neurological symptoms7. A wide spectrum of abnormalities had been categorized depending on the locations; including on the surface of the brain, in the ventricular system, and brain tissue8. Some sonographic findings are more common in some pathogens7,9,10, which the common pathogens causing meningitis in each country differ due to different immunization programs2,4,11,12. Therefore, this study aimed to review the spectrum of CRS findings in neonates and infants with acute bacterial meningitis in our hospital in the last 10 years. We also evaluated CRS findings in each causative pathogen.
Materials and Methods
Patient and Imaging Selection
This study was approved by the Ethics Committee for Human Research, Khon Kaen University (HE621330). Informed consent from patients and their families was waived given the retrospective nature.
All patients under 1 year of age with a diagnosis of acute bacterial meningitis who underwent CRS at Srinagarind Hospital, Khon Kaen University between February 2009 and May 2018 were enrolled. Patients with unavailable clinical/laboratory/imaging data, pre-existing neurological abnormality, or brain anomaly/malformation were excluded. A total of 39 out of 89 patients were eligible. Twenty-one patients had follow-up sonography and all studies were retrospectively reviewed.
Clinical and laboratory data were collected from an online database of our hospital using PRAXIS Total Information and Collaboration (PRAXTICOL) and Health Object (HO) programs. The imaging studies were reviewed via Picture Archiving and Communication System (PACS). Demographic data comprised age, sex, prematurity, and treatment. Laboratory data comprised cerebrospinal fluid (CSF) profiles and CSF pathogens. All data were managed using Research Electronic Data Capture (REDCap) hosted at Khon Kaen University13.
Imaging protocol
CRS was performed using a 7.5-10 MHz linear transducer approaching through the anterior fontanelle. Six coronal images and five sagittal images were taken according to standard planes14.
Additional views such as mastoid view, posterior fontanelle/foramen magnum, and trans-temporal view might be performed for specific purposes15. Color Doppler sonography was applied for ruling out venous sinus thrombosis in all cases and for additional characterization of certain gray-scale findings8.
Imaging analysis
Two pediatric radiologists (N.T., with 5 years of experience, and T.R., with 2 years of experience) retrospectively reviewed sonographic findings by consensus and were blinded to the clinical and laboratory data. The sonograms were reviewed for the presence of echogenic sulci, ventriculomegaly and its degree including mild, moderate, severe, ventriculitis, parenchymal changes [either focal (abscess, infarction, hemorrhage) or diffuse (cerebritis)], accumulation of extra-axial fluid including subdural effusion and empyema, and venous sinus thrombosis8,12,16.
Statistical analysis
All statistical analyses were performed using STATA Version 10. Descriptive statistics were used for describing patient demographic data. Categorical data were presented as numbers and percentages. Correlation between detection of pathogens in CSF and abnormalities in CRS was evaluated using Fishers exact test. A p-value of less than 0.05 was considered statistically significant.
Results
Patients
A total of 39 (43.8%) out of 89 patients diagnosed with acute bacterial meningitis during the study period were enrolled. Of which, there were 24 males (61.5%) and 15 females (38.5%). The median age of patients was 40 days (range 3-300 days). There were 22 patients under 2 months of age, most of which were less than 1 month (20/39, 51.3%). In terms of maturity of the patients, there were 21 term (21/35, 61.8%) and 13 preterm (13/35, 38.2%) infants. The patients maturity data were not available in 5 patients.
Four out of 39 cases (10.3%) referred from other hospitals had no CSF profiles documented in the hospital data. Therefore, there were 35 cases (89.7%) with available and abnormal CSF profiles which approximately half of them (19 out of 35, 54.3%) showed negative bacterial organisms in CSF culture. Group B Streptococcus (GBS) was the most common organism (5 out of 16, 31.3%), which was almost isolated in the first month of age (4 out of 5, 80.0%), while the other occurred in a 2-month-old infant. The second and third most common organisms were Haemophilus influenzae (H. influenzae) (4 out of 16, 25.0%) and Salmonella (3 out of 16, 18.8%), respectively. The latter was found isolated in 5-7-month-old infants.
Sonographic findings
Out of 39 included cases, 18 cases (46.2%) showed normal CRS, whereas 21 cases (53.8%) found abnormal sonographic findings including 18 (46.2%) echogenic sulci (Fig. 1), 12 (30.8%) accumulation of extra-axial fluid (Fig. 1), 8 (20.5%) ventriculitis (Fig. 2), 6 (15.4%) ventriculomegaly (Fig. 2 and 3), 5 (12.8%) parenchymal changes (Fig. 3 and 4) and 2 (5.1%) venous sinus thrombosis (Fig. 4).
