In the emergency department setting, there is known variability in the diagnostic imaging workup of patients with suspected acute intracranial infection. For example, although there are well established criteria as published in 2004 by the Infectious Diseases Society of America for when to obtain head computed tomography (CT) in adult patients with suspected bacterial meningitis before lumbar puncture, it has been found that most clinicians do not adhere to these guidelines.1–3 In this particular setting, the noncontrast CT would be obtained as a precaution to screen for mass effect that could increase the risk for a procedural complication of cerebral herniation.
Moreover, there are no clear guidelines for when or when not to incorporate intravenous iodinated contrast if CT is pursued in this setting. The 2004 Infectious Diseases Society of America practice guidelines do not mention the use of contrast in the discussion of CT. The American College of Radiology Appropriateness Criteria document for acute mental status change, delirium, and new onset psychosis states that, when there is an acute mental status change with clinical suspicion for infection (or other processes such as intracranial tumor or inflammatory pathology), a contrast-enhanced CT “may be appropriate,” with further explanation that contrast-enhanced CT can be considered but that it “may not add significant value over noncontrast head CT examinations.”4 However, this statement is based on the citation of work by Shuaib et al,5 who did not specifically identify any patients with clinically suspected intracranial infection in their study population and who also encountered only 1 case of a positive contrast-enhanced CT after a negative noncontrast CT in a patient who had Klippel-Trenauney-Weber syndrome, a hereditary condition that was completely incidental.5
A study by Wood et al6 investigated the value of contrast-enhanced CT of the head in nontrauma emergency department patients; however, this investigation did not specifically study patients suspected of having an intracranial infection, and none of their patients with an abnormal CT had a final diagnosis of an infection as the cause. Therefore, to our knowledge, there has been no investigation specifically addressing the value of contrast-enhanced CT in patients with clinically suspected intracranial infection in the emergency setting.
Computed tomography examinations without and with contrast performed in tandem should be avoided whenever a noncontrast CT alone is adequate to answer the clinical question. This halves the radiation dose that a patient would receive, reduces imaging cost, decreases any potential patient discomfort from venipuncture and contrast injection, and decreases the risk of an adverse event or complication such as allergic reaction to the contrast, contrast-induced nephropathy, or contrast extravasation. Furthermore, the shortage of iodinated contrast that temporarily occurred in 2022 highlighted the importance of judicious use of contrast and the importance of conservation of resources.7
This study was undertaken to determine the proportion of patients with suspected intracranial infection and positive contrast-enhanced CT findings who also have companion positive noncontrast CT images showing a correlative abnormality. We hypothesized that the majority of these cases have a noncontrast CT abnormality that on its own would merit further evaluation with magnetic resonance imaging (MRI), which is considered the preferred criterion standard for evaluation of central nervous system pathology, rendering a contrast-enhanced CT potentially unnecessary in this setting.
MATERIALS AND METHODS
Before the initiation of this investigation, institutional review board approval was obtained. The study was carried out in compliance with the Health Insurance Portability and Accountability Act. Patient informed consent was not required on the basis of institutional policy and the retrospective nature of this investigation.
The study population consisted of all patients who had clinically suspected intracranial infection and who were imaged with a CT head without and with contrast protocol while in the emergency department of our tertiary care hospital during the period January 1, 2004, to October 31, 2021; patients meeting this inclusion criteria were identified by using a keyword search of history and clinical information fields of radiology reports using mPower software (Nuance, Burlington, MA). Keywords included fever, bacteremia, sepsis, meningitis, abscess, and human immunodeficiency virus (HIV). The search results were manually reviewed to ensure accurate data capture. Patients with a history of head surgery were excluded because of the inherent nonspecific findings that may be present such as postsurgical fluid collections, resection cavities, postoperative edema, and chronic postsurgical reactive changes. Patients with a history of malignancy were excluded because of the possibility of intracranial metastatic disease that could manifest as confounding enhancing findings. This resulted in 343 patients (195 males and 148 females; mean age, 43 years; age range, 1–77 years) imaged with a CT head without and with contrast protocol.
Computed tomography examinations were performed using standard department protocols including the following parameters: 120 kVp, variable tube current (ranging from 95 to 540 mA), 2.5 mm reconstructed slice thickness, 0.9 pitch in adults, and 0.75 pitch in children. Scanner types included 16-MDCT (Sensation 16; Siemens, Munich, Germany), 64-MDCT (Sensation 64, Siemens; Revolution, GE HealthCare, Chicago, IL), Discover CT750 HD (GE HealthCare), and 256-MDCT (SOMATOM Definition Flash, Siemens). Postconstrast CT was acquired 5 minutes after the bolus intravenous power injection (1.5 mL/s) of 80 mL iohexol 350 (Omnipaque, GE HealthCare) for adults and with weight-based contrast dosing for children of 1 mL/kg with maximum dose of 80 mL.
