Ropień mózgu – Patofizjologia i mechanizm

Ropień mózgu
Patofizjologia i mechanizm

Ropień mózgu to ogniskowe zakażenie miąższu mózgu, rozwijające się od zapalenia (cerebritis) do ropnia otoczonego torebką włóknistą. Etiologia obejmuje szerzenie przez ciągłość (45-50%), szerzenie krwiopochodne (25-35%) oraz bezpośrednią inokulację (ok. 10%). Najczęstsze patogeny to bakterie tlenowe (Streptococcus anginosus, S. aureus), beztlenowe (Bacteroides, Prevotella) oraz pałeczki Gram-ujemne (Enterobacteriaceae, Pseudomonas). U pacjentów immunosupresyjnych lub w specyficznych regionach etiologia może obejmować grzyby (Aspergillus, Candida), mykobakterie (M. tuberculosis) i pierwotniaki (Toxoplasma gondii). Proces chorobowy przebiega przez cztery fazy: od ostrego nacieku zapalnego i obrzęku, przez tworzenie martwicy i włóknistej torebki, aż do uformowania dobrze unaczynionej torebki ropnia, która chroni otaczającą tkankę, ale może prowadzić do powikłań, takich jak przebicie do układu komorowego z 80% śmiertelnością.

Patogeneza ropnia mózgu (Brain abscess Pathogenesis)

Ropień mózgu (brain abscess) to ogniskowe, zlokalizowane zakażenie miąższu mózgu, które rozwija się początkowo jako obszar zapalenia (cerebritis), a następnie ewoluuje w ognisko ropne otoczone dobrze unaczynioną torebką włóknistą. Zakażenie to stanowi poważne zagrożenie dla życia, z roczną zachorowalnością sięgającą do 8% w krajach rozwijających się. Infekcja może prowadzić do zniszczenia tkanki nerwowej, zarówno bezpośrednio przez drobnoustroje, jak i pośrednio przez odpowiedź zapalną gospodarza.¹²³

Drogi szerzenia się infekcji

Istnieją trzy główne mechanizmy patofizjologiczne powstawania ropnia mózgu:¹²

Szerzenie przez ciągłość (45-50% przypadków) – zakażenie rozprzestrzenia się bezpośrednio z sąsiadujących ognisk zapalnych, takich jak zapalenie ucha środkowego (5%), zapalenie zatok przynosowych (30-50%), zapalenie wyrostka sutkowatego lub infekcje zębowo-dziąsłowe. Tą drogą powstają zwykle pojedyncze ropnie mózgu.¹²
Szerzenie krwiopochodne (25-35% przypadków) – zakażenie rozprzestrzenia się z odległych ognisk, takich jak przewlekłe infekcje płuc, ropnie płuc, ropniaki opłucnej (szczególnie u osób z rozstrzeniami oskrzeli i mukowiscydozą), zapalenie wsierdzia, zakażenia jamy brzusznej i układu moczowego. Ropnie powstałe tą drogą są często mnogie i wielokomorowe, najczęściej zlokalizowane w obszarze unaczynienia tętnicy środkowej mózgu, na granicy istoty szarej i białej.¹²³
Bezpośrednia inokulacja (około 10% przypadków) – drobnoustroje dostają się do mózgu w wyniku urazu penetrującego czaszki, złamania otwartego z przerwaniem opony twardej lub w następstwie procedur neurochirurgicznych.¹²³

W około 10-35% przypadków ropni mózgu nie udaje się zidentyfikować pierwotnego źródła zakażenia, określając je jako kryptogenne.¹²

Czynniki predysponujące

Do głównych czynników ryzyka rozwoju ropnia mózgu należą:¹²

Wrodzone wady serca, szczególnie z przeciekiem prawo-lewym (np. ubytki przegrody międzykomorowej)
Przewlekłe zakażenia zatok przynosowych, ucha środkowego i mastoiditis
Infekcje zębowo-dziąsłowe
Przetoki tętniczo-żylne płucne (PAVM) – około 10% pacjentów z PAVM rozwija ropnie mózgu
Stany immunosupresji związane z zakażeniem HIV, chorobami nowotworowymi, chemioterapią, cukrzycą czy alkoholizmem
Marskość wątroby – z powodu dysfunkcji układu siateczkowo-śródbłonkowego i przecieków wrotno-systemowych

Etiologia ropnia mózgu

Ropnie mózgu są często zakażeniami polimikrobialnymi. Najczęściej izolowanymi patogenami są:¹²³

Bakterie tlenowe: paciorkowce (szczególnie z grupy Streptococcus anginosus i Streptococcus viridans), Staphylococcus aureus
Bakterie beztlenowe: Bacteroides, Prevotella, Fusobacterium
Pałeczki Gram-ujemne: Enterobacteriaceae, Pseudomonas, Escherichia coli, Klebsiella pneumoniae
Inne: Actinomyces, Nocardia

W przypadku pacjentów z obniżoną odpornością lub w specyficznych regionach geograficznych, czynnikami etiologicznymi mogą być również:¹²

Grzyby: Aspergillus, Candida, Cryptococcus, Mucorales
Mykobakterie: Mycobacterium tuberculosis
Pierwotniaki: Toxoplasma gondii, Entamoeba histolytica

Etapy rozwoju ropnia mózgu

Rozwój ropnia mózgu to proces sekwencyjny, przebiegający przez cztery charakterystyczne etapy:¹²³

Wczesne zapalenie mózgu (wczesna cerebritis)

Ta faza trwa od 1 do 3 dni od momentu wniknięcia patogenu do tkanki mózgowej i charakteryzuje się:

Naciekiem zapalnym okołonaczyniowym złożonym z neutrofilów, komórek plazmatycznych i monocytów
Obrzękiem tkanki mózgowej
Martwicą tkanki
Brakiem wyraźnego odgraniczenia zmiany zapalnej

Na tym etapie zmiana jest słabo odgraniczona i związana z lokalnym obrzękiem. Występuje ostry stan zapalny, ale bez martwicy tkanki.¹²

Późne zapalenie mózgu (późna cerebritis)

Faza ta występuje od 4 do 9 dnia i charakteryzuje się:

Dominującym naciekiem makrofagów i limfocytów
Pojawieniem się fibroblastów
Początkiem tworzenia się strefy martwicy
Dalszym obrzękiem tkanki mózgowej

W ciągu 2-3 tygodni dochodzi do procesów martwicy i upłynnienia tkanki mózgowej w centrum zmiany.¹²

