1. CNS Infections 11-23-04 Chapter 235

2. Bacterial Meningitis

3. Epidemiology 400 per 100,000 in neonates 400 per 100,000 in neonates 1-2 per 100,000 in adults 1-2 per 100,000 in adults S pneumoniae & N meningitidis m/c S pneumoniae & N meningitidis m/c HIB vaccine has been very effective HIB vaccine has been very effective Mortality Mortality 5% in children beyond infancy 5% in children beyond infancy 25% in neonates and in adults 25% in neonates and in adults

4. Pathophysiology S. pneumonia and N. meningitidis (and H. influenzae) are encapsulated which provides them with increased ability to invade BBB S. pneumonia and N. meningitidis (and H. influenzae) are encapsulated which provides them with increased ability to invade BBB Upper airway  bloodstream  subarachnoid space  subcapsular constituents trigger inflammation  fever, meningimus, change in MS  brain/meningeal edema  decreased CSF drainage  hydrocephalus  increased ICP  ICP>CPP Upper airway  bloodstream  subarachnoid space  subcapsular constituents trigger inflammation  fever, meningimus, change in MS  brain/meningeal edema  decreased CSF drainage  hydrocephalus  increased ICP  ICP>CPP

5. Clinical Features 25% of adult cases “classic” 25% of adult cases “classic” Rapid development of Rapid development of Fever Fever HA HA Stiff neck Stiff neck Photophobia Photophobia Change in MS Change in MS Nonspecific signs/symptoms in very young/old Nonspecific signs/symptoms in very young/old 25% will develop seizures 25% will develop seizures

6. Clinical Features History History Living conditions Living conditions College dorm/barracks  N meningitidis College dorm/barracks  N meningitidis Trauma Trauma Recent neurosurgery  Staph/gram(-) rod Recent neurosurgery  Staph/gram(-) rod Immunocompetence Immunocompetence Immunization hx Immunization hx None  HiB None  HiB Antibiotic use Antibiotic use

7. Clinical Feratures Physical Exam Physical Exam Brudzinski Brudzinski Passive neck flex  hips & knees flex Passive neck flex  hips & knees flex Kernig Kernig Flex hip, ext knee  hamstrings contract Flex hip, ext knee  hamstrings contract Skin Skin Purpura Purpura Petechiae/splinter hem, pustular lesions  microemboli Petechiae/splinter hem, pustular lesions  microemboli Fundi Fundi Neuro Exam Neuro Exam

8. Diagnosis Parenchymal Parenchymal CT is the imaging of choice CT is the imaging of choice Brain abscess, encephalitis, toxoplasmosis Brain abscess, encephalitis, toxoplasmosis Meningeal Meningeal Lumbar puncture Lumbar puncture Neoplasm, CNS vasculitis, SAH Neoplasm, CNS vasculitis, SAH

9. Diagnosis Parameter (normal) BacterialViralNeoplasticFungal OP (<170 mm CSF) >300mm200mm200300mm WBC (<5mononuclear) >1000<1000<500<500 %PMN’s (0) >80%1-50%1-50%1-50% Glucose (>40mg/dL) <40>40<40<40 Protein (<50mg/dL) >200<200>200>200 Gram stain (-) +_-_ Cytology (-) __++

10. Diagnosis An aseptic profile An aseptic profile Must think about… Must think about… Partially treated bacterial infection Partially treated bacterial infection Bacterial infections adjacent to the subarachnoid space Bacterial infections adjacent to the subarachnoid space

11. Diagnosis Tests to order on the CSF Tests to order on the CSF Tube #1 cell count with diff Tube #1 cell count with diff Tube #2 protein,glucose Tube #2 protein,glucose Tube #4 cell count with diff, gram stain/culture Tube #4 cell count with diff, gram stain/culture Tube #3 Tube #3 Viral cultures Viral cultures Borrelia (lyme disease) Borrelia (lyme disease) India ink/cryptococcal antigen (immunocomp) India ink/cryptococcal antigen (immunocomp) Acid fast stain/culture for mycobacteria (TB) Acid fast stain/culture for mycobacteria (TB) Latex agglutination for bacterial Antigens Latex agglutination for bacterial Antigens PCR PCR Herpes, arbovirus Herpes, arbovirus

12. Lumbar Puncture Contraindications Contraindications Infection in overlying skin Infection in overlying skin Relative Relative Coagulopathy Coagulopathy Thrombocytopenia Thrombocytopenia If delay is anticipated obtain blood cultures and GIVE antibiotics If delay is anticipated obtain blood cultures and GIVE antibiotics You have 2 hours after ATB given before sensitivity is effected You have 2 hours after ATB given before sensitivity is effected

13. Lumbar Puncture Considerations for not obtaining CT before performing LP Considerations for not obtaining CT before performing LP Age <60 Age <60 Immunocompetent Immunocompetent No h/o CNS disease No h/o CNS disease No recent seizure (<1week) No recent seizure (<1week) Normal sensorium & cognitition Normal sensorium & cognitition No papilledema No papilledema No focal neuro deficits No focal neuro deficits

