Potential use of glucocorticosteroids (GCs) in CSF1R mutation carriers

The thoughts presented below by Drs. Dulski, Stanley, Chitu and Wszolek have significant limitations and must be read only as their personal views, and not as forming any recommendations or guidelines.

Key points: Drs. Dulski, Stanley, Chitu and Wszolek, recently found that glucocorticosteroids (GCs) have a possible protective effect in CSF1R mutation carriers against developing symptomatic CSF1R-related leukoencephalopathy.

Their observations on pathogenic CSF1R mutation carriers exposed to long-term immunosuppressive therapy who did not develop symptomatic disease prompted them to evaluate the effects of glucocorticosteroids (GCs) on the disease course.

They found that individuals exposed to GCs were less likely to develop symptomatic disease, or to become dependent in the activities of daily living, and less frequently had white matter lesions and corpus callosum involvement on neuroimaging.

As the harm associated with GC-therapy and GC-related toxicity depends on the dose and duration of the therapy, the goal is the lowest effective dose for the shortest duration. The ultimate benefit-versus-risk balance depends on the GC therapy regimen (dose and duration) and the individual patient profile.

An important point to understand is that based on basic science studies, at least partial preservation of microglia is a prerequisite for GCs to exert their positive effects. They speculate that GCs could be a potential benefit in the early stages of the disease when a substantial fraction of microglia still functions properly and may also be beneficial at the early stages of symptomatic disease. No benefit can be expected at the advanced stages of the disease when most microglia are damaged and dysfunctional.

Dosage: The starting GC regimen in asymptomatic CSF1R mutation carriers would include a 7-day prednisone course of 5 mg per day every 3-4 months.

Clinical visits and Follow-Up: An annual comprehensive clinical assessment with neurological, neuropsychological, and neuroimaging evaluations, remains the best strategy to monitor asymptomatic CSF1R mutation carriers, detect early first signs of conversion from asymptomatic to symptomatic disease, and monitor symptomatic disease progression.

Donations: If you are interested in donating to research, or to a multicenter collaboration to provide further evidence on GCs please donate at Ways to Give – Sisters’ Hope Foundation | ALSP Community (sistershopefoundation.org). Please note that you would like your donation to be used towards research.

For more information please refer to the full publication: Potential use of glucocorticosteroids in CSF1R mutation carriers – current evidence and future directions | Dulski | Neurologia i Neurochirurgia Polska (viamedica.pl)

Additional publications regarding GCs can be found at: Glia | Neurobiology Journal | Wiley Online Library and Protective Effect of Glucocorticoids against Symptomatic Disease in CSF1R Variant Carriers – Dulski – 2023 – Movement Disorders – Wiley Online Library.