The significance of multimodality approach in the management of non‐lesional drug‐resistant focal parietal lobe epilepsies

Abstract

Due to extensive connectivity of the parietal lobe, non‐lesional drug‐resistant (DRE) parietal lobe epilepsies (PLEs) are difficult to localize and often imitate other epilepsies. Therefore, patients with PLEs have low rates of seizure freedom following epilepsy surgery. Previous studies have highlighted the need to combine EEG and semiology for more accurate localization of PLEs. As sophisticated tools for localization become more available, the use of multiple different neuroimaging and neurophysiologic diagnostic tests may more readily identify PLE. We hereby report a unique case of a complex localization in a non‐lesional PLE, which was initially falsely localized to frontal lobe. This case underscores the utility of voxel‐based morphometry (VBM) in identifying an epileptogenic lesion on a non‐lesional MRI and the significance of multimodality approach including PET, magnetoencephalopathy (MEG), interictal and ictal EEG, semiology and cortical stimulation for accurate localization of PLEs. Understanding epilepsy through multimodality approach in this fashion can help with accurate localization especially in difficulty to localize and deceptive non‐lesional PLEs.

Plain Language Summary

Parietal lobe epilepsies are hard to pinpoint in the brain and can mimic other types of epilepsy, especially when brain MRIs appear normal. As sophisticated tools for locating epilepsies in the brain become more available, using multiple diagnostic tests may help identify parietal lobe epilepsies more easily. We describe a unique case of a parietal lobe epilepsy patient with normal brain MRI whose epilepsy was initially misidentified as being in the frontal lobe. Using various advanced diagnostic tests, we accurately found the epilepsy's true location in the parietal lobe and successfully treated the patient with surgery.

Key points.

• Due to connectivity of parietal lobe, non‐lesional drug resistant parietal lobe epilepsies are difficult to localize.

• The use of multimodality approach include interictal, ictal EEG, semiology, MRI, PET, MEG, SPECT and VBM can significantly improve the localization of parietal lobe epilepsies.

• Understanding functional connectivity through interictal EEG in addition to DTI and functional MRI can additionally be useful in accurate localizing parietal lobe epilepsies.

1. INTRODUCTION

Drug‐resistant (DRE) parietal lobe epilepsies (PLEs) often imitate other epilepsies and can be difficult to localize. ¹ The parietal lobe is widely interconnected due to its function as an integrator of sensory information. ¹ This wide connectivity often leads to false localization in PLE which makes it very important to utilize multimodality approach to accurately localize suspected PLEs. Additionally, understanding epilepsy as a network disease through white matter corridors has also become increasingly important in accurate localization of PLEs because of its extensive connectivity. ² , ³

We report a unique case of non‐lesional (i.e., without a lesion on visual review of an MRI with standard epilepsy‐specific sequences). ⁴ DRE that highlights the significance of adjunctive testing with a multimodality approach to assist in localization of non‐lesional PLEs, and potential pitfalls that may lead to incorrect localization. In addition, our case underscores the significance of IEDs in providing evidence of rapid white matter propagation that helped with accurate localization in a non‐lesional PLE, which was initially falsely localized to the frontal lobe.

2. CASE PRESENTATION

An 18‐year‐old male with DRE was admitted for presurgical evaluation. His seizure semiology was initially described by witnesses as behavioral arrest, left head turning, and left gaze deviation with secondary tonic–clonic activity. Prior electroencephalograms (EEGs) had noted IEDs broadly across the right hemisphere with a consistent phase reversal (longitudinal bipolar montage) and highest amplitude (referential montage) over the right frontal (F4) region (Figure 1). MRI brain was unrevealing for an epileptogenic focus or lesion. Based on his seizure semiology and the findings from prior EEGs, he had been referred for surgical evaluation with a presumptive diagnosis of frontal lobe epilepsy.

FIGURE 1.

