Blurring in patients with temporal lobe epilepsy: clinical, high-field imaging and ultrastructural study

Garbelli, Rita; Milesi, Gloria; Medici, Valentina; Villani, Flavio; Didato, Giuseppe; Deleo, Francesco; D’Incerti, Ludovico; Morbin, Michela; Mazzoleni, Giulia; Giovagnoli, Anna Rita; Parente, Annalisa; Zucca, Ileana; Mastropietro, Alfonso; Spreafico, Roberto

doi:10.1093/brain/aws149

Cited by 100 publications

(138 citation statements)

References 39 publications

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“…In our study, it was present in 45% of children with HS. This is in line with the literature, which reports that temporopolar blurring is present in 32‐66% of adults with TLE and HS39 and in 57% of children 42. It has previously been postulated to be caused by vasculometabolic changes,43 cortical dysplasia,44 inflammatory changes,45 increased perivascular spaces, abnormal water content,46 widespread gliosis45 as well as myelin loss 45.…”

Section: Discussionsupporting

confidence: 93%

“…Ipsi‐lesional blurring of the gray‐white matter boundary can often be seen on visual inspection of T1w MRI scans of patients with TLE 39, 40, 41. In our study, it was present in 45% of children with HS.…”

Section: Discussionsupporting

confidence: 50%

“…It has previously been postulated to be caused by vasculometabolic changes,43 cortical dysplasia,44 inflammatory changes,45 increased perivascular spaces, abnormal water content,46 widespread gliosis45 as well as myelin loss 45. A recent study by Garbelli and colleagues relating histopathology to high‐field imaging carefully attempted to disentangle these factors and found that blurring was associated with axonal degeneration and reduced axonal numbers in the white matter 39. Interestingly, they observed no difference in blurring between patients with or without subtle cortical dysplasias in the temporal pole.…”

Section: Discussionmentioning

confidence: 99%

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Multimodal computational neocortical anatomy in pediatric hippocampal sclerosis

Adler

Blackwood

Northam

et al. 2018

Ann Clin Transl Neurol

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ObjectiveIn contrast to adult cohorts, neocortical changes in epileptic children with hippocampal damage are not well characterized. Here, we mapped multimodal neocortical markers of epilepsy‐related structural compromise in a pediatric cohort of temporal lobe epilepsy and explored how they relate to clinical factors.MethodsWe measured cortical thickness, gray–white matter intensity contrast and intracortical FLAIR intensity in 22 patients with hippocampal sclerosis (HS) and 30 controls. Surface‐based linear models assessed between‐group differences in morphological and MR signal intensity markers. Structural integrity of the hippocampus was measured by quantifying atrophy and FLAIR patterns. Linear models were used to evaluate the relationships between hippocampal and neocortical MRI markers and clinical factors.ResultsIn the hippocampus, patients demonstrated ipsilateral atrophy and bilateral FLAIR hyperintensity. In the neocortex, patients showed FLAIR signal hyperintensities and gray–white matter boundary blurring in the ipsilesional mesial and lateral temporal neocortex. In contrast, cortical thinning was minimal and restricted to a small area of the ipsilesional temporal pole. Furthermore, patients with a history of febrile convulsions demonstrated more pronounced FLAIR hyperintensity in the ipsilesional temporal neocortex.InterpretationPediatric HS patients do not yet demonstrate the widespread cortical thinning present in adult cohorts, which may reflect consequences of a protracted disease process. However, pronounced temporal neocortical FLAIR hyperintensity and blurring of the gray–white matter boundary are already detectable, suggesting that alterations in MR signal intensities may reflect a different underlying pathophysiology that is detectable earlier in the disease and more pervasive in patients with a history of febrile convulsions.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

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Multimodal computational neocortical anatomy in pediatric hippocampal sclerosis

Adler

Blackwood

Northam

et al. 2018

Ann Clin Transl Neurol

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“…25 (17-34) 36 (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) 186 (88) 145 ( Most published studies aimed at identifying the factors predicting outcomes are mainly based on electroclinical parameters, but it has been pointed that etiology may play a role in influencing the long-term efficacy of TLE surgery. 21 We therefore evaluated outcomes in relation to the pathologic categories of IHS and HS associated with other pathologies (FCD IIIa or DP).…”

