Subdural empyema in immunocompetent pediatric patients with recent SARS-CoV-2 positivity: case report

Abstract

Subdural empyema refers to the collection of purulent material in the subdural space and the most source of it is bacterial meningitis in infants while sinusitis and otitis media in older children. It has been very recently reported that coronaviruses (CoV) exhibit neurotropic properties and may also cause neurological diseases. CoV-related complications as hypercoagulability with thrombosis and associated inflammation, catastrophic cerebral venous sinus thrombose sand bacterial-fungal superinfections have been well documented in adult patients. Hereby, we describe 15-year-old and 12-year-old female children with subdural empyema after SARS-CoV2. The patients presented limitation of eye in the outward gaze, impaired speech, drowsiness, fever, vomiting and they also were tested positive for COVID-19. MRI indicated subdural empyema and surgical interventions were needed to relieve intracranial pressure and drain pus after receiving broad spectrum antibiotics treatments. The microbiological analysis of abscess material revealed Streptococcus constellatus which is extremely rare in an immunocompetent child and the patients received appropriate IV antibiotic therapy. Eventually, patients became neurologically intact. Pediatric patients with CoV infections should be closely monitored for neurological symptoms. Further research and more data on the correlation between CoV infections would provide better recognition and treatment options in an efficient manner in children.

Introduction

Subdural empyema (SDE) is an acute neurological condition and a pyogenic infection, located between the dura and arachnoid mater. The incidence of SDE is approximately 1–2% in infants mainly due to pyogenic bacterial meningitis. The most common cause is meningitis in infants while the main source of infection are sinusitis and otitis media in older children [1, 2]. The common clinical features are fever, headache, altered sensorium, seizure, hemiparesis, monoparesis and cranial nerve deficits, respectively [2]. The surgical interventions via craniotomy is old but the best method to treat and diagnosis of SDE and subsequent treatment with antibiotics targeting the bacteria is required [1, 3].

COVID-19 is a severe acute respiratory syndrome (SARS), caused by SARS-CoV-2 was first reported in December 2019 in the Wuhan city of China and shortly after spread to the entire world [4]. It has been reported that CoV infections can affect the nervous system and CoV can transform these infections into permanent infections that can lead to neurological diseases in harmony with the host immune mechanisms [5]. Secondary infections especially as bacterial pneumonia and bloodstream infections occur in patients treated for SARS-CoV-2 [6]. Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus species are common bacterial pathogens. Compared to bacterial infections, fungal secondary infections are less abundant but Candida species the most encountered fungal pathogens in terms of prevalence [7, 8]. In the literature, cases of intracranial abscess formation in adults and pediatric patients with type 1 diabetes mellitus tested positive for SARS-CoV2 were indicated [9, 10]. Recently, intracranial complications of hypercoagulability and superinfection in the setting of COVID-19 were exemplified in three adolescent patients [11]. To our knowledge, this is the second case reported for bacterial SDE after SARS-CoV2 in immunocompetent pediatric patients. Here, we report a potential link between SDE formation and SARS-CoV-2 in 15-year-old and 12-year-old female children.

Case presentations

Case 1

On 17 of September 2021, a 15-year-old girl, complaining swelling in the eye thinking of possible infection applied to the regional hospital and was prescribed antibiotics. On September 22, the patient was admitted to the same hospital due to development of impaired speech and drowsiness. One day later, the patient with positive RT-PCR for COVID-19 was admitted to the COVID service with the diagnosis of subdural empyema by leptomeningeal staining with magnetic resonance imaging (MRI). The patient received meningitis treatment and transferred to our hospital due to need of 3rd step intensive care facility. The patient’s general condition was moderate with localization the painful stimulus and limitation of the right eye in the outward gaze. The disoriented patient was admitted to the intensive care unit and antibiotic treatment with cefotaxime sodium (4 × 2.5 g), clindamycin (4 × 500 mg) and vancomycin (4 × 500 mg) were administered. The follow-up MRI on October 3 indicated SDE, extending to the level of the left tentorium in the interhemispheric fissure, showing peripheral contrast staining in the right tentorium localization and left frontotemporal localization, with mass effect midline to the right shift (Fig. 1). Besides, a small contrast stained abscess in the size of 12 × 26 mm was also noted in the frontal soft tissues under the skin, described as Pott’s puffy tumor (Fig. 1c). Vancomycin combined with cefotaxime therapy was given to the patient for 9 days at the dose of meningitis.

Fig. 1.

