Clinical Scenarios

For paediatric cerebral abscess, cranial extradural abscess, and subdural empyema see paediatric section of the book (Varthalitis, El-Adwan and Usher, Child with an Acute Intracranial Infection, Elements in Emergency Neurosurgery, Cambridge University Press, forthcoming).

A fifty-five-year-old lady presented with a few weeks of feeling unwell and was found unconscious at home. She was initially GCS 15, then became more confused and agitated. CT with contrast of the head showed left middle ear opacity and an intracerebral abscess within the left temporal lobe. She underwent a neuro-navigated burr hole drainage of left temporal abscess and a left-sided modified radical mastoidectomy by our ENT colleagues. She initially recovered well and was on long-term antibiotics (meropenem and metronidazole). However, a month after her initial surgery, her abscess recurred despite being on antibiotics. Another neuro-navigated aspiration was performed. This time the abscess was successfully treated and follow-up imaging only showed a small area of enhancement within the abscess wall, likely representing the remnant abscess capsule (Figure 1).

Figure 1 Clinical scenario for adult cerebral abscess (A) CT head on bone windows showing left mastoid air cell opacification. (B) Initial CT with contrast showing a ring-enhancing lesion in the left temporal lobe. This was treated via a neuro-navigated aspiration of the abscess. (C) One month following the initial treatment a follow-up scan showed that there was a recurrence of the abscess. (D) Three months from the initial scan, almost complete resolution of the abscess is seen with a small area of enhancement.

Core Knowledge

Definition

Adult cerebral abscess (CA) is a focal infection of the brain that begins as a localised area of cerebritis that eventually progresses into a collection of pus within the brain.

Epidemiology

It has an incidence of 0.4/100,000 per year (Reference Helweg-Larsen, Astradsson and Richhall1) in the developed world, but it is found to be higher in developing countries. It has a female preponderance (M:F, 1:3) and represents around 1% of all radiologically diagnosed intracranial space-occupying lesions.

Aetiology

The microorganism that causes CA can arrive to the brain via three different routes. The most common is haematogenous spread from infections arising from sites such as the heart (acute bacterial endocarditis), lungs (lower respiratory chest infections, lung abscess, and empyema), skin (cellulitis), tooth extraction, bone (osteomyelitis), or bowel. Contiguous spread occurs from sites adjacent to the brain, such as infective sinusitis and tooth infections. Infections of the air sinuses can lead to local osteomyelitis and spread to the brain via emissary vein phlebitis. In contiguous abscesses, the location of the sinusitis is adjacent to the location of the CA. For example, middle ear infections and mastoid air sinusitis tend to cause temporal or cerebellar abscess, whereas sphenoid sinusitis tends to cause cavernous sinus thrombosis and temporal lobe abscesses. Tooth infections tend to cause frontal lobe abscesses via contiguous spread through calvarial osteomyelitis or can occur within four weeks of a dental procedure through haematological spread (Reference Hollin, Hayashi and Gross2). The third route for infection to spread to the brain is through direct inoculation, either from neurosurgical procedures or from penetrating head injury. Cerebral abscess has been described in a variety of neurosurgical procedures, including craniotomies and/or implantation of intracranial devices. The causative organisms in penetrating head injury can be from the air sinuses if they are along the projectiles path or from normal flora from the skin or clothes (Figure 2).

Figure 2 Infective routes for cerebral abscesses

Risk Factors

Patients who are immunocompromised or have pulmonary shunting, in the form of congenital heart disease or conditions such as Osler–Weber–Rendu syndrome, are at a higher risk of CA. Immunosuppression can be from AIDS or medical treatment such as chemotherapy or long-term steroids use. Five per cent of patients with Osler–Weber–Rendu syndrome developed CA secondary to the pulmonary arteriovenous fistula that causes pulmonary shunting (Reference Dupuis-Girod, Giraud and Decullier3).

Pathogen

A study by Helweg-Larsen et al. in 2012 has shown that the most common pathogens found within CA were Streptococci (54%), Staphylococci (15%), Gram-negative bacteria (8%), anaerobic bacteria (17%), and Nocardia (2%) (Reference Helweg-Larsen, Astradsson and Richhall1). The incidence of no growth in pus cultures obtained from drainage of the CA can be as high as 41% (Reference Kao, Tseng, Liu, SC and Lee4). This is likely to be due to the use of antibiotics prior to abscess drainage. The type of pathogens is closely associated with the source of infection, for example, strep. Milleri and strep. Anginosus are commonly seen in abscess due to frontal and ethmoidal sinusitis, whereas staph. Aureus and Clostridium spp. are seen in direct inoculation from penetrating brain injuries (Reference Darlow, McGlashan and Kerr5). Cerebral abscess associated with lung abscesses can be due to Fusobacterium, actinomyces, and Nocardia Spp. Fusobacterium, actinomyces are commonly seen in CA secondary to dental infections (Reference Li, Tronstad and Olsen6). Pathogens such as Mycobacterium, toxoplasma Gondii, Nocardia asteroids, listeria monocytogenes, and fungal infections (Aspergillus fumitagus and Cryptococcus Neoformans) are found in immunocompromised patients with CA (Reference Weerakkody, Palangasinghe, Wadanambi and Wijewikrama7).

Stages of Abscess Formation

Britt et al. using a canine model of infection with α-haemolytic streptococci defined four different stages of in the formation of a CA (Reference Britt, Enzmann and Yeager8). Although these stages are not distinct, they are a good model of understanding how abscesses form and how they transform radiologically over time (Table 1). The four stages are early cerebritis, late cerebritis, early capsule formation, and late capsule formation.

