Impaired oligodendroglial turnover is associated with myelin pathology in focal cortical dysplasia and tuberous sclerosis complex

Scholl, Theresa O.; Mühlebner, Angelika; Ricken, Gerda; Gruber, Victoria‐Elisabeth; Fabing, Anna; Samueli, Sharon; Gröppel, Gudrun; Dorfer, Christian; Czech, Thomas; Hainfellner, Johannes A.; Prabowo, Avanita S.; Reinten, Roy J.; Hoogendijk, Lisette; Anink, Jasper J.; Aronica, Eleonora; Feucht, Martha

doi:10.1111/bpa.12452

Cited by 59 publications

(78 citation statements)

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“…Copy number variations in SMO a receptor in the Shh pathway have been recently shown in hypothalamic hamartoma associated with gelastic seizures and DEPDC5 and NPRL3 mutations reported in FCDII . Further histological features in common between MVNT and FCD IIB include the striking hypomyelination of involved white matter which may relate to deficiencies in oligodendroglial lineages . Also the distinctive MCM2 positivity of VC is reminiscent of balloon cells in FCD .…”

Section: Discussionmentioning

confidence: 92%

“…L. SMI94 for myelin basic protein, as well as demonstrating the diminished myelination in the white matter nodules (see also Figure 2), also showed membranous labelling of the VC (arrow). Bar 3 histological features in common between MVNT and FCD IIB include the striking hypomyelination of involved white matter which may relate to deficiencies in oligodendroglial lineages (46,51,55,70). Also the distinctive MCM2 positivity of VC is reminiscent of balloon cells in FCD (61).…”

Section: Neoplasia or Malformationmentioning

confidence: 99%

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Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

et al. 2017

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Multinodular and vacuolating neuronal tumor (MVNT) is a new pattern of neuronal tumour included in the recently revised WHO 2016 classification of tumors of the CNS. There are 15 reports in the literature to date. They are typically associated with late onset epilepsy and a neoplastic vs. malformative biology has been questioned. We present a series of ten cases and compare their pathological and genetic features to better characterized epilepsy‐associated malformations including focal cortical dysplasia type II (FCDII) and low‐grade epilepsy‐associated tumors (LEAT). Clinical and neuroradiology data were reviewed and a broad immunohistochemistry panel was applied to explore neuronal and glial differentiation, interneuronal populations, mTOR pathway activation and neurodegenerative changes. Next generation sequencing was performed for targeted multi‐gene analysis to identify mutations common to epilepsy lesions including FCDII and LEAT. All of the surgical cases in this series presented with seizures, and were located in the temporal lobe. There was a lack of any progressive changes on serial pre‐operative MRI and a mean age at surgery of 45 years. The vacuolated cells of the lesion expressed mature neuronal markers (neurofilament/SMI32, MAP2, synaptophysin). Prominent labelling of the lesional cells for developmentally regulated proteins (OTX1, TBR1, SOX2, MAP1b, CD34, GFAPδ) and oligodendroglial lineage markers (OLIG2, SMI94) was observed. No mutations were detected in the mTOR pathway genes, BRAF, FGFR1 or MYB. Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro‐glial cell type showing aberrant maturation.

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Section: Discussionmentioning

confidence: 92%

Section: Neoplasia or Malformationmentioning

confidence: 99%

Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

et al. 2017

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“…Interestingly, in the experimental model synaptic transmission is abolished during a P‐type seizure (but not at its onset), possibly because of potassium‐induced fiber depolarization; in principle, this hypothesis could be verified in patients with an appropriate, ethically approved protocol designed for testing the response to low‐amplitude local stimulation of the EZ during P‐type seizures. The ictogenic mechanism proposed for P‐type seizures in the experimental animal model may be relevant to explain seizure generation in focal cortical dysplasia type IIb and in the cortex of TLE patients with and without associated dysplasia, where unmyelinated fibers in the subcortical white matter are pathologically augmented.…”

Section: Discussionmentioning

confidence: 99%

Two main focal seizure patterns revealed by intracerebral electroencephalographic biomarker analysis

