Gray matter volumes and cognitive ability in the epileptogenic brain malformation of periventricular nodular heterotopia

Walker, Linsey M.; Katzir, Tami; Liu, Tianming; Ly, Jenny; Corriveau, Kathleen H.; Barzillai, Mirit; Chu, Felicia; O’Connor, Margaret; Hackney, David B.; Chang, Bernard S.

doi:10.1016/j.yebeh.2009.05.009

Cited by 17 publications

(17 citation statements)

References 31 publications

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“…Our results here demonstrate that unique developmental anomalies of cerebral anatomy can lead to distinct functional alterations that are associated with a form of dyslexia. Notably, there was no consistent association between the anatomical location of the activated regions of heterotopia or cortex and the type of reading-related task during which such aberrant circuit activation was seen, supporting previous volumetric evidence that the neural correlates of these and other cognitive functions may be different in the setting of neuronal migration failure [30]. …”

Section: Discussionsupporting

confidence: 66%

Integration of gray matter nodules into functional cortical circuits in periventricular heterotopia

Christodoulou

Barnard

Tufo

et al. 2013

Epilepsy & Behavior

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Alterations in neuronal circuitry are recognized as an important substrate of many neurological disorders, including epilepsy. Patients with the developmental brain malformation of periventricular nodular heterotopia (PNH) often have both seizures and dyslexia, and there is evidence to suggest that aberrant neuronal connectivity underlies both of these clinical features. We used task-based functional MRI (fMRI) to determine whether heterotopic nodules of gray matter in this condition are integrated into functional cortical circuits. Blood oxygenation level-dependent (BOLD) fMRI was acquired in eight participants with PNH during the performance of reading-related tasks. Evidence of neural activation within heterotopic gray matter was identified, and regions of cortical co-activation were then mapped systematically. Findings were correlated with resting-state functional connectivity results and with performance on the fMRI reading-related tasks. Six participants (75%) demonstrated activation within at least one region of gray matter heterotopia. Cortical areas directly overlying the heterotopia were usually co-activated (60%), as were areas known to have functional connectivity to the heterotopia in the task-free resting state (73%). Six of seven (86%) primary task contrasts resulted in heterotopia activation in at least one participant. Activation was most commonly seen during rapid naming of visual stimuli, a characteristic impairment in this patient population. Our findings represent a systematic demonstration that heterotopic gray matter can be metabolically coactivated in a neuronal migration disorder associated with epilepsy and dyslexia. Gray matter nodules were most commonly coactivated with anatomically overlying cortex and other regions with resting-state connectivity to heterotopia. These results have broader implications for understanding the network pathogenesis of both seizures and reading disabilities.

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Section: Discussionsupporting

confidence: 66%

Integration of gray matter nodules into functional cortical circuits in periventricular heterotopia

Christodoulou

Barnard

Tufo

et al. 2013

Epilepsy & Behavior

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“…This indicates that the corpus callosum changes we identified are specific to the corpus callosum and not driven by an overall change in white matter volume, which has been reported in previous studies (Walker, Katzir et al 2009, Gonzalez, Vedolin et al 2013). …”

Section: Resultssupporting

confidence: 84%

Quantitative assessment of corpus callosum morphology in periventricular nodular heterotopia

et al. 2015

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We investigated systematic differences in corpus callosum morphology in periventricular nodular heterotopia (PVNH). Differences in corpus callosum mid-sagittal area and subregional area changes were measured using an automated software-based method. Heterotopic gray matter deposits were automatically labeled and compared with corpus callosum changes. The spatial pattern of corpus callosum changes were interpreted in the context of the characteristic anterior-posterior development of the corpus callosum in healthy individuals. Individuals with periventricular nodular heterotopia were imaged at the Melbourne Brain Center or as part of the multi-site Epilepsy Phenome Genome project. Whole brain T1 weighted MRI was acquired in cases (n = 48) and controls (n = 663). The corpus callosum was segmented on the mid-sagittal plane using the software “yuki”. Heterotopic gray matter and intracranial brain volume was measured using Freesurfer. Differences in corpus callosum area and subregional areas were assessed, as well as the relationship between corpus callosum area and heterotopic GM volume. The anterior-posterior distribution of corpus callosum changes and heterotopic GM nodules were quantified using a novel metric and compared with each other. Corpus callosum area was reduced by 14% in PVNH (p = 1.59 × 10−9). The magnitude of the effect was least in the genu (7% reduction) and greatest in the isthmus and splenium (26% reduction). Individuals with higher heterotopic GM volume had a smaller corpus callosum. Heterotopic GM volume was highest in posterior brain regions, however there was no linear relationship between the anterior-posterior position of corpus callosum changes and PVNH nodules. Reduced corpus callosum area is strongly associated with PVNH, and is probably associated with abnormal brain development in this neurological disorder. The primarily posterior corpus callosum changes may inform our understanding of the etiology of PVNH. Our results suggest that interhemispheric pathways are affected in PVNH.

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“…In their study they did not find any relationship between heterotopic GM volume and full scale IQ or reading fluency in individuals with PVNH. 17 These findings suggest that spatially localized disruptions to brain networks may explain clinical and cognitive features of individuals with PVNH, rather than overall heterotopic GM load.…”

Section: Discussionmentioning

confidence: 91%

Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy

Fallil

Pardoe

Bachman

et al. 2015

Epilepsy & Behavior

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Purpose Periventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA negative patients with seizures and bilateral periventricular heterotopia. Methods Participants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy and MRI confirmed bilateral PVNH. MRI studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry and laterality. Key Findings We analyze data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6%. There was at least one other family member with epilepsy in 36.9% of this population. Developmental delay was present in 21.8%. Focal onset seizures were the most common type of seizure presentation (79.3%). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset and duration of epilepsy. Significance A direct correlation was observed between high heterotopia burden, female gender and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicate that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue.

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Gray matter volumes and cognitive ability in the epileptogenic brain malformation of periventricular nodular heterotopia

Cited by 17 publications

References 31 publications

Integration of gray matter nodules into functional cortical circuits in periventricular heterotopia

Integration of gray matter nodules into functional cortical circuits in periventricular heterotopia

Quantitative assessment of corpus callosum morphology in periventricular nodular heterotopia

Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy

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