Central Nervous System 4. Infections

1. Central Nervous System4. Infections

4. BRAIN ABSCESS  space occupying lesion MCC Streptoc. & Staphyloc. Predisposing conditions: Acute bacterial endocarditis. Cyanotic Congenital Heart Diseases (right to left shunt). Blood bypassing filtering action of lung and go directly to brain Chronic pulmonary suppurations. Lung abscess, cystic fibrosis Direct spread: otitis media, mastoiditis or sinusitis. Clinical picture: Focal neurologic deficits ?ICP, ?CSF protein & ?cell count, but normal glucose. Morphology: Central focus of suppuration, surrounded by edema Later a fibrous capsule & reactive gliosis. Fibroblasts from larger vessels of brain try to wall of infection to form fibrous cap Brain has no fibroblasts however in an abscess fibroblasts from the BV form fibrosis. Other damage has liquefaction necrosis

5. BRAIN ABSCESS  space occupying lesion Complications: Herniation of fibrous capsule Abscess rupture: ventriculitis, meningitis Rupture into left temporal horn of lateral ventricle causing ventriculitis ? usually a fatal complication Prognosis: With surgery & antibiotics mortality rate is < 10%

6. VIRAL ENCEPHALITIS (VE) life-threatening infection of the brain Characterized by Perivascular & parenchymal mononuclear cellular infiltrate lymphocyte infiltrate Microglial nodules Focal proliferations of microglia, try to phagocyte Neuronophagia Individual neurons undergoing necrosis surrounded by phagocytic cells � PMN�s and microglia In some VE, inclusion bodies are diagnostic; e.g. Intranuclear �Cowdry type A, pink in colour� in HSV1 present in the temporal lobe Cytoplasmic �Negri bodies� in Rabies hippocampus

7. VIRAL ENCEPHALITIS (VE) Lesions of VE tend to localize in specific areas (viral tropism); e.g. HSV -- temporal lobe with hemorrhagic necrosis JC virus -- cerebral white matter. (oligodendrocytes disease is PML = progressive multifocal leukoencephalopathy ) Rabies � brain stem Present with focal or diffuse neurologic symptoms & signs and altered level of consciousness. CSF profile is similar to viral meningitis. Clear, glucose is normal and some lymphocytes in CSF

8. VIRAL ENCEPHALITIS (VE) Subacute Sclerosing panencopla = measles virus or vaccine ( bulbar poles is 1% and deadly polio affects the anterior horn)Subacute Sclerosing panencopla = measles virus or vaccine ( bulbar poles is 1% and deadly polio affects the anterior horn)

9. ARTHROPOD-BORNE VE Outbreaks of �epidemic� viral encephalitis. All have animal hosts (wild birds, forest rodents) & mosquito or tick vectors (zoonoses) Clinical course varies widely Characterized by: Perivascular infiltrates Foci of necrosis with Neuronophagia Necrotizing vasculitis No inclusion bodies Major types in USA: Eastern Equine (EEE). Seen in Atlantic, Gulf areas. Most serious fulminant form of encephalitis ? death in 4-5 days Western Equine (WEE), seen in West, Midwest. Venezuelan Equine (VEE), seen in South. St. Louis (SLE), seen in all regions of USA. California (CE), seen in East, North-Central regions. NB no inclusion bodies NB no inclusion bodies

10. Herpes Simplex (HSV) Encephalitis HSV-1 (Labialis) Encephalitis: MCC of sporadic Viral Encephalitis in USA Seen in children & young adults Causes a hemorrhagic, necrotizing encephalitis Localized in the Temporal lobes. HSV-1 resides in the Gasserian ganglion in patients with labial herpes Sensory ganglion on the 5th CN that sends out sensory nerve fibers in the lip Also has sensory fibers that go out over the temporal lobe � virus can get to the brain via these fibers Only ~ 10% have a Hx of recurrent labial herpes

11. Herpes Simplex (HSV) Encephalitis �Cowdry type A� intranuclear inclusion bodies Eosinophilic intranuclear inclusions with poorly defined halo Found in both neurons & Glia. Presents with classic temporal signs: Alterations in mood, behavior & memory. HSV-2 (Genitalis) Encephalitis: Causes generalized severe encephalitis ( not limited to temporal lobe) in up to 50% of neonates born by vaginal delivery to women with active HSV-2 infection. Prevent with C section delivery

