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Case Report: Taxifolin for neurosurgery-associated early-onset cerebral amyloid angiopathy.

ABSTRACT: Cases of iatrogenic cerebral amyloid angiopathy (CAA) have been increasingly reported recently, particularly those associated with neurosurgery. Preclinical studies have shown taxifolin to be promising for treating CAA. We describe a young 42-year-old man with a history of childhood traumatic brain injury that required a craniotomy for hematoma evacuation. He later presented with recurrent lobar intracerebral hemorrhage (ICH) decades later, which was histologically confirmed to be CAA. Serial ¹¹C-Pittsburgh compound B positron emission tomography (¹¹C-PiB-PET) imaging showed a 24% decrease in global standardized uptake value ratio (SUVR) at 10 months after taxifolin use. During this period, the patient experienced clinical improvement with improved consciousness and reduced recurrent ICH frequency, which may be partly attributable to the potential amyloid-β (Aβ) clearing the effect of taxifolin. However, this effect seemed to have diminished at 15 months, CAA should be considered in young patients presenting with recurrent lobar ICH with a history of childhood neurosurgery, and serial ¹¹C-PiB-PET scans warrant further validation as a strategy for monitoring treatment response in CAA for candidate Aβ-clearing therapeutic agents such as taxifolin.

SUBMITTER: Choi MCY

PROVIDER: S-EPMC10985332 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Case Report: Taxifolin for neurosurgery-associated early-onset cerebral amyloid angiopathy.

Choi Maxwell C Y MCY Law Tiffany H P THP Chen Sirong S Cheung William S K WSK Yim Carmen C Ng Oliver K S OKS Au Lisa W C LWC Mok Vincent C T VCT Woo Peter Y M PYM

Frontiers in neurology 20240319

Cases of iatrogenic cerebral amyloid angiopathy (CAA) have been increasingly reported recently, particularly those associated with neurosurgery. Preclinical studies have shown taxifolin to be promising for treating CAA. We describe a young 42-year-old man with a history of childhood traumatic brain injury that required a craniotomy for hematoma evacuation. He later presented with recurrent lobar intracerebral hemorrhage (ICH) decades later, which was histologically confirmed to be CAA. Serial <s ...[more]

PMID: 38566852

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Project description:Cerebral amyloid angiopathy (CAA) induces various forms of cerebral infarcts and hemorrhages from vascular amyloid-? accumulation, resulting in acceleration of cognitive impairment, which is currently untreatable. Soluble amyloid-? protein likely impairs cerebrovascular integrity as well as cognitive function in early stage Alzheimer's disease. Taxifolin, a flavonol with strong anti-oxidative and anti-glycation activities, has been reported to disassemble amyloid-? in vitro but the in vivo relevance remains unknown. Here, we investigated whether taxifolin has therapeutic potential in attenuating CAA, hypothesizing that inhibiting amyloid-? assembly may facilitate its clearance through several elimination pathways. Vehicle- or taxifolin-treated Tg-SwDI mice (commonly used to model CAA) were used in this investigation. Cognitive and cerebrovascular function, as well as the solubility and oligomerization of brain amyloid-? proteins, were investigated. Spatial reference memory was assessed by water maze test. Cerebral blood flow was measured with laser speckle flowmetry and cerebrovascular reactivity evaluated by monitoring cerebral blood flow changes in response to hypercapnia. Significantly reduced cerebrovascular pan-amyloid-? and amyloid-?1-40 accumulation was found in taxifolin-treated Tg-SwDI mice compared to vehicle-treated counterparts (n?=?5). Spatial reference memory was severely impaired in vehicle-treated Tg-SwDI mice but normalized after taxifolin treatment, with scoring similar to wild type mice (n?=?10-17). Furthermore, taxifolin completely restored decreased cerebral blood flow and cerebrovascular reactivity in Tg-SwDI mice (n?=?4-6). An in vitro thioflavin-T assay showed taxifolin treatment resulted in efficient inhibition of amyloid-?1-40 assembly. In addition, a filter trap assay and ELISA showed Tg-SwDI mouse brain homogenates exhibited significantly reduced levels of amyloid-? oligomers in vivo after taxifolin treatment (n?=?4-5), suggesting the effects of taxifolin on CAA are attributable to the inhibition of amyloid-? oligomer formation. In conclusion, taxifolin prevents amyloid-? oligomer assembly and fully sustains cognitive and cerebrovascular function in a CAA model mice. Taxifolin thus appears a promising therapeutic approach for CAA.

Project description:ObjectiveEpileptic seizures occurring in late adulthood often remain of unknown origin. Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease characterized by intracerebral hemorrhage, microhemorrhage and superficial siderosis, occurring mostly in elderly. This observational case-control study aimed to assess the occurrence of CAA in patients experiencing their first seizure in late adulthood.MethodsWe enrolled consecutive patients aged ≥55 years presenting with late-onset seizures (LOS) to the emergency departments or outpatient clinics of two Italian centers, from April 2021 to October 2022. Two age-matched control subjects with neurological symptoms other than epileptic seizure were recruited for each enrolled case. All participants underwent brain MRI (1.5 Tesla) including blood-sensitive sequences and were assessed for probable CAA diagnosis according to Boston criteria 2.0. Chi-squared test was performed to evaluate group differences. Univariate logistic regression analysis tested the association between clinical variables and CAA.ResultsWe included 65 patients with LOS (27 females; mean age 72.2 ± 8.9 years) and 130 controls (49 females; mean age 70.3 ± 8.9 years). Diagnosis of probable CAA was achieved in 10.8% (7/65) of LOS patients and 2.3% (3/130) controls, with a statistically significant difference (p = 0.011). The OR for CAA in the LOS group was 5.2 as compared to the control group (95% CI = 1.3-20.6, p = 0.02).SignificanceThe frequency of CAA is significatively higher in patients with LOS as compared to other neurological diseases, suggesting that a portion of LOS of unknown or vascular origin are associated with CAA.Plain language summaryLate-onset seizures (LOS) are very frequent in the elderly and often have no clear cause. Cerebral amyloid angiopathy (CAA) is a condition where amyloid proteins build up in the blood vessels of the brain, causing them to become weak and prone to bleeding. In this study, we explored the occurrence of CAA in people with LOS. We found that people with LOS were more likely to have a diagnosis of CAA than controls (i.e., people with other neurological diseases).

Dataset Information

Case Report: Taxifolin for neurosurgery-associated early-onset cerebral amyloid angiopathy.

Publications

Case Report: Taxifolin for neurosurgery-associated early-onset cerebral amyloid angiopathy.

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