Wczesna formacja torebki

Ta faza rozpoczyna się około 10-13 dnia i charakteryzuje się:

Tworzeniem się włóknistej torebki wokół ogniska martwicy
Zwiększonym unaczynieniem torebki ropnia
Gromadzeniem komórek zapalnych (fibroblastów, neutrofilów i makrofagów)

Późna formacja torebki

Faza ta rozpoczyna się od 14 dnia i charakteryzuje się:

Dobrze uformowaną torebką włóknistą, skutecznie odgraniczającą zmianę
Rozległym unaczynieniem torebki
Ochroną otaczającego prawidłowego miąższu mózgu przed dodatkowym uszkodzeniem

Torebka ropnia jest zwykle najgrubsza od strony korowej, a najcieńsza przyśrodkowo, co powoduje, że ropień ma tendencję do powiększania się w kierunku układu komorowego i może do niego przebić, co stanowi poważne powikłanie z 80% śmiertelnością.¹²³

Mechanizmy immunopatogenetyczne

Reakcja zapalna i uszkodzenie tkanki mózgowej

Uszkodzenie tkanki mózgowej w przebiegu ropnia mózgu wynika głównie z odpowiedzi zapalnej gospodarza na inwazję patogenów. Ta reakcja obronna, choć niezbędna do eliminacji drobnoustrojów, przyczynia się również do zniszczenia otaczającej prawidłowej tkanki mózgowej.¹²³

Kluczowe elementy tego procesu obejmują:

Aktywację komórek glejowych (mikrogleju i astrocytów), które wydzielają mediatory prozapalne
Napływ komórek zapalnych z krążenia obwodowego (neutrofile, makrofagi, limfocyty)
Wydzielanie cytokin prozapalnych, takich jak IL-1, TNF-α, MIP-2, które utrzymują się na podwyższonym poziomie nawet przez 14-21 dni po ekspozycji na S. aureus
Niszczenie bariery krew-mózg, co zwiększa przepuszczalność naczyń i nasilenie obrzęku mózgu

Proces zapalny często rozprzestrzenia się poza pierwotne ognisko zakażenia, prowadząc do uszkodzenia dużych obszarów tkanki mózgowej, co obserwuje się zarówno w modelach eksperymentalnych, jak i w przypadkach klinicznych.¹²

Rola neutrofilów i chemotaksji

Neutrofile stanowią główną populację komórek naciekających rozwijający się ropień mózgu i pełnią kluczową rolę w eliminacji bakterii. Ich działanie bakteriobójcze opiera się na:¹

Produkcji reaktywnych form tlenu i azotu
Wydzielaniu enzymów hydrolitycznych
Tworzeniu pułapek neutrofilowych (NETs – Neutrophil Extracellular Traps)

Chemokiny wiążące się z receptorem CXCR2 są głównymi sygnałami chemotaktycznymi kierującymi napływ neutrofilów do ropnia mózgu. Badania wykazały, że ich aktywności nie mogą zastąpić alternatywne czynniki chemotaktyczne, takie jak składniki dopełniacza (C3a, C5a), prostaglandyny, leukotrieny czy inne chemokiny.¹

Czynniki wirulencji bakterii

W patogenezie ropnia mózgu istotną rolę odgrywają również czynniki wirulencji bakterii. Przykładowo, α-toksyna produkowana przez S. aureus prowadzi do tworzenia porów w błonach komórkowych, powodując osmotyczną lizę komórek. Mechanizm ten pozwala na eliminację:¹²

Rezydujących w OUN komórek immunokompetentnych (mikroglej i astrocyty)
Profesjonalnych fagocytów naciekających ropień (neutrofile i makrofagi)

Upośledzenie skuteczności odpowiedzi przeciwbakteryjnej umożliwia niekontrolowane namnażanie się bakterii w ostrej fazie choroby. Badania na mutantach S. aureus pozbawionych zdolności do produkcji α-toksyny wykazały zmniejszoną wirulencję bakterii, choć nie całkowitą jej utratę, co sugeruje udział także innych czynników wirulencji w zakażeniu mózgu.¹

Hiperosmolarność ropnia i mechanizm ekspansji

Nowe badania wykazują, że ropnie mózgu powiększają się w czasie, nawet podczas skutecznej antybiotykoterapii. Mechanizm ten może być związany z hiperosmolarnością ropy, która przyciąga wodę do jamy ropnia, powodując jego ekspansję.¹²

Średni dzienny przyrost wielkości ropnia wynosi około 23% (zakres 0-176%). Proces ten prawdopodobnie wynika z:

Ciągłego napływu neutrofilów do jamy ropnia i ich śmierci w procesie NETosis
Rozkładu makromolekuł (białek, kwasów nukleinowych) do silnych osmolanów, takich jak aminokwasy i amoniak
Pobierania wody z naczyń włosowatych dobrze unaczynionej torebki ropnia

Te odkrycia sugerują, że opóźnienie w drenażu ropnia mózgu może prowadzić do jego ekspansji, niezależnie od obecności żywych bakterii w ropie.¹

Znaczenie kliniczne i terapeutyczne

Potencjalne następstwa ropnia mózgu

Jeśli ropień mózgu nie zostanie wcześnie wykryty i właściwie leczony, może prowadzić do poważnych konsekwencji:¹²

Zastąpienie obszaru ropnia blizną włóknistą
Utrata tkanki mózgowej przez wycięcie chirurgiczne
Pęknięcie ropnia do układu komorowego (powikłanie z 80% śmiertelnością)
Trwałe uszkodzenie mózgu i zaburzenia funkcji poznawczych
Zgon pacjenta

Implikacje terapeutyczne

Zrozumienie patogenezy ropnia mózgu ma istotne znaczenie dla optymalizacji leczenia:¹²³

Kontrolowanie intensywności i/lub czasu trwania odpowiedzi immunologicznej w mózgu może umożliwić skuteczną eliminację bakterii przy jednoczesnym zminimalizowaniu uszkodzeń otaczającej tkanki mózgowej
Interwencja z użyciem związków przeciwzapalnych po wystarczającej neutralizacji bakterii może być skuteczną strategią minimalizującą uszkodzenie otaczającego miąższu mózgu
Wczesne rozpoznanie i drenaż chirurgiczny ropnia w ciągu 24 godzin od diagnozy mogą zapobiec ekspansji ropnia i dalszemu uszkodzeniu tkanki mózgowej
Terapia antybiotykowa musi być dobrana na podstawie znajomości prawdopodobnych patogenów i ich wrażliwości

