A Distinct Asymmetrical Pattern of Cortical Malformation: Large Unilateral Malformation of Cortical Development with Contralateral Periventricular Nodular Heterotopia in Three Pediatric Cases

Abstract Background Periventricular nodular heterotopia (PNH) is a malformation of cortical development characterized by nodules of abnormally migrated neurons. The cause of posteriorly placed PNH is not well characterised and we present a case that provides insights into the cause of posterior PNH. Case presentation We report a fetus with extensive posterior PNH in association with biallelic variants in LAMC3. LAMC3 mutations have previously been shown to cause polymicrogyria and pachygyria in the occipital cortex, but not PNH. The occipital location of PNH in our case and the proposed function of LAMC3 in cortical development suggest that the identified LAMC3 variants may be causal of PNH in this fetus. Conclusion We hypothesise that this finding extends the cortical phenotype associated with LAMC3 and provides valuable insight into genetic cause of posterior PNH.

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In vivo Interictal Neuronal Signatures of Human Periventricular Nodular Heterotopia

10.1101/816173 ◽

2019 ◽

Author(s):

Valerio Frazzini ◽

Stephen Whitmarsh ◽

Katia Lehongre ◽

Pierre Yger ◽

Jean-Didier Lemarechal ◽

...

Keyword(s):

Epileptic Activity ◽

Neuronal Firing ◽

Periventricular Nodular Heterotopia ◽

Firing Rates ◽

Neuronal Populations ◽

Malformation Of Cortical Development ◽

Nodular Heterotopia ◽

Epileptic Spikes ◽

Drug Resistant Epilepsy

AbstractPeriventricular nodular heterotopia (PNH) is a common type of malformation of cortical development and a cause of drug-resistant epilepsy. In contrast with other cortical malformations, no consistent interictal patterns have yet been identified in PNH, and it remains controversial whether epileptic activity originates within nodules. The current study addresses the heterogeneity in LFP signatures, as well as the question of epileptogenicity of nodules, by means of microelectrode recordings implanted within PNH tissues in two epileptic patients. Microelectrodes also allowed the first in vivo recording of heterotopic neurons in humans, permitting the investigation of neuronal firing rates during patterns of interictal activity. Highly consistent interictal patterns (IPs) were identified within PNH: 1) trains of periodic slow waves and 2) isolated slow deflections, both with superimposed fast activity, and 3) epileptic spikes. Neuron firing rates were significantly modulated during all IPs, suggesting that different IPs were generated by the same local neuronal populations. To conclude, this study presents the first in vivo microscopic description of local PNH microcircuits in humans and their organization into multiple epileptic neurophysiological patterns, providing a first pathognomonic signature of human PNH.

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Bilateral Posterior Periventricular Nodular Heterotopia: A Recognizable Cortical Malformation with a Spectrum of Associated Brain Abnormalities

American Journal of Neuroradiology ◽

10.3174/ajnr.a3427 ◽

2013 ◽

Vol 34 (2) ◽

pp. 432-438 ◽

Cited By ~ 20

Author(s):

S.A. Mandelstam ◽

R.J. Leventer ◽

A. Sandow ◽

G. McGillivray ◽

M. van Kogelenberg ◽

...

Keyword(s):

Brain Abnormalities ◽

Cortical Malformation ◽

Periventricular Nodular Heterotopia ◽

Nodular Heterotopia

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ARF1 haploinsufficiency causes periventricular nodular heterotopia with variable clinical expressivity

Journal of Medical Genetics ◽

10.1136/jmedgenet-2021-107783 ◽

2021 ◽

pp. jmedgenet-2021-107783

Author(s):

Simone Gana ◽

Antonella Casella ◽

Sara Cociglio ◽

Elena Tartara ◽

Elisa Rognone ◽

...

Keyword(s):

Neuronal Migration ◽

Ectodermal Dysplasia ◽

Neural Progenitors ◽

Actin Dynamics ◽

Vesicle Formation ◽

Hypohidrotic Ectodermal Dysplasia ◽

Clinical Expression ◽

Cortical Malformation ◽

Periventricular Nodular Heterotopia ◽

Nodular Heterotopia

The primary anatomical defect leading to periventricular nodular heterotopia occurs within the neural progenitors along the neuroepithelial lining of the lateral ventricles and results from a defect in the initiation of neuronal migration, following disruption of the neuroependyma and impaired neuronal motility. Growing evidence indicates that the FLNA-dependent actin dynamics and regulation of vesicle formation and trafficking by activation of ADP-ribosylation factors (ARFs) can play an important role in this cortical malformation. We report the first inherited variant of ARF1 in a girl with intellectual disability and periventricular nodular heterotopia who inherited the variant from the father with previously undiagnosed single nodular heterotopia and mild clinical expression. Additionally, both patients presented some features suggestive of hypohidrotic ectodermal dysplasia. These clinical features showed similarities to those of three previously reported cases with ARF1 missense variants, confirming that haploinsufficiency of this gene causes a recognisable neurological disorder with abnormal neuronal migration and variable clinical expressivity.

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27. EEG-fMRI of nodule-cortex interaction during interictal spiking in periventricular nodular heterotopia

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2009.07.052 ◽

2009 ◽

Vol 16 (11) ◽

pp. 1533-1534

Author(s):

JS Archer ◽

DF Abbott ◽

R Masterton ◽

S Palmer ◽

GD Jackson

Keyword(s):

Periventricular Nodular Heterotopia ◽

Nodular Heterotopia

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Electroencephalographic Recordings of Focal Seizures in Patients Affected by Periventricular Nodular Heterotopia: Role of the Heterotopic Nodules in the Genesis of Epileptic Discharges

Journal of Child Neurology ◽

10.1177/08830738040190031701 ◽

2004 ◽

Vol 19 (3) ◽

pp. 369-377

Author(s):

Giorgio Battaglia ◽

Silvana Franceschetti ◽

Luisa Chiapparini ◽

Elena Freri ◽

Stefania Bassanini ◽

...

Keyword(s):

Brain Regions ◽

Periventricular Nodular Heterotopia ◽

Focal Seizures ◽

Ictal Eeg ◽

Epileptic Discharges ◽

Nodular Heterotopia ◽

Eeg Recordings ◽

Drug Resistant Epilepsy ◽

Video Eeg

Patients affected by periventricular nodular heterotopia are frequently characterized by focal drug-resistant epilepsy. To investigate the role of periventricular nodules in the genesis of seizures, we analyzed the electroencephalographic (EEG) features of focal seizures recorded by means of video-EEG in 10 patients affected by different types of periventricular nodular heterotopia and followed for prolonged periods of time at the epilepsy center of our institute. The ictal EEG recordings with surface electrodes revealed common features in all patients: all seizures originated from the brain regions where the periventricular nodular heterotopia were located; EEG patterns recorded on the leads exploring the periventricular nodular heterotopia were very similar both at the onset and immediately after the seizure's end in all patients. Our data suggest that seizures are generated by abnormal anatomic circuitries, including the heterotopic nodules and adjacent cortical areas. The major role of heterotopic neurons in the genesis and propagation of epileptic discharges must be taken into account when planning surgery for epilepsy in patients with periventricular nodular heterotopia. ( J Child Neurol 2005;20:369—377).

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