1. Integrated Course Microbiology & Pathologyof
CNS Infections I
(viral etiology)
Jaroslava Dušková
Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague

2. Portals of Entry to CNS hematogenous (pyemia, sepsis, viremia)
directly
via plexus chorioideus
local source
directly (trauma)
bone melting (sinusitis, otitis)
vv. emissariae
along nerves (filla olfactoria)

3. CNS Inflammation nonspecific circumscribed „specific“ (granulomatous)
purulent
nonpurulent
„specific“ (granulomatous)
circumscribed
diffuse

4. 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…)

5. „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)
Clinic: meningeal irritation
Prognosis: mostly favourable, rarely recurrences and intermeningeal fibrosis

6. Morphological Features of Nonpurulent Encephalitis
Macroscopy - mostly non-characteristic
Microscopy
cellular infiltration
proliferation of microglia
neuronal changes
inclusions
white matter changes
vascular component

7. POLIO PAN encephalitis LEUCO
Descriptive Classification of Nonpurulent Encephalitides according to prevailing morphological features
POLIO
PAN encephalitis
LEUCO
Recently – ETIOLOGY CLASSIFICATION

8. Poliotrophic Encephalitides
Poliomyelitis anterior acuta
Lyssa
E. herpetica
E. cytomegalica
Varicella e.
Prionoses

9. Panencephalitides mostly poliotrophic (viral)
Tick-borne
Middle-European e.
Russian spring-summer e.
Mosquito-borne
Japanese
ecquine
mostly leucotropic (rickettsiae)
SSPE van Bogaert, HIVRE

10. Leucoencephalitides acute para-infectious post-vaccination
acute hemorrhagic leucoencephalitis Hurst
chronic
sclerosis cerebrospinalis multiplex disseminata MS
neuromyelitis optica Devic
progressive multifocal encephalopathy PME

11. Panencephalitides mostly poliotrophic (viral)
Tick-borne
Middle-european e.
Russian spring-summer e.
Mosquito-borne
Japanese
ecquine
mostly leucotropic (rickettsiae)
SSPE van Bogaert, HIVRE

12. CNS complications of measles
Rima BK, Duprex WP.: Morbilliviruses and Human Disease J Pathol Jan;208(2):
CNS complications of measles
Acute Demyelinating EncephaloMyelitis ADEM
5-6days after the rash, 1:1000, perivascular demyel.
Measles Inclusion Body Encephalomyelitis MIBE
2-6 mths after inf. in immunocompromised. No hyperimmune antibody response.
Subacute Sclerosing PanencEphalitis SSPE
~ 8 years after inf.. 1: Hyperimmune response B cell AB in both the serum and the CSF
Morbilliviruses are a group of viruses that belong to the family Paramyxoviridae. The most instantly recognizable member is measles virus (MV) and individuals acutely infected with the virus exhibit a wide range of clinical symptoms ranging from a characteristic mild self-limiting infection to death. Canine distemper virus (CDV) and rinderpest virus (RPV) cause a similar but distinctive pathology in dogs and cattle, respectively, and these, alongside experimental MV infection of primates, have been useful models for MV pathogenesis. Traditionally, viruses were identified because a distinctive disease was observed in man or animals; an infectious agent was subsequently isolated, cultured, and this could be used to recapitulate the disease in an experimentally infected host. Thus, satisfying Koch's postulates has been the norm. More recently, particularly due to the advent of exceedingly sensitive molecular biological assays, many researchers have looked for infectious agents in disease conditions for which a viral aetiology has not been previously established. For these cases, the modified Koch's postulates of Bradford Hill have been developed as criteria to link a virus to a specific disease. Only in a few cases have these conditions been fulfilled. Therefore, many viruses have over the years been definitely and tentatively linked to human diseases and in this respect the morbilliviruses are no different. In this review, human diseases associated with morbillivirus infection have been grouped into three broad categories: (1) those which are definitely caused by the infection; (2) those which may be exacerbated or facilitated by an infection; and (3) those which currently have limited, weak, unsubstantiated or no credible scientific evidence to support any link to a morbillivirus. Thus, an attempt has been made to clarify the published data and separate human diseases actually linked to morbilliviruses from those that are merely anecdotally associated.
ADEM vždy nesmrtí, MIBE a SSPE ano.

13. Neuropathology of AIDS
Direct HIV effect
Opportune infections
Neoplastic processes

14. Neuropathology of AIDS
Direct HIV effect
HIV encephalitis
leucoencephalopathy
vacuolar myelopathy
neuropathy
myopathy
vasculitides, AIDS-Dementia complex, pediatric AIDS

15. cognitive decline, personality change, and motor deficits.
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 Sep;167(3):
~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.
HIV enters the CNS via macrophages, resides in them and microglia (= resid. mf). Neurons affected mainly by chemokines, cytokines endoth. adh. molecules

16. Neuropathology of AIDS
Opportune infections
parasites: toxoplasmosis
mycoses, mycobacteria, spirochetes:
Aspergillus, Candida, Cryptococcus
Mycobacterium avium intracellulare
Treponema pallidum
viral
Cytomegalovirus
Herpes simplex
Herpes zoster
Polyoma PML

17. Neuropathology of AIDS
Tumours
Primary cerebral lymphoma
mostly B type
often multicentric
EB virus proven in some
Kaposi sarcoma (HHV8 related)
exceptionally meta to CNS

18. 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)
COMBINED LESIONS!!!
DIAGNOSIS
stereotactic biopsy
intraoperative cytology
CSF investigation
therapeutic trial followed by biopsy
Elison D.,Love S. et al.: A reference text of CNS pathology. 2nd ed. Mosby, 2004

19. Leucoencephalitides acute para-infectious post-vaccination
acute hemorrhagic leucoencephalitis Hurst
chronic
sclerosis cerebrospinalis multiplex disseminata MS
neuromyelitis optica Devic
progressive multifocal encephalopathy PME

20. Inflammation – autoimmune Organ autoimmune diseases – CNS
ANTIBODY
acetylcholin rec.
basic myelin protein
DISEASE
myasthenia gravis
disseminated sclerosis

21. decreased– opportune infections
Immunity
increased – autoimmune damage

22. Sclerosis cerebrospinalis multiplex disseminata MS
Def.
chronic autoimmune disease with myelin breakdown

23. 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….)
v Evropě prevalence kolísá kolem 1 promile

24. Sclerosis cerebrospinalis multiplex disseminata MS
Clinical features
Disorders of
Course
sight
sensation
motorics
cont. progressive
saw-like

25. Sclerosis cerebrospinalis multiplex disseminata MS
Morphological features
myelinic plaques
acute
chronic

26. Sclerosis cerebrospinalis multiplex disseminata MS
Pathogenesis
genetic predisposition
viruses

27. 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)

28. MS – viral influence (2) Pathogenesis
infection of endothelia – microangiitis
hematoencephalic barier disorder
serum and CSF CD4, CD8
(mirror image to AIDS)

29. Thank You