1. Dr. Mansoureh Togha
Professor of Neurology
Tehran University of Medical sciences

2. CHANGES IN EPIDEMIOLOGY OF BRAIN ABSCESS (in the last 2-3 decades)
Lower incidence of otogenic brain abscesses
With increase in # of immunocompormised patients (transplant, AIDS,…), increased incidence of brain abscess seen in that population, including those caused by opportunistic pathogens (e.g., fungi, toxo, Nocardia)

3. PATHOGENESIS Direct spread from contiguous foci (40-50%)
Hematogenous spread (25-35%)
Penetrating trauma/surgery (10%)
Cryptogenic (15-20%)

4. DIRECT SPREAD From: By: Otitis media & mastoiditis Sinusitis
Dental infection (<10%), typically with molar infections
Meningitis rarely complicated by brain abscess (more common in neonates with Citrobacter diversus meningitis, of whom 70% develop brain abscess)
By:
Direct extension through infected bone
Spread through emissary/diploic veins, local lymphatics

5. HEMATOGENOUS SPREAD (from remote foci)
empyema, lung abscess, bronchiectasis
endocarditis,
wound infections,
pelvic infections, intra-abdominal source, etc…
may be facilitated by cyanotic HD, AVM.
Abscess mostly at middle cerebral artery distribution, and often multiple

6. PREDISPOSING CONDITION LOCATION OF ABSCESS
Otitis/mastoiditis
Temporal lobe,
Cerebellum
Frontal/ethmoid sinusitis
Frontal lobe
Sphenoidal sinusitis
Frontal lobe,
Sella turcica
Dental infection
Frontal > temporal lobe.
Remote source
Middle cerebral artery distribution (often multiple)

7. MICROBIOLOGY OF BRAIN ABSCESS
AGENT FREQUENCY (%)
Streptococci (S. intermedius, including S. anginosus) 60–70
Bacteroides and Prevotella spp. 20–40
Enterobacteriaceae –33
Staphylococcus aureus 10–15
Fungi * –15
Streptococcus pneumoniae <1
Haemophilus influenzae <1
Protozoa, helminths † (vary geographically) <1
*Fungi (Aspergillus Agents of mucor Candida Cryptococci Coccidiodoides Cladosporium trichoides Pseudallescheria boydii) †Protozoa, helminths (Entamoeba histolytica, Schistosomes Paragonimus Cysticerci) CTID,2001

8. PREDISPOSING CONDITION USUAL MICROBIAL ISOLATES
Lung abscess, empyema, bronchiectasis Fusobacterium, Actinomyces, Bacteroides Prevotella spp., streptococci, Nocardia
Bacterial endocarditis S. aureus, streptococci
Congenital heart disease Streptococci, Haemophilus spp.
Neutropenia Aerobic gram-negative bacilli, Aspergillus Mucorales, Candidaspp.
Transplantation Aspergillus spp., Candida spp., Mucorales, Enterobacteriaceae, Nocardia spp., Toxoplasma gondii
HIV infection Toxoplasma gondii, Nocardia spp., Mycobacterium spp., Listeria monocytogenes, Cryptococcus neoformans
PPID, 2000

9. PATHOPHYSIOLOGY of Brain Abscess
Begins as localized cerebritis (1-2 wks)
Evolves into a collection of pus surrounded by a well-vascularized capsule (3-4 wks)
Lesion evolution (based on animal models):
Days 1-3: “early cerebritis stage”
Days 4-9: “late cerebritis stage”
Days 10-14: “early capsule stage”
> day14: “late capsule stage”

10. Effect of Brain Abscess
Direct destruction
Compression of parenchyma
Elevation of intracranial pressure
Interfering with blood &/or CSF flow

11. CLINICAL MANIFESTATIONS
OF BRAIN ABSCESS
Headache 70%
Fever
Focal neurologic findings >60
Triad of above three <50
Altered mental status <70
Nausea/vomiting
Seizures 25–35
Nuchal rigidity 25
Papilledema 25
PPID,2005

12. HEADACHE in Brain Abscess
Usually non-specific, dull, and poorly localized.
If abrupt & extremely severe headache: consider meningitis or SAH.
Sudden worsening in H/A w meningismus: consider rupture of brain abscess into ventricle.

