RÉSUMÉ
STUDY OBJECTIVES: Growing evidences have documented various abnormalities of the white matter bundles in people with narcolepsy. We sought to evaluate topological properties of brain structural networks, and their association with symptoms and neuropathophysiological features in people with narcolepsy. METHODS: Diffusion tensor imaging was conducted for people with narcolepsy (nâ =â 30) and matched healthy controls as well as symptoms assessment. Structural connectivity for each participant was generated to analyze global and regional topological properties and their correlations with narcoleptic features. Further human brain transcriptome was extracted and spatially registered for connectivity vulnerability. Genetic functional enrichment analysis was performed and further clarified using in vivo emission computed tomography data. RESULTS: A wide and dramatic decrease in structural connectivities was observed in people with narcolepsy, with descending network degree and global efficiency. These metrics were not only correlated with sleep latency and awakening features, but also reflected alterations of sleep macrostructure in people with narcolepsy. Network-based statistics identified a small hyperenhanced subnetwork of cingulate gyrus that was closely related to rapid eye movement sleep behavior disorder (RBD) in narcolepsy. Further imaging genetics analysis suggested glutamatergic signatures were responsible for the preferential vulnerability of connectivity alterations in people with narcolepsy, while additional PET/SPECT data verified that structural alteration was significantly correlated with metabotropic glutamate receptor 5 (mGlutR5) and N-methyl-D-aspartate receptor (NMDA). CONCLUSIONS: People with narcolepsy endured a remarkable decrease in the structural architecture, which was not only closely related to narcolepsy symptoms but also glutamatergic signatures.
Sujet(s)
Encéphale , Imagerie par tenseur de diffusion , Narcolepsie , Humains , Narcolepsie/physiopathologie , Narcolepsie/génétique , Narcolepsie/imagerie diagnostique , Mâle , Adulte , Femelle , Encéphale/imagerie diagnostique , Encéphale/physiopathologie , Encéphale/anatomopathologie , Réseau nerveux/physiopathologie , Réseau nerveux/imagerie diagnostique , Substance blanche/imagerie diagnostique , Substance blanche/physiopathologie , Substance blanche/anatomopathologie , Trouble du comportement en sommeil paradoxal/physiopathologie , Trouble du comportement en sommeil paradoxal/imagerie diagnostique , Trouble du comportement en sommeil paradoxal/génétique , Études cas-témoins , Adulte d'âge moyenRÉSUMÉ
Autoimmune encephalitis (AE) is the result of an autoimmune process that occurs as a rapidly advancing encephalopathy. Autoimmune encephalitis was commonly linked to herpes simplex virus 1 (HSV-1) as the most frequently identified virus. The main areas affected by this invasion are the temporal lobe, frontal lobe, and limbic system. Limbic encephalitis is a highly uncommon occurrence involving anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and anti-IgLON family member 5 (IgLON5) disease, both belonging to the rare category. As far as we know, this is the first report showing that a patient diagnosed with AMPAR encephalitis overlapped with anti-IgLON5 disease post herpes simplex virus encephalitis (HSE), which helps to broaden the range of this uncommon autoimmune disease. We recommend autoantibody testing in all patients with HSE, particularly those involving neurological relapses or progression.
Sujet(s)
Encéphalopathies , Encéphalite à herpès simplex , Maladie de Hashimoto , Herpèsvirus humain de type 1 , Humains , Molécules d'adhérence cellulaire neuronale , Encéphalite à herpès simplex/traitement médicamenteuxRÉSUMÉ
BACKGROUND: Inosine monophosphate dehydrogenase-1 is the target of mycophenolate mofetil. This research investigated the association between the gene polymorphism of inosine monophosphate dehydrogenase-1 and effectiveness of mycophenolate mofetil therapy in neuromyelitis optica spectrum disorder patients. METHODS: Fifty-nine neuromyelitis optica spectrum disorder patients accepted Mycophenolate Mofetil therapy for 1 year at least were divided into two groups: relapsing (n=21) and non-relapsing (n=38). Four single-nucleotide polymorphisms (SNPs: rs2228075, rs2278294, rs2288550, and rs3793165) in the inosine monophosphate dehydrogenase-1 gene were detected. Then we analyzed the allelic frequencies and the genotypes of SNPs in two groups. RESULTS: The allelic frequency of rs2278294 distributed differently between the relapse and non-relapsing patients (P=0.03), while no significant difference found in rs2228075, rs2288550 and rs3793165 between two groups. The genotypes C/C, C/T and T/T of rs2278294 (P = 0.031) also distributed differently between the two groups. Logistic regression analysis (adjusted by optic neuritis) showed that compared to the wild genotype C/C, C/T genotype had a 9-fold protection against relapse (OR=0.111 (0.022-0.548)), and T/T genotype had a 6.7-fold protection against relapse (OR=0.149 (0.026-0.854)). CONCLUSION: Our study provides preliminary evidence that the genotype of rs2278294 is associated with the response of neuromyelitis optica spectrum disorder patients to mycophenolate mofetil therapy. And compared to wild allelic C, the mutation to T tended to respond better to MMF.