Cns infections
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Cns infections






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Cns infections Cns infections Presentation Transcript

  • INFECTIONS 4 routes which infectious agents can enter the CNS a) hematogenous spread i) most common - usually via arterial route - can enter retrogradely (veins) b) direct implantation i) most o ften is traumatic ii) iatrogenic (rare) via lumbar puncture iii) congenital (meningomyelocele) c) local extension (secondary to established infections)
    • i ) most often from mastoid and frontal sinuses, infected tooth, etc.
    • d) PNS into CNS
    • i) viruses
    • - rabies
    • - herpes zoster
    • Meningitis refers to an inflammatory
    • process of leptomeninges and CSF
    • Meningoencephalitis refers to inflammation
    • to meninges and brain parenchyma
    • Meningitis often associated with infection
    • a) may be chemical
    • i) agent introduced into subarachnoid space
    • Meningitis classified:
    • a) acute pyogenic
    • i) usually bacterial meningitis
    • b) aseptic
    • i) usually acute viral meningitis
    • c) chronic
    • i) usually TB, spirochetes, cryptococcus
    • d) these types are based on the inflammatory exudate of CSF
    • Acute Pyogenic (Bacterial) Meningitis
    • Microorganism vary with age of the patient
    • a) neonates
    • i) E. coli
    • ii) Strep. pneumonia
    • iii) Listeria monocytogenes
    • b) adolescents and young adults
    • i) Neisseria meningitidis (most common)
    • ii) Haemophilus influenza
    • - immunizations have markedly reduced this pathogen
    • - most common among infants now is S. pneumoniae
    • Clinical S & S
    • a) systemic signs of infection superimposed on clinical evidence of meningeal irritation and neurologic impairment
    • i) headache
    • ii) photophobia
    • iii) irritability
    • iv) neck stiffness
    • v) nausea, vomitting
    • b) spinal tab yields
    • i) cloudy or frankly purulent CSF
    • ii) increased pressure
    • iii)  neutrophils
    • iv)  CSF protein concentration
    • v) markedly  glucose concentration
    • c) untreated can be fatal
    • d) Waterhouse-Friderichsen syndrome
    • i) results from meningitis-associated septicemia
    • - hemorrhagic infarction of the adrenal glands
    • - cutaneous petechiae
    • - common with menigococcal and
    • pneumococcal meningitis
    • In immunosuppressed patients, other
    • pathogens may be involved
    • a) Klebsiella
    • 2. Acute Aseptic (Viral Meningitis)
    • Actually a misnomer
    • a) refers to absence of any recognizable organism
    • b) generally viral
    • c) clinical course is less fulminant compared to bacterial
    • Clinical S & S:
    • a) CSF glucose near normal
    • b) protein only moderately elevated
    • c) lymphocytic pleocytosis
    • d) usually self limiting
    • e) most common is the enterovirus
    • i) polio, echovirus, coxsackievirus
    • f) no distinctive macroscopic characteristics, except
    • i) brain swelling
    • ii) mild, if any, infiltration of the leptomeninges with lymphocytes
    • Some class of drugs have been implicated
    • with a true noninfectious meningitis (“drug-
    • induced aseptic meningitis” )
    • a) NSAID
    • b) antibiotics
    • c) CSF is sterile
    • d) glucose normal (CSF)
    • e) pleocytosis with neutrophils
    • f)  CSF protein
    • Brain abscess
    • a) may arise from a variety of routes
    • (see slides # 1 and 2 for details)
    • i) often from primary infected site in the heart (acute bacterial endocarditis), lungs, tooth decay, bones
    • b) Strep and Staph are the most common bacteria
    • c) cerebral abscesses are destructive lesions
  • i) central liquefactive necrosis surrounded by fibrous cap - edema in surrounding area ii) common sites (in descending order) - frontal lobe - parietal lobe - cerebellum iii) present with progressive focal deficits - signs of  ICP
    • - CSF under  pressure
    • - WBC and protein 
    • - glucose normal
    • iv) rupture of abscess can cause ventriculitis, meningitis and venous sinus thrombosis
    • v) surgery and antibiotics have decreased lethality to less that 10 %
    • Subdural Empyema
    • a) bacteria and fungus can spread to subdural space  subdural empyema
    • b) arachnoid and subarachnoid spaces usually unaffected
    • c) thrombophlebitis may develop in bridging veins  venous occlusion and infarct
    • d) clinical:
    • i) febrile
    • ii) headache
    • iii) neck stiffness
    • iv) untreated may develop lethargy and coma
    • v) CSF profile similar to abscess
    • Extradural Abscess
    • a) commonly associated with osteomyelitis
    • b) usually arise from adjacent site of infection
    • i) sinusitis or a surgical procedure
    • ii) when occurring in spinal epidural space  spinal compression