13. Diagnostic work-up MRI is the procedure of choice
more sensitive especially for early cerebritis, satellite lesions, necrosis, ring, edema, especially for posterior fossa & brain stem abscesses
CT scan with contrast enhancement is 95% sensitive
Skull roentgenograms usually normal
Biopsy or aspiration needed for definitive diagnosis
Laboratory findings often not helpful
Lumbar puncture contraindicated

14. LABORATORY TESTS
BRAIN ABSCESS
Aspirate: Gram/AFB/fungal stains & cultures, cytopathology (+/-PCR for TB)
WBC Normal in 40%, only moderate leukocytosis in ~ 50%,
& only 10% have WBC >20,000
CRP almost always elevated
ESR Usually moderately elevated
BC Often negative, BUT Should still be done
AVOID LP!! Risk of herniation 15-30%
May even have normal CSF findings, but:
Usually elevated CSF protein & cell count (lymphs)
Unremarkable CSF glucose
CSF culture rarely positive

15. DIFFERENTIAL DIAGNOSIS
Malignancy
Abscess has hypodense center, with surrounding smooth, thin-walled capsule, & areas of peripheral enhancement.
Tumor has diffuse enhancement & irregular borders.
PET scan may differentiate.
CRP??
CVA
Hemorrhage
Aneurysm
Subdural empyema
Epidural abscess

16. TREATMENT Medical & surgical Obtain Neurosurgical Consult ASAP
Aspiration or excision
Antibiotics
Initially selected based on:
-Likely pathogen: considering primary source, underlying condition, & geography
-Antibiotic characteristics: MICs for usual pathogens, CNS penetration, activity in abscess cavity
Duration of abx: usually 6-8 wks
After surgical excision, a shorter course may suffice

17. ANTIBIOTICS TREATMENT ONLY (WITHOUT SURGERY)
Only in pts with prohibitive surgical risk:
poor surgical candidate,
multiple abscesses
a dominant location
Abscess size <2.5 cm
concomitant meningitis, ependymitis
early abscess (cerebritis?)
In pt already showing improvement on abx

18. MONITOR RESPONSE CLOSELY WITH SERIAL IMAGING

19. USUAL APPEARANCE OF CEREBRAL ABSCESS ON MRI
Post-Gd T1WI: Abscess in the right thalamus shows low signal intensity within its cavity and an enhancing rim. Note subtle hypointense outer rim, corresponding to edema.

20. USUAL APPEARANCE OF CEREBRAL ABSCESS ON MRI
T2WI: Same patient with right thalamic abscess. There is high signal in the abscess cavity and in the surrounding edema. Note low signal intensity in the rim surrounding the cavity which is thought to be secondary to susceptibility artifact from presence of local free radicals, and indicates a mature abscess.

21. USUAL APPEARANCE OF CEREBRAL ABSCESS ON MRI
DWI: Same patient in previous two slides. There is marked high signal intensity in the abscess corresponding to restricted diffusion of water molecules in the cavity. Note mild hyperintensity surrounding the cavity due to “T2 shine through” from edema.

22. USUAL APPEARANCE OF CEREBRAL ABSCESS ON MRI
Left and right frontal abscesses: Another example of the expected appearance of abscesses on MRI. The abscess cavities show low and high signal on T1- and T2WI, respectively. There is surrounding vasogenic edema and mature capsules. There is corresponding high signal on trace DWI. Dark signal on ADC map confirms restricted diffusion.
35-year-old male presenting with seizure, left sided weakness, and urinary incontinence. Drainage was performed and cultures grew Streptococcus anginosus.

