Lessons learned from a sporadic FUSopathy in a young man: a case report

Abstract

Background: In frontotemporal dementia (FTD) spectrum, younger patients may correspond to fusopathy cases, and cognitive decline could be rapidly progressive. We present a clinical and neuropathological description of a patient.

Case presentation: A 37-year-old man, without a family history of neurodegenerative diseases, was brought by his family to consult for dysarthria and behavioural change. Initial exploration showed spastic dysarthria and disinhibition. He progressively worsened with a pseudobulbar syndrome, right-lateralized pyramidal signs, left hemispheric corticobasal syndrome and, finally, lower motor neuron signs in his right arm. He died four years after the initiation of the syndrome from bronchopneumonia. Laboratory tests (including blood and cerebrospinal fluid (CSF)) were normal. Magnetic resonance imaging (MRI) and fluorodeoxyglucose-containing positron emission tomography (PET-¹⁸F-FDG) showed left fronto-insular atrophy and hypometabolism. Subsequently, 123I-ioflupane (DaT-SCAN®) single-photon emission computed tomography (SPECT) was pathologic, manifesting bilaterally decreased activity with greater affection on the left side. Only a third electromyogram (EMG) detected denervation in the last year of evolution. No mutations were found in genes such as Tau, progranulin, C9orf72, FUS, TDP-43, CHMP2B, or VCP. In necropsy, severe frontotemporal atrophy with basophilic neuronal cytoplasmic and intranuclear inclusions, negative for tau and TAR DNA binding protein 43 (TDP-43), but positive for fused in sarcoma (FUS) consistent with specifically basophilic inclusions body disease (BIBD) type was found.

Conclusions: In patients affected by FTD, particularly the youngest, with rapidly progressive decline and early motor affection, fusopathy must be suspected. These cases can include motor signs described in the FTD spectrum. Lower motor neuron affection in EMG could be detected late.

Keywords: Frontotemporal lobar degeneration; Neurodegenerative diseases; RNA-Binding protein FUS.

Fig. 1

Neuropathological features of FTLD-ALS with FUS positive inclusions. Post-mortem examination confirmed a severe fronto-temporal atrophy and caudate nucleus degeneration (a-b) Images corresponds to the left hemisphere (the most affected). Histological examination revealed numerous compact basophilic cytoplasmic inclusions in cortical neurons (H&E, c) that are positive with FUS immunohistochemistry (e). Some ubiquitin-positive neuronal intranuclear inclusions (NIIs) were identified in cortex (H&E, d and ubiquitin IHC, f). Scale Bars = 50 μm