A randomized, blinded, placebo-controlled, prospective clinical study to evaluate the effectiveness of a diluted liposomal-encapsulated bupivacaine suspension in dogs undergoing a ventral midline celiotomy.

Objective: To evaluate the effectiveness of a liposomal-encapsulated bupivacaine suspension (LEBS; Nocita), at a 1:5 dilution with 0.9% NaCl, for the reduction of postoperative pain scores and a related reduction in the need for postoperative opioids in dogs undergoing ventral midline celiotomy. Hypothesis: When infused at a 1:5 dilution, LEBS results in less postoperative pain (as indicated by pain scale scores), and a reduction in postoperative opioids, in dogs undergoing ventral midline celiotomy. The use of LEBS does not affect wound healing when compared to placebo. Study design: This was a randomized, blinded, prospective clinical trial. Animals: We studied 40 client-owned dogs undergoing abdominal surgery via a ventral midline celiotomy. Procedure: Dogs undergoing a ventral midline celiotomy were enrolled and randomly allocated to 1 of 2 groups: those receiving LEBS or a placebo injection protocol into tissue planes during closure. The Glasgow Composite Pain Scale-Short Form (GCPS-SF) was used by an observer blinded to the treatment group to assess patients at 0, 1, 2, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, and 72 h after extubation. Dogs with a score of ≥ 3 in any single category or ≥ 6 total were given a rescue analgesia. Data were analyzed to compare the number of rescue therapy doses administered between the 2 treatment groups. Results: Forty dogs completed the study. Dogs that received a diluted LEBS protocol were equally likely to require a rescue therapy as those that received the placebo (0.9% NaCl). There were no significant difference in the pain scores or the total number of opioid injections required between the 2 treatment groups. Conclusion and clinical relevance: In dogs undergoing ventral midline celiotomy, 1:5 diluted LEBS administration alone should not be considered the sole method of pain relief. Liposomal-encapsulated bupivacaine suspension should be used in conjunction with systemic opioids as part of a multimodal analgesic regime. This multimodal approach would allow a reduction in dose or frequency of opioids, therefore lessening the undesired side effects associated with opioids while also decreasing client costs.

Une étude clinique prospective, randomisée, en aveugle, contrôlée par placebo, visant à évaluer l'efficacité d'une suspension diluée de bupivacaïne encapsulée dans des liposomes chez des chiens subissant une cœliotomie via la ligne médiane ventrale. Objectif: Évaluer l'efficacité d'une suspension de bupivacaïne encapsulée dans des liposomes (LEBS; Nocita), à une dilution de 1:5 avec 0,9 % de NaCl, pour la réduction des scores de douleur postopératoire et une réduction connexe du besoin d'opioïdes postopératoires chez des chiens subissant une céliotomie via la ligne médiane ventrale. Hypothèse: Lorsqu'il est perfusé à une dilution de 1:5, LEBS entraîne moins de douleur postopératoire (comme l'indiquent les scores de l'échelle de douleur) et une réduction des opioïdes postopératoires chez les chiens subissant une cœliotomie via la ligne médiane ventrale. L'utilisation du LEBS n'affecte pas la cicatrisation des plaies par rapport au placebo. Design expérimental: Il s'agissait d'un essai clinique prospectif, randomisé et en aveugle. Animaux: Nous avons étudié 40 chiens appartenant à des clients subissant une chirurgie abdominale par cœliotomie via la ligne médiane ventrale. Procédure: Les chiens subissant une cœliotomie via la ligne médiane ventrale ont été recrutés et répartis au hasard dans 1 groupe sur 2 : ceux recevant du LEBS ou un protocole d'injection de placebo dans les plans tissulaires pendant la fermeture. Le Glasgow Composite Pain Scale-Short Form (GCPS-SF) a été utilisé par un observateur aveugle au groupe de traitement pour évaluer les patients à 0, 1, 2, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66 et 72 h après l'extubation. Les chiens avec un score ≥ 3 dans n'importe quelle catégorie ou ≥ 6 au total ont reçu une analgésie de secours. Les données ont été analysées pour comparer le nombre de doses de thérapie de secours administrées entre les 2 groupes de traitement. Résultats: Quarante chiens ont complété l'étude. Les chiens ayant reçu un protocole LEBS dilué étaient tout aussi susceptibles de nécessiter une thérapie de secours que ceux ayant reçu le placebo (NaCl à 0,9 %). Il n'y avait aucune différence significative dans les scores de douleur ou le nombre total d'injections d'opioïdes nécessaires entre les 2 groupes de traitement. Conclusion et pertinence clinique: Chez les chiens subissant une cœliotomie via la ligne médiane ventrale, l'administration de LEBS dilué à 1:5 seule ne doit pas être considérée comme la seule méthode de soulagement de la douleur. La suspension de bupivacaïne encapsulée dans des liposomes doit être utilisée en association avec des opioïdes systémiques dans le cadre d'un régime analgésique multimodal. Cette approche multimodale permettrait de réduire la dose ou la fréquence des opioïdes, réduisant ainsi les effets secondaires indésirables associés aux opioïdes tout en diminuant également les coûts pour les clients.(Traduit par Dr Serge Messier).

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.

Clinical significance of ictal magnetoencephalography in patients undergoing epilepsy surgery.

