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PATHOLOGY of the CNS - Coggle Diagram

- - - - active plaques: myelin depletion with inflammatory elements and macrophages
      - inactive plaques: no myelin, gliosis
      - shadow plaques: re-myelination by pre-existing oligodendrocytes
- - - - amyloid beta peptide
        
        total tau protein
        
        tau phosphorylated at threonine 181
        
        Abeta1-42/Abeta1-40 ratio
    - - preclinical: cognitively unimpaired with normal performing subjects on cognitive testinf, who may report subjective cognitive decline
      - AD with cognitive impairment: evidence of cognitive impairment and evidence of decline in cognitive performance from baseline in an individual who performs daily living activities independently
      - AD with dementia: substantial progressive cognitive impairment that affects several domains and/or neurobehavioral symptoms and results in a clearly evident functional impact on daily life
    - - variable cortical atrophy
        
        vacuolar degeneration of the hippocampus
        
        neurofibrillary bodies in the cytoplasm of neurons, flame-shaped
        
        amyloid plaques: EC deposition of beta amyloid
        
        amyloid angiopathy: in capillaries and arteries
  - - - amyotrophic lateral sclerosis
        
        fatal degenerative disorder of upper and lower motor neurons
        
        sporadic, pts >50 y
        
        familial in 10%, younger age, associated with hexanucleotide repeat expansion
        
        pathology
        
        degeneration and loss of motor neurons
        
        gliosis, microglial activation and cytoplasmic deposition of TDP-43, ubiquitin and SOD1
        
        eosinophilic cytoplasmic inclusions (Bunina bodies)
        
        muscular atrophy due to denervation atrophy
  - - - alpha synuclein accumulation, impairing the function of mitochondria, lysosomes and endoplasmic reticulum, interfering with microtubular transport
        
        Lewy bodies: large alpha synuclein aggregates forming round lamellated eosinophilic cytoplasmic inclusions in the neuronal body
        
        Lewy neurites: fibrils made of insoluble polymers of alpha synuclein in neuronal processes and in astrocytes and oligodendroglial cells
        
        dopamine-producing neurons of the substantia nigra are mostly affected
- - - - epi-dural
        hematoma
        
        location
        
        fronto-parietal-temporal or posterior fossa (children)
        
        causes
        
        rupture of the middle meningeal artery, diploic veins, cavernous sinuses
        
        pathology
        
        fibrin debris and coagulated blood
        
        small/large masses
        
        associated lesions
        
        hernia
        
        due to dural/leptomeningeal/parenchymal involvement and consequent compression
        
        evolution
        
        small size --> fibrotic reaction --> scar / cyst
        
        large size --> exitus
      - sub-dural
        hematoma
        
        causes
        
        rupture of vessels inside the dural layer (cerebral veins, middle meningeal artery)
        
        more common in elderly
        
        location
        
        at convexities or at the base
        
        associated with parenchymal hematoma
        
        "satellite hematoma"
        
        forms
        
        acute:
        
        associated with meningeal and parenchymal lesions
        
        small or large
        
        in severe trauma
        (after 2-3 days)
        
        subacute:
        
        mild trauma --> loss of consciousness
        
        clot +/- fibrinous tissue
        
        chronic:
        
        mild or inapparent trauma
        
        parietal, bilateral
        
        variable thickness
        
        possible cystic evolution (HYGROMA)
        
        more common in elderly
        
        cortical brain atrophy --> increased subdural space
        
        more delicate venous network prone to rupture
      - subarachnoidal hemorrhage
        
        causes
        
        rupture of aneurysms
        
        extension from extradural or subdural hematomas
        
        extension from intracerebral hemorrhage
        
        tumors
        
        vascular malformations
        
        rupture of aneurysms may be a consequence of hypertension
        
        common cause of sudden death
        
        in particular in young patients
        
        in elderly, instead, consider more commonly the event of intra-parenchymal hemorrhage
    - - concussion
      - contusion
- - - - bacteria
        