14. Treatment First priority First priority Antibiotics Antibiotics Second priority in some cases Second priority in some cases Anti-inflammatories Anti-inflammatories Third priority Third priority Counter the adverse effects of increased ICP & vasculopathy Counter the adverse effects of increased ICP & vasculopathy

15. Emperic Antibiotics Age/Special Gram Stain Drug 18-50y/oNegative Ceftriaxone 2g IV + vanco 1g IV or rifampin vanco 1g IV or rifampin >50 y/o NegativeCeftriaxone+ampicillin+ vanco or rifampin Recent penetrating head injury/ surgery/shunt Negative Vanco 25mg/kg then 19mg/kg using Matzke nonogram + ceftazidime ceftazidime immunocompromised Negative-------------------------------------  GPC------------------------------------------  GNC-----------------------------------------  GPR------------------------------------------  GNR-----------------------------------------  Vanco+ amp+ ceftazidime Ceftriaxone + vanco Pen G Amp + gent Cetazidime + aminoglycoside

16. Emperic Antivirals Concern of herpes Concern of herpes Acyclovir 10mg/kg IV Q 8 hours Acyclovir 10mg/kg IV Q 8 hours

17. Steroids Dexamethasone Dexamethasone 10mg IV 15 minutes prior to antibiotics 10mg IV 15 minutes prior to antibiotics Shown to decrease M&M in S. pneumoniae but NOT N. meningitidis Shown to decrease M&M in S. pneumoniae but NOT N. meningitidis N Engl J Med 2002; 347:1549-1556, Nov 14, 2002. N Engl J Med 2002; 347:1549-1556, Nov 14, 2002.

18. Complications Seizures Seizures Hyponatremia Hyponatremia SIADH SIADH CVA CVA Coagulopathies Coagulopathies Cognitive deficits, epilepsy, hydrocephalus, hearing loss affect 25% of survivors Cognitive deficits, epilepsy, hydrocephalus, hearing loss affect 25% of survivors

19. Chemoprophylaxis Household/school/daycare contacts last 7 days Household/school/daycare contacts last 7 days Direct exposure to secretions Direct exposure to secretions Kissing, sharing utensils/toothbrushes, mouth to mouth, intubation without a mask Kissing, sharing utensils/toothbrushes, mouth to mouth, intubation without a mask First line: rifampin 10mg/kg (max dose 600mg) Q12h x 4 doses First line: rifampin 10mg/kg (max dose 600mg) Q12h x 4 doses Alternative: ceftriaxone, cipro, sulfisoxazole Alternative: ceftriaxone, cipro, sulfisoxazole

20. Viral Meningitis

21. Viral Menigitis 85% secondary to 85% secondary to Echo- Echo- Coxsackie Coxsackie Entero- Entero- Also consider HSV, and EBV Also consider HSV, and EBV Neutrophils may predominate in the CSF in the first 24 hours Neutrophils may predominate in the CSF in the first 24 hours Consider starting ATB’s until cultures come back (-) Consider starting ATB’s until cultures come back (-)

22. Viral Encephalitis

23. Infection of brain parenchyma Infection of brain parenchyma Presents of neurological abnormalities distinguish it from meningitis Presents of neurological abnormalities distinguish it from meningitis

24. Epidemiology Incidence is 1/10 of bacterial meningitis Incidence is 1/10 of bacterial meningitis HSV-1, zoster, EBV,CMV, rabies, arbo HSV-1, zoster, EBV,CMV, rabies, arbo Arbo Arbo LAC (La Crosse)-diagnosed most frequently LAC (La Crosse)-diagnosed most frequently SEE(St Louis)-20% mortality in elderly SEE(St Louis)-20% mortality in elderly WEE(Western)- causes seizures in 90% of infected infants, permanent neuro deficits in 50% WEE(Western)- causes seizures in 90% of infected infants, permanent neuro deficits in 50% EEE(Eastern)- most devastating, mortality 70% EEE(Eastern)- most devastating, mortality 70% WNV(West Nile) WNV(West Nile)

25. Pathophysiology Portals of entry Portals of entry Arbo-transmitted by mosquitoes, ticks Arbo-transmitted by mosquitoes, ticks Rabies-bite by infected animal Rabies-bite by infected animal Hematogenous dissemination v. travel backwards on axons (HSV,HZV,rabies) Hematogenous dissemination v. travel backwards on axons (HSV,HZV,rabies) Dysfunction & damage caused by disruption of neural cell function & inflammation Dysfunction & damage caused by disruption of neural cell function & inflammation

26. Pathophysiology cont. Gray matter predominately affected Gray matter predominately affected Cognitive/psychiatric signs, lethargy, seizures Cognitive/psychiatric signs, lethargy, seizures White matter affected in post-infectious encephalomyelitis White matter affected in post-infectious encephalomyelitis

27. Clinical features New psych symptoms New psych symptoms Cognitive deficit (aphasia, amnesia, confusion) Cognitive deficit (aphasia, amnesia, confusion) Seizure Seizure Movement d/o Movement d/o

28. Diagnosis MRI-more sensitive than CT MRI-more sensitive than CT CT CT EEG EEG LP-findings consistent with aseptic meningitis LP-findings consistent with aseptic meningitis

