Frontal Disconnection for Treating Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE) in the Frontal Lobe

Summary

Here, we present a protocol to describe the epilepsy outcome and complications of 8 patients with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) in the frontal lobe after frontal disconnection. The procedure is characterized by its simplicity, user-friendliness, and fewer postoperative complications.

Abstract

Malformation of cortical development is an important cause of drug-resistant epilepsy in young children. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) has been added to the last focal cortical dysplasia (FCD) classification and commonly involves the frontal lobe. The semiology at the onset of epilepsy is dominated by non-lateralizing infantile spasm; the boundaries of the malformation are usually difficult to determine by magnetic resonance imaging (MRI) and positron emission tomography (PET), and electroencephalography (EEG) findings are often widespread. Therefore, the traditional concept and strategy of preoperative evaluation to determine the extent of the epileptogenic zone by comprehensive anatomo-electro-clinical methods are difficult to implement.

Frontal disconnection is an effective surgical method for the treatment of epilepsy, but there are few related reports. A total of 8 children with histo-pathologically confirmed MOGHE were retrospectively studied. MOGHE was located in the frontal lobe in all patients, and frontal disconnection was performed. The periinsular approach was used in the disconnective procedures, divided into several surgical steps: the partial inferior frontal gyrus resection, the frontobasal and intrafrontal disconnection, and the anterior corpus callosotomy.

One patient presented with a short-term postoperative speech disorder, while another patient exhibited transient postoperative limb weakness. No long-term postoperative complications were observed. At 2 years after surgery, 75% of patients were seizure-free, with cognitive improvement in half of them. This finding suggested that frontal disconnection is an effective and safe surgical procedure for the treatment of MOGHE instead of extensive resection in the frontal lobe.

Introduction

Malformation of cortical development (MCD) is an important cause of drug-resistant epilepsy and developmental delay in young children. There are many types of MCD, among which FCD is the most common type¹. According to the latest updated FCD classification in 2022, MOGHE is described and classified as a predominantly white matter lesion in contrast to juxta-cortical localized FCD² that was primarily described as proliferative oligodendroglial hyperplasia with epilepsy (POGHE) in 2013³ and first proposed in 2017⁴. MOGHE is defined by an increase in heterotopic neurons in the white matter and deep cortical layers above 2200 Olig2-immunoreactive cells/mm² in specimen^2,4,5.

Clinically, MOGHE is most commonly observed in the frontal lobe, and epileptic spasms are the most common initial seizure type⁶. The interictal EEG pattern was usually multifocal or widespread in young children⁶. In younger children, MRI showed an increased laminar signal at the gray-white matter junction. In older children, reduced subcortical T2/FLAIR signals and blurring at the gray-white matter transition were observed⁷. An accurate delineation of MOGHE is very difficult in clinical practice. Therefore, the traditional concept and strategy of preoperative evaluation to determine the extent of the epileptogenic zone by comprehensive anatomo-electro-clinical evaluation is difficult to implement. Herein, a pediatric cohort with MOGHE in the frontal lobe was analyzed to extend the knowledge of surgical treatment for MOGHE.

Protocol

The study was approved by the IRB of Peking University First Hospital, and written informed consent was obtained from all participants.

NOTE: All children with intractable epilepsy who underwent frontal disconnection at the Pediatric Epilepsy Center of Peking University First Hospital from January 1, 2017, to March 1, 2022, were included and analyzed. Those who met the clinical and radiological criteria of MOGHE and whose MRI suggested that the epileptogenic lesion was confined to the frontal lobe were included. The histopathological diagnostic criteria for MOGHE have been previously described⁶. Semiology, ictal and interictal electroencephalography (EEG), magnetic resonance imaging (MRI), interictal ¹⁸fluorodeoxyglucose positron emission tomography (PET), and developmental assessment were performed for preoperative evaluation. Children over 7 years of age were evaluated by the Wechsler Intelligence Scale-IV, and children under 7 years of age were evaluated by the Griffith Developmental Assessment Scale. The outcome of epilepsy was evaluated by the ILAE classification, and patients with an ILAE 1 were considered seizure-free⁸. Semiology was divided into 3 groups (focal, spasm/generalized seizure, and mixed type). Interictal EEG was divided into focal (regional discharge), multifocal (several unilateral hemispheric regional discharges), and diffuse (contralateral involved). Ictal EEG was divided into focal (regional onset), diffuse (unilateral hemispheric onset or nonlocalizing EEG), and focal/diffuse (coexistence of 2 patterns)⁹. Based on the typing of MOGHE by Hartlieb et al.⁷, the MRI findings of the 8 patients were also classified as type 1 (Figure 1A, B) or type 2. Figure 1 shows representative intraoperative photos and pre-and postoperative images of frontal disconnection in patient 8.

