Frontotemporal lobar degeneration without lobar atrophy.
BACKGROUND
Frontotemporal lobar degeneration with ubiquitin-only-immunoreactive neuronal inclusions (FTLD-U) is the most common form of frontotemporal dementia. Neuronal loss and gliosis in cornu ammonis 1 and the subiculum of the hippocampus are features of hippocampal sclerosis (HpScl), which occurs in many cases of FTLD-U.


OBJECTIVE
To determine if there were any clinical or magnetic resonance imaging correlates of HpScl in FTLD-U.


METHODS
We reviewed demographics and clinical features of 24 cases of FTLD-U and subjectively assessed the severity of neuronal loss and frequency of ubiquitin-positive neuronal lesions in the frontal and temporal cortices and the dentate gyrus of the hippocampus.


METHODS
Mayo Clinic, Rochester, Minn. Patients Twenty-six cases were identified from the medical records linkage system query that met clinical criteria and had autopsy material available for additional studies. Two cases were excluded from further analysis after pathologic studies revealed coexisting Alzheimer disease, leaving 24 cases included in the study. Cases were subdivided based on the presence or absence of HpScl.


METHODS
Patterns of gray matter atrophy were assessed in cases of FTLD-U with and without HpScl using voxel-based morphometry.


RESULTS
Six of the 24 cases of FTLD-U did not have HpScl. No differences were found in demographic or clinical features, including disease duration, between cases with and without HpScl; however, voxel-based morphometry analysis revealed minimal cortical atrophy in cases without HpScl, which was significantly different from the pattern of moderate to severe frontal and temporal lobe atrophy in FTLD-U with HpScl. This finding was in keeping with histopathologic observations.


CONCLUSIONS
Despite similar clinical features, cases of FTLD-U with HpScl differ from those without HpScl with respect to pathologic findings and structural imaging. Specifically, FTLD-U without HpScl showed on average minimal or no cortical atrophy, even at end-stage disease. Consequently, FTLD-U without HpScl does not conform to the proposed FTLD staging scheme, is underrecognized, and may have different genetic and environmental underpinnings.
Josephs
Keith A
KA
Department of Neurology, Division of Behavioral Neurology and Movement Disorders, Mayo Clinic, Rochester, MN 55905, USA. josephs.keith@mayo.edu
Whitwell
Jennifer L
JL
Jack
Clifford R
CR
Parisi
Joseph E
JE
Dickson
Dennis W
DW
D000368:Aged; D000369:Aged, 80 and over; D001931:Brain Mapping; D016923:Cell Death / Q000502:physiology; D003704:Dementia / Q000150:complications* / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D020774:Pick Disease of the Brain / Q000473:pathology; D025801:Ubiquitin / Q000378:metabolism*
D025801:Ubiquitin