Hereditary diffuse leukoencephalopathy with spheroids - a volumetric and radiological comparison with multiple sclerosis patients and healthy controls

• Published in: European journal of neurology Vol. 23; no. 4; pp. 817 - 822
• Main Authors: Granberg, T., Hashim, F., Andersen, O., Sundal, C., Karrenbauer, V. D.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2016; John Wiley & Sons, Inc
• Subjects: Adult; Atrophy - pathology; Brain - diagnostic imaging; Brain - pathology; Cerebellum - diagnostic imaging; Cerebellum - pathology; Clinical Medicine; Cross-Sectional Studies; CSF1R; Female; Gray Matter - diagnostic imaging; Gray Matter - pathology; hereditary diffuse leukoencephalopathy with spheroids; Humans; Klinisk medicin; Leukoencephalopathies - diagnostic imaging; Leukoencephalopathies - pathology; Magnetic Resonance Imaging; Male; Medicin och hälsovetenskap; Middle Aged; MRI; Multiple sclerosis; Multiple Sclerosis - diagnostic imaging; Multiple Sclerosis - pathology; Mutation; volumetry; White Matter - diagnostic imaging; White Matter - pathology; CSF1R; volumetry; MRI; hereditary diffuse leukoencephalopathy with spheroids; multiple sclerosis
• ISSN: 1351-5101; 1468-1331; 1468-1331
• DOI: 10.1111/ene.12948

Background and purpose 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.