1 / 52

CNS infections

CNS infections. Dr. Amy Yu May 11, 2011. Outline. Case-based with specific teaching points Reference AAN Continuum for CNS infections from 2006 Bradley Chapter 57. Case 1. 58M HCT for myelodysplastic syndrome HCT 3 wks ago On cyclosporine + mycophenolate H/A & confusion x 3d

farhani
Download Presentation

CNS infections

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. CNS infections Dr. Amy Yu May 11, 2011

  2. Outline • Case-based with specific teaching points • Reference • AAN Continuum for CNS infections from 2006 • Bradley Chapter 57

  3. Case 1 • 58M HCT for myelodysplastic syndrome • HCT 3 wks ago • On cyclosporine + mycophenolate • H/A & confusion x 3d • Exam: T 38, disoriented, 0/3 recall, normal motor, sensory, coordination • Next step?

  4. Case 1 • CSF studies • 720 WBC (92% lymphocytes) • Gluc/Prot normal • Gram stain negative • Diagnosis? • Treatment?

  5. Case 1 • Patient fails to improve on Acyclovir, day 3 • Continues to be febrile • Continues to be confused • How do you confirm the diagnosis of Herpes encephalitis? • 8 human herpes virus • Herpes group PCR

  6. HHV-6 encephalitis • HHV-6 is a common cause of encephalitis in the immunocompromised • Population sero-prevalence is >90% (most 1ry infection before age 2) • Predilection for temporal lobes • Dx: viral PCR amplification in CSF & confirm with CSF HHV-6 IgM • CSF HHV-6 nucleic acid is not definitive evidence that it is the etiological organism of the encephalitis • Rx: Ganciclovir or Foscarnet IV • Acyclovir is not active against virus • Repeat CSF analysis in 14-21 days • D/C therapy when CSF cleared

  7. Why not acyclovir? • Acyclovir is converted into acyclo-guanosine monophosphate (acyclo-GMP) by viral thymidine kinase • 3000x more effective than cellular thymidine kinase • Further phosphorylated into acyclo-GTP • Very potent inhibitor of viral DNA polymerase • Resistance to acyclovir: deficiency or mutation to viral thymidine kinase • HHV-6 lacks thymidine kinase

  8. Transplant patients • Expansion of inclusion criteria • Increase lifespan of transplant recipients • More transplant institutions • Neurological complication • 42% solid organ transplant (SOT) • 65% hematopoietic cell transplant (HCT)

  9. Timing of CNS infection s/p tx • Early • Nosocomial: line infections, ventilator-assocaited pneumonia • Donor-to-recipient viral transmission • Middle • Viral and fungal opportunistic infections peak • Late • Related to evidence of graft rejection (serology, organ failure, biopsy)  degree & type immunosuppression • Viral and fungal

  10. Continuum CNS infections 2006

  11. Hematopoietic cell transplant • Chemotherapy +/- radiation  cells or cord blood infusion • 11% had neurological infection • 26% death due to CNS infection • Most susceptible immediately after transplant •  Risk if donor and recipient are genetically closer • Autologous: least immunosuppressed • Reduced-intensity SCT • Less marrow and immunosuppression • More GVHD  more long-term immune suppression

  12. Travel history • Coccidioides, histoplasmosis, WNV • Risk of zoonoses • Neurobrucellosis (cattle) • Bartonella, Toxoplasmosis (cats litter, raw meat) • Listeriorisis (unpasteurized dairy) • Immunosuppressant & prophylaxis • Level and degree of immunosuppression

  13. Take home message • Immunocompromised patients • Common and uncommon infections • Concurrent multiple infections • Culture +/- biospy • Blood, CSF, +/- sputum, urine, skin lesions • Start with broad-spectrum coverage • Bacteria • Virus • Fungus • Protozoal

  14. Case 2 • 57F, SLE, Rx chronic prednisone + cyclophosphamide • 3 d h/a & confusion • Acute seizure today • CXR RLL nodule • Ring-enhancing lesions • RLL opacification

  15. Case 2 Which of the following is the least likely pathogenic organism? • Nocardia • Listeria • Aspergillus • Tuberculosis • Mucor

  16. Case 2 Which of the following is the least likely pathogenic organism? • Nocardia • Listeria basal meningitis • Aspergillus • Tuberculosis • Mucor Don’t forget neoplasm!

  17. Nocardia • Pleomorphil, acid-fast bacillus • Often late infection with chronic immune suppression • 90% of CNS Nocardia have associated pulmonary findings • Dx: Culture from BAL or biopsy • Rx: Sx drainage, high-dose TMP-SMX for > 6 months • Px: Fair if dx early!!!

