Abstract
Background
The Streptococcus anginosus group is known for its pathogenicity and tendency for abscess formation. The S anginosus group also causes brain abscesses, yet few studies describe this presentation in the pediatric neurology literature. We describe 5 patients with central nervous system infection due to S anginosus group evaluated by child neurologists at the University of Iowa from 2014 to 2020.
Methods
We performed a retrospective case series review of electronic medical records detailing the clinical presentation and course of pediatric patients with S anginosus group–associated central nervous system infection.
Results
We identified 4 males and 1 female (8, 11, 14, 16, and 21 years). Brain imaging showed abscesses in 4 cases and empyema in 1. All underwent neurosurgical intervention and antibiotic treatment. Cultures obtained during the neurosurgical procedure grew S anginosus group (4 cases with Streptococcus intermedius and 1 with Streptococcus constellatus). An 8-year-old boy with a delayed diagnosis died from brain herniation.
Conclusions
Central nervous system infections due to the S anginosus group can be life-threatening. Neuroimaging plays a key role in the early identification of abscesses. Prompt surgical intervention and timely initiation of antibiotics are critical for optimal outcomes.
Introduction
Bacterial infections of the central nervous system continue to cause significant morbidity and mortality in children and adults. Focal bacterial central nervous system infections include both brain abscesses and subdural empyema. Brain abscesses are focal areas of necrosis with a surrounding membrane within the brain parenchyma caused by the spread of contiguous head or neck infections (otitis media, mastoiditis, or paranasal sinus infections) or by hematogenous dissemination. 1 Several pathogens can lead to brain abscesses. These infections have a high mortality rate if they are not promptly recognized and treated with appropriate antibiotics.
The Streptococcus anginosus group (SAG), previously known as the Streptococcus milleri group, has a strong propensity to form brain abscesses. 2 The S anginosus group is part of the normal human bacterial flora of the mouth, throat, gastrointestinal, and urogenital tract. It comprises 3 distinct species: S anginosus, Streptococcus constellatus, and Streptococcus intermedius. The terminology of this group has been confusing over the years. Before the 2000s, the S anginosus group was not routinely distinguished from other viridans streptococci owing to this group's confusing taxonomy and the labor-intensive techniques required for its identification. 3 Prior studies have found a high association of S intermedius with abscess formation, including in the central nervous system, compared to S anginosus or S constellatus. 4 Here, we describe the neurologic course of 5 patients with central nervous system infection due to the S anginosus group evaluated by child neurologists to raise awareness of this bacterial group.
Methods
All patients were either known to the Pediatric Neurology Division at the University of Iowa Hospitals and Clinics or identified using the TriNetX, a global federated health research network, by searching the keywords “streptococcus anginosus, CSF, meningitis, and brain abscess.” All pediatric patients from birth to 21 years at the time of diagnosis were included in the search. 5 We conducted a retrospective case series review of the identified patients, their clinical presentation, course of illness, laboratory tests, imaging, and treatment. Our institutional review board approved the study before initiation.
Results
We identified 5 cases (4 males and 1 female; ages: 8, 11, 14, 16, and 21 years [median age 14 years]) with invasive central nervous system infections due to the S anginosus group, 4 with brain abscess, and 1 with subdural empyema between 2014 and 2020. All patients received neurosurgical intervention and antimicrobial therapy. Table 1 summarizes the individual clinical information.
Patients' clinical summary.
Patient Descriptions
Patient 1
A 16-year-old boy presented to a local emergency department with headaches, altered mental status, intermittent aphasia, nausea, and vomiting. He had a history of presumed pulmonary histoplasmosis (positive serology, negative urine antigen), treated with itraconazole for 8 months, and prednisolone for 2 weeks, which was completed 6 months before his presentation. His noncontrast head computed tomography (CT) showed left temporal hypodensity concerning for a brain abscess (Figure 1). He was transferred to our center and underwent left hemicraniectomy with abscess drainage followed by an external ventricular and Hemovac drain. The brain abscess culture grew S constellatus, but cerebrospinal fluid and blood cultures remained negative. Echocardiography did not show evidence of infective endocarditis. The patient was treated with antibiotics and liposomal amphotericin B (Table 1). The antifungal was stopped after the histoplasma testing returned negative.
