Abeta-related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy

Brain. 2005 Mar;128(Pt 3):500-15. doi: 10.1093/brain/awh379. Epub 2005 Jan 19.

Abstract

Idiopathic or primary angiitis of the CNS (PACNS) and cerebral amyloid angiopathy (CAA) are unusual vasculopathies generally regarded as unrelated disorders. A few case reports have, however, described granulomatous angiitis in patients with sporadic, amyloid beta peptide (Abeta)-related CAA. Here we describe the clinical, neuroradiological and neuropathological features of nine patients with Abeta-related angiitis (ABRA). Combining these with the individual case reports drawn from the literature has allowed us to define ABRA as a clinical entity and to compare its features with those of PACNS. The mean age of presentation of ABRA (67 years) is higher than that of PACNS but lower than that of sporadic non-inflammatory Abeta-related CAA. Alterations in mental status (59%), headaches (35%), seizures and focal neurological deficits (24%) are common. Hallucinations are a presenting manifestation in 12% of cases. Most patients have white matter hyperintensities on MRI but these are of similar appearance to those in PACNS. Cerebrospinal fluid usually shows modest elevation of protein and pleocytosis. Neuropathology reveals angiodestructive inflammation, often granulomatous, and meningeal lymphocytosis. Abeta is consistently present in abundance in affected blood vessels but usually scanty within the parenchyma of the cerebral cortex. However, the cortex includes numerous activated microglia, occasionally in a plaque-like distribution and containing cytoplasmic Abeta. The cerebral white matter shows patchy gliosis and rarefaction, in some cases marked. Our findings (i) help to dissect one separate clinicopathological entity from what is likely to be a spectrum of primary angiitides of the CNS; (ii) have important therapeutic implications for one category of patients with amyloid-related vasculopathy; and (iii) may provide valuable insights into the development of amyloid-associated inflammation, of relevance not only to ABRA but also to Abeta-immunization-related encephalitis and to Alzheimer's disease.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / analysis*
  • Cerebral Amyloid Angiopathy / complications*
  • Cerebral Amyloid Angiopathy / diagnosis
  • Cerebral Amyloid Angiopathy / therapy
  • Cerebral Angiography
  • Electroencephalography
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prognosis
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Vasculitis, Central Nervous System / complications*
  • Vasculitis, Central Nervous System / diagnosis
  • Vasculitis, Central Nervous System / therapy

Substances

  • Amyloid beta-Peptides