
==== Front
J Neurosurg Case Lessons
J Neurosurg Case Lessons
J Neurosurg Case Lessons
Journal of Neurosurgery: Case Lessons
2694-1902
American Association of Neurological Surgeons

39250831
10.3171/CASE23394
CASE23394
CongenitalCongenitalInfectionInfectionTechniqueTechniqueDiagnostic-TechniqueDiagnostic TechniqueCase Lesson
Cerebral abscess in Down syndrome: a systematic review on treatment and prognosis. Illustrative case
Hamilton Preci DM 18*
Valentin Eisenring Christian MD 2*
Burn Felice MD 3
Aziz Waseem MD 45
Vasankari Ville MD 6
Rossmann Tobias MD 7
Veldeman Michael MD 9*
Thakur Jitendra MS 10*
1 Department of Surgery, Division of Neurosurgery, Cornwall Regional Hospital, Montego Bay, Jamaica
2 Department of Neurosurgery, FMH, Hirslanden Klinik Hirslanden, Zürich, Switzerland
3 Institute of Radiology and Neuroradiology, Cantonal Hospital Aarau, Aarau, Switzerland
4 Department of Neurosurgery, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
5 Department of Neurosurgery, Alexandria University School of Medicine, Alexandria, Egypt
6 Department of Neurosurgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
7 Department of Neurosurgery, Neuromed Campus, Kepler University Hospital, Johannes Kepler University, Linz, Austria
8 Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Preston, United Kingdom
9 RWTH Aachen University Hospital, Aachen, Germany
10 Department of Neurosurgery, Nepal Medical College & Teaching Hospital, Kathmandu, Nepal
Correspondence Preci Hamilton: Cornwall Regional Hospital, Montego Bay, Jamaica. precihamilton@regionalneuroscience.com.
INCLUDE WHEN CITING Published September 9, 2024; DOI: 10.3171/CASE23394.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

* P.H. and C.V.E. contributed equally to this work, and M.V. and J.T. contributed equally to this work.

09 9 2024
09 9 2024
8 11 CASE2339427 7 2023
11 6 2024
© 2024 the authors
2024
the authors
https://creativecommons.org/licenses/by-nc-nd/4.0/ CC BY-NC-ND 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

BACKGROUND

No universal protocol exists for treating cerebral abscesses in Down syndrome. An illustrative case supplemented with a systematic literature review on brain abscesses in Down syndrome is presented, comprising a total of 16 cases. Preoperative infectious disease workups, cardiac examinations including echocardiography, as well as reported surgical and antibiotic treatments were correlated in the reported cohorts.

OBSERVATIONS

Overall, 18.8% of cases (n = 3) had no reported cardiac evaluation. The majority of cases were treated surgically (n = 8), with aspiration (n = 3), drainage (n = 2), or other operations (n = 3); 25% (n = 4) were treated with antibiotics only. Strikingly, 25% of cases (n = 4) reported neither surgical nor antibiotic therapy, a significantly higher rate compared to 0%–3% of patients with brain abscess in other reported cohorts.

Half of the patients (n = 8) who died either lacked a cardiac evaluation or had existing heart conditions. This mortality rate was about 4 times higher than the rates observed in other studies.

LESSONS

Down syndrome patients with cerebral abscess have a high morbidity rate, mainly due to cardiac disease. Therefore, early diagnostic workup, including echocardiography, allows proactive management with an improved outcome.

https://thejns.org/doi/10.3171/CASE23394

brain abscess
Down syndrome
optimal treatment strategy
antibiotic management
surgical drainage
stereotactic aspiration
ABBREVIATIONS

ADC = apparent diffusion coefficient
CRP = C-reactive protein
CT = computed tomography, DWI = diffusion-weighted imaging
GCS = Glasgow Coma Scale
IVROBA = intraventricular rupture of brain abscess
MRC = Medical Research Council
MRI = magnetic resonance imaging
ORL = otorhinolaryngology.
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pmcDown syndrome is associated with a variety of immunological impairments, including an increased susceptibility to nasopharyngeal infections. The congenital aberrant morphology of the eustachian tube in patients with Down syndrome predisposes them to the ascent of bacteria from the nasopharynx, leading to otitis media.1 Furthermore, congenital heart disease, especially atrioventricular septal defects and valvular dysfunction, is more frequent in this group of patients, with a reported incidence of approximately 40%.2–4 These factors combined portend a greater risk of cerebral abscesses from paradoxical septic emboli, with a higher incidence of morbidity and mortality compared to those in the general population.