  18. Aspergillus • #1 cause of focal CNS infection in transplant population • Angioinvasive fungus  CVA! • Dx: sputum, BAL, bx culture • Galactomannan • Ab immunoassay to detect a polysaccharide marker on Aspergillus cell wall surface • Serum sensitivity and specificity >80% • BAL sensitivity 75% • CSF? No data • Fungal culture, Aspergillus PCR • Rx: Ampho B, Caspofungin, Voriconazole

  19. Case 2 Which other organism is angioinvasive? • CMV • West Nile virus • Cryptococcus • Toxoplasmosis • Mucor

  20. Case 2 Which other organism is angioinvasive? • CMV • West Nile virus • Cryptococcus • Toxoplasmosis • Mucor (Zygomycetes class: Rhizopus, Mucor, Absidia, Cunningbamella)

  21. Take home message • Narrow your differential diagnosis • Clinical setting (age, degree + type of immunosuppression) • Neurological condition (meningitis, abscess, encephalitis, ischemia, myelitis) • Be alert for associated findings • Respiratory, GI symptoms • Rash, retinitis, weakness,… • E.g. Leukopenia + thrombocytopenia + petechial rash = ? Rocky mountain spotted fever!

  22. Case 2 • Who has prescribed Prednisone for > 1 month? • Who has prescribed PCP prophylaxis? • Who needs Septra?

  23. Who should receive PCP prophylaxis? • Prednisone ≥20 mg QD equivalent ≥ 1 month • Immunocompromised state • Alemtuzumab: minimum 2 mths after completion of therapy or until the CD4 count is >200 • Temozolomide + Rtx until recovery of lymphopenia • ALL & Allo HCT (on immunosupp and/or the CD4 count is <200), selected autologous HCT recipients • SOT (min 6-12 mths + periods of high doses of immunosuppressive medications eg acute rejection) • Certain primary immunodeficiencies • Combination with 2nd immunosuppressive drug • E.g. Cyclophosphamide (not MTX) • PM/DM + IPF may benefit

  24. Prophylaxis for the MG? • Dr. Chalk says “No.” • 1 case report • Ruiz-Ruiz, J. Miastenia gravis y neumonia por Pneumocystis carinii. Revista de Neurologia. 25(148):2069-70, 1997 Dec.

  25. Prophylaxis for CNS infections • Acyclovir • HSV 1 and 2 • Antifungal (e.g. Fluconazole) • Candida • TMP-SMX (Septra) • Listeria, nocardia

  26. Case 3 • 70M, presents in midsummer • Confusion, left LE weakness, diplopia, fever (39C x 3d) • What do you want to know? • CSF: 100 WBC (PMN predominance), glucose normal, protein slightly elevated, Gram stain negative

  27. Case 3 • Altered mental status • No clear cranial neuropathy • Left leg flaccid weakness • DTR 0 • Kinetic tremor

  28. West Nile virus • Arboviruses, single-stranded RNA virus • Vectors: mosquito and tick • Reservoirs: birds, mammals • 3 primary families • Togavirus • Flaviviruses (e.g. WNV, St Louis encephalitis) • Alphaviruses (e.g. Eastern equine encephalomyelitis) • Reovirus • Bunyavirus (e.g. California encephalitis virus)

  29. West Nile virus • #1 cause epidemic meningoencephalitis NA • 1st isolated in West Nile province of Uganda in 1937 • 1999 1st case in NA (New York state) • 2002 1st case in Canada (Quebec/Ontario) • Most widely distributed of all arboviruses • Waves of outbreak • Identified all parts of the US except Hawaii, Alaska, Washington

  30. West Nile virus • 80% remain asymptomatic • 20% self-limited flulike illness • Fever, h/a, myalgia, GI sxs, 50% non-specific rash • <1% Neuroinvasive presentation • Aseptic meningitis, meningoencephalitis • Encephalitis age>50 RR 20 folds! • Acute flaccid paralysis syndrome  Ddx?? • Brainstem encephalitis, movement disorder, CN palsies, polyneuropathy, optic neuritis • Varies with epidemic season, locale

  31. West Nile virus • CSF • Pleocytosis (PMN or lymphocytic) • Unique: plasmacytoid appearance of lymphocytes • Elevated protein • Normal glucose • CSF for West Nile virus IgM is diagnostic • MRI: usually normal • EEG: diffuse irregular slowing in encephalitis • Seizures are rare

  32. West Nile virus • Treatment is supportive • No person-to-person transmission reported • Ongoing studies • Passive immunization, interferon alpha, vaccine development • Mortality: 2-7% • 12-15% due to encephalitis • Long-term fatigue, myalgia, residual tremor & parkinsonism

  33. Rabies • Should be considered in any rapidly progressive encephalitis • Invariably fatal (1 case of survival reported in 2004) • Retrograde axonal transport • 1ry carriers in US: bats, raccoons, foxes, coyotes, and skunks, not rodents • Central & South America: dogs and cattles • 8000 cases of rabies/yr in wild & domestic animals in US & Puerto Rico

