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Integrated Course Microbiology & Pathology
Pathology
of
CNS Infections I
(viral etiology)Jaroslava Dušková
Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague
Portals of Entry to CNShematogenous (pyemia, sepsis, viremia)
directlyvia plexus chorioideus
local sourcedirectly (trauma)bone melting (sinusitis, otitis)vv. emissariaealong nerves (filla olfactoria)
CNS Inflammation
nonspecific– purulent
– nonpurulent
„specific“ (granulomatous)
circumscribed
diffuse
Haematoencephalic Barrier (1921)
capillary endothelia without fenestrations molecules traverse via pinocytosis leukocytes in inflammation cross via
emperipolesis
All infectious agents are able to cross :
Bacteria ( pyogenic, mycobacteria,treponemae, boreliae…) Viri (polio-, arbo-, herpes, CMV, HIV, morbilli, lyssa…) Fungi (candida, cryptococcus…) Protozoa (toxoplasma, plasmodium, amaebae,
trypanosoma…)
„Aseptic Meningitis“ – non purulent
meningeal inflammation caused by:
viruses - all
bacteria –treponemae- Lyme disease, syphilis
tumours – dissemination
drugs – e.g. ibuprofen
Macro: edema
Micro: lymphoplasmocellular infiltrate
Dg.: CSF – nonpurulent pleocytosis (lymphocytes, plasma cells,monocytes)
Prognosis: mostly favourable, rarely recurrences and intermeningeal fibrosis
Clinic: meningeal irritation
Morphological Features of Nonpurulent Encephalitis
Macroscopy - mostly non-characteristicMicroscopy
cellular infiltration proliferation of microglia neuronal changes inclusions white matter changes vascular component
Descriptive Classification of Nonpurulent Encephalitides according to prevailing morphological features
POLIOPAN encephalitisLEUCO
Recently – ETIOLOGY CLASSIFICATION
Poliotrophic Encephalitides
Poliomyelitis anterior acutaLyssaE. herpeticaE. cytomegalicaVaricella e. ------------Prionoses
Panencephalitides mostly poliotrophic (viral)
Tick-borne – Middle-European e.– Russian spring-summer e.
Mosquito-borne– Japanese– ecquine
mostly leucotropic (rickettsiae) SSPE van Bogaert, HIVRE
Leucoencephalitidesacute
para-infectious post-vaccination acute hemorrhagic leucoencephalitis
Hurst
chronic sclerosis cerebrospinalis multiplex
disseminata MS neuromyelitis optica Devic progressive multifocal encephalopathy
PME
Panencephalitides mostly poliotrophic (viral)
Tick-borne – Middle-european e.– Russian spring-summer e.
Mosquito-borne– Japanese– ecquine
mostly leucotropic (rickettsiae) SSPE van Bogaert, HIVRE
Rima BK, Duprex WP.: Morbilliviruses and Human Disease. J Pathol. 2006 Jan;208(2):199-214 CNS complications of measles
1. Acute Demyelinating EncephaloMyelitis ADEM 5-6days after the rash, 1:1000, perivascular demyel.
2. Measles Inclusion Body Encephalomyelitis MIBE 2-6 mths after inf. in immunocompromised. No hyperimmune
antibody response.
3. Subacute Sclerosing PanencEphalitis SSPE ~ 8 years after inf.. 1:25000. Hyperimmune response B cell AB
in both the serum and the CSF
Neuropathology of AIDS
Direct HIV effect
Opportune infections
Neoplastic processes
Neuropathology of AIDS
Direct HIV effect HIV encephalitis leucoencephalopathy vacuolar myelopathy neuropathy myopathy
vasculitides, AIDS-Dementia complex, pediatric AIDS
Nardacci R, Antinori A, Larocca LM, Arena V, Amendola A, Perfettini JL, Kroemer G, Piacentini M.: Characterization of cell death pathways in human immunodeficiency virus-associated
encephalitis. Am J Pathol. 2005 Sep;167(3):695-704.
~10% patients with AIDS suffer from HIV-associated dementia - a neurodegenerative syndrome:
cognitive decline, personality change, and motor deficits.
HIV-associated encephalitis (HAE) characterized by formation of multinucleated giant cells or syncytia.
Neuropathology of AIDSOpportune infections
parasites: toxoplasmosismycoses, mycobacteria, spirochetes:
Aspergillus, Candida, Cryptococcus Mycobacterium avium intracellulare Treponema pallidum
viral Cytomegalovirus Herpes simplex Herpes zoster Polyoma PML
Neuropathology of AIDS
TumoursPrimary cerebral lymphoma
mostly B type often multicentric EB virus proven in some Kaposi sarcoma (HHV8 related)
exceptionally meta to CNS
Commonest Causes of a Mass Lesion in the Brain of a Patient with HIV
toxoplasmosis primary CNS lymphoma fungal infection (esp.
Aspergillus, Cryptococcus)
tuberculoma PML CMV infection pathology not (directly)
related to HIV (e.g. glioma, metastatic cancer)
DIAGNOSIS stereotactic biopsy intraoperative cytology CSF investigation therapeutic trial
followed by biopsy
COMBINED LESIONS!!!
Elison D.,Love S. et al.: A reference text of CNS pathology. 2nd ed. Mosby, 2004
Leucoencephalitidesacute
para-infectious post-vaccination acute hemorrhagic leucoencephalitis
Hurst
chronic sclerosis cerebrospinalis multiplex
disseminata MS neuromyelitis optica Devic progressive multifocal encephalopathy
PME
Inflammation – autoimmune Organ autoimmune diseases – CNS
ANTIBODY
acetylcholin rec.
basic myelin protein
DISEASE
myasthenia gravis
disseminated sclerosis
decreased– opportune infections
increased – autoimmune damage
Sclerosis cerebrospinalis multiplex disseminata MS
Def.
chronic autoimmune disease with myelin breakdown
Sclerosis cerebrospinalis multiplex disseminata - viral infection influence (morbilli, herpes, EB…bacteria?... )
Pathogenesis
interaction of the macroorganism and virus – limited AB production
(only 10-20% produced viruses are virulent)
mutation of the virus & immunosupresion (age, pregnancy, stress, other diseases….)
Sclerosis cerebrospinalis multiplex disseminata MSClinical features Disorders of
Course
sight sensation motorics
cont. progressive
saw-like
Sclerosis cerebrospinalis multiplex disseminata MS
Morphological features – myelinic plaques
acute chronic
Sclerosis cerebrospinalis multiplex disseminata MS
Pathogenesis genetic predisposition viruses
MS – viral influence (morbilli, herpes,…)
Pathogenesis interaction macroorganism x virus
limited production of Ig (only 10-20% produced viruses are virulent)
virus mutation & immunosuppression (age, pregnancy, stress, other disease)
MS – viral influence (2)
Pathogenesis infection of endothelia – microangiitis hematoencephalic barier disorder serum and CSF CD4, CD8
(mirror image to AIDS)