Intracerebral abscesses constitute a potentially fatal neurosurgical disease, necessitating expedited treatment to avoid rapid deterioration from mass effect or overwhelming sepsis.5–7 The aim is usually to perform early microbiological analysis and prevent these devastating complications. The most favorable treatment strategies range from nonsurgical management with intravenous antibiotics to various operative procedures performed for either therapeutic or diagnostic purposes to influence antibiotic stewardship.8 Surgery includes open craniotomy and evacuation of the pus, as well as image guidance using ultrasound and minimally invasive stereotactic procedures with computed tomography (CT) or magnetic resonance imaging (MRI).9 There is no universal treatment protocol; however, neurological, radiological, and inflammatory surrogate markers should be regularly monitored to assess the response to therapy.

Herein, we report the case of a patient with Down syndrome who presented with multiple abscesses in eloquent and noneloquent areas of the brain. The abscesses were treated with a combination of open and stereotactic operations, along with concomitant systemic antibiotics. Evidence-based guidelines for the diagnostic workup and treatment of cerebral abscesses, particularly in patients with Down syndrome, were systematically reviewed and are presented herein.

Illustrative Case

A 39-year-old man with Down syndrome presented to the emergency department of a hospital in northwest England, complaining of otalgia for 1 week, confusion, unsteady gait, and left upper-limb weakness for 3 days. The remainder of his medical history was unremarkable. Despite his trisomy 21, he did not have a known cardiac abnormality or malignancy.

In the emergency department, his vital signs were all within the normal range. He was mildly confused, with a Glasgow Coma Scale (GCS) score of 14, and had Medical Research Council (MRC) grade 3/5 power in his left upper and lower limbs. The otorhinolaryngology (ORL) team confirmed a small amount of middle ear fluid using both otoscopy and a thin-slice CT scan of the temporal bone. Blood investigations showed a normal leukocyte count and a negative human immunodeficiency virus test. C-reactive protein (CRP) was elevated to 70 mg/L (normal value: 0.5–5.0). A CT scan of the brain showed right frontal (1.5 cm × 1.9 × cm × 2.2 cm [length × width × height]), bilateral temporal (left: 2 cm × 2.2 cm × 1.9 cm, right: 1.5 cm × 1.9 cm × 2.2 cm), and right basal ganglia (2.4 cm × 1.8 cm × 2.9 cm) space-occupying lesions with ring enhancement of contrast agent, significant vasogenic edema, and mass effect (Figs. 1 and 2). Differential diagnoses such as cerebral abscess, glioblastoma, metastasis, lymphoma, and toxoplasmosis were considered, as a high diffusion-weighted imaging (DWI) signal with reduced apparent diffusion coefficient (ADC) confirmed restricted diffusion on MRI. A short preoperative course of dexamethasone 4 mg twice daily was administered intravenously. Due to the relatively rapid development of symptoms and the fulminant imaging findings, an invasive procedure aimed at rapid volume reduction was deemed warranted. Primarily, the patient underwent stereotactic aspiration of both temporal abscesses, with craniotomy and partial evacuation of the right frontal abscess. The aspirated pus was sent for cultures. The deep abscess was not targeted at first due to the risk of further neurological deficits and the risk of inadvertent rupture into the ventricular system. No intralesional drain was placed, and no intracavity antimicrobial therapy was administered. Systemic antibiotic treatment was commenced with intravenous ceftriaxone 2 g every 12 hours, and intravenous metronidazole 500 mg every 8 hours, according to the local antibiotic guidelines. FIG. 1. Axial contrast-enhanced CT scans obtained at different levels, demonstrating multiple superficial right frontal and bilateral temporal (white arrows) and deep right thalamic (black arrow) ring-enhancing cerebral abscesses.

FIG. 2. DWI (A, C, and E) and ADC map (B, D, and F) sequences demonstrating the typical pattern of high DWI signal and low (hypointense) ADC, indicative of restricted diffusion in all lesions: frontal (A and B), right thalamic (C and D), and bilateral temporal (E and F).

