The dorsolateral prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex are typically affected, according to Tenatoprazole? neuroimaging and neuropathologic studies [20,21,26,35], and this topography readily explains the full bvFTD spectrum of behavioral features. Yet there are those who do not have neuroimaging evidence of frontal atrophy or hypometabolism [21], and as noted above, perhaps the cerebellar degeneration contributes to these behavioral features similar to the hypothesis that such degeneration might explain executive dysfunction. These ‘frontally impaired but frontally normal on neuroimaging’ cases clearly deserve ample study, as understanding the neuroanatomic correlates of their impairment will not only aid in understanding the disease of c9FTD/ALS but also enhance our understanding of brain-behavior correlations in general.

A few investigators have observed that some c9FTD/ALS cases exhibit the most bizarre behavioral manifestations they have ever witnessed among all of the bvFTD patients they have cared for [21,28]. Psychotic features, obsessive-compulsive behaviors, odd ritualistic behaviors, and so on are often striking. A summary of observations by clinicians is presented in Table ?Table22. Table 2 Descriptions of dramatic behavioral manifestations associated with c9FTD/ALS Other clinical features Whereas the documentation of other clinical features varied across reports, many cases with frontal release signs, parkinsonism, upper or lower motor neuron dysfunction (or both) not fulfilling criteria for ALS, and the full ALS phenotype were observed.

Limb apraxia was rarely documented. Atypical features Atypical features are already emerging. A very interesting (and, for many clinicians, somewhat frightening) finding is the identification of the C9ORF72 mutation in rare cases of the FTD phenocopy syndrome [47]. The FTD phenocopy refers to those individuals who clearly exhibit cognitive and behavioral changes suggestive of bvFTD, but neuropsychological tests and neuroimaging studies tend to be more normal than not during the initial years of symptoms [48,49]. The ‘typical’ FTD phenocopy patient does not show progression on longitudinal clinical, neuropsychological, and neuroimaging evaluations, and such cases are now Brefeldin_A considered to usually have a non-degenerative substrate for their features. When first encountering patients who clearly have bvFTD features but no corroborating evidence of an underlying neurodegenerative disorder, the clinician is faced with the obvious challenge selleck kinase inhibitor of establishing a confident diagnosis and predicting what the future holds. And since so few cases have come to autopsy, the underlying substrate for their symptoms has not been well characterized.