Leukoencephalopathy with spheroids (HDLS) and pigmentary leukodystrophy (POLD): a single entity?

Abstract

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and familial pigmentary orthochromatic leukodystrophy (POLD) present as adult-onset dementia with motor impairment and epilepsy. They are regarded as distinct diseases. We review data from the literature that support their being a single entity. Apart from a slightly older age at onset, a more rapid course, and more prominent pyramidal tract involvement, familial POLD is clinically similar to HDLS. Moreover, the pathologic hallmarks of the two diseases, axonal spheroids in HDLS and pigmented macrophages in POLD, can be identified in both conditions. This supports HDLS and POLD being referred collectively as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).

Figure Neuropathologic features of three patients (A, B) Patient III-6 diagnosed with hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS). (C, D) New patient, a 31-year-old woman with a 6-year history of depression and personality changes, followed by dementia and seizures, who was diagnosed with features of HDLS and pigmentary orthochromatic leukodystrophy. (E, F) Patient IV-5, diagnosed with HDLS. Immunohistochemistry for amyloid precursor protein (APP; 22C11, Chemicon, Temecula, CA) (A) and neurofilament (NF; SMI-31, Sternberger Monoclonals, Lutherville, MD) (B), and staining with hematoxylin-eosin (H-E) (C) and Luxol fast blue (F) show axonal spheroids in the white matter of all three patients (arrows). Pigmented macrophages are seen on H-E (D, E, arrows) in two patients.