23. ATYPICAL APPEARANCE OF BACTERIAL ABSCESS ON DWI
Mixed signal: Abscess located in the left temporooccipital region. There is a hypointense cavity with an enhancing rim on the post-Gd T1WI. FLAIR image (middle) shows high signal in the rim, surrounding tissues and in the anterior part of the cavity corresponding to areas of edema and pus. There are also isointense areas in the cavity. (Continued)

24. ATYPICAL APPEARANCE OF BACTERIAL ABSCESS ON DWI
Mixed signal: (Continued) DWI (right) shows high signal in the cavity corresponding to the region of hyperintensity on the FLAIR image and decreased signal corresponding to isointense region which indicates either free diffusion or susceptibility, such as that from focal hemorrhage.

25. TUBERCULOMA
Early lesions are usually isointense on T1- and T2WI, and have variable Gd enhancement.
Mature lesions have ring enhancement on post-Gd T1WI and low signal centrally on T2WI.
Normal DWI signal is common even in mature tuberculomas.

26. TUBERCULOMA
Normal DWI signal: Images show a tuberculoma in the left frontotemporal region. There is bright rim enhancement, characteristic hypointensity in its central portion on T2WI and vasogenic edema. The central area is isointenste to gray matter DWI and there is mild “T2 shine through” from edema. ADC map (far right) shows minimally restricted diffusion.
3-year-old female with miliary TB. At biopsy, fluid could noto be aspirated from the cavity.

27. TUBERCULOMA
Two examples of tuberculomas with low signal on DWI: DWI of right occipital (top) and right cerebellar (bottom) show that neither of these lesions have restricted diffusion.

28. NOCARDIA
Renal transplant patient: Post-Gd T1WI (top) shows multiple punctate lesions. Note that individual lesions are not discriminated on the trace DWI and that the abnormalities are seen as confluent areas of high signal due to “T2 shine through.”

29. Nocardia Genus : aerobic actinomycetes
G+ branching filamentous bacteria
Subgroup: aerobic nocardiform actinomycetes
-Mycobacterium
-Corynebacterium
-Nocardia
-Rhodococcus
-Gordona
-Tsukamurella

30. Nocardia :ECOLOGY& EPIDEMIOLOGY
The risk of pulmonary or disseminated disease
*deficient cell-mediated *
-Alcoholism
-Diabetes
-Lymphoma
-Transplantation
-Glucocorticoid therapy
-AIDS CD4+ < 250
Transmission
Inhalation
Skin

31. CLINICAL MANIFESTATIONS : 4 main form
Lymphocutaneous syndrome
Pulmonary :Pneumonia
CNS : Brain abscess
Disseminated disease
CNS
Eyes (particularly the retinaKeratitis),
Skin& subcutaneous
Kidneys,
Joints, bone
Heart

32. Pulmonary disease Pneumonia Endobronchial inflammatory mass
Subacute(more acute in immunosuppressed)
Cough**
Small amounts of thick, purulent sputum
Fever, anorexia, weight loss, malaise
Endobronchial inflammatory mass
Lung abscess
Cavitary disease
Inadequate therapy Progressive fibrotic diseaseฆ
Cerebral imaging,should be performed in all cases of pulmonary and disseminated nocardiosis

33. Nocardial pneumonia. Discrete nodular in midlung on both sides

34. CT scan (A),CXR (B) from : multiple abscesses : Nocardia farcinica

35. CNS : Brain abscess
Insidious presentations : mistaken for neoplasia !!!
Granulomatous , abscesses
Cerebral cortex, basal ganglia and midbrain***
Less commonly: spinal cord or meninges.
Brain tissue diagnosis in pulmonary nocardiosis
: not necessary
However,
cerebral biopsy:considered early in immunocompromised

36. brain abscess ; Nocardia farcinica
Nocardial abscess :rt. occipital lobe

37. LABORATORY DIAGNOSIS Gram-positive, beaded, branching filaments
usually weak acid fast+ve .
Standard blood culture :48 hrs to several wks, but
typical = 3 to 5 days
Colonization of sputum
:underlying pulmonary dz +
not receiving steroid therapy no specific therapy
Susceptibility testing
-Deep-seated /disseminated dz. fail initial therapy
-Relapse after therapy
-Alternatives to sulfonamides are being considered

38. MANAGEMENT :Medication
Sulfonamides : the mainstay of therapy
treatment of choice :N. brasiliensis
N. asteroides complex
N. transvalensis.
severely ill patients, CNS /disseminated/ immunosuppressed patients =/> 2 drugs
Amikacin and Carbapenem or
3rd generation cephalosporin.

