CSF1R Gene Screening In A Cohort Of 218 Primary Progressive Multiple Sclerosis (PPMS) Patients From The Norwegian And Swedish National PPMS Registries (S34.009)

OBJECTIVE: To present the CSF1R screening in 218 PPMS patients and to report the clinical features of a case of Hereditary Diffuse Leukoencephalopathy with Spheroids (HDLS) with a novel CSF1R mutation, who was initially diagnosed as PPMS. BACKGROUND: HDLS is a devastating hereditary, white matter (WM) disorder with heterogenous neuropsychiatric features with a variable age of onset and disease duration. DESIGN/METHODS: Sequencing of CSF1R exons 12-22 in a cohort of 218 PPMS patients selected from the Swedish and Norwegian national MS registries. RESULTS: One patient out of 218 PPMS patients was found to harbor 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 lower left extremity. The cerebrospinal fluid was normal for cell count, albumin, neurofilaments and Alzheimer’s biomarkers, but there were 4 enriched oligoclonal bands. An MRI performed 4 years after symptom onset demonstrated patchy periventricular WM lesions. She was diagnosed with MS and treated with intramuscular interferon beta 1a (Avonex®), but due to slow progression of pyramidal symptoms and additional memory decline and cerebellar symptoms such as dystaxia and an unsteady gait she was switched to subcutaneous interferon beta 1a (Rebif®), without any benefit. Finally natalizumab (Tysabri®) was offered but the patient refused it. The updated pedigree indicated that 4 relatives, 3 of whom had been clinically diagnosed with MS, were affected by a neurological disorder starting in adult age. The patient has a highly suspected hereditary neurological disorder. However, at the present time we were not able to analyze her relatives. CONCLUSIONS: Our study indicates that a chronic course of HDLS might mimic PPMS clinically, radiologically and in the CSF. This underscores the importance of excluding HDLS when diagnosing atypical forms of PPMS with a family history indicating a neurological disorder. Study Supported by: Disclosure: Dr. Sundal has received research support from Anna-Lisa och Bror Bjrnssons-, Gamla Tjnarinnor Foundations, The Swedish Society of Medicine Gothenburg (GLS), The Swedish Society of Medicine Sweden and Gothenburg Societies for the Neurologically. Dr. Baker has nothing to disclose. Dr. Karrenbauer has nothing to disclose. Dr. Myhr has received personal compensation for activities with Bayer Schering, Biogen Idec, Merck Serono, Novartis, and Sanofi-Aventis Pharmaceuticals Inc. Dr. Haugarvoll has nothing to disclose. Dr. Fujioka has nothing to disclose. Dr. Harbo has nothing to disclose. Dr. Aasly has nothing to disclose. Dr. Hillert has received personal compensation for activities with Biogen Idec as an advisory board member, with Merck Serono as a consultant, and with Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience as a speaker. Dr. Hillert has received research support from Sanofi-Aventis Pharmaceuticals Inc., Bayer Schering, Biogen Idec, and Merck Serono. Dr. Wszolek has received personal compensation in an editorial capacity for Parkinsonism and Related Disorders, and for the European Journal of Neurology. Dr. Wszolek has received license fee payments from Mayo Clinic. Dr. Wright has received research support from the National Institutes of Health, Mayo Clinic Florida, and the Dystonia Medical Research Foundation. Dr. Rademakers has nothing to disclose. Dr. Andersen has nothing to disclose.