1. Positioning

1. Administer general anesthesia to the patient using standard techniques.
2. Locate the Sylvian fissure, coronal suture, and central sulcus according to anatomical landmarks as a reference for drawing surgical incision lines. Make a "7"-shaped skin incision 1.0 cm off the midline and 2-3 cm anterior to the coronal suture. Ensure that the posterior margin of the incision includes the precentral gyrus and extends down to the pterygoid region (Figure 1D)
3. Place the patient supine with the head turned to the opposite side. Place a shoulder pad under the shoulder to help the head turn.
4. Maintain sterile conditions throughout the procedure by sterilely preparing the skin and draping the surgical area.

2. Opening

1. Incise the scalp and muscles. Take care to cut the muscles in layers.
2. Separate the scalp and periosteum with a scalpel.
   NOTE: Preservation of the periosteum reduces postoperative subcutaneous hydrops.
3. Drill three 1 cm holes using a high-speed drill of 1 cm diameter and mill down the bone flap with a 1 mm wide milling cutter.
   NOTE: Adequate exposure of the sphenoid ridge is required to facilitate subsequent disconnection of the frontal base.
4. Use bone wax, gelatin sponge, and bipolar cautery to achieve hemostasis.
5. Drill 4-5 1 mm holes in the bone margin and suspend the dura to avoid epidural hematoma.
6. Cut open the dura 0.5 cm away from the bone margin. Expose the precentral gyrus, the posterior part of the inferior frontal gyrus, and the beginning of the lateral fissure. (Figure 1E)

3. Frontal disconnection procedures

1. Use the stereotactic system software for surgical planning before surgery. Import the 3D T1, flair weighted images, and PET data into the software for registration and 3D reconstruction¹⁰.
   NOTE: The precentral sulcus was delineated by a 3D coregistration. Intraoperative mapping of the central gyrus was not performed (Figure 1C).
2. Select the area with the most severe abnormality on preoperative imaging for histological examination.
3. Resect the posterior part of the inferior frontal gyrus to fully expose the 1 and 2 short gyri of the insula.
   NOTE: In children under 5 years of age with suspected frontal MOGHE, preservation of the speech area is not considered in order to maximize the extent of disconnection of the epileptogenic zone.
4. Disconnect the base of the frontal lobe and the fibers along the anterior insula to the sphenoid ridge and then to the midline.
   NOTE: The anterior cerebral artery and the olfactory triangle are landmarks of the posterior boundary of the disconnection. The gyrus rectus is located medial to the olfactory nerve, and the disconnection of the base of the frontal lobe needs to reach the midline pia. The contralateral brain tissue must be well preserved.
5. Dissect the gray and white matter along the precentral sulcus. The boundary of disconnection at the midline is the cerebral falx, and down to the cingulate gyrus, disconnect it accordingly.
   1. When performing intrafrontal disconnection along the precentral sulcus, disconnect the white matter under the bottom of the sulcus slightly forward to make the pyramidal tract intact.
   2. On the other hand, because MOGHE is a white matter lesion with blurred gray-white matter boundaries, perform a sufficiently deep resection/disconnection to achieve the highest chance of seizure freedom.
6. Incise the corpus callosum to open the ipsilateral ventricles, dissect the arcuate fibers completely along the top of the ventricles to the anterior horn, and then meet the frontal base disconnection line.
   NOTE: The entire anterior lateral ventricle is completely open so far.
7. Disconnect the anterior corpus callosum to the anterior commissure within the lateral ventricles, where the posterior portion of the frontobasal disconnection reaches the level of the callosal disconnection.
8. Expose the anterior cerebral artery, which can be an anatomical landmark in the disconnection of the corpus callosum. Finally, resect the paraterminal gyrus and posterior gyrus rectus behind the anterior cerebral artery with suction.
   NOTE: The frontobasal disconnection should be complete, including the paraterminal gyrus and posterior gyrus rectus; otherwise, the seizure outcome will be greatly affected. Frontal disconnection is frequently accompanied by resection of the 1 or/and 2 insular short gyri according to the preoperative evaluation, thereby facilitating a more comprehensive excision of the epileptogenic zone. The photos after disconnection and postoperative MRI are shown in Figure 1. Resection of the 1 and 2 short insular gyri should be actively considered, especially if preoperative MRI and PET suggest abnormalities.

