Magnetoencephalography: at the forefront of optimizing epilepsy surgery

Approximately 50 million people are affected by epilepsy worldwide [1]. About 30% of these patients are expected to develop drug-resistant epilepsy (DRE) and are a potential candidate for epilepsy surgery work up. Therefore professional organizations and clinical guidelines recommend that patients with DRE discuss or undergo evaluation at a comprehensive epilepsy center for consideration of epilepsy surgery or other specialized services [2].

Magnetoencephalography (MEG) scan offers a non invasive technology for presurgical evaluation of patients with DRE. Utilizing MEG also provides the potential to achieve better outcomes for patients by localizing seizure onset and allowing for more precise pre-surgical evaluations. Despite its demonstrated success in seizure localization and being approved for the presurgical evaluation of refractory epilepsy, MEG continues to be overlooked by epilepsy and neurosurgical communities [3].

There is an abundance of evidence that incorporating MEG scans significantly increases the number of surgical candidates and improves surgical outcomes [4]. Offering current thinking on the modality’s efficacy, this article highlights the benefits of MEG-based diagnosis and its ability to precisely localize epileptogenic focus in children. It also discusses the thought-provoking insights of the author and his colleagues gained utilizing MEG at their hospital.

MEG in comparison with EEG & functional MRI

Despite the fact that MEG technology has supported the diagnosis and pre-surgical evaluation of epilepsy patients for more than 30 years, its adoption by clinicians compared with traditional modalities like EEG and functional magnetic resonance imaging (fMRI) have been relatively slow. Data from a recent survey of US centers of research, as well as a similar study covering European centers confirmed this inconsistent adoption [5].

Contending for the gold standard in epileptic presurgical evaluation is the EEG. When weighing the relative diagnostic utility and efficacy of EEG versus a MEG scan, certain practical aspects of the procedure serve to highlight critical distinctions between the modalities. This also helps to elevate the clinical and therapeutic value of a MEG scan as standalone and supplement to other diagnostic tools in armamentarium.

A MEG scan has significant advantages for seizure localization as compared with surface EEG due to its high temporal and spatial resolution [6]. Magnetic waves in addition have insensitivity to tissue inhomogeneities.

It is increasingly clear that many frontal lobe epilepsy patients diagnosed with ‘generalized’ epilepsy on EEG may in fact have focal epilepsy and be a surgical candidate. An old misconception that ‘spikeless or negative EEG patients are unlikely to benefit from MEG has been debunked’ [7]. MEG is approximately expected to identify spikes in a third or more of patients without EEG spikes [8,9]. High-density EEG recordings (128–256 channels) are also expected to have limitations in source localization due to electrical/tissue interface properties.

MEG’s high spatio-temporal resolution over other imaging modalities

MEG measures minute magnetic fields generated by neuronal electrical activity with superb spatio- temporal resolution. Therefore, it offers high temporal (<1 ms), spectral (<1 Hz) and spatial (<1 cm) resolution, making it very suitable to investigate not only interictal spikes but also other physiological signals like auditory, sensory and speech perception. Other imaging modalities often have time resolution ranging from several seconds (fMRI) to tens of min PET scan. Further, a MEG study does not require injecting patients with radioactive tracers or contrast media. At last, MEG studies eliminate the claustrophobic space, strong magnetic fields and loud noises that MRI and fMRI studies produce.

MEG’s potential role in optimizing care

The benefits of epilepsy surgery have been unequivocally established. Many studies have shown that including MEG into the workup significantly increases the number of surgical candidates and improves outcomes. Despite this evidence, epilepsy surgery and MEG continued to be under-used. One reason why MEG is currently under utilized may be attributable to the fact that fewer patients are being evaluated for epilepsy surgery. Of the 100,000–200,000 people in the USA who are deemed epilepsy surgery candidates, only 4000 epilepsy surgeries are conducted per year. Only about 22% of patients diagnosed with epilepsy in the US go to specialist epilepsy centers, with even fewer admitted to level 4 centers, meaning patients are even less likely to receive surgery (National Association of Epilepsy Centers, [NAEC] published data).

Convenient access to a MEG scanner is of course another critical factor when assessing MEG’s under utilization. In a 2017 NAEC survey, only 40 of 240 epilepsy centers reported that their institution owned a MEG scanner. This is supported by the American Clinical MEG Society (ACMEGS), which identified that only 27% of centers owned a MEG scanner [10]. A European consortium, E-pilepsy: Pilot European Network (ERN) noted seven of their 24 centers indicated that they use a MEG scan to aid diagnosis [11].