Blood and urine cultures did not reveal an infection, and there were no signs of endocarditis on the transesophageal echocardiogram, which was normal. The acquired microbiological samples demonstrated significant growth of Streptococcus intermedius with sensitivity to cephalosporin; therefore, a change in the antibiotic regimen was not warranted. The patient became fully alert and oriented; however, his left hemiparesis persisted. Repeat MRI of the brain 8 days postoperatively demonstrated no change in the size of the nonsurgically treated right thalamic abscess (Fig. 3A). Stereotactic aspiration of approximately 6 ml of pus from the right thalamic abscess was then performed via a right frontal craniotomy using the VarioGuide neuronavigation system (Brainlab). The left upper-limb weakness improved transiently following this intervention. FIG. 3. Axial (A) and coronal (B) postcontrast T1-weighted MRI demonstrated the right thalamic abscess with a thick enhancing capsule abutting and exerting mass effect on the right lateral ventricle. Axial postcontrast T1-weighted MRI (C and D) showed complete resolution of all abscesses at 8 months’ follow-up. Gliosis can be seen in the right frontal lobe where the abscess was located.

Further MRI of the brain, 1 week later, demonstrated an increase in the size of the previously aspirated right thalamic abscess. The patient again underwent stereotactic aspiration of the lesion. This time, collapse of the space-occupying lesion was confirmed in real time with intraoperative ultrasound. Culture and sensitivity results were as before, and therefore his antimicrobial regimen remained unaltered. Progress was monitored regularly by clinical evaluation, biochemical inflammatory surrogate markers, and radiological response after discharge to a local rehabilitation unit. Based on the patient’'s confirmed bacterial infection that responded well to antibiotic treatment, the decision was made to continue the treatment for a period of 8 weeks postoperatively, at which time complete resolution of the infection and no signs of recurrence were confirmed.

At 8 months’ follow-up, final contrast-enhanced MRI of the brain showed complete resolution of all abscesses (Fig. 3C and D). The weakness of the left upper extremity had improved to MRC level 4/5 and there were no other neurological deficits.

Literature Review Search and Exclusion Criteria

The literature review involved a systematic search of the PubMed database and Google Scholar, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.10 The search initially identified 43 records through PubMed and an additional 2985 records through Google Scholar. After removing duplicates, 998 records were screened, and 64 full-text articles were assessed for eligibility. With our case included in the analysis, 16 cases were ultimately included in the analysis.

The systematic review registration identification number of the international Prospective Register of Systematic Reviews is 205291. The search terms used were “cerebral abscess,” “brain abscess,” “Down syndrome,” or “trisomy 21.” The abstracts of 998 records were screened. We excluded those with no human subjects, for which the search terms were not connected in a meaningful way, or that were reported in a language other than English, French, Spanish, or German. Sixty-four full-text articles were assessed, and 49 were excluded when the identification of both trisomy 21 and cerebral abscess in the same subject was not possible.

The resultant 15 reports of patiens with both cerebral abscess and Down syndrome, along with our case, are presented in Table 1.11–25 The average age was 22 years ± 11 standard deviation. Fifty percent (n = 8) of the infections had an unspecified origin, followed by 25% (n = 4) spreading from the otorhinolaryngological system. The most frequently reported (37.5%) infectious agent was viridians streptococci (n = 5), while 31.3% (n = 5) of origins remained undisclosed. Staphylococcus aureus was the causative agent in 12.5% (n = 2) of the reported cases. TABLE 1. Summary of the reported cases of Down syndrome with cerebral abscess

