Quantitative Evaluation of Brain Stem Atrophy Using Magnetic Resonance Imaging in Adult Patients with Alexander Disease

Abstract

Brain MRI in adult patients with Alexander disease (AxD) mainly shows atrophy in the medulla oblongata. However, currently there is no quantitative standard for assessing this atrophy. In this study, we quantitatively evaluated the brain stem of AxD patients with glial fibrillary acidic protein (GFAP) mutation using conventional MRI to evaluate its usefulness as an aid to diagnosing AxD in daily clinical practice. Nineteen AxD patients with GFAP mutation were compared with 14 patients negative for GFAP mutation in whom AxD was suspected due to “atrophy of the medulla oblongata.” In the GFAP mutation-positive group, the sagittal diameter of the medulla oblongata, the ratio of the diameter of the medulla oblongata to that of the midbrain (MO/MB), and the ratio of the sagittal diameter of the medulla oblongata to that of the pons (MO/Po) were significantly smaller compared to those of the GFAP mutation-negative group (p < 0.01). The sensitivity and specificity of each parameter were 87.5 and 92.3%, 91.7 and 81.3%, and 88.2 and 100% with a sagittal diameter of the medulla oblongata <9.0 mm, MO/MB <0.60, and sagittal MO/Po <0.46, respectively. These parameters can provide very useful information to differentially diagnose AxD from other disorders associated with brain stem atrophy in adult patients.

Towards genomic database of Alexander disease to identify variations modifying disease phenotype

“… a These patients had been diagnosed with the bulbospinal type 8 , but they were subsequently classified with the intermediate form based on strict re-evaluation in this study.Ref = reference; F = female; M = male; NA = not available. Phenotypic differences in patients with the same genotype may be due to genetic modifiers.…”

“…a These patients had been diagnosed with the bulbospinal type 8 , but they were subsequently classified with the intermediate form based on strict re-evaluation in this study.…”

Pearls & Oy-sters: Adult-Onset Alexander Disease With Transient Swelling of the Medulla Oblongata

“…He was unable to walk in tandem gait, and had nystagmus, diplopia and slight dysarthria. Atrophy, from the medulla oblongata to the superior cervical cord, is a well-known feature of AOAD in MRI, and the sagittal diameter of the medulla oblongata (< 9.0 mm) is useful for the diagnosis of the disease with high sensitivity and specificity 3,4 .…”

“…It was rather swollen in the early stages of the disease. We compared the sagittal diameter of the medulla oblongata in this case with the diameter of the cases in the control group included in a study reported by Yoshida et al 4 . The medullary diameter of the control group was 12.3 ±1.5 mm (mean ±SD), and the Z-scores at each age (45, 50, 55, and 58 years) in this case were 3.13,…”

Clinical characteristics and diagnostic criteria on Alexander disease

“…B, C: a 3-month-old early-onset ALXDRD patient. 46) . In elderly patients or mild cases, abnormal signals of the pyramid of the MO, which are like "eye spots" of butterflies, can be shown (B) 45) .…”