        M. TUBERCULOSIS
        
        DD
        
        parenchymal focal lesions: tumors
        
        single lesion: primary tumor of the brain
        
        necrosis in the centre of the lesion: glioblastoma
        
        multiple focal lesions: metastases
        
        key point:
        
        clinical history
        
        cytology examination of CSF
        --> lymphocytes infiltration
        and epithelioid cells
        
        PCR
        
        meningitis:
        
        onset as meningeal TBC (Rich's focus)
        
        subarachnoidal spread from rupture of tubercoli
        
        gray gelatinous exudate typically located at the base
        
        lymphocytes, plasma cells,
        epithelioid macrophages
        
        complications
        
        cranic nerves involvement
        
        communicating hydrocephalus
        
        vasculitis of the arteries
        --> ischemia and stroke
        
        MENINGITIS
        
        epidural abscesses
        
        bacterial origin:
        
        mastoid
        
        paranasal sinuses
        
        vertebral osteomyelitis
        
        paravertebral infections
        
        pathology:
        
        skull: well-demarcated
        
        vertebral column: multiple segments involvement
        
        complications:
        
        subdural extension
        
        thrombophlebitis of epidural veins
        (--> spine ischemia)
        
        subdural empyema
        
        pathogens:
        
        staphylococci
        
        streptococci
        
        pathogenesis:
        
        adults: from epidural abscesses, thrombophlebitis, trauma
        
        children: from leptomeningitis
        
        pathology:
        widespread
        
        bacterial leptomeningitis
        
        general findings:
        
        multiple ways of dissemination
        
        more frequently from hematogenous spread
        
        easy spread
        
        pathogenesis:
        bacteremia -> choroid plexus invasion -> acute plexitis -> liquoral spread in sub-arachnoidal spaces
        
        different depending on the age of the patient
        
        0-1m: E. coli, Streptococcus beta, L. monogenes
        
        3m-6y: Hemophylus, S. pneumoniae, N. meningitidis
        
        6-20y: Neisseria meningitidis, S. pneumoniae
        
        adults: S. pneumoniae
        
        very difficult treatment due to:
        
        difficult for antibiotics to get to these structures due to BBB
        
        CSF is ideal for bacterial growth
        
        pathology
        
        brain edema
        
        vascular congestion in the pia
        
        exudate in the subarachnoidal space from the skull to the spine
        
        limited parenchymal extension
        (Virchow-Robin spaces)
        
        evolution:
        
        2 more items...
        
        BRAIN ABSCESSES
        
        multiple
        
        hematogenous (middle meningeal artery)
        
        site: border between gray and white matter
        
        from heart (endocarditis), lungs
        
        immunocompromised patients
        
        complications
        
        ventricular involvement
        
        endocardial hypertansion
        
        brain herniation
        
        hydrocephalus (abscess in the posterior fossa)
        
        solitary
        
        from local extension:
        
        frontal lobes: sinusitis, dental infections
        
        temporal lobes: otitis media
        
        cerebellar lobes: mastoid infections
        
        strep, staph
      - fungi
        
        rare in the past
        
        relatively frequent in immunocompromised patients (opportunistic)
        
        usually secondary to other primary locations
        
        different forms: meningitis, cerebritis, focal lesions, "Stroke-like syndromes", compressive spinal symptoms
        
        spores infection --> meningitis
        
        hyphae infection --> micro-abscesses
        
        lesions may mimic tuberculosis with necrotic areas and epithelioid cells
        
        PAS+ and silver staining
        
        candidosis
        
        hematogenous spread
        
        multiple micro-abscesses
        
        meningitis
        
        cryptococcosis:
        
        hematogenous spread
        
        localized lesions
        
        gelatinous meningitis with
        mild inflammation
        
        mucor:
        
        from nasal cavity
        
        bone erosions, basilar necrosis, brain infarcts, neutrophilic cerebritis
        
        aspergillosis;
        
        hematogenous spread (lungs) and local (paranasal sinuses, orbit, ear)
        
        multiple necrotic areas
      - parasites and protozoa
        
        toxoplasmosis
        
        congenital:
        