Contrast enhanced axial (a) T1-weighted (The yellow arrows indicate empyemas and the red arrow represents direction of brain shift.) and (b) T2-weighted MRI scans. (c) T2-weighted sagittal (The yellow arrow showed Pott’s puffy tumor) and (d) contrast enhanced coronal MRI scans. Images obtained from Case 1 with subdural empyema along a left frontotemporoparietal and right tentorium

Her preoperative labs revealed a white blood cell count (WBCs) of 20.85 × 10³/µL [3.71–10.19 × 10³/µL] (on peripheral smear neutrophil of 86%, lymphocyte of 8%, monocyte of 6%), hemoglobin of 10.7 g/dL [ref: 11.33–14.56 g/dL], platelet count of 304 × 10³µL [ref: 130–400 × 10³µL], total protein of 60.6 g/L [ref: 66–83 g/L], albumin of 27 g/dL [ref: 35–52 g/dL], C-Reactive Protein (CRP) of 126.1 mg/L [ref: < 5 mg/L], procalcitonin of 1.71 µg/L [ref: < 0.5 µg/L], and sedimentation rate of 29 mm/h for 1 h [ref: 0–20 mm/h for 1 h].

On 4 of October 2021, surgical intervention to relieve intracranial pressure (ICP) was planned due to the deterioration of the patient's general condition, paralysis on right side, and fast-growing of abscess and the subdural empyema was drained with a left frontotemporoparietal craniotomy. After 2 days, the patient’s sedation was gradually discontinued. The abscess material was sent for microbiological analysis and gram-positive cocci in chains were reported. Its culture grew Streptococcus constellatus ssp but no fungus detected. The patient was vancomycin (4 × 500 mg) combined with clindamycin (4 × 500 mg) and ceftazidime (3 × 2 g) intravenous antibiotic treatment for 30 days. Tests for primary immunodeficiency were normal. Post-op tomography and MRI follow-ups have showed a decrease in the size of abscess. Eye movements improved on the 10th post-op day.

Case 2

On 07 of October 2021, a 12-year-old girl complaining a runny nose had a positive COVID-19 RT-PCR test and was followed up in isolation at home for 1 week. After 1 week, her fever increased to 39.5 °C in addition to vomiting, and she was sent home after being prescribed antipyretic. Two days later, she had a fever of 40.5 °C, swelling and redness in her left eye, and was prescribed antibiotic drops and nasal spray. After 1 day, the patient started to have impaired speech and applied to the local hospital, where paralysis was determined in her right side, and subdural empyema was noticed in her MRI. The patient was transferred to our hospital’s the Pediatric Intensive Care Unit after consultation with the Pediatric Infection Service due to need of 3rd step intensive care facility. Intravenous antibiotic treatment with ceftriaxone (2 × 2 g), clindamycin (4 × 600 mg), vancomycin (2 × 500 mg) were administered. In terms of seizures, keppra (30 mg/kg), decort (4 × 6 mg) and 3% hypertonic saline solution infusion were started to reduce brain edema, and decort treatment was continued by decreasing 2 mg every 3 days. The surgery was scheduled immediately after the patient’s general condition worsened, consciousness deteriorated, and neurological deficit developed. The patient was localizing the painful stimuli on the left before the operation but there was total hemiplegia on the right.

The follow-up MRI on October 10 revealed subdural empyema along to the falx cerebri at the level of vertex and in the left frontoparietal convexity in addition to cytotoxic edema in the left frontal lobe (Fig. 2a–b). due to the deterioration of the patient’s general condition, contrast-enhanced CT performed on 12 October showed an increase in subdural empyema at the level of vertex (Fig. 2c, d).

Fig. 2.

(a) Contrast enhanced coronal T1-weighed and, (b) coronal T2-weighted MRI scans. Contrast enhanced (c) axial and (d) coronal tomography. Yellow arrows indicate interhemispheric subdural empyema on vertex level. Images obtained in Case 2

Her preoperative labs revealed a white blood cell count (WBCs) of 15.69 × 10³/µL [ref: 3.71–10.19 × 10³/µL] (on peripheral smear neutrophil of 86%, lymphocyte of 10%, monocyte 4%) hemoglobin of 10.7 g/dL [ref: 11.33–14.56 g/dL], platelet count of 258 × 10³µL [ref: 130–400 × 10³µL], total protein of 62 g/L [ref: 66–83 g/L], albumin of 30.7 g/dL [ref: 35–52 g/dL], CRP of 80.12 mg/L [ref: < 5 mg/L], procalcitonin of 3.07 µg/L [ref: 0.5 < µg/L], and sedimentation rate of 90 mm/h [ref: 0–20 mm/h].

On 13 of October 2021, surgical intervention to relieve ICP was performed and the subdural empyema was drained with a left frontoparietal craniotomy. After 2 days, the patient’s sedation was gradually discontinued and the loss of strength gradually returned to normal within 3 days. The abscess material was sent for microbiological analysis and gram-positive cocci in chains were reported. Its culture grew Streptococcus constellatus ssp and the patient was treated with cefotaxime (4 × 3 g), clindamycin (4 × 600 mg) and vancomycin (4 × 500 mg) for 30 days and, keppra (30 mg/kg) in terms of seizures. Tests for primary immunodeficiency were normal. The patient’s symptoms gradually improved within 1 week. The control MRI taken 1.5 months later was normal.

