Infections on Nervous System Flashcards
Reminder: unique features of brain/spinal cord:
–________: protects from organisms, but also restricts immune system access
–________: with inflammation -> swelling & neurologic damage
Blood brain barrier
Rigid skull/vertebral canal
Leptomeningeal inflammation =
Encephalitis/cerebritis/myelitis (spinal cord) or Brain abscess =
Meningitis
Parenchymal inflammation
( When meninges and brain tissue are affected: meningoencephalitis)
Subdural or epidural inflammation =
Subdural/epidural empyemas
Routes of infection in the brain
- Hematogeneous spread: Arterial spread = Retrograde venous spread from Anastomotic connections between face veins & cerebral circulation or Paravertebral venous plexus, Batson
- Local extension – air sinuses, infected tooth
- Neural Route (Extension from PNS to CNS)
- Direct implantation - trauma, iatrogenic
Neurotropism ie special affinity for brain
What are some mechanisms?
- Viral specific Rs on brain
- Capsule proteisn adhere to meninges and have antiphogocytic properties
- Viral spread along nerves
Viral specific receptors on brain cells: what are two examples?
Poliovirus for motor neurons of anterior horns of spinal cord
Mumps virus for ependymal cells lining ventricles
Group B streptococci, E. coli subtypes modality of entering brain
Capsule proteins that adhere to meninges and possess antiphagocytic properties
Herpes simplex virus, Rabies, Varicella zoster virus enter brain:
Viral spread along nerves
Headache, photophobia, stiff neck (nuchal rigidity), clouded consciousness, fever
Meningitis
Hyperacute (<24 hrs) meningtis; see sparse inflammation, numerous organisms, congestion
– Meningococcal meningitis
Acute (2-7 days) - most common infection in CNS
– Usually bacterial
– Usually results from hematogeneous spread
Subacute/chronic (> 1 week)
– Tuberculosis, syphilis (often brain parenchyma also affected)
– Lymphocytes, plasma cells, macrophages appear in exudate
much less fulminant than bacterial meningitis & less severe symptoms
– Summer & early fall
– Lymphocytic infiltrate in meninges
“Aseptic” (usually viral) -
What do we see on histology of acute bacterial meningitis
exudate present, numerous PMNS, leukocytes in the subarachnoid spce
Complications of bacterial meningitis
Brain infarcts, secondary vasculitis, phlebitis may occur and cause infart of underlying brain tissue
Aseptic meningitis causitive organsims:
Arboviruses or Enterovirus (most common) :Echovirus and Coxsackie
- Circumscribed focus of infection
- Clinical S/S: focal deficits, raised intracranial pressure
- Usually bacterial or fungal origin
Parenchynal infections: BRAIN ABSCESSES
–liquifactive necrosis
Cause of brain abcess in immunocompetent host
Step and staph
Brain abcesses are caused by what pathogens in immunocompromised hosts?
Toxo, Listeria, gram neg bacilli, myco, fungi
DEscribe a brain abcess histologically
center is necrotic and thre are inflammatory cells and fibrous capsule
*we also see giant cell; granulomatous and early fibrous wall
Inflammation of brain
• Spinal cord-myelitis
• Meninges and brain-meningoencephalitis
• May be bacterial, viral, or fungal in origin
examples of parenchymal infections: encephalitis
Causes of bacterial mengioencephalitis
• Tuberculosis
- Syphilis
- Lyme disease
Cause of TB
Mycobacterium tuberculosis
- CNS involvement in 10-15%
- HIV infection is risk factor
Most common form of TB in CNS
What do we see in CSF levels?
Meningoencephalitis
CSF: elevated pressure & protein, decreased glucose, lymphocytic pleocytosis
Cultures for AFB are positive in 50% t**hus PCR for TB now** always performed
Sigs and symptoms of TB meningioencephalitis are simular to other meningitis; what do we see in the meninges?
Meninges contain lymphocytes, macrophages, granulomas with extension into underlying brain
Describe findings on scan and grossly in pt infected with TB mengioencephalitis
Gross; see exudate located in base of brain
scan see enhancement of meninges over brain base
Describe histological findings in pt with TB meningioencephalitis
Leptomeningeal vessels with arteritis; Hydrocephalus and infarcts may occur secondary to vessel occlusion
oh myyyy, what is this mean?
