1. Focal CNS Infections Donnie Tyler MD Department of Neurosurgery University of Mississippi Medical Center

2. Anatomic Relationships of the Meninges Bone Epidural Abscess Dura Mater Subdural Empyema Arachnoid Meningitis Pia Mater Brain

3. Anatomic relationships of the Brain Frontal Lobe Frontal and Ethmoidal Sinuses Sella Turcica Sphenoidal sinuses Temporal Lobe Middle Ear, Mastoid, Maxillary Sinuses Cerebellum, Brain Stem Middle Ear, Mastoid

4. Brain Abscess 50% - Local Source otitis media, sinusitis, dental infection 25% Hematogenous spread adults - lung abscess, bronchiectasis and empyema children - cyanotic congenital heart disease (4-7%) pulmonary AVM - Osler-Weber-Rendu syndrome (5%) rarely bacterial endocarditis 10% trauma / surgery

5. Brain Abscess - pathology Location temporal > frontal > other lobes >10% are multiple Stages - based on histologic findings 1. Early cerebritis - poorly demarcated from surrounding brain 2. Late cerebritis - reticular marix (collagen precursor) and developing necrotic center 3. Early capsule formation - neovascularity, necrotic center, developing capsule 4. Late capsule formation - collagen capsule, necrotic center, gliosis surrounding capsule

6. Early Abscess (Cerebritis) – Poorly localized area of discoloration and softening.

7. Later Cerebritic / Early Abscess Stage – increasing necrosis of center with beginnings of capsule formation

8. Mature abscess (Late Stage) - dense fibro-gliotic capsular wall and purulent center

9. Brain Abscess - microbiology Streptococcus most frequent (33-50%), Multiple organisms(80-90%) of cases, May also include anaerobes (Bacteroides sp.) When secondary to frontal-ethmoidal sinusitis: Strep. Milleri, Strep. Anginosus When from otitis media, mastoiditis, or lung multiple organisms including anaerobic strep., bacteroides, enterobacter (proteus) Post Traumatic Abscess include: Staph. aureus and Enterobacteriaceae:

10. Abscess wall – inner portion formed by a layer of neutrophils and fibrin, middle layer with mainly fibrin (Blue on trichrome stain) and the outer portion with reactive glia.

11. Pyogenic meningitis – note the neutrophils are collected in the subarachnoid space.

12. Brain Abscess - Clinical Presentation Symptoms are non-specific for abscess and are normally due to increased intracranial pressure / mass effect: Headache, Nausea/Vomiting, or Lethargy. Occasionally Seizures.

13. Abscess – CT presentation CT appeareance dependent on stage Cerebritic stage – thick diffuse ring of enhancement, further diffusion on contrast into central lumen or lack of decay of contrast on delayed scan 30-60 minutes later. Capsular stage – faint rim present on pre contrast CT. (Necrotic center with edematous surrounding brain makes the collagen capsule easier to see.). Thin ring on enhancement and there is decay of enhancement on delayed scans.

14. Abscess – MRI presentation MRI presentation also varies with capsule formation Early Cerebritic stage – hyperintense in T2 with poor contrast enhancement on T1. Later Cerebritic Stage – central region of necrosis is hyperintense to brain on T2, rim is isointense to mildly hyperintense on T1. The capsule enhances with contrast. Early and Late Capsule Stages – Capsule is easily visible on unenhanced scans as a well deliniated isointense to slightly hyperintence ring with becomes hyperintense with contrast on T1. Capsule is hypointense on T2

15. Intraparenchymal abscess

16. Initial management of Brain Abscess Blood Cultures (rarely helpful) LP role is dubious because of risk of transtentorial herniation. CSF is typically abnormal but cultures are usually negative. initiate antibiotic therapy (preferably after biopsy specimen is obtained), regardless of which management mode is chosen.

17. Brain Abscess Antibiotics If pathogen is unknown or S aureus is suspected: Vancomycin - Adult 1 gm q 12 hours PLUS 3rd generation cephalosporin (e.g Claforan) PLUS Metronidazole Adult (30mg/kg/d) divided q12 or q6 hours OR Chloramphenicol Adult 1 gm IV q 12 hours OR for post traumatic abscess use po rifampin 9mg/kg/d qd

18. Brain Abscess - medical treatment Medical therapy alone is more successful if: The treatment is begun before complete encapsulation The lesion is 0.8-2.5cm in diameter or less (3.0 cm is the typical cutoff) The duration of symptoms is < 2 weeks The patients should show improvement in the first 2 weeks of treatment

19. Brain Abscess - surgical treatment, indications significant mass effect exerted by lesion proximity to ventricle poor neurological condition Inability to obtain weekly CT scans In patient undergoing medical treatment Intervention, if neurological deterioration occurs, anatomic progression of abscess towards ventricles, or after 2 weeks of therapy if abscess is enlarged. Also consider if there is no decrease in abscess size by 4 weeks of treatment.