Table 1Stages of cerebral abscess formation. (References: Britt et al. (8) and Erdogan and Cansever (2008))

Table 1Long description

The table consists of 4 main columns: Early cerebritis, Late cerebritis, Early capsule formation, and Late capsule formation, along with a column for the particulars. It reads as follows. Days: Early cerebritis: 1 to 3. Late cerebritis: 4 to 9. Early capsule formation: 10 to 13. Late capsule formation: more than 14. Resistance of capsule to needle aspiration: Early cerebritis: Intermediate resistance. Late cerebritis: No resistance. Early capsule formation: No resistance. Late capsule formation: Firm resistance. Has ‘give’ on entering. Necrotic centre: Early cerebritis: Acute inflammatory cells; bacteria present on Gram stain. Late cerebritis: Enlarging necrotic centre reaching maximal size. Early capsule formation: Decrease in necrotic centre. Late capsule formation: Further decrease in necrotic centre. Inflammatory border: Early cerebritis: Acute inflammatory cells. Late cerebritis: Inflammatory cells, macrophages, and fibroblast. Early capsule formation: Increasing numbers of fibroblast and macrophages. Late capsule formation: Further increase in number of fibroblasts. Cerebritis and neovascularity: Early cerebritis: Rapid perivascular infiltration of neutrophils, plasma cells, and mononuclear cells. Late cerebritis: Maximal extent of cerebritis, Rapid increase in new vessel formation. Early capsule formation: Maximal degree of neovascularization. Late capsule formation: Cerebritis restricted to the outside of the collagen capsule. Collagenous capsule: Early cerebritis: Reticulin formation begins by day 3. Late cerebritis: Appearance of fibroblasts with rapid formation of reticulin. Early capsule formation: Evolution of mature collagen. Late capsule formation: Capsule completed by end of second week. Reactive gliosis and cerebral oedema: Early cerebritis: Marked cerebral oedema. Late cerebritis: Prominent cerebral oedema, Appearance of reactive astrocytes. Early capsule formation: Regression of cerebral oedema, Increase in reactive astrocytes. Late capsule formation: Regression of cerebral oedema, Marked gliosis outside capsule by third week. C T (accompanied by corresponding C T scan examples): Early cerebritis: Partial ring contrast enhancement on day 1 evolving to well-developed ring enhancement by day 3, Steroids reduce degree of contrast enhancement (especially in cerebritis). Late cerebritis: Thick ring enhancement, Diffusion of contrast medium into the lucent centre on delayed scans (30 to 60 minutes after contrast infusion) is salient C T finding of cerebritis stage. Early capsule formation: Ring enhancement with less diffusion of contrast material into the lucent centre. Late capsule formation: Ring enhancement without diffusion of contrast material into the lucent centre. M R I (the Early capsule formation column has corresponding M R I scan examples): Early cerebritis: T1: Hypointense; T2: Hyperintense. Early capsule formation: T1: Core is hypointense, Capsule is mildly hyperintense, Perilesional oedema is hypointense; T2: Core is iso/hyperintense, Capsule is hypointense, Perilesional oedema is hyperintense, D W I: Restricted; T1 plus C: Ring-enhancing lesion.

Early cerebritis occurs between days 1 and 3. The core of the infective elements contains acute inflammatory cells with bacteria present on gram staining. The border of the involved brain and infective element contains acute inflammatory cells. During this period, a collagenous capsule made of reticulin starts to form. The surrounding brain starts to show marked oedema. Radiologically during the early cerebritis stage, there is partial ring enhancement on CT with contrast, but later this ring enhancement gets more pronounced. Steroids given during the early cerebritis stage can dampen down the degree of contrast enhancement. Late cerebritis starts around day 4 and ends around day 10. During this time, the core of the infective elements starts to become necrotic and enlarges to its maximum size. The previously acute inflammatory cell border will now have macrophages and fibroblasts. Due to the presence of the fibroblasts, there is now a rapid formation of the collagenous wall. The surrounding brain oedema is still present with appearance of reactive astrocytes within the normal brain. During the first two cerebritis stages, the T1-weighted and T2-weighted MRI show hypointensity and hyperintensity of the affected brain, respectively. During this period there is a delay in diffusion of contrast into the lucent centre, whereas later in the capsule formation stages, there is less diffusion of contrast material into the lucent centre.

In the early capsule formation stage, which begins and ends from day 10 and day 13, respectively, there is a start in the decrease in the volume of the necrotic centre. There is also a further increase in fibroblast and macrophage translocation into the inflammatory border. There is also now maximal neovascularization of the abscess. The collagen within the capsule is maturing. One of the characteristic features of the early capsule formation stage is regression of cerebral oedema. In the late capsule formation stage, which occurs after day 14, the cerebritis is restricted to the outside of the now matured collagen capsule. Due to the presence of a matured collagen capsule, this is the stage where one would feel a firm resistance when passing a needle into the abscess. The capsule facing the cortical surface has higher oxygen availability and thus can form a thicker capsular wall when compared to the capsular wall facing the deeper ventricular surface. This explains why CA tends to rupture into the ventricular system rather than rupturing on the cortical surface. The surrounding brain will start to show signs of gliosis. Radiologically on MRI the necrotic core will be hypointense on T1-weighted sequences, and hyper or iso intense on T2-weighted sequences. This is in contrast to the capsule, which is hyperintense on T1-weighted imaging and hypointense on T2-weighted imaging. Diffusion-weighted imaging (DWI) will show restriction due to the presence of pus. T1 post-contrast studies will show the classical ring-enhancing lesion.

Clinical Presentation

Patients with CA frequently present with headache, fever (60%), nausea or vomiting (40%), and/or focal neurological (57%) deficits depending on the location of the abscess (Reference Helweg-Larsen, Astradsson and Richhall1). Frontal lobe abscess is more common than temporal or parietal abscess. Later during the disease, the patient can also present with seizure (21%) and impaired consciousness (45%). These symptoms are due to the mass effect and local irritatory effects of the perilesional oedema and the CA itself. Unlike other intracranial infections, CA does not generally present with meningism. Sudden worsening of the headache, accompanied by the new onset of meningism, may suggest the rupture of the abscess into the ventricular space (Reference Lee, Chang and Su9).

Investigation

White cell count and CRP can be raised or normal in patients with CA. Blood cultures should be done if patients are pyrexial. Lumbar puncture should be avoided as there is a risk of herniation if the CA is large enough to cause a significant mass effect. It is important to be aware that normal inflammatory markers do not rule out a CA.

Samples obtained from the abscess by surgical drainage can be studied through gram staining and microscopy for can help guide immediate antibiotic choice. Abscess culture can allow identification of the pathogen involved and also allow for antibiotic sensitivity testing.

Radiologically the classical description of CA is of a ring-enhancing lesion. Cerebral abscess tends to localise in the grey-white matter junction and in watershed areas of the brain where the oxygen tension is lower. They tend to be multiple in 21% of cases (Reference Helweg-Larsen, Astradsson and Richhall1). CT with contrast shows a uniform thickness ring-enhancing lesion with surrounding cerebral hypodensity signifying cerebral oedema.