Section: (4-15)mentioning

confidence: 99%

Short‐ and long‐term surgical outcomes of temporal lobe epilepsy associated with hippocampal sclerosis: Relationships with neuropathology

et al. 2015

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SUMMARYObjective: Hippocampal sclerosis (HS) is the most frequent neuropathologic finding in patients undergoing surgery for intractable temporal lobe epilepsy (TLE). The International League Against Epilepsy (ILAE) has recently proposed a new classification of HS based on specific patterns of cell loss. The aim of this study was to investigate the relationships between HS types, their etiologic factors, and the short-and long-term postsurgical outcomes of patients undergoing surgery because of drug-resistant TLE with HS. Methods: Two hundred thirteen patients with a neuropathologic diagnosis of HS and a minimum follow-up of 2 years were divided on the basis of their ILAE HS type and further classified into: (1) isolated HS, (2) HS associated with focal cortical dysplasia (FCD IIIa), or (3) HS associated with other lesions. Their clinical and neuropathologic data were correlated with their Engel class postsurgical outcomes. Results: The main findings were the following: (1) HS type 1 was associated with a longer duration of epilepsy; (2) >80% of the patients had an Engel class I short-and long-term outcomes, regardless of HS type and associated pathology; (3) short-and long-term postsurgical outcomes were less satisfactory in the patients who were completely seizure-free (Engel class Ia), and patients with HS type 2 had better long-term seizure outcomes than those with type 1; (4) the concomitant presence of FCD contributed to a worse outcome, regardless of HS type; and (5) a shorter duration of epilepsy significantly correlated with an Engel class Ia outcome. Significance: These data suggest that HS type and associated pathologies may predict the risk of recurrence, but other variables such as the duration of epilepsy need to be considered. A common neuropathologic classification system may help to identify preoperative predictive factors and improve the selection of patients who may benefit from epilepsy surgery.

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“…Many studies correlating MRI and histology have been done without the use of computational methods for 3D image registration (Eriksson et al, 2005;Lockwood-Estrin et al, 2012;Garbelli et al, 2012). These rely on visual matching of anatomy or lesions, usually on a slice by slice basis, and are suitable if the tissue of interest (lesion, or anatomy) can be reliably identified in both modalities.…”

Section: Discussionmentioning

confidence: 99%

Registration of in-vivo to ex-vivo MRI of surgically resected specimens: A pipeline for histology to in-vivo registration

Goubran

Ribaupierre

Hammond

et al. 2015

Journal of Neuroscience Methods

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h i g h l i g h t s• We present a protocol for registration of in-vivo to ex-vivo brain specimens.• This protocol completes a registration pipeline for histology to in-vivo MRI.• A TRE of 1.35 ± 0.11 mm (neocortex) and 1.41 ± 0.33 mm (hippocampus) was found.• Deformable registration significantly improved the registration accuracy.• This pipeline allows for the assessment of pathological correlates in MRI. a r t i c l e i n f o t r a c tBackground: Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to develop and evaluate a protocol for deformable image registration of in-vivo to ex-vivo resected brain specimen MRI. This protocol, in conjunction with our previous work on ex-vivo to histology registration, completes a registration pipeline for histology to in-vivo MRI, enabling voxel-based validation of novel and existing MRI techniques with histopathology. New method: A combination of image-based and landmark-based 3D registration was used to register in-vivo MRI and the ex-vivo MRI from patients (N = 10) undergoing epilepsy surgery. Target registration error (TRE) was used to assess accuracy and the added benefit of deformable registration. Results: A mean TRE of 1.35 ± 0.11 and 1.41 ± 0.33 mm was found for neocortical and hippocampal specimens respectively. Statistical analysis confirmed that the deformable registration significantly improved the registration accuracy for both specimens.Comparison with existing methods: Image registration of surgically resected brain specimens is a unique application which presents numerous technical challenges and that have not been fully addressed in previous literature. Our computed TRE are comparable to previous attempts tackling similar applications, as registering in-vivo MRI to whole brain or serial histology. Conclusion: The presented registration pipeline finds dense and accurate spatial correspondence between in-vivo MRI and histology and allows for the spatially local and quantitative assessment of pathological correlates in MRI.

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Blurring in patients with temporal lobe epilepsy: clinical, high-field imaging and ultrastructural study

Cited by 100 publications

References 39 publications

Multimodal computational neocortical anatomy in pediatric hippocampal sclerosis

Multimodal computational neocortical anatomy in pediatric hippocampal sclerosis

Short‐ and long‐term surgical outcomes of temporal lobe epilepsy associated with hippocampal sclerosis: Relationships with neuropathology

Registration of in-vivo to ex-vivo MRI of surgically resected specimens: A pipeline for histology to in-vivo registration

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