Sunday, November 15, 2015

DTI and tuber epileptogenicity

Yogi A, Hirata Y, Karavaeva E, Harris RJ, Wu JY, Yudovin SL, Linetsky M,
Mathern GW, Ellingson BM, Salamon N. DTI of tuber and perituberal tissue can
predict epileptogenicity in tuberous sclerosis complex. Neurology. 2015 Nov 6.
pii: 10.1212/WNL.0000000000002202. [Epub ahead of print]

Abstract

OBJECTIVE:

To evaluate whether diffusion tensor imaging (DTI) can predict epileptogenic tubers by measuring apparent diffusion coefficient (ADC), fractional anisotropy, axial diffusivity, and radial diffusivity in both tubers and perituberal tissue in pediatric patients with tuberous sclerosis complex (TSC) undergoing epilepsy surgery.

METHODS:

We retrospectively selected 23 consecutive patients (aged 0.4-19.6 years, mean age of 5.2; 13 female, 10 male) who underwent presurgical DTI and subsequent surgical resection between 2004 and 2013 from the University of California-Los Angeles TSC Clinic. We evaluated presurgical examinations including video-EEG, brain MRI, 18F-fluorodeoxyglucose-PET, magnetic source imaging, and intraoperative electrocorticography for determining epileptogenic tubers. A total of 545 tubers, 33 epileptogenic and 512 nonepileptogenic, were identified. Two observers generated the regions of interest (ROIs) of tubers (ROItuber), the 4-mm-thick ring-shaped ROIs surrounding the tubers (ROIperituber), and the combined ROIs (ROItuber+perituber) in consensus and calculated maximum, minimum, mean, and median values of each DTI measure in each ROI for all tubers.

RESULTS:

The Mann-Whitney U test demonstrated that the epileptogenic group showed higher maximum ADC and radial diffusivity values in all ROIs, and that maximum ADC in ROItuber+perituber showed the strongest difference (p = 0.001). Receiver operating characteristic analysis demonstrated that maximum ADC measurements in ROItuber+perituber (area under curve = 0.68 ± 0.05, p < 0.001) had 81% sensitivity and 44% specificity for correctly identifying epileptogenic tubers with a cutoff value of 1.32 μm2/ms.

CONCLUSIONS:

DTI analysis of tubers and perituberal tissue may help to identify epileptogenic tubers in presurgical patients with TSC more easily and effectively than current invasive methods.
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2 comments:

  1. Galen Breningstall, MDNovember 16, 2015 at 12:13 PM

    Peters JM, Prohl AK, Tomas-Fernandez XK, Taquet M, Scherrer B, Prabhu SP,
    Lidov HG, Singh JM, Jansen FE, Braun KP, Sahin M, Warfield SK, Stamm A. Tubers are neither static nor discrete: Evidence from serial diffusion tensor imaging.
    Neurology. 2015 Nov 3;85(18):1536-45.

    Abstract


    OBJECTIVE:

    To assess the extent and evolution of tissue abnormality of tubers, perituber tissue, and normal-appearing white matter (NAWM) in patients with tuberous sclerosis complex using serial diffusion tensor imaging.

    METHODS:

    We applied automatic segmentation based on a combined global-local intensity mixture model of 3T structural and 35 direction diffusion tensor MRIs (diffusion tensor imaging) to define 3 regions: tuber tissue, an equal volume perituber rim, and the remaining NAWM. For each patient, scan, lobe, and tissue type, we analyzed the averages of mean diffusivity (MD) and fractional anisotropy (FA) in a generalized additive mixed model.

    RESULTS:

    Twenty-five patients (mean age 5.9 years; range 0.5-24.5 years) underwent 2 to 6 scans each, totaling 70 scans. Average time between scans was 1.2 years (range 0.4-2.9). Patient scans were compared with those of 73 healthy controls. FA values were lowest, and MD values were highest in tubers, next in perituber tissue, then in NAWM. Longitudinal analysis showed a positive (FA) and negative (MD) correlation with age in tubers, perituber tissue, and NAWM. All 3 tissue types followed a biexponential developmental trajectory, similar to the white matter of controls. An additional qualitative analysis showed a gradual transition of diffusion values across the tissue type boundaries.

    CONCLUSIONS:

    Similar to NAWM, tuber and perituber tissues in tuberous sclerosis complex undergo microstructural evolution with age. The extent of diffusion abnormality decreases with distance to the tuber, in line with known extension of histologic, immunohistochemical, and molecular abnormalities beyond tuber pathology.

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  2. Galen Breningstall, MDNovember 17, 2015 at 4:42 PM

    A prevailing model of TSC pathogenesis postulates that tubers are due to abnormalities of neural progenitor cells during early brain development.8 As tubers originate during human embryogenesis, such models led to the notion that tubers are static lesions. However, results from MRI studies challenge this notion, showing clear changes over time in patients with TSC.9 These findings, coupled with imaging data from patients treated with mTOR inhibitors,10 again support the notion that the natural history of tubers may not be static and, in fact, their appearance and possibly (dys)function can be modulated by therapeutic interventions...

    Peters et al. provide additional support for tubers being dynamic entities and show that more subtle gradations of brain pathologies likely exist along a continuum from subtle to severe. The clear implications of these findings include a possibly more aggressive approach to epilepsy surgery in patients with TSC as regions anatomically distinct from overt tubers will more likely be considered for resection. In addition to surgical interventions, their findings support a therapeutic window that can be identified if tuber dynamism unveiled by DTI is correlated with epileptogenicity or the onset of intellectual disabilities and autism spectrum disorders in children with TSC. The judicious use of mTOR inhibitors or other therapeutics when coupled with DTI may be tested to determine whether they positively alter developmental trajectories of patients with TSC and lead to much better overall outcomes.

    Ess KC, Chugani HT. Dynamic tubers in tuberous sclerosis complex: A window for
    intervention? Neurology. 2015 Nov 3;85(18):1530-1.

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