Infections of the CNS Flashcards
1
Q
What is pertinent clinical and demographic information?
A
- Patient age
- Geographic distribution
- Tempo of disease onset and progression
- Acute vs subacute/chronic
- H/o trauma or surgery
- Immune status (if on immunosuppressive therapy)
- Exposures
2
Q
What are the three main types of infections?
A
-
Meningitis
- Inflammation of the leptomeninges (brain coverings)
-
Encephalitis/meningoencephalitis (BOTH)
- Infection of brain parenchyma - neurons and glial cells
- Usually accompanied by meningitis (meningitis can occur alone)
- Diffuse or focal (one lobe)
-
Brain abscess
- localized infection-single or multiple
3
Q
What are the FIVE categories of MENINGITIS?
A
- once meningitis is suspected a lumbar puncture is done
- necess to culture CSF and start empirical AB
- can be delayed if:
- pt has thrombocytopenia or deficient clotting factors, or if an infection is present along the skin of the back
- can be postponed if:
- pts appears to have elevated intracraniel pressure or an intracraniel mass with edema
- young kids recovering from meningitis must be observed for any subsequent deafness which may impede their ability to learn to talk
-
Bacterial
- Acute
- usually colonize nasopharyngeal area with their special features (capsule) and penetrate.
- capsule prevents neutrophilic phagocytosis; go from bloodstream and spread to the nervous system
- Acute
-
Fungal
- Immune-compromised
- becoming more common because these pts are living longer due to new therapies
- Immune-compromised
-
Amebic and tuberculous
- Granulomatous (usually)
-
Viral
- ASEPTIC meningitis, self-limiting
-
Non-Infectious
- Chemical (e.g. post-operative)
- Meningeal carcinomatosis
4
Q
What are the common pathogens for ACUTE bacterial Meningitis? (**depends on age)
A
- organisms may spread in one of two ways:
- through the bloodstream from a distant infection (eg pneumonia)
- spread directly from an adjacent infection to the subarachnoid space (otitis, sinusitis)
- Initial tx: broader spectrum AB, CEFTRIAXONE plus VANCOMYCIN (for S. pneumo-resistant to penicillin)
- Add AMPICILLIN for Listeria in elerdy pts/neonates
-
< 1 month:
- Aerobic Gram-negative bacilli (E. coli)
- Group B (baby) streptococci
-
1 – 12 months:
- S. pneumoniae (Pneumococcus)
- Tx: IV DEXAMETHASONE
- Haemophilus influenzae – less common now due to vaccination
- S. pneumoniae (Pneumococcus)
-
12 months – 16 years:
- Neisseria meningitis
- H. influenzae
- S. pneumoniae
-
16 – 50 years:
- S. pneumoniae
- Neisseria meningitidis
- petechial rash, from tiny skin hemorrhages (red spotted boxers)
-
Age extremes (very young and very old):
- L. monocytogenes
- Pseudomonas aeruginosa
5
Q
(ACUTE) Bacterial meningitis Diagnostics
A
- CP:
- symptoms and signs evolve rapidly in hours to days:
- fever, HA, malaise, lethargy, N/V
- impaired consciousness, nuchal rigidity (stiff neck), meningeal signs
- more severe, fulminant, may be fatal if not treated early and aggressively
- symptoms and signs evolve rapidly in hours to days:
-
Gross:
- bacterial meningitis=purulent meningitis
- yellow, thick, creamy and cloudy
- protein-rich leptomeningeal exudate in subarachnoid space obscuring normally translucent leptomeninges
- pus in the subarachnoid space
- Blood smear: multi-lobed nuclei
- General: small hemorrhages and congestion/brain edema (if fulminant edema may lead to herniation and death)
-
CSF Findings:
- fluid quality: cloudy
- cells present: **PMN WBCs (leukocytosis with > 100 cells/microliter)
- protein level: VERY HIGH
- ***glucose level (relative to plasma level): low
- opening pressure: HIGH
-
Histo:
- leptomeninges filled with inflammatory cells (acute inflamm)