Figure 1 Thickened meninges and subdural empyema. Coronal CRS in a 5-month-old term male infant with Salmonella meningitis demonstrated echogenic thickening of leptomeninges (arrowhead) and widening of extra-axial spaces along bilateral parasagittal frontal convexities with internal septation on the right and echogenic content on the left.
Figure 2 Ventriculitis. Coronal CRS of a 36-day-old term male infant with unidentified pathogen in bacterial meningitis (A) showed severe ventriculomegaly with thickened and echogenic ependymal lining (yellow arrow) of bilateral lateral ventricles. (B) demonstrated intraventricular debris (asterisk) and septation (white arrow).
Figure 3 Diffuse parenchymal changes. Coronal CRS of a 7-month-old term male infant with Salmonella meningitis showed diffusely increased parenchymal echogenicity with well-demarcated hypoechoic areas at right frontal lobe (yellow asterisk) and bilateral thalami (white asterisk); representing cerebral infarction. Severe ventriculomegaly was found symmetrically.
Figure 4 Venous sinus thrombosis and focal parenchymal changes. Coronal CRS of a 12-day-old term male neonate with GBS meningitis showed hyperechogenicity within superior sagittal sinus without intravascular flow, compatible with venous sinus thrombosis (arrowhead). Well-defined hyperechoic lesions at bilateral parasagittal frontal lobes (red circle) were also depicted; representing acute intraparenchymal hematomas.
Of six cases with ventriculomegaly, 5 (83.3%) patients had severe dilatation whereas 1 (16.7%) patient had mild dilatation. Most of which (4/6, 66.7%) found symmetrical ventricular dilatation.
Four out of 5 cases (80.0%) with parenchymal changes found diffusely increased parenchymal echogenicity, and a case showed focal parenchymal lesions. A 7-month-old term male infant with Salmonella meningitis showed diffusely increased echogenicity of brain parenchyma, bilaterally and well-demarcated hypoechoic areas at the right frontal lobe and bilateral thalami; representing cerebral infarction at right MCA territory and bilateral thalami (Fig. 3). Two complicated cases with venous sinus thrombosis at superior sagittal sinus were proved to be GBS meningitis and one of which had associated parenchymal hematomas at bilateral parasagittal frontal lobes (Fig. 4).
Of thirty-five patients with available CSF culture results, only 16 patients (45.7%) identified etiologies. Four of 15 cases (26.7%) with normal CRS revealed positive pathogens in CSF culture, including 2 GBS, 1 Methicillin-Resistant Staphylococcus epidermidis (MRSE), and 1 Escherichia coli (E. coli). Whereas 12 out of 20 cases (60.0%) with abnormal CRS revealed positive pathogens. Of which, there were 4 (33.3%) H. influenzae, 3 (25.0%) GBS, 3 (25.0%) Salmonella, 1 (8.3%) E. coli, and 1 (8.3%) Acinetobacter baumannii (A. baumannii) (Table 1). The correlation between detection of pathogens in CSF and abnormalities in CRS was not statistically significant (p = 0.05).
Table 1 Sonographic findings of each pathogen in CSF.
|
Pathogens (No.) |
Normal
(No.) |
Abnormal sonographic findings (No.) |
|
Echogenic sulci |
Ventriculomegaly |
Ventriculitis |
Accumulation of
extra-axial
fluid |
Parenchymal
change |
Venous sinus thrombosis |
|
H. influenzae (4) |
0 |
4 |
1 |
0 |
4 |
0 |
0 |
|
GBS (5) |
2 |
2 |
1 |
1 |
2 |
2 |
2 |
|
Salmonella (3) |
0 |
3 |
1 |
3 |
1 |
3 |
0 |
|
E. coli (2) |
1 |
1 |
0 |
0 |
1 |
0 |
0 |
|
MRSE (1) |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
|
A. baumannii (1) |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
|
Unidentified (19) |
11 |
8 |
2 |
3 |
4 |
0 |
0 |
|
N/A (4) |
3 |
0 |
1 |
0 |
0 |
0 |
0 |
|
Total |
18 |
18 |
6 |
8 |
12 |
5 |
2 |
Note.- H. influenzae = Haemophilus influenzae, GBS = Group B Streptococcus, E. coli = Escherichia coli, MRSE = Methicillin-Resistant Staphylococcus epidermidis, A. baumannii = Acinetobacter baumannii, N/A = not available data.
Discussion
Bacterial meningitis remains a devastating infection with high mortality and severe lifelong disability17,18. Children, particularly at the age of less than 2 months, are more vulnerable to meningitis, particularly encapsulated bacteria because of relatively immature immune systems4,19. Our study found the highest incidence of acute bacterial meningitis in the 0-1 month age group patients (51.3%).
