Role of optically pumped magnetometers in presurgical epilepsy evaluation: Commentary of the American Clinical Magnetoencephalography Society.

One of the major challenges of modern epileptology is the underutilization of epilepsy surgery for treatment of patients with focal, medication resistant epilepsy (MRE). Aggravating this distressing failure to deliver optimum care to these patients is the underuse of proven localizing tools, such as magnetoencephalography (MEG), a clinically validated, non-invasive, neurophysiological method used to directly measure and localize brain activity. A sizable mass of published evidence indicates that MEG can improve identification of surgical candidates and guide pre-surgical planning, increasing the yield of SEEG and improving operative outcomes. However, despite at least 10 common, evidence supported, clinical scenarios in MRE patients where MEG can offer non-redundant information and improve the pre-surgical evaluation, it is regularly used by only a minority of USA epilepsy centers. The current state of the art in MEG sensors employs SQUIDs, which require cooling with liquid helium to achieve superconductivity. This sensor technology has undergone significant generational improvement since whole head MEG scanners were introduced around in 1990s, but still has limitations. Further advances in sensor technology which may make ME G more easily accessible and affordable have been eagerly awaited, and development of new techniques should be encouraged. Of late, optically pumped magnetometers (OPMs) have received considerable attention, even prompting some potential acquisitions of new MEG systems to be put on hold, based on a hope that OPMs will usher in a new generation of MEG equipment and procedures. The development of any new clinical test used to guide intracranial EEG monitoring and/or surgical planning must address several specific issues. The goal of this commentary is to recognize the current state of OPM technology and to suggest a framework for it to advance in the clinical realm where it can eventually be deemed clinically valuable to physicians and patients. The American Clinical MEG Society (ACMEGS) strongly supports more advanced and less expensive technology and looks forward to continuing work with researchers to develop new sensors and clinical devices which will improve the experience and outcome for patients, and perhaps extend the role of MEG. However, currently, there are no OPM devices ready for practical clinical use. Based on the engineering obstacles and the clinical tradeoffs to be resolved, the assessment of experts suggests that there will most likely be another decade relying solely on "frozen SQUIDs" in the clinical MEG field.

Brain Connectivity in Dystonia: Evidence from Magnetoencephalography.

Magnetoencephalography (MEG) detects synchronized activity within a neuronal network by measuring the magnetic field changes generated by intracellular current flow. Using MEG data, we can quantify brain region networks with similar frequency, phase, or amplitude of activity and thereby identify patterns of functional connectivity seen with specific disorders or disease states. In this review, we examine and summarize MEG-based literature on functional networks in dystonias. Specifically, we inspect literature evaluating the pathogenesis of focal hand dystonia, cervical dystonia, embouchure dystonia, the effects of sensory tricks, treatment with botulinum toxin and deep brain stimulation, and rehabilitation approaches. This review additionally highlights how MEG has potential for application to clinical care of patients with dystonia.

Centromedian thalamic neuromodulation for the treatment of idiopathic generalized epilepsy.

Idiopathic generalized epilepsy (IGE) is a common type of epilepsy and despite an increase in the number of available anti-seizure medications, approximately 20-30% of people with IGE continue to experience seizures despite adequate medication trials. Unlike focal epilepsy, resective surgery is not a viable treatment option for IGE; however, neuromodulation may be an effective surgical treatment for people with IGE. Thalamic stimulation through deep brain stimulation (DBS) and responsive neurostimulation (RNS) have been explored for the treatment of generalized and focal epilepsies. Although the data regarding DBS and RNS in IGE is limited to case reports and case series, the results of the published studies have been promising. The current manuscript will review the published literature of DBS and RNS within the centromedian nucleus of the thalamus for the treatment of IGE, as well as highlight an illustrative case.

Magnetoencephalography-identified preictal spiking correlates to preictal spiking on stereotactic EEG.

