Background: Hyperintensities in the splenium of the corpus callosum (CCS) have been proposed as a radiographic diagnostic criterion for fragile X-associated tremor ataxia syndrome (FXTAS).
Methods: Magnetic resonance images from patients with FXTAS and from nonpremutation carriers with movement disorders were viewed by a radiologist who was blinded to gene status, and radiographic criteria for FXTAS were scored. Phenotypic data used for diagnosis of FXTAS also were collected.
Results: Twenty-two patients with FXTAS and 23 controls were included. Hyperintensity in the CCS (the CCS sign) was more common in men with FXTAS versus controls (87% vs. 40%) but not in women with FXTAS (100% vs. 50% in controls). The CCS sign had higher sensitivity compared with the middle cerebellar peduncle sign (white matter lesions in middle cerebellar peduncle) in both men (0.87 vs. 0.67) and women (1 vs. 0.29) with FXTAS, but it had lower specificity in both men (0.6 vs. 0.8) and women (0.5 vs. 1).
Conclusions: The CCS sign is common in patients with FXTAS, but it is not significantly more prevalent in women with FXTAS compared with controls. This may be due to small sample sizes in the current study. Other signs, such as brainstem white matter disease, were more common in women with FXTAS and differed from those in men with FXTAS. This finding suggests that additional studies evaluating the diagnostic criteria for FXTAS need to be conducted, ideally with neuropathological confirmation of the disease.
Keywords: fragile X mental retardation 1 (FMR1); fragile X‐associated tremor ataxia syndrome; magnetic resonance imaging; middle cerebellar peduncle; splenium of the corpus callosum.