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Background: Previously, T2-relaxation time (T2 app ) and proton spin density (ρ) detected nerve injury in a small group of ATTRv amyloidosis. Here, we aim to quantify peripheral nerve impairment in a large cohort of symptomatic and asymptomatic ATTRv amyloidosis and correlate T2-relaxometry markers with clinical parameters and nerve conduction studies (NCS)., Methods: Eighty participants with pathologic variants of the transthyretin gene ( TTRv ) and 40 controls prospectively underwent magnetic resonance neurography. T2-relaxometry was performed, allowing to calculate tibial ρ, T2 app and cross-sectional-area (CSA). Detailed clinical examinations and NCS of tibial and peroneal nerves were performed., Results: Forty participants were classified as asymptomatic TTRv -carriers, 40 as symptomatic patients with polyneuropathy. ρ, T2 app and CSA were significantly higher in symptomatic ATTRv amyloidosis (484.2 ± 14.8 a.u.; 70.6 ± 1.8 ms; 25.7 ± 0.9 mm 2 ) versus TTRv- carriers (413.1 ± 9.4 a.u., p  < 0.0001; 62.3 ± 1.3 ms, p  = 0.0002; 19.0 ± 0.8 mm 2 , p  < 0.0001) and versus controls (362.6 ± 7.5 a.u., p  < 0.0001; 59.5 ± 1.0 ms, p  < 0.0001; 15.4 ± 0.5 mm 2 , p  < 0.0001). Only ρ and CSA differentiated TTRv- carriers from controls. ρ and CSA correlated with NCS in TTRv -carriers, while T2 app correlated with NCS in symptomatic ATTRv amyloidosis. Both ρ and T2 app correlated with clinical score., Conclusion: ρ and CSA can detect early nerve injury and correlate with electrophysiology in asymptomatic TTRv -carriers. T2 app increases only in symptomatic ATTRv amyloidosis in whom it correlates with clinical scores and electrophysiology. Our results suggest that T2-relaxometry can provide biomarkers for disease- and therapy-monitoring in the future. more...

Background: Hereditary transthyretin amyloidosis is caused by pathogenic variants in the TTR gene and typically manifests, alongside cardiac and other organ dysfunctions, with a rapidly progressive sensorimotor and autonomic polyneuropathy (ATTRv-PN) leading to severe disability. While most prospective studies have focussed on endemic ATTRv-PN, real-world data on non-endemic, mostly late-onset ATTRv-PN are limited., Methods: This retrospective study investigated ATTRv-PN patients treated at the Amyloidosis Centre of Heidelberg University Hospital between November 1999 and July 2020. Clinical symptoms, survival, prognostic factors and efficacy of treatment with tafamidis were analysed. Neurologic outcome was assessed using the Coutinho ATTRv-PN stages, and the Peripheral Neuropathy Disability (PND) score., Results: Of 346 subjects with genetic TTR variants, 168 patients had symptomatic ATTRv-PN with 32 different TTR variants identified. Of these, 81.6% had the late-onset type of ATTRv-PN. Within a mean follow-up period of 4.1 ± 2.8 years, 40.5% of patients died. Baseline plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) ≥900 ng/l (HR 3.259 [1.421-7.476]; p  = .005) was the main predictor of mortality in multivariable analysis. 64 patients were treated with tafamidis and presented for regular follow-up examinations. The therapeutic benefit of tafamidis was more pronounced when treatment was started early in ATTRv-PN stage 1 (PND scores II vs. I; HR 2.718 [1.258-5.873]; p  = .011)., Conclusions: In non-endemic, mostly late-onset ATTRv-PN, cardiac involvement assessed by NT-proBNP is a strong prognosticator for overall survival. Long-term treatment with tafamidis is safe and efficacious. Neurologic disease severity at the start of treatment is the main predictor for ATTRv-PN progression on tafamidis. more...

Cerebral amyloid angiopathy (CAA) is a progressive microvascular amyloidosis affecting the small- and medium-sized arterioles and the capillaries of brain parenchyma and leptomeninges, and is recognized as a cause of lobar intracerebral hemorrhage (ICH). We report two patients who experienced recurrent ICH due to CAA at an age of 37 (A) and 42 (B) years, respectively. The classic and modified Boston criteria for the diagnosis of CAA include an age limit of 55 years if no biopsy or postmortem examination is performed; CAA is typically not considered in the differential diagnosis of lobar ICH in younger patients. We assume that sporadic CAA is an underdiagnosed entity in younger adults with lobar ICH. more...