The organisms causing bacterial meningitis in children are varied in different countries and different age groups2,4,11,12. Unlike the incidence of bacterial meningitis in Thailand of Muangchana et al2 in 2009, our study found that GBS is the most common pathogens, particularly in the 0-1 month of age group. This might be due to the implementation of conjugated vaccines against bacteria that commonly cause meningitis in the last three decades. The effectiveness of vaccines shows a dramatic decrease in the incidence of H. influenzae type b meningitis worldwide20.
A combination of physical examination, CSF analysis, and imaging modality has been used to establish the diagnosis of bacterial meningitis. CSF culture is the gold standard for diagnosis, however, only 30-40% of the confirmed cases were identified causative pathogens21,22. Our study reported 45.7%. CRS is imaging of choice for intracranial evaluation, but it may be normal in mild and early meningitis. In the present study, CRS was normal in 46.2%, while it was reported in 30-40% in the previous studies9,2224. The most frequent sonographic abnormality found in the present study was echogenic sulci (18/39 cases, 46.2%) which is similar to published papers9,22,24. The echogenic sulci were seen in both cases with identified and unidentified causative pathogen, most notably in H. influenzae meningitis. This is due to the accumulation of inflammatory exudate in subarachnoid space causing increased echogenicity and thickness of the sulci9,12,24 which is often a transient abnormality7,8.
We observed an accumulation of extra-axial fluid as a second most common finding (30.8%) which is consistent with Han et al9. Nevertheless, other published papers reported other findings: ventriculomegaly in Soni et al24 and Edwards et al25, and abnormal parenchymal echoes in Mahajan et al23. An extra-axial fluid collection is seen as widening extra-axial fluid space. Subdural effusion represents sterile, reactive fluid which is usually clear fluid. Subdural empyema is rare9 and appears as a subdural fluid collection with internal echogenic debris or septation. It sometimes has a pressure effect on the adjacent brain parenchyma. It is difficult to distinguish between sterile subdural effusion and early empyema by ultrasound7, however, the presence of persistent fever, new focal neurological deficits, or seizure raises the suspicion of empyema7. The accumulation of extra-axial fluid in this study was most frequently seen in infants with H. influenzae meningitis.
This study found 20.5% of ventriculitis which was seen as thick, irregular, and echogenic appearance of ependyma, presence of intraventricular debris, septation and often associated with ventricular dilatation. Choroid plexitis may be found associated with ventriculitis and appears as increased echogenicity and irregular contour. Ventriculitis was mostly noted in Salmonella meningitis in our study.
Ventricular dilatation may be seen in approximately 30%12 of patients with bacterial meningitis, which was only seen in 15.4% in this study. Ventriculomegaly is often mild and reversible during acute illness. It can progress to moderate or severe dilatation due to obstruction or loss of brain parenchyma9. The ventricular dilatation may be either symmetry or asymmetry. Our study observed that most cases with ventriculomegaly were symmetrical and severe dilatation.
We demonstrated a case of Salmonella meningitis who had diffusely increased echogenicity of the brain parenchyma and cerebral infarction at right MCA territory and bilateral thalami. Meningitis may result in arterial spasm or direct arteritis which often affects the basal ganglia26. However, the larger arteries may be involved resulting in large territory infarctions.
Our study has several limitations. Firstly, as its retrospective design, there were the limited sample size and incomplete laboratory data documentation due to transferring from other hospitals. This affects the power of the study to detect sonographic abnormalities of each pathogen and the correlation between sonographic findings and causative pathogens. Secondly, CRS is highly operator-dependent. Hence, a retrospective review of the images by reviewers might not be as precise as by a real-time operator. Thirdly, we did not have a standardized protocol in our institute of a certain date for the sonographic evaluation of meningitis resulting in a lack of demonstration of early and late signs of the disease. Therefore, we could not advance in the knowledge of the correlation between causative organisms and sonographic changes over time. Finally, this is a single-center study in Thailand. The results may not extrapolate to other countries where the etiology prevalence differs. Since acute bacterial meningitis in neonates and infants is an uncommon disease, a prospective multi-center study in the future could be beneficial to enhance the understanding of sonographic findings in a certain bacterial organism of meningitis.
In conclusion, spectrum of sonographic findings in acute bacterial meningitis included both normal and a large number of abnormalities. Therefore, recognizing of these findings is essential because a prompt diagnosis and appropriate treatment reduce the risk of acute complications and long-term sequelae.
References
1. Janowski AB, Hunstad DA. Central nervous infections. In: Kliegman RM, St Geme JW, Blum NJ, Shah SS, Tasker RC, Wilson KM, editors. Nelson Textbook of Pediatrics. 21st ed. Philadelphia, PA: Elsevier; 2020: 1252312554.
2. Muangchana C, Chunsuttiwat S, Rerks-Ngarm S, Kunasol P. Bacterial meningitis incidence in Thai children estimated by a rapid assessment tool. Southeast Asian J Trop Med Public Health 2009; 40(3): 10.
