Chorea as a clinical feature of the basophilic inclusion body disease subtype of fused-in-sarcoma-associated frontotemporal lobar degeneration

Abstract

Choreoathetoid involuntary movements are rarely reported in patients with frontotemporal lobar degeneration (FTLD), suggesting their exclusion as a supportive feature in clinical diagnostic criteria for FTLD. Here, we identified three cases of the behavioral variant of frontotemporal dementia (bvFTD) that display chorea with fused in sarcoma (FUS)-positive inclusions (FTLD-FUS) and the basophilic inclusion body disease (BIBD) subtype. We determined the behavioral and cognitive features in this group that were distinct from other FTLD-FUS cases. We also reviewed the clinical records of 72 FTLD cases, and clarified additional clinical features that are predictive of the BIBD pathology. Symptom onset in the three patients with chorea was at 44.0 years of age (±12.0 years), and occurred in the absence of a family history of dementia. The cases were consistent with a clinical form of FTD known as bvFTD, as well as reduced neurological muscle tone in addition to chorea. The three patients showed no or mild parkinsonism, which by contrast, increased substantially in the other FTLD cases until a later stage of disease. The three patients exhibited severe caudate atrophy, which has previously been reported as a histological feature distinguishing FTLD-FUS from FTLD-tau or FTLD-TAR DNA-binding protein 43. Thus, our findings suggest that the clinical feature of choreoathetosis in bvFTD might be associated with FTLD-FUS, and in particular, with the BIBD subtype.

Review: Neuropathology of non‐tau frontotemporal lobar degeneration

“…BI may be weakly argyrophilic and their basophilia has been attributed to their RNA content. The reported clinical presentation associated with BIBD pathology is very heterogeneous including FTD, juvenile or adultonset ALS, combined FTD/ALS, parkinsonism, chorea, dysarthria and gaze palsy [130,149]. BIs strongly label for FUS and other FET proteins, but most importantly FET immunohistochemistry reveals much more and widespread NCI pathology with a wide spectrum of morphologies present in many cortical and subcortical regions (e. g. thalamus, basal ganglia, brainstem), and LMNs ( Figure 3H-J) [130,146] and GCIs ( Figure 3K) are a consistent finding.…”

Globular glial tauopathy presenting as non-fluent/agrammatic variant primary progressive aphasia with chorea

“…Chorea is one of the abnormal involuntary and hyperkinetic movements which has rarely been reported in FTLD [3]. Here, we report a Korean GGT case presenting nonfluentagrammatic primary progressive aphasia (nfvPPA) who developed generalized chorea in the late stage of disease.…”

“…Chorea is one of the key clinical features of HD associated with striatal atrophy. Even though the association between HD phenocopy syndrome and C9ORF72 expansions has recently been described, chorea rarely occurs in patients with underlying FTLD, especially FTLD-tau [3]. Likewise, chorea has never been reported in GGT as a combined extrapyramidal symptom.…”

“…Because diabetes was well controlled when chorea developed, it is not as likely that diabetes was the cause of the patient’s choreic movement. Chorea can be caused by diffuse or focal damage of the cerebral cortex, basal ganglia, substantia nigra, subthalamic nucleus, or cerebellum [3] which can be affected in GGT or other 4R tauopathies (e.g. Progressive supranuclear palsy).…”

Frontotemporal dementia with trans‐activation response DNA‐binding protein 43 presenting with catatonic syndrome

“…In some previous studies, the relation between clinical bvFTD and pathological FTLD‐TDP type A, type B, FTLD‐tau and FTLD‐FET have been noted . Other studies considered the correlation between accumulating proteins as TDP‐43 or FUS and various psychoneurotic phenotypes of FTLD . Still, such studies are small in number, and strict one‐to‐one correlations remain to be elucidated …”