Christina Sundal1,2, Matt Baker3, Rosa Rademakers3, Oluf Andersen1, Virginija Karrenbauer4, Marte Gustavsen5, Sahl Bedri4, Anna Glaser4, Kjell-Morten Myhr6,7, Kristoffer Haugarvoll2, Henrik Zetterberg8,9, Hanne Harbo5, Ingrid Kockum4, Jan Hillert4, Zbigniew Wszolek3. 1. Department of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 2. Department of Neurology, Haukeland University Hospital, Bergen, Norway. 3. Department of Neurosciences and Neurology, Mayo Clinic, Jacksonville, FL, USA. 4. Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. 5. Department of Neurology, Oslo University Hospital, Ullevål and University of Oslo, Norway. 6. KG Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen, Norway. 7. Norwegian MS Registry and Biobank, Department of Neurology, Haukeland University Hospital, Bergen, Norway. 8. Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 9. UCL Institute of Neurology, Queen Square, London, United Kingdom.
Abstract
BACKGROUND AND PURPOSE: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a devastating, hereditary white matter (WM) disorder with heterogeneous neuropsychiatric features. Colony stimulating factor 1 receptor (CSF1R) mutations were looked for in primary progressive multiple sclerosis (PPMS) patients and the clinical features of a family with a novel CSF1R mutation are reported. METHODS: CSF1R exons 12-22 in a cohort of 220 PPMS patients from the Swedish and Norwegian national multiple sclerosis registries were sequenced. RESULTS: One patient had a novel mutation, c.2562T>A; p.Asn854Lys, in the CSF1R gene. Her symptoms started at the age of 29 years with insidious onset of pyramidal weakness in the left leg. The cerebrospinal fluid examination showed four intrathecal immunoglobulin G bands. A magnetic resonance imaging scan performed 4 years after symptom onset demonstrated patchy deep WM lesions. She was diagnosed as having PPMS and treated with intramuscular interferon beta 1a. Due to slow disease progression, the development of memory decline and cerebellar signs, she was given subcutaneous interferon beta 1a without any benefit. The updated pedigree indicated that five siblings also had the CSF1R gene mutation; one was diagnosed with PPMS. Six more distant relatives also had a neurological disorder; four were clinically diagnosed with PPMS. CONCLUSIONS: Our study indicates that a chronic course of HDLS may mimic PPMS. Genetic testing for CSF1R gene mutations in PPMS cases with a positive family history of neurological disorders may establish the diagnosis of HDLS.
BACKGROUND AND PURPOSE:Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a devastating, hereditary white matter (WM) disorder with heterogeneous neuropsychiatric features. Colony stimulating factor 1 receptor (CSF1R) mutations were looked for in primary progressive multiple sclerosis (PPMS) patients and the clinical features of a family with a novel CSF1R mutation are reported. METHODS:CSF1R exons 12-22 in a cohort of 220 PPMS patients from the Swedish and Norwegian national multiple sclerosis registries were sequenced. RESULTS: One patient had a novel mutation, c.2562T>A; p.Asn854Lys, in the CSF1R gene. Her symptoms started at the age of 29 years with insidious onset of pyramidal weakness in the left leg. The cerebrospinal fluid examination showed four intrathecal immunoglobulin G bands. A magnetic resonance imaging scan performed 4 years after symptom onset demonstrated patchy deep WM lesions. She was diagnosed as having PPMS and treated with intramuscular interferon beta 1a. Due to slow disease progression, the development of memory decline and cerebellar signs, she was given subcutaneous interferon beta 1a without any benefit. The updated pedigree indicated that five siblings also had the CSF1R gene mutation; one was diagnosed with PPMS. Six more distant relatives also had a neurological disorder; four were clinically diagnosed with PPMS. CONCLUSIONS: Our study indicates that a chronic course of HDLS may mimic PPMS. Genetic testing for CSF1R gene mutations in PPMS cases with a positive family history of neurological disorders may establish the diagnosis of HDLS.
Authors: Christina Sundal; Shinsuke Fujioka; Jay A Van Gerpen; Christian Wider; Alexandra M Nicholson; Matt Baker; Elizabeth A Shuster; Jan Aasly; Salvatore Spina; Bernardino Ghetti; Sigrun Roeber; James Garbern; Alex Tselis; Russell H Swerdlow; Bradley B Miller; Anne Borjesson-Hanson; Ryan J Uitti; Owen A Ross; A Jon Stoessl; Rosa Rademakers; Keith A Josephs; Dennis W Dickson; Daniel Broderick; Zbigniew K Wszolek Journal: Parkinsonism Relat Disord Date: 2013-06-17 Impact factor: 4.891
Authors: C Sundal; S Ekholm; C Nordborg; L Jönsson; A Börjesson-Hanson; T Lindén; H Zetterberg; M Viitanen; O Andersen Journal: Acta Neurol Scand Date: 2011-11-18 Impact factor: 3.209
Authors: Christina Sundal; Jay A Van Gerpen; Alexandra M Nicholson; Christian Wider; Elizabeth A Shuster; Jan Aasly; Salvatore Spina; Bernardino Ghetti; Sigrun Roeber; James Garbern; Anne Borjesson-Hanson; Alex Tselis; Russell H Swerdlow; Bradley B Miller; Shinsuke Fujioka; Michael G Heckman; Ryan J Uitti; Keith A Josephs; Matt Baker; Oluf Andersen; Rosa Rademakers; Dennis W Dickson; Daniel Broderick; Zbigniew K Wszolek Journal: Neurology Date: 2012-07-25 Impact factor: 9.910
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