- subarachnoid space is expanded with inflammatory cells
- cortex contains large neuron cells in laminar fashion; mostly spared
- on higher magnification can see PMN and thick proteinacious exudate filling up the subarachnoid space
- Complications:
- hydrocephalus from pus obstructing CSF pathway
- secondary inflammation and edema of cortex (meningoencephalitis)
- infarction from thrombosis of inflamed superficial vessels of cortex
- spinal cord deafness (monitor hearing in children)
- fluid should be cultured or do PCR to discern inciting agent
6
Q
(CHRONIC) Bacterial meningitis
A
- more subtle symptoms over weeks or months time
-
Causative agents-dont typically infect healthy patients {eldery, malnourished, immunocompromised most susceptible}
- CP (subtle): confusion, low grade fever, mild HA, no obvious meningeal signs
- Tuberculous (Mycobacterium tuberculosis)
- Fungal (Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis)
-
Parasitic
- Syphilis (Treponema pallidum, rare)
- Borreliosis (Borrelia burgdorferi, rare)
- Non-infectious (Neurosarcoid)
-
Gross:
- thick exudate at the base of the brain in TB meningitis
-
Histo:
- necrotizing granulomatous inflammation
- necrotic center surrounded by proliferation of histiocytes (multinucleated giant cells)–all surrounded by T-lymphocytes
-
CSF Findings:
- cells present: Lymphocytes
- protein level: moderate high
- glucose level (relative to plasma level): mildly low
- Diagnosis:
- need special cultures (titers) of CSF
- –or– PCR testing (TB)
7
Q
Fungal meningitis
A
- Fungi can also cause encephalitis and brain abscess
- Secondary vasculitis
- Vascular invasion->infarction (and thrombosis)
- Mycotic aneurysm->hemorrhage (usually in the setting of infectious endocarditis)
- infectious aneurysms that are pseudo, due to vessel wall damage by the infecting organism (fungal or bacterl {staph or strep})
- hemorrhage also compresses the lateral ventricle
- Microscopic findings:
- Mononuclear infiltrate (not PMN like acute bacterial), variably granulomatous inflammation (overlaps with TB)
- Special stains for diagnosis:
- Periodic acid-Schiff (PAS): stains pink
- Mucicarmine: stains fungi with mucin capsules
- Grocott methenamine silver (GMS): stains fungal form black , background green
- Simplified Taxonomy:
- Hyphal and pseudohyphal fungi
- Candida-hematogenous
- Aspergillus-hematogenous
- Angio-invasive aspergillus (GMS stain):
- vessel wall with fungal hyphae [located in the muscular wall of the artery]
- Angio-invasive aspergillus (GMS stain):
- Zygomycetes (Mucor)-direct spread from sinuses
- Fusarium
- Yeasts (usually budding)
- Histoplasma
- Blastomyces
-
Cryptococcus-common form of fungal meningitis (diagnosed by India Ink stain of CSF)
- Gross:
- thickened pale meninges
- clear cystic lesions in basal ganglia-“Swiss cheese” effect
- Path:
- involves meninges and parenchyma (in white and grey matter) of the brain
- found in immunocompromised pts
- lives in soil and feces of birds
- infection to respiratory system, may go unnoticed, may spread to the CNS (in immunocompromised)
- Histo
- clear (budding) yeasts [tennis rackets] with mucoid capsule=the hole in the brain
- inflammation is focal and limited
- infiltration of Virchow-Robin space in the white matter (on H&E stain)
- also stains with Mucicarmine
- Gross:
- Hyphal and pseudohyphal fungi
8
Q
Parasitic CNS Infections
A
-
Cysticercosis
- Most common cerebral parasite (causes neurocysticercosis [NCC])
- Southwestern states and Mexico
- Pork tapeworm, Taenia solium
- CP=seiures
- Path:
- after ingesting food/water that is infected with the feces, it will travel from gut to muscle, eye, brain