MRI is more sensitive than CT in detecting CA. It can detect early cerebritis and satellite lesions that tend to be missed on CT. T1-weighted imaging shows the central necrotic core that is low intensity surrounded by a slightly hyperintense rim representing the capsule. Surrounding the capsule, the surrounding vasogenic oedema in the brain will be low intensity. T2-weighted or FLAIR imaging shows that the rim is of low intensity whereas the area of cerebral oedema is high intensity. T1-weighted post-contrast imaging shows a ring-enhancing lesion.

In immunocompromised patients, there may be a relative lack of contrast enhancement which can make diagnosis difficult. Due to the presence of necrotic material within the abscess core which can restrict the motion of water, there is a high signal intensity on DWI and low apparent apparent diffusion coefficient (ADC) values within the core of the cavity. DWI can be used to monitor treatment response, and it is most useful in differentiating between a neoplastic process vs an infectious one (Table 2) (Reference Cartes-Zumelzu, Stavrou and Castillo10).

Table 2Differentiating intracranial tumour vs abscess. (References : Cartes- Zumelzu et al. (10) and Luthra et al. (11)).

Table 2Long description

The table consists of three columns: Features, Tumour, and Abscess. The rows read the following data. Row 1. C T or M R I: Less uniform ring-enhancing thickness; More uniform ring-enhancing thickness. Row 2. C T or M R I: Relatively less oedema; Relatively more oedema. Row 3. C T or M R I: Relatively slower growing; Relatively faster growing. Row 4. D W I: Core D W I hypointense, high A D C values; Core D W I hyperintense, low A D C values. Row 5. D W I: Wall D W I hyperintense, low A D C values; Wall D W I hypointense, high A D C values. Row 6. M R S: Decrease in N A A and creatine peaks; Decrease or absent in N A A and C r peaks. Row 7. M R S: Increase in choline, lipids, and lactate peaks; Increase in lipids or lactate, succinate, acetate, and amino acids (alanine, valine, leucine, and isoleucine) peaks.

MRS shows elevated peaks of metabolites that are associated with hypoxia and cellular breakdown, such as lipids/lactate, succinate, acetate, and amino acids (alanine, valine, leucine, and isoleucine). MRS can also help differentiate the various types of CA: Pyogenic abscesses have raised cytosolic amino acids, acetate, and succinate; Tubercular abscesses have raised lipid/lactate peaks; and fungal abscesses showed raised lipid, lactate, amino acids, and trehalose peaks (Reference Luthra, Parihar and Nath11). Like DWI MRS can help delineate infection from tumour (Table 2).

Acute Management

The goal of CA treatment is to obtain a sample for diagnosis, reduce the infective load within the brain, and relieve the pressure effects of the abscess onto the brain. The mainstay of treatment is surgical aspiration or excision of the abscess followed by long-term antibiotics. The primary source of infection should also be treated acutely. This can be done with the assistance of ENT or maxillofacial surgery. It is reasonable to give anti-convulsants prophylactically in some cases, but must be started if there is evidence of seizure activity, with Levetiracetam the most used initial agent. If seizures are not well controlled with a single agent, another agent can be added with neurology advice.

Steroids use in the context of CA have been controversial. The theory behind their use is that it can improve the vasogenic oedema help control mass effect. However, steroids can decrease host immunity, delay the formation of an abscess wall therefore allowing more destruction of the surrounding normal brain. Studies have shown that steroid use has been associated with higher mortality, and it does not seem to improve overall outcomes (Reference Helweg-Larsen, Astradsson and Richhall1). If they are going to be used to control mass effect, this should be for a short duration.

Pure antibiotic treatment of a CA without surgery is used in certain clinical circumstances. One would be the late referral of a patient that was showing signs of improvement after starting antibiotics, if the lesion were small (<1.7 cm), or if the patient had an irreversible coagulopathy. Local anaesthetic drainage can be considered in patients with medical comorbidity. Patients with multiple small abscesses or the abscess in a poorly accessible location (Reference Arlotti, Grossi and Pea12) can be treated with antibiotics alone and this is often done in the paediatric population with associated congenital heart disease/endocarditis where the organism is known.

Pure antibiotic treatment is less effective in the treatment of CA because the pathogens are contained within a thick capsular wall with poor blood supply, and the acidic environment within the abscess readily denatures the antibiotics. The choice of antibiotic agents should be discussed with the local infectious diseases team. The choice of antibiotics is based on the source of infection, which dictates the type of pathogen involved. For infections from sinusitis or tooth infections, a 3rd-generation cephalosporin and metronidazole should be used, whereas for infections from a post-traumatic or post-surgical source a 3rd-generation cephalosporin and vancomycin should be used. The duration of antibiotic should be for at least six to eight weeks, and this should be guided by clinical, biochemical, and radiographic response to treatment (Reference Arlotti, Grossi and Pea12).

Indications for surgical management of CA are if the abscess is expanding towards the ventricles, neurological deterioration, failure of pure antibiotic treatment, uncertainty of diagnosis, raised ICP and mass effect, presence of a foreign body within the abscess, abscesses that are large (>2.5 cm) and/or multiloculated (Reference Rosenblum, Hoff, Norman, Edwards and Berg13). The surgical options are needle aspiration, open surgical drainage, or surgical excision. Needle aspiration is the easiest to do with the lowest complication rate. It can be done for most patients and can be done under General or local anaesthetic with a scalp block. It is also the technique of choice for deeply seated lesions. One of the downsides of needle aspiration is that it does not allow complete removal of the infective material, therefore resulting in a higher recurrence of the abscess. Open surgical drainage, on the other hand, may reduce recurrence risk and on occasions has been shown to reduce antibiotic duration (Reference Helweg-Larsen, Astradsson and Richhall1). It can allow for any foreign body to be removed and to drain any multiloculated lesions. However, this procedure is more complicated and has a higher complication rate than needle aspiration. Surgical drainage should only be performed in abscesses that are in the late capsular phase, where there is well formed collagenous capsular wall. Surgical excision like surgical drainage can only be done during the late capsular stage but unlike surgical drainage here the abscess is removed like a tumour. As a result of this surgical excision has a higher risk of damaging the viable brain surrounding the abscess. Surgical excision is usually only employed for abscesses that contain a foreign body, known fungal or nocardia abscesses or needle drainage-resistant abscesses. If there are multiple abscesses, the largest lesion or the most symptomatic abscess should be targeted in the first instance (Reference Mamelak, Mampalam, Obana and Rosenblum14).

