PT - JOURNAL ARTICLE AU - David S Lynch AU - Zane Jaunmuktane AU - Una-Marie Sheerin AU - Rahul Phadke AU - Sebastian Brandner AU - Ionnis Milonas AU - Andrew Dean AU - Nin Bajaj AU - Nuala McNicholas AU - Daniel Costello AU - Simon Cronin AU - Chris McGuigan AU - Martin Rossor AU - Nick Fox AU - Elaine Murphy AU - Jeremy Chataway AU - Henry Houlden TI - Hereditary leukoencephalopathy with axonal spheroids: a spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series AID - 10.1136/jnnp-2015-310788 DP - 2016 May 01 TA - Journal of Neurology, Neurosurgery & Psychiatry PG - 512--519 VI - 87 IP - 5 4099 - http://jnnp.bmj.com/content/87/5/512.short 4100 - http://jnnp.bmj.com/content/87/5/512.full SO - J Neurol Neurosurg Psychiatry2016 May 01; 87 AB - Background Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a hereditary, adult onset leukodystrophy which is characterised by the presence of axonal loss, axonal spheroids and variably present pigmented macrophages on pathological examination. It most frequently presents in adulthood with dementia and personality change. HDLS has recently been found to be caused by mutations in the colony stimulating factor-1 receptor (CSF1R) gene.Methods In this study, we sequenced the CSF1R gene in a cohort of 48 patients from the UK, Greece and Ireland with adult onset leukodystrophy of unknown cause.Results Five pathogenic mutations were found, including three novel mutations. The presentations ranged from suspected central nervous system (CNS) vasculitis to extrapyramidal to cognitive phenotypes. The case histories and imaging are presented here, in addition to neuropathological findings from two cases with novel mutations.Conclusion We estimate that CSF1R mutations account for 10% of idiopathic adult onset leukodystrophies and that genetic testing for CSF1R mutations is essential in adult patients presenting with undefined CNS vasculitis or a leukodystrophy with prominent neuropsychiatric signs or dementia.