- will spend several years there, then when they die will have inflammatory reaction and cause neuro symptoms
- Gross/CT scans:
- can see cyst containing scolex
- usually small cystic lesions throughout the brain
- Histo:
- cyst wall
- PROTOSCOLEX
- branching body cavity
-
Toxoplasmosis
- Protozoan
- primary host: cat
- Cysts in meat or oocysts in cat feces
- Crosses placenta (pregnant women should avoid changing cat litter)
- Brain abscess - ring enhancing lesion on MRI; simulates a tumor
- Congenital toxoplasmosis
- Part of TORCH infections (Toxoplasmosis, Others, Rubella, CMV, Herpes virus)
- all have similar CP, but are caused by VERY different agents
- “Classic triad” found in newborn or fetus:
- chorioretinitis
- hydrocephalus
- intracranial calcifications
- Diagnosis:
- Serology-specific Ab
- Biopsy-or PCR
- Amoebiasis
- Histology:
- On H&E can see Brady-zoites (little blue dots)
- usually accompanied by necrosis and acute inflammation
- On H&E can see Brady-zoites (little blue dots)
- Part of TORCH infections (Toxoplasmosis, Others, Rubella, CMV, Herpes virus)
-
Naegleria fowleri
- Free living amoeba
- the MOST Fulminant acute meningoencephalitis
- causes necrotizing hemorrhagic encephalitis (of grey and white matter)
- rapidly progressive, usually fatal
- Swimming in freshwater lakes – invades nasal mucosa and enters via cribriform plate
- exposure common, infection is uncommon
- Histo:
- similar to histiocytes
- see small trophozoites-vacuolated cytoplasm with prominent nucleolus
- Diagnosis: wet mount or PCR
- Entamoeba histolytica
- Balamuthia mandrillaris
9
Q
Viral Meningitis (ASEPTIC)
A
- Peak incidence – summer and early fall (enterovirus and arbovirus)
- CP triad: HA, visual disturbances, and neck stiffness
- (common) Causes of viral meningitis:
- Enteroviruses** (>75% of cases for which specific etiology can be identified)
- Arboviruses
- HSV2
- WNV
- intermediate to uncommon:
- HSV1
- EBV
- VZV
- HIV
- HHV-6
- Gross examintion:
- usually nml
- may have: hyperem, congestion of meninges, or edema of brain
- Microscopic changes are subtle/scanty:
- Lymphocytic meningeal infiltrates
- Perivascular lymphocytic extension along Virchow-Robin spaces
- CSF findings:
- fluid quality: clear
- cell present: lymphocytes (like TB)
- protein: slightly high
- glucose: nml
- Tx: benign, nonfatal, untreatable but resolves spontaneously
10
Q
Viral Encephalitis
A
- Inflammation of brain parenchyma (also primary site of infection), diffuse or regional
- symptoms evolve over hours to days, involve fever and HA and S/S indicative of brain involvement itself: seizures, focal neurological dficits, behavioral changes, and impairment of consciousness
- Mostly caused by viruses, usually with meningeal inflammation (= meningoencephalitis)
- CNS targets of particular viruses
- **motor neurons (especially LMN inthe SC)-Polio (ingestion) and Enterovirus**
- Neurons and glia: Herpes virus (inhalalation/reactivation), rabies, measles
- Oligodendroglia: Papovavirus (usually immuncompromised)
- Microglia: HIV
- Meninges: mups, enterovirus, coxsackie, HIV
- Neurons, glia and endothelium: CMV (in immunocompromised)
- DRG: HSV, VZV
- VZV-remains latent for years in DRG after a childhood putbreak of chickenpox
- years later, as adult, as immune fxn wanes, virus is REACTIVATED
- Zoster or shingles consists of eruption of a vesicular rash with severe neuralgic pain along one or two adjacent dermatomes
- Tx: ACYCLOVIR ASAP
- VZV-remains latent for years in DRG after a childhood putbreak of chickenpox
- Fetal nervous system: Rubella, CMV
- Viral infections differ from bacterial in that seasonal and geographic features are the most important rather than patient age or underlying risk factors.