Technical Note – For Needle Aspiration of CA

Preoperatively measure the volume of CA on available imaging. This can be done using your local Picture Archiving and Communication System (PACS) or the ABC/2 formula, where A, B, and C are the largest length of the CA in all three dimensions that are at right angles to each other. A needle aspiration is an image-guided minimally invasive approach that can be done with frame or frameless stereotaxis and/or ultrasound guidance. The author’s preference is with frameless stereotaxis using Neuronavigation for deep CA and USS guidance as backup or for more superficial CA. Plan a trajectory with the shortest route, not traversing any major vessel or ventricles, and preferably choose a gyrus rather than a sulcus as the entry point. The target of the aspiration needle should stay away from the deepest, ventricular-facing wall so to prevent accidental fenestration of the CA into the ventricle. The frameless stereotactic apparatus should be set up according to the manufacturer’s guidelines. The hair is clipped, and a small incision is made as to allow a perforator to be used to make a burr hole. The burr hole is made so that the needle is located at the centre of the burr hole. The burr hole sometimes needs to be bevelled to ensure that the aspiration needle is not touching the surrounding bone. A 15-blade stab incision is made on the dura. A bipolar diathermy is then passed through this dural defect, and the cortex is coagulated. This ensures that the dura is only opened slightly to prevent CSF loss and brain shift, and at the same time to perform a corticortomy. The frameless stereotactic apparatus is then repositioned into place and the needle is passed smoothly without obstructions into the CA. Often, when penetrating through the abscess capsule, some resistance can be felt. Aspirate the contents of the CA until dry and send the sample for both microbiology and pathology analysis. Measure the volume of CA aspirated before removing the needle and closing.

If an ultrasound is used instead, the authors prefer using the small probe with a probe guide. The entry point should be planned on CT and the entry point marked out using callipers. A perforator is used to perform a burr hole that is then widened to allow access for both the aspiration needle and the ultrasound probe. The durotomy and corticortomy is performed as previously discussed. At the end of the aspiration, the USS can be used to visualise any remaining large collections.

Management Algorithms

See cerebral abscess flow diagram (Figure 3)

Figure 3 Cerebral abscess pathophysiology, investigations, and management

Figure 3Long description

Flowchart 1: The first flowchart starts from three parameters: Haematogenous spread from distant sites, Contiguous spread from adjacent sites, and Direct inoculation.

Haematogenous spread from distant sites is divided into Infants: congenital cyanotic heart disease, Acute bacterial endocarditis, and G I infection.

Infants: congenital cyanotic heart disease leads to inc. percent H b plus hypoxic environment plus losing lung filtration, which further leads to Ischaemic brain increases septic embolization spread, and then to Infants: Gram Neg because I g M do not cross placenta: Citrobacter, Bacteroides, Proteus, gram-negative bacilli. This leads to the formation of cerebral abscess.

Acute bacterial endocarditis leads to Staph. haemolytic and Strep. This leads to the formation of cerebral abscess. G I infection leads to via Batson plexus. This leads to the formation of cerebral abscess.

Contiguous spread from adjacent sites leads to Purulent sinusitis, Dental infection, and Dental procedure (last 4 weeks).

Purulent sinusitis leads to Local osteomyelitis and phlebitis of emissary veins, which together lead to strep. Milleri and strep. Anginosus. This leads to the formation of cerebral abscess.

Dental infection and dental procedure together lead to Mixed Fusobacterium, Prevotella, Actinomyces, Bacteroides spp., streptococci. This leads to the formation of cerebral abscess.

Direct inoculation divides into Post neurosurgical operations: craniotomies or Shunts, E V D, I C P monitor, halo traction, and penetrating trauma.

These parameters lead to Staph. Epidermidis, Staph. Aureus and Staph. Aureus, Staph. Enterobacteriae, respectively, and then lead to the formation of cerebral abscess.

Risk increased leads to Immunosuppressed: H I V positive, AIDS, Immunosuppressive treatment (Chemotherapy, Steroids), and then to the formation of cerebral abscess.

Risk increased also leads to Osler Weber Rendu syndrome or Pulmonary A V F, which is followed by Shunting of blood bypasses pulmonary filtration and Increases risk of spreading of systemic infections into the brain, which finally leads to the formation of cerebral abscess.

Formation of cerebral abscess involves: early cerebritis leading to late cerebritis, then to early capsule formation, and finally to late capsule formation.

Formation of cerebral abscess is divided into three: Inflammation of brain and meninges, Mass effect from abscess or perilesional oedema, and fever 60 percent.

Inflammation of brain and meninges and mass effect from abscess or perilesional oedema, together lead to Neck stiffness (25 percent), seizure (21 percent), H slash A, N slash V (40 percent), Low G C S (45 percent), Infants (Macrocranium), and Focal neurologic deficit (57 percent).

A textbox at the bottom left reads frequency: Streptococci 54 percent, Staphylococci 15 percent, Gram-negative bacteria 8 percent, Anaerobic bacteria 17 percent, Nocardia 2 percent.

Flowchart 2: The second flowchart depicts the clinical suspicion of cerebral abscess at the top. This is divided into two: General and Radiological features. Radiological features are listed as: can vary depending on stage of abscess formation, perilesional parenchymal reaction, grey white matter junction, and ring-enhancing on contrast studies.

General is divided into two: Bloods: raised W C C and C R P culture, and Lumbar puncture: not to be done, and lists not helpful and can be dangerous due to herniation risk and C S F culture unlikely to be positive.

The radiological features are divided into two: C T and M R I. C T reads lesion is hypodense (but denser than C S F), C T plus contrast: ring-enhancing lesion, and look for contiguous spread from adjacent sites dental and sinuses.

M R I lists: T 1 Hypo-intense, T 2 Hyper-intense, M R I plus contrast including ring enhancing lesion, M R I plus D W I listing: diffusion restriction within the core of the abscess, Hyperintense on D W I, hypointense on A D C maps, good to monitor treatment response, and good to differentiate tumour vs abscess, and M R S listing: elevated peaks of lipids, lactate, succinate, acetate, and amino acids (alanine, valine, leucine, and isoleucine).

