Path 3 Cns Infect

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CNS INFECTIONS - WILSON - FRIDAY JAN 26

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what is the most common route for entry of infection into the nervous system?

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hematogenous

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what is the most common way for infectious material to be directly implanted?

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secondary to trauma

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what examples were given of direct extension of infectious material (2)?

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1) infected tooth; 2) infected sinus

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what other way can infections reach the CNS?

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from the peripheral nervous system

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what examples were given (2)?

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1) herpes zoster (shingles); 2) rabies

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ACUTE PYOGENIC (BACTERIAL) MENINGITIS

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what is meningitis and in what area does it occur?

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inflammation of the leptomeninges and CSF in the subarachnoid space

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what visual symptoms often occur?

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photophobia (abnormal visual intolerance of light)

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what other symptoms often occur (4)?

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1) mental changes; 2) neck stiffness; 3) fever; 4) headache

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what is the most important diagnostic test for meningitis?

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lumbar puncture

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what happens to the pressure in the CSF?

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it becomes elevated

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what is the normal range?

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70-180 m

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what cells are found in the CSF?

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PMNs (polymorphonuclear cells)

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what is the normal level of mononuclear cells and PMNs?

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<5 mononuclear cells; 0 PMNs - any number of granulocytes in the CSF is abnormal

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what else is elevated in the CSF, and what is the normal range?

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protein - normal range <40

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what may be very low in the CSF in pyogenic meningitis and what is the normal range?

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glucose - normal range 40-70 - glucose may be very low in pyogenic meningitis

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what patients may have atypical clinical presentation or CSF findings?

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immunosuppressed patients

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what organisms are the most common causes of acute pyogenic meningitis in neonates (2)?

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1) group B strep; 2) E. coli

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what organism is the most common cause in infants?

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Streptococcus pneumoniae

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what is the most common cause in adolescents and young adults?

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N. meningitidis

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what are the most common causes in the elderly (2)?

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1) Streptococcus pneumoniae; 2) L. monocytogenes

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what are five main complications of acute pyogenic meningitis?

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1) hydrocephalus; 2) infarcts; 3) sensory loss; 4) seizure disorder; 5) Waterhouse-Friderichsen syndrome

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how is hydrocephalus caused?

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leptomeningeal fibrosis obstructs CSF flow (obliterates subarachnoid space)

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what might lead to cerebra/brain stem/spinal cord infarcts?

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meningeal vasculitis leads to thrombosis

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what types of sensory deficits may be caused (3)?

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1) blindness; 2) deafness; 3) ocular palsies

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what may cause these deficits?

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inflammation/injury of cranial nerves

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how does seizure disorder come about?

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inflammatory injury of cerebral cortex results in epileptogenic foci

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what organisms are particularly likely to cause Waterhouse-Friderichsen syndrome (2)?

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1) meningococcus; 2) pneumococcus

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what happens in WF syndrome (2) and what is the cause?

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1) hemorrhagic adrenal infarction; 2) cutaneous petechiae - these result from septicemia

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ASEPTIC (VIRAL) MENINGITIS

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what is the difference in typical symptoms between bacterial and viral meningitis (2)?

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viral meningitis is milder and self-limiting

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what is the CSF pressure like?

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elevated

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what cells are present in CSF?

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lymphocytes

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what is the protein like in the CSF?

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elevated

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what is the glucose like in the CSF?

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normal

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what is the most common family of virus to cause meningitis?

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enterovirus

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what three specific viruses are 80% of cases due to?

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1) echovirus; 2) cocksackie virus; 3) nonparalytic poliovirus

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CHRONIC MENINGITIS

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what does chronic meningitis frequently represent?

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a meningoencephalitis

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what are the most common groups of organisms to cause chronic meningitis (2)?

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1) Mycobacterium (mainly tuberculosis - tuberculous meningitis) but other mycobacteria also; 2) fungi

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what patients are normally affected by fungal meningitis?

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immunocompromised

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what are the most common organisms causing fungal meningitis (4)?

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1) cryptococcus; 2) mucor; 3) aspergillus; 4) candida

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which of these organisms causes meningitis frequently in AIDS patients?

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cryptococcus

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what other disease does a specific fungal organism have a tendency to cause meningitis on top of, and what organism is this?

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mucor has a prediliction for diabetics with ketoacidosis

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which fungal organisms have a major tendency to invade blood vessels (2) and produce overtly hemorrhagic lesions?

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1) aspergillus; 2) mucor

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how do typical symptoms of chronic meningitis compare to pyogenic meningitis?