4. Closure

1. Suture the dura with 4-0 absorbable sutures to achieve a tight closure.
2. Place an epidural drain for 2 days.
3. Fix the bone using 3 absorbable cranial bone locks.
4. Close the subcutaneous layer with 4-0 subcuticular sutures.
5. Suture the skin with a stapler.

Results

According to the inclusion criteria, a total of 8 eligible patients were included in the analysis. The group consisted of 8 boys. The age of onset was 4-28 months (median 6 months), and the age of surgery ranged from 17-135 months (median 38 months). The duration of epilepsy ranged from 13 to 121 months (median 32 months). The semiology of 4 patients was epileptic spasms, 3 had focal seizures, and 1 had mixed seizures. Interictal EEG indicated focal in 3 patients, multifocal in 3 patients, and diffuse in 2 patients. Ictal EEG suggested focal in 5 patients, diffuse in 2 patients, and focal/diffuse in 1 patient. MRI findings suggested that the lesion was located in the left frontal lobe in 5 patients and in the right frontal lobe in 3 patients. In all patients, the lesions were diffusely distributed in the frontal lobe, but the boundaries were difficult to determine. There were four patients with type 1 and type 2, respectively. The age at surgery of type 2 patients was significantly higher than that of type 1 patients. PET suggested that hypometabolism was not evident in 2 patients, hypometabolism was localized to the epileptogenic zone in 2 patients, and the extent of hypometabolism extended beyond the epileptogenic zone in 4 patients. Detailed information is shown in Table 1.

All patients underwent frontal disconnection. One patient presented with postoperative aphasia, while another patient exhibited postoperative limb weakness. However, both symptoms recovered within 2 weeks after surgery. No long-term postoperative complications, such as limb weakness or hydrocephalus, were observed. After an average of 2 years of follow-up, 6 patients were seizure-free, with a seizure-free rate of 75%. All 8 patients had developmental delays before surgery. Developmental assessment was performed 3 months to 1 year after surgery and revealed that 4 patients experienced cognitive improvement. Detailed information is shown in Table 2.

Figure 1: Intraoperative photos and pre- and postoperative images of frontal disconnection in patient 8. (A,B) Axial T2 FLAIR-weighted MR image of subtype I lesions in the frontal lobe. The white arrows mark increased laminar T2 signals at the corticomedullary junction. (C) Preoperative 3D reconstruction of the MR image helps us to distinguish the location of the central sulcus. The red line shows the left precentral sulcus. The dashed line shows the central sulcus. (D) A "7"-shaped skin incision was made 0.5 cm off the midline and 2-3 cm anterior to the coronal suture. The white arrow points to the coronal suture; the black arrow shows the midline. (E) The precentral gyrus, the posterior part of the inferior frontal gyrus, and the beginning of the lateral fissure were exposed. The white arrow points to the lateral fissure; the black arrow shows the precentral sulcus. (F) Intraoperative photos after disconnection. The posterior part of the inferior frontal gyrus was resected. (G-I) Postoperative images of frontal disconnection. Please click here to view a larger version of this figure.

Patient	Gender	Onset age (m)	Epilepsy duration (m)	Surgery age (m)	Seizure types	Interictal EEG	Ictal EEG	MRI/type		Hypometablism in PET
1	M	4	26	30	Spasms	Diffuse	Diffuse	Left frontal/type 1		No hypometablism
2	M	14	121	135	Focal/spasms	Multifocal	Focal/Diffuse	Right frontal/type 2		Right frontal, insula and temporal
3	M	4	13	17	Spasms	Multifocal	Focal	Left frontal/type 1		No hypometablism
4	M	28	67	95	Focal	Focal	Focal	Left frontal/type 2		Left frontal
5	M	4	21	25	Spasms	Focal	Focal	Right frontal/type 1		Bilateral frontal, right temporal
6	M	8	75	83	Spasms	Multifocal	Diffuse	Left frontal/type 2		Left frontal, right temporal
7	M	8	36	44	Focal	Focal	Focal	Right frontal/type 2		Bilateral frontal, right temporal
8	M	4	28	32	Focal	Diffuse	Focal	Left frontal/type 1		Bilateral frontal, left temporal

Table 1: Clinical data of the 8 patients.