Flowchart 3: The third flowchart begins with clinical and/or radiological suspicion or diagnosis of cerebral abscess.

This leads to the general management, associated with anticonvulsants, treat primary source, and steroids, listed on the left, and antibiotic, listed on the right.

Anticonvulsants reads optional to be given prophylactically, must be given if seizures occur, duration: 1 year.

Treat primary source is exploration and drainage of the primary source.

Steroids are given where there is concern of raised I C P and short course.

Antibiotic lists Sinusitis, otogenic: third generation cephalosporins plus metronidazole, post trauma or post neurosurgical: third generation cephalosporins plus vancomycin, duration: 6 to 8 weeks, depending on clinical or radiological response, route: I V and/or intrathecal if intraventricular spread or rupture.

General management leads to expanding towards ventricles, neurological deterioration or significant mass effect or raised I C P, not successfully treated with antibiotics alone, diagnostic uncertainly, and large greater than 2.5 centimeters.

If this is no, then antibiotics only are considered as: by itself generally not adequate to treat cerebral abscess, and indicated: early in the infection prior to cerebritis stage, S and S lesser than 2 weeks, patients shows sign of improvement within first week, very small lesion (less than 1.7 centimeters), poor surgical candidate, multiple abscess if small, and abscess in poorly accessible location (brain stem).

If yes, then surgical is considered. Surgical is divided into three: Non-Loculated, unwell patient, deep lesion leading to needle aspiration; Multiloculated, has foreign body, superficial lesion leading to open drainage; and Superficial and large abscess, has foreign body, fungal infection, not responded to multiple aspirations leading to surgical excision.

Clinical Scenarios

A twenty-year-old male patient presented with two weeks of feeling unwell with nasal discharge and fevers. Patient had difficulty opening his eyes and a frontal headache and forehead swelling. CT with contrast showed an enhancing subdural collection and opacification of the maxillary and ethmoidal sinuses. This was treated via a left frontal craniotomy and endoscopic sinus surgery. The patient was placed on long-term antibiotics and the three-month follow-up scan showed only residual reactive enhancement of the dura (Figure 4).

Figure 4 Clinical scenario for adult cerebral subdural empyema (A) CT head on bone windows showing maxillary and ethmoidal sinuses opacification. (B) Initial CT with contrast showing an extradural collection. This was treated via a craniotomy and endoscopic sinus surgery. (C) Three months following the initial treatment a follow-up MRI scan with contrast showed that there is only residual reactive enhancement of the dura.

Core Knowledge

Definition

Adult subdural empyema (SE) is a collection of pus in the subdural space.

Epidemiology

It occurs more often in males (M:F, 3:1), peaking in the third decade of life. It is five times less common than CAs (Reference Osborn and Steinberg15).

Aetiology

Similar to a CA, the causative microorganism can reach the brain haematogenously, by contiguous spread or by direct inoculation. In contrast to an abscess, the haematogenous route is less common and most arise from contiguous spread from infected air sinuses or by direct inoculation from neurosurgical procedures or penetrating brain injuries. The most common surgical procedure associated with SE is drainage of chronic subdural haematomas (CSDH). This is especially true when subdural haematomas are drained via a craniotomy rather than burr holes (Reference Munusamy and Dinesh16).

Pathogen

The most common causative pathogens are aerobic and anaerobic streptococci, which are associated with infections of the middle ear. Post craniotomy, the commonest organisms are staphylococci and gram-negative species, whereas Propionibacterium acnes, a ubiquitous skin commensal is commonly found in CSDH patients (Reference Critchley and Strachan17). Staphylococci and gram-negative species infections are also found in patients with penetrating head injuries. Failure to identify an organism can occur in up to 40% of cases, and this may be due to previous exposure to antibiotics and difficulties in culturing anaerobic organisms (Table 3).

Pathology

SE has the propensity to spread rapidly due to a lack of a fibrin capsule and anatomical barriers in the subdural space. Most (80%) SE are localised over the convexity, but some do localise in the para-falcine region (20%). Concomitant presentation of a CA or an epidural abscess occurs in up to 22% and 17% of cases, respectively.

Clinical Presentation

In contrast to patients with CA, who frequently present with headache (86%) and fever (95%), in SE patients 83% present with meningism and 80% with unilateral hemispheric dysfunction. Affected patients can deteriorate rapidly with seizures in 63% and reduced conscious level in 76% (Reference Cowie and Williams18). The median time from the onset of symptoms to diagnosis is two days (Reference French, Schaefer, Keijzers, Barison and Olson19). Other common symptoms include tenderness over the affected air sinuses (42%) and forehead or eye swelling secondary to emissary vein thrombosis may occur (Reference Kubik and Adams20). The clinical presentation is secondary to the mass effect, inflammation of the brain and meninges and thrombophlebitis of the cerebral veins or venous sinuses.

Investigation

White cell count and CRP can be raised in affected patients. Blood cultures should be done if the patient is pyrexial. Lumbar puncture should be avoided as there is a risk of herniation, and the yield of a positive culture is low unless there is an associated meningitis.

The radiological features of a SE a crescent-shaped collection with dense enhancement of the medial membrane (Reference Weisberg21). As it is in the subdural space, it will not be constrained by suture lines and overlies the surface of the brain.

On a plain CT scan, it is a hypodense collection that is hard to differentiate from a chronic subdural haematoma, and small lesions may be difficult to see. In a contrast-enhanced CT, a brightly enhancing rim is suggestive of an empyema but a lack of contrast enhancement does not fully exclude a SE, as it could mean that the empyema is chronic and is well organised (Reference Munusamy and Dinesh16).

On MRI, T1-weighted sequences show a hypointense and T2-weighted sequences show a hyperintense subdural collection. Contrast-enhanced T1-weighted MRI is more sensitive than CT with contrast in detecting SEs. It is also useful for identifying collections located at the skull base, post fossa and along the falx cerebri. Subdural empyema restricts on DWI. It can help distinguish SE from subdural haematoma (Reference Wong, Zimmerman, Simon, Pollock and Bilaniuk22).