20. Brain Abscess - surgical treatment modern methods Needle aspiration - recommended for thin walled (immature) or multiple lesions Surgical excision - only can be performed on mature abscess Historical methods Tube drainage - 34% morality marsupialiaztion - remove overlying cortex and pack - 23% mortality Decompressive craniectomy with spontaneous migration of abscess

21. Treatment of Brain Abscess in 1895 If symptoms of abscess exist – trephine the skill at once. If there are localizing symptoms open over that region. If pus is not found in the epi/sub dural spaces and the brain bulges very much and is not seen to pulsate then instert a grooved director to 2.5 inches, if no pus the redirect and reinsert.

22. 1895 medicine continued When pus is found, incise the brain overlying he cavity. Scrape out the granulation tissue in the abscess cavity. Irrigate with hot salt solution. Place a rubber drainage tube to externally drain. Close dura and skin. Slowly remove the rubber tube over the next 4-7 days. (Pennicillin – 1943)

23. Mortality / Morbidity pre-CT era - 40-60% morality post CT era - 0-10% (Improvement due to better antibiotics, surgical methods and ability to diagnose earlier) neurologic disability 45% late focal or generalized seizures - 27% hemiparesis - 29%

24. Multiple abscesses in a 6 year old

25. Presumed source of polymicrobial abscesses.

26. Cerebellar Abscess from open skull fracture.

27. Subdural Empyema Located in the potential space between the dura and the arachnoid. May spread rapidly due to lack of anatomical boundaries. Less mass effect than brain abscess Surgical Emergency Usually from a local source of infection >50% stem from a paranasal sinusitis (fronto-ethmoidal) trauma or surgery progression of an epidural abscess, ostermyelitis

28. Etiologies of SDE paranasal sinusitis - 67-75% otitis-14% post neurosurgical - 4% trauma -3% meningitis (mainly peds) - 2% congenital heart disease - 2% other 7%

29. Subdural Empyema - clinical fever -95% focal neurological deficit (mainly hemiparesis) - 80- 90% nuchal rigidity - 80% headache 77% Seizures - 50-60% Forehead or eye swelling from emissary vein thrombosis - 30% Vomiting - 20% Male to female ratio - 3:1

30. Subdural Empyema - evaluation CT of head both with and without contrast LP - hazardous - risk of transtentorial herniation Location - convexity 70-80% falcine 10-20% 32/10,000 autopsies

31. Subdural empyema - Bacteriology Aerobic Streptococcus - 30-50% Staphylococcus - 15-20% Microaerophilic and anaerobic strep - 15-25% Anaerobic Gm negative rods- 5-10% other 5-10%

32. Management of Subdural empyema Craniotomy - relatively emergency to debride and drain wide craniotomy is used because of septations / loculations Antibiotics - initially Vancomycin and chloramphemicol OR Cefotaxime and flagyl Modify based on culture results

33. Meningitis progression to subdural empyema

34. Subdural Empyema

35. Intracranial Epidural Abscess Localized between dura and bone sharply defined - mainly be dural adherence to bone at suture lines focal osteomyelitis associated with subdural empyema Management and etiology same as subdural empyema

36. Mixed Abscess Location

37. Spinal Epidural Abscess clinical presentation back pain fever spine tenderness major risk factors diabetes IV drug abuse chronic renal failure alcoholism

38. Spinal Epidural Abscess - Exam myelopathic distal to lesion deterioration of exam with time classic presentation of a “skin boil” in 15% of patients Patients complain of excruciating pain localized to the spine Also may note bowel/bladder disturbances

39. Spinal Epidural Abscess Average time course Back pain to root problems - 3 days Root problems to weakness - 4.5 days Weakness to paraplegia - 24 hours

40. Spinal Epidural Abscess Epidemeology.2-1.2 / 10,000 hospital admissions 40-60 years old incidence increasing

41. Spinal Epidural Abscess -source Hematogenous spread Skin infections Parenteral infections (IVDA) Bacterial endocarditis UTI Respiratory infection Dental abscess

42. Spinal Epidural Abscess -source direct decubitus ulcer psoas abscess trauma pharyngeal infection mediastinitis pyelonephritis

43. Spinal Epidural Abscess -source Following spinal procedures open procedure for example disectomy closed procedure LP Epidural catheter No source in 50% of patients in some series

44. Spinal Epidural Abscess - location Cervical – 15% Thoracic - 50% Lumbar - 35% Posterior to the Cord - 82%

45. Spinal Epidural Abscess - treatment Surgery goal is to determine causative organism and debridement is necessary immobilization - infected segments may become unstable Non-surgical management indications: patients with prohibitive operative risk factors involvement of an extensive length of the spinal canal complete paralysis for >3 days absence of neurological deficit (controversial)