    • - neurosurgical emergency
    • TB
    • a) headaches
    • b) malaise and confusion
    • c) vomiting
  • d) CSF: i) moderate pleocytosis - PMN and MN ii) proteins markedly  iii) glucose slightly  or normal e) Subarachnoid space  fibrous exudate i) most often at base of brain ii) often obliterating the cisterns iii) encasing cranial nerves f) development of a single intraparenchymal mass  tuberculoma i) may cause significant mass effect
    • g) clinical:
    • i) most serious is arachnoid fibrosis and
    • - hydrocepahlus
    • ii) obliterative endarteritis
    • - arterial occlusion and infarction
    • iii) spinal cord roots may be involved
    • Neurosyphilis
    • a) tertiary stage
    • i) ~ 10% of untreated patients
    • b) major forms of meningovascular neurosyphilis are
    • i) paretic, and tabes dorsalis
  • - meningovascular neurosyphilis is chronic meningitis involving base of the brain, spinal leptomeninges and cerebral convexities. Obliterative endarteritis (Heubner arteritis) - paretic neurosyphilis caused by invasion of the brain by T. pallidum. Progressive loss of mental and physical functions with mood alterations - Tabes dorsalis is a result of damage by the spirochete to the sensory nerves in dorsal roots, causing locomotor ataxia and sense of position, loss of pain sensation,
    • Neuroborreliosis (Lyme disease)
    • a) Borrelia burgdorferi
    • b) S & S vary
    • i) aseptic meningitis
    • ii) facial nerve palsies
    • iii) mild encephalopathy
    • iv) polyneuropathies
    • Viral encephalitis
    • a) parenchymal infection
    • i) meningeal inflammation (i.e., meningoencephalitis)
  • ii) and sometimes spinal cord involvement (encephalomyelitis) b) most characteristic features i) perivascular and ii) parenchymal mononuclear cell infiltration c) intrauterine viral infections may cause congenital malformations i) rubella d) slowly progressive degenerative disease may occur many years after viral illness i) postencephalitic parkinsonism - post WW 1
    • Arthropod-borne viral encephalitis
    • a) arboviruses
    • i) important cause of epidemic encephalitis
    • - especially in tropical regions
    • b) most important types in Western world are
    • i) western and eastern equine
    • ii) Venezuelan
    • iii) St. Louis
    • iv) La Crosse
    • v) recently in USA, west nile virus
  • c) Clinical: i) generalized neurologic deficits - seizures - confusion - delirium - stupor and coma ii) CSF usually colorless - slightly  pressure - initially a neutrophilic pleocytosis, which rapidly - converts to lymphocytes - proteins are  - glucose is normal
    • HSV type 1 (HSV-1)
    • a) occur at any age
    • i) most common in children and young adults
    • b) most common S & S are mood and memory change
    • c) most often begins in the temporal lobes
    • d) and orbital gyri of frontal lobes
    • HSV type 2 (HSV-2)
    • a) in adults as meningitis
    • b) ~ 50% of neonates develop severe encephalitis to mothers having active
    • primary genital HSV infections
    • Varicella-Zoster virus (Herpes Zoster)
    • a) childhood chickenpox
    • b) reactivation in adults (i.e., “shingles”)
    • i) painful vascular skin eruptions
    • ii) usually is self limited, however
    • iii) may be a persistent postherpetic
    • neuralgia syndrome
    • - ~ 10% of patients
    • c) overt CNS manifestations are rare
    • i) however, when present do produce more severe signs
    • - granulomatous arteritis
    • Cytomegalovirus
    • a) occurs in fetuses and immunosupprressed
    • i) outcome in utero is periventricular
    • necrosis
    • - severe brain destruction with
    • later microcephaly and periventricular calcification
    • b) most common opportunistic viral pathogen in patients with AIDS
    • i) affects 15-20% of patients
    • c) localize in paraventricular subependymal regions of the brain
    • i) severe hemorrhagic necrotizing
    • Poliomyelitis
    • a) picorra group of enteroviruses
    • b) Clinical:
    • i) CNS infections manifest with
    • - meningeal irritation
    • - CSF similar to aseptic meningitis
    • ii) with spinal cord involvement, produces flaccid paralysis
    • - muscle wasting
    • - hyporeflexia in corresponding portion of the body
    • - acute affects can cause death by respiratory muscle paralysis
    • - myocarditis as complicating factor
    • iii) late neurologic syndrome:
    • - “postpolio syndrome” develops 25-30 years after initial resolution  progressive weakness, decreased muscle mass and pain  pathogenesis is unclear
    • Rabies
    • a) severe encephalitis
    • b) transmitted to humans via rabid animals
  • c) Clinical: i) virus enters the CNS in ascending fashion - along PNS around wound site - incubation 1-3 months - as infection advances, patients exhibit extraordinary excitability where slightest touch is painful. Violent motor responses  seizures ii) contraction of pharyngeal muscles on swallowing  foaming at the mouth  aversion to swallowing, even water (hydrophobia)
