LETTERS TO THE EDITOR
|Year : 2021 | Volume
| Issue : 6 | Page : 1009-1011
Post-operative seizure freedom need not be elusive in mild oligodendroglial hyperplasia and epilepsy (MOGHE)
Aparajita Chatterjee1, Ravindranadh C Mundlamuri1, Ajay Asranna1, Raghavendra Kenchaiah1, GK Bhargava2, Mariyappa Narayanan1, Radhika Mhatre3, Karthik Kulanthaivelu4, Sandhya Mangalore4, Chandana Nagaraj4, Rose Dawn Bharath4, Jitender Saini4, Nishanth Sadashiva5, A Arivazhagan5, Malla Bhaskara Rao5, Anita Mahadevan3, Sanjib Sinha1
1 Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India
2 Department of Clinical Neurosciencesv, National Institute of Mental Health and Neurosciences, Bangalore, India
3 Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India
4 Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bangalore, India
5 Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India
|Date of Submission||20-Nov-2020|
|Date of Acceptance||19-Jan-2021|
|Date of Web Publication||04-Aug-2021|
Dr. Sanjib Sinha
Department of Neurology, NIMHANS, Bengaluru - 560 029, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Chatterjee A, Mundlamuri RC, Asranna A, Kenchaiah R, Bhargava G K, Narayanan M, Mhatre R, Kulanthaivelu K, Mangalore S, Nagaraj C, Bharath RD, Saini J, Sadashiva N, Arivazhagan A, Rao MB, Mahadevan A, Sinha S. Post-operative seizure freedom need not be elusive in mild oligodendroglial hyperplasia and epilepsy (MOGHE). Ann Indian Acad Neurol 2021;24:1009-11
|How to cite this URL:|
Chatterjee A, Mundlamuri RC, Asranna A, Kenchaiah R, Bhargava G K, Narayanan M, Mhatre R, Kulanthaivelu K, Mangalore S, Nagaraj C, Bharath RD, Saini J, Sadashiva N, Arivazhagan A, Rao MB, Mahadevan A, Sinha S. Post-operative seizure freedom need not be elusive in mild oligodendroglial hyperplasia and epilepsy (MOGHE). Ann Indian Acad Neurol [serial online] 2021 [cited 2022 Jul 7];24:1009-11. Available from: https://www.annalsofian.org/text.asp?2021/24/6/1009/323154
The histopathologic spectrum of cortical lesions causing epilepsy is ever expanding. Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a clinicopathologic entity that has been described fairly recently. The first description was in a series of frontal lobe epilepsy patients, which had been initially classified as non-lesional on histopathology.
MOGHE is characterized by clusters of hyperplastic oligodendroglial cells exhibiting increased proliferation near cortico-medullary junctions, with subcortical white matter T2/FLAIR hyperintensity suggestive of focal cortical dysplasia (FCD). The previous descriptions have been restricted to frontal and rare temporal lobe epilepsies, and with poor post-surgical outcomes.,,
Below we present a patient with medically refractory epilepsy and histology-proven MOGHE with an excellent postoperative outcome, and discuss possible strategies by which the same may be ensured in patients with suspected MOGHE.
A 28-year-old agriculturist with an uneventful past history, presented with daily nocturnal seizures since 12 years of age, despite being on 4 anti-seizure medications (ASMs). These events were all brief, hypermotor, associated with fear, irrelevant verbalization, and left upper limb dystonic posturing. Examination was unremarkable.
Video EEG showed interictal spikes over the right fronto-central regions (F4, C4). Multiple habitual events were captured of the semiology described above, electrographically characterized by pre-ictal spiking over the right frontal region with spread to the midline parasagittal (F4, Fz) regions [Figure 1]a.
|Figure 1: (a) Pre-ictal spiking seen over right frontal and midline anterior parasagittal leads (F4, Fz) prior to obscuration by myogenic artifacts. (b) Axial 3D FLAIR images showing ill-defined area of blurred gray-white junction in the posterior aspect of the right middle frontal gyrus (c) PET-MR showing hypometabolism in the same region. (d) Magnetoencephalogram (MEG) shows right >> left posterior frontal dipole clusters. (e) Functional MRI showing activation away from the lesional zone (red arrow) during left hand motor task. (f) T2/FLAIR post-operative MRI showing excision cavity in the right middle frontal gyrus corresponding to the PET hypometabolism|
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A 3-Tesla epilepsy protocol MR brain showed ill-defined T2/FLAIR hyperintensity in the posterior part of the right middle frontal gyrus, with poor gray-white junction differentiation. Neuropsychological assessment was suggestive of pre-frontal dysfunction. PET-MRI showed hypometabolism extending beyond the lesional zone in the right frontal region. Magnetoencephalogram (MEG) showed bilateral posterior frontal (right > left) dipoles. Functional MRI obtained to localize the left hand motor function, showed activation away from the lesional zone on MRI [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f.