Postępy w zrozumieniu immunopatogenezy ropnia mózgu, w tym identyfikacja kluczowych cytokin i chemotaksyn odpowiedzialnych za rekrutację komórek zapalnych, mogą w przyszłości prowadzić do opracowania ukierunkowanych terapii immunomodulujących, które mogłyby poprawić wyniki leczenia i zmniejszyć neurologiczne następstwa tej choroby.¹²

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Materiały źródłowe

#1 Immunopathogenesis of brain abscess
https://pmc.ncbi.nlm.nih.gov/articles/PMC516022/
Brain abscesses develop in response to a parenchymal infection with pyogenic bacteria, beginning as a localized area of cerebritis and evolving into a suppurative lesion surrounded by a well-vascularized fibrotic capsule. The leading etiologic agents of brain abscess are the streptococcal strains and S. aureus, although a myriad of other organisms have also been reported. […] Following infection, the potential sequelae of brain abscess include the replacement of the abscessed area with a fibrotic scar, loss of brain tissue by surgical excision, or abscess rupture and death. Indeed, if not detected early, an abscess has the potential to rupture into the ventricular space, a serious complication with an 80% mortality rate. […] The most common sources of brain abscess are direct or indirect cranial infection arising from the paranasal sinuses, middle ear, and teeth. Other routes include seeding of the brain from distant sites of infection in the body (i.e. endocarditis) or penetrating trauma to the head.
#1 Brain abscess: A narrative review | Neurology perspectives
https://www.elsevier.es/en-revista-neurology-perspectives-17-articulo-brain-abscess-a-narrative-review-S2667049622000291
Brain abscess is a severe focal infection of the central nervous system (CNS) with an annual incidence of up to 8% in developing countries. […] The main pathophysiological mechanisms are related to bacterial spread from adjacent or distal foci. […] Three main pathophysiological mechanisms have been described: inoculation of pathogenic microorganisms normally found on the skin (eg, in the context of head trauma or neurosurgery), contiguous spread of bacteria (eg, mastoiditis, otitis media, sinusitis), and haematogenous spread from distal foci (eg, bacterial endocarditis, lung abscess, skin and dental infections). […] When the blood-brain barrier is damaged (eg, due to brain trauma or a neurosurgical procedure), the brain becomes extremely vulnerable to bacterial infection. […] Brain abscess development has classically been divided into 4 stages: 1) early cerebritis (perivascular infiltration of neutrophils, plasma cells, and mononuclear cells); 2) late cerebritis (macrophage and fibroblast infiltration is also observed); 3) early capsule formation; and 4) late capsule formation. […] The most frequently isolated pathogens are Staphylococcus aureus and Streptococcus viridans, with anaerobic microorganisms being found in up to 40% of cases.
#1 Brain Abscess: Background, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/212946-overview
Infection may enter the intracranial compartment directly or indirectly via three routes. […] Contiguous suppurative focus (45%-50% of cases) […] Direct extension usually causes a single brain abscess and may occur from necrotic areas of osteomyelitis in the posterior wall of the frontal sinus, the sphenoid and ethmoid sinuses, and mandibular dental infections, as well as from subacute and chronic otitis media and mastoiditis. […] Hematogenous spread from a distant focus (25% of cases) […] These abscesses are more commonly multiple and multiloculated and are frequently found in the distribution of the middle cerebral artery. The most commonly affected lobes (in descending frequency) are the frontal, temporal, parietal, cerebellar, and occipital.
#1 Brain Abscess – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441841/
Infections in the head and neck region can lead to the development of brain abscesses. Otitis media (5%) and mastoiditis are associated with abscesses in the inferior temporal lobe and cerebellum. Paranasal sinus infections account for 30% to 50% of cases, frequently leading to brain abscesses development. Infections from the frontal or ethmoid sinuses may spread to the frontal lobes, while dental infections commonly result in frontal lobe abscesses. […] Infectious hematogenous seeding of the brain can arise from various conditions, with the lungs being the most common source. Pulmonary infections, including lung abscesses and empyemas, are frequently seen in individuals with bronchiectasis, and cystic fibrosis is a significant contributing factor. […] Approximately 10% of patients with PAVMs develop brain abscesses. Bacteremia-related brain abscesses often result in multiple abscesses, primarily located in the middle cerebral artery distribution, typically at the gray-white matter junction. The most commonly isolated microbial pathogens in brain abscesses are staphylococci and streptococci, with Staphylococcus aureus and viridans streptococci being the most prevalent bacterial species. […] A meta-analysis of 9699 patients from 123 studies identified the following list of causative pathogens in brain abscesses: Streptococcus species, Staphylococcus species, Enterococcus species, Gram-negative enteric bacteria, Actinomycetales species, and others.
#1 Brain Abscess: Background, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/212946-overview
Brain abscess is caused by intracranial inflammation with subsequent abscess formation. The most frequent intracranial locations (in descending order of frequency) are frontal-temporal, frontal-parietal, parietal, cerebellar, and occipital lobes. In at least 15% of cases, the source of the infection is unknown (cryptogenic). […] The most frequent causative pathogens in community-acquired brain abscess are oral cavity bacteria such as Streptococcus anginosus group, Fusobacterium spp, and Aggregatibacter spp, which are often associated with dental and chronic ear infections. Other less common etiologies include Staphylococcus aureus and Gram-negative bacilli in post-neurosurgical brain abscess, Mycobacterium tuberculosis in endemic areas, and Nocardia spp, fungi, and parasites in the severely immune-compromised.
#1 Brain Abscess – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441841/
A brain abscess is a localized area of necrosis within the brain parenchyma, often resulting from infectious agents, such as Staphylococcus and Streptococcus, or trauma or surgery. In addition, infections in the head and neck may contribute to abscess development. Abscesses often arise from local infections in areas such as the ear, teeth, sinuses, mastoid air cells, or epidural spaces, but they may also originate from distant sites such as the lungs or heart. In young children, congenital heart disease can be a risk factor. Although brain abscesses can occur at any age, they are most common in the third decade of life. Treatment involves medical and surgical approaches, depending on the size and location of the abscess. […] Brain abscesses can originate locally and spread to other parts of the body. They often form from infections in nearby areas, such as the ear or sinuses, and may occasionally extend from more distant sites, such as the lungs or heart.
#1 Brain abscess – Wikipedia
https://en.wikipedia.org/wiki/Brain_abscess