Noncontrast head computed tomography with a left temporal lobe lesion and surrounding vasogenic edema.
He had right facial, upper, and lower extremity weakness and difficulty finding words in the immediate postoperative period. His right-sided weakness resolved by the time of discharge. Brain magnetic resonance imaging (MRI) 3 months after his initial presentation showed near-total resolution of his brain abscess, and the antibiotics were stopped at that time. His abscess was completely resolved on the brain MRI done at 5 months. On follow-up, he admitted to intravenous drug abuse (heroin) in the past and licking the needle before insertion, pointing toward bacteremia as a probable cause of his brain abscess.
Patient 2
A 21-year-old man with Becker muscular dystrophy (ambulatory at baseline and not on immunosuppressants), cardiomyopathy, and anxiety was admitted to a local hospital with sepsis, nausea, vomiting, pneumonia, and cavitary lesions in the lungs. He was treated with antibiotics. On hospital day 16, he developed a severe headache and blurry vision without any focal neurologic deficit. Noncontrast head CT showed multiple lesions concerning for abscesses in the cerebellum, left frontal, right, and left occipital regions. He was given dexamethasone and transferred to our center for further management. Brain MRI showed multiple enhancing and diffusion restricting lesions with moderate surrounding vasogenic edema consistent with abscesses. There was also a moderate mass effect into the fourth ventricle without hydrocephalus (Figure 2).
(A) Axial T2-weighted images show hyperintense lesions and associated vasogenic edema in the left frontal lobe, and (B) occipital regions bilaterally. (C) T1-weighted postgadolinium demonstrating associated ring-enhancing lesions in the bilateral occipital region and cerebellum (D).
He underwent burr hole drainage and a biopsy of the left frontal lesion. The brain abscess culture grew S intermedius. Echocardiography did not show any evidence of infective endocarditis.
He was at his neurologic baseline throughout the hospital stay and was discharged home on antibiotics after 8 days (24 days since initial hospitalization; Table 1). After 5 days, he presented with a right thigh abscess and femur osteomyelitis requiring incision and drainage, which did not grow any organisms. He was discharged on the same antibiotics. At 2 and 3 months, repeat brain MRIs showed persistent brain abscesses, and his antibiotic therapy was extended. The antibiotics were stopped after the brain MRI at 4 months showed improvement and interval resolution of the abscesses. He recovered without any new neurologic deficits.
Patient 3
A 14-year-old boy with a history of psoriasis on a low oral dose of weekly methotrexate (17.5 mg) presented with 2 weeks of rhinorrhea, sore throat, and less than 24 hours of fever, headache, change in mental status, and right lower extremity weakness. Brain MRI showed pachymeningeal enhancement of the left cerebral hemisphere with subdural empyema most appreciable at the left para-falcine region (Figure 3). He underwent left hemicraniectomy and subdural empyema evacuation, followed by the placement of an external ventricular drain.
(A) Axial T2-weighted and (B) T1-weighted postgadolinium images demonstrating pachymeningeal enhancement of the left cerebral hemisphere with subdural empyema most notably in the left parafalcine region and a smaller component in the left high frontal area. Note the fluid levels in frontal sinuses.
Repeat brain MRI showed right to left midline shift and mild herniation through the craniectomy site. He was started on levetiracetam for seizure prophylaxis and dexamethasone along with hypertonic saline to treat his cerebral edema. Hypertonic saline was discontinued on hospital day 6 as his neurologic status improved. Repeat brain MRI on hospital day 10 showed persistent left para-falcine subdural collection. His neurologic status improved throughout the stay with antibiotic treatment (Table 1).
Subdural fluid culture grew S intermedius, methicillin-susceptible Staphylococcus aureus, and Corynebacterium striatum. The antibiotics were changed to linezolid and meropenem based on the culture and continued at discharge. At discharge, he had a mild decrease in sensation in the right plantar surface and an otherwise normal neurologic exam. At the 6-month follow-up, he had a normal neurologic examination. Repeat brain MRI showed near-complete resolution of the brain abscess.