Each CT examination was reviewed in consensus by 2 board-certified neuroradiologists. Each patient's noncontrast CT was first reviewed to assess for presence or absence of either vasogenic edema, mass effect, or both as markers or a possible acute infection. The noncontrast CT images were also reviewed for background nonspecific hypodense white matter changes, as they may decrease sensitivity for detecting hypodense vasogenic edema; the white matter changes were graded as either absent, mild/scattered, or confluent. Examples of background white matter changes under this grading system are included on Figure 1. Subsequently, the companion contrast-enhanced CT images were assessed for presence or absence of an enhancing abnormality, and if there was an enhancing abnormality, the locations (intra-axial, subarachnoid, subdural, or epidural) and number of lesions were recorded, as well as the widest axial dimension of the smallest lesion seen. The medical record was checked to confirm that an infectious process was the ultimate diagnosis in patients with enhancing abnormalities. Six patients had noninfectious enhancing findings; these included enhancing subacute territorial cortical infarcts (n = 5) that were also evident on noncontrast CT and confirmed by subsequent MRI, and a meningioma (n = 1) that was a known chronically stable finding seen on prior comparison imaging.
The performance of noncontrast CT as a screening test for an abnormality suspicious for acute intracranial infection was calculated in relation to presence of enhancing findings on contrast-enhanced CT based on the number of true positives, false positives (type I error), true negatives, and false negatives (type II error). Positive predictive value, negative predictive value, sensitivity, specificity, and accuracy were calculated using IBM SPSS Statistics version 24 (IBM).
In the study population of 343 patients, 39 had an enhancing abnormality (prevalence, 11.3%) that per chart review was ultimately diagnosed as an infection related abnormality. The spaces of involvement were intra-axial (n = 35), epidural (n = 1, an epidural abscess), and subarachnoid/leptomeningeal (n = 3). The number of lesions in patients with intra-axial enhancing lesions ranged from 1 to 14 (mean, 4), and the size of the smallest ranged from 0.5 cm to 2.7 cm (mean, 1.1 cm). The epidural enhancing finding, a rim-enhancing epidural abscess secondary to frontal sinusitis (Pott Puffy tumor), measured 0.5 cm. Of note, 30 of these 39 patients had MRI examinations performed during the same admission as the abnormal CT; in the patients who did not have an MRI examination, the reasons were a contraindication due to presence of a noncompatible medical device or foreign body, inability of the patient to tolerate the examination, or the patient declining the MRI.
The ultimate clinical diagnoses for patients with enhancing abnormalities were central nervous system (CNS) toxoplasmosis (n = 29), meningitis (n = 3 [pathogens: Cryptococcus neoformans (n = 2), streptococcus pneumonia (n = 1)]), intra-axial abscess (n = 6 [pathogens: staphylococcus aureus (n = 3), Nocardia (n = 1), group F streptococcus (n = 1), streptococcus anginosus (n = 1)]), and epidural abscess secondary to streptococcus. In patients with an enhancing abnormality, the provided clinical histories for the CT examination requests included seizure (n = 15), headache (n = 13), altered mental status (n = 10), fever (n = 4), dizziness (n = 3), vision change (n = 3), and scalp cellulitis (n = 1). Out of the total population of 343 patients, 233 had a known diagnosis of HIV, including 32 of the 39 patients with an enhancing abnormality.
Thirty-two of the 39 patients with an enhancing abnormality also had correlative conspicuous findings on the noncontrast CT. All of the patients in this subset had vasogenic edema corresponding to subsequently visualized intra-axial enhancing lesions, and 22 also had corresponding mass effect; 2 examples are depicted in Figure 2 and Figure 3. The patients in this subset also had variable background nonspecific white matter changes: none (n = 24), mild/scattered (n = 4), and confluent (n = 4).
Seven of the 39 patients with an enhancing abnormality on contrast-enhanced CT had no conspicuous finding on noncontrast CT; that is, the acute abnormality was occult on noncontrast CT, with no detectable vasogenic edema or mass effect. This included the 3 cases of meningitis with leptomeningeal enhancement (example depicted on Fig. 4), the small 0.5 cm epidural abscess secondary to frontal sinusitis, and 3 cases with intra-axial enhancing findings. Notably, in each of the 3 cases with intra-axial lesions where noncontrast CT was negative, there was confluent hypodense background white matter change that appeared to obscure detection of hypodense vasogenic edema (example depicted on Fig. 5).
When the performance of noncontrast CT is analyzed as a screening test for enhancing abnormalities on contrast-enhanced CT, in our population, there were 32 true positives, 304 true negatives, 0 false positives, and 7 false negatives. This is summarized on Table 1. Therefore, in this setting in our population, noncontrast CT had a positive predictive value of 100%, negative predictive value of 97.7%, sensitivity of 82.1%, specificity of 100%, and accuracy of 98.0%.
