frontotemporal lobar degeneration (FTLD)
Frontotemporal lobar degeneration (FTLD) is the pathological description of a group of neurodegenerative disorders characterized by focal atrophy of the frontal and temporal cortices. FTLD results in variable clinical manifestation as one of the frontotemporal dementia (FTD) syndromes with behavioral and language variants, which in turn overlap with some related motor degenerative conditions.
Terminology
The conditions grouped under this term vary from publication to publication, depending on whether clinical, pathological or genetic factors are used in the classification and when they were published. More recent publications, due to the recognition that the type of proteinaceous accumulation correlates with clinical manifestations of FTLDs, has lead to the inclusion of motor variants which encompass amyotrophic lateral sclerosis (ALS), corticobasal degeneration and progressive supranuclear palsy (PSP) .
Terms to use with care
The term frontotemporal dementia (FTD) should be used to denote the clinical syndrome caused by FTLD and should then be followed by the phenotypic variant (behavioral, language, etc).
Older terms, such as Pick disease should probably be avoided especially when discussing the clinical presentation. Rather it should be reserved for the pathological entity characterized by Pick bodies (a form of tauopathy).
Epidemiology
The majority of cases are sporadic, however, 20-40% may relate to an autosomal gene. Typically FTLDs occurs in younger patients than Alzheimer, usually with onset between 40 to 60 years of age.
Given the difficulty in clearly defining this group, the incidence is similarly fuzzy, however, it is thought to be the fourth most common cause of progressive dementia (after Alzheimer disease, vascular dementia and Lewy body dementia) accounting for up to 20% of cases.
Clinical presentation
A convenient division based on clinical presentation is into behavioral and language variants. The former demonstrates predominantly frontal lobe changes whereas the latter has a predilection for the temporal lobe (particularly the left), and is further subdivided into a number of clinical distinct entities. As such frontotemporal lobar degeneration can be divided as follows :
- behavioral variant frontotemporal dementia (bvFTD)
- primary progressive aphasia (PPA) aka language variant frontotemporal dementia (lvFTD)
- non-fluent variant primary progressive aphasia (nfvPPA)
- semantic variant primary progressive aphasia (svPPA)
- logopaenic variant primary progressive aphasia (lvPPA)
- motor disorders
It should be noted that the motor disorders are generally considered separate entities but, however, frequently have overlapping features of FTD .
Pathology
Over the past decade or two, it has become apparent that FTLD is an umbrella term for a heterogeneous group of disease that can be characterized based on the type of glial and neuronal proteinaceous inclusions or underlying genetic mutation .
Proteinaceous inclusions
Three major types of FTLD can be defined histologically/biochemically on the basis of the type of proteinaceous inclusions :
Genetic mutation
Numerous genetic mutations have been identified that usually correlate with both phenotypic and histological/biochemical variants.
- FTLD-tau: MAPT gene (tau)
- FTLD-TDP: GRN (progranulin), VCP, TARBP (TDP-43) and C9ofr72 genes.
Radiographic features
Although, as the name suggests, the frontal and temporal lobes are predominantly affected, depending on the genetic and clinical phenotype, individuals demonstrate very variable regional atrophy.
As a general rule the following dominant patterns of regional loss are demonstrated :
- behavioral variant FTD: bilateral frontal lobes
- semantic variant of PPA: left temporal lobe
- non-fluent variant of PPA: left insula and frontal operculum (including Broca's area)
- FTLD-FUS: bilateral caudate nuclei
- FTLD-TDP due to GRN mutation: right frontal, lateral temporal and parietal lobes, often markedly asymmetric when comparing hemispheres
- FTLD-TDP due to C9orf72 mutation: bilateral hemispheres (generalized)
- FTLD-tau: due to MAPT mutation: bilateral temporal lobes
In addition to these features that overlap with amyotrophic lateral sclerosis (ALS), corticobasal degeneration, progressive supranuclear palsy (PSP) may be present .
Siehe auch:
- Lewy-Körper-Demenz
- Frontotemporale Demenz
- semantic dementia
- language variant of FTLD
- temporal variant of FTLD
- Morbus Alzheimer
- neurodegenerative Erkrankung
und weiter:
Assoziationen und Differentialdiagnosen zu frontotemporal lobar degeneration (FTLD):