Bacterial abscesses rarely (if ever) arise de novo within the brain although establishing a cause can be difficult in many cases. There is almost always a primary lesion elsewhere in the body that must be sought assiduously because failure to treat the primary lesion will result in relapse. […] The location of the primary lesion may be suggested by the location of the abscess: infections of the middle ear result in lesions in the middle and posterior cranial fossae; congenital heart disease with right-to-left shunts often result in abscesses in the distribution of the middle cerebral artery; and infection of the frontal and ethmoid sinuses usually results in collection in the subdural sinuses. […] Fungi and parasites may also cause the disease. Fungi and parasites are especially associated with immunocompromised patients. Other causes include: Nocardia asteroides, Mycobacterium, Fungi (e.g. Aspergillus, Candida, Cryptococcus, Mucorales, Coccidioides, Histoplasma capsulatum, Blastomyces dermatitidis, Bipolaris, Exophiala dermatitidis, Curvularia pallescens, Ochroconis gallopava, Ramichloridium mackenziei, Pseudallescheria boydii), Protozoa (e.g. Toxoplasma gondii, Entamoeba histolytica, Trypanosoma cruzi, Schistosoma, Paragonimus), and Helminths (e.g. Taenia solium). […] These organisms are associated with certain predisposing conditions: Sinus and dental infections, Penetrating trauma, Pulmonary infections, Congenital heart disease, HIV infection, Transplantation, Neutropenia.
#1 Immunopathogenesis of brain abscess | Journal of Neuroinflammation | Full Text
https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-1-16
The early stage or early cerebritis occurs from days 1-3 and is typified by neutrophil accumulation, tissue necrosis, and edema. […] The intermediate, or late cerebritis stage, occurs from days 4-9 and is associated with a predominant macrophage and lymphocyte infiltrate. […] The final or capsule stage occurs from days 10 onward and is associated with the formation of a well-vascularized abscess wall, in effect sequestering the lesion and protecting the surrounding normal brain parenchyma from additional damage. […] In addition to limiting the extent of infection, the immune response that is an essential part of abscess formation also destroys surrounding normal brain tissue. […] This phenomenon is also observed in human brain abscess, where lesions can encompass a large portion of brain tissue, often spreading well beyond the initial focus of infection.
#1 Pathogenesis, clinical manifestations, and diagnosis of brain abscess – UpToDate
https://www.uptodate.com/contents/pathogenesis-clinical-manifestations-and-diagnosis-of-brain-abscess
Tissue damage seen in brain abscess is primarily caused by the host’s acute inflammatory response to the invading pathogen. The clinical findings depend in part upon the duration of disease. As an example, the early lesion that occurs in the first one to two weeks is poorly demarcated and is associated with localized edema. During this early stage (commonly called cerebritis), there is evidence of acute inflammation but no tissue necrosis. However, after two to three weeks, necrosis and liquefaction occur, and the lesion becomes surrounded by a fibrotic capsule. […] An understanding of the pathogenesis of brain abscess is important for the interpretation of computed tomographic (CT) scan and magnetic resonance imaging (MRI) findings.
#1 Immunopathogenesis of brain abscess
https://pmc.ncbi.nlm.nih.gov/articles/PMC516022/
The mechanisms elucidated to date in the immunopathogenesis of brain abscess are depicted in Figure 1. […] This phenomenon is also observed in human brain abscess, where lesions can encompass a large portion of brain tissue, often spreading well beyond the initial focus of infection. Therefore, controlling the intensity and/or duration of the anti-bacterial immune response in the brain may allow for effective elimination of bacteria while minimizing damage to surrounding brain tissue. […] The immune response that is an essential part of abscess formation also destroys surrounding normal brain tissue. […] Specifically, the continued release of proinflammatory mediators by activated glia and infiltrating peripheral immune cells may act through a positive feedback loop to potentiate the subsequent recruitment and activation of newly recruited inflammatory cells and glia.
#1 Immunopathogenesis of brain abscess | Journal of Neuroinflammation | Full Text
https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-1-16
The IL-1 KO animals used for these studies were deficient in both IL-1 and IL-1; therefore, potential caveats arising from redundancy in the activities of these two proteins were avoided. […] Despite the fact that these cytokines share many overlapping functional activities, IL-1 and TNF- appear to play an important role in dictating the ensuing anti-bacterial response in brain abscess. […] Neutrophils are potent bactericidal effector cells and represent the major peripheral cell infiltrate associated with developing brain abscesses. […] Neutrophils exert their bactericidal activity through the production of reactive oxygen and nitrogen intermediates and hydrolytic enzymes that directly destroy bacteria. […] These studies demonstrate that CXCR2 ligands are the major chemotactic signals required for neutrophil influx into brain abscesses and that their activity cannot be substituted by alternative chemotactic factors such as complement split products (i.e. C3a, C5a), prostaglandins, leukotrienes, or other chemokines.
#1 Immunopathogenesis of brain abscess
https://pmc.ncbi.nlm.nih.gov/articles/PMC516022/
We proposed that in wild type bacteria, -toxin, which leads to pore formation in mammalian cell membranes and subsequent osmotic lysis, serves as an effective mechanism to eliminate CNS resident immunocompetent cells (i.e. microglia and astrocytes) as well as professional phagocytes that infiltrate brain abscesses and exert potent anti-bacterial activity (i.e. neutrophils and macrophages). […] This would effectively impair the efficacy of the ensuing anti-bacterial immune response, allowing bacterial burdens to expand unchecked during the acute phase of disease. […] The absence of GFAP influences brain abscess evolution in such a dramatic manner, as astrocytes are still present and functional in these mice. […] The continued use of transgenic and knockout mice for in vivo studies will facilitate our understanding of immune mechanisms contributing to brain abscess pathogenesis.
#1 Immunopathogenesis of brain abscess | Journal of Neuroinflammation | Full Text
https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-1-16
We proposed that in wild type bacteria, -toxin, which leads to pore formation in mammalian cell membranes and subsequent osmotic lysis, serves as an effective mechanism to eliminate CNS resident immunocompetent cells (i.e. microglia and astrocytes) as well as professional phagocytes that infiltrate brain abscesses and exert potent anti-bacterial activity (i.e. neutrophils and macrophages). […] This would effectively impair the efficacy of the ensuing anti-bacterial immune response, allowing bacterial burdens to expand unchecked during the acute phase of disease. […] However, it is likely that additional virulence factors participate in S. aureus infection in the brain since the -toxin mutant was not completely avirulent. […] Collectively, the studies to date performed in the mouse experimental brain abscess model have begun to elucidate critical mediators in the pathogenesis of disease and host cytokines that play a pivotal role in the generation of the CNS anti-bacterial immune response. […] Addressing these issues may facilitate the design of effective therapeutic regimens for brain abscess that would be capable of pathogen elimination without the accompanying destruction of surrounding brain parenchyma that normally occurs in disease.