Magnetoencephalography (MEG) is a noninvasive diagnostic modality that directly measures neuronal signaling by recording the magnetic field created from dendritic, intracellular, electrical currents of the neuron at the surface of the head. In clinical practice, MEG is used in the epilepsy presurgical evaluation and most commonly is an "interictal" study that can provide source localization of spike-wave discharges. However, seizures may be recorded during MEG ("ictal MEG") and mapping of these discharges may provide more accurate localization of the seizure onset zone. In addition, spike-negative EEG with unique MEG spike-waves may be present in up to 1/3 of MEG studies and unique MEG seizures (EEG-negative seizures) have been reported. This case report describes a patient with unique MEG seizures that exhibited MEG pre-ictal spiking in a tight cluster consistent with the independent interictal epileptiform activity. Stereotactic EEG demonstrated pre-ictal spiking concordant with the MEG pre-ictal spiking.

Outcomes of seizures, status epilepticus, and EEG findings in critically ill patient with COVID-19.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a myriad of neurological manifestations and its effects on the nervous system are increasingly recognized. Seizures and status epilepticus (SE) are reported in the novel coronavirus disease (COVID-19), both new onset and worsening of existing epilepsy; however, the exact prevalence is still unknown. The primary aim of this study was to correlate the presence of seizures, status epilepticus, and specific critical care EEG patterns with patient functional outcomes in those with COVID-19. METHODS: This is a retrospective, multicenter cohort of COVID-19-positive patients in Southeast Michigan who underwent electroencephalography (EEG) from March 12th through May 15th, 2020. All patients had confirmed nasopharyngeal PCR for COVID-19. EEG patterns were characterized per 2012 ACNS critical care EEG terminology. Clinical and demographic variables were collected by medical chart review. Outcomes were divided into recovered, recovered with disability, or deceased. RESULTS: Out of the total of 4100 patients hospitalized with COVID-19, 110 patients (2.68%) had EEG during their hospitalization; 64% were male, 67% were African American with mean age of 63 years (range 20-87). The majority (70%) had severe COVID-19, were intubated, or had multi-organ failure. The median length of hospitalization was 26.5 days (IQR = 15 to 44 days). During hospitalization, of the patients who had EEG, 21.8% had new-onset seizure including 7% with status epilepticus, majority (87.5%) with no prior epilepsy. Forty-nine (45%) patients died in the hospital, 46 (42%) recovered but maintained a disability and 15 (14%) recovered without a disability. The EEG findings associated with outcomes were background slowing/attenuation (recovered 60% vs recovered/disabled 96% vs died 96%, p < 0.001) and normal (recovered 27% vs recovered/disabled 0% vs died 1%, p < 0.001). However, these findings were no longer significant after adjusting for severity of COVID-19. CONCLUSION: In this large multicenter study from Southeast Michigan, one of the early COVID-19 epicenters in the US, none of the EEG findings were significantly correlated with outcomes in critically ill COVID-19 patients. Although seizures and status epilepticus could be encountered in COVID-19, the occurrence did not correlate with the patients' functional outcome.

The 10 Common Evidence-Supported Indications for MEG in Epilepsy Surgery: An Illustrated Compendium.

Unfamiliarity with the indications for and benefits of magnetoencephalography (MEG) persists, even in the epilepsy community, and hinders its acceptance to clinical practice, despite the evidence. The wide treatment gap for patients with drug-resistant epilepsy and immense underutilization of epilepsy surgery had similar effects. Thus, educating referring physicians (epileptologists, neurologists, and neurosurgeons) both about the value of epilepsy surgery and about the potential benefits of MEG can achieve synergy and greatly improve the process of selecting surgical candidates. As a practical step toward a comprehensive educational process to benefit potential MEG users, current MEG referrers, and newcomers to MEG, the authors have elected to provide an illustrated guide to 10 everyday situations where MEG can help in the evaluation of people with drug-resistant epilepsy. They are as follows: (1) lacking or imprecise hypothesis regarding a seizure onset; (2) negative MRI with a mesial temporal onset suspected; (3) multiple lesions on MRI; (4) large lesion on MRI; (5) diagnostic or therapeutic reoperation; (6) ambiguous EEG findings suggestive of "bilateral" or "generalized" pattern; (7) intrasylvian onset suspected; (8) interhemispheric onset suspected; (9) insular onset suspected; and (10) negative (i.e., spikeless) EEG. Only their practical implementation and furtherance of personal and collective education will lead to the potentially impactful synergy of the two-MEG and epilepsy surgery. Thus, while fulfilling our mission as physicians, we must not forget that ignoring the wealth of evidence about the vast underutilization of epilepsy surgery - and about the usefulness and value of MEG in selecting surgical candidates - is far from benign neglect.

