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CNS Infections

CNS Infections. ELS Wednesday, August 6th 2008 Amal Al-Hashmi. Outline. Viral meningitis Viral encephalitis Bacterial meningitis Etiology Pathophysiology Clinical Presenation Pathophysiology Diagnostic tools CT, MRI head, LP,EEG Treatment. Viral meningitis. Definition

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CNS Infections

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  1. CNS Infections ELS Wednesday, August 6th 2008 Amal Al-Hashmi

  2. Outline • Viral meningitis • Viral encephalitis • Bacterial meningitis • Etiology • Pathophysiology • Clinical Presenation • Pathophysiology • Diagnostic tools • CT, MRI head, LP,EEG • Treatment

  3. Viral meningitis • Definition an inflammatory response to viral infection of leptomeningeal cells and the subarachnoid space • account for the majority, at least 70%, of cases of aseptic meningitis

  4. Etiology • In Europe and US nonpolio enteroviruses are the most common case of viral meningitis ( Kupila et al 2006) for both children & adults (coxsackie & enteric cytopathogenic human orphan virus [echovirus]), are the most common causal agents

  5. Etiology followed by mumps arboviruses herpesviruses lymphocytic choriomeningitis HIV at the time of seroconversion

  6. Clinical presentation • Children under 2 years of age show fever, irritability, or seizures , but may never develop signs of meningeal irritation • Adult pts present with fever, malaise, headache, nausea, vomiting, nuchal rigidity, & photophobia

  7. CSF 1- slightly elevated opening pressure 2- mild to moderate pleocytosis with 10–500 white blood cells (WBC)/µl, predominantly lymphocytes 3- mildly elevated protein (<100 mg/dl), 4- normal glucose

  8. CSF • RT-CRP has now replaced viral cultures as diagnostic procedure of choice for establishing enteroviral infections ( Ramers et al 2000) • computed tomography or magnetic resonance imaging (MRI) scans in general are normal

  9. Viral Encephalitis • Etiology • C/F • CSF findings • Neuroimaging

  10. Viral Encephalitis • Most common cause are herpes simplex and arboviruses • HSV-1 most common cause of fetal encephalitis in US accounting for 10% overall& 90% in adult frequency 1/250,000 • HSV-2 more commonly isolated in monophasic or recurrent meninigitis & congenitally acquired neonatal HSV meningoencephalitis

  11. Viral Encephalitis • C/F Fever 90% Headache 80% Altered mentation 70% Personality changes 70-80% Seizures 40-67% Memory disturbance 25-45% Motor deficit 30-40% Aphaisa 33% Olfactory hallucination

  12. Viral Encephalitis • No set of signs or symptoms is pathognomonic of HSE (Whitly 2006)

  13. CSF • increased opening pressure • Normal glucose • Moderalty elevated protien • Lymphocytic pleocytosis 10-1000/microlitter • Xanthochromia and red cells may occur • Cultures negative in 95%

  14. CSF • PCR of HSE is the diagnostic procedure of choice ( lakeman & whitely 1995) • False negative ( Weil et al. 2002)

  15. Neuroimaging • particularly MRI,may show temporal or orbitofrontal cortex enhancement or edema in HSE ( Raschilas et al 2002) • In most other acute viral encephalitis, neuroimaging findings are nonspecific • Brain MRI or CT serve to exclude brain abscess, subdural empyema, cranial extradural abscess, or septic venous thrombosis

  16. EEG • Diffuse slowing • Focal abnormalities in the temporal region ( 75% with +ve PCR) • PLEDS

  17. Brain Biopsy • Atypical cases • Poor response to treatment • Findings: hemorrahgic necrosis HSV antigen in infected neurons acidophilic intranuclear inclusions

  18. Treatment • Empiric therapy with acyclovir should be started immediately • Stander Rx course is IV acyclovir 10mg/kg Q8h in adults 20mg/kg Q8h in neonate and children • Duration 14-21 days

  19. Treatment • Steroid ? Retrospective studies suggested no obvious harm and be some benefit ( Kamie et al 2006) Controlled clinical trails are needed

  20. Prognosis • Mortality rate in untreated cases is 70% which reduced to 19-27%with rx • Morbidity remains high only 37% of all pt PCR proven and treated with acyclovir survive with no or mild residual deficits (Raschilas et al2002)

  21. Prognosis • Clinical relapse can occur and more often in children and neonate • Consider Foscarnet in cases of acyclovir resistant stains or in who are allergic

  22. Bacterial meningitis • Incidence of 3-5/100 000/year in US (quagliarello 1997) • More than 1500 death/yr in US

  23. Etiology - General • Pneumococcus (Streptococcus Pneumoniae) • Most common in adults >20 • Account for ½ of reported cases • 2° to pneumonia/otitis, splenectomy/DM2 • ’ing incidence of pen-resistance in pneumococcus (25-45% to pen, 10% to Ceph,+ to chloramphenicol)

  24. Etiology - General • HiB (Haemophilus Influenzae type B) • Before vaccination, most common case in US 45% of meningitis caused by Hib • Now accounts for less than 10%– • still in elderly, HIV pts

  25. Etiology - General • Meningococcus (Neisseria Meningitidis) • Mainly children and young adults (army/college) • 2° to asymptomatic nasopharyngeal colonization

  26. Etiology – Special Populations • Neonate • GBS, E. coli & other gram neg., Listeria (10%) • Post head trauma/Neurosurgery • Staph Aureus & CNS, Enteric gram neg. • Elderly • Listeria and Hib • Listeria = Impaired cellular immunity • Pregnancy, Chronic disease, Elderly, Alcohol