Longitudinal bipolar montage showing (A) diffuse right hemispheric discharge with right frontal (F4) phase reversal (arrow) of the interictal epileptiform discharge (IED). (B) Referential montage showing the same IED (arrow). (C) Increasing time base demonstrates that the initial component of all discharges is located in the right parieto‐occipital (P4/O2) region with a slight delay in the negativity seen over the F4 region (small arrows), likely demonstrating rapid white matter propagation (big orange arrow) from the parietal to frontal lobe. (D) Right parietal onset on intracranial stereo‐EEG (E) Longitudinal bipolar montage demonstrating seizure onset on scalp EEG. An initial herald right hemispheric, frontally maximal spike (red arrow) was seen consistently with each seizure, followed by rhythmic right hemispheric spike‐and‐wave (settings: LFF 1 Hz; HFF 70 Hz; Sensitivity 15 uV/mm).

However, a detailed IED analysis using a broadened time base and referential montage demonstrated a posterior to anterior time lag with an initial spike component over the right parieto‐occipital (P4/O2) region (Figure 1A,B,C) closely followed by frontal involvement (F4/Fp2). Seizure onset was broadly across the right hemisphere which started with an initial spike demonstrating a posterior to anterior lag (Figure 1E). Analysis of his recorded seizure semiology on video EEG also showed a subtle nystagmus prior to left gaze deviation and generalization. Thus, recorded semiology also raised concerns for involvement of parieto‐occipital regions in ictal onset.

Further investigation with voxel‐based morphometry (VBM) analysis of his non‐lesional brain MRI identified a lesion in the right superior parietal lobule (Figure 2B,D and F). PET scan (Figure 3A and B) showed an area of hypometabolism corresponding to the VBM lesion. Magnetoencephalography (MEG) also showed a dipole cluster over the right parietal lobe (Figure 3C), also concordant with the VBM lesion and interictal EEG.

FIGURE 2.

T1‐weighted MPRAGE MRI Brain demonstrating no visible lesion (A, C, and E). VBM analysis of the same MRI (B, D, F) demonstrates a gray‐white junction abnormality in the right superior parietal lobe (green crosshairs mark the VBM lesion and the corresponding area on the MRI).

FIGURE 3.

PET scan superimposed on a T1‐weighted MRI in coronal (A) and axial (B) planes demonstrating focal hypometabolism in the right superior parietal lobe (green crosshairs), and an averaged MEG dipole corresponding to the same location on a 3D MRI reconstruction (C).

During phase II evaluation, stereo‐EEG implantation confirmed epileptogenic zone (EZ) in the right superior parietal lobe VBM lesion with rapid spread to frontal lobe. Cortical stimulation of the right superior parietal lobule VBM lesion led to nystagmus similar to that of his spontaneous seizures along with ictal discharges. The patient also reported a visual phenomenon that was atypical for his usual semiology. He underwent successful laser ablation of the right superior parietal lobule lesion. In the months following surgery, he experienced a few seizures. After some medication adjustments, at 1 year from surgery, he was seizure free.

3. DISCUSSION

This case underscores the usefulness of VBM in identifying epileptogenic lesions on a non‐lesional MRI, and the significance of multimodality approach including MRI, PET, EEG, semiology, MEG, and VBM in accurately localizing suspected PLEs. VBM is a post‐processing technique that performs a voxel‐by‐voxel comparison between the brain regions of interest to a set of normal controls, and is able to detect subtle cortical abnormalities such as regions of cortical thickening or gray‐white matter blurring that may correspond to focal cortical dysplasias on non‐lesional brain MRIs. ⁵ , ⁶ Similarly, MEG, which records the small magnetic fields generated by cortical electrical activity, can identify and localize dipoles with greater sensitivity than scalp EEG, particularly for dipoles generated within a sulcus and tangentially oriented dipoles. ⁷ , ⁸ Both VBM and MEG in our patient were helpful in identifying a lesion and a dipole cluster which could subsequently be targeted by stereo EEG to confirm the epileptogenic zone.