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similar, but less fulminating

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what happens to CSF pressure?

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elevated

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what cells are found in the CSF?

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mononuclear or mixed

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what happens to protein in tuberculous/fungal meningitis?

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elevated - may be very high

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what is glucose like in CSF in chronic meningitis?

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normal or moderately low

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what area does chronic meningitis have a predeliction for?

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basal meninges

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what type of inflammatory reaction occurs?

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granulomatous rather than pyogenic

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what are two main problems with chronic meningitis?

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1) hard to eradicate; 2) high complication rate

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what complications were said to occur in chronic meningitis (4) and what does each result from?

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1) hydrocephalus (from meningeal fibrosis); 2) infarcts (from vasculitis); 3) blindness/deafness/ocular palsies; 4) seizures (secondary to cortical damage)

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BRAIN ABSCESS

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what are the most common bacteria causing abscesses (2)?

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1) streptococci; 2) staphylococci

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formation of what structure is most often induced by pyogenic organisms?

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fibrous capsule

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what other groups of organisms cause brain abscesses in immunodeficient individuals?

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1) protozoa; 2) fungi

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what is the most common organism to cause abscess in immunocompromised individuals, and who does it cause it in?

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toxoplasma - common cause of focal brain lesion in AIDS

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what is the other most common cause of focal brain lesions in AIDS?

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primary CNS lymphoma

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what conditions predispose someone to brain abscesses (5)?

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1) acute bacterial endocarditis; 2) cyanotic congenital heart disease; 3) chronic lung infections; 4) ear or sinus infections; 5) diseased teeth/tooth extraction

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what are grave complications of brain abscess (2)?

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1) herniation due to mass effect; 2) rupture into ventricles

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VIRAL ENCEPHALITIS

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what is encephalitis?

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infection of brain parenchyma

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what is viral parenchymal infection typically accompanied by?

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viral meningeal inflammation (it is usually a meningoencephalitis)

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what are the most characteristic histologic features of viral encephalitis (4)?

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1) mononuclear cell infiltrates; 2) glial reactions; 3) neuronphagia; 4) viral inclusion bodies (intranuclear or cytoplasmic or both)

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what is neuronophagia?

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phagocytosis of necrotic neurons in the setting of a single-cell neuronal necrosis

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what are four infective trains common to certain encephalitogenic viruses and various systemic viruses (4)?

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1) tropism; 2) latency; 3) slow infection (slow-virus infection); 4) triggering factor for immune-mediated disease

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what is tropism?

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preferential involvement of specific types of cells or particular regions of the nervous system

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what is slow infection, and what does it follow?

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development of severe progressive disease after a long latency period

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what is arboviral encephalitis?

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arthropod born

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what are the most important arboviruses in the Western Hemisphere (2 classes)?

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1) Eastern/Western equine / Venezuelan / St. Louis / La Crosse; 2) West Nile

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what is the most common cause of sporadic acute encephalitis in temperate areas (including US)?

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type 1 HSV encephalitis

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what trait does HSV-1 exemplify?

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tropism

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what does HSV-1 encephalitis exhibit tropism for (2)?

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1) inferior temporal lobes; 2) frontal lobes

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how much does labial herpes affect the level of risk?

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it is not a significant risk factor

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how is HSV-1 encephalitis treated?

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acyclovir

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who does HSV-2 mainly cause encephalitis in (2)?

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1) neonates; 2) immunocompromised

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what usually occurs as far as CNS infection with HSV-2 in immunocompetent individuals?

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aseptic viral meningitis

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who is at high risk for HSV-2 encephalitis?

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neonates born vaginally to women with active primary genital herpes - indication for Caesarian section

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where is encephalitis generally located in neonates?

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generalized (panencephalitis) rather than tropic for inferior temporal and frontal lobes

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what type of CNS infection does herpes zoster (shingles, VZV) typically cause?

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a posterior ganglionitis (inflammation of a sensory ganglion)

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what trait does VZV exemplify?

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latency - reactivation in adulthood of chicken-pox virus

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where does it remain latent, and what does it cause when released?

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sensory ganglion - causes pain and vesicular skin eruption in corresponding dermatome when released

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what does rabies encephalitis exemplify?

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peripheral nervous system as route of entry of CNS infection

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how long does it take the virus to ascend along peripheral nerves to the CNS from the bite site?

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1 to 3 months

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what type of disease does rabies cause (main feature)?

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severe encephalitis with CNS hyperexcitability

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what are two examples of CNS hyperexcitability?

