Lecture 2 Neuropathology of CNS Infections Flashcards
How do infectious organisms access the CNS?
- hematogenous spread
- local extension (middle ear)
- retrograde transport
- direct implantation (surgery)
Pachymeningitis
spread of infection into layers of the dura mater
-“pachy” = thick
Meningitis/Leptomeningitis
inflammation of the pia and arachnoid
What does lepto mean
“thin”…so leptomeningitis = thin
Encephalitis
inflammation of the brain parenchyma with MONONUCLEAR cells
-usually caused by VIRAL agent
Mononuclear infiltration of brain parenchyma
Encephalitis
Cerebritis
inflammation of the brain parenchyma with neutrophils
-usually caused by a bacterial agent
Polynuclear infiltration of brain parenchyma
Cerebritis
Myelitis
inflammation of the spinal cord
Poliomyelitis
inflammation of spinal gray matter (like the ventral root/horn)
Ganglionitis
inflammation of the dorsal root ganglia
Radiculitis
inflammation of the intradural spinal nerve roots
What is granulamatous inflammation associated with in brain?
- mycobacteria
- spirochetes
- fungi
- parasites
What are microglial nodules associated with?
Viral encephalitis
What are the most common bacterial infections?
- Acute bacterial meningitis ACUTE
- Bacterial abscess ACUTE
- Mycobateria (tuberculosis) CHRONIC
- Multisystem bacterial infections CHRONIC
What layer of the brain most commonly gets fucked in bacterial CNS infections?
Subarachnoid space (leptomeningitis/meningitis)
What are the most common bacteria that cause acute bacterial meningitis in NEONATES (0-6months)?
- Group B Streptococcus
- E. coli
- Listeria monocytogenes
What are the most common bacteria that cause acute bacterial meningitis from 6mos – 60 years?
- Streptococcus pneumonia
- Neisseria meningitides
- Haemophilis influenza
(accounts for 80% of all cases)
What are the most common bacteria that cause bacterial meningitis in >60 y.o. and immunosuppressed patients?
- Strep pneumonia
2. Listeria monocytogenes
How does acute bacterial meningitis present in gross examination? histological examination?
- Pus
2. Polys
What are abscesses?
Focal, destructive lesions of the brain parenchyma due to necrosis
Mediated by ACUTE inflammation in response to bacterial infection
Bacterial meningitis = second most common CNS infection?
What is most common CNS infection? Second most?
- bacterial meningitis
2. bacterial abscess
What are the characteristics of brain abscesses and what are the most common organisms?
Transmitted either locally (sinusitis otitis) or hematogenously (septic or cardiac emboli)
-infectious emboli can travel from heart
Oragnisms:
-staph
-streptococci
-What are the three most common causes of bacterial chronic inflammation?
- Mycobacterium tuberculosis (most common)
- Neurosyphilis (Treponema pallidum)
- Neuroborreliosis (Borrelia burgdoferi … Lyme disease)
What are the symptoms of CNS TB?
Meningitis present over 2-3 weeks
- combination of headache, lethargy, nausea and vomiting
- involves CRANIAL NERVE PALSIES
- lymphocytosis in CSF
- affects basal part of brain, hence cranial nerve involvement
What organism causes neurosyphilis?
Treponema Pallidum
What are the three symptomatologies of neurosyphilis?
- Meningovascular neurosyphilis (chronic basal meningitis…lots of lymphocytes seen)
- Paretic neurosyphilis (fucks with cerebral cortex, loss of neurons, gliosis and microglia proliferation
- Tabes dorsalis (Treponema pallidum spirochetes invade the dorsal columns)
What are symptoms of neuroborreliosis (Lyme disease)?
Caused by spirochete Borrelia burgdorferi
- facial nerve palsy
- polyradiculitis
- encephalopathy
- aseptic lymphocytic meningitis
What are the four most classic manifestations of viral infections?
- Aseptic meningitis (meninges)
- Polioencephalitis/poliomyelitis (grey matter)
- Panencephalitis/panmyelitis (grey and white matter)
- Leukoencephalitis (white matter)
What are most cases of aseptic meningitis caused by?