  34. Rabies • Many cases of confirmed rabies have bat exposure history • Often not evident on history from patient • Diagnosis: ab staining or PCR on nuchal skin bx, corneal smears, serum, buccal mucosa • Gold standard: brain biopsy with direct immunofluorescent antibody against rabies • Best treatment: Post-exposure prophylaxis • Vaccine and immune globulin

  35. Take home message – Encephalopathy • Infectious encephalitis • Fever, seizures, focal neuro signs, abnormal CSF • Autoimmune encephalopathy • ADEM • Steroid-responsive • Paraneoplastic • Seizure disorder • Metabolic/Toxic disturbances

  36. Encephalitis etiologies • Glaser et al. California Encephalitis Project 1998-2000. Clin Infect Dis 2003 • 9% viral • 3% bacterial • 1% parasitic • 10% non-infectious • 3% non-encephalitic infections • Urgent: treatable life-threatening etiology • Bacterial meningitis • Herpes encephalitis

  37. Encephalitis therapy • Antiviral agents • Acyclovir, Gancyclovir, etc. • Seizure control • Antipyretics • Monitor for SIADH • Monitor for increased ICP • Corticosteroids controversial

  38. Subacute/Chronic meningitis • A mimick of encephalitis

  39. ID of organism from CSF establishes the dx, but… • Organism colony in low number • Bound to meninges, in granulomas, in exudates • Fastidious and difficult to isolate • Special culture media, long incubation time, may degenerate if sample refrigerated • CSF nucleic acid or protein • Detection of IgM ab usually identifies agent (v. large molecule that poorly crosses the BBB) • PCR may detect virus that may not be the causative agent

  40. Subacute/Chronic meningitis • Infectious • Virus, bacteria, rickettsia, fungus, parasite • Suspected infectious • Neurosarcoidosis, Behcet’s, VKH syndrome, Mollaret’s meningitis • Non-infectious • Vasculitis (GCA, amphetamine/cocaine) • CT disease (SLE) • Chemical (dermoid cyst) • Iatrogenic (TMP-SMX, IVIG, craniotomy) • Neoplastic (Leptomeningeal metastasis) • Vascular (Leaky aneurysm)

  41. CSF profile • PMN  Mononuclear WBC • Most viral infections • Except HIV associated CMV radiculitis and West Nile virus encephalitis • Neutrophil predominance • Bacteria, most fungus, non-infectious causes • >10% eosinophilia • Certain fungus (Coccidioides immitis) • Most parasites (Angiostrongylus, Echinococcus, Schistosoma, Taenia, Trichinella) • Some non-infectious causes (SLE, lymphoma)

  42. Neurological examination • CN palsies – basilar meningitis (or  ICP) • TB, Lyme, fungal, parasites • Neurosarcoidosis, neoplastic meningitis • Focal signs (hemiparesis, aphasia, VF defect) • Tuberculoma, abscess, infarction, hemorrhage • Ophthalmological examination • Papilledema • Retinitis (CMV, histoplasmosis) • Iritis or uveitis (Behcet’s, sarcoidosis, syphilis, Sjogren)

  43. Don’t forget – General examination • Lungs, joints, and skin • Unusual skin lesion or nodule  biopsy • Swollen, warm joints  XRay & aspirate • Pulmonary illness  Bronchoscopy & consider TTNA/open biopsy

  44. Meningeal biopsy • Yield of the biopsy dependant on MRI scan with gadolinium (Cheng et al, 1994) • 80% if focal areas of meningeal enhancement • 10% if no enhancement is seen • Open or stereotaxic • Yield is slightly higher if posterior fossa • Include some underlying brain • Common diagnoses • Neurosarcoidosis, hypertrophic pachymeningitis, leptomeningeal metastasis, vasculitis • Candida, Aspergillus, Zygomycetes, and Acanthamoeba +/- TB, Histoplasma, Blastomyces, Coccidiodes

  45. What is the #1 cause of chronic meningitis world-wide? • Treponema pallidum • Borrelia burgdorferi • Mycobacterium tuberculosis • Human immunodeficiency virus • Cryptococcus neoformans

  46. What is the #1 cause of chronic meningitis world-wide? • Treponema pallidum • Borrelia burgdorferi • Mycobacterium tuberculosis • Human immunodeficiency virus • Cryptococcus neoformans

  47. Tuberculous meningitis • >50% active TB meningitis do not have an active pulmonary infection • CXR: look for calcified mediastinal LN (Ghon complexes) • PPD positive in 50% • CSF PCR assay available • Sensitivity 56% (same as culture, but result available in days vs. 3-6 weeks), Specificity 98% • Culture still needed for sensitivity profile • If high-grade meningitis and RF for TB  treatment is usually recommended • Role of empiric corticosteroids is unclear

More Related