OBJECTIVE: The significance of ictal magnetoencephalography (MEG) is not well appreciated. We evaluated the relationships between ictal MEG, MRI, intracranial electroencephalography (ICEEG), surgery and postoperative seizure outcome. METHODS: A total of 45 patients (46 cases) with ictal MEG who underwent epilepsy surgery was included. We examined the localization of each modality, surgical resection area and seizure freedom after surgery. RESULTS: Twenty-one (45.7%) out of 46 cases were seizure-free at more than 6 months follow-up. Median duration of postoperative follow-up was 16.5 months. The patients in whom ictal, interictal single equivalent current dipole (SECD) and MRI lesion localization were completely included in the resection had a higher chance of being seizure-free significantly (p < 0.05). Concordance between ictal and interictal SECD localizations was significantly associated with seizure-freedom. Concordance between MRI lesion and ictal SECD, concordance between ictal ICEEG and ictal and interictal SECD, as well as concordance between ictal ICEEG and MRI lesion were significantly associated with seizure freedom. CONCLUSIONS: Ictal MEG can contribute useful information for delineating the resection area in epilepsy surgery. SIGNIFICANCE: Resection should include ictal, interictal SECDs and MRI lesion localization, when feasible. Concordant ictal and interictal SECDs on MEG can be a favorable predictor of seizure freedom.

Electrographic Features of Epilepsy With Eyelid Myoclonia With Photoparoxysmal Responses.

PURPOSE: Epilepsy with eyelid myoclonia (EMA) is characterized by eyelid myoclonia, eyelid closure sensitivity, and photosensitivity. EEG may manifest with frontal-predominant (FPEDs) or occipital-predominant epileptiform discharges (OPEDs). Data on clinical and electrographic features of these two subtypes are lacking. The purpose of our research was to look at baseline electroclinical features of EMA subtypes and to study electrographic findings of patients with EMA during intermittent photic stimulation (IPS). METHODS: We retrospectively identified all patients who had photoparoxysmal responses on EEGs performed at Cleveland clinic between January 01, 2012, and December 31, 2019. Patients who met diagnostic criteria for EMA were studied further. RESULTS: Of the 249 patients with photoparoxysmal responses, 70 (28.1%) had EMA (62 [88.6%] female; the mean age of epilepsy onset: 7.0 ± 7.9 years). Patients with EMA had either FPEDs or OPEDs. Eleven patients with EMA (15.7%) had seizures (4 absence, 5 myoclonic and 2 bilateral tonic-clonic) during IPS. Patients with OPEDs were more likely to have drug-resistant epilepsy; occipital focal IEDs and other focal IEDs (other than frontal/occipital) on baseline EEG; and generalized IEDs with occipital predominance, generalized IEDs with no predominance, or focal IEDs during IPS. Predictors of seizure occurrence during photic stimulation included the presence of focal occipital IEDs on baseline EEG, generalized IEDs with frontal predominance during IPS, and photoparoxysmal response outlasting the stimulus. CONCLUSIONS: Our study provides evidence that EMA has two distinct subtypes, which differ in clinical characteristics, baseline EEG, and EEG during photic stimulation. We highlight diagnostic and prognostic implications of these findings. Our study also details EEG characteristics of patients with EMA during IPS.

Utility of Functional MRI and Magnetoencephalography in the Diagnosis of Infantile Spasms and Hypsarrhythmia.

SUMMARY: Neuroimaging and neurophysiology techniques can add a significant contribution to the comprehension of infantile spasms (IS) and hypsarrhythmia. Functional MRI and magnetoencephalography (MEG) are two noninvasive tools that can be used in young children with IS. In the past two decades, interesting data about IS have emerged from functional MRI and MEG studies. Regarding their clinical utility, MEG has supported the concept that epileptic spasms can have a focal origin. Moreover, MEG might contribute to the localization of the epileptogenic zone in children with IS under investigation for epilepsy surgery. Functional MRI data have contributed to improve the knowledge about the physiopathology of IS and hypsarrhythmia. It has demonstrated abnormal brainstem involvement during the high-amplitude slow waves of hypsarrhythmia and cortical involvement during the epileptiform discharges. Since the feasibility of these techniques has been demonstrated in infants, it is possible that, in the future, larger functional MRI and MEG studies might contribute to the treatment and the definition of the long-term prognosis of children with IS.

Multimodal Image Integration for Epilepsy Presurgical Evaluation: A Clinical Workflow.

Multimodal image integration (MMII) is a promising tool to help delineate the epileptogenic zone (EZ) in patients with medically intractable focal epilepsies undergoing presurgical evaluation. We report here the detailed methodology of MMII and an overview of the utility of MMII at the Cleveland Clinic Epilepsy Center from 2014 to 2018, exemplified by illustrative cases. The image integration was performed using the Curry platform (Compumedics Neuroscan™, Charlotte, NC, USA), including all available diagnostic modalities such as Magnetic resonance imaging (MRI), Positron Emission Tomography (PET), single-photon emission computed tomography (SPECT) and Magnetoencephalography (MEG), with additional capability of trajectory planning for intracranial EEG (ICEEG), particularly stereo-EEG (SEEG), as well as surgical resection planning. In the 5-year time span, 467 patients underwent MMII; of them, 98 patients (21%) had a history of prior neurosurgery and recurring seizures. Of the 467 patients, 425 patients underwent ICEEG implantation with further CT co-registration to identify the electrode locations. A total of 351 patients eventually underwent surgery after MMII, including 197 patients (56%) with non-lesional MRI and 223 patients (64%) with extra-temporal lobe epilepsy. Among 269 patients with 1-year post-operative follow up, 134 patients (50%) had remained completely seizure-free. The most common histopathological finding is focal cortical dysplasia. Our study