Acute Management

Almost all SEs need surgical drainage due to poor antibiotic penetration into the subdural space. Pure antibiotic management can be trialled for patients with no neurological deficit, small collections and patients that have had an early good symptomatic response (Reference Mauser, Ravijst, Elderson, van Gijn and Tulleken23). Delayed treatment for more than seventy-two hours is associated with a poorer outcome. Antibiotic treatment should ideally be started after surgical sampling of the subdural has occurred. However, broad-based empirical antibiotic therapy should not be delayed in a septic, systemically unwell patient. The choice of antibiotic should be targeted on the presumed source of the infection. After obtaining culture and sensitivity results, the antibiotics should be modified as per microbiology advice. Duration of antibiotics should be at least six weeks and guided by clinical, biochemical, and radiological responses (Reference Leys, Destee, Petit and Warot24).

Like CA prophylactic antiepileptic medication should be considered but anticonvulsants must be started if there is any evidence of seizure secondary to the SE. The primary source of the infection should also be treated or drained as soon as possible to prevent recurrence of the SE.

Subdural empyema can be drained via a burr hole, craniotomy, or a craniectomy. Burr hole drainage is suitable for an empyema that is not viscous or loculated. Since it is a simpler operation, it is suitable for critically unwell patients. However, burr hole drainage has a higher recurrence rate, and about 20% of cases will require a craniotomy for more definitive treatment. The use of a craniotomy is generally indicated for thick organised empyema (Reference Munusamy and Dinesh16). It is also more effective in treating loculated empyema. Generally, a wide craniotomy is needed. Frequently, there is an organised membrane on the surface of the cortex, and if this is not flushable with normal saline washes, they should not be stripped from the brain, as this can lead to cortical injury and bleeding. A craniectomy is sometimes needed if there is a worry about brain swelling underlying the empyema. This is especially true, the SE has started to affect the cortex and cause cerebritis. A craniectomy is also sometimes required if the bone overlying the empyema is infected and de-vascularized in the context of a post-operative or post-penetrative traumatic head injury. All three methods have been shown to be effective if empyema can be successfully drained (Reference Bok and Peter25). Early post-operative imaging will confirm the effectiveness of drainage and will guide further surgical management.

Technical Note – Craniotomy for SE

Preoperatively study the MRI and/or CT scan to identify the location of the SE and if there are any interhemispheric/skull base components of it. Plan a craniotomy centred around the SE. Skin incision made, and a bone flap is raised. The dura is then opened. Pus collected and sent for microbiology analysis. Wash pus out with warm saline. Do not attempt to peel any pus that is adherent to the cortex. Wash out any pus in the skull base or interhemispheric space, but be careful not to over-flush these spaces with wash and keep these spaces open with long-patties to prevent the brain from swelling above the craniotomy site. Clean the dura. Agents like Hydrogen Peroxide can be used, but be aware that they can foam and cause brain expansion if there is it is trapped in tight spaces within the brain. Standard closure should then be done. Frequently, if there is a concomitant infective source, we would invite the ENT surgeon or the Maxillofacial surgeon to drain the primary infective source.

Management Algorithms

See subdural empyema flow diagram (Figure 5).

Figure 5 Subdural empyema pathophysiology, investigations, and management

Figure 5Long description

Flowchart 1: The first flowchart depicts the causes and effects involved in the subdural collection of pus: empyema.

The flowchart starts with 5 parameters at the top. They are: Mastoiditis or otitis media or sinusitis: Aerobic and microaerophilic Streptococci; Post-operative and post-traumatic: immunocompetent Staphylococcus aureus and Immunocompromised Klebsiella pneumonia; Purulent bacterial meningitis; Hematogenous dissemination; and Skull Osteomyelitis.

All these parameters, together, lead to propensity to spread rapidly due to lack of fibrin capsule and anatomical barriers in the subdural space, commonly over the convexity and under the frontal bone, and M:F, 3:1.

This then leads to Local infective invasion into the brain that leads to Localized cerebritis and then to Cerebral abscess, Inflammation of brain and meninges, Mass effect, fever, Direct spread or septic emboli, and Symptoms from the primary source of infection, for example, sinusitis.

Inflammation of brain and meninges and mass effect lead to Meningismus, Seizure (63 percent of patients), low G C S, and Focal neurologic deficit: hemiparesis, speech difficulties, visual deficits.

Direct spread or septic emboli leads to thrombophlebitis of cerebral veins and/or venous sinuses, which divides into two: Emissary vein thrombosis leading to forehead or eye swelling, and Cortical venous thrombosis leading to venous infarction.

Flowchart 2: The second flowchart starts with clinical suspicion of subdural empyema, listing meningismus, unilateral hemisphere dysfunction, fever, and recent history of sinusitis, mastoiditis, surgery, or open head injury.

It is divided into two: general and radiological features.

The general features are bloods: raised W C C, C R P, culture; and Lumbar puncture: not helpful and can be dangerous due to herniation risk, C S F culture in most cases would not be positive.

Radiological features are crescent shaped collection, dense enhancement, crosses suture lines, on the surface of the brain, and enhances on contrast studies.

This is divided into two: C T and M R I. C T may miss small lesions, lesion is hypodense (but denser than C S F), C T with contrast may show no enhancement due to chronic empyema forming well-organized subdural pus. M R I lists: T 1 hypo-intense; T 2 Hyper-intense; M R I with contrast: more sensitive than C T with contrast in detecting: chronic organized empyema, and empyema located at the skull base and posterior fossa or along the falx; M R I plus D W I: diffusion restriction, hyperintense on D W I, hypointense on A D C maps, and can reliably distinguish subdural empyema from subdural hematoma or reactive subdural effusion.

Flowchart 3: The third flowchart begins with clinical and/or radiological diagnosis of subdural empyema.

This leads to the general management, associated with anticonvulsants and treat primary source, listed on the left, and antibiotic, listed on the right.

Anticonvulsants reads optional to be given prophylactically, but must be given if seizures occur.

Treat primary source is exploration and drainage of the primary source.

Antibiotic lists: initial broad-based empirical antibiotic therapy: to be started immediately if patient is septic and otherwise start after samples acquired from subdural; further antimicrobial therapy targeted based on gram stains, bacterial culture, and knowledge of the bacterial profile at the primary site of infection; duration: 4 to 6 weeks, depending on clinical or radiological response.