    • iii) Death from respiratory center failure
    • HIV/AIDS
    • a) ~ 60% of AIDS patients develop
    • neurologic dysfunction (see chapt. 6
    • for details)
    • b) HIV aseptic meningitis occurs within 1- 2 weeks of seroconversion in ~ 10% of patients
    • HIV meningoencephalitis (subacute
    • encephalitis)
    • a) remarkable neurologic disorder
    • i) present with dementia (AIDS dementia
    • complex- - - ADC)
    • - mental slowing
    • - memory loss
    • - mood disturbances
    • - motor abnormalities (ataxia)
    • - bladder/bowel incontinence
    • - seizures
    • b) chronic inflammatory reaction
    • i) microglial infiltrates (microglial nodules)
    • - multinucleated giant cell
    • Vacuolar Myelopathy
    • a) spinal cord disorder
    • i) 20-30 % of AIDS patients in USA
  • ii) similar to subacute combined degeneration (Vit B 12 deficiency) iii) Vit B 12 is not changed in Vacuolar myelopathy iv) pathogenesis unknown 3. Myopathy and Peripheral Neuropathy a) inflammatory myopathy i) most often described disorder in patients with HIV - proximal weakness - pain -  serum CK
  • b) most commonly reported syndromes i) acute and chronic inflammatory demyelinating polyneuropathy - segmental dymyelination - axonal degeneration 4. AIDS in children a) microcephaly with mental retardation b) motor development delay i) spasticity of limbs c) most frequent abnormality i) calcification of small and large vessels and parenchyma within basal ganglia
    • ii) Delay in myelination
    • iii) opportunistic infections rare in children with AIDS as compared with adults.
    • Progressive Multifocal Leukoencephalopathy
    • a) PML progressive viral encephalitis caused by:
    • i) JC polyomavirus
    • - preferentially infects oligodendrocytes
    • - demyelination is primary pathology
    • ii) almost always occurs in immunosuppressed individuals
    • iii) thought to be from reactivation
    • of virus as a result of immunosuppression
    • - ~ 65% of normal people have titers of virus
    • Subacute Sclerosing Panencephalitis
    • a) rare progressive disease
    • i) characterized by cognitive decline
    • ii) spasticity of limbs
    • iii) seizures
    • b) occurs in children and young adults
    • i) months or years after initial infection with measles
    • - altered measles virus
    • c) myelin degeneration
    • d) viral inclusions (within nuclei) of oligodendrocytes and neurons
    • e) inflammation of white and grey matter with neurofibrillary tangles
    • f) with widespread measles vaccinations,
    • disease nearly has disappeared (rare cases around world)
    • Encountered primarily in immunosuppressed
    • individuals
    • a) brain involved late in disease
    • i) blood borne
    • b) types:
    • i) Candida albicans
    • ii) Mucor
    • iii) Aspergillus fumigatus
    • iv) Cryptococcus neoformans
    • - chronic meningitis signs
    • - affecting basal leptomeninges
    • - may obstruct outflow of CSF
    • Three major patterns of fungal infections
    • a) chronic meningitis
  • b) vasculitis (thrombosis and infarcts) i) Mucor ii) Aspergillus c) parenchymal invasion i) granulomas or abscess ii) occur with most of the organisms iii) Candida and Cryptococcus are most common here iv) Candida  multiple micro abscesses
    • Protozoan diseases (review chapter 8 for
    • details)
    • Cerebral toxoplasmosis (T. gondii)
    • a)  importance since AIDS epidemic
    • i) one of most common causes of neurologic symptoms
    • - ~ 4 – 30% on autopsy
    • b) Clinical (subacute in nature):
    • i) evolving over 1-2 weeks
    • ii) focal or diffuse
  • iii) “ring” enhancing lesions - other pathologies also show these lesions. CNS lymphoma, TB and fungal infections iv) brain frequently shows multiple abscesses (necrotic lesions) - cortical areas near white-grey matter junction and deep grey nuclei - areas of necrosis v) may occur in the fetus (i.e., early during pregnancy)
    • Naegleria sp.
    • a) rapidly fatal necrotizing encephalitis
    • Acanthamoeba
    • a) chronic granulomatous meningoencephalitis
    • Transmissible spongiform encephalitis
    • a) Creutzfeldt-Jacob disease
    • b) Gerstmann-Sträussler-Scheinker syndrome
    • c) fatal familial insomnia
    • d) kuru
    • All these disease are associated with an
    • abnormal form of a specific protein
    • a) prion protein (PrP)
    • i) infectious and transmissible
    • b) predominantly characterized by spongiform changes.
    • i) caused by intracellular vacuoles
    • - neurons
    • - glia
    • c) most patients develop progressive dementia
    • i) most common clinical picture is
    • Creutzfeldt-Jacob disease