Alexander disease (AxD)
https://www.sciencedirect.com/science/article/pii/S1096719226004725
Alexander disease (AxD) is a rare leukodystrophy, where Type 1 AxD usually begins in infancy or early childhood and is caused by pathogenic variants, in the GFAP gene, which provides instructions for making glial fibrillary acidic protein (GFAP) in astrocytes. Pathogenic variants are changes in the DNA that have been confirmed to cause disease. Astrocytes are the largest glial cells in the central nervous system and are involved in various cell processes including helping with communication between neurons. Children with type 1 AxD can experience developmental delay, seizures and difficulties with movement, but disease progression varies considerably. In this study, researchers investigated whether patterns seen on magnetic resonance imaging (MRI) could help predict disease progression. They analysed the first brain MRI scans from 47 people with genetically confirmed type 1 AxD from leukodystrophy centres worldwide. Patients were classified into subtypes 1a–1d, which reflect increasing levels of developmental achievement and longer-term stability. The researchers found that areas of abnormal white matter on MRI were associated with more severe disease. For example, involvement of the parietal subcortical white matter was strongly associated with type 1b AxD, a subtype in which children do not achieve independent walking. The parietal subcortical white matter is a section of deep white matter in the midbrain between the cerebral cortex and ventricles, it controls sensory, visual, visuospatial (visual and spatial awareness), and language functions. Abnormalities in regions including the occipital and temporal white matter, corpus callosum and cerebellum, were also linked with type 1b disease. Changes in the occipital periventricular white matter helped distinguish type 1c from type 1d, potentially identifying children at greater risk of losing independent walking before adolescence. These findings suggest that MRI could provide an early prognostic tool to predict what will likely happen for type 1 AxD. The authors developed a preliminary MRI scoring system and clinical flowchart to support early disease stratification which is a system to separate people into risk groups depending on characteristics of disease. However, larger prospective studies are needed to validate these findings before the approach can be used routinely.