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Keith A. Josephs, MST, MD; Jennifer L. Whitwell, PhD; Clifford R. Jack, MD; Joseph E. Parisi, MD; Dennis W. Dickson, MD

Arch Neurol. 2006;63:1632-1638.

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.

Design  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.

Setting  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.

Main Outcome Measures  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.

Author Affiliations: Departments of Neurology, Division of Behavioral Neurology and Movement Disorders (Dr Josephs), Radiology Research (Drs Whitwell and Jack), and Laboratory Medicine and Pathology (Dr Parisi), Mayo Clinic, Rochester, Minn; and Department of Neuroscience, Division of Neuropathology, Mayo Clinic, Jacksonville, Fla (Dr Dickson).

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