Gnatkovsky

Pelliccia²,

Curtis

et al. 2018

Epilepsia

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Objective: Long-term recording with intracerebral electrodes is commonly utilized to identify brain areas responsible for seizure generation (epileptogenic zone) and to tailor therapeutic surgical resections in patients with focal drug-resistant epilepsy. This invasive diagnostic procedure generates a wealth of data that contribute to understanding human epilepsy. We analyze intracerebral signals to identify and classify focal ictal patterns. Methods: We retrospectively analyzed stereo-electroencephalographic (EEG) data in a cohort of patients either cryptogenic (magnetic resonance imaging negative) or presenting with noncongruent anatomoelectroclinical data. A computer-assisted method based on EEG signal analysis in frequency and space domains was applied to 467 seizures recorded in 105 patients submitted to stereo-EEG presurgical monitoring. Results: Two main focal seizure patterns were identified. P-type seizures, typical of neocortex, were observed in 73 patients (69.5%), lasted 22 ± 13 seconds (mean + SD), and were characterized by a sharp-onset/sharp-offset transient superimposed on low-voltage fast activity (126 ± 19 Hz). L-type seizures were observed in 43 patients (40.9%) and consistently involved mesial temporal structures; they lasted longer (93 ± 48 second), started with 116 ± 21 Hz low-voltage fast activity superimposed on a slow potential shift, and terminated with large-amplitude, periodic bursting activity. In 23 patients (21.9%), the L-type seizure was preceded by a P seizure. Spasmlike and unclassifiable EEG seizures were observed in 11.4% of cases. Significance: The proposed computer-assisted approach revealed signal information concealed to visual inspection that contributes to identifying two principal seizure patterns typical of the neocortex and of mesial temporal networks. K E Y W O R D Sepilepsy surgery, epileptogenic zone, seizure pattern, stereo-EEG

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“…Although Hamilton and Nesbit 5 did not identify FCD I in their case of oligodendroglial hyperplasia, the authors suggested that this could be the mildest end of the spectrum of a neuronal migrational disorder or microdysgenesis. In a recent study, Scholl et al19 also identified oligodendroglial hyperplasia in malformations of cortical development, with the exception of FCD IIb and cortical tubers.…”

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confidence: 93%

MRI, Magnetoencephalography, and Surgical Outcome of Oligodendrocytosis versus Focal Cortical Dysplasia Type I

Mata‐Mbemba¹,

Iimura

Hazrati³

et al. 2018

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE:Abnormalities of oligodendrocytes have been reported in surgical specimens of patients with medically intractable epilepsy. The aim of this study was to compare the MR imaging, magnetoencephalography, and surgical outcome of children with oligodendrocytosis relative to focal cortical dysplasia I. MATERIALS AND METHODS:Oligodendrocytosis included oligodendroglial hyperplasia, oligodendrogliosis, and oligodendroglial-like cells in the white matter, gray matter, or both from children with medically intractable epilepsy. Focal cortical dysplasia I included radial and tangential cortical dyslamination. The MR imaging, magnetoencephalography, type of operation, location, and seizure outcome of oligodendrocytosis, focal cortical dysplasia I, and oligodendrocytosis ϩ focal cortical dysplasia I were compared. RESULTS:Eighteen subjects (39.1%) had oligodendrocytosis, 21 (45.7%) had focal cortical dysplasia I, and 7 (15.2%) had oligodendrocytosis ϩ focal cortical dysplasia I. There were no significant differences in the type of seizures, focal or nonfocal epileptiform discharges, magnetoencephalography, and MR imaging features, including high T1 signal in the cortex, high T2/FLAIR signal in the cortex or subcortical white matter, increased cortical thickness, blurring of the gray-white junction, or abnormal sulcation and gyration among those with oligodendrocytosis, focal cortical dysplasia I, or oligodendrocytosis ϩ focal cortical dysplasia I (P Ͼ .01). There were no significant differences in the extent of resection (unilobar versus multilobar versus hemispherectomy), location of the operation (temporal versus extratemporal versus both), or seizure-free outcome of oligodendrocytosis, focal cortical dysplasia I, and oligodendrocytosis ϩ focal cortical dysplasia I (P Ͼ .05). CONCLUSIONS:Oligodendrocytosis shared MR imaging and magnetoencephalography features with focal cortical dysplasia I, and multilobar resection was frequently required to achieve seizure freedom. In 15% of cases, concurrent oligodendrocytosis and focal cortical dysplasia I were identified. The findings suggest that oligodendrocytosis may represent a mild spectrum of malformations of cortical development.ABBREVIATIONS: EEG ϭ electroencephalography; FCD ϭ focal cortical dysplasia; ILAE ϭ International League Against Epilepsy; MEG ϭ magnetoencephalography;MEGSS ϭ MEG spike sources; MOGHE ϭ mild malformation of cortical development with oligodendroglial hyperplasia; PD ϭ proton density; ST ϭ slice thickness

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Impaired oligodendroglial turnover is associated with myelin pathology in focal cortical dysplasia and tuberous sclerosis complex

Cited by 59 publications

References 50 publications

Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

Two main focal seizure patterns revealed by intracerebral electroencephalographic biomarker analysis

MRI, Magnetoencephalography, and Surgical Outcome of Oligodendrocytosis versus Focal Cortical Dysplasia Type I

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