title: Hereditary diffuse leukoencephalopathy with spheroids - a volumetric and radiological comparison with multiple sclerosis patients and healthy controls.
abstract: OBJECTIVE
  Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant disorder caused by colony-stimulating factor 1 receptor (CSF1R) gene mutations, resulting in demyelination and axonal degeneration with spheroids. The clinical expression is variable, including behavioral changes, cognitive impairment, motor symptoms and parkinsonism. Magnetic resonance imaging (MRI) reveals white matter (WM) changes and atrophy. The indistinct phenotype has led to misdiagnoses. This study's aim was to compare brain volumetry and radiological ratings in HDLS with multiple sclerosis (MS) patients and controls.
  
  
  METHODS
  Five HDLS patients with c.2562T>A p.Asn854Lys CSF1R mutation, five age- and gender-matched MS patients and five healthy controls were cross-sectionally studied. All patients were examined neurologically. HDLS patients underwent Mini-Mental State Examination (MMSE). Brain MRI scans were analyzed volumetrically with FreeSurfer and Lesion Segmentation Toolbox and neuroradiologically with the brain MRI scoring system for HDLS.
  
  
  RESULTS
  Patients with HDLS had lower brain, grey matter and WM fractions (66.3%; 37.9%; 27.6%) compared with controls (78.5%, P = 0.008; 44.4%, P = 0.008; 32.0%, P = 0.008), but not compared with MS patients (65.7%, P = 0.7; 36.8%, P = 0.4; 27.3%, P = 0.7). Cerebellar WM changes and atrophy were not seen in the HDLS group. The HDLS lesion volume fraction correlated with MMSE scores (r = -0.90, P = 0.04).
  
  
  CONCLUSIONS
  Brain volume fractions in HDLS were lower than in controls and similar to those seen in MS. The cerebellum was relatively spared in HDLS, which may help in differentiating HDLS WM changes from MS. The strong relationship of HDLS lesions with MMSE scores indicates that accumulating WM pathology in HDLS is associated with cognitive decline.
authors.affiliation: Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.|Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Granberg
authors.affiliation: Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.|Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Hashim
authors.affiliation: The Sahlgrenska Academy, Department of Neuroscience and Physiology, Section of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
authors.forename: O
authors.initials: O
authors.lastname: Andersen
authors.affiliation: The Sahlgrenska Academy, Department of Neuroscience and Physiology, Section of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.|Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: C
authors.initials: C
authors.lastname: Sundal
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: V D
authors.initials: VD
authors.lastname: Karrenbauer
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000473:pathology*; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*
keywords: CSF1R; MRI; hereditary diffuse leukoencephalopathy with spheroids; multiple sclerosis; volumetry