Gadoxetate-enhanced abbreviated MRI is highly accurate for hepatocellular carcinoma screening.

The primary objective was to compare the performance of 3 different abbreviated MRI (AMRI) sets extracted from a complete gadoxetate-enhanced MRI obtained for hepatocellular carcinoma (HCC) screening. Secondary objective was to perform a preliminary cost-effectiveness analysis, comparing each AMRI set to published ultrasound performance for HCC screening in the USA. This retrospective study included 237 consecutive patients (M/F, 146/91; mean age, 58 years) with chronic liver disease who underwent a complete gadoxetate-enhanced MRI for HCC screening in 2017 in a single institution. Two radiologists independently reviewed 3 AMRI sets extracted from the complete exam: non-contrast (NC-AMRI: T2-weighted imaging (T2wi)+diffusion-weighted imaging (DWI)), dynamic-AMRI (Dyn-AMRI: T2wi+DWI+dynamic T1wi), and hepatobiliary phase AMRI (HBP-AMRI: T2wi+DWI+T1wi during the HBP). Each patient was classified as HCC-positive/HCC-negative based on the reference standard, which consisted in all available patient data. Diagnostic performance for HCC detection was compared between sets. Estimated set characteristics, including historical ultrasound data, were incorporated into a microsimulation model for cost-effectiveness analysis. The reference standard identified 13/237 patients with HCC (prevalence, 5.5%; mean size, 33.7 ± 30 mm). Pooled sensitivities were 61.5% for NC-AMRI (95% confidence intervals, 34.4-83%), 84.6% for Dyn-AMRI (60.8-95.1%), and 80.8% for HBP-AMRI (53.6-93.9%), without difference between sets (p range, 0.06-0.16). Pooled specificities were 95.5% (92.4-97.4%), 99.8% (98.4-100%), and 94.9% (91.6-96.9%), respectively, with a significant difference between Dyn-AMRI and the other sets (p < 0.01). All AMRI methods were effective compared with ultrasound, with life-year gain of 3-12 months against incremental costs of US$ < 12,000. NC-AMRI has limited sensitivity for HCC detection, while HBP-AMRI and Dyn-AMRI showed excellent sensitivity and specificity, the latter being slightly higher for Dyn-AMRI. Cost-effectiveness estimates showed that AMRI is effective compared with ultrasound. • Comparison of different abbreviated MRI (AMRI) sets reconstructed from a complete gadoxetate MRI demonstrated that non-contrast AMRI has low sensitivity (61.5%) compared with contrast-enhanced AMRI (80.8% for hepatobiliary phase AMRI and 84.6% for dynamic AMRI), with all sets having high specificity. • Non-contrast and hepatobiliary phase AMRI can be performed in less than 14 min (including set-up time), while dynamic AMRI can be performed in less than 17 min. • All AMRI sets were cost-effective for HCC screening in at-risk population in comparison with ultrasound

The Cycad Genotoxin MAM Modulates Brain Cellular Pathways Involved in Neurodegenerative Disease and Cancer in a DNA Damage-Linked Manner

Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of adult C57BL6 wild-type mice treated with a single systemic dose of MAM acetate display DNA damage (O6-methyldeoxyguanosine lesions, O6-mG) that remains constant up to 7 days post-treatment. By contrast, MAM-treated mice lacking a functional gene encoding the DNA repair enzyme O6-mG DNA methyltransferase (MGMT) showed elevated O6-mG DNA damage starting at 48 hours post-treatment. The DNA damage was linked to changes in the expression of genes in cell-signaling pathways associated with cancer, human neurodegenerative disease, and neurodevelopmental disorders. These data are consistent with the established developmental neurotoxic and carcinogenic properties of MAM in rodents. They also support the hypothesis that early-life exposure to MAM-glucoside (cycasin) has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for food or medicine, or both. These findings suggest environmental genotoxins, specifically MAM, target common pathways involved in neurodegeneration and cancer, the outcome depending on whether the cell can divide (cancer) or not (neurodegeneration). Exposure to MAM-related environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer's disease

Is Neurodegenerative Disease a Long-Latency Response to Early-Life Genotoxin Exposure?

Western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia complex, a disappearing neurodegenerative disease linked to use of the neurotoxic cycad plant for food and/or medicine, is intensively studied because the neuropathology (tauopathy) is similar to that of Alzheimer’s disease. Cycads contain neurotoxic and genotoxic principles, notably cycasin and methylazoxymethanol, the latter sharing chemical relations with nitrosamines, which are derived from nitrates and nitrites in preserved meats and fertilizers, and also used in the rubber and leather industries. This review includes new data that influence understanding of the neurobiological actions of cycad and related genotoxins and the putative mechanisms by which they might trigger neurodegenerative disease

Trans-synaptic degeneration of the optic radiation from optic nerve atrophy

Fourty-seven-year-old woman with 5-year history of progressive decreased left eye vision. Optical coherence tomography showed optic nerve atrophy (left > right) and brain MRI revealed T2 hyperintense signal along the course of left optic radiations. We present a case of a trans-synaptic degeneration of the optic radiation in a patient with confirmed optic atrophy. Trans-synaptic degeneration of the optic radiation without associated infarct or inflammatory disease has not been reported before in patients with optic atrophy