Authors & Year	Age (yrs), Gender	Initial Neurological Deficit	Most Probable Etiology	Infectious Agent	Cardiac Disease	Solitary or Multiple	Location	Treatment	Duration Until Last FU (mos)	Outcome	
Billheden et al.,
198711	36, M	Lt-sided hemiparesis	Urological malformation pyuria	Group B Streptococci	Vegetations on mitral leaflet	Multiple	Multifocal	Antibiotic therapy	12	Epileptic seizures, paresis	
Stafstrom et al.,
199112	—	Seizures	—	S. intermedius	—	Solitary	Frontal lobe	Needle aspiration	—	—	
Stapleton et al.,
199313	27, M	Epilepsy, GCS score 10	—	Viridans streptococci	Atrial septal defect	Solitary	Parieto-occipital, lt	CT-guided stereotactic aspiration of pus & antibiotic therapy	24	Good outcome	
Bonomo et al.,
199814	31, M	Fever, weakness	Scabies & endocarditis	S. aureus	Vegetation, foramen ovale	Multiple	Middle cerebral artery region, cerebellar hemispheres	Antibiotic therapy	0.02	Died	
Michelow et al.,
200015	2.5, F	Lethargy, hypotonia	Dental caries	Abiotrophia spp.	Atrioventricular septal defect	Solitary	Rt centrum semiovale	Antibiotic therapy & ventriculostomy for CSF drainage	4	Hemiplegia	
Chung et al.,
200416	29, F	Seizure, hemiparesis	Dental caries	—	Eisenmenger syndrome	Solitary	—	Removal of teeth & amoxicillin	0.25	No complications	
Goodkin et al.,
200417	—	—	Septicemia	S. aureus	Congenital heart disease	Multiple	Cerebral hemispheres & subcortical structures	—	0	Died	
Worley et al.,
200418	8, F	Focal weakness	Carious teeth	Viridans streptococci	Eisenmenger physiology	Solitary	Lt frontal lobe	Surgical drainage	6	Died	
Kowlessar et al.,
200619	17, F	—	—	Viridans streptococci	—	Multiple	Multifocal	Burr hole drainage	0	Died	
Auvichayapat et al.,
200720	—	—	—	—	Endocardial cushion defect	Solitary	—	Palliative treatment	0	Died	
Duffels et al.,
200921	—	—	—	—	Eisenmenger syndrome	Solitary	—	—	14	Died	
Shachor-Meyouhas et al.,
201022	18, F	—	—	Viridans streptococci	Eisenmenger complex	Solitary	Parietal	Operation & antibiotic treatment	168	Died	
Vis et al.,
201323	30, M	—	—	—	Atrioventricular septal defect	Solitary	—	—	—	Died	
Kheir et al.,
201724	12, M	Focal convulsions & rt-sided weakness	Septicemia	Mycobacterium tuberculosis	Normal echocardiogram	Multiple	Lt temporal & frontoparietal lobes	Antituberculosis drugs (isoniazid, ethambutol, pyrazinamide, & rifampicin), steroids	1	Good	
Chen et al.,
201825	10, M	Rt-sided weakness	—	No pathogen in blood cultures	Not obvious	Multiple	Parieto-occipital & basal ganglia	Burr hole aspiration	1.5	Rt-sided weakness	
Present case	38, M	Otalgia, confusion, focal paresis	Middle ear infection	Viridans streptococci	No pathological finding	Multiple	Frontal, bitemporal, basal ganglia	Stereotactic aspiration, resection, 2 repeated aspirations	8	Good	
FU = follow-up; — = not available.

Of those 12 with a reported microbiological test, 41.7% (n = 5) died, 33.3% (n = 4) had neurological deficits, 16.7% (n = 2) had a described “good outcome," while the outcome was not reported in the remaining case. Of the 4 cases where no microbiological test was reported, 3 patients died, while the other had no complications.

Cardiac Abnormality

A cardiac abnormality was reported in 62.5% (n = 10) of cases, including septal defects (n = 8), of which 4 cases had an Eisenmenger reaction. Fifty percent of cases (n = 8) were treated surgically, with aspiration (n = 3), open drainage (n = 2), or other operations (n = 3). There was 1 case with a good outcome after aspiration, 3 cases of neurological deficit after aspiration and other operations, and 3 reported deaths: 2 following open drainage and the other subsequent to another operation. There were no reported fatalities following aspiration of a cerebral abscess.

Nonoperative Management

Twenty-five percent (n = 4) of the patients were treated with antibiotics only, with evenly spread outcomes reported as good, without complications, neurological deficits, or fatal. Another 25% (n = 4) of cases were either treated with supportive care (n = 1) or had no reported treatment (n = 3), all of whom eventually died.