General management leads to minimal neurologic involvement, limited extension, limited mass effect, and early favourable response to antibiotics.

If this is yes, then nonsurgical is considered.

If no, then surgical is considered as non-viscous empyema, non-loculated empyema, critically ill patients with localized S D E, and non-thickened organized empyema.

If yes, it leads to Burr hole drainage. If no, craniotomy is considered, leading to significant brain swelling and intraoperative suspicion of osteomyelitis of the bone flap, which leads to craniectomy.

Clinical Scenarios

An eighteen-year-old female presented with fever, headache, and nasal discharge. CT with contrast showed opacification of the Maxillary sinus and an extradural enhancing collection. She underwent a right frontal brainlab-guided drainage of extradural abscess and an endoscopic sinus surgery. As the burr hole is over the forehead, we used Hydrocet a bone cement to cover the defect. (Figure 6)

Figure 6 Clinical scenario for adult extradural abscess (A) CT head on bone windows showing left maxillary sinus opacification. (B) Initial CT with contrast showing an enhancing extradural collection under the right frontal bone. This was treated via a burr hole aspiration of the collection. (C) CT on bone window at one month following the initial treatment showing that the burr hole was covered by Hydrocet, a bone cement. (D) CT with contrast at one month from the initial scan, shows complete resolution of the abscess.

Core Knowledge

Definition

Adult cranial extradural abscess (CEA) is a collection of pus that arises between the skull and the dura.

Epidemiology

It is less common than CA and SE. It affects all ages and represents 1.8% of all intracranial infections (Reference Nathoo, Nadvi and van Dellen26).

Aetiology

Cranial extradural abscess commonly occurs by contiguous spread from sinusitis or mastoiditis. Other sources of contiguous spread are skull osteomyelitis or dental infections. Direct spread through neurosurgical procedures or open skull fractures can also occur.

Pathogen

The microorganisms associated with CEA are similar to the spectrum seen in SE, such as Staph Aureus, Streptococci, and gram-negative bacilli (Reference Pradilla, Ardila, Hsu and Rigamonti27).

Pathology

The growing inflammatory mass of the CEA slowly dissects the dura away from the skull, which explains the insidious onset of clinical presentation. Most CEA are on the convexity and rarely occur in the skull base as the dura is more tightly adherent to the skull.

Clinical Presentation

Patients with CEA frequently present with fever (57%), headache (37%), and meningism (35%). A frontal subperiosteal abscess, also known as ‘Pott’s puffy tumour’, can be associated with a contiguous frontal CEA (46%) will present with forehead swelling. If there are associated seizures (11%) present, it might suggest meningitis or cerebral involvement (Reference Nathoo, Nadvi and van Dellen26). In CEA secondary to a neurosurgical cause, wound infection is almost always present (95.7%). Complications that can arise from CEA are skull osteomyelitis and thrombosis of emissary veins.

Investigation

Similar to CA and SE, lumbar puncture should be avoided as there is a risk of herniation and a low yield of a positive CSF microbiology result (Reference Nathoo, Nadvi and van Dellen26).

Radiologically CEA is described as a lentiform-shaped enhancing collection. CT might show bony destruction or mastoid opacification. MRI is useful to detect small abscesses and abscesses around the skull based that are easily missed on CT (Reference Weingarten, Zimmerman and Becker28). Diffusion-weighted MRI can help differentiate SE from CEAs. High signal intensity on DWI tends to favour a SE diagnosis, while for CEA, a low or mix signal intensity is more frequently seen (Reference Tsuchiya, Osawa and Katase29). Diffusion weighted MRI can also help differentiate whether a post op extradural collection is a sterile or infective.

Acute Management

Management of CEA consists of drainage of the abscess, controlling the source of the infection and antibiotics. Empirical antibiotics should be started immediately after microbiological samples have been taken or if the patient is septic. For spontaneous CEA, a 3rd-generation cephalosporin and metronidazole should be given, while for post-operative or post-traumatic CEA, vancomycin and meropenem should be used instead. After obtaining culture results, antibiotic therapy should be modified according to the sensitivities.

The aim of surgery is to reduce the mass effect of the CEA, reduce the infective load and obtain material for culture. In contrast to SE, a more limited surgical procedure in the form of a burr hole/craniectomy to allow adequate drainage of the extradural space is usually employed. A craniectomy is sometimes needed to resect localised osteomyelitis. It is also important to drain/treat any contiguous pathology at the same time as draining the cranial collection.

Management Algorithms

See extradural abscess flow diagram (Figure 7).

Figure 7 Extradural abscess pathophysiology, investigations, and management

Figure 7Long description

Flowchart 1: The first flowchart depicts three parameters: Mastoiditis or otitis media or sinusitis, post-operative and post-traumatic, and skull osteomyelitis. These parameters together lead to C E A.

C E A leads to Local infective invasion, Inflammation of brain and meninges leading to headache and meningism, mass effect leading to Focal neurologic deficit: hemiparesis, speech difficulties, visual deficits, fever, direct spread or septic emboli, and symptoms from the primary source of infection, for example, sinusitis.

Local infective invasion leads to into brain, into skull, and into subgaleal space.

Into brain leads to subdural empyema, followed by localized cerebritis, and then to cerebral abscess. Into skull leads to osteomyelitis. Into subgaleal space leads to Pott puffy tumour.

Direct spread or septic emboli leads to Thrombophlebitis of cerebral veins and/or venous sinuses, which divides into Emissary vein thrombosis leading to Forehead or eye swelling and Cortical venous thrombosis leading to venous infarction.

Flowchart 2: The flowchart is depicted as follows: Clinical suspension of C E A, divided into general and radiological features.

Clinical suspension of C E A lists fever; headache; meningism; and recent history of sinusitis, mastoiditis, neurosurgery or open head injury. The general features are bloods: raised W C C, C R P culture; and Lumbar puncture: not helpful and can be dangerous due to herniation risk, C S F culture in most cases would not be positive.

Radiological features are lentiform-shaped collection, enhancing, does not cross suture lines, and convexity based. This is divided into two: C T and M R I. C T may miss small lesions, and collection is hypodense (but denser than C S F). M R I lists: T 1 Mild hyper-intense; T 2 Hyper-intense; M R I plus C: More sensitive than C T plus C in detecting, small abscesses, abscess located at the skull base or posterior fossa or along the falx; and M R I plus D W I: can distinguish subdural empyema from C E A and can distinguish infective and noninfective extradural collection.

