An autopsy case of frontotemporal dementia with severe dysarthria and motor neuron disease showing numerous basophilic inclusions

Abstract

We report a clinicopathological study of a patient suffering from frontotemporal dementia (FLD) with severe dysarthria and concomitant motor neuron disease (MND). The patient was a 52-year-old woman with almost simultaneous emergence of severe dysarthria and FTD. The severe dysarthria subsequently evolved into anterior opercular syndrome. Motor neuron signs then emerged, and the patient developed akinetic mutism approximately 2 years after the onset of the disease. The patient died of pneumonia after a 7-year clinical illness. Pathologically, severe and widespread degeneration in the frontal and temporal lobes, including the anterior opercular area, limbic system, basal ganglia, spinal cord and cerebellum, and frequent ubiquitin- and tau-negative basophilic inclusions were observed. The pyramidal tracts and anterior horns of the cervical cord also showed marked degeneration. Cases showing basophilic inclusions reported so far have been divided into two groups: early onset FTD and MND with basophilic inclusions. Our case presented clinicopathological features of both FTD and MND, which suggests that cases showing basophilic inclusions may constitute a clinicopathological entity of FTD/MND.

An autopsied case of sporadic adult-onset amyotrophic lateral sclerosis with FUS-positive basophilic inclusions

“…22 Interestingly, the present case had the oldest age at onset of all reported sporadic cases with BIs and presented with a classical form of ALS, while other cases usually showed atypical symptoms (Table 1). [13][14][15][16][17][18] From a clinicopathological point of view, these results may indicate the heterogeneity of ALS with BIs or FTLD-FUS (BIBD) in the FTLD spectrum. 22 BIs showed immunoreactivity for p62 and LC3.…”

“…Although half the reported cases of sporadic ALS with BIs have been examined and demonstrated FUS immunoreactivity, 11,15,17,18 these reports raise the possibility that atypical ALS with BIs is separated into FUS proteinopathy, but does not completely overlap FTLD-FUS (BIBD). 22 Interestingly, the present case had the oldest age at onset of all reported sporadic cases with BIs and presented with a classical form of ALS, while other cases usually showed atypical symptoms (Table 1).…”

“…We report an autopsy case of sporadic senile-onset ALS with numerous BIs, which were FUS-immunoreactive and 15 Sasaki et al 16 Kusaka et al 17 Kusaka et al 18 Mizutani et al 19 Present case were investigated ultrastructurally. As far as we know this is the first report of a sporadic ALS case with BIs in which absence of exonal mutations in the FUS gene is confirmed.…”

“…The distribution of BIs was analyzed in comparison with reported sporadic cases with BIs (Table 1) [14][15][16][17][18][19] and these are shown in Figure 2. The inclusions were most frequently found in the red nuclei, the oculomotor nuclei, the motor nuclei of trigeminal nerves, the facial and pontine nuclei, inferior olivary nuclei, the ambiguous and hypoglossal nuclei and anterior horns of the spinal cord irrespective of neuronal loss and gliosis.…”

“…Little is known about adult-onset ALS with BIs; only few sporadic cases have been so far documented to have atypical symptoms, such as ophthalmoplegia, autonomic dysfunction, cerebellar ataxia or a frontal lobe syndrome. [14][15][16][17][18][19] One familial adult-onset case with posterior column degeneration and basophilic inclusion bodies has been reported. 20 BIs are present in BIBD and not found in cases of classic ALS.…”