The Corpus Callosum Splenium Sign in Fragile X‐Associated Tremor Ataxia Syndrome

Abstract

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.

A Novel Clinical Phenotype of Fragile X‐Associated Tremor/Ataxia Syndrome

“…Atrophy, white matter changes, and hyperintensities in the splenium of the corpus callosum have also been reported …”

Prevalence of fragile X‐associated tremor/ataxia syndrome: A survey of essential tremor patients with cerebellar signs or extrapyramidal signs

“…CCS sign is another imaging marker, defined by hyperintensity in the splenium of the corpus callosum. One study reported its sensitivity and specificity in men to be 0.87 and 0.6, respectively (Deborah, Hall, & P, Meghan Hermanson BS, Emily Dunn MD, The, ). In our study, MCP sign was present only in patients with FXTAS.…”

Fragile X premutation and associated health conditions: A review

“…and in the splenium of the corpus callosum (CCS). [48][49][50][51] White matter lesions in the MCP is a highly specific, 48 but not pathognomonic, MRI finding of FXTAS. This MCP sign is more common among male carriers than female carriers (60 vs. 13%) 50 and associated with more severe cognitive deficits and a longer history of symptoms.…”

“…52 While the lesions in MCP are a distinguishing sign of FXTAS, white matter lesions in the CCS seem to provide a higher sensitivity in both male and female carriers, though with lower specificity. 51 A recent study suggested the decrease of middle cerebellar peduncle width as an early radiological change of emerging FXTAS. 53 Although FXTAS has been known for about two decades, it is believed to be underdiagnosed for there is no pathognomonic presentation and the clinical symptoms can mimic or co-occur with other common neurological illnesses such as Parkinson disease or Alzheimer disease.…”