TY - JOUR
T1 - Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS)
T2 - A misdiagnosed disease entity
AU - Sundal, Christina
AU - Lash, Jennifer
AU - Aasly, Jan
AU - Øygarden, Sarka
AU - Roeber, Sigrun
AU - Kretzschman, Hans
AU - Garbern, James Y.
AU - Tselis, Alex
AU - Rademakers, Rosa
AU - Dickson, Dennis W.
AU - Broderick, Daniel
AU - Wszolek, Zbigniew K.
N1 - Funding Information:
Work was partially supported by the NIH/NINDS 1RC2NS070276, NS057567, P50NS072187 , Mayo Clinic Florida (MCF) Research Committee CR program (MCF # 90052030 ), Dystonia Medical Research Foundation , and a gift from Carl Edward Bolch, Jr., and Susan Bass Bolch (MCF #90052031/PAU #90052).
Funding Information:
DWD was supported by P50NS072187 and a gift from Carl Edward Bolch, Jr., and Susan Bass Bolch. SR and HK were both funded by BMBF (Brain-Net-Germany (01GI0505)).
Funding Information:
Rademakers: NIH R01 AG026251-03A2, P50AG 16574, R01NS065782, ALS Association, Society for Progressive Supranuclear Palsy, Frontotemporal Dementia Research, Fidelty Foundation
Funding Information:
CS was sponsored by Anna-Lisa och Bror Björnssons, Sven and Dagmar Saléns, Signe och Olof Wallenius and Gamla Tjänarinnor Foundations, Sweden. The Swedish Society of Medicine Gothenburg (GLS), Sweden, The Swedish Society of Medicine Sweden, The Swedish and Gothenburg Societies for the Neurologically Disabled and The Gothenburg Foundation for Neurological Research.
PY - 2012/3/15
Y1 - 2012/3/15
N2 - 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.
AB - 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.
KW - Autosomal dominant
KW - Cognitive problems
KW - Depression
KW - HDLS
KW - Parkinsonism
KW - Personality changes
KW - White matter disease
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U2 - 10.1016/j.jns.2011.10.006
DO - 10.1016/j.jns.2011.10.006
M3 - Article
C2 - 22050953
AN - SCOPUS:84857038050
SN - 0022-510X
VL - 314
SP - 130
EP - 137
JO - Journal of the neurological sciences
JF - Journal of the neurological sciences
IS - 1-2
ER -