Enteroviruses
-less severe than bacterial
What are arboviruses?
Arthropod Born viruses
RNA motherfuckers
Causes SEASONAL acute viral encephalitis
What are the common causes of ACUTE viral encephalitis?
SEASONAL, ARBOVIRUSES
-West nile virus, Japanese encephalitis, St. Louis encephalitis, Eastern/Western equine encephalitis
NONSEASONAL:
-HSV 1, 2, 6; VZV; EBV; CMV; Rabies; H1N1
What are the four pathological features of acute viral encephalitis?
- perivascular lymphocytic infiltrate
- neuronophagia (ingestion of dying neurons by macrophages)
- Intranuclear viral inclusions
- Microglial nodules
What are the delineating features of herpetic encephalitis (HSV-1)?
Necrosis of TEMPORAL LOBES
-bilateral, asymmetrical hemorrhagic necrosis
When you see bilateral, asymmetrical hemorrhagic necrosis of the temporal lobes, think what?
HSV-1
-most common cause of encephalitis
Where do you see CMV encephalitis most commonly?
- Intrauterine infection (congenital CMV)
2. Immunosuppression (post-transplant, HIV)
What is the significance of VZV encephalitis?
Very rare viral cause of encephalitis
- seen in zoster patients of advanced age or immunosuppressed patients
- causes granulamotous arteritis mimicking CNS vasculiitis
What are key characteristics of rabies encephalitis?
- negri bodies
- can be furious (insomnia agitation, aggressive behavior) or dumb rabies (ascending paralysis of one or more limbs, simulating Guillain-Barre)
What do negri bodies look like histologically?
Round to oval eosinophilic inclusions in neuronal cytoplasm of Purkije cells, hippocampal pyramidal neurons
What is the DDx of ringed lesion in brain?
Bacterial Abscess OR fungal infection
What are the most common fungal infections of CNS?
- Cryptococcus neoformans (in immunosuppressed hosts)
- Aspergillosis (hemorrhagic infarcts)
- hemorrhage abscess capsule/granulomas
- Zygomycosis (seen in diabetic ketoacidotic patients…seizures)
- immunocompromised patients
What are the most common parasitic infections?
- Amoebic encephalitis (Naegleria fowleri)
2. Cysticercosis (cysticerci from taenia solium)
What is the classic helminthic (worm or worm parasite) organism that lives in brain?
Cysticerci
-larvae of Taenia solium, a tapeworm
What are Naegleria fowleri?
An amoeba that is transmitted through olfactory bulbs
-causes fulminant, acute meningoencephalitis
What is cysticerosis?
Most common helminthic CNS disease
Caused by cysticerci
Causes a shitload of cysts
What are the most common CNS infections of the immunocompromised hosts?
- cryptococcal meningitis
- taxoplasmosis
- HIV encephalopathy
- Progressive multifocal encephalopathy
What are the delineating characteristics of cyrpotococcal meningitis?
- most common cause of fungal meningitis
- Identified in CSF via India ink
- Produces cystic dilations of VIRCHOW-ROBIN spaces (“bubbles) with little surrounding gliosis/inflammation
- fever, debility, headache, irritability, insomnia…can worsen over weeks, months or years
Domestic Cats
Definitive host for toxoplasma gondii
-leads to ring-enhancing lesions/brain abscesses
What are key characteristics of HIV encephalitis?
- multinucleated giant cells
- leukoencephalopathy with patchy demyelination and variable gliosis
- low-grade inflammation with perivascular and parenchymal lymphocytes/microglial nodules
What is leukoencephalopathy?
A type of change associated with WHITE matter
What are the delineating features that separate fungal and viral meningitis?
CSF composition
What are the key characteristics of progressive multifocal leukoenceophalopathy
Caused by: JC = John Cunningham Virus; Polyomavirus JC
- tropism for oligodendroglia…WHITE MATTER ONLY BITCHES
- ill defined demyelinating lesions; lipid laden macrophages; intranuclear viral inclusion; bizarre astrocytes with atypia