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1) slight touch --> pain / violent motor responses / convulsions; 2) swallowing --> pharyngospasm (hydrophobia)

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what is pathognomonic for rabies?

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a cytoplasmic inclusion body called a Negri body

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what viruses can encephalitis arise secondary to (2)?

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1) CMV; 2) PML (progressive multifocal leukoencephalopathy)

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who is susceptible to CMV (2)?

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1) fetuses; 2) immunocompromised

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what type of lesions are seen secondary to CMV, and where are they located?

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periventricular localization of necrotizing lesions (ventriculoencephalitis)

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what type of virus causes PML (family) and what is it called?

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JC virus - polyoma virus

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who is susceptible to PML / JC virus?

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immunodeficient patients

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what trait does PML / JC virus exemplify?

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tropism

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what does it have tropism for?

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oligodendrocytes

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what damage does it cause in the brain?

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demyelination

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how susceptible is the nervous system to the effects of HIV?

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it is a major target for HIV, in addition to the lymphoid system - brain, spinal cord, and peripheral nerves all susceptible

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what are the predominant cells infected by HIV in the CNS (3)?

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1) macrophages; 2) multinucleate giant cells; 3) microglial cells

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what cells were mentioned not to appear to be infected by HIV-1?

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neurons

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what are the clinical symptoms of HIV infection in the CNS (5)?

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1) dementia; 2) motor abnormalities; 3) ataxia; 4) incontinence; 5) seizures

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what are the main pathologic changes from HIV (2)?

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1) cerebral atrophy/ventriculomegaly; 2) chronic inflammation

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what is seen in chronic inflammation from HIV (cells) and how are they distributed?

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widely distributed microglial nodules that include multinucleate giant cells

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what are two main indirect CNS consequences of HIV infection?

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1) opportunistic infections; 2) primary CNS lymphoma

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what opportunistic infections were mentioned to affect the CNS after AIDS (4)?

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1) toxoplasmic cerebritis; 2) CMV encephalitis; 3) cryptococcal meningitis; 4) PML

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what are the two most common causes of focal brain lesions in AIDS?

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1) toxoplasmic cerebritis; 2) primary CNS lymphoma

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what are the CNS effects of congenital AIDS (2)?

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1) mental retardation; 2) motor debility

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SPIROCHETAL INFECTIONS

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what spirochetal infections of the CNS must we know (2)?

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1) neuroborreliosis (Lyme disease); 2) neurosyphilis

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is Lyme disease common, what is happening to is incidence, and why?

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it is a common arthropod-borne disease, and its incidence is increasing secondary to reforestation

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how many stages does Lyme disease evolve through?

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three - affects multiple organ system

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what is the causative organism of Lyme disease?

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Borrelia burgdorferi

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in what % of untreated individuals does neurosyphilis develop?

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10%

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what stage of syphilis is neurosyphilis?

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tertiary stage

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what is the causative organism of neurosyphilis?

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Treponema pallidum

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TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

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what are these the only known infectious agents that are devoid of?

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nucleic acid

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what types of etiologies can prion diseases be due to (3) and what is the mechanism of each?

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1) sporadic (spontaneous alteration of conformation of PrPc); 2) genetic (mutation of gene encoding PrPc); 3) infectious (inoculation of PrPSc into host)

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what does disease result from?

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accumulation of PrPSc

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what is the fundamental event underlying prion diseases (specific change)?

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structural transition from alpha-helices to beta sheet in PrP (transition from PrPc to PrPSc)

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what are prion diseases a localized form of?

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amyloidosis

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what do particular diseases appear to be associated with?

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particular isoforms of PrPSc (which can have a variety of conformations)

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what is the spectrum of symptoms like (list)?

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dementia, ataxia, insomnia, paraplegia, parasthesias, deviant behavior

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what pathologic change was mentioned, and how does it vary?

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vacuolation - spongiform degeneration of the tissue - varies from sparse to widespread

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what accounts for 85% of prion disease in humans?

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sporadic Creutzfeld-Jakob disease (CJD)

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what % of prion diseases are infectious?

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<1%

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how can patients acquire CJD from infectious method (2)?

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1) contaminated grafts, hormone preparations, corneal transplants, EEG electrodes, etc. 2) contaminated beef

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what are inherited forms of CJD (3)?

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1) familial CJD; 2) Gerstmann-Straussler-Scheinker disease; 3) fatal familial insomnia

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what are the typical manifestations of CJD (2)?

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1) myoclonus; 2) dementia

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what is the course of CJD?

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progressive and rapidly fatal (1 year)