#1
https://journals.lww.com/neurosurgery/fulltext/2024/05000/bacterial_brain_abscesses_expand_despite_effective.22.aspx
A bacterial brain abscess is an emergency and should be drained of pus within 24 hours of diagnosis, as recently recommended. […] In this cross-sectional study, we investigated whether delaying pus drainage entails brain abscess expansion and what the underlying mechanism might be. […] Abscesses expanded during antibiotic therapy and even if the pus did not contain viable bacteria. […] A mechanism likely underlying pus hyperosmolarity was the recruitment of neutrophils to the abscess cavity with ensuing neutrophil cell death and decomposition of neutrophil proteins and other macromolecules to osmolytes: Pus analysis showed the presence of neutrophil proteins (protein-arginine deiminases, citrullinated histone, myeloperoxidase, elastase, cathelicidin). […] We hypothesized that, with time, a brain abscess would increase in size because the pus would be hyperosmolar, drawing water into the abscess cavity.
#1
https://journals.lww.com/neurosurgery/fulltext/2024/05000/bacterial_brain_abscesses_expand_despite_effective.22.aspx
The average increase in abscess size per day was 23% (median value; range 0-176) in the whole group of 47 patients. […] Thus, antibiotic treatment did not prevent brain abscess expansion. […] One likely mechanism underlying brain abscess expansion was pus hyperosmolarity, which would draw water into the abscess cavity; the water would probably come from capillaries in the highly vascularized brain abscess capsule. […] The mechanism behind the high osmolarity of pus probably relies on 2 factors. First, the continuous recruitment of neutrophils to the abscess cavity and their death by NETosis would supply the pus with macromolecules (protein, nucleic acids) that on their degradation would become potent osmolytes, such as amino acids and ammonia. […] We conclude that brain abscesses expand with time, even during effective antibiotic treatment.
#1 Immunopathogenesis of brain abscess
https://pmc.ncbi.nlm.nih.gov/articles/PMC516022/
Recent studies support persistent immune activation associated with experimental brain abscesses with elevated levels of IL-1, TNF-, and MIP-2 detected from 14 to 21 days following S. aureus exposure. […] Collectively, these findings suggest that intervention with anti-inflammatory compounds subsequent to sufficient bacterial neutralization may be an effective strategy to minimize damage to surrounding brain parenchyma during the course of brain abscess development, leading to improvements in cognition and neurological outcomes. […] The potential roles these chemokines play in the pathogenesis of brain abscess development remain to be defined. However, they could be envisioned to influence the accumulation of monocytes and lymphocytes into the brain and possibly the establishment of adaptive immune responses.
#2 Brain abscess: A narrative review | Neurology perspectives
https://www.elsevier.es/en-revista-neurology-perspectives-17-articulo-brain-abscess-a-narrative-review-S2667049622000291
Brain abscess is a severe focal infection of the central nervous system (CNS) with an annual incidence of up to 8% in developing countries. […] The main pathophysiological mechanisms are related to bacterial spread from adjacent or distal foci. […] Three main pathophysiological mechanisms have been described: inoculation of pathogenic microorganisms normally found on the skin (eg, in the context of head trauma or neurosurgery), contiguous spread of bacteria (eg, mastoiditis, otitis media, sinusitis), and haematogenous spread from distal foci (eg, bacterial endocarditis, lung abscess, skin and dental infections). […] When the blood-brain barrier is damaged (eg, due to brain trauma or a neurosurgical procedure), the brain becomes extremely vulnerable to bacterial infection. […] Brain abscess development has classically been divided into 4 stages: 1) early cerebritis (perivascular infiltration of neutrophils, plasma cells, and mononuclear cells); 2) late cerebritis (macrophage and fibroblast infiltration is also observed); 3) early capsule formation; and 4) late capsule formation. […] The most frequently isolated pathogens are Staphylococcus aureus and Streptococcus viridans, with anaerobic microorganisms being found in up to 40% of cases.
#2 Brain abscess: A narrative review | Neurology perspectives
https://www.elsevier.es/en-revista-neurology-perspectives-17-avance-resumen-brain-abscess-a-narrative-review-S2667049622000291
Brain abscess is a severe focal infection of the central nervous system (CNS) with an annual incidence of up to 8% in developing countries. […] The main pathophysiological mechanisms are related to bacterial spread from adjacent or distal foci. […] Three main pathophysiological mechanisms have been described: inoculation of pathogenic microorganisms normally found on the skin (eg, in the context of head trauma or neurosurgery), contiguous spread of bacteria (eg, mastoiditis, otitis media, sinusitis), and haematogenous spread from distal foci (eg, bacterial endocarditis, lung abscess, skin and dental infections). […] When the blood-brain barrier is damaged (eg, due to brain trauma or a neurosurgical procedure), the brain becomes extremely vulnerable to bacterial infection. […] Brain abscess development has classically been divided into 4 stages: 1) early cerebritis (perivascular infiltration of neutrophils, plasma cells, and mononuclear cells); 2) late cerebritis (macrophage and fibroblast infiltration is also observed); 3) early capsule formation; and 4) late capsule formation. […] The most frequently isolated pathogens are Staphylococcus aureus and Streptococcus viridans. […] The proportion of brain abscesses of fungal aetiology has increased with the use of immunosuppressants and broad-spectrum antibiotics, amounting to approximately 1% of all brain abscesses.
#2 Brain abscess – Infectious Disease Advisor
https://www.infectiousdiseaseadvisor.com/home/decision-support-in-medicine/infectious-diseases/brain-abscess/
Brain abscess is a focal suppurative process of the brain parenchyma. The abscess begins initially as an area of focal inflammation, called cerebritis, which with time and without effective treatment progresses to an abscess. Brain abscesses usually develop in a four-stage process. These stages are early and late cerebritis (days 1-3 and 4-9, respectively) and early and late capsule formation (days 10-13 and day 14 and later, respectively) and represent a continuum rather than discrete steps. The evolution of this process is dependent on the causative organism, host immunologic status, and effective antimicrobial therapy. […] There are three major pathogenetic factors predisposing to brain abscess. […] 1. Contiguous spread: Brain abscesses most commonly are the result of contiguous spread of infection from the oropharynx (odontogenic), middle ear, and paranasal sinuses; direct extension; and, more commonly, retrograde thrombophlebitis through the valveless diploic veins. Brain abscesses are more common in children, adolescents, and young adults (7-20 years of age) than in other age groups because they are likely to have highly vascular diploic bone, which increases valveless bidirectional flow between frontal sinus mucosa and the dural venous drainage.
