1. CNS ABSCESSES M.MOLAVI MD

2. CNS ABSCESSES Focal pyogenic infections of the central nervous system Exert their effects mainly by: –Direct involvement & destruction of the brain or spinal cord –Compression of parenchyma –Elevation of intracranial pressure –Interfering with blood &/or CSF flow Include: Brain abscess, subdural empyema, intracranial epidural abscess, spinal epidural abscess, spinal cord abscess

3. BRAIN ABSCESS Accounts for ~ 1 in 10,000 hospital admissions in US (1500-2500 cases/yr) Major improvements realized in diagnosis & management the last century, & especially over the past three decades, with:

4. BRAIN ABSCESS Was uniformly fatal before the late 1800’s Mortality down to 30-60% from WWII-1970’s –Introduction of abx (penicillin, chloramphenicol...) –newer surgical techniques Mortality down to 0-24% over the past three decades, with: –Advent of CT scanning (1974), MRI –Stereotactic brain biopsy/aspiration techniques –Further improvement in surgery –Newer abx (e.g. cephalosporins, metronidazole..) –Better treatment of predisposing conditions

5. CHANGES IN EPIDEMIOLOGY OF BRAIN ABSCESS (in the last 2-3 decades) –Marked drop in mortality overall –Lower incidence of otogenic brain abscesses –improved treatment of chronic ear infections –With increase in No. of immunosuppressed patients: increased incidence of brain abscess seen in that population (Transplant, AIDS,…) More incidence of brain abscess caused by opportunistic pathogens (fungi, toxo…)

6. PATHOPHYSIOLOGY 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 experimental animal models ): –Days 1-3: “early cerebritis stage” –Days 4-9: “late cerebritis stage” –Days 10-14: “early capsule stage” –> day14: “late capsule stage”

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

8. DIRECT SPREAD (from contiguous foci) Occurs by: –Direct extension through infected bone –Spread through emissary veins, diploic veins, local lymphatics The contiguous foci include: 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)

9. HEMATOGENOUS SPREAD (from remote foci) Sources: –Empyema, lung abscess, bronchiectasis, endocarditis, wound infections, pelvic infections, intra-abdominal source, etc… – may be facilitated by cyanotic HD, AVM. Results in brain abscess(es) at middle cerebral artery distribution Often multiple

10. PREDISPOSING CONDITION & LOCATION OF BRAIN ABSCESS Otitis/mastoiditisTemporal lobe, Cerebellum Frontal/ethmoid sinusitisFrontal lobe Sphenoidal sinusitisFrontal lobe, Sella turcica Dental infectionFrontal > temporal lobe. Remote source Middle cerebral artery distribution (often multiple)

11. Microbiology of Brain Abscess Dependent upon: Site of primary infection Patient’s underlying condition Geographic location Usually streptococci and anaerobes Staph aureus, aerobic GNR common after trauma or surgery 30-60 % are polymicrobial

12. Predisposing Conditions & Microbiology of Brain Abscess Predisposing Condition Usual Microbial Isolates Otitis media or mastoiditisStreptococci (anaerobic or aerobic), Bacteroides and Prevotella spp., Enterobacteriaceae Sinusitis (frontoethmoid or sphenoid)Streptococci, Bacteroides spp., Enterobacteriaceae, Staph. aureus, Haemophilus spp. Dental sepsisFusobacterium, Prevotella and Bacteroides spp., streptococci Penetrating trauma or postneurosurgicalS. aureus, streptococci, Enterobacteriaceae, Clostridium spp. PPID,2000

13. PREDISPOSING CONDITION USUAL MICROBIAL ISOLATES Lung abscess, empyema, bronchiectasis Fusobacterium, Actinomyces, Bacteroides Prevotellaspp., 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

14. MICROBIOLOGY OFBRAIN ABSCESS MICROBIOLOGY OF BRAIN ABSCESS AGENT FREQUENCY (%) Streptococci ( S. intermedius, including S. anginosus )60–70 Bacteroides and Prevotella spp.20–40 Enterobacteriaceae23–33 Staphylococcus aureus10–15 Fungi * 10–15* Streptococcus pneumoniae <1 Haemophilus influenzae <1 Protozoa, helminths † (vary geographically) <1† *Yeasts, fungi ( Aspergillus Agents of mucor Candida Cryptococci Coccidiodoides Cladosporium trichoides Pseudallescheria boydii) †Protozoa, helminths (Entamoeba histolytica, Schistosomes Paragonimus Cysticerci) CTID,2001

15. CLINICAL MANIFESTATIONS Non-specific symptoms Mainly due to the presence of a space- occupying lesion H/A, N/V, lethargy, focal neuro signs, seizures Signs/symptoms influenced by Location Size Virulence of organism Presence of underlying condition