Time to reassess the diagnostic benefits of MEG

Beyond entrenched clinical norms, healthcare’s inability to adopt MEG more widely into presurgical evaluation protocols may be attributed to less informed assumptions relative to the technology. One perceived issue among clinicians is that MEG data processing requires many in-house or outsourced physicists and engineers to obtain scan results, complicating the administration of the test by the clinical team at the point-of-care.

Another barrier preventing wider adoption of MEG is the absence of dedicated training and certification of technologists and clinical neurophysiologists needed to perform and evaluate the scan. Further complications can also arise due to inconsistent and complicated healthcare reimbursement mechanisms, making financial planning challenging for healthcare providers.

Unlocking the future of MEG in presurgical evaluation

In 2020, the ACMEG provided a guideline for a clinical situation where a MEG scan can be helpful in pre-surgical evaluation [12]. This case scenario included, but was not limited to:

• Circumstances where EEG failed to establish hypotheses regarding seizure onset.

• Concern about seizure onset in the temporal lobe. Mesial versus neo cortex/Insula.

• Multiple lesions on the MRI with one ‘hot’ focus.

• A large lesion on MRI, but concern for focal seizure onset.

• Patients with failed previous epilepsy surgery.

• An EEG with a bilateral or generalized pattern and concern for frontal focal epilepsy.

• Intrasylvian or interhemispheric onset seizures.

• A spike-less EEG.

Another remarkable feature of a MEG scan is its ability to supplement two relatively effective modalities in epilepsy surgery, Stereo EEG and laser interstitial thermal ablation. In the past two decades, those two technologies have gained traction as modality of choice for patients with DRE undergoing surgery. Due to its precise lesion localization, a MEG scan can significantly reduce the number of electrodes required for investigation and facilitate the determination of trajectories required for successful thermal ablation.

MEG in action

MEG is currently being used by clinicians and researchers who are working with patients with disorders like epilepsy, traumatic brain injury, dementia, spasticity and autism. Our Center at Cook Children’s Hospital acquired its MEG capabilities in 2012. As the department’s epileptologists became comfortable with technology and began to better understand its uses, the numbers of MEG scans conducted annually increased steadily from 26 in 2016 to 80 in 2019 and onward.

It is worth emphasizing that the Center’s that are acquiring MEG do not need to wait a long time before getting comfortable with this modality. There is abundant evidence that a MEG scan is not an ‘investigational’ or ‘research’ tool, but instead should be considered as indispensable for centers catering to epilepsy surgical candidates.

Overcoming a patient’s imaging challenges with MEG

A recent case involving a young postpubescent patient demonstrated just how effective a MEG scan can be. This case highlighted the benefits of using MEG in evaluating the potential for surgical intervention in a drug resistant epileptic patient with ambiguous results from an initial EEG.

This patient was previously evaluated with surface and intracranial EEG testing at another institute and was not deemed a surgical candidate. Despite multiple medications, she was having daily seizures. Her MRI scan results also reported ‘normal’ responses. She underwent a MEG scan at our institute. What looked like a bifrontal spike and wave activity on EEG, was clearly lateralized to the right frontal area. Magnetic source imaging showed a large tight cluster of dipoles in the right anterior insula.

A hindsight review of the MRI was concerning for blurring of the grey, white junction under the cluster. An overnight hospital admission and laser interstitial thermal ablation procedure released her from 16 years of debilitating seizures [13].

Time to recognize MEG’s value for patients with refractory epilepsy

It's becoming clear there is a need to introduce more people to the clinical practice guidelines issued by the ACMEG society and by the American Clinical Neurophysiology Society (ACNS), both of which highlight MEG’s efficacy and importance. MEG technology vendors have also made great strides in engineering systems more appropriate for an advanced commercial role in epileptic care.

When it comes to treating epileptic patients more effectively, the research community needs to work even harder to convince clinicians – whether highly specialized epileptologists or pediatricians and neurologists – that MEG is not just another enhanced EEG offering little more than incremental diagnostic value presurgery. At last, clinical practice guidelines need to be disseminated industry wide at symposiums where epileptologists and other doctors involved in seizure diagnosis can unequivocally demonstrate why MEG should be part of most patient evaluations for epilepsy surgery.