#2 Brain Abscess: Background, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/212946-overview
Infection may enter the intracranial compartment directly or indirectly via three routes. […] Contiguous suppurative focus (45%-50% of cases) […] Direct extension usually causes a single brain abscess and may occur from necrotic areas of osteomyelitis in the posterior wall of the frontal sinus, the sphenoid and ethmoid sinuses, and mandibular dental infections, as well as from subacute and chronic otitis media and mastoiditis. […] Hematogenous spread from a distant focus (25% of cases) […] These abscesses are more commonly multiple and multiloculated and are frequently found in the distribution of the middle cerebral artery. The most commonly affected lobes (in descending frequency) are the frontal, temporal, parietal, cerebellar, and occipital.
#2 Brain abscess – Infectious Disease Advisor
https://www.infectiousdiseaseadvisor.com/home/decision-support-in-medicine/infectious-diseases/brain-abscess/
2. Cranial trauma. The prevalence of brain abscess after penetrating trauma or neurosurgical procedures ranges from 2%-14%. […] 3. Hematogenous spread from distant focus of infection: Hematogenous spread can occur in the setting of endocarditis, cardiac shunts, chronic pyogenic lung infection, intraabdominal abscess, and urinary tract infections. Hematogenous abscesses are usually multiple, are identified at the gray-white matter junction, and are located in the middle cerebral artery distribution. […] These pathogens cause brain abscess through contiguous spread (e.g., from oropharyngeal and upper respiratory tract infection), direct inoculation (e.g., after cranial trauma), or hematogenous spread from a distant focus of infection (e.g., in a setting of intravascular infection such as endocarditis and/or cardiac shunt).
#2 Pathogenesis, clinical manifestations, and diagnosis of brain abscess – UpToDate
https://www.uptodate.com/contents/pathogenesis-clinical-manifestations-and-diagnosis-of-brain-abscess
Brain abscess is a focal infectious collection within the brain parenchyma, which can arise as a complication of another infection or through trauma or surgery. […] The pathogenesis, clinical manifestations, and diagnosis of brain abscess will be presented here. […] Bacteria can invade the brain either by direct spread or through hematogenous seeding. Direct spread accounts for 25 to 50 percent of cases. The location reflects the site of the primary infection that spreads to the cerebral cortex. These locations, in order of decreasing frequency, are: the frontal or temporal lobes; frontal-parietal region; parietal lobe; cerebellum; and occipital lobe. Bacteremic spread typically causes multiple lesions. No primary site or underlying condition can be identified in 10 to 35 percent of patients with brain abscess depending upon the series.
#2 Multiple Brain Abscesses of Odontogenic Origin. May Oral Microbiota Affect Their Development? A Review of the Current Literature
https://www.mdpi.com/2076-3417/11/8/3316
Immunodeficiency due to HIV infection, alcohol abuse, diabetes, chemotherapy or cancer may promote the development of BAs. […] Anaerobic infections (bacilli and Gram-positive cocci) are associated with incidence of acute signs and symptoms, such as pain, sensitivity to pressure and cellulitis and are characterized by abscess formation, foul-smelling pus and tissue destruction. […] Most dental abscesses are caused by the resident oral microbiota that enters normally sterile tissues. […] The microbiota specificity in odontogenic infections has been more clearly delineated with technological advances in sampling and anaerobic culture. […] The major isolates are streptococci and anaerobic bacteria, which are regarded as normal flora of the tooth and gingival crevice. […] The most common pathogens involved in the development of multiple BAs were Streptococcus viridans (with its different species), that was identified in 31.3% of cases, and Aggregatibacter actinomycetemcomitans (18.8% of cases). […] Oral pathogens are necessary, but not sufficient for odontogenic BAs. The role of microbiota is strictly connected with the immune system that appears to be the crucial determinant of disease susceptibility and severity.
#2 Brain Abscess: Background, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/212946-overview
Brain abscess is caused by intracranial inflammation with subsequent abscess formation. The most frequent intracranial locations (in descending order of frequency) are frontal-temporal, frontal-parietal, parietal, cerebellar, and occipital lobes. In at least 15% of cases, the source of the infection is unknown (cryptogenic). […] The most frequent causative pathogens in community-acquired brain abscess are oral cavity bacteria such as Streptococcus anginosus group, Fusobacterium spp, and Aggregatibacter spp, which are often associated with dental and chronic ear infections. Other less common etiologies include Staphylococcus aureus and Gram-negative bacilli in post-neurosurgical brain abscess, Mycobacterium tuberculosis in endemic areas, and Nocardia spp, fungi, and parasites in the severely immune-compromised.
#2 Immunopathogenesis of brain abscess | Journal of Neuroinflammation | Full Text
https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-1-16
The early stage or early cerebritis occurs from days 1-3 and is typified by neutrophil accumulation, tissue necrosis, and edema. […] The intermediate, or late cerebritis stage, occurs from days 4-9 and is associated with a predominant macrophage and lymphocyte infiltrate. […] The final or capsule stage occurs from days 10 onward and is associated with the formation of a well-vascularized abscess wall, in effect sequestering the lesion and protecting the surrounding normal brain parenchyma from additional damage. […] In addition to limiting the extent of infection, the immune response that is an essential part of abscess formation also destroys surrounding normal brain tissue. […] This phenomenon is also observed in human brain abscess, where lesions can encompass a large portion of brain tissue, often spreading well beyond the initial focus of infection.
#2 Intracranial and Intraventricular Abscess â Neurosurgical Management | IntechOpen
https://www.intechopen.com/chapters/1159106
A brain abscess (BA) is a focal infection of brain parenchyma most frequently caused by bacteria in an individual with underlying risk factors. […] The presence of an intracranial abscess can be life threatening, especially if intraventricular rupture occurs, often leading to massive cerebral edema, herniation syndrome, and death. […] An intracranial abscess initially begins as an area of cerebritis, secondary to iatrogenic introduction of an infection, hematogenous spread from an infection elsewhere in the body, or from an immunocompromised state, making the host more susceptible to infection. […] The early cerebritis stage lasts approximately 3 days, followed by progressive or late cerebritis which over the course of an additional 4 to 5 days becomes a capsule. […] If the abscess abuts the ventricular system, the capsule is thinnest where it contacts the ventricle, making this area not only the most likely source of spread of the infection, but also the most lethal, as intraventricular rupture sets off an inflammatory cascade that can lead to increased intracranial pressure and, eventually, to cerebral herniation syndrome and death.
