Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): A misdiagnosed disease entity

Christina Sundal, Jennifer Lash, Jan Aasly, Sarka Øygarden, Sigrun Roeber, Hans Kretzschman, James Y. Garbern, Alex Tselis, Rosa Rademakers, Dennis W. Dickson, Daniel Broderick, Zbigniew K. Wszolek

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) was originally described in a large Swedish pedigree. Since then, 22 reports describing a total of 13 kindreds and 11 sporadic cases have been published. Inheritance is autosomal dominant, albeit the gene is unknown. Here we report on the clinical findings, genealogical data, brain MRI data, and autopsy/biopsy findings of four probands from three independently ascertained novel families from Norway, Germany and US. We identified a 39-year-old female and her twin sister, a 52-year-old male and a 47-year-old male with progressive neurological illness characterized by personality changes, cognitive decline and motor impairments, such as gait problems, bradykinesia, tremor and rigidity. Brain MRI showed white matter abnormalities with frontal prominence. Brain biopsy/autopsies were consistent with HDLS. HDLS is an under-recognized disease and in reporting these cases, we aim to increase the awareness of the disorder. Due to varied and wide phenotypic presentations, which may imitate several neurodegenerative diseases, HDLS can be difficult to diagnose. Definitive diagnosis can be established only by direct brain tissue examination. Familiarity with the clinical presentation and typical neuroimaging findings may be helpful in narrowing the diagnosis.

Original languageEnglish (US)
Pages (from-to)130-137
Number of pages8
JournalJournal of the neurological sciences
Volume314
Issue number1-2
DOIs
StatePublished - Mar 15 2012

Keywords

  • Autosomal dominant
  • Cognitive problems
  • Depression
  • HDLS
  • Parkinsonism
  • Personality changes
  • White matter disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Sundal, C., Lash, J., Aasly, J., Øygarden, S., Roeber, S., Kretzschman, H., Garbern, J. Y., Tselis, A., Rademakers, R., Dickson, D. W., Broderick, D., & Wszolek, Z. K. (2012). Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): A misdiagnosed disease entity. Journal of the neurological sciences, 314(1-2), 130-137. https://doi.org/10.1016/j.jns.2011.10.006