Table 1.
Key elements of rare forms of cerebral amyloid angiopathy compared to CAA.
| CAA-ri | i-CAA | CAA | |
|---|---|---|---|
| Pathogenesis | Not fully understood. Current hypothesis: (a) Aβ deposition because of inflammation; (b) inflammatory reaction to cerebral vascular deposits of Aβ; (c) coexistence of Aβ and vascular inflammation | Prion like transmission of Aβ by human pituitary derived growth hormone, prior neurosurgical intervention with exposure to cadaveric material | Sporadic or hereditary deposition of Aβ in cortical and leptomeningeal vessels |
| Age at diagnosis | Mean age at diagnosis ~66 years | Symptom onset before the age of 55 years is possible, depending on exposure and latency; however diagnosis should be considered in people aged 55 years or above | Incidence is strongly age dependent; diagnosis is made in individuals over 55 years of age |
| Clinical presentation | Usually subacute cognitive impairment, focal neurological signs, seizures or headache, rather than ICH | TFNEs, focal seizures (with or without secondary generalization), cognitive impairment not attributable to another causes including AIS | ICH, cognitive impairment, TFNEs, epilepsy, headache |
| MRI findings in T2* sequences: GRE, echo-planar, SWI | CMBs, T2 FLAIR hyperintensities, often asymmetrical with contrast enhancement and confluent large distribution between the frontal, temporal, parietal, and occipital lobes | Multiple lobar CMBs, cSS (focal or disseminated), SAH, WMHs, CSO-PVS, cortical atrophy | Multiple lobar CMBs, cSS (focal or disseminated), SAH, WMHs, CSO-PVS, cortical atrophy |
| Diagnostic criteria | Similar to Boston 2.0 criteria, but definite diagnosis requires brain biopsy or autopsy | UCL diagnostic proposed criteria; definite diagnosis requires brain biopsy or autopsy | Boston 2.0 criteria; definite diagnosis requires brain biopsy or autopsy |
| CSF | Elevated protein, pleocytosis; rarely anti-β-amyloid antibodies | Reductions of Aβ − 42 and Aβ − 40. | Reduction up to 50% in levels of Aβ − 42 and Aβ − 40. Possible mildly increased total tau levels |
| ApoE genotype | Mostly ε4/ε4 | ε3/ε3 predominance | Carriers of alleles ε2 and ε4 appear to have greater risk for CAA-related ICH |
| Therapy | Immunomodulatory and anti-inflammatory drugs, steroids | No therapy known, reduction of risk factors is proposed: i.e. hypertension, antithrombotic therapy, head injury | Reduction of risk factors: antithrombotic therapy, hypertension, potential head injury |
| Outcome | High effectiveness of immunosuppressive therapy | Data published to date suggest a better prognosis and evolution compared to sporadic CAA | Unfavorable features including lobar ICH, recurrent ICH and presence of cSS indicates much higher risk of ICH |
FLAIR, Fluid attenuated inversion recovery; CAA, Cerebral amyloid angiopathy; CAA-ri, CAA-related inflammation; i-CAA, iatrogenic cerebral amyloid angiopathy; MRI, magnetic resonance imaging; GRE, gradient echo sequences; SWI, susceptibility weighted imaging; CSF, cerebrospinal fluid; ApoE, Apolipoprotein E; Aβ, amyloid-β; AIS, acute ischemic stroke; ICH, intracerebral haemorrhage; TFNE, transient neurological episode; CMBs, cerebral microbleeds; cSS, cortical superficial siderosis; SAH, subarachnoid haemorrhage; WMH, white matter hyperintensities; ARIA, amyloid-related imaging abnormalities; CSO-PVS, enlarged perivascular spaces in the centrum semiovale; PANCS, primary angiitis of the central nerval system.