29. Differential Exclude the killers Exclude the killers Bacterial meningitis & SAH Bacterial meningitis & SAH More meningeal symptoms More meningeal symptoms Lyme, TB, fungal, bacterial, viral, neoplastic Lyme, TB, fungal, bacterial, viral, neoplastic More parenchymal symptoms More parenchymal symptoms Abscess, bacterial endocarditis, post-infectious encephalomyelitis, toxic or metabolic encephalopathy Abscess, bacterial endocarditis, post-infectious encephalomyelitis, toxic or metabolic encephalopathy

30. Treatment HSV: acyclovir 10mg/kg IV HSV: acyclovir 10mg/kg IV CMV: ganciclovir CMV: ganciclovir Rabies/EEE/HSV  devastating & usually fatal or residual deficits Rabies/EEE/HSV  devastating & usually fatal or residual deficits

31. Brain Abscess

32. Focal pyogenic infection Focal pyogenic infection Pus-filled cavity ringed by granulation tissue & outer fibrous capsule surrounded by edematous brain tissue Pus-filled cavity ringed by granulation tissue & outer fibrous capsule surrounded by edematous brain tissue

33. Epidemiology Paranasal sinus focus Paranasal sinus focus 10-30 y/o 10-30 y/o Otic Otic Bimodal: 40 y/o Bimodal: 40 y/o

34. Pathophysiology Hematogenous spread Hematogenous spread 1/3 of cases 1/3 of cases Contiguous (middle ear, sinus, teeth) Contiguous (middle ear, sinus, teeth) 1/3 of cases 1/3 of cases Otogenic (Bacteroides)  temporal lobe/cerebellum Otogenic (Bacteroides)  temporal lobe/cerebellum Sinogenic & odontogenic(anaerobic & microaerophilic streptococci)  frontal lobe Sinogenic & odontogenic(anaerobic & microaerophilic streptococci)  frontal lobe

35. Clinical Features Classic triad Classic triad HA, fever, focal deficit HA, fever, focal deficit <1/3 of cases <1/3 of cases Toxic appearance is rare Toxic appearance is rare Seizures, vomiting, confusion, obtundation possible Seizures, vomiting, confusion, obtundation possible Frontal lobe-hemiparesis Frontal lobe-hemiparesis Temporal lobe- homonymous superior quadrant visual field deficit or aphasia Temporal lobe- homonymous superior quadrant visual field deficit or aphasia Cerebellum-limb incoordination or nystagmus Cerebellum-limb incoordination or nystagmus

36. Diagnosis CT with contrast CT with contrast LP contraindicated LP contraindicated Biopsy or aspiration for confirmation Biopsy or aspiration for confirmation

37. Treatment Presumed Source Primary Empiric Tx Alternative Tx Otogenic Cefotaxime 2g IV q8h Bactrim 5mg/kg IV q6h + Flagyl 1giv then 500mg q6 or chloramphenicol Sinogenic or odontogenic Pen 24 million units/d IV divided q4h + Flagyl 1g IV then 500mg q6h Pen (same dose) + Chloramphenicol 100mg/kg/d divided q6h Penetrating trauma or neurosurgery Nafcillin 2g IV q4h + Ceftazidime 2g IV q8h Vanco 15mg/kg (max 1g)IV q6h + Ceftazidime 2g IV Hematogenous Pen 24 million units/d divided q4h + Flagyl 1g then 500mg q6h Pen (same dose) + Chloramphenicol 100mg/kg/d divided q6h No obvious source Cefotaxime 2g IV q6h + Flagyl 1g IV then 500mg q6h No recommendations

38. Questions 1. CSF analysis returns with the following values: glucose 20 WBC 1200 Protein 300. This profile is consistent with 1. CSF analysis returns with the following values: glucose 20 WBC 1200 Protein 300. This profile is consistent with A. Bacterial meningitis A. Bacterial meningitis B. viral meningitis B. viral meningitis C. Fungal meningitis C. Fungal meningitis 2. Which of the following is an absolute contraindication to performing an LP 2. Which of the following is an absolute contraindication to performing an LP A. Coagulopathy A. Coagulopathy B. Infection of the overlying skin B. Infection of the overlying skin C. thrombocytopenia C. thrombocytopenia

39. Questions 3. T/F Steroids have been shown to decrease morbidity & mortality in meningitis caused by Strep pneumo 3. T/F Steroids have been shown to decrease morbidity & mortality in meningitis caused by Strep pneumo 4. T/F Brain abscesses are confirmed by LP. 4. T/F Brain abscesses are confirmed by LP. 5. Which antibiotic regimen should be initiated in an immunocompromised patient suspected of having bacterial meningitis without any allergies 5. Which antibiotic regimen should be initiated in an immunocompromised patient suspected of having bacterial meningitis without any allergies A. Pen G A. Pen G B. Ceftriaxone & vanco B. Ceftriaxone & vanco C. Vanco, gent, & ceftazidime C. Vanco, gent, & ceftazidime Answers: 1. A 2. B 3. T 4. F 5. C Answers: 1. A 2. B 3. T 4. F 5. C