16. CLINICAL MANIFESTATIONS OF BRAIN ABSCESS Headache70% Fever50 Altered mental status 50-60 Triad of above three <50 Focal neurologic findings50 Nausea/vomiting25-50 Seizures25–35 Nuchal rigidity25 Papilledema25 CTID,2001. PPID,2000

17. CLINICAL MANIFESTATIONS CLINICAL MANIFESTATIONS Headache Often dull, poorly localized (hemicranial?), non- specific –Abrupt, extremely severe H/A: think meningitis, SAH. –Sudden worsening in H/A w meningismus: think rupture of brain abscess into ventricle (often fatal)

18. LOCATION & CLINICAL FEATURES FRONTAL LOBE: H/A, drowsiness, inattention, hemiparesis, motor speech disorder, AMS TEMPORAL LOBE: Ipsilateral H/A, aphasia, visual field defect PARIETAL LOBE: H/A, visual field defects, endocrine disturbances CEREBELLUM: Nystagmus, ataxia, vomiting, dysmetria

19. DIFFERENTIAL DIAGNOSIS Malignancy –Abscess has hypo-dense center, with surrounding smooth, thin- walled capsule, & areas of peripheral enhancement. –Tumor has diffuse enhancement & irregular borders. –SPECT (PET scan) may differentiate. CRP too? CVA Hemorrhage Aneurysm Subdural empyema/ICEpidural abscess

20. DIAGNOSIS High index of suspicion Contrast CT or MRI Drainage/biopsy, if ring enhancing lesion (s) are seen

21. IMAGING STUDIES MRI –more sensitive for early cerebritis, satellite lesions, necrosis, ring, edema, especially posterior fossa & brain stem CT scan 99m Tc brain scan –very sensitive; useful where CT or MRI not available Skull x-ray : insensitive, –if air seen, consider possibility of brain abscess

22. 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 invariably elevated ESR Usually moderately elevated BC Often negative BUT Should still be done LP Contraindicated in patients with known/suspected brainabscess Risk of herniation 15-30% If done, may have normal CSF findings, but: Usually elevated CSF protein & cell count (lymphs) Unremarkable glucose & CSF cultures rarely positive

23. TREATMENT Combined medical & surgical Aspiration or excision empirical abx Empirical antibiotics are selected based on: Likely pathogen (consider primary source, underlying condition, & geography) Antibiotic characteristics: usual MICs, CNS penetration, activity in abscess cavity Modify abx based on stains Duration: usually 6-8 wks after surgical excision, a shorter course may suffice

24. CT Scan

25. MRI scan

26. MRI Scan

27. MRI scan

28. MR spectroscopy

29. Tips for Dx on MRI

30. Treatment Options

31. Goals & advantages of stereotactic-guided surgical approach

32. Surgical indications

33. Contraindications

34. Complications

35. Outcome & prognosis

43. Armstrong ID, Mosby inc 1999

44. MEDICAL TREATMENT ONLY Only in pts with prohibitive surgical risk: –poor surgical candidate, –multiple abscesses, –in a dominant location, –Abscess size <2.5 cm –concomitant meningitis, ependymitis, –early abscess (cerebritis?) –with improvement on abx, [Better-vascularized cortical lesions more likely to respond to abx alone] [ Subcortical/white-matter lesions are poorly vascularized]

46. CTID,2001

47. SERIAL IMAGING IMPORTANT TO MONITOR RESPONSE

48. Before Rx After completion of Rx Armstrong ID,Mosby inc 1999

49. POOR PROGNOSTIC MARKERS Delayed or missed diagnosis Inappropriate antibiotics. Multiple, deep, or multi-loculated abscesses Ventricular rupture (80%–100% mortality) Fungal, resistant pathogens. Neurological compromise at presentation Short duration w severe AMS, Rapidly progressive neuro. Impairment Immunosuppressed host Poor localization, especially in the posterior fossa (before CT) Modified from CTID,2001

51. EPIDURAL ABSCESSES Spinal > intracranial (9:1) Intracranially, the dura is adherent to bone True spinal epidural space is present posteriorly throughout the spine, thus posterior longitudinal spread of infection is common. –Anterior spinal epidural very rare (usually below L1 & cervical)

52. American Family Physician April 1, 2002

53. SPINAL EPIDURAL ABSCESS INTRODUCTION Rare, 0.2-1.2 per 10,000 hospital admissions Median age 50 yrs (35 yrs in IVDU) Thoracic>lumbar>cervical Majority are acquired hematogenously

54. COMMON PREDISPOSING CONDITIONS HEMATOGENOUS SPREAD: from remote infections & w IVDU DIRECT SPREAD: Vertebral osteomyelitis, diskitis, decubitus ulcers, penetrating trauma, surgery, epidural catheters Via paravertebral venous plexus: from abdominal/pelvic infections

55. PATHOGENESIS PATHOGENESIS SPINAL EPIDURAL ABSCESS Often begins as a focal disc or disc-vertebral junction infection Damage of spinal cord can be caused by: –Direct compression –Thrombosis, thrombophlebitis –Interruption of arterial blood supply –Focal vasculitis –Bacterial toxins/mediators of inflammation Even a small SEA may cause serious sequelae

