Meningomyeloencephalitis secondary to Mycobacterium haemophilum infection in AIDS

Infections by opportunistic non-tuberculous mycobacteria (ntm) are rising in global incidence

Abstract WP127: Cerebral Microbleeds, Cerebral Amyloid Angiopathy, And Their Relationships To Quantitative Markers Of Neurodegeneration

Introduction: Age-related cognitive impairment is driven by the complex interplay of neurovascular and neurodegenerative disease. There is a strong relationship between cerebral microbleeds (CMBs), cerebral amyloid angiopathy (CAA), and the cognitive decline observed in conditions such as Alzheimer’s disease. In the early, preclinical phase of cognitive impairment, the extent to which CMBs and underlying CAA impact volumetric changed in the brain related to neurodegenerative disease remains unclear. Methods: We performed cross-sectional analyses from 3 large cohorts: The Northern Manhattan Study (NOMAS), Alzheimer’s Disease Neuroimaging Initiative (ADNI), and the Epidemiology of Dementia in Singapore study (EDIS). We conducted a confirmatory analysis of 82 autopsied cases from the Brain Arterial Remodeling Study (BARS). We implemented multivariate regression analyses to study the association between two related markers of cerebrovascular disease – MRI-based CMBs and autopsy-based CAA, as independent variables, and volumetric markers of neurodegeneration, as dependent variables. Results: We included 2657 participants with available MRI data and 82 autopsy cases from the BARS. In a meta-analysis of NOMAS, ADNI and EDIS, superficial CMBs were associated with larger gray (β=4.49 ± 1.13, P=0.04) and white (β=4.72 ± 2.1, P=0.03) matter volumes. The association between superficial CMBs and larger white matter volume was more evident in participants with one CMB (B=5.17 ± 2.47, P=0.04) than in those with ≥ 2 CMBs (β=1.97 ± 3.41, P=0.56). In the BARS, CAA was associated with increased cortical thickness (β = 6.5 ± 2.3, P=0.016) but not with increased brain weight (β=1.54 ± 1.29, P=0.26). Discussion: Superficial CMBs are associated with larger morphometric brain measures. This association is strongest in brains with fewer CMBs, suggesting that the CMBs/CAA contribution to neurodegeneration may not relate to tissue loss, at least in early stages of disease

Cerebral Microbleeds, Cerebral Amyloid Angiopathy, and Their Relationships to Quantitative Markers of Neurodegeneration

Background and Objectives Age-related cognitive impairment is driven by the complex interplay of neurovascular and neurodegenerative disease. There is a strong relationship between cerebral microbleeds (CMBs), cerebral amyloid angiopathy (CAA), and the cognitive decline observed in conditions such as Alzheimer disease. However, in the early, preclinical phase of cognitive impairment, the extent to which CMBs and underlying CAA affect volumetric changes in the brain related to neurodegenerative disease remains unclear. Methods We performed cross-sectional analyses from 3 large cohorts: The Northern Manhattan Study (NOMAS), Alzheimer's Disease Neuroimaging Initiative (ADNI), and the Epidemiology of Dementia in Singapore study (EDIS). We conducted a confirmatory analysis of 82 autopsied cases from the Brain Arterial Remodeling Study (BARS). We implemented multivariate regression analyses to study the association between 2 related markers of cerebrovascular disease-MRI-based CMBs and autopsy-based CAA-as independent variables and volumetric markers of neurodegeneration as dependent variables. NOMAS included mostly dementia-free participants age 55 years or older from northern Manhattan. ADNI included participants living in the United States age 55-90 years with a range of cognitive status. EDIS included community-based participants living in Singapore age 60 years and older with a range of cognitive status. BARS included postmortem pathologic samples. Results We included 2,657 participants with available MRI data and 82 autopsy cases from BARS. In a meta-analysis of NOMAS, ADNI, and EDIS, superficial CMBs were associated with larger gray matter (beta = 4.49 +/- 1.13, p = 0.04) and white matter (beta = 4.72 +/- 2.1, p = 0.03) volumes. The association between superficial CMBs and larger white matter volume was more evident in participants with 1 CMB (beta = 5.17 +/- 2.47, p = 0.04) than in those with >= 2 CMBs (beta = 1.97 +/- 3.41, p = 0.56). In BARS, CAA was associated with increased cortical thickness (beta = 6.5 +/- 2.3, p = 0.016) but not with increased brain weight (beta = 1.54 +/- 1.29, p = 0.26). Discussion Superficial CMBs are associated with larger morphometric brain measures, specifically white matter volume. This association is strongest in brains with fewer CMBs, suggesting that the CMB/CAA contribution to neurodegeneration may not relate to tissue loss, at least in early stages of disease

Huntington disease oligodendrocyte maturation deficits revealed by single-nucleus RNAseq are rescued by thiamine-biotin supplementation

The complexity of affected brain regions and cell types is a challenge for Huntington's disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex and striatum from R6/2 mice and human HD post-mortem tissue. We identify cell type-specific and -agnostic signatures suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) are arrested in intermediate maturation states. OL-lineage regulators OLIG1 and OLIG2 are negatively correlated with CAG length in human OPCs, and ATACseq analysis of HD mouse NeuN-negative cells shows decreased accessibility regulated by OL maturation genes. The data implicates glucose and lipid metabolism in abnormal cell maturation and identify PRKCE and Thiamine Pyrophosphokinase 1 (TPK1) as central genes. Thiamine/biotin treatment of R6/1 HD mice to compensate for TPK1 dysregulation restores OL maturation and rescues neuronal pathology. Our insights into HD OL pathology spans multiple brain regions and link OL maturation deficits to abnormal thiamine metabolism

Cerebral Microbleeds, Cerebral Amyloid Angiopathy, and Their Relationships to Quantitative Markers of Neurodegeneration

10.1212/WNL.0000000000200142NEUROLOGY9816E1605-E161