CNS nontumor

• Sporadic disease (J Neurol Sci 2021;424:117425):
  • More common in elderly patients, particularly in the seventh and eighth decades of life
  • May coincide with (or be independent of) arteriolosclerotic cerebrovascular disease or Alzheimer disease neuropathologic change
• A large retrospective autopsy series detected sporadic disease in 73% of all subjects and 98% of patients with Alzheimer disease (J Neurol 2008;255:70)
• APOE mutations and cerebral amyloid angiopathy (CAA) (Lancet Neurol 2021;20:68):
  • Mutations in the ε4 allele are associated with sporadic onset CAA and increased severity of disease
  • Mutations in the ε2 allele may be protective
• Familial / hereditary disease (Arch Neurol 2010;67:987):
  • Hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA D)
    • Earlier onset (sixth decade) CAA symptoms with cerebral hemorrhages
    • Autosomal dominant mutation of APP gene (E693Q) on chromosome 21
  • Hereditary cerebral hemorrhage with amyloidosis - Icelandic type (HCHWA I)
    • Cerebral hemorrhages in young to middle aged adults
    • Mutations in cystatin C / gamma trace gene
    • Also known as hereditary cystatin C amyloid angiopathy (HCCAA)
    • Associated with mural deposition of gamma trace protein in arterioles
  • Familial British and Danish forms
    • Mutations in BR12 gene (chromosome 13)
    • Less consistently associated with intraparenchymal hemorrhage
  • Flemish form: APP gene mutations at codon 692 (Neurobiol Dis 1998;5:281)
  • APP gene mutations at codon 694 (Alzheimer disease neuropathologic change with prominent CAA) (Ann Neurol 2001;49:697)
  • Finnish type: autosomal dominant mutations in GSN gene with gelsolin deposition in vessels (Crit Rev Biochem Mol Biol 2012;47:282)
  • Hereditary transthyretin amyloidosis (ATTR): systemic amyloidosis that can affect the central nervous system (Acta Neuropathol 2023;145:113)
  • Additional familial cohorts have been described (Int J Mol Sci 2020;21:3435, Arch Neurol 2010;67:987)

Images hosted on other servers:

Images hosted on other servers:

Contributed by Jared T. Ahrendsen, M.D., Ph.D. and Nicolas Kostelecky, M.D.

Images hosted on other servers:

A 67 year old man in otherwise good health presents with a catastrophic lobar hemorrhage. Microscopic sections at brain autopsy show thickened vessel walls with a double barrel appearance, as shown in the photomicrograph above. What stain will confirm your histologic suspicion?

1. Alpha synuclein
2. Beta amyloid
3. GFAP
4. Luxol fast blue
5. Tau

B. Beta amyloid will be positive in small to medium caliber blood vessels in the cerebral cortex and leptomeninges in patients with cerebral amyloid angiopathy (CAA). Alpha synuclein can be helpful to highlight Lewy bodies. GFAP is a marker of astrocytes and glial tumors. Luxol fast blue highlights myelin and can be helpful to identify areas with demyelination and tau can be helpful to highlight neurofibrillary tangles. Tau can be helpful to highlight neurofibrillary tangles.

Comment Here

Reference: Cerebral amyloid angiopathy

Postmortem examination of a patient who died of intracerebral hemorrhage reveals cortical vessels with associated vessels. Beta amyloid immunohistochemistry establishes this to be a case of cerebral amyloid angiopathy (CAA). How might the inflammatory subtypes of CAA (including cerebral amyloid angiopathy related inflammation [CAAri] and amyloid beta related angiitis [ABRA]) be distinguished?

1. ABRA and CAAri are indistinguishable on histopathologic findings alone
2. ABRA with fibrinoid vessel necrosis; CAAri with perivascular lymphocytic cuffing with extravascular foreign body giant cell reaction
3. ABRA with noncaseating granulomatous inflammation; CAAri with fibrinoid vessel necrosis
4. ABRA with predilection for optic chiasm; CAAri with a predilection for cerebellum

B. ABRA with fibrinoid vessel necrosis; CAAri with perivascular lymphocytic cuffing with extravascular foreign body giant cell reaction. Answer A is incorrect, as these subtypes are distinguishable by the following features: fibrinoid necrosis and granuloma formation (ABRA) and perivascular inflammation and foreign body giant cell reaction without vessel involvement by inflammation (CAAri). Answer C is incorrect because the inflammation does not involve the vessel wall in CAAri. Answer D is incorrect because in ABRA, there is a predilection for the posterior aspect of the brain. The optic chiasm is more commonly affected in neurosarcoidosis. In CAAri, there is a predilection for the posterior aspect of the brain.

Comment Here

Reference: Cerebral amyloid angiopathy