The 16 reported cases of Down syndrome with cerebral abscess were compared to the cohorts5–7 presented in Table 2. TABLE 2. Comparison of the systematically reviewed cases of Down syndrome with cerebral abscess to unselected cases with cerebral abscess

Characteristic	Down Syndrome	Nathoo et al., 20115	Bodilsen et al., 20237	Kameda-Smith et al., 20226	
No. of patients	16	973	485	139	
Mean age ± SD, yrs	22 ± 11	24.36 ± 15.1	59	A: 56.15 ± 13.67; P: 8.67 ± 6.40	
Females among specified genders, %	33	25.8	34	31.7	
Males among specified genders, %	67	74.2	66	68.3	
No reported gender, %	25	NA	NA	NA	
Origin of infection, %					
 ORL	6	38.6	14	13	
 Unspecified	50	NA	NA	NA	
 Systemic	6	NA	NA	16.5	
 Trauma	NA	32.8	NA	NA	
 Other	NA	8.6	6	5.0	
 Pulmonary	NA	6.8	NA	NA	
 Cryptogenic	NA	4.6	NA	NA	
 Postsurgical	NA	3.2	11	19.5	
 Meningitis	NA	2.8	NA	3.6	
 Cardiac	13	2.7	NA	NA	
 Cryptogenic	NA	4.6	NA	29.5	
 Urinary tract	6	NA	NA	NA	
 Dental	13	0.9	19	12.9	
Multiple abscesses, %	44	7.8	NA	18.7	
Solitary abscesses, %	56	NA	NA	81.3	
Reported infectious agent, %					
 Gram-positive cocci	NA	42.2	NA	NA	
  Streptococcus anginosus	NA	NA	NA	24.5	
  Virdans streptococci	38	1.3	NA	NA	
  S. aureus	13	14.4	6	7.9	
  Group B streptococci	6	6.2	NA	NA	
  Abiotrophia spp.	6	NA	NA	NA	
  Staphylococcus epidermidis	NA	6.8	NA	NA	
  Other gram-positive cocci	NA	20.2	NA	6.4	
  Gram-positive bacilli	NA	1.3	NA	NA	
  Nocardia	NA	0.3	NA	2.1	
 Gram-negative bacteria					
  Enterobacteriaceae	NA	1.5	3	NA	
  Other gram-negative bacteria	NA	23	NA	6.4	
 M. tuberculosis (n = 23)	6	2.4	NA	NA	
 Fungal	NA	0.6	NA	4.3	
 Mixed	NA	15.2	NA	28	
 Sterile (no growth)	31	30.1	NA	20.1	
 Undisclosed/no data	NA	1.6	NA	NA	
Cardiac abnormality, %	75	2.5	NA	NA	
 Septal defect	62.5	NA	NA	NA	
 Eisenmenger reaction	50	NA	NA	NA	
 No abnormality upon workup	12.1	NA	NA	NA	
 No cardiac workup	12.1	NA	NA	NA	
Surgical treatment, %	50	97.1	75	99.8	
 Aspiration/surgical drainage/resection	37.5	98	75	26.6/64	
 Other/unspecified operations	12.5	NA	NA	NA	
 Nonsurgically w/ antibiotics	25	2	NA	NA	
 No treatment or palliative	6.1	NA	NA	NA	
 Not documented	18.7	NA	NA	NA	
Descriptive outcome, %					
 Good	25	81.3	NA	54	
 Persistent neurological deficit	19	24.9	NA	37.9	
 Fatal outcome	50	13.4	12	11.5	
 Not reported	6	NA	NA	NA	
Mean FU ± SD, mos	18 ± 49	7.4 ± 13.3	6	7.1 ± 12.7	
A = adult; NA = not available; P = pediatric.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Index Case

Cerebral abscesses constitute a neurosurgical emergency. Therefore, it is necessary to maintain a high index of suspicion to prompt timely imaging confirmation of the diagnosis and the location of the lesion(s). Classically, these lesions demonstrate ring enhancement after contrast administration on both CT and MRI scans, with significant associated vasogenic edema. DWI shows hyperintense signal, and restricted diffusion is confirmed by hypointensity on the ADC map sequence. While this is 96% sensitive and specific for cerebral abscesses, these findings could also represent toxoplasmosis, metastatic brain lesions, or highly cellular brain tumors such as lymphoma or high-grade glioma. In this instance, with clearly elevated inflammatory markers, the presenting complaint of otalgia preceding the acute deterioration made cerebral abscess the most likely diagnosis.26

Three of the abscesses were suitable candidates for neurosurgical excision, as they were superficial and not directly associated with eloquent cortex. Despite this, only the right frontal abscess was excised because of its large size and thick capsule that was encountered at the time of the attempted aspiration. Thus, maximal safe resection of the abscess capsule was performed.