12. Herpes Simplex (HSV) Encephalitis

13. POLIOMYELITIS Clinical: Mild gastroenteritis ? meningitis ? paralysis May have paralysis of respiratory muscles Fecoroal infection Morphology: Virus attacks the anterior horn motor neurons & sometimes cranial nerve motor nuclei ? lower motor neuron paralysis (flaccid paralysis). Process: Early: perivascular infiltrates, Chromatolysis & Neuronophagia Late: loss of motor neurons & gliosis Vaccines: Sabin (live virus) & Salk (killed virus). Chromatosis � nucleus pushed to the side

14. POLIOMYELITIS Entero-viruses that enter via oral-fecal route 3 strains of poliovirus Live vaccines (sabin) must not be given to immuno-compromised children! Post-polio Syndrome: Progressive weakness, ? muscle mass (especially calf), pain: this is only in a few cases Don�t know why this occurs

15. POLIOMYELITIS

16. HIV-1 & CNS 1. HIV-1 aseptic meningitis: Seen in 10% of patients, 1-2 weeks after seroconversion Virus can be isolated from CSF Usually self limited infection 2. HIV-1 encephalitis: After AIDS develop Occurs late Presents with AIDS dementia motor complex: Insidious onset of dementia, apathy, motor abnormalities, ataxia, bladder & bowel incontinence Brain shows Mild cerebral atrophy, mainly involving subcortical gray & white matter Virus-containing microglial nodules with multinucleated giant cells (***CLASSIC FINDING) fusion of microglial cells Demyelination & reactive gliosis

17. HIV-1 & CNS 3. Vacuolar myelopathy: Involvement of the spinal cord Demyelination of posterior column Results in ataxia Demyelination of lateral columns Results in spastic paraparesis � UMN signs in lower extremities This is not due to direct HIV virus � Virus NOT identified in spinal cord (It looks like subacute demyelination of the cord due to vitamin deficiency, Probably due to impaired utilization of vitamin B12 ) HIV enters the CNS via monocytes/macrophages Have CD4 markers which interact with the envelope protein of the virus. Microglia and protoplasmic astrocytes are vehicles for HIV entry into the brain ie the have markers

18. HIV-1 & CNS Microglia & astrocytes also have CD4 markers They become infected & destroyed by the virus Fusion of macrophages produces Multi-nucleated giant cells, which are characteristic of AIDS (AIDS Dementia Complex) Inflammatory reaction causes damage: Cytokines, viral products (e.g. gp 120) & cross-reacting antibodies may cause damage to: Oligodendrocytes (demyelination) Neurons (neurologic deficit) Opportunistic infections of the CNS further complicate the clinical picture: Toxoplasmosis, Cryptococcosis, CMV, JC virus (PML), Herpes, Varicella-Zoster, Tuberculosis.

19. PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) Infection of Oligodendrocytes by a Polyoma virus (JC virus). This virus infects the vast majority of normal individuals before the age of puberty, without causing symptomatic disease. In immunocompromised persons (*AIDS) it causes Diseases is very aggressive Multifocal demyelinating disease Most probably represents reactivation. Insidious onset of: Weakness, visual loss, ataxia, dementia ? death within 6 months. Myelin stain � Normally should be all blue � (luxol fast blue) also used to stain axons De-myelinated punched out pink areas throughout the entire brain

20. PML Morphology: Lesions consist of patches of demyelination Oligodendrocytes show large nuclei with intranuclear viral inclusions Astrocytes show atypical nuclei Polyoma viruses are Oncogenic & the nuclear atypia may be an expression of ? risk for Gliomas (esp. Astrocytomas)

21. PML Myelin stain � stains myelin BLUE Normally should be all blue � but see completely demyelinated punched out pink areas throughout the entire brain

22. FUNGAL INFECTIONS OF THE CNS Seen in immunocompromised patients As a terminal event in a more disseminated systemic infection. MCC: Candida albicans, Mucor, Aspergillus fumigatus Cryptococcus neoformans (true in AIDS patients) � involves the basal meninges ( negatively staining capsule with India ink) Cryptococcus in the CNS is AIDS defining diagnoses Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis. MUCO MICOSES MOST COMMON ORIGINATION FRON RINAL SINUSMUCO MICOSES MOST COMMON ORIGINATION FRON RINAL SINUS

23. Patterns of CNS disease include: Chronic Meningitis: MCC Cryptococcus neoformans Affects the basal Leptomeninges ? may cause non-communicating hydrocephalus. ? Fibrosis � block flow to 4th ventricle Vasculitis: MCC Mucor & Aspergillus fumigatus ? Invade walls of vessels, intravascular thrombosis & infarction. Focal Encephalitis; with granulomas & abscesses: MCC Candida, Cryptococcus

24. Cryptococcal Meningitis Cryptococcal meningitis � India ink preparation quick and easy diagnosis note the big thick mucoid capsule that doesn�t pick up the stain