Patient 4
An 8-year-old boy with a history of febrile seizures and epilepsy on levetiracetam developed fever and left facial pain. Over the next 2 weeks, he developed headaches, diarrhea, vomiting, photophobia, and urinary incontinence. He had a short episode where he could not identify his family members a week before admission. He presented to the local emergency department fatigued and drowsy with a Glasgow Coma Scale score of 15. Lumbar puncture revealed a cerebrospinal fluid protein of 206 mg/dl and glucose of 49 mg/dl. Noncontrast head CT showed a large lesion in the left frontal lobe with foci of gas concerning for an abscess in addition to ventriculitis, hydrocephalus, cerebral edema with mass-effect, and rightward midline shift of 10 mm. He also had paranasal sinus disease (Figure 4). He was intubated for airway protection and transferred to our center.
(A and B) Axial noncontrast head computed tomography showing a hypodense mass of 3.8 × 2.7 cm in the left frontal lobe with air lining the wall, surrounded by edematous parenchyma. There is a left to right midline shift along with subfalcine herniation.
On arrival at our center, his Glasgow Coma Scale score had decreased to 3 (over 3 hours). His pupils were dilated and fixed. He had no response to noxious stimuli and absent brainstem reflexes. He was taken to the operating room for bifrontal craniectomy, abscess drainage, and limited frontal lobectomy. Intraoperatively, there was pus draining out of the frontal sinus and brain edema with herniation. His neurologic status remained unchanged after the surgery with no respiratory effort and no spontaneous movements or eye-opening. Medical support was withdrawn after discussion with the family, and the patient died soon after. Abscess culture grew S intermedius, also identified in the histopathologic brain tissue samples collected during the autopsy. The events timeline at the local hospital emergency department suggests that the lumbar puncture was performed before head imaging.
Patient 5
An 11-year-old girl with Moebius syndrome and speech delay presented to the emergency department with a new-onset seizure. She was discharged home with a plan for outpatient brain MRI and electroencephalography (EEG). She subsequently developed headaches and vomiting over the next 2 days and presented again to the emergency department. Brain MRI showed a right frontal lobe abscess (Figure 5). The abscess was drained and grew S intermedius. She had a dental abscess on the right that was thought to be the source of infection. Her echocardiogram did not show intracardiac vegetations or shunt. She did not have any new deficits on the neurologic examination, did well postoperatively, and was discharged home on antibiotics (Table 1). There was abscess resolution on brain MRI at a 2-month follow-up, and she continued to do well without any new deficits or seizures.
(A) Axial T2-weighted brain magnetic resonance imaging (MRI) showing a 2.9 × 2.4-cm hyperintense lesion in the right frontal lobe with contrast enhancement on (B) T1-weighted image postgadolinium. There is an associated right to left shift and overlying leptomeningeal enhancement.
Discussion
In this single-center case series, we present 5 pediatric cases of S anginosus group causing central nervous system infection. S anginosus group, previously referred to as the S milleri group, 6 was first described by Guthof in 1956 after being isolated from dental abscesses. 7 Since then, there have been reports and studies on several types of abscesses caused by S anginosus group. The recognition of these organisms in abscesses has increased continuously over the past 2 decades owing to better isolation and identification methods. 6 It is unclear why S anginosus group has a predilection for abscess formation, and the molecular determinants of its virulence factors are poorly understood. 6
S anginosus group is a bacterium commonly associated with intracranial abscesses, 8 involving the brain, epidural, and subdural spaces. S anginosus group can also cause meningitis and cerebral venous sinus thrombosis.9,10 S intermedius has been more closely associated with central nervous system infections than S anginosus or S constellatus,3,6 as shown in a recent study looking at sinusitis and otitis media complications caused by S anginosus group. 10 Similarly, 80% of our patients had S intermedius infections. In our patient with S constellatus infection, bacteremia from his intravenous drug use likely caused his brain abscess, consistent with the previously noted association of S constellatus and bacteremia. 3
Clinically, there was a male predominance in our case series. Although our case series is small, the sex distribution is similar to reported cases showing a higher incidence of S anginosus group–related brain abscess in males.2,10
Regarding S anginosus group's route of entry into the brain in our patients, one had a dental abscess complicated with bacteremia. Unfortunately, there is no mention of dental health in the medical records of the other patients. Two of our patients had evidence of sinusitis on imaging, arguing for a local spread. Finally, bacteremia and hematogenous spread likely caused the brain abscess in the patient with intravenous drug abuse and in the patient who had evidence of systemic infection with lung abscess and osteomyelitis. We also note that it is unclear what role host immunity plays in the predisposition to S anginosus group brain abscesses, as 3 of our patients may have had a lower immune status due to concomitant pathology: history of presumed pulmonary histoplasmosis (patient 1), cavitary lesions in the lungs (patient 2), and methotrexate use (patient 3).
