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Glucose metabolism in the brain in LMNB 1‐related autosomal dominant leukodystrophy
Author(s) -
Finnsson Johannes,
Lubberink Mark,
Savitcheva Irina,
Fällmar David,
Melberg Atle,
Kumlien Eva,
Raininko Raili
Publication year - 2019
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/ane.13024
Subject(s) - carbohydrate metabolism , metabolism , cerebellum , white matter , lipid metabolism , leukodystrophy , medicine , endocrinology , biology , disease , magnetic resonance imaging , radiology
Objective LMNB 1 ‐related autosomal dominant leukodystrophy is caused by an overexpression of the protein lamin B1, usually due to a duplication of the LMNB 1 gene. Symptoms start in 5 th to 6 th decade. This slowly progressive disease terminates with death. We studied brain glucose metabolism in this disease using 18 F‐fluorodeoxyglucose positron emission tomography ( PET ). Methods We examined 8 patients, aged 48‐64 years, in varying stages of clinical symptomatology. Two patients were investigated with quantitative PET on clinical indications after which six more patients were recruited. Absolute glucose metabolism was analyzed with the PVE lab software in 6 patients and 18 healthy controls. A semiquantitative analysis using the Cortex ID software was performed in seven investigations, relating local metabolism levels to global glucose metabolism. Results The clinical quantitative PET revealed low global glucose metabolism, with the most marked reduction in the cerebellum. In the PVE lab analysis, patients presented low mean glucose metabolism in the cerebellum, brainstem and global grey matter. In the semiquantitative analysis, 2 patients showed a decreased metabolism in the cerebellum and 4 patients a relatively higher metabolism in parts of the temporal lobes. Since none of the patients showed an increased metabolism in the quantitative analysis, we interpret these increases as “pseudo‐increases” related to a globally reduced metabolism. Conclusions Global reduction of grey matter glucose metabolism in this white matter disease most likely depends on a combination of cortical afferent dysfunction and, in later stages, neuronal loss. The lowest metabolism in the cerebellum is consistent with histopathological findings and prominent cerebellar symptoms.