AFB + stain seen in pts with TB
- Mass lesion with central necrotic core of caseation, surrounded by fibroblasts, epithelioid histiocytes, giant cells & lymphocytes
- AFB are present in necrosis
Tuberculoma
Describe what you see on pathology of caseous necrosis in TB
see caseous necrosis with granulomatous inflammation
there are epitheliod histiocytes surrounding lesion
•Spondylitis (Pott’s disease)
- Granulomatous process involves vertebral bodies & discs
- Causes epidural abscess
- Cord compression, vertebral collapse
•Epidural extension of the granulomatous inflammation
Tuberculosis osteomyelitis
• General paresis (paretic neurosyphilis) • Meningovascular • Tabes dorsalis
these are all possible progressions of what?
untreated Treponema pallidum: devos into neurosyphillis = tertiary syphillis
Describe what you see in general paresis caused by neurosyphillis
- Gradual impairment of cognition/attention
- Meningo-encephalitis:Thickened meninges and atrophic brain ad meningeal & parenchymal perivascular lymphocytes, plasma cells, & microglia
Meningovascular type Chronic meningitis and multifocal arteritis from tertiary syphillis:
Located at:
causes:
- Severe at base of brain
- Causes infarcts & hydrocephalus
What do we see on histology in meningovasculr type chornic meningitis from tertiary syphillis?
- Meningeal & arterial/arteriolar lymphocytes & plasma cells with collagenous thickening of wall and eventual occlusion
- Often focal neurologic deficits due to vascular compromise secondary to arteritis
Location of damage from Tabes Dorsalis
• Chronic inflammation in dorsal roots & ganglia with loss of neurons and associated degeneration of posterior columns (axons & myelin)
• ‘Lightening pains’ or paraesthesias in affected roots, eventual loss of position/vibration sense; shuffling broad-based gait
Tabes dorsalis: d/t chronic inflammation in degen of posterior columns
• General features: perivascular lymphocytes, microglial nodules, neuronophagia
Viral meningo-encephalitis
Organisms responsible for viral (meningo)encephalitis
- Arboviral encephalitis
- Herpes virus infections (Herpes simplex 1, Herpes simplex 2, Cytomegalovirus, Varicella-zoster)
- Human immunodeficiency virus
- Progressive multifocal leukoencephalopathy (PML)
What are these little buggers?
What disease are they associated with?
What else on histology would we expect to see?
Microglial nodules seen in viral ifnection!
will also see perivascular and parenchymal lymphocytic infiltration
Whats going on with these buggers?
Neuronophagia: see remnant of neuronal cell body getting eaten up by inflammatory cells
- Most common cause of sporadic acute viral encephalitis in temperate climates
- Headache, fever, mood, memory, behavior abnormalities, drowsiness, coma
- MRI- focal abnormalities in frontal or temporal lobes
Herpes virus infection in CNS
Pt comes in with headache, fever and drowsiness. Partner says they ahve been behaving different and struggling to remember things. You suspect encephalitis and below are the CSF labs:
Lymphocitic pleocytosis
Elevated protein
Increased pressure
What is your Dx and how do you confirm?
HSV-1 infection in CNS
Dx via PCR for HSV1
What part of brain do HSV1 infections LOOOVE
frontal and temporal regions
What do we see grossly in HSV1 encephalitis?
very hemorrhagic process with congestion, swelling, hemorragic necrosis of TEMPORAL lobes, cingulate, orbital cortex
Where would you see these little nugglets?
Cowdry type A = intranuclear viral inclusion seen in HSV1 encephalitis
on the left is necrotizing hemorrhagic inflammation
When would you see HSV2 CNS infections?
- Herpes simplex virus type 2
- Meningitis in neonates passing through birth canal in mother with active HSV2 infection
• Commonest opportunist viral infection in AIDS patient that causes Subacute encephalitis
Cytomegalovirus
What do we see on histology in pt with CMV infection?
Microglial nodules and viral inclusions-may be either intranuclear or intracytoplasmic
Reactivation of latent virus residing in sensory ganglia:Vesicles in dermatome distribution followed by scar and pain
Varicella Zoster:
Dorsal root ganglia or sensory cranial nerve ganglia have lymphocytes, sometimes necrosis
Important cause of epidemic encephalitis
Generalized neurological deficits (seizures, confusion, stupor, delirium, coma) & focal signs
Arboviral meningoencephalitis : west nile, venezuelan, St.Louis, California
*PCR is key for id of specific virus
HIV - ________virus, retrovirus
•_______ are most common cell infected in CNS by HIV
•______ is a major target of HIV infection
RNA
Microglia
CNS
Types of CNS involvement seen in HIV infected pts
- HIV meningitis
- HIV encephalitis/leukoencephalopathy
• Vacuolar myelopathy
Present in > 75% of autopsied HIV patients
Clinical S/S (AIDS dementia complex) Cognitive and behavioral deterioration, eventually dementia, ataxia & tremor
Slight diffuse atrophy
HIV encephalitis/leukoencephalopathy
What is the classic lesion seen in HIV encephalitis/leukoencephalopathy
microglial nodule containing multinucleated microglial cells (contain HIV virus)
• Also perivascular lymphocytes, patchy demyelination and astrocytosis
- Occurs in immunosuppressed hosts (often AIDS patients)
- Caused by JC virus, polyomavirus, infects oligodendrocytes
- Most have serologic evidence of prior JC virus infection by adolescence. JC virus is re-activated with immunosuppression
Progressive multifocal leukoencephalopathy
You note small gray areas of focal necrosis on a brain specimen
on staining, your preceptor points out irregular poorly defined areas of demylenation
Progressive multifocal leukoencephalopathy
Where would you see oligodendrocyte inclusions?
