Open AccessEnlarging the Nosological Spectrum of Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids ( HDLS )
Author(s) -
Hoffmann Sarah,
Murrell Jill,
Harms Lutz,
Miller Kelly,
Meisel Andreas,
Brosch Thomas,
Scheel Michael,
Ghetti Bernardino,
Goebel HansHilmar,
Stenzel Werner
Publication year - 2014
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12120
Subject(s) - pathology , leukoencephalopathy , white matter , myelin , medicine , cognitive decline , central nervous system , magnetic resonance imaging , dementia , disease , radiology
Abstract Hereditary diffuse leukoencephalopathy with axonal spheroids ( HDLS ) is an autosomal dominant disease clinically characterized by cognitive decline, personality changes, motor impairment, parkinsonism and seizures. Recently, mutations in the colony‐stimulating factor‐1 receptor ( CSF1R ) gene have been shown to be associated with HDLS . We report clinical, neuropathological and molecular genetic findings of patients from a new family with a mutation in the CSF1R gene. Disease onset was earlier and disease progression was more rapid compared with previously reported patients. Psychiatric symptoms including personality changes, alcohol abuse and severe depression were the first symptoms in male patients. In the index, female patient, the initial symptom was cognitive decline. Magnetic resonance imaging ( MRI ) showed bilateral, confluent white matter lesions in the cerebrum. Stereotactic biopsy revealed loss of myelin and microglial activation as well as macrophage infiltration of the parenchyma. Numerous axonal swellings and spheroids were present. Ultrastructural analysis revealed pigment‐containing macrophages. Axonal swellings were detected by electron microscopy not only in the central nervous system ( CNS ) but also in skin nerves. We identified a heterozygous mutation (c.2330G>A, p. R 777 Q ) in the CSF1R gene. Through this report, we aim to enlarge the nosological spectrum of HDLS , providing new clinical descriptions as well as novel neuropathological findings from the peripheral nervous system.