Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP.
OBJECTIVE
To examine the relationship between early clinical features, pathologies, and biochemistry of the frontotemporal lobar degenerations (FTLDs), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD).


METHODS
The authors conducted pathologic reexamination with the most recent immunohistochemistry of all cases diagnosed with FTLD, PSP, and CBD between 1970 and 2004. The authors also reviewed the early clinical features for clinical diagnosis and application of published research criteria.


RESULTS
Of 127 cases analyzed, 57 had a pathologic diagnosis of FTLD, 49 PSP, and 21 CBD. Of these, 38 were clinically reclassified as frontal variant frontotemporal dementia (FTD), 13 as progressive non-fluent aphasia (PNFA), 21 as CBD-like, 33 as PSP-like, and 13 with frontotemporal dementia with coexisting motor neuron disease (FTD-MND). The authors were unable to classify nine cases. All cases of FTD-MND were tau-negative and had pathologic evidence of motor neuron degeneration. All cases classified as PSP-like or CBD-like had tau-positive pathology. Of the 13 cases with PNFA, PSP and CBD accounted for almost 70% of the cases, while FTD was almost equally divided between tau-positive and tau-negative diseases.


CONCLUSIONS
Frontotemporal lobar degeneration, corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP) have overlapping clinical features. The prediction of tau-positive pathology from a CBD or PSP-like presentation is good, while the frontotemporal dementia (FTD)-motor neuron disease syndrome almost certainly predicts motor neuron degeneration. Surprisingly, PSP and CBD accounted for most cases classified as progressive non-fluent aphasia. Frontal variant FTD is an unpredictable disease in terms of its biochemistry.
Josephs
K A
KA
Division of Movement Disorders, Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. josephs.keith@mayo.edu
Petersen
R C
RC
Knopman
D S
DS
Boeve
B F
BF
Whitwell
J L
JL
Duffy
J R
JR
Parisi
J E
JE
Dickson
D W
DW
D000368:Aged; D018888:Aphasia, Primary Progressive / Q000175:diagnosis / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D003704:Dementia / Q000145:classification / Q000175:diagnosis* / Q000503:physiopathology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000145:classification / Q000175:diagnosis / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D013494:Supranuclear Palsy, Progressive / Q000145:classification / Q000175:diagnosis* / Q000503:physiopathology; D024801:Tauopathies / Q000145:classification / Q000175:diagnosis* / Q000503:physiopathology; D016875:tau Proteins / Q000378:metabolism
D015415:Biomarkers; D016875:tau Proteins