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000276321 1001_ $$00000-0003-0683-5386$$aKrohn, Stephan$$b0
000276321 245__ $$aCognitive Deficits in Anti-LGI1 Encephalitis Are Linked to Immunotherapy-Resistant White Matter Network Changes.
000276321 260__ $$aPhiladelphia, Pa.$$bWolters Kluwer$$c2025
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000276321 520__ $$aCognitive deficits represent a major long-term complication of anti-leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E). Although severely affecting patient outcomes, the structural brain changes underlying these deficits remain poorly understood. In this study, we hypothesized a link between white matter (WM) networks and cognitive outcomes in LGI1-E.In this cross-sectional study, we combined clinical assessments, comprehensive neuropsychological testing, diffusion tensor MRI, probabilistic WM tractography, and computational network analysis in patients with LGI1-E referred to Charité-Universitätsmedizin Berlin. Healthy individuals were recruited as control participants and matched to patients for age and sex with logistic regression propensity scores.Twenty-five patients with LGI1-E (mean age = 63 ± 12 years, 76% male) and 25 healthy controls were enrolled. Eighty-eight percent of patients presented persistent cognitive symptoms at postacute follow-up (median: 12 months from onset, interquartile range: 6-23 months)-despite treatment with immunotherapy and good overall recovery (modified Rankin Scale [mRS] score at peak illness vs postacute: z = -4.1, p < 0.001, median mRS score at postacute visit: 1). Neuroimaging revealed that WM networks in LGI1-E are characterized by (1) a systematic reduction in whole-brain connectivity (t = -2.16, p = 0.036, d = -0.61), (2) a cortico-subcortical hypoconnectivity cluster affecting both limbic and extralimbic brain systems, and (3) a 'topological reorganization' marked by a bidirectional shift in the relative importance of individual brain regions in the WM network. The extent of this WM reorganization was strongly associated with long-term deficits of verbal memory (r = -0.56), attention (r = -0.55), and executive functions (r = -0.60, all pFDR = 0.017).Although traditionally viewed as a form of limbic encephalitis, our study characterizes LGI1-E as a 'network disorder' that affects the whole brain. Structural reorganization of WM networks was linked to long-term and multidomain cognitive impairment, which was not prevented by immunotherapy. These findings highlight the need for closer monitoring and improved treatment strategies to mitigate long-term cognitive impairment in LGI1-E.
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000276321 650_7 $$2NLM Chemicals$$aLGI1 protein, human
000276321 650_7 $$2NLM Chemicals$$aanti-leucine-rich glioma-inactivated 1 autoantibody
000276321 650_7 $$2NLM Chemicals$$aIntracellular Signaling Peptides and Proteins
000276321 650_7 $$2NLM Chemicals$$aAutoantibodies
000276321 650_2 $$2MeSH$$aHumans
000276321 650_2 $$2MeSH$$aMale
000276321 650_2 $$2MeSH$$aFemale
000276321 650_2 $$2MeSH$$aMiddle Aged
000276321 650_2 $$2MeSH$$aWhite Matter: diagnostic imaging
000276321 650_2 $$2MeSH$$aWhite Matter: pathology
000276321 650_2 $$2MeSH$$aCognitive Dysfunction: etiology
000276321 650_2 $$2MeSH$$aCognitive Dysfunction: physiopathology
000276321 650_2 $$2MeSH$$aCognitive Dysfunction: diagnostic imaging
000276321 650_2 $$2MeSH$$aAged
000276321 650_2 $$2MeSH$$aCross-Sectional Studies
000276321 650_2 $$2MeSH$$aImmunotherapy: methods
000276321 650_2 $$2MeSH$$aNerve Net: diagnostic imaging
000276321 650_2 $$2MeSH$$aNerve Net: physiopathology
000276321 650_2 $$2MeSH$$aNerve Net: pathology
000276321 650_2 $$2MeSH$$aEncephalitis: diagnostic imaging
000276321 650_2 $$2MeSH$$aEncephalitis: immunology
000276321 650_2 $$2MeSH$$aIntracellular Signaling Peptides and Proteins
000276321 650_2 $$2MeSH$$aAutoantibodies: blood
000276321 650_2 $$2MeSH$$aDiffusion Tensor Imaging
000276321 7001_ $$00000-0002-6388-9375$$aMüller-Jensen, Leonie$$b1
000276321 7001_ $$aKuchling, Joseph$$b2
000276321 7001_ $$00000-0003-1257-9593$$aRomanello, Amy$$b3
000276321 7001_ $$00000-0003-0952-5658$$aWurdack, Katharina$$b4
000276321 7001_ $$00000-0002-6161-6621$$aRekers, Sophia$$b5
000276321 7001_ $$00000-0001-8387-5731$$aBartsch, Thorsten$$b6
000276321 7001_ $$00000-0002-8972-515X$$aLeypoldt, Frank$$b7
000276321 7001_ $$00000-0002-6378-0070$$aPaul, Friedemann$$b8
000276321 7001_ $$00000-0003-0983-4530$$aPloner, Christoph J$$b9
000276321 7001_ $$0P:(DE-2719)2810931$$aPrüss, Harald$$b10
000276321 7001_ $$0P:(DE-2719)9001141$$aFinke, Carsten$$b11
000276321 773__ $$0PERI:(DE-600)2767740-0$$a10.1212/NXI.0000000000200360$$gVol. 12, no. 2, p. e200360$$n2$$pe200360$$tNeurology: Neuroimmunology & Neuroinflammation ; official journal of the American Academy of Neurology$$v12$$x2332-7812$$y2025
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