Severe traumatic brain injury in early adulthood and cerebral amyloid angiopathy

Recent research has increasingly recognized a potential link between severe traumatic brain injury (TBI) decades ago and the later development of cerebral amyloid angiopathy (CAA). Although the precise mechanisms linking these two pathologies are incompletely understood, there is a hypothesis that TBI may disrupt amyloid β (Aβ) turnover, with its resultant progressive accumulation within the walls of cerebral vessels. We present the case of a woman with biopsy-confirmed CAA and a history of severe TBI in her early adulthood, who suffered three recurrent intracerebral hemorrhages (ICHs) in the right occipital region, during the course of 1 month. Two of the ICHs necessitated neurosurgical evacuation, and the patient showed a fairly good recovery. This case further extends our previously reported series on the relationship between preceding childhood TBI and the development of CAA. TBI increases amyloid precursor protein production enhancing Aβ levels and promoting chronic blood–brain barrier dysfunction, impairing Aβ clearance. The glymphatic system and intramural periarterial drainage pathways may be compromised following TBI. Additionally, the inflammatory response to TBI promotes vascular oxidative stress and endothelial dysfunction, which may further exacerbate Aβ accumulation. A repeated ICH may be associated with a much worse clinical outcome, necessitating prolonged meticulous observation after the first bout of an ICH in these patients. Further research is needed to clarify TBI's role in CAA progression.