A lack of florid systemic inflammatory response syndrome was not surprising, given that approximately 25%–40% of patients with brain abscesses are apyrexial with normal CRP at presentation.27, 28 The abscess enlargement and neurological deterioration following initial aspiration signified an increased risk of the intraventricular rupture of brain abscess (IVROBA), as the capsule is usually thinnest along the ventricular side.29 IVROBA has a high mortality rate because of the resultant ventriculitis and meningoencephalitis and may warrant intraventricular antibiotics.

Endoscopic treatment was an option for the deep-seated thalamic cerebral abscesses.30, 31 Endoscopy would not only have afforded an aspiration port, but could have made way for direct visualization of the abscess capsule, in particular, the interface with the ventricular wall, cavity lavage, and drain placement under direct vision. Endoscopy has been shown to be a safe and effective approach with results comparable to microsurgical excision of the abscess capsule.30, 31 Earlier surgical decompression of the thalamic abscess would have been a justified option despite the increased risks outlined a priori.

This case demonstrated the consideration and application of combined medical and varying approaches to multiple intracerebral abscesses with an encouraging result, consistent with Mamelak’s series of patients with brain abscesses.32 This underscores the importance of managing cerebral abscesses by critically evaluating and treating not only each patient but also, importantly, each lesion individually.

Literature Review

The 16 systematically reviewed cases of Down syndrome with cerebral abscess differ from nonselected cohorts regarding the mode of disease spread, presence of congenital cardiac malformations, intracranial disease burden, proportion of patients who had surgery, and mortality rates.

Prognostic Value of a Cardiac Comorbidity in Patients with Cerebral Abscesses (Down syndrome versus General Population)

Interestingly, none of the 8 patients with cardiac septal defects had multiple cerebral abscesses (Table 1). On the other hand, cardiac vegetations were diagnosed in 2 patients who had multiple cerebral abscesses. Two patients did not have cardiac pathology, 1 had full improvement in motor power, and the other had residual left hemiparesis. Of the 3 patients for whom there was no mention of a cardiac workup, 1 died and 1 survived with residual hemiparesis; the outcome of the third patient was not reported. While patients with an unrepaired cardiac septal defect demonstrate an increased risk of complications from brain abscess, those who have their cardiac defects repaired have improved cardiovascular function and a reduced risk of complications related to the abscess.4

Fatal outcomes occurred in 50% (n = 8) of the patients, all of whom were found to have cardiac pathology. In one of these patients, only supportive care was initiated because of the unfavorable prognosis in combination with an endocardial cushion defect,20 while another patient had congenital heart disease, multiple abscesses, and S. aureus septicemia.17 These mortality rates are high compared to the 13.4% rate reported for a cohort of the general population with brain abscess.5 Note that 3% of the patients did not receive neurosurgical therapy, 2% had comorbidities, and 1% had either died before or refused neurosurgical intervention.

Treatment Strategy and Outcome with Multiple Cerebral Abscesses

Of the 43.8% (n = 7) reported cases with multiple cerebral abscesses, 3 were managed surgically, of whom 1 died and 2 had a residual neurological deficit. Three patients were treated with antibiotics, of whom 1 died, 1 had a neurological deficit, and 1 had a good outcome. The treatment administered to 1 patient who died was not reported.

In another cohort of the general population, it was reported that 17.1% (n = 13) of subjects with multiple cerebral abscesses had a poor outcome, whereas 14.5% died.5

Paradoxical Embolism Causing Brain Abscess

Paradoxical embolism occurs when an embolus travels from the right to the left side of the heart into the systemic circulation.33 In one survey, 19% of patients with trisomy 21 had a history of presumed or documented paradoxical embolism, with 22% having sustained atrial arrhythmias as a result of septic emboli.4 About 63% (n = 10) of the cases in our review were reported in association with cardiac pathology, compared to 2.7% in a general cohort, of which approximately 20% had multiple cerebral abscesses.5 It is noteworthy that the mortality rate in Down syndrome decreases from 40% to 4% with the advent of cardiac surgery to correct cardiovascular defects in the 1st year of life.4

For patients with Down syndrome, early echocardiography may reveal the source of cerebral abscesses, such as a cardiac septal defect or bacterial colonization of cardiac valves. Early cardiac septal defect closure appears to confer a prognostic benefit regarding the development or complications of cerebral abscesses.

