Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy; a PET study
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LMNB1-related autosomal dominant leukodystrophy is caused by an overexpression of the protein lamin B1, usually due to a duplication of the LMNB1-gene. Symptoms start in adulthood, and the disease is slowly progressive over decades and terminates with pseudobulbar palsy and finally death. Here, we present 18F-fluorodeoxyglucose positron emission tomography findings in eight patients, aged 48-64 years, with varying stages of clinical symptomatology. Initially, two patients were investigated with quantitative positron emission tomography on clinical indications after which six more were recruited. Absolute glucose metabolism in six patients was analysed with the PVElab software and compared to findings in eighteen healthy controls. A semiquantitative analysis using the CortexID software was performed in seven of the investigations, relating local metabolism levels to global glucose metabolism. In the PVElab analysis of absolute glucose metabolism, patients presented low mean glucose metabolism in the cerebellum, brainstem and global grey matter. The earlier clinical quantitative positron emission tomography also revealed low global glucose metabolism, with the most marked reduction in the cerebellum. In the semiquantitative analysis, two patients showed a decreased metabolism in the cerebellum and four patients an apparent increased metabolism in parts of the temporal lobes, compared to global glucose metabolism. However, since none of the patients showed an increased metabolism in the quantitative analysis, we interpret these findings as ‘pseudo-increases’ related to a globally reduced metabolism. The lowest metabolism in the cerebellum is consistent with the clinical cerebellar symptoms and previous histopathological findings in the disease. The global reduction of glucose metabolism most likely depends on a combination of cortical afferent dysfunction and neuronal loss.
Radiology, Nuclear Medicine and Medical Imaging
IdentifiersURN: urn:nbn:se:uu:diva-303170OAI: oai:DiVA.org:uu-303170DiVA: diva2:970982