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  1. Article ; Online: Altered structural connectome in non-lesional newly diagnosed focal epilepsy: Relation to pharmacoresistance.

    Kreilkamp, Barbara A K / McKavanagh, Andrea / Alonazi, Batil / Bryant, Lorna / Das, Kumar / Wieshmann, Udo C / Marson, Anthony G / Taylor, Peter N / Keller, Simon S

    NeuroImage. Clinical

    2021  Volume 29, Page(s) 102564

    Abstract: Despite an expanding literature on brain alterations in patients with longstanding epilepsy, few neuroimaging studies investigate patients with newly diagnosed focal epilepsy (NDfE). Understanding brain network impairments at diagnosis is necessary to ... ...

    Abstract Despite an expanding literature on brain alterations in patients with longstanding epilepsy, few neuroimaging studies investigate patients with newly diagnosed focal epilepsy (NDfE). Understanding brain network impairments at diagnosis is necessary to elucidate whether or not brain abnormalities are principally due to the chronicity of the disorder and to develop prognostic markers of treatment outcome. Most adults with NDfE do not have MRI-identifiable lesions and the reasons for seizure onset and refractoriness are unknown. We applied structural connectomics to T1-weighted and multi-shell diffusion MRI data with generalized q-sampling image reconstruction using Network Based Statistics (NBS). We scanned 27 patients within an average of 3.7 (SD = 2.9) months of diagnosis and anti-epileptic drug treatment outcomes were collected 24 months after diagnosis. Seven patients were excluded due to lesional NDfE and outcome data was available in 17 patients. Compared to 29 healthy controls, patients with non-lesional NDfE had connectomes with significantly decreased quantitative anisotropy in edges connecting right temporal, frontal and thalamic nodes and increased diffusivity in edges between bilateral temporal, frontal, occipital and parietal nodes. Compared to controls, patients with persistent seizures showed the largest effect size (|d|>=1) for decreased anisotropy in right parietal edges and increased diffusivity in edges between left thalamus and left parietal nodes. Compared to controls, patients who were rendered seizure-free showed the largest effect size for decreased anisotropy in the edge connecting the left thalamus and right temporal nodes and increased diffusivity in edges connecting right frontal nodes. As demonstrated by large effect sizes, connectomes with decreased anisotropy (edge between right frontal and left insular nodes) and increased diffusivity (edge between right thalamus and left parietal nodes) were found in patients with persistent seizures compared to patients who became seizure-free. Patients who had persistent seizures showed larger effect sizes in all network metrics than patients who became seizure-free when compared to each other and compared to controls. Furthermore, patients with focal-to-bilateral tonic-clonic seizures (FBTCS, N = 11) had decreased quantitative anisotropy in a bilateral network involving edges between temporal, parietal and frontal nodes with greater effect sizes than those of patients without FBTCS (N = 9). NBS findings between patients and controls indicated that structural network changes are not necessarily a consequence of longstanding refractory epilepsy and instead are present at the time of diagnosis. Computed effect sizes suggest that there may be structural network MRI-markers of future pharmacoresistance and seizure severity in patients with a new diagnosis of focal epilepsy.
    MeSH term(s) Adult ; Brain/diagnostic imaging ; Connectome ; Epilepsies, Partial/diagnostic imaging ; Epilepsies, Partial/drug therapy ; Humans ; Magnetic Resonance Imaging ; Seizures
    Language English
    Publishing date 2021-01-19
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701571-3
    ISSN 2213-1582 ; 2213-1582
    ISSN (online) 2213-1582
    ISSN 2213-1582
    DOI 10.1016/j.nicl.2021.102564
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Fiber ball white matter modeling in focal epilepsy.

    Bryant, Lorna / McKinnon, Emilie T / Taylor, James A / Jensen, Jens H / Bonilha, Leonardo / de Bezenac, Christophe / Kreilkamp, Barbara A K / Adan, Guleed / Wieshmann, Udo C / Biswas, Shubhabrata / Marson, Anthony G / Keller, Simon S

    Human brain mapping

    2021  Volume 42, Issue 8, Page(s) 2490–2507

    Abstract: Multicompartment diffusion magnetic resonance imaging (MRI) approaches are increasingly being applied to estimate intra-axonal and extra-axonal diffusion characteristics in the human brain. Fiber ball imaging (FBI) and its extension fiber ball white ... ...

