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@ARTICLE{Krohn:276321,
author = {Krohn, Stephan and Müller-Jensen, Leonie and Kuchling,
Joseph and Romanello, Amy and Wurdack, Katharina and Rekers,
Sophia and Bartsch, Thorsten and Leypoldt, Frank and Paul,
Friedemann and Ploner, Christoph J and Prüss, Harald and
Finke, Carsten},
title = {{C}ognitive {D}eficits in {A}nti-{LGI}1 {E}ncephalitis
{A}re {L}inked to {I}mmunotherapy-{R}esistant {W}hite
{M}atter {N}etwork {C}hanges.},
journal = {Neurology: Neuroimmunology $\&$ Neuroinflammation ;
official journal of the American Academy of Neurology},
volume = {12},
number = {2},
issn = {2332-7812},
address = {Philadelphia, Pa.},
publisher = {Wolters Kluwer},
reportid = {DZNE-2025-00284},
pages = {e200360},
year = {2025},
abstract = {Cognitive 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.},
keywords = {Humans / Male / Female / Middle Aged / White Matter:
diagnostic imaging / White Matter: pathology / Cognitive
Dysfunction: etiology / Cognitive Dysfunction:
physiopathology / Cognitive Dysfunction: diagnostic imaging
/ Aged / Cross-Sectional Studies / Immunotherapy: methods /
Nerve Net: diagnostic imaging / Nerve Net: physiopathology /
Nerve Net: pathology / Encephalitis: diagnostic imaging /
Encephalitis: immunology / Intracellular Signaling Peptides
and Proteins / Autoantibodies: blood / Diffusion Tensor
Imaging / LGI1 protein, human (NLM Chemicals) /
anti-leucine-rich glioma-inactivated 1 autoantibody (NLM
Chemicals) / Intracellular Signaling Peptides and Proteins
(NLM Chemicals) / Autoantibodies (NLM Chemicals)},
cin = {AG Prüß},
ddc = {610},
cid = {I:(DE-2719)1810003},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39879565},
doi = {10.1212/NXI.0000000000200360},
url = {https://pub.dzne.de/record/276321},
}