- Seasonal Prevalence of Viral Encephalitis (bold**=important in the US):
- Summer/Early Fall: Arboviruses (West Nile virus)**, Enterovirus, Rocky Mountain Spotted Fever (NON-viral infections that can mimic viral encephalitis)
- WNV: bird epidemic in past few summers, spread to humans by mosquitoes
- CP: encephalitis (fever, HA, rash)
- weakness from affecting peripheral nerves or anterior horn cells (similar to polio)
- WNV: bird epidemic in past few summers, spread to humans by mosquitoes
- Fall and Winter: LCMV
- Winter and Spring: mumps
- ANY season: HSV**, EBV, CMV, [Mycoplasma and Leptospira-NON-viral infections that can mimic viral encephalitis]
- Summer/Early Fall: Arboviruses (West Nile virus)**, Enterovirus, Rocky Mountain Spotted Fever (NON-viral infections that can mimic viral encephalitis)
- Greater grey matter than white matter involvement
- Diffuse or focal
- CSF:
- similar to viral meningitis; lymphocytic pleocytosis and nml or slightly decreased CSF glucose
- Microscopic findings:
- Perivascular inflammation (with lymphocyteic infiltrate)
- Leptomeningeal inflammation (same as with meningitis)
- Microglial clusters (=microglial nodules );largely scattered throughout the brain
-
Neuronophagia
- neurons that are infected and die are surrounded by T-lymphocytes and microglial cells
- T-lymphocytes predominate (some PMNs {neutrophils} can be present in acute phase)
- Diagnosis:
- Check Ab titer to suspected virus in CSF and serum
- esepcially: check HSV-1 with PCR testing
- Tx: antiviral drugs for Herpes virus
- otherwise: hospitalized in the ICU-can treat raised intracranial pressure or seizures with anticonvulsants and sedatives (IV dexamethasone)
- Prognosis: range from full recovery-to-survival with residual deficits-to-death
11
Q
Polio Encephalitis
A
- Poliovirus
- Fecal-oral transmission – replicates in oropharynx and small intestine
- Spreads to CNS via hematogenous route.
-
Infection/invasion and destruction of anterior horn cells (LMN-in brain stem, SC)
- mild regional weakness to severe generalized paralysis, even of respiratory muscles
- Virus recovered from stool or throat
- survivors often have asymmetrical atrophy and weakness in controlateral limb (PMA-postpolio muscular atrophy)
12
Q
Rabies
A
- Exposure to rabid dogs most common cause worldwide (in US: bat, raccoon, skunk)
- Incubation can be last from <10 days to more than one year depending on bite location
- closer to the CNS=the faster the symptoms develop
- avg: 1-3 months
- Prodrome of flu-like symptoms
- Negri bodies (cytoplasmic inclusions) seen in neurons of brainstem, hippocampus and cerebellum (Purkinje cells)
- Histo: bullet/rod-shaped Rhabdovirus
13
Q
Herpes simplex Encephalitis
A
- Usually HSV-1 (cause of oral herpes)…HSV-2 causes genital herpes
- Transmitted via saliva
- non-epidemic and non-seasonal
- Latent infection in trigeminal (sensory) ganglion
- **Example of focal encephalitis:
- (inferior frontal and) Medial temporal lobes - edema, hemorrhage and necrosis (acutely)
- Gross Findings:
- bilateral, usually asymmetrical hemorrhagic necrosis of temporal (and inferior frontal) lobes (especially anteriorly and inferiorly) and to a lesser extent, the insulae, cingulate gyri, and thalamus
- inflammation usually accompanying brain edema (especially in the acute phase)
- “Burnt-out” herpes encephalitis - chronic phase:
- hemorrhagic necrosis will progress to cavitation and atrophy (of ventricles)
- in long-term survivors affected parts of the brain appear shrivelled and brown
- Histo: intranuclear inclusion/”owl’s eye”
-
CP:
- aphasia
- behavioral changes
- memory deficits
- Tx: ACYCLOVIR should be started if there is high clinical suspicion of HSE
14
Q
Cytomegalovirus (CMV)
A
- Particularly important in fetal/neonate population – TORCH
- Toxoplasma, (Other), Rubella, CMV, Herpes simplex
- Common opportunistic infection in AIDS, affecting the CNS in 10-20% of cases
- Large intracytoplasmic and intranuclear inclusions
15
Q
Congenital CMV Encephalitis
A
- Moderately dilated ventricles and several foci of calcifications in the periventricular region.
- Microscopic:
- Meningoencephalitis
- Cytomegalic inclusions in all cellular elements of the brain, including neurons, most numerous in the periventricular regions.
- Postnatal infection: numerous microglial nodules, only occasional cytomegalic cells with inclusions.
- Gross: moderately dilated ventricles and several foci of calcifications in periventricular white matter: wite spots (could be due to any of the TORCH spectrum of pathogens)
- Histo: cytomegalic inclusion in neuronal nucleus