#2 Immunopathogenesis of brain abscess | Journal of Neuroinflammation | Full Text
https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-1-16
Therefore, controlling the intensity and/or duration of the anti-bacterial immune response in the brain may allow for effective elimination of bacteria while minimizing damage to surrounding brain tissue. […] The mechanisms elucidated to date in the immunopathogenesis of brain abscess are depicted in Figure 1. […] This would effectively perpetuate the anti-bacterial inflammatory response via a vicious pathological circle culminating in extensive collateral damage to normal brain tissue. […] Recent studies support persistent immune activation associated with experimental brain abscesses with elevated levels of IL-1, TNF-, and MIP-2 detected from 14 to 21 days following S. aureus exposure. […] Collectively, these findings suggest that intervention with anti-inflammatory compounds subsequent to sufficient bacterial neutralization may be an effective strategy to minimize damage to surrounding brain parenchyma during the course of brain abscess development, leading to improvements in cognition and neurological outcomes.
#2 Immunopathogenesis of brain abscess | Journal of Neuroinflammation | Full Text
https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-1-16
We proposed that in wild type bacteria, -toxin, which leads to pore formation in mammalian cell membranes and subsequent osmotic lysis, serves as an effective mechanism to eliminate CNS resident immunocompetent cells (i.e. microglia and astrocytes) as well as professional phagocytes that infiltrate brain abscesses and exert potent anti-bacterial activity (i.e. neutrophils and macrophages). […] This would effectively impair the efficacy of the ensuing anti-bacterial immune response, allowing bacterial burdens to expand unchecked during the acute phase of disease. […] However, it is likely that additional virulence factors participate in S. aureus infection in the brain since the -toxin mutant was not completely avirulent. […] Collectively, the studies to date performed in the mouse experimental brain abscess model have begun to elucidate critical mediators in the pathogenesis of disease and host cytokines that play a pivotal role in the generation of the CNS anti-bacterial immune response. […] Addressing these issues may facilitate the design of effective therapeutic regimens for brain abscess that would be capable of pathogen elimination without the accompanying destruction of surrounding brain parenchyma that normally occurs in disease.
#2
https://journals.lww.com/neurosurgery/fulltext/2024/05000/bacterial_brain_abscesses_expand_despite_effective.22.aspx
The average increase in abscess size per day was 23% (median value; range 0-176) in the whole group of 47 patients. […] Thus, antibiotic treatment did not prevent brain abscess expansion. […] One likely mechanism underlying brain abscess expansion was pus hyperosmolarity, which would draw water into the abscess cavity; the water would probably come from capillaries in the highly vascularized brain abscess capsule. […] The mechanism behind the high osmolarity of pus probably relies on 2 factors. First, the continuous recruitment of neutrophils to the abscess cavity and their death by NETosis would supply the pus with macromolecules (protein, nucleic acids) that on their degradation would become potent osmolytes, such as amino acids and ammonia. […] We conclude that brain abscesses expand with time, even during effective antibiotic treatment.
#2
https://www.nhs.uk/conditions/brain-abscess/
A brain abscess is a pus-filled swelling in the brain. It usually occurs when bacteria or fungi enter the brain tissue after an infection or severe head injury. […] There are 3 main ways a brain abscess can develop. These are: an infection in another part of the skull such as an ear infection, sinusitis or dental abscess, which can spread directly into the brain; an infection in another part of the body for example, the infection that causes pneumonia spreading into the brain via the blood; trauma, such as a head injury that cracks open the skull, allowing bacteria or fungi to enter the brain. […] A brain abscess is regarded as a medical emergency. Swelling caused by the abscess can disrupt the blood and oxygen supply to the brain. There’s also a risk of the abscess bursting (rupturing). […] If left untreated, a brain abscess can cause permanent brain damage and could be fatal.
#2
https://journals.sbmu.ac.ir/nbm/article/view/45322
Pyogenic brain abscess is a severe neurological infection associated with significant morbidity and mortality. […] This article reviews the current understanding of the epidemiology, pathogenesis, diagnosis, and treatment of pyogenic brain abscesses, highlighting the importance of a multidisciplinary approach to improve patient outcomes. […] Pyogenic brain abscess is a life-threatening condition that requires prompt diagnosis and treatment. A multidisciplinary approach involving neurosurgeons, infectious disease specialists, and radiologists is necessary to manage pyogenic brain abscesses successfully. […] Early recognition, appropriate antibiotic therapy, and timely neurosurgical intervention are essential for improving patient outcomes and minimizing neurological sequelae. […] Continued research is needed to improve our understanding of this complex condition and develop more effective treatment strategies.
#3 Immunopathogenesis of brain abscess | Journal of Neuroinflammation | Full Text
https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-1-16
Brain abscesses develop in response to a parenchymal infection with pyogenic bacteria, beginning as a localized area of cerebritis and evolving into a suppurative lesion surrounded by a well-vascularized fibrotic capsule. […] The leading etiologic agents of brain abscess are the streptococcal strains and S. aureus, although a myriad of other organisms have also been reported. […] Following infection, the potential sequelae of brain abscess include the replacement of the abscessed area with a fibrotic scar, loss of brain tissue by surgical excision, or abscess rupture and death. […] The most common sources of brain abscess are direct or indirect cranial infection arising from the paranasal sinuses, middle ear, and teeth. […] At the histological level, brain abscess is typified by a sequential series of pathological changes that have been elucidated using the experimental rodent models described in detail below.
#3 Brain abscess – Infectious Disease Advisor
https://www.infectiousdiseaseadvisor.com/home/decision-support-in-medicine/infectious-diseases/brain-abscess/
2. Cranial trauma. The prevalence of brain abscess after penetrating trauma or neurosurgical procedures ranges from 2%-14%. […] 3. Hematogenous spread from distant focus of infection: Hematogenous spread can occur in the setting of endocarditis, cardiac shunts, chronic pyogenic lung infection, intraabdominal abscess, and urinary tract infections. Hematogenous abscesses are usually multiple, are identified at the gray-white matter junction, and are located in the middle cerebral artery distribution. […] These pathogens cause brain abscess through contiguous spread (e.g., from oropharyngeal and upper respiratory tract infection), direct inoculation (e.g., after cranial trauma), or hematogenous spread from a distant focus of infection (e.g., in a setting of intravascular infection such as endocarditis and/or cardiac shunt).