What else would you see?
Progressive multifocal leukoencephalopathy
*Enlarged oligodendrocyte nuclei immunostained for JC virus, at edge of area of early myelin loss
ommonly occur in immunocompromised hosts (and occasionally in immunocompetent hosts):
FUNGAL (meningo)encephalitis
• Candida, Mucor, Aspergillus, Cryptococcus, Histoplasma, Coccidiodes, Blastomyces
Patterns of disease seen in Fungal (meningo)encephalitis
- Chronic meningitis
- Parenchymal invasion (encephalitis)
- Vasculitis (especially Aspergillus and Mucor) • Cause hemorrhagic infarcts
What would you expect to see on an MRI of pt with Aspergillis brain infection
multiple focal areas of necrosis
What do you see on histology of pt with Aspergillus brain infection?
Necrosis with inflammation, Vessel wall lined with fungal hyphae of aspergillus
Affects lungs first usually & spreads hematogeneously to brain
Most often in immunosuppressed patients but may occur in immunocompetent hosts
Organism found in soil and bird excreta
Cryptococcus neoformans
What are the main forms of cryptococcosis brain infectoins?
Main forms:
– Meningitis with or without brain parenchymal cysts (encephalitis)
– Abscesses (Cryptococcomas)
What is CSF like in Cryptococcosis infection?
lymphocytes, high protein, normal or reduced glucose,
– Assay for presence of Cryptococcal antigen is more sensitive
– India ink stains allows identification of organism (by negative staining of capsule)
: on the right is Organisms are single round yeast forms surrounded by capsule
What does a gross specimen with crytococcal meningoencephalitis look like?
thickened meninges particularly over the sulci
Multiple intraparenchymal “cysts” Also called “soap bubbles” (secondary to gelatinous capsular material)
Occur in 50% of cases in addition to meningeal involvement
Histological finding of cryptococcal meningitis
Also called “soap bubbles”
Organisms are single round yeast forms surrounded by capsule (clear space around organism)
Usually minimal inflammatory reaction
- Single-cell organisms
- Infection occurs in immunocompetent and immunosuppressed (where the infection is more severe)
• Cause **meningoencephalitis or abscesses **
Parasites
• Amoeba
- Plasmodium (Malaria)
- Toxoplasma
- Trypanosoma (Sleeping sickness)
• Cysticercus (Taenia solium)
- Man is intermediate host (cat is definitive host)
- Infection secondary to ingestion of contaminated food (cat feces) or raw/undercooked meat from another intermediate host (sheep, pig)
- Congenital disease
- Transmission to fetus if infection occurs during pregnancy
Toxoplasma gondii - protozoa
- Important infection in immunocompromised hosts, esp. AIDS patients
- Most common cause of mass lesions in CNS in AIDS patients
- Uncommon in healthy adults
Toxoplasma gondii - protozoa
What do we see on histology in pt with toxoplasmosis?
organism w/in pseudocysts as well as lying free
Epidural and subdural empyemas
- Usually ___________
- Local extension of infectious proces
bacterial (staph or strep commonly)
Causes of epidural and subdural empyema
- From frontal or mastoid sinusitis
- Otitis media
- Trauma
- Osteomyelitis
- Surgical procedure
- Disease may be inherited or idiopathic but also transmissible
- Types of disease: Idiopathic, inherited, transmissible
Prion disease (transmissible spongiform encephalopathy)
MOst common form of idiopathic prion disease
• Sporadic Creutzfeldt-Jakob disease (CJD) – most common form (also has iaotrogenic form you get when from growth hormone or corneal tranpslant
What agent is responsible for prion disease, what conformation is it in?
PrPsc = abnormal disease causing form of protein, has an abnormal ß-pleated sheet (a type of amyloid) conformation
Prion diesase does not contain _______ and is resistant to usual methods of denaturation (i.e., formalin fixation
nucleic acid
Normal function and physciology of prion protein
PrPc = normal prion protein
Physiological function uncertain but likely participates in signaling pathways
Membrane sialoglycoprotein located on Gene (PRNP) on chr. 20
Normal prion protein is normally found in brain (neurons) and selected other organs
Describe pathology of BSE and varient CJD
- BSE epidemic
- Diets contained feed from scrapie infected sheep
- Spread by addition of infected cow tissues to cattle feed
- Ban on feeding ruminant-derived protein to ruminants (1988)
- Ban on cattle offal in human food (1989)
- Coincidence of vCJD and BSE in time and space
- Similarity in biological strain phenotypes of vCJD and BSE