        leptomeningitis, ependymitis, calcifications
        
        gliosis around the aqueduct of Sylvius --> hydrocephalus
        
        presence of parasites
        
        acquired:
        
        immunocompromised patients
        
        necrotising cerebritis, abscesses
        --> rupture of subarachnoidal space
        
        presence of parasites
        
        metazoa
        
        tenia solium
        
        trematodes --> schistosoma
        
        nematodes --> trichinella
        
        echinococcus --> intracerebral cysts
      - viruses
        
        encephalitis
        
        at histology:
        
        perivascular inflammation with lymphocytes, plasma cells and monocytes
        
        glial nodules
        
        viral nuclear inclusions and neuronophagia
        
        at the early stages in particular,
        with perivascular localization
        
        either endemic or sporadic
        
        endemic form is frequently associated with arboviruses infection
        
        sporadic form is associated with HSV
        
        HSV1
        
        more frequent in children
        
        acute / subacute
        
        temporal lobe / periorbital
        
        micro: Cowdry viral inclusions in neurons and glial cells
        
        necrotizing and hemorrhagic lesions
        
        HSV2
        
        transmission at birth
        
        CMV-associated:
        
        ependymal and sub-ependymal
        
        classic nuclear inclusion
        
        necrotizing
        
        fetal life and immunocompromised patients
        
        polio enterovirus-associated:
        
        oro-fecal transmission
        
        anterior motoneurons in the spine
        
        clinical forms: fulminant or worsening flaccid paralysis
        
        neurogenic muscle atrophy caused by denervation
        
        rabies-associated:
        
        neuronal ascending bite transmission
        
        macro: edema and vascular congestion
        
        micro: edema and inflammation of basal ganglia, eosinophilic intracytoplasmic bodies (Negri) in the hippocampus
        
        symptoms: hypersensitivity, convulsions, muscle contraction of the pharynx
        
        death from respiratory paralysis
        
        HIV-associated:
        
        aseptic meningitis:
        1-2 weeks from seroconversion
        
        meningo-encephalitis:
        
        AIDS-dementia complex
        
        insidious onset, memory loss and mood alterations
        
        macro: diffuse pallor of white matter
        
        micro: micro-glial nodules, necrosis, giant cells
        
        viruses in macrophages, microglia and endothelia
        
        neurons and oligodendrocytes not infected, but damaged by cytotoxic cytokines
        
        vacuolar myelopathy:
        
        20-30% of AIDS patients
        
        vacuolization of white matter and spine posterior/lateral horns
        
        unclear pathogenesis: no HIV detected
        
        myopathies and cranial/peripheral neuropathies:
        
        subacute myopathy with weakness and necrosis of muscular fibers
        
        demyelinating neuropathy
        
        polioma JC
        
        --> progressive multifocal leukoencephalopathy
        
        destruction of oligodendrocytes
        
        opportunistic infection
        
        irregular and diffuse disarrangement of white matter with foci of demyelinationwith tendence to be confluent
        
        viral inclusions in the nuclei of oligodendrocytes
        
        gliosis
        
        foamy macrophages full of empty myelin debris
        
        poor or absent lymphocytic infiltration
        
        death within 6 months
- - - - resistant to protease digestion
        
        resistant to disinfection using chemical or physical agents
        
        PrPSc itself facilitates conversion of PrPc to PrPSc
        
        damage occurs due to:
        
        accumulation of PrPSc
        
        depletion of PrPc
    - - sporadic: spontaneous conversion
      - familial: mutations of PRNP
        
        fatal familial insomnia
        
        Gerstmann-Straussler-Scheinker disease
        
        genetic CJD
      - acquired: exposure to exogenous PrPSc
        
        kuru
        
        variant CJD
        
        iatrogenic CJD
    - - brain MRI: hyper-intensity in caudate and putamen is sensitive and specific for sCJD
      - CSF biomarkers: specific (detect PrPs) and non-specific (rapid neurodegeneration signs, e.g. tau)
      - EEG: periodic sharp wave complexes not completely specific and sensitive
      - brain biopsy: NOT USED
      - pathology findings
        
        spongiosis
        
        microglia activation
        
        plaques