  27. Clinical Presentation • Triad of Headache, fever and neck stiffness: 85% of patients • N/V, photophobia, myalgia ( common) • Alteration in LOC, Seizures (40%) • Nuchal rigidity: resistance to passive flexion • Kernig’s: extension of the knee with thigh flexed pain, neck flexion • Brudzinsky’s • Flexion of neck causes hip flexion

  28. Clinical Presentation • Cranial nerve palsies 3rd, 6th , 7th (10-20%) • Occasionally focal neurological deficit hemiparesis, dysphasia

  29. Clinical Presentation • Classical c/f are commonly absent in neonates look for high pitched crying, refusal to feed, irritability • In elderly less act onset of lethrgy, mild or no fever

  30. Certain clinical features • Promient rash particually extrimities (Meningococcus) erythemaous, macular evolving into petechial • Rhinorrhea or otorrhea with S pneumoniae

  31. Pathophysiology • Bacteria spread by droplets and colonize nasopharynx • bacteremia then meningeal spread thru chroroid plexus epithelial cells • Multiply rapidly because of absence of immune cells • Lysis of bacterial cell wall in SAS • Stimulate microglia inflammatory cytokine production of IL-1 and TNF

  32. Roos, seminars in neurology 2000

  33. Pathophysiology • Alteration of BBB w/ vasogenic edema + loss of autoregulation AND entry of PMN w/ cytotoxic edema SO formation of purulent exudate  Hydrocephalus  narrows arteries in SAS and invades wall (vasculitis; leads to CVA)  Continous rise of ICP and coma

  34. CSF • ↑ pressure 20-50 mm H20 • ↑ WBC (100-10000 wbc/mm3, mainly PMN) • ↓ glucose (less than 40% of serum glu) • ↑ Protein (1.0-5.0 mg/dl) • Positive gram stain/culture in 70-90% • Less if Abx before; sterile only after 12h • Bx if skin lesions

  35. Diagnosis • Blood Cultures (50%) • Abx before LP if CT/LP delay Tx (no change in WBC +/- in sterility for hours) • +/- Decadron • CT head (?) • Lumbar Puncture

  36. CT Head before LP? • CT will be abnormal, if you have : • Seizure • clinical evidence of increased ICP • Hx of CNS disease • Immuncompromised status • Age>60 • Abnormal neurological exam (including mental status) Hasbun et al. CT head before LP in suspected meningitis. NEJM 345:1727, 2001 Kastenbauer et al. CT head before LP in suspected meningitis. NEJM 346:1248, 02

  37. CT SCAN PRIOR TO LUMBAR PUNCTURE IN SUSPECTED MENINGITIS • 235 patients with suspected meningitis underwent CT • 56/235 (24%) had abnormal CT; 11 (5%) with mass effect Hasbun et al. NEJM 2001;345:1727.

  38. CT SCAN PRIOR TO LUMBAR PUNCTURE IN SUSPECTED MENINGITIS • 96 patients without above features who underwent CT • 93 had normal CT; 1 had mass effect • All had lumbar puncture with no evidence of brain herniation Hasbun et al. NEJM 2001;345:1727.

  39. CT before LP • Kastenbauer: Nothing predicts herniation (Abnormal CT in 2/10 herniations and 27/65 w/ no herniation) of Kastenbauer et al. N Engl J Med 2002;346(16):1248-1251. (189K)

  40. Treatment

  41. Treatment • Based on age • Always bactericidal • Consider intrathecal Vanco • Alternatives: • Cefepime or meropenem instead of 3rd generation Ceph • If severe Pen allergy: Vanco + chloramphenicol or Vanco + septra (listeria) • 3rd generation Cephalosporin • Ceftriaxone 2g q12h – jaundice in neonates • Cefotaxime 2g q4h • Ceftazidime 2g q 8h

  42. Tx of contacts • Contact Public Health for meningococcus and HiB • Need to treat close contacts (potentially share secretions) • Rifampin bid for two days C • Or Cipro 500mg once • Or zithromax 500mg once

  43. Prevention • Pneumovax for surgical or functional asplenia (sickle cell, chronic illness, immunosuppression, older age…)

  44. Steroids • Morbidity and mortality of meningitis related of inflammatory reaction rather than bacteria themselves • Decadron inhibits IL-1 and TNF m-RNA production and  CSF outflow resistance and stabilizing BBB • Lots of small studies 1950’s-2002; big studies are rare, especially in adults.

  45. Steroid • The available evidence on adjunctive dexamethasone therapy confirms a benefit for treating H influenza type b in reducing audiological sequelae and suggest benefit in reducing the audiological and neurological sequelae in H influenza type b and pneumococcal in children • (sebire et al 2006) …….( weisfelt et al 2006)

  46. Cochrane Review 2003 • 18 RCT • Mainly kids • General • Lower mortality RR 0.76 [.59-.98] • Hearing loss 0.36 [.22-.60] • Neuro Sequelae 0.66 [.44-.99] • In Children • Lower hearing loss in non Hib meningitis 0.42 [.2 - .89] • In adults • Lower mortality 0.48 [0.24-0.96]

  47. Systematic Review in adults • 5 RCT in adults • Overall mortality and neuro sequelae 0.6 • Pneumococcus mortality 0.5 • Meningococcal sequelae 0.5 and mortality 0.9 • No increased side effects with steroids

  48. Vanco level controversy • Experimental evidence of decreased absorption if steroids given • One RCT study in children demonstarted reliable penetration of vanco if 60mg/kg doses used. • 4/11 pts in adults failed vanco with steroids but used lower dosages

  49. Steroids Do not use if immunosuppressed

  50. Thank You! Questions?

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