After discussion in pre-surgical meet, patient underwent surgical resection under electrocorticography and neuronavigation guidance. On the basis of the non-invasive investigations that indicated that the epileptogenic zone possibly extended beyond the MR-lesional zone, and ECoG showing spiking till the right pre-motor strip, an extended resection was preferred over standard lesionectomy. Histopathology of the biopsy specimen showed preserved cortical lamination with hexalaminar architecture, with no evidence of dysmorphic neurons or balloon cells. The white matter showed increased nuclear density due to oligodendroglial hyperplasia with prominent perineuronal and perivascular satelittosis. On immunohistochemistry, Olig-2, which specifically labels oligodendroglial cells, highlighted their increased density. No MIB-1 labeled cells were seen [Figure 2]. Based on the clinical, radiological, and biopsy findings, a diagnosis of MOGHE was made.
|Figure 2: Histopathology of the biopsy specimen: (a) NeuN immunohistochemistry showing preserved cor tical hexalaminar architecture, with heterotopic neurons (*) in the subjacent white matter (dotted line represents the gray white junction. (b) White matter shows increased cellularity with oligodendroglial hyperplasia, as evident on Olig2 stain (c)|
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Patient continues to be seizure-free 3 years post-surgery, and is currently on three ASMs. EEG performed one year post-operatively showed no epileptiform discharges.
The range of epilepsy surgery specimens that are classified as non-lesional range from 2 to 26% in various series.,, In a series of 1381 resected epilepsy surgery brain specimens, Schurr et al. found that 52 (3.7%) cases could not be classified histopathologically and were labeled non-lesional. However, on re-evaluation, in a subset (42%) of these patients, an increase of Olig2-, and PDGFR-alpha-immunoreactive oligodendroglia in white matter and deep cortical layers was noted, with heterotopic neurons in white matter and increased subcortical oligodendroglial cells. They coined the term “Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE)” to describe this new entity. The heterotopic neurons were found subjacent to corticomedullary junction, and not in the deep (>500 μm from cortical layer) white matter, which differentiates these from Palmini Type II mild malformations of cortical development (MCD). Dysmorphic neurons, balloon cells, and dyslamination are absent, unlike in focal cortical dysplasias (FCDs). Absence of inflammation and neuroepithelial tumor infiltration are the other criteria for MOGHE. All the patients in this cohort had drug-resistant frontal lobe epilepsy with median age of onset at 3 years, T2/FLAIR hyperintensities at the gray-white junction, and multifocality. Post-operatively, only 33% of the patients were free from disabling seizures. Duration of epilepsy correlated with the degree of oligodendroglial hyperplasia; with younger patients have higher proliferation rates.
Garganis et al. described two patients with “temporal-plus” epilepsy and biopsy-proven MOGHE, demonstrating that MOGHE need not be limited only to the frontal lobe. They suggested that when “temporal-plus” epilepsies present with normal hippocampi or subtle T2/FLAIR abnormalities only on MR, and refractory epilepsy, MOGHE should also be considered.
The good postoperative outcome in our patient could be attributed to the comprehensive mutltimodality evaluation and intra-operative corticography that ensured the complete excision of the epileptogenic zone. Due to the additional information available, a more extensive resection was undertaken rather than the standard lesionectomy. This demonstrates that good surgical outcomes are not unachievable in MOGHE, provided the workup and the resection is complete.
Hatlieb et al. demonstrated two distinct MR imaging subtypes in 25 MOGHE patients; subtype I was characterized by increased laminar T2/FLAIR signal at the corticomedullary junction, whereas subtype II showed reduced corticomedullary differentiation due to increased signal of the adjacent white matter. They hypothesized that MR changes in MOGHE are age-related and the first subtype is seen in younger patients (median age of 2.6 years), and the second subtype is seen in older children (median age of 14.1 years). The laminar hyperintensities seen in type I are presumably due to delayed myelination, whereas heterotopic neurons and immature oligodendroglial precursor cells (OPCs) are responsible for the hyperintensities in type II. Imaging subtypes in MOGHE are dynamic and possibly evolve from subtype I to II as the brain matures. At some point, OPCs overcome the maturational arrest and differentiate to a limited extent into mature myelinating oligodendrocytes.
The role of aberrant glial cells in epileptogenesis is ambiguous; though some reports of oligodendroglial lesions being associated with epilepsy are available. Subgranular cortical layers may be compromised by oligodendroglial hyperplasia, leading to aberrant network activity. Also, recurrent seizures may themselves trigger oligodendrogliogenesis. Further research into mechanisms by which oligodendroglia contribute to epileptogenesis is needed.
MOGHE is an emerging cause of refractory epilepsy; awareness of this entity might impact the pre-operative evaluation and surgical planning and hence postoperative outcomes. Seizure freedom can be achieved with multimodality evaluation and extended resections.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]