An autopsy case of type A FTLD-TDP with a GRN mutation presenting with the logopenic variant of primary progressive aphasia at onset and with corticobasal syndrome subsequently.
Takafumi TomenagaShinobu MinataniHiroto NambaAkitoshi TakedaTakahito YoshizakiJoji KawabeNazere KeyoumuHiroyuki MorinoMakoto HiguchiTomoyasu MatsubaraHiroyuki HatsutaMasato HasegawaShigeo MurayamaYoshiaki ItohPublished in: Neuropathology : official journal of the Japanese Society of Neuropathology (2024)
A 68-year-old woman presented with difficulty finding words and writing characters. Neurological examination led to clinical diagnosis at onset of the logopenic variant of primary progressive aphasia accompanied with ideomotor apraxia, visuospatial agnosia on the right, and Gerstmann syndrome. Bradykinesia and rigidity on the right with shuffling gait developed after one year. Treatment with L-dopa had no effect. The patient was diagnosed with corticobasal syndrome (CBS). Brain magnetic resonance imaging revealed diffuse cortical atrophy dominantly on the left, especially in the temporal, parietal, and occipital lobes. Positron emission tomography did not reveal any significant accumulation of amyloid β or tau protein. She died five years later. Neuropathological examination revealed diffuse cortical atrophy with severe neuronal loss and fibrous gliosis in the cortex. Neuronal cytoplasmic inclusions, short dystrophic neurites, and, most notably, neuronal intranuclear inclusions, all immunoreactive for phosphorylated TDP-43, were observed. Western blotting revealed a full length and fragments of phosphorylated TDP-43 at 45 and 23 kDa, respectively, confirming the pathological diagnosis of type A FTLD-TDP. Whole exome sequencing revealed a pathogenic mutation in GRN (c.87dupC). FTLD-TDP should be included in the differential diagnosis of CBS.
Keyphrases
- amyotrophic lateral sclerosis
- case report
- positron emission tomography
- single cell
- computed tomography
- magnetic resonance imaging
- cerebral ischemia
- multiple sclerosis
- working memory
- low grade
- functional connectivity
- south africa
- white matter
- resting state
- pet ct
- pet imaging
- magnetic resonance
- gene expression
- genome wide
- subarachnoid hemorrhage
- dna methylation
- high grade
- drug induced
- combination therapy