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Título

Adult-Onset Leukoencephalopathies: a diagnostic challenge

RESUMO

Introduction: Male patient, 58 years old, hypertensive, with a history of colon cancer in 2011 (treated with resection and chemotherapy) and hypogonadotropic hypogonadism. He began with attention difficulties in September/2021, which worsened over the next months with cognitive-behavioral changes like aggressiveness, irritability and apathy, sleep disturbances, memory disfunction and difficulties to perform daily tasks (paying bills on the phone, financial controlling). On neurologic examination, the patient only presented cognitive changes, with pronounced executive dysfunction. He was then hospitalized for investigation. Cerebrospinal fluid examination showed slightly elevated protein level, and brain MRI showed symmetric frontal white matter hyperintensity with spared subcortical U fibers on FLAIR images, besides no contrast enhancement and no restricted diffusion foci. Metabolic, infectious, and serologic tests were normal. The patient underwent further investigation, including genetic testing to Adult Leukodystrophies, which revealed heterozygosity for the GBE1 gene.

Discussion: Leukodystrophies are hereditary disorders that present with progressive white matter dysmyelination or defects of myelin biosynthesis and metabolism. The pattern of white matter involvement is essential to narrowing the diagnosis process. Although rare, it is an important differential diagnosis to be considered in patients with cognitive decline. Even with advances in imaging and genetic testing, about 40% of patients remain undiagnosed. Mutations in the GBE1 gene is associated with Adult Polyglucosan Body Disease, an autosomal recessive disease that presents as neurodegenerative condition with involvement of the central and peripheral nervous system.

Conclusion: Leukoencephalopathy disorders represent a diagnostic challenge for the neurologist, requiring an extensive investigation, including infectious, immune-mediated, degenerative, vascular, metabolic, and neoplastic process, in addition to genetic causes. This last group constitutes the major diagnostic challenge, mainly due to the availability of diagnostic resources in health services. For this reason, a systematic approach to the investigation of these patients is mandatory.