Radiological features of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its longitudinal progression
Rajasimhan Rajagovindan1, Ryan O’Mara1, Andreas Meier1, James MacDougall2, Elizabeth Finger3, Jennifer Orthmann-Murphy4, Daniel Broderick5, Zbigniew Wszolek6, Spyros Papapetropoulos1
1Vigil Neuroscience, 2Senior Statistical Consultant, 3LHSC, 4University of Pennsylvania, 5Mayo Clinic, 6Mayo Clinic- Jacksonville
Objective:
To characterize the radiological features of ALSP and its progression to aid with accurate diagnosis and to inform the design of therapeutic intervention studies in ALSP.
Background:
ALSP is a rare, rapidly progressing fatal neurologic disorder commonly caused by dominant variants in the CSF1R gene. Demyelination of brain white matter, swollen axons and pigmented glial cells are the pathological hallmarks of this disorder. ALSP is characterized by a constellation of symptoms including personality changes, cognitive dysfunction and motor impairments, which can mimic several neurodegenerative diseases and thus is often difficult to diagnose. Treatment options for ALSP are limited. Furthermore, limited natural history data are available to inform clinical trial design of novel therapeutics.
Design/Methods:
This was a retrospective, multicenter, natural history study of patients diagnosed with ALSP. Data including demographics, medical/clinical history, diagnostic results, interventions/medications and MRI were acquired through retrospective review of EHR/medical records of deidentified patients. MRI severity score (Sundal et al. 2012), white matter lesion and regional brain volumes were derived for available MRI exams.
Results:
Records of 62 patients were reviewed. Brain MRIs were available for 19 patients. Among these 19 patients, 16 had documentation of CSF1R gene mutation, 10 were women, mean age at diagnosis was 48.7±12.9 years and 9 had longitudinal MRI exams available. Brain MRI findings included white matter lesions (100%) with a fronto-parietal distribution, corpus callosum thinning (79%), brain atrophy (84%) and enlarged ventricles (37%). The average MRI severity score was 14.3±6.5 (range: 3-25). Progression in MRI severity score, white matter lesion volume and regional brain volume loss were observed in most individuals with longitudinal MRI scans.
Conclusions:
Recognition of the differential MRI patterns of ALSP may improve diagnostic evaluation. Qualitative and quantitative measures of MRI disease severity demonstrate potential as sensitive outcome measures in therapeutic intervention studies in ALSP.