HDLS cases have been located in Germany, Norway, Sweden, and the United States, showing an international distribution focusing between Northern Europe and the United States.Through the study of numerous kindred, it was found that the disease did not occur among just males or females, but rather was evenly distributed indicative of an autosomal rather than a sex-linked genetic disorder. It was also observed that the HDLS cases did not skip generations as it would occur with a recessive inheritance, and as such has been labeled autosomal dominant. History
This disease was first described in 1984 by Axelsson et al. in a large Swedish pedigree. It is a disorder better known to neuropathologists than clinicians. A neuropathologist with an interest in HDLS, Dr. Dennis W. Dickson, has identified a number of cases from neuropathology study of brains submitted for investigation of familial adult-onset dementia and movement disorders in New York and later in Florida. Recognition of the importance of this disorder as a cause of adult onset dementia and movement disorders was further heightened in 1997 at the Mayo Clinic when Dr. Zbigniew K. Wszolek identified a family with HDLS that was initially thought to be due to another disease process (FTDP-17), but only an autopsy of one and then other family members revealed it to be HDLS. Wszolek established an international consortium in 2005 to identify other families and to collect DNA or brain samples from family members for neuropathologic confirmation and genetic research at the Mayo Clinic in Florida.
POLD exhibits noninflammatory demyelination of axons with initial symptoms of euphoria, apathy, headache, and executive dysfunction. While HDLS is autosomal dominant, some families with POLD have features that suggest autosomal recessive inheritance. Nevertheless, POLD has recently been shown to have the same genetic basis as HDLS. Clinical and genealogic studies
To gain a better understanding of the disease, researchers have retrospectively reviewed medical records of probands and others who were assessed through clinical examinations or questionnaires. Blood samples are collected from the families of the probands for genetic testing. These family members are assessed using their standard medical history, on their progression of Parkinsons like symptoms (Unified Parkinsons Disease Rating Scale), and on their progression of cognitive impairment such as dementia (Folstein Test). Neuroimaging
Standard MRI scans have been performed on 1.5 Tesla scanners with 5 mm thickness and 5 mm spacing to screen for white matter lesions in identified families. If signal intensities of the MRI scans are higher in white matter regions than in grey matter regions, the patient is considered to be at risk for HDLS, although a number of other disorders can also produce white matter changes and the findings are not diagnostic without genetic testing or pathologic confirmation. Pathology
Tissue sections from brain biopsies or autopsy brains are commonly embedded in paraffin from which sections are cut an mounted on glass slides for histologic studies.