Patient	Outcome	Preoperative DQ/IQ	Postoperative DQ/IQ
1	ILAE 1	10	30
2	ILAE 1	56	51
3	ILAE 4	31	19
4	ILAE 1	65	61
5	ILAE 1	45	41
6	ILAE 1	10	19
7	ILAE 4	30	50
8	ILAE 1	32	41

Table 2: Epilepsy outcomes and developmental assessments

Discussion

MOGHE is a new white matter entity predominantly at the GM/WM boundaries but shows no cortical layer disorganization as is typical for FCDs². The untypical semiology and extensive EEG make it very difficult to determine the location of the epileptogenic zone using traditional methods of anatomo-electro-clinical evaluation, which creates difficulties in surgical decision-making. Previous studies reported that patients with MOGHE achieved good outcomes after wide resection^6,11, but detailed information is lacking. However, there were literature reports that after extensive frontal resection, the seizure-free rate of patients with MOGHE was only 40%-55.3%^12,13. This may be related to the diffuse lesions of MOGHE and the difficulty in determining the resection boundary. The resection range in the literature may still not be large enough. The frontal disconnection procedure described here provided an alternative for complete resection of the frontal lobe, preserving the central gyrus. We reported 8 patients with MOGHE in the frontal lobe with ambiguous boundaries identified by preoperative MRI and confirmed by postoperative pathology, among whom only 1 patient had completely consistent anatomo-electro-clinical findings. All 8 patients underwent frontal disconnections with sparing of the central gyrus, and the postoperative epilepsy control was 75% seizure freedom. The satisfactory outcome suggested that frontal disconnection effectively eliminated the epileptogenic zone associated with MOGHE in the frontal lobe.

Lobar disconnections have been increasingly popularized in the treatment of pediatric epilepsy in recent years. Both hemispherotomy and temporo-parietooccipital (TPO) disconnection surgeries have been reported to be equally effective in the treatment of epilepsy as resection, with fewer complications^14,15,16,17. Despite being a relatively recent approach in epilepsy treatment, numerous studies have substantiated the efficacy of frontal disconnection^9,18,19. The surgical effect of frontal disconnection necessitates complete disconnection as a fundamental prerequisite. Incomplete disconnection is often an important reason for epilepsy recurrence after surgery.

Resection of the posterior part of the inferior frontal gyrus before the disconnection procedures facilitated the following operations: (1) the brain tissue can be used for pathological examination; (2) expose parts of the insula to facilitate subsequent insula resection; (3) provide operational space for the frontobasal disconnection; (4) effectively alleviate postoperative symptoms of intracranial hypertension caused by edema.

The surgical approach described in this study has the following advantages: (1) The surgical procedure is based on peri-insular hemispherotomy, which is more readily performed by neurosurgeons at specialized epilepsy centers. (2) Surgical procedures are beginner-friendly, with clear anatomical marks at each step. The above two points can help to slope the learning curve of the technique (3) it is not easy to damage important structures, such as the hypothalamus and the anterior cerebral artery; (4) if each step is executed in accordance with the specified requirements, complete disconnection of the entire frontal lobe will be achieved, ensuring no residual frontal lobe tissue except for the precentral gyrus. In this manner, the incidence of postoperative complications is low. Epileptic seizures and neurological deficits are common complications in the early postoperative period¹⁹. Neurological deficits present mainly as contralateral mild limb weakness due to the slight involvement of supplementary sensory-motor area (SSMA) or primary motor areas, and most patients will recover within a few weeks¹⁸. No instances of hydrocephalus have been reported following frontal disconnection, which shows the superiority of this disconnection procedure to resection.

Positive MRI findings are frequently observed in patients with MOGHE^7,11. Positive MRI manifestations in the frontal lobes were observed in 8 patients, with lesions involving part or the entire frontal lobe. Even if a focal positive lesion is found on MRI, the true extent of the lesion is very difficult to delineate. Considering all the above situations, satisfactory epilepsy outcomes were obtained after frontal disconnection, which confirmed the efficacy of frontal disconnection in the treatment of frontal lobe MOGHE. In patients whose precentral gyrus is suspected to be abnormal prior to surgery, staged surgery can be considered on the premise of normal function of the patient, and it is also possible to control epilepsy.

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Absorbable cranial bone lock	Braun Inc.	FF016
Drainage	Branden Inc.	Fr12
High-speed drill	Stryker	5400-050-000
Microscope	Leica Inc.	M525F40
NIHON KOHDAN EEG system	NIHON KOHDAN Inc.	EEG-1200C	EEG
Philips PET-CT system	Philips Inc.	Gemini GXL	PET-CT
Sinovation Stereotactic system	Sinovation Inc.	SR1	3D construction