Dados do Trabalho

Título

Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia

RESUMO

A 45-year-old man consulted his doctor with a year's onset of memory problems and behavioral changes. He worked as a delivery man for a company and began to mix up his deliveries and get lost in previously known streets. His wife also noticed he was forgetting to pay the bills, a task he had always done without problem, and that he was using the money for other purposes. Because these problems were getting worse and affecting the life of the patient and his family, the wife chose to take him for a medical examination. He underwent cognitive testing and his results were indicative of mild cognitive impairment, especially in the memory and visual-spatial areas. Screening tests were ordered. His blood tests were normal and the CSF showed only a slight increase in total protein. The MRI revealed atrophy and white matter lesions in the frontal lobe of the cerebrum and around the lateral ventricles, making those appear enlarged; a thinning of the anterior corpus callosum; and small calcifications in the white matter around the semi-oval centers, radiated crowns, and knee of the corpus callosum. These findings suggested Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) and a genetic test was done for further research. A Variant of Uncertain Significance, c.2522A>G (p.Tyr841Cys), was identified in the colony-stimulating factor-1 receptor (CSF1R) gene, which is associated with autosomal dominant hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD). Once both disorders were linked to CSF1R gene variants, they became known as ALSP. Treatment was initiated with a cholinesterase inhibitor and antipsychotic drugs, with a partial response from the patient, mostly in behavioral symptoms. Non-pharmacological approaches were also established. The family was oriented about the diagnosis, and the disease's progressive nature, and THEY were sent to genetic counseling.

ALSP is a rare, progressive neurological disease that causes leukodystrophy, forming lesions in certain brain areas due to disease-causing variants in the CSF1R gene. It is estimated to occur in 10 to 25% of adult-onset leukodystrophies. Lesions of the white matter lead to major changes in personality, cognition, and muscle function. There are currently no approved treatments for ALSP and current treatment options do not reverse brain damage but instead are meant to manage symptoms.