Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis. (13th October 2014)

• Record Type: Journal Article
• Authors: Sundal, C.; Baker, M.; Karrenbauer, V.; Gustavsen, M.; Bedri, S.; Glaser, A.; Myhr, K.‐M.; Haugarvoll, K.; Zetterberg, H.; Harbo, H.; Kockum, I.; Hillert, J.; Wszolek, Z.; Rademakers, R.; Andersen, O.
• Is Part Of: European journal of neurology. Volume 22:Number 2(2015:Feb.)
• Page Start: 328
• Page End: 333
• Publication Date: 2014-10-13
• Subjects: Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.12572
• Languages: English
• ISSNs: 1351-5101

Abstract

<abstract abstract-type="main" id="ene12572-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ene12572-sec-0001" sec-type="section"> <title>Background and purpose</title> <p>Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a devastating, hereditary white matter (WM) disorder with heterogeneous neuropsychiatric features. Colony stimulating factor 1 receptor (<italic>CSF1R</italic>) mutations were looked for in primary progressive multiple sclerosis (PPMS) patients and the clinical features of a family with a novel <italic>CSF1R</italic> mutation are reported.</p> </sec> <sec id="ene12572-sec-0002" sec-type="section"> <title>Methods</title> <p> <italic>CSF1R</italic> exons 12−22 in a cohort of 220 PPMS patients from the Swedish and Norwegian national multiple sclerosis registries were sequenced.</p> </sec> <sec id="ene12572-sec-0003" sec-type="section"> <title>Results</title> <p>One patient had a novel mutation, c.2562T>A; p.Asn854Lys, in the <italic>CSF1R</italic> 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 <italic>CSF1R</italic> gene mutation; one was diagnosed with PPMS. Six more distant relatives also had a neurological disorder; four were clinically diagnosed with PPMS.</p> </sec> <sec id="ene12572-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Our study indicates that a chronic course of HDLS may mimic PPMS. Genetic testing for <italic>CSF1R</italic> gene mutations in PPMS cases with a positive family history of neurological disorders may establish the diagnosis of HDLS.</p> </sec> </abstract>