Dental manipulations and sinusitis are reported as significant risk factors for S anginosus group brain abscesses. 2 S anginosus group was described as the dominant pathogen in 2 studies looking at intracranial complications of pediatric sinusitis.11,12 Our series and the literature suggest these risk factors might be limited to older children. The median age in a recent sizeable pediatric study analyzing the complications of otitis media and sinusitis caused by S anginosus group was 11.4 years, with the youngest being 9.2 years old. 10 Similarly, our youngest patient was 8 years old. The lack of S anginosus group–associated brain abscesses due to sinusitis and otitis media in young children could be due, in part, to undeveloped sinuses in young children.
The common presenting symptoms in our patients were headache, vomiting, fever, and nausea. Yet, some had localizing symptoms like blurry vision and lower extremity weakness. Seizures or abnormal neurologic examination at presentation have been associated with neurologic sequelae in patients with focal intracranial infections, 11 but this was not observed in our patients.
In patient 4, the timeline of events at the local emergency department suggests that lumbar puncture was performed before head imaging, which showed a space-occupying lesion. Even though it is hard to pinpoint the cause of brain herniation, the lumbar puncture performed before head imaging might be one of the many contributing factors for the patient's brain herniation. Because of the risk of brain herniation, lumbar puncture should be avoided in patients with brain abscesses.
The management of brain abscesses should be multidisciplinary, with a neurosurgery and an infectious disease consultant, both of whom were involved in our patients’ treatment. Cefotaxime plus metronidazole is an adequate empirical treatment for brain abscesses with excellent efficacy but many reversible side effects. 13 After speciation, antibiotic therapy should be tailored based on sensitivity. For patients with brain abscesses by S anginosus and a Glasgow Coma Scale score ≤11, treatment may include cefotaxime at higher doses, metronidazole, the addition of rifampicin, and neurosurgical drainage. 14 Intravenous antibiotic therapy should continue for 4-6 weeks with monthly brain imaging using CT/MRI for at least 3 months to monitor therapeutic response. 15 The duration of antibiotics in our patients ranged from 6 weeks to 4 months, based on the abscess resolution on brain imaging. 11
Our case series has limitations inherent to a retrospective case review. TriNetX was used as a search engine to identify patients for this study using keywords that might have resulted in underdetection of patients. Details regarding oral hygiene were not available in all patients’ medical records, and follow-up periods varied across patients.
Conclusion
Our case series illustrates clinical presentations of focal central nervous system infections by S anginosus group in the pediatric population to facilitate early recognition by child neurologists. S anginosus group should be high in the differential as a causative pathogen in patients presenting with brain abscesses. These infections can be life-threatening, but patients can have good outcomes with early recognition and management with broad-spectrum antibiotics and neurosurgical drainage as appropriate.
Footnotes
Acknowledgments
The authors would like to thank all the clinicians who contributed to the care of these patients.
Author Contributions
SM design the work, acquired, analysed and interpreted the data, and drafted the article. SM, KM, JG help with data interpretation, and critical review and editing of the manuscript.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: JG was supported by the Iowa Neuroscience Institute. The other authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval
Our institutional review board approved the study before initiation.
