Demystifying lobar degenerations

Two articles from investigators at the Mayo Clinic published in this issue^1,2 address clinical issues in the diagnosis of disorders in the spectrum of frontotemporal lobar degenerations (FTLD) from the perspective of the underlying pathologies. The FTLDs represent a complex group of disorders with muddled and confusing nomenclature. Attempts to clarify the relationships between clinical and neuroimaging features and the underlying pathologies may improve phenotypic characterizations, which in turn may lead to better understanding of salient pathogenic mechanisms and ultimately aid the development of specific therapies and management strategies. These two articles take as their starting point autopsy-confirmed cases of FTLD, corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP) that had been entered into the Mayo Clinic medical records database from 1970 through 2004 and then extensively re-examined with state-of-the-art immunohistochemistry.

The study of Josephs et al.¹ sought to match clinical diagnosis, based on early features conforming to published consensus guidelines, with a final pathologic diagnosis. The approach is retrospective and grants to pathology its traditional status as the gold standard. The medical record review yielded an autopsy series of 127 cases (57 FTLD, 49 PSP, and 21 CBD). The pathology was re-assessed in isolation from clinical and diagnostic data using the most current methods and diagnostic guidelines. Simultaneously the clinical records were screened in isolation from pathologic data for diagnostic features that might discriminate among disorders of the FTLD spectrum.

Pathologically two broad categories emerged, cases with tau pathology (classified as Pick's disease, CBD, PSP, multisystem tauopathy, and frontotemporal dementia …