56. MICROBIOLOGY SPINAL EPIDURAL ABSCESS The most common pathogens are: Staph aureus >60% Streptococci18% Aerobic GNR13% Polymicrobial 10% (Note: TB may cause up to 25% in some areas)

57. CLINICAL MANIFESTATIONS SPINAL EPIDURAL ABSCESS Four clinical stages have been described: 1. Fever and focal back pain; 2. Nerve root compression with nerve root pain; “shooting pain” 3. Spinal cord compression with accompanying deficits in motor/sensory nerves, bowel/bladder sphincter function; 4. Paralysis (respiratory compromise may also be present if the cervical cord is involved). Armstrong, ID, Mosby inc,2000

58. DIAGNOSIS SPINAL EPIDURAL ABSCESS (Thinking of it is key, in a pt with fever, severe, focal back pain) MRI, CT Abscess drainage Blood cultures Routine Labs rarely helpful ESR,CRP usually elevated, BUT non-specific WBC may or may not be elevated LP contraindicated

59. D/DX D/DX SPINAL EPIDURAL ABSCESS Metastases Vertebral diskitis and osteomyelitis Meningitis Herpes Zoster infection Other disc/bone disease

60. TREATMENT TREATMENT SPINAL EPIDURAL ABSCESS Early surgical decompression/drainage (preferably within first 24h) Antibiotics –Empiric abx should cover Staph, strep, & GNR –Duration of Rx : 4-6 weeks

61. (SEA/SDE) 90% epidural abscesses are spinal Most SEA occur in thoracic (the longest) Majority of SEA (>70%) are posterior to the cord Most SEA caused hematogenous spread & Staph aureus is the leading cause. 95% SDE are in intracranial Majority of SDE pts have associated sinusitis

63. INTRACRANIAL EPIDURAL ABSCESS Less common & less acute than SEA Rounded, well-localized (because dura is firmly adherent to bone) Pathogenesis: –Direct ext. from contiguous foci (sinusitis, otitis/mastoiditis) – trauma,or surgery

64. INTRACRANIAL EPIDURAL ABSCESS MICROBIOLOGY: Micraerophillic Strep, Propioni, Peptostrept, few aerobic gNR, fungi. Postop: Staph, GNR. CLINICAL MANIFESTATION: from SOL/ systmic igns of infection –Fever, HA, N/V, lethargy DX:- Think of it, imaging, drainage D/Dx: Tumor, other ICAbscesses Rx: Surgery + abx Mortality w appropriate Rx < 10%

65. SUBDURAL EMPYEMA 15-20 % of all focal intracranial infections Motly a complication of sinusitis, otitis media, mastoiditis. Most common complication of sinusitis (60% of such cases), mostly from frontal/ethmoid sinusitis. Trauma/post-op & rarely hematogenous M>F

66. SUBDURAL EMPYEMA Clinical Manifestations Fever Headache Focal Neuro defects Vomiting Mental status changes Seizures Mass effect more common w SDE than w ICEA DX: CT, MRI (LP contraindicated) Rx: Surgery. Abx (3-6 wks)

67. (Armstrong, ID,1999, Mosby Inc)

69. PARASITIC PARASITIC BRAIN ABSCESS Toxoplasmosis Neurocysticercosis Amebic Echinococcal

70. NOCARDIA BRAIN ABSCESS Usually in immunosuppresed (CMI) >50% no known predisposing factor All pts w pulmonary nocardiosis should undergo brain imaging to r/o subclinical CNS nocardiosis Rx: Sulfa (T/S invitro synergy), imipenem, ceftriaxone, amikacin, minocin –Duration of abx <a year. – Needle aspiration or surgical excision needed in most. Relapse common

71. BRAIN ABSCESS IN AIDS Toxoplasmosis is the most common Seropositive d/dx lymphoma Often empiric Rx given & biopsy only non- responders Listeria, Nocardia, tb, fungi…

72. BRAIN TB Rare cause of brain abscess Usually in immunocompromised Tuberculoma is a granuloma (not a true abscess ) Biopsy/drainage (send for PCR too )

73. FUNGAL BRAIN ABSCESS FUNGAL BRAIN ABSCESS (Aspergillus, Mucor...) IMMUNOCOMPROMISED Poor inflammatory response, less enhancement on CT. May present w much more advanced disease (seizure, stroke more common) High mortality Rx: aggressive surgery + antifungal

74. BRAIN ABSCESS SEQUELAE Seizure in 30-60% Neuro deficits 30-50% Mortality 4-20%

75. YIELD OF CULTURES YIELD OF CULTURES SPINAL EPIDURAL ABSCESS SOURCEYIELD Abscess fluid aspirate90% Blood culture62% CSF* 19% *LP often contraindicated