The treatment of brain abscesses, including in patients with Down syndrome, involves a comprehensive approach comprising intravenous antibiotics and potentially neurosurgical drainage, as summarized by Corsini Campioli et al. and Bodilsen et al.8, 34

This strategy is underscored by evidence-based guidelines on the diagnostic workup of brain abscesses and emphasizes the critical role of early diagnosis, appropriate antibiotic choice, and surgical interventions tailored to the individual case to improve outcomes and survival rates. More specific recommendations are described in the European Society of Clinical Microbiology and Infectious Diseases guidelines on brain abscess diagnosis and treatment.34

The Role of Dexamethasone

The use of dexamethasone to treat associated brain edema in patients with cerebral abscess has been controversial, raising concerns about its immunosuppressive effect and antibiotic penetration. A systematic review and meta-analysis, including 7 studies, reported no increased mortality with dexamethasone use and therefore concluded that the use of this steroid in patients with cerebral abscess is at the discretion of the treating physician.35

Strengths and Limitations

The generalizability of the findings of this systematic review is limited given its retrospective nature. It is further limited by the degree of missing data becausethe information was not collected or was underreported. While there is currently a paucity of data and guidelines concerning cerebral abscess with Down syndrome, our results may serve as a basis for the development of more evidence-based strategies for such patients.

Observations

Our systematic review and the illustrative case of a cerebral abscess in a patient with Down syndrome reveal several critical observations. A significant percentage (18.8%) of the compiled cases lacked cardiac evaluation prior to treatment. Surgical interventions were predominant (50%), with varied outcomes indicating the various approaches to managing cerebral abscesses in this population. The mortality rate in the compiled cases was markedly higher than in other cohorts, highlighting the severe impact of underlying cardiac conditions in patients with Down syndrome.

These observations underline the necessity for comprehensive preoperative evaluations and tailored treatment strategies for patients with Down syndrome, emphasizing the need for interdisciplinary care.

While the higher prevalence of cardiac anomalies in patients with Down syndrome is well-documented, the correlation between unassessed cardiac conditions and higher mortality rates in cerebral abscess cases has not been extensively reported. This gap in the literature accentuates the need for further research into integrated care strategies.

Lessons

The recovery rate with good outcomes was 81% for a cohort of the general population and 19% for patients with Down syndrome. Survival rates were higher for those Down syndrome cases that had a cardiac evaluation before the operation and reported therapy. Early cardiac evaluation and timely management of a cardiac abnormality should therefore be considered in patients with Down syndrome. Additionally, Down syndrome patients with cerebral abscess should be treated similarly to other cerebral abscess patients, with an appropriate antibiotic regimen and surgical procedures adapted to the individual case, to improve outcomes and survival.

Acknowledgments

We would like to thank Mr. Gareth Roberts and Mrs. Marcia Donaldson-Hugh from the Royal Preston Hospital, Lancashire, Preston, United Kingdom, and Michelle Baumann, MD, Infectious Diseases Consultancy Service, University Hospital Basel, for insightful management guidance and manuscript reviews.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Hamilton, Eisenring, Vasankari, Thakur. Acquisition of data: Hamilton, Eisenring, Burn, Thakur. Analysis and interpretation of data: Hamilton, Eisenring, Aziz, Rossmann, Thakur. Drafting the article: Hamilton, Eisenring, Aziz, Thakur. Critically revising the article: all authors. Reviewed submitted version of manuscript: Hamilton, Eisenring, Aziz, Vasankari, Veldeman, Thakur. Approved the final version of the manuscript on behalf of all authors: Hamilton. Statistical analysis: Hamilton, Eisenring, Thakur. Administrative/technical/material support: Hamilton, Eisenring, Burn, Veldeman. Study supervision: Hamilton, Eisenring, Thakur.

Correspondence

Preci Hamilton: Cornwall Regional Hospital, Montego Bay, Jamaica. precihamilton@regionalneuroscience.com.
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