Enlarging the nosological spectrum of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS)

Sarah Hoffmann, Jill Murrell, Lutz Harms, Kelly Miller, Andreas Meisel, Thomas Brosch, Michael Scheel, Bernardino Ghetti, Hans Hilmar Goebel, Werner Stenzel

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.R777Q) 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.

Original languageEnglish (US)
Pages (from-to)452-458
Number of pages7
JournalBrain pathology (Zurich, Switzerland)
Volume24
Issue number5
DOIs
StatePublished - Sep 1 2014
Externally publishedYes

Fingerprint

Colony-Stimulating Factor Receptors
Macrophage Colony-Stimulating Factor
Mutation
Personality
Macrophages
Genes
Peripheral Nervous System
Cerebrum
Parkinsonian Disorders
Myelin Sheath
Alcoholism
Psychiatry
Disease Progression
Molecular Biology
Electron Microscopy
Seizures
Central Nervous System
Magnetic Resonance Imaging
Depression
Biopsy

Keywords

  • ALSP
  • CSF1R
  • HDLS
  • POLD

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

Cite this

Hoffmann, S., Murrell, J., Harms, L., Miller, K., Meisel, A., Brosch, T., ... Stenzel, W. (2014). Enlarging the nosological spectrum of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS). Brain pathology (Zurich, Switzerland), 24(5), 452-458. https://doi.org/10.1111/bpa.12120

Enlarging the nosological spectrum of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS). / Hoffmann, Sarah; Murrell, Jill; Harms, Lutz; Miller, Kelly; Meisel, Andreas; Brosch, Thomas; Scheel, Michael; Ghetti, Bernardino; Goebel, Hans Hilmar; Stenzel, Werner.

In: Brain pathology (Zurich, Switzerland), Vol. 24, No. 5, 01.09.2014, p. 452-458.

Research output: Contribution to journalArticle

Hoffmann, S, Murrell, J, Harms, L, Miller, K, Meisel, A, Brosch, T, Scheel, M, Ghetti, B, Goebel, HH & Stenzel, W 2014, 'Enlarging the nosological spectrum of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS)', Brain pathology (Zurich, Switzerland), vol. 24, no. 5, pp. 452-458. https://doi.org/10.1111/bpa.12120
Hoffmann, Sarah ; Murrell, Jill ; Harms, Lutz ; Miller, Kelly ; Meisel, Andreas ; Brosch, Thomas ; Scheel, Michael ; Ghetti, Bernardino ; Goebel, Hans Hilmar ; Stenzel, Werner. / Enlarging the nosological spectrum of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS). In: Brain pathology (Zurich, Switzerland). 2014 ; Vol. 24, No. 5. pp. 452-458.
@article{3292624063c340349286e7b3fe598790,
title = "Enlarging the nosological spectrum of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS)",
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.R777Q) 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.",
keywords = "ALSP, CSF1R, HDLS, POLD",
author = "Sarah Hoffmann and Jill Murrell and Lutz Harms and Kelly Miller and Andreas Meisel and Thomas Brosch and Michael Scheel and Bernardino Ghetti and Goebel, {Hans Hilmar} and Werner Stenzel",
year = "2014",
month = "9",
day = "1",
doi = "10.1111/bpa.12120",
language = "English (US)",
volume = "24",
pages = "452--458",
journal = "Brain Pathology",
issn = "1015-6305",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Enlarging the nosological spectrum of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS)

AU - Hoffmann, Sarah

AU - Murrell, Jill

AU - Harms, Lutz

AU - Miller, Kelly

AU - Meisel, Andreas

AU - Brosch, Thomas

AU - Scheel, Michael

AU - Ghetti, Bernardino

AU - Goebel, Hans Hilmar

AU - Stenzel, Werner

PY - 2014/9/1

Y1 - 2014/9/1

N2 - 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.R777Q) 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.

AB - 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.R777Q) 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.

KW - ALSP

KW - CSF1R

KW - HDLS

KW - POLD

UR - http://www.scopus.com/inward/record.url?scp=85027953558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027953558&partnerID=8YFLogxK

U2 - 10.1111/bpa.12120

DO - 10.1111/bpa.12120

M3 - Article

C2 - 24428556

AN - SCOPUS:85027953558

VL - 24

SP - 452

EP - 458

JO - Brain Pathology

JF - Brain Pathology

SN - 1015-6305

IS - 5

ER -