#3 Brain Abscess | Neupsy Key
https://neupsykey.com/brain-abscess/
Trauma can lead to brain abscess formation as a result of an open cranial fracture with dural breach or foreign body injury or as a sequela of neurosurgery. The incidence of traumatic brain abscess in the civilian population ranges from 2.5% to 10.9%. […] In military populations, the incidence of brain abscess after head trauma ranges from 3% to 17%, and they usually occur secondary to retained bone fragments or contamination of initially uninfected missile sites with bacteria from skin, clothes, or the environment. […] The brain appears to be significantly more sensitive to infection than many other tissues. In a rat model of experimental brain abscess, injection of 104 colony-forming units (CFUs) of S. aureus or 106 CFUs of E. coli failed to cause infection in the skin, but abscess formation in brain tissue was induced by a level as low as 102 CFUs of either organism. […] Despite the presence of virulence factors of the organism that resist host defense mechanisms, the host inflammatory response is important in containment of the abscess.
#3 Multiple Brain Abscesses of Odontogenic Origin. May Oral Microbiota Affect Their Development? A Review of the Current Literature
https://www.mdpi.com/2076-3417/11/8/3316
Immunodeficiency due to HIV infection, alcohol abuse, diabetes, chemotherapy or cancer may promote the development of BAs. […] Anaerobic infections (bacilli and Gram-positive cocci) are associated with incidence of acute signs and symptoms, such as pain, sensitivity to pressure and cellulitis and are characterized by abscess formation, foul-smelling pus and tissue destruction. […] Most dental abscesses are caused by the resident oral microbiota that enters normally sterile tissues. […] The microbiota specificity in odontogenic infections has been more clearly delineated with technological advances in sampling and anaerobic culture. […] The major isolates are streptococci and anaerobic bacteria, which are regarded as normal flora of the tooth and gingival crevice. […] The most common pathogens involved in the development of multiple BAs were Streptococcus viridans (with its different species), that was identified in 31.3% of cases, and Aggregatibacter actinomycetemcomitans (18.8% of cases). […] Oral pathogens are necessary, but not sufficient for odontogenic BAs. The role of microbiota is strictly connected with the immune system that appears to be the crucial determinant of disease susceptibility and severity.
#3 Intracranial and Intraventricular Abscess â Neurosurgical Management | IntechOpen
https://www.intechopen.com/chapters/1159106
A brain abscess (BA) is a focal infection of brain parenchyma most frequently caused by bacteria in an individual with underlying risk factors. […] The presence of an intracranial abscess can be life threatening, especially if intraventricular rupture occurs, often leading to massive cerebral edema, herniation syndrome, and death. […] An intracranial abscess initially begins as an area of cerebritis, secondary to iatrogenic introduction of an infection, hematogenous spread from an infection elsewhere in the body, or from an immunocompromised state, making the host more susceptible to infection. […] The early cerebritis stage lasts approximately 3 days, followed by progressive or late cerebritis which over the course of an additional 4 to 5 days becomes a capsule. […] If the abscess abuts the ventricular system, the capsule is thinnest where it contacts the ventricle, making this area not only the most likely source of spread of the infection, but also the most lethal, as intraventricular rupture sets off an inflammatory cascade that can lead to increased intracranial pressure and, eventually, to cerebral herniation syndrome and death.
#3 Intracranial and Intraventricular Abscess â Neurosurgical Management | IntechOpen
https://www.intechopen.com/chapters/1159106
Within an encapsulated abscess, several histologic patterns are expected, most importantly a necrotic core of infection, followed by a layer of inflammatory cells, including fibroblasts, neutrophils, and macrophages. […] Bacterial pathogens are by far the most common etiology of BA, and it is of paramount importance to identify the source of the bacteria as this will guide diagnostic work up and eventual therapeutic management. […] Hematologic spread of infection is quoted to represent between 30 and 40 percent of intracranial abscesses, with sources from the mouth, lungs, and heart being the most common. […] Interestingly, odontogenic pathogens are becoming a more common cause of BA, up to 32% in one study. […] The proposed mechanism for preferential rupture into the ventricles rather than subarachnoid space is differential blood supply, resulting in reduced thickness of the abscess wall along the ventricles. […] Identifying patients at risk for rupture is critical to optimize medical management and prioritize surgical intervention for BA with high-risk features, such as proximity to the ventricles.
#3
https://journals.lww.com/ijpm/abstract/2006/49030/pathogenesis_and_pathology_of_brain_abscess_.1.aspx
Brain abscess continues to be a serious medical problem with increasing incidence despite advances in diagnostic and surgical methods, and advent of new antibiotics. […] The morbidity, mortality and long term sequelae of brain abscess like cognitive impairment and poor neurological outcome are due to persistent release of proinflammatory mediators by activated microglia, astrocytes and infiltrating inflammatory cells, along with disruption of blood brain barrier. […] The route of spread, the type and virulence of the organism, thickness of the capsule, location and number of abscesses in the brain, and immune status of the host are important determinants of outcome. […] Identification of microorganisms and insights into pathogenesis allow appropriate therapeutic interventions to improve outcome.
#3 Immunopathogenesis of brain abscess | Journal of Neuroinflammation | Full Text
https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-1-16
We proposed that in wild type bacteria, -toxin, which leads to pore formation in mammalian cell membranes and subsequent osmotic lysis, serves as an effective mechanism to eliminate CNS resident immunocompetent cells (i.e. microglia and astrocytes) as well as professional phagocytes that infiltrate brain abscesses and exert potent anti-bacterial activity (i.e. neutrophils and macrophages). […] This would effectively impair the efficacy of the ensuing anti-bacterial immune response, allowing bacterial burdens to expand unchecked during the acute phase of disease. […] However, it is likely that additional virulence factors participate in S. aureus infection in the brain since the -toxin mutant was not completely avirulent. […] Collectively, the studies to date performed in the mouse experimental brain abscess model have begun to elucidate critical mediators in the pathogenesis of disease and host cytokines that play a pivotal role in the generation of the CNS anti-bacterial immune response. […] Addressing these issues may facilitate the design of effective therapeutic regimens for brain abscess that would be capable of pathogen elimination without the accompanying destruction of surrounding brain parenchyma that normally occurs in disease.