Methods

Written informed consents for publication were obtained from the patients’ next of kin. The authors vouch for the accuracy and completeness of the data in this report.

Discussion

The most common cause of subdural empyema in adolescences is chronic otitis media or pansinusitis leading to subdural infection during the course of treatment or occasionally after completion of treatment. The infection may be spread to the intracranial compartment through the valveless diploic veins, often with associated thrombophlebitis [12]. It is also indicated that bacteria sinusitis and its potential complications as sinus thrombosis are known successors of viral infections but the complex features of COVID-19 may allow to create the perfect storm for sinusitis-related complications. Both in adults and adolescences patients with a history of chronic sinusitis reported for subdural empyemas after COVID-19 [9, 11]. Hypercoagulability-induced thromboses and superinfection-induced thrombophlebitis were reported playing a compound role in development of a severe empyema in COVID-19 infected healthy adolescents [11]. Additionally, SARS-CoV-2 infection damages the choroid plexus epithelium, leading to leakage across this important barrier, which normally prevents entry of pathogens, immune cells, and cytokines into the CSF and the brain [13]. A viral encephalitis case caused by the novel CoV attacking the central nervous system was reported and presence of SARS-CoV-2 in cerebrospinal fluid was confirmed by genome sequencing. Thus, it was proved SARS-CoV-2 cause nervous system damage [13] by destroying the blood–brain barrier resulted in and secondary intracranial infections [5]. These documented conditions may have been effective during development of subdural empyema on our cases due to presence of chronic sinusitis and confirmation of COVID-19 in both cases.

Streptococcus constellatus, one of the member of the Streptococcus anginosus group (SAG, S. anginosus, S. intermedius, and S. constellatus) is often associated with serious disease and abscess formation. The Streptococcus anginosus group is primarily commensals of the oral mucosa and is among the most frequently isolated in cases as the otitis media and sinusitis [14]. These organisms have also been more rarely associated with otitis media complications, including intracranial empyema and mastoiditis [14, 15]. Infections with empyema related to Streptococcus constellatus are mostly found in the thoracic region. It causes purulent infections of the pleuro-pulmonary, intra-abdominal, genitourinary, soft tissue and, rarely central nervous system [16]. Faden and Mohmand [17] reported that S. constellatus rarely associated with infections of the head and neck and more commonly associated with acute appendicitis in children. All SAG isolates were susceptible to ampicillin, ceftriaxone and vancomycin [14]. Additionally, subdural empyema due to Streptococcus constellatus is extremely rare in children and few cases were reported [11, 16, 18, 19].

We highlight the unique presentation of our cases due to multiple reasons. Firstly, our pediatric patients had very few risk factors, both of them considered immunocompetent without a previous neurosurgical procedure or history of head trauma. Secondly, the rapid formation after infected by COVID-19 and progression of empyema despite using vancomycin plus cefotaxime therapy. Finally, our patients had surgical intervention to relieve intracranial pressure and drainage of the subdural abscess. The key to management is appropriate IV antibiotic therapy of similar presentation of S. constellatus with surgical intervention (pus drainage) and close neuroimaging.

Conclusion

Considering the infection and patient cultures associated with COVID-19, it supports the idea that CoV infections may affect the presence of bacteria in certain anatomical regions. These cases are the second reported cases of subdural empyema caused by S. constellatus after having infection of COVID-19 in immunocompetent children. Therefore, patients with CoV infections should be closely monitored for neurological symptoms as headache, consciousness, disorder, paresthesia, impaired speech, drowsiness and other pathological signs. Further research and more data on the correlation between CoV infections would ascertain the risk and treatment in an efficient manner in children.

Author contribution

Uğur Yazar drafted the article and designed the figures. Uğur Yazar, Zeynep Gökçe Gayretli Aydın, Ahmet Kağan Özkaya, Kaan Kırımlı and Ali Rıza Güvercin performed clinical managements of the patients. Zeynep Gökçe Gayretli Aydın and Ahmet Kağan Özkaya reviewed and edited the manuscript. All authors contributed to the article and approved the submitted version.

Availability of data and material

All datasets generated for this study are included in the article.

Declarations

Ethics approval and consent to participate

This study was performed in line with the principles of the Declaration of Helsinki. The patient’s parents gave their written informed consent to participate.

Consent for publication

Consent to publish this article was obtained from the patient’s parents.

Conflict of interest

The authors declare no competing interests.