In addition, the posterior‐to‐anterior lag of IEDs in our case provided evidence of rapid propagation from the parietal to frontal lobe. The posterior‐to‐anterior lag of the IED and initial nystagmus on review was consistent with a generator in the right parietal lobe with subsequent rapid propagation to the frontal lobe, likely facilitated through the superior longitudinal fasciculus, the largest associative fiber bundle connecting superior parietal lobule to frontal lobe, ⁹ , ¹⁰ which was consistent with findings of VBM and other presurgical modalities including PET scan and MEG, and phase II evaluation.

The accurate localization of IEDs is a critical step in the determination of candidacy for epilepsy surgery for patients with DRE. Accurate localization of IEDs is particularly important for patients who have non‐lesional epilepsy, as the rate of surgical success is lower in this group compared to lesional epilepsies (38% vs. 66%, respectively). ⁸ False localization of IEDs may account for some of these failures. ² , ³ IEDs and seizures arising from the parietal lobe may mimic those from one of its interconnected regions, leading to a mistaken localization and an unfavorable surgical outcome. ¹ Indeed, EEG localization is least accurate for ictal and interictal activity arising from the parietal lobe and the correct localization of IEDs to the parietal lobe is an independent predictor of surgical success. ¹¹ , ¹² Thus, in the absence of reliable EEG localization in PLE, a multimodal approach, including MEG and post‐processing neuroimaging techniques like VBM, should be pursued in cases of suspected PLE. ⁵ , ⁶ , ¹³

If PLE is suspected, a detailed history and careful video review of semiological features, such as nystagmus in our patient, should be thoroughly sought which can provide additional clues in multimodality approach to seizure localization.

Our case also highlights the need to enhance our understanding of functional interconnectivity within the brain along white matter tracts for improved accurate localization of interictal activity and subsequent surgical success. ³ Beyond the superior longitudinal fasciculus connection to the frontal lobe, the parietal lobe has widespread connections through the arcuate fasciculus and cingulum, which can lead to a wide seizure network and semiology that can be poorly localizing to the parietal lobe. ¹³ Conventional methods of studying brain connectivity such as DTI and functional MRI are useful tools but can be expensive and are not routinely performed in all patients undergoing epilepsy surgery evaluation. Therefore, the study of IEDs on EEG may provide additional insight into how epileptic networks propagate epileptogenicity through white matter tracts, and should be explored further.

To improve the surgical outcomes of patients with non‐lesional MRIs, using every available modality to identify a possible localization target is a logical approach, with more concordant data leading to a more confident localization, and can be effective strategy as our case demonstrates. Modalities such as VBM and MEG, which may not be regularly utilized or available in all epilepsy centers, can be vital in a successful outcome, and are worth the effort of pursuing in non‐lesional cases. Hopefully, as MRI post‐processing tools such as VBM become more sophisticated and easily available, it will be part of regular practice to perform VBM analysis after an initial non‐lesional MRI. Understanding epilepsy through multimodality approach in this fashion can help with accurate localization especially in difficulty to localize and deceptive non‐lesional PLEs.

AUTHOR CONTRIBUTIONS

Dr. Patrick Hartnett drafted the introduction and discussion. Dr. Naseem Zomorodi drafted the abstract and case presentation. Drs. Ifrah Zawar and Howard P. Goodkin critically revised this article for intellectual content.

CONFLICT OF INTEREST STATEMENT

None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

ETHICS STATEMENT

No identifiable data are presented in this case. Ethics approval was not required for this study in accordance with national guidelines.

Hartnett P, Zomorodi N, Goodkin HP, Zawar I. The significance of multimodality approach in the management of non‐lesional drug‐resistant focal parietal lobe epilepsies. Epilepsia Open. 2024;9:1604–1610. 10.1002/epi4.13000

DATA AVAILABILITY STATEMENT

All relevant data gathered can be found within this article. Further inquiries can be made to the author.