TY - JOUR
T1 - MRI characteristics and scoring in HDLS due to CSF1R gene mutations
AU - Sundal, Christina
AU - Van Gerpen, Jay A.
AU - Nicholson, Alexandra M.
AU - Wider, Christian
AU - Shuster, Elizabeth A.
AU - Aasly, Jan
AU - Spina, Salvatore
AU - Ghetti, Bernardino
AU - Roeber, Sigrun
AU - Garbern, James
AU - Borjesson-Hanson, Anne
AU - Tselis, Alex
AU - Swerdlow, Russell H.
AU - Miller, Bradley B.
AU - Fujioka, Shinsuke
AU - Heckman, Michael G.
AU - Uitti, Ryan J.
AU - Josephs, Keith A.
AU - Baker, Matt
AU - Andersen, Oluf
AU - Rademakers, Rosa
AU - Dickson, Dennis W.
AU - Broderick, Daniel
AU - Wszolek, Zbigniew K.
N1 - Funding Information:
C. Sundal reports no disclosures. J. Van Gerpen reports receiving funding from the Mayo Clinic Florida Research Committee CR program for research on hereditary leukoencephalopathy with axonal spheroids (MCF #90052030). A. Nicholson, C. Wider, E. Shuster, J. Aasly, S. Spina, B. Ghetti, and S. Roeber report no disclosures. J. Garbern is now deceased. We cannot confirm his disclosures, but as far as we know he had no disclosures relevant to this manuscript. A. Borjesson-Hanson, A. Tselis, R. Swerdlow, B. Miller, S. Fujioka, and M. Heckman report no disclosures. R. Uitti serves as an associate editor for Neurology®. K. Josephs, M. Baker, and O. Andersen report no disclosures. R. Rademakers reports receiving funding from the Mayo Clinic Florida Research Committee CR program for research on hereditary leukoencephalopathy with axonal spheroids (MCF #90052030). D. Dickson reports receiving funding from the Mayo Clinic Florida Research Committee CR program for research on hereditary leukoencephalopathy with axonal spheroids (MCF #90052030). D. Broderick reports no disclosures. Z. Wszolek reports receiving funding from the Mayo Clinic Florida Research Committee CR program for research on hereditary leukoencephalopathy with axonal spheroids (MCF #90052030). Go to Neurology.org for full disclosures.
Funding Information:
C.S. was partially supported by Sven and Dagmar Saléns Stiftelse, Signe och Olof Wallenius Stiftelse, Stiftelsen for Gamla Tjänarinnor, and Anna-Lisa och Bror Björnsson Stiftelse (2008−2010), Sweden, The Swedish Society of Medicine Gothenburg (GLS), the Swedish Society of Medicine Sweden (2010), The Swedish and Gothenburg Societies for the Neurologically Disabled, the Gothenburg Foundation for Neurological Research, Stiftelson Edit Jacobsons Donationsfond Sweden, and the American Scandinavian Foundation: Haakon Styri Fund. A.M.N. was partially supported by an Association for Frontotemporal Degeneration Postdoctoral Fellowship. R.H.S. was partially supported by the University of Kansas Alzheimer's Disease Core Center Funding Agency (P30-AG035982) . B.G. was partially supported by the National Institutes of Health, Public Health Service (P30-AG10133). J.A.V.G., R.R., D.W.D., and Z.K.W. were partially supported by Mayo Clinic Florida (MCF) Research Committee CR program (MCF #90052030). R.R. was partially supported by the National Institutes of Health (R01-NS065782, R01-AG26251, and P50-AG16574) . D.W.D. and Z.K.W. were partially supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke (P50-NS072187–01S2) . D.W.D. was partially supported by an anonymous Mayo benefactor. Z.K.W. was also partially supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke (1RC2-NS070276 and R01-NS057567) and the Dystonia Medical Research Foundation.
PY - 2012/8/7
Y1 - 2012/8/7
N2 - Objective: To describe the brain MRI characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS) with known mutations in the colony-stimulating factor 1 receptor gene (CSF1R) on chromosome 5. Methods: We reviewed 20 brain MRI scans of 15 patients with autopsy- or biopsy-verified HDLS and CSF1R mutations. We assessed sagittal T1-, axial T1-, T2-, proton density-weighted and axial fluid-attenuated inversion recovery images for distribution of white matter lesions (WMLs), gray matter involvement, and atrophy. We calculated a severity score based on a point system (0-57) for each MRI scan. Results: Of the patients, 93% (14 of 15) demonstrated localized WMLs with deep and subcortical involvement, whereas one patient revealed generalized WMLs. All WMLs were bilateral but asymmetric and predominantly frontal. Fourteen patients had a rapidly progressive clinical course with an initial MRI mean total severity score of 16.7 points (range 10-33.5). Gray matter pathology and brainstem atrophy were absent, and the corticospinal tracts were involved late in the disease course. There was no enhancement, and there was minimal cerebellar pathology. Conclusion: Recognition of the typical MRI patterns of HDLS and the use of an MRI severity score might help during the diagnostic evaluation to characterize the natural history and to monitor potential future treatments. Indicators of rapid disease progression were symptomatic disease onset before 45 years, female sex, WMLs extending beyond the frontal regions, a MRI severity score greater than 15 points, and mutation type of deletion.
AB - Objective: To describe the brain MRI characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS) with known mutations in the colony-stimulating factor 1 receptor gene (CSF1R) on chromosome 5. Methods: We reviewed 20 brain MRI scans of 15 patients with autopsy- or biopsy-verified HDLS and CSF1R mutations. We assessed sagittal T1-, axial T1-, T2-, proton density-weighted and axial fluid-attenuated inversion recovery images for distribution of white matter lesions (WMLs), gray matter involvement, and atrophy. We calculated a severity score based on a point system (0-57) for each MRI scan. Results: Of the patients, 93% (14 of 15) demonstrated localized WMLs with deep and subcortical involvement, whereas one patient revealed generalized WMLs. All WMLs were bilateral but asymmetric and predominantly frontal. Fourteen patients had a rapidly progressive clinical course with an initial MRI mean total severity score of 16.7 points (range 10-33.5). Gray matter pathology and brainstem atrophy were absent, and the corticospinal tracts were involved late in the disease course. There was no enhancement, and there was minimal cerebellar pathology. Conclusion: Recognition of the typical MRI patterns of HDLS and the use of an MRI severity score might help during the diagnostic evaluation to characterize the natural history and to monitor potential future treatments. Indicators of rapid disease progression were symptomatic disease onset before 45 years, female sex, WMLs extending beyond the frontal regions, a MRI severity score greater than 15 points, and mutation type of deletion.
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U2 - 10.1212/WNL.0b013e318263575a
DO - 10.1212/WNL.0b013e318263575a
M3 - Article
C2 - 22843259
AN - SCOPUS:84866127047
SN - 0028-3878
VL - 79
SP - 566
EP - 574
JO - Neurology
JF - Neurology
IS - 6
ER -