Progressive anterior operculum syndrome due to FTLD-TDP: a clinico-pathological investigation

Pathological investigation of progressive anterior operculum syndrome has rarely been reported. We describe clinico-pathological findings in a patient with progressive anterior operculum syndrome. A 74-year-old right-handed man had noticed speech and swallowing difficulties 1 year previously. Neurological examinations showed no abnormality other than a slight limitation of upward gaze and slow tongue movement without fibrillation. We investigated the patient using neuroimaging and neuropsychological examinations and observed him for 2 years until his death, at which point we obtained pathological findings. The patient's facial and masseteric muscles seemed hypotonic with drooling, but he could laugh and yawn normally, showing automatic voluntary dissociation. Palatal and pharyngeal reflexes were normal. Magnetic resonance imaging showed cortical atrophy in the temporal lobes bilaterally. (123)IMP single photon emission computed tomography and positron emission tomography showed decreased blood flow and activity in the frontotemporal lobes, predominantly on the left side. Neuropsychological examinations showed no aphasia, dementia or other neuropsychological abnormality. Intubation fiberscopy, laryngoscopy and video fluorography showed no abnormality. After 6 months his anarthria and dysphagia became aggravated. He died of aspiration pneumonia 2 years after onset. Postmortem examination revealed neuronal degeneration with TDP-43-positive inclusions in the frontal, temporal and insular cortices, consistent with frontotemporal lobar degeneration with TDP inclusions (FTLD-TDP). However, neuronal loss with gliosis was more prominent in the inferior part of the motor cortices, bilaterally. Progressive anterior operculum syndrome could be classified as a variant of FTLD-TDP.