TABLE 1 -
Performance of NCCT as a Screening Test for Detecting Markers Predictive of Positive Enhancing Abnormalities on CECT
CECT indicates contrast-enhanced computed tomography; FN, false negative; FP, false positive; NCCT, noncontrast computed tomography; TN, true negative; TP, true positive.
In our study, a substantial majority of patients who had intracranial intra-axial enhancing abnormalities in the setting of a subsequently diagnosed acute intracranial infection also had correlative conspicuous noncontrast CT findings that were highly concerning for underlying abnormality; these findings were vasogenic edema with often coinciding mass effect. When encountering such new findings on noncontrast CT in any setting and when the diagnosis is not certain, it is generally the standard of care to obtain an MRI examination, as it is the criterion standard for evaluating CNS pathology. Magnetic resonance imaging is particularly useful for the differentiation of rim-enhancing lesions, whereas, in cases of leptomeningeal enhancement, the findings can be nonspecific even on MRI.
There were 7 patients who had an enhancing intracranial finding from an infection that did not have a correlative finding detected on noncontrast CT (“false negatives”). Three of these patients had intra-axial lesions that we believe were occult on noncontrast CT because of the presence of confluent background hypodense white matter changes that obscured the vasogenic edema. It should be noted, however, that there were 4 other patients graded with confluent white matter changes in whom vasogenic edema was still detected as a marker for an enhancing lesion subsequently seen on contrast-enhanced CT; therefore, extensive or confluent hypodense white matter changes may mask vasogenic edema, but this is not always the case. Nevertheless, our study shows that, in patients with confluent hypodense white matter changes, contrast-enhanced CT may add diagnostic sensitivity for the detection of an intra-axial lesion that could be missed on noncontrast CT. Vasogenic edema was always detected on noncontrast CT in patients with either no background white matter changes or mild/scattered white matter changes. The hypodense background white matter changes in the brain encountered in this study are commonly seen, especially in older patients, with the pathological and clinically significance not fully known,8 and which are also often termed chronic small vessel disease or chronic microangiopathy.
Another 3 of the 7 patients in the false-negative group had leptomeningeal enhancement consistent with leptomeningitis. Although our study results categorize these as false negatives, it must be acknowledged that the contrast-enhanced CT was of no clinical significance in each of these cases. The noncontrast CT fulfilled its role of ruling out any finding that might be a contraindication for performing a lumbar puncture. Each of these patients had lumbar punctures with cerebrospinal fluid analysis providing the answer of the exact pathogen to treat. Therefore, iodinated contrast was unnecessary in these three patients.
The last of the 7 patients in the false-negative group was a child with frontal sinusitis presenting as Pott Puffy tumor who had a 0.5-cm extra-axial abscess at the frontal aspect secondary to the frontal sinusitis and located deep to the inner table of the frontal sinus. Of note, this patient also subsequently had an MRI to evaluate for intracranial complication and assess for osteomyelitis. Although no vasogenic edema or mass effect was detected on noncontrast CT to raise concern for the aforementioned intracranial extra-axial finding, the abscess was considered by surgical consultants to be negligible and too small to warrant any change in the patient's management; an extra-axial abscess of greater concern might be one large enough to cause mass effect, a secondary finding that is readily detectable on noncontrast CT.
From a public health perspective, it is notable that, in our study, a substantial majority of patients (32 of 39) who presented with acute intracranial infections with enhancing findings had a history of HIV, and 31 had a final diagnosis of an intracranial AIDS-defining illness (29 with CNS toxoplasmosis and 2 with cryptococcal meningitis).
There are several limitations of our study. This a retrospective analysis that may be subject to selection bias. Our retrospective search criteria included patients based on clinical history and information given to the radiology department by the referring provider, which would not capture cases where a referring provider gave a generalized, vague, or inaccurate clinical history; however, this is a common dilemma confronted in the practice of radiology.9,10 Because of the low sample size of patients with background white matter changes that had enhancing findings on CT, we were not able to assess for possible statistical association between white matter changes and missed findings on noncontrast CT; however, patients included in this study were from a period of almost 18 years at a major regional tertiary care center, and this suggests an inherent rarity of encountering enhancing findings in this clinical scenario. In addition, local practice preference with regard to the utilization of CT in general and contrast-enhanced CT in particular may have affected our sample, and a larger multi-institutional study would be beneficial to further evaluate our findings.
In summary, most acute intracranial infections with an enhancing CT finding also have a correlative conspicuous noncontrast CT finding that on its own would merit further evaluation with MRI, the criterion standard for investigating CNS disease, and therefore, in the setting of suspected intracranial infection, contrast-enhanced CT is redundant in most cases. Contrast-enhanced CT primarily provides diagnostic benefit in patients with confluent background white matter changes that may mask vasogenic edema on noncontrast CT.
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