Flowchart 3: The third flowchart depicts Clinical and/or radiological diagnosis of C E A at the top. This leads to general management, involving treat primary source: exploration and drainage of the primary source on the left and antibiotic on the right. Antibiotic reads: initial broad based empirical antibiotic therapy to be started immediately if patient is septic or otherwise start after samples acquired from subdural; further antimicrobial therapy targeted based on sensitivity; and duration: 4 to 6 weeks, depending on clinical or radiological response. This is followed by surgical, then to suspicion of osteomyelitis of the bone flap, which, if no leads to Burr holes and, if yes, leads to craniectomy.

Cryptococcosis

Cryptococcosis is the second most common cerebral fungal infection, with the first being candidiasis. It is due to cryptococcosis neoformans, which is normally found in bird faeces. It can present in two forms, the more common cryptococcal meningitis and the rarer crytococcoma, also known as mucinous pseudocyst. Cryptococcal meningitis occurs more frequently in patients who are immunocompromised (Reference Mitchell and Perfect30). It can present as fever, tiredness, headaches, and with signs of meningeal irritation. The organism gains access to the human body through inhalation of basidiospores, which then spread to the brain via the haemato-lymphatic route. Some patients can present with raised intracranial pressure. Radiologically, there can be dilatation of the Virchow–Robbins spaces. Cryptococcoma is exclusively found in patients with AIDS with the lesions arising in the basal ganglia. The diagnosis of cryptococcosis is established via positivity in the serum or CSF cryptococcus antigen. It is treated with Amphotericin B and fluconazole for two to six weeks, depending on CSF clearance of the antigen (Reference Kaplan, Benson and Holmes31). Raised intracranial pressure may need to be managed with daily lumbar punctures, a lumbar drain or CSF shunting.

Cysticercosis

Cysticercosis is the most common CNS parasitic infection. It is due to Taenia Solium, which is a tapeworm where the human body is the definitive host. Taenia Solium, if it infects a human in its adult phase of life, causes taeniasis, however if it infects a human in its larval form, it causes cysticercosis. Humans can ingest the eggs via contaminated food or water. In the duodenum, the eggs hatch and burrow through the intestinal wall to enter the lymphatic or vascular system. The newly hatched embryos, also known as oncospheres, enter the brain where it forms a cyst which eventually present as Neurocysticercosis (32).

Neurocysticercosis occurs in 60–92% of cases of cysticercosis (Reference Garcia and Del33). It can take up to two to five years from the ingestion of eggs to symptomatic neurocysticercosis. Cysts are commonly found in the subarachnoid spaces or within the brain parenchyma. Rarely, it can also be found within the ventricular system. These cysts can cause local inflammation in the form of vasculitis, leading to stroke, meningitis, arachnoiditis, or ependymitis or obstruction leading to hydrocephalus. Most patients present with seizures (69%), headaches (46%), and/or visual disturbance (13%). The diagnosis is made based on radiological studies and serological testing. Eosinophils in the blood and CSF can be raised. Enzyme-linked immunoelectrotransfer blot against anti-cysticercal antibodies has a high sensitivity and specificity (Reference Tsang, Brand and Boyer34). Radiologically, a cystic lesion with an associated scolex, which is seen as a 1- to 3-mm mural nodule is diagnostic.

Many cysts resolve spontaneously therefore the use of Anthelmintics such as Praziquantel and Albendazole is not necessarily needed (Reference Mitchell and Crawford35). These drugs, although have been shown to increase the likelihood of radiologic cyst resolution, they do carry significant side effects such as headaches, dizziness, and seizures. Generally, Seizures secondary to neurocysticercosis respond well to a single antiepileptic agent (Reference Del Brutto, Santibañez and Noboa36). The most used antiepileptic agents are phenytoin and carbamazepine. Risk factors for recurrent seizures include calcified brain lesions, multiple seizures, and multiple brain cysts (Reference Del37). Steroids are commonly used to manage peri-cystic inflammation. It is always used with anthelmintics. Surgery in the management of neurocysticercosis is limited to managing hydrocephalus through CSF diversion, establishing a diagnosis via stereotactic biopsy or occasionally removal of a giant cyst that is causing neuronal compression or ventricular obstruction by endoscopic or open microsurgery.

Echinococcus

Echinococcus, also known as hydatid disease, is due to an infection by E. Granulosa, a dog tapeworm. This tapeworm is around 2–5 mm in length and uses sheep and man as its intermediate host (Reference Brunetti and White38). E. Granulosa infects humans through direct contact with dogs or by eating food contaminated with E. Granulosa eggs. When the eggs enter the human body, they hatch to form embryos which can burrow through the duodenal wall to gain spread through the body via a haematogenous route. The liver, lung and brain are common sites for the cyst to form (Reference Brunetti and White38). CNS involvement occurs in 3% of all Echinococcus infections. Cysts are normally located in the white matter, they can be solitary or multiple, but they do grow slowly. Symptoms arising from the cyst do not appear unless the cyst reaches a significant size to cause mass effect. Therefore, the symptoms arising from a hydatid cyst comprises of raised ICP, seizure, and focal neurological deficit. Enzyme-linked immunosorbent assay can help diagnose patients with Echinococcus.

Radiologically, the cyst is of similar characteristics to CSF. The cyst itself does not enhance but the surrounding parenchyma can enhance slightly due to perilesional inflammation (Reference Abdel Razek, El-Shamam and Abdel Wahab39). The cyst can contain multiple protoscolexes which, when ruptures, can cause the formation of multiple cysts in the surrounding tissue or allergic reactions. The management of echinococcus consists of anthelmintic therapy, such as Albendazole and surgery. The aim of surgery is to remove as the cyst with its content intact. Care must be taken while raising the craniotomy and performing the durotomy. Bipolar coagulation should be kept to a minimum, and the cyst wall should be kept moist to prevent rupture. Hydro-dissection using a rubber catheter within the lesion-brain plane can allow careful separation of the cyst from the surrounding brain. If the cyst ruptures, immediately suction up any cyst content and remove the capsule. The lesion cavity must then be washed thoroughly, and all instruments, gloves, and gowns should be changed (Reference Carrea, Dowling and Guevara40).