39. MANAGEMENT :Medication
TMP-SMX :currently preferred
:drugs in serum:CSF = 1:20
:high MICs  good therapeutic responses
-General:5-10 mg/kgTMP & mg/kgSMX divide2- 4times
-Cerebral abscesses,severe,disseminated,AIDS
:15 mg/kg TMP and 75 mg/kg SMX)
-Cutaneous infection: 5 mg/kg/day (TMP) + DB
Hypersensitivity reactions :Desensitization

40. MANAGEMENT Medication:alternative therapeutic drugs
Failed sulfonamide Rx: N. otitidiscaviarum
Intolerant : hypersensitivity,GI toxicity, myelotoxicity)
Parenteral : Imipenem & amikacin
: Meropenem
: 3rd-gen cephalosporins Ceftriaxone, cefotaxime
Oral:Amoxicillin clavulanate
:Minocycline(100–200 mg twice daily)
:Linezolid :new oxazolidinone ;effective orally
(bioavailability~100%), good CSF penetration

41. MANAGEMENT Surgical drainage: depend on site
Extraneural aspirate,drainage, excision
Brain abscesses
1) Accessible and relatively large AND
2.1) Lesions progress within 2 wks or
2.2) No reduction in abscess size within a month.

42. Duration of Therapy : at least 12 mo. +
Clinical improvement: most days
Parenteral 3 to 6 wks oral regimen
Primary cutaneous infection :1-3 mo.
Nonimmunosuppressed
-Pulmonary /systemic nocardiosis: at least 6 mo
-CNS involvement : for 12 months
Immunocompromised
HIV-negative immunosuppressed
:12 mo or longer if there are intercurrent increases in immunosuppression
AIDS
: at least 12 mo. +
low-dose maintenance
(long life)

43. Outcome of therapy Cure rates -skin or soft tissue : almost 100%
-pleuropulmonary disease : 90%
-disseminated infection : 63%
-brain abscess : 50%
Mortality
-brain abscesses :31%
-multiple abscesses :41%
-immunocompromised patients :55%

44. MONITORING TREATMENT WITH DWI
The following are three examples of cerebral abscesses which were followed with serial MRI examinations, including DWI after surgical drainage.
The appearance of the abscess cavity on DWI can indicate success or failure of treatment.

45. Example 1: 2-year-old female with seizures and right-sided paraparesis
Example 1: 2-year-old female with seizures and right-sided paraparesis. Initial MRI shows a left posterior frontal abscess. The edema is best seen on T2WI (far left) and the mild peripheral enhancement on post-Gd T1WI (2nd from left). There is restricted diffusion in the cavity (DWI image, 3rd from left) confirmed on ADC map (far right). (Continued)

46. Example 1: (Continued) Images obtained approximately 2 months after surgery. In the region of the abscess there is a non-enhancing linear area without abnormal signal on DWI, consistent with focal gliosis (no recurrence). Clinically, the patient was cured.

47. Example 2: Serial MRI studies (post-Gd T1WI, DWI, ADC) obtained at one-week intervals in a 40-year-old man presenting with fever, headache and vision disturbance. The left occipital abscess was drained. The lesion has similar characteristics to that shown in the previous case with a notable change on DWI following drainage and resolution of the lesion over time.

48. CONCLUSIONS Pyogenic abscesses have a typical appearance on DWI
TB and toxoplasmosis usually little restriction of water motion when compared to pyogenic abscesses
Fungal abscess have a variable DWI appearance
DWI can be use to monitor cerebral abscesses during the course of therapy