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Treatment of Leukoencephalopathy With Calcifications and Cysts With Bevacizumab
Alex J Fay1, Allison A King2, Joshua S Shimony3
1Department of Neurology, University of California, San Francisco, San Francisco, California.
Insights
Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, shows promise for treating leukoencephalopathy with calcifications and cysts (LCC). A single patient experienced improved motor function and reduced brain lesions after over a year of treatment.
Area of Science:
- Neuroscience
- Vascular Biology
- Genetics
Background:
- Leukoencephalopathy with calcifications and cysts (LCC) is a rare, autosomal recessive cerebral microangiopathy.
- LCC causes progressive white matter disease, brain calcifications, and cysts, leading to psychomotor regression, seizures, and movement disorders.
- LCC shares features with Coats plus, a disorder affecting multiple organs, and Coats disease, a retinopathy.
Observation:
- Vascular endothelial growth factor (VEGF) inhibition with bevacizumab successfully treats retinal manifestations in Coats disease.
- The study hypothesized that VEGF inhibition could also benefit LCC and Coats plus, as neither has a current therapy.
Findings:
- An 18-year-old male with LCC received biweekly bevacizumab infusions for over a year.
- Clinical examinations and brain imaging revealed improved bradykinesia, enhanced range of motion, and significant reduction in cyst volume and white matter lesions.
Implications:
- VEGF inhibition demonstrates potential as a novel therapeutic strategy for LCC.
- Further clinical studies are needed to confirm the efficacy of bevacizumab in a larger patient cohort for LCC treatment.
Background:
Leukoencephalopathy with calcifications and cysts is a rare, autosomal recessive cerebral microangiopathy that causes progressive white matter disease, calcifications, and cysts within the brain. It is typically associated with slowly progressive psychomotor regression, seizures, and movement disorders. Although leukoencephalopathy with calcifications and cysts affects only the central nervous system, it demonstrates remarkable neuropathologic and radiologic overlap with Coats plus, a disorder of small vessels of the brain, eyes, gastrointestinal tract, and bone. Coats disease without extraocular involvement, a genetically distinct disorder from Coats plus, is characterized by retinal telangiectasias and exudative retinopathy, accompanied by neovascularization. Inhibition of vascular endothelial growth factor (VEGF) signaling with the monoclonal anti-VEGF antibody bevacizumab can improve retinal edema and exudates in Coats disease. Given these observations, we reasoned that VEGF inhibition might also be effective in treating leukoencephalopathy with calcifications and cysts and Coats plus, neither of which has any known therapy.
Methods:
We treated an 18-year-old man with leukoencephalopathy with calcifications and cysts using biweekly infusions of the VEGF inhibitor bevacizumab for more than one year and performed clinical examinations and brain imaging at three month intervals.
Results:
After treatment for more than one year, the patient showed improved bradykinesia and range of motion, and brain magnetic resonance imaging demonstrated a marked reduction in cyst volume and white matter lesions.
Conclusions:
Further studies in a cohort of patients are warranted to investigate the efficacy of VEGF inhibition as a treatment for leukoencephalopathy with calcifications and cysts.