46. Spinal Epidural Abscess - treatment Antibiotics 3rd generation cephalosporin PLUS Vancomycin - until MRSA is ruled out PLUS Rifampin po Duration of treatment 3-4 weeks IV followed by 4 weeks of po mortality 18-23%

47. Discitis with local osteomyelitis and epidural empyema

48. Parasitic Infections - Cysticercosis Most common parasitic infection in CNS Caused by larval stage of Taenia solium- pork tapeworm Incubation period from months to decades 83% of cases show symptoms within 7 years of exposure Infection with the adult form - tapeworm in gut man is the only know permanent host for the worm eggs are excreted in the feces - does not cause neurocysticercosis

49. Parasitic Infections - Cysticercosis Infection with the larva animals (pigs) serve as an intermediate host larva burrow through the small bowel to gain access to the systemic circulation mainly infect the following sites: Brain (60-92% of cases) Skeletal muscle Eye Subcutaneous Tissue

50. Parasitic Infections - Cysticercosis Common routes of infection Food (usually vegetables) or water containing eggs from human feces Fecal - Oral autoinfection (poor sanitation habits) Autoinfection from reverse peristalsis - (theory possibly offered by patients who autoinfected themselves)

51. Parasitic Infections - Cysticercosis cystercercus cellulosae - (3-20 mm) regular round thin walled cyst, produces only mild inflammation larva in cyst cystercercus racemosus - (4-12 cm) active growing grape like clusters intense inflammation no larva in cyst

52. Parasitic Infections - Cysticercosis Location: meningeal 27-56% parenchymal 30-63% ventricular 12-18% (may cause hydrocephalus) mixed - 23% Clinical symptoms of increased intracranial pressure

53. Parasitic Infections - Cysticercosis serology antibody titers significant if 1:64 in the serum and 1:8 in the CSF CT scan ring enhancing / calcified lesions, multiple

54. Parasitic Infections - Cysticercosis Treatment Steroids - symptomatic relief Antihelmintic drugs Praziquantal - (DOC for intestinal infestation) - 50mg/kg divided tid for 15 days Albendazole -15mg/kg divided bid po tid for 3 months Niclosamide - may be given orally for GI infestation

55. Cystercercus cellulosae - (3-20 mm) regular round thin walled cyst, produces only mild inflammation larva in cyst

56. Parasitic Infections - Echinococcosis “Hydatid Cyst” - caused by ingestion of the dog tapeworm (Uruguay, Australia, New Zealand) Treatment - Surgical excision without cyst rupture Cyst is full of worms Adjunctive treatment Albendazole - 400mg po BID for 28 days

57. Echinococcus Cyst – intraoperative

58. Fungal Infections Cryptococcosis - most common fungal infection in CNS diagnosed in live patients Cryptococcoma (mucinous pseudocyst) - occurs almost entirely in the HIV population 3-10mm, most commonly in the basal ganglia Candidiasis - most common fungal infection in CNS diagnosed in dead patients rare in healthy individuals Aspergillosis Coccidiomycosis - normally causes meningitis

59. Cryptococcosis

60. Aspergillosis – Abscess in the centrum ovale. (Also may cause diffuse cerebritic infections) Note many satellite lesions common among fungal infections. (Patient was on steroid therapy for leukemia.)

61. Mucor – aggressive and locally destructive infection.

62. Toxoplasmosis CNS manifestations Mass lesion (most common) Meningoencephalitis Encephalopathy

63. Toxoplasmosis CT findings Mass lesion - comprises 70-80% of cerebral masses in AIDS patients large low density area with mild to moderate edema Ring enhancement with contrast most commonly in the basal ganglia Often multiple Most patients with CT diagnosed toxoplasmosis also have evidence of cerebral atrophy

64. Toxoplasmosis Treatment Pyrimethamine 200mg loading dose then 75-100mg/d PLUS Sulfadiazine 75mg/kg po loading dose then 25mg/kg/q6 hours PLUS Folic Acid 5-40mg/d (usually 10mg with each dose of Pyrimethamine) Should show radiologic response in 3 weeks. If response is good then continue dose for 6-12 weeks then reduce by 50% and continue for life

65. Toxoplasmosis Biopsy in following settings: negative toxo titers (keep in mind the patient may be anergic) accessible lesions atypical for toxo (non-enhancing, not in basal ganglia, etc) in patients with extraneural infections or malignancies that may involve CNS Single lesion The role of biopsy for non-enhancing lesions is less well defined as the diagnosis normally does not influence therapy (most are PML or the biopsies are non-diagnostic), it may, however, be useful for prognostic purposes.

66. Toxoplasmosis

68. Texas Tapeworm

69. END