Frontotemporal dementia (FTD) is a clinical entity that comprises at least two distinct diseases:
Pick's disease with Pick bodies and
frontotemporal lobar degeneration with tau-negative and
ubiquitin-positive inclusions (
FTLD-U).
FTLD-U is now usually referred to as
FTLD-TAR
DNA binding protein 43 (TDP-43). FTLD-TDP-43, but not
Pick's disease with tau-positive Pick bodies, is often associated with
motor neuron disease (MND). More than 200 cases of this combined form, i.e., FTD-MND, have been reported in Japan. The neuropathological characteristics of MND in patients with FTD are essentially similar to the MND in patients without
dementia. However the other characteristics of the combination of FTD and MND are such that the author has considered this disease a unique clinicopathological entity. These characteristics are as follows: (1) frontotemporal lobe-type
dementia with insidious onset, usually in the presenile period; (2) neurogenic muscular wasting during the course of the illness [
amyotrophic lateral sclerosis (ALS)]-- or [spinal
progressive muscular atrophy (SPMA)]-like symptoms); (3) duration from the onset of illness to death is 2-5 years (average duration, 30.6 months); (4) both extrapyramidal symptoms and definite sensory deficiency are less commonly observed; (5) no characteristic abnormalities in the cerebrospinal fluid (CSF) or on the electroencephalogram (EEG) in screening tests; (6) no known parental consanguinity or familial occurrence; and (7) nonspecific mild-to-slight degenerative changes in the frontotemporal cortex, hypoglossal nuclei, spinal cord, and frequently in the substantia nigra. FTD-MND is characterized by
ubiquitin-immunoreactive intraneuronal inclusions in cortical layers II and III and the hippocampal dentate granule cells. The occurrence of
ubiquitin-positive, tau-negative and ubiquitinated TDP-43 positive inclusions could be the key to determining the pathological background of this disease. Further studies are required clinicopathological differentiation between FTD-MND and ALS-
dementia (ALS-D).