3. Maimaiti N, Md Isa Z, Rahimi A, Kouadio IK, Ghazi HF, Aljunid SM. Incidence of bacterial meningitis in South East Asia region. BMC Public Health 2012; 12(S2) :A30, 1471-2458-12-S2-A30.
4. Thigpen MC, Messonnier NE, Hadler JL, Reingold A, Schaffner W, Scallan E. Bacterial meningitis in the United States, 19982007. N Engl J Med 2011; 364(21): 20162025.
5. Khetsuriani N, Holman RC, Lamonte-Fowlkes AC, Selik RM, Anderson LJ. Trends in encephalitis-associated deaths in the United States. Epidemiol Infect 2007; 135(4): 583591.
6. Chávez-Bueno S, McCracken GH. Bacterial meningitis in children. Pediatr Clin North Am 2005 ; 52(3): 795810.
7. Yikilmaz A, Taylor GA. Sonographic findings in bacterial meningitis in neonates and young infants. Pediatr Radiol 2008; 38(2): 129137.
8. Gupta N, Grover H, Bansal I, Hooda K, Sapire JM, Anand R, et al. Neonatal cranial sonography: ultrasound findings in neonatal meningitisa pictorial review. Quant Imaging Med Surg 2017 ; 7(1): 123131.
9. Han BK, Babcock DS, McAdams L. Bacterial meningitis in infants: sonographic findings. Radiology 1985; 154(3): 645650.
10. Tatsuno M, Hasegawa M, Okuyama K. Ventriculitis in infants: diagnosis by color Doppler flow imaging. Pediatr Neurol 1993; 9(2): 127130.
11. Mann K, Jackson MA. Meningitis. Pediatr Rev 2008; 29(12): 417430.
12. Littwin B, Pomiećko A, Stępień-Roman M, Spârchez Z, Kosiak W. Bacterial meningitis in neonates and infants the sonographic picture. J Ultrason 2018; 18(72): 6370.
13. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42(2): 377381.
14. Lowe LH, Bailey Z. State-of-the-art cranial sonography: part 1, modern techniques and image interpretation. Am J Roentgenol 2011; 196(5): 10281033.
15. Shuman W, Rogers J, Mack L, Alvord E, Christie D. Real-time sonographic sector scanning of the neonatal cranium: technique and normal anatomy. Am J Roentgenol 1981; 137(4): 821828.
16. Morris JE, Rickard S, Paley MNJ, Griffiths PD, Rigby A, Whitby EH. The value of in-utero magnetic resonance imaging in ultrasound diagnosed foetal isolated cerebral ventriculomegaly. Clin Radiol 2007; 62(2): 140144.
17. Polin RA, Harris MC. Neonatal bacterial meningitis. Semin Neonatol 2001; 6(2): 157172.
18. Heath PT, Okike IO, Oeser C. Neonatal Meningitis: Can We Do Better? In: Curtis N, Finn A, Pollard AJ, editors. Hot Topics in Infection and Immunity in Children VIII [Internet]. New York, NY: Springer New York; 2012 [cited 2021 Apr 3]. p. 1124. (Advances in Experimental Medicine and Biology; vol. 719). Available from: http://link.springer.com/10.1007/978-1-4614-0204-6_2
19. Makwana N, Riordan FAI. Bacterial meningitis: the impact of vaccination. CNS Drugs 2007; 21(5): 355366.
20. Dery MA, Hasbun R. Changing epidemiology of bacterial meningitis. Curr Infect Dis Rep 2007; 9(4): 301307.
21. Sáez-Llorens X, McCracken GH. Bacterial meningitis in children. Lancet 2003; 361(9375): 21392148.
22. Baruah D, Gogoi N, Gogoi R. Ultrasound evaluation of acute bacterial meningitis and its sequale in infants. Indian J Radiol Imaging 2006; 16(4): 553.
23. Mahajan R, Lodha A, Anand R, Patwari AK, Anand VK, Garg DP. Cranial sonography in bacterial meningitis. Indian Pediatr 1995; 32(9): 989993.
24. Soni JP, Gupta BD, Soni M, Gupta M, Dabi DR, Nemal KR. Cranial ultrasonic assessment of infants with acute bacterial meningitis. Indian Pediatr 1994; 31(11): 13371343.
25. Edwards MK, Brown DL, Chua GT. Complicated infantile meningitis: evaluation by real-time sonography. AJNR 1982; 3(4): 431434.
26. Hughes DC, Raghavan A, Mordekar SR, Griffiths PD, Connolly DJA. Role of imaging in the diagnosis of acute bacterial meningitis and its complications. Postgrad Med J 2010; 86(1018): 478485.
|