    Abstract Multicompartment diffusion magnetic resonance imaging (MRI) approaches are increasingly being applied to estimate intra-axonal and extra-axonal diffusion characteristics in the human brain. Fiber ball imaging (FBI) and its extension fiber ball white matter modeling (FBWM) are such recently described multicompartment approaches. However, these particular approaches have yet to be applied in clinical cohorts. The modeling of several diffusion parameters with interpretable biological meaning may offer the development of new, noninvasive biomarkers of pharmacoresistance in epilepsy. In the present study, we used FBI and FBWM to evaluate intra-axonal and extra-axonal diffusion properties of white matter tracts in patients with longstanding focal epilepsy. FBI/FBWM diffusion parameters were calculated along the length of 50 white matter tract bundles and statistically compared between patients with refractory epilepsy, nonrefractory epilepsy and controls. We report that patients with chronic epilepsy had a widespread distribution of extra-axonal diffusivity relative to controls, particularly in circumscribed regions along white matter tracts projecting to cerebral cortex from thalamic, striatal, brainstem, and peduncular regions. Patients with refractory epilepsy had significantly greater markers of extra-axonal diffusivity compared to those with nonrefractory epilepsy. The extra-axonal diffusivity alterations in patients with epilepsy observed in the present study could be markers of neuroinflammatory processes or a reflection of reduced axonal density, both of which have been histologically demonstrated in focal epilepsy. FBI is a clinically feasible MRI approach that provides the basis for more interpretive conclusions about the microstructural environment of the brain and may represent a unique biomarker of pharmacoresistance in epilepsy.
    MeSH term(s) Adult ; Biomarkers ; Diffusion Tensor Imaging/methods ; Drug Resistant Epilepsy/diagnostic imaging ; Drug Resistant Epilepsy/pathology ; Epilepsies, Partial/diagnostic imaging ; Epilepsies, Partial/pathology ; Female ; Humans ; Male ; Middle Aged ; Models, Theoretical ; White Matter/diagnostic imaging ; White Matter/pathology
    Chemical Substances Biomarkers
    Language English
    Publishing date 2021-02-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1197207-5
    ISSN 1097-0193 ; 1065-9471
    ISSN (online) 1097-0193
    ISSN 1065-9471
    DOI 10.1002/hbm.25382
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: High b-value diffusion tractography: Abnormal axonal network organization associated with medication-refractory epilepsy.

    Gleichgerrcht, Ezequiel / Keller, Simon S / Bryant, Lorna / Moss, Hunter / Kellermann, Tanja S / Biswas, Shubhabrata / Marson, Anthony G / Wilmskoetter, Janina / Jensen, Jens H / Bonilha, Leonardo

    NeuroImage

    2021  Volume 248, Page(s) 118866

    Abstract: Diffusion magnetic resonance imaging (dMRI) tractography has played a critical role in characterizing patterns of aberrant brain network reorganization among patients with epilepsy. However, the accuracy of dMRI tractography is hampered by the complex ... ...

    Abstract Diffusion magnetic resonance imaging (dMRI) tractography has played a critical role in characterizing patterns of aberrant brain network reorganization among patients with epilepsy. However, the accuracy of dMRI tractography is hampered by the complex biophysical properties of white matter tissue. High b-value diffusion imaging overcomes this limitation by better isolating axonal pathways. In this study, we introduce tractography derived from fiber ball imaging (FBI), a high b-value approach which excludes non-axonal signals, to identify atypical neuronal networks in patients with epilepsy. Specifically, we compared network properties obtained from multiple diffusion tractography approaches (diffusion tensor imaging, diffusion kurtosis imaging, FBI) in order to assess the pathophysiological relevance of network rearrangement in medication-responsive vs. medication-refractory adults with focal epilepsy. We show that drug-resistant epilepsy is associated with increased global network segregation detected by FBI-based tractography. We propose exploring FBI as a clinically feasible alternative to quantify topological changes that could be used to track disease progression and inform on clinical outcomes.
    MeSH term(s) Adolescent ; Adult ; Axons/pathology ; Case-Control Studies ; Diffusion Tensor Imaging/methods ; Drug Resistant Epilepsy/pathology ; Female ; Humans ; Male ; Middle Aged ; Neural Pathways/pathology
    Language English
    Publishing date 2021-12-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1147767-2
    ISSN 1095-9572 ; 1053-8119
    ISSN (online) 1095-9572
    ISSN 1053-8119
    DOI 10.1016/j.neuroimage.2021.118866
    Database MEDical Literature Analysis and Retrieval System OnLINE

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