Language Mapping With Magnetoencephalography: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines.

Numerous studies have shown that language processing is not limited to a few brain areas. Visual or auditory stimuli activate corresponding cortical areas, then memory identifies the word or image, Wernicke's and Broca's areas support the processing for either reading/listening or speaking and many areas of the brain are recruited. Determining how a normal person processes language helps clinicians and scientist to understand how brain pathologies such as tumor or stroke can affect changes in language processing. Patients with epilepsy may develop atypical language organization. Over time, the chronic nature of epileptic activity, or changes from a tumor or stroke, can result in a shift of language processing area from the left to the right hemisphere, or re-routing of language pathways from traditional to non-traditional areas within the dominant left hemisphere. It is important to determine where these language areas are prior to brain surgery. MEG evoked responses reflecting cerebral activation of receptive and expressive language processing can be localized using several different techniques: Single equivalent current dipole, current distribution techniques or beamformer techniques. Over the past 20 years there have been at least 25 validated MEG studies that indicate MEG can be used to determine the dominant hemisphere for language processing. The use of MEG neuroimaging techniques is needed to reliably predict altered language networks in patients and to provide identification of language eloquent cortices for localization and lateralization necessary for clinical care.

Visual Mapping With Magnetoencephalography: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines.

Using visual evoked fields (VEFs) to differentiate healthy, normal brain function from dysfunctional cortex has been demonstrated to be both valid and reliable. Currently, VEFs are widely implemented to guide intracranial surgeries for epilepsy and brain tumors. There are several areas of possible future clinical use of VEFs, including early identification of disorders, such as multiple sclerosis, Parkinson's disease, stroke, and human immunodeficiency virus-associated neurocognitive disorders. These studies have suggested that VEFs could be used to study disease pathophysiology or as a biomarker for early identification of a disorder. The current clinical practice guidelines of the American Clinical Magnetoencephalography Society for VEFs are sufficient. At this time, VEFs should be used clinically to identify visual cortex and potentially tailor surgical resections.

Sensorimotor Integration and GABA-ergic Activity in Embouchure Dystonia: An Assessment with Magnetoencephalography.

Background: Embouchure dystonia (ED) is a task-specific dystonia affecting musicians thought to be related to alteration in sensorimotor processing and loss of cortical inhibition. Case Report: Magnetoencephalography-coherence source imaging (MEG-CSI) was used to map connectivity between brain regions by imaging neuronal oscillations that are coherent across the brain in patient with ED at rest and while using the index finger to evoke dystonia normally triggered by playing the flute. Discussion: During rest, there was increased coherence in the bilateral frontal and parietal regions that became more focal during dystonia. Diffuse hyperexcitability and increased coherence persisted in bilateral parietal regions as well as the bilateral frontal regions.

Post-operative nonketotic hyperglycemic induced focal motor status epilepticus related to treatment with corticosteroids following standard anterior temporal lobectomy.

•Complications from standard ATL are uncommon and the use of post-operative corticosteroids may reduce complications.•Following standard ATL, FMSE was present after treatment with corticosteroids that resolved after blood sugar control.•After epilepsy surgery, corticosteroids should be used cautiously in people with comorbid diabetes mellitus.

Cervical Dystonia and Executive Function: A Pilot Magnetoencephalography Study.

