Author: Ana Ferreira Ponciano

Leiria Hospital Center, Portugal.

While sporadic cerebral amyloid angiopathy (CAA) is usually age-related and a well-known cause of lobar haemorrhage in older people, several cases of CAA in younger patients have been reported recently. Interestingly, these cases share a common ground of past neurosurgery, procedures, or interventions involving cadaveric human material.1

So far, there was no clear evidence of amyloid-beta transmission and thus it has been classified as an iatrogenic form of CAA. Clinical presentation remains with intracerebral haemorrhage, but cognitive impairment and seizures may also occur. The latter remains unclear whether it is related to younger age at presentation or is due to a different mechanism. There is usually a background of exposure to amyloid-beta with latency between two to four decades until evidence of clinical hallmarks. Therefore, iatrogenic CAA is often associated with early onset, typically in the third to fifth decade, concerning for exposure during neurosurgical procedures during childhood. Most may occur during childhood an involve the use of dura mater, for example. Neuroimaging markers on brain magnetic resonance and cerebral spinal fluid are like those observed in sporadic CAA.2

Some diagnostic criteria have been proposed which include symptom onset before age of 55 years, history of exposure to cadaveric human nervous tissue or other neurosurgical procedures, neuroimaging features of CAA, evidence of amyloid-beta accumulation in the brain (by either lumbar puncture, PET scan, or biopsy), and exclusion of genetic causes.1

Further study of these cases may also contribute to understanding the pathophysiology of the disease. Findings suggest that amyloid-beta can circulate in the central nervous system before deposition, since haemorrhage usually occur in a site distant from tissue exposure. Further, there is a preference for deposition in the cerebral vessels, similar to sporadic CAA. Therefore, seed-to-bleed seems to be a mechanistic pathway to disease, reinforcing the importance of amyloid perivascular clearance and intracerebral haemorrhage.2

Despite being considered rare, the number of case reports has been increasing. Therefore, high clinical suspicion is important to find potential cases, especially in those with CAA at early age and without family history suggesting a genetic cause, although optimal management, incidence and prognosis remains uncertain.

1-Banerjee G, Collinge J, Fox NC, Lashley T, Mead S, Schott JM, Werring DJ, Ryan NS. Clinical considerations in early-onset cerebral amyloid angiopathy. Brain. 2023 Jun 6:awad193.

2-Banerjee G, Samra K, Adams ME, Jaunmuktane Z, Parry-Jones AR, Grieve J, Toma AK, Farmer SF, Sylvester R, Houlden H, Rudge P, Mead S, Brandner S, Schott JM, Collinge J, Werring DJ. Iatrogenic cerebral amyloid angiopathy: an emerging clinical phenomenon. J Neurol Neurosurg Psychiatry. 2022 May 16:jnnp-2022-328792.

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