BACKGROUND: Cervical dystonia (CD) patients have impaired working memory, processing speed and visual-motor integration ability. We used magnetoencephalography (MEG) to investigate changes in cerebral oscillations in CD patients during an executive function test, before and after administration of botulinum toxin. METHODS: MEG data were collected from five CD patients while they performed a visual continuous performance task (CPT), before and after they received a botulinum toxin injection. MEG data was also collected on five controls matched for age and gender. Coherence source imaging was performed to quantify network connectivity of subjects. RESULTS: Controls demonstrated two errors with visual CPT; CD patients demonstrated six and three errors pre- and post-botulinum toxin respectively. After botulinum toxin, mean time from cue to correct response was 0.337 s in controls, 0.390 s in patients before botulinum toxin injection, and 0.366 s after the injection. Differences in coherence between controls and patients were found in the following brain regions: Fronto-frontal, fronto-parietal, fronto-striatal, fronto-occipital, parieto-parietal and temporo-parietal. Intrahemispheric and interhemispheric networks were affected. Post injection, there was minimal change in coherence in the above-mentioned networks. DISCUSSION: Neuropsychological testing suggests difference in coherence in frontal circuits between CD cases and controls during the visual CPT, which may reflect subjects' increased difficulty with the task. Botulinum toxin is associated with minimal improvement with executive function in CD.

Sensory Trick in a Patient with Cervical Dystonia: Insights from Magnetoencephalography.

BACKGROUND: The proposed mechanisms for the sensory trick include peripheral sensory feedback to aid in correcting abnormal posture or movement. CASE REPORT: A 53-year-old woman with cervical dystonia underwent magnetoencephalography pre- and post-botulinum toxin injection and sensory trick, which was described as yawning. Study revealed connectivity between the left frontal and inferior frontal gyrus before yawning, which changed to the visual cortex and right middle frontal gyrus with yawning. Beta frequencies reduced and gamma frequencies increased after yawning. DISCUSSION: The increase in gamma frequency bands may indicate increased GABAergic activity. Increase in connectivity in the right cerebellar region underscores the importance of cerebellum in pathogenesis of dystonia.

The Effect of Botulinum Toxin on Network Connectivity in Cervical Dystonia: Lessons from Magnetoencephalography.

Background: Pharmacological management of cervical dystonia (CD) is considered to be symptomatic in effect, rather than targeting the underlying pathophysiology of the disease. Magnetoencephalography (MEG), a direct measure of neuronal activity, while accepted as a modality for pre-surgical mapping in epilepsy, has never been used to explore the effect of pharmacotherapy in movement disorders. Methods: Resting state MEG data were collected from patients with CD, pre- and post-botulinum toxin injections. All of these patients exhibited good clinical benefit with botulinum toxin. Resting state MEG data from four age- and gender-matched healthy controls with no neurological disorders were also collected. Results: Our exploratory study reveals a difference in coherence between controls and patients in the following regions: fronto-striatal, occipito-striatal, parieto-striatal, and striato-temporal networks. In these regions there is an increase after botulinum toxin. Specifically, increased coherence in the left putamen and right superior parietal gyrus was noticeable. Both intrahemispheric and interhemispheric networks were affected. Discussion: This is the first attempt to directly assess changes in functional connectivity with pharmacotherapy using MEG. Botulinum toxin might affect sensorimotor integration, leading to clinical benefit. The presence of increased interhemispheric coherence and intrahemispheric coherence points to the importance of global and local networks in the pathophysiology of dystonia.

Multimodal Imaging in a Patient with Hemidystonia Responsive to GPi Deep Brain Stimulation.

BACKGROUND: Dystonia is a syndrome with varied phenomenology but our understanding of its mechanisms is deficient. With neuroimaging techniques, such as fiber tractography (FT) and magnetoencephalography (MEG), pathway connectivity can be studied to that end. We present a hemidystonia patient treated with deep brain stimulation (DBS). METHODS: After 10 years of left axial hemidystonia, a 45-year-old male underwent unilateral right globus pallidus internus (GPi) DBS. Whole brain MEG before and after anticholinergic medication was performed prior to surgery. 26-direction diffusion tensor imaging (DTI) was obtained in a 3 T MRI machine along with FT. The patient was assessed before and one year after surgery by using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). RESULTS: In the eyes-closed MEG study there was an increase in brain coherence in the gamma band after medication in the middle and inferior frontal region. FT demonstrated over 50% more intense ipsilateral connectivity in the right hemisphere compared to the left. After DBS, BFMDRS motor and disability scores both dropped by 71%. CONCLUSION: Multimodal neuroimaging techniques can offer insights into the pathophysiology of dystonia and can direct choices for developing therapeutics. Unilateral pallidal DBS can provide significant symptom control in axial hemidystonia poorly responsive to medication.

Periodic Discharges: Insight From Magnetoencephalography.

PURPOSE: This study used magnetoencephalography (MEG) dipole localization and coherence measurement to evaluate the magnetic fields associated with periodic discharges. The primary goal of the study was to evaluate whether MEG could consistently localize quasiperiodic discharges that were observed on the EEG portion of the recording. The secondary objective was to evaluate whether coherence measurements would correlate with topographic maxima of epileptiform activity. METHODS: A total of 13 inpatients, whose electrographic records demonstrated lateralized periodic discharges (LPDs), were recruited from Henry Ford Hospital neurology and intensive care units. Nine patients were found clinically to be in status epilepticus before the EEG determination of LPDs. Spontaneous cortical brain activity was recorded with 148-channel MEG for 10 minutes. Data were sampled at 508 Hz and DC-100 Hz and filtered from 1 Hz to 40 Hz. Interictal events were imaged with single equivalent current dipole localization. Magnetoencephalography coherence source imaging analysis was performed and compared with the cortical topography of LPD patterns and with the focal lesions seen on the MRI (9 patients) or computed tomography (5 patients) imaging modalities. RESULTS: The morphology of periodic waveforms was similar between EEG and MEG portions of the study. In patients with substrate positivity on imaging studies, coherence analysis revealed a tendency for LPDs to arise from the interface between the lesion and the surrounding, uncompromised cortex rather than from the lesion itself. In nonlesional patients with recent status epilepticus, the localization of maximal coherence was in the temporal lobes. CONCLUSIONS: This study demonstrated that MEG is able to detect and localize LPDs arising from damaged and adjacent cortex. The MEG coherence source imaging measurements also suggest the presence of epileptogenic networks perilesionally in cases with focal lesions on imaging. In patients without acute anatomic abnormality, the MEG coherence identified the epileptogenic networks in temporal lobe structures. Magnetoencephalography coherence source imaging may provide physicians with markers for differentiating between LPDs arising from acute injury currents versus LPDs arising from prolonged status epilepticus.

Controllable yawning expressed as focal seizures of frontal lobe epilepsy.

Excessive yawning was described in some neurological conditions as part of periictal or ictal manifestations of epilepsy, most commonly temporal lobe. We present the first case of controllable yawning as a primary seizure semiology with dominant frontal lobe involvement in a 20-year-old man. Video electroencephalography recorded 8 yawning episodes accompanied with right arm movement correlating with rhythmic diffuse theta range activity with left hemispheric predominance. Magnetoencephalography coherence source imaging was consistent with persistent neuronal networks with areas of high coherence reliably present over the left lateral orbitofrontal region. Epileptogenic areas may have widespread networks involving the dominant frontal lobe in unique symptomatogenic areas.

MEG Coherence and DTI Connectivity in mTLE.

Magnetoencephalography (MEG) is a noninvasive imaging method for localization of focal epileptiform activity in patients with epilepsy. Diffusion tensor imaging (DTI) is a noninvasive imaging method for measuring the diffusion properties of the underlying white matter tracts through which epileptiform activity is propagated. This study investigates the relationship between the cerebral functional abnormalities quantified by MEG coherence and structural abnormalities quantified by DTI in mesial temporal lobe epilepsy (mTLE). Resting state MEG data was analyzed using MEG coherence source imaging (MEG-CSI) method to determine the coherence in 54 anatomical sites in 17 adult mTLE patients with surgical resection and Engel class I outcome, and 17 age- and gender- matched controls. DTI tractography identified the fiber tracts passing through these same anatomical sites of the same subjects. Then, DTI nodal degree and laterality index were calculated and compared with the corresponding MEG coherence and laterality index. MEG coherence laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in insular cortex and both lateral orbitofrontal and superior temporal gyri (p < 0.017). Likewise, DTI nodal degree laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in gyrus rectus, insular cortex, precuneus and superior temporal gyrus (p < 0.017). In insular cortex, MEG coherence laterality correlated with DTI nodal degree laterality ([Formula: see text] in the cases of mTLE. None of these anatomical sites showed statistically significant differences in coherence laterality between right and left sides of the controls. Coherence laterality was in agreement with the declared side of epileptogenicity in insular cortex (in 82 % of patients) and both lateral orbitofrontal (88 %) and superior temporal gyri (88 %). Nodal degree laterality was also in agreement with the declared side of epileptogenicity in gyrus rectus (in 88 % of patients), insular cortex (71 %), precuneus (82 %) and superior temporal gyrus (94 %). Combining all significant laterality indices improved the lateralization accuracy to 94 % and 100 % for the coherence and nodal degree laterality indices, respectively. The associated variations in diffusion properties of fiber tracts quantified by DTI and coherence measures quantified by MEG with respect to epileptogenicity possibly reflect the chronic microstructural cerebral changes associated with functional interictal activity. The proposed methodology for using MEG and DTI to investigate diffusion abnormalities related to focal epileptogenicity and propagation may provide a further means of noninvasive lateralization.

Application of MEG coherence in lateralization of mTLE.

Magnetoencephalography (MEG) is a noninvasive imaging method for localization of focal epileptiform activity in patients with epilepsy. This study investigates the cerebral functional abnormalities quantified by MEG coherence laterality in mesial temporal lobe epilepsy (mTLE). Resting state MEG data was analyzed using MEG coherence source imaging (MEG-CSI) method to determine the coherence in 54 anatomical sites in 12 adult mTLE patients and 12 age- and gender-matched controls. MEG coherence laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in insular cortex and both lateral orbitofrontal and superior temporal gyri (p<;0.025). None of these anatomical sites showed statistically significant differences in coherence laterality between right and left sides of controls. Coherence laterality was in agreement with the declared side of epileptogenicity in insular cortex (in 75% of patients) and both lateral orbitofrontal (83%) and superior temporal gyri (84%). Combining all significant laterality indices improved the lateralization accuracy to 92%. The proposed methodology for using MEG to investigate the abnormalities related to focal epileptogenicity and propagation can provide a further means of noninvasive lateralization.

Application of DTI connectivity in lateralization of mTLE.

Diffusion tensor imaging (DTI) is a noninvasive imaging method for measuring the diffusion properties of the underlying white matter tracts through which epileptiform activity is propagated. This study investigates the structural abnormalities quantified by DTI in mesial temporal lobe epilepsy (mTLE). Fiber tracts passing through 54 anatomical sites in 12 adult mTLE patients and 12 age- and gender-matched controls were identified using DTI tractography. DTI nodal degree (ND) and laterality index were then calculated. ND laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in gyrus rectus, insular cortex, precuneus and superior temporal gyrus (p<;0.025). None of these anatomical sites showed statistically significant differences in ND laterality between right and left sides of the controls. Laterality models determined by logistic regression on the ND laterality data agreed with the side of epileptogenicity as it pertained to the gyrus rectus, insular cortex, precuneus and superior temporal gyrus for 89%, 72%, 83% and 92% of the patients, respectively. Combining the laterality measures in these four anatomical sites improved the results further with correct lateralization of 100% for all patients. The proposed methodology for using DTI connectivity to investigate diffusion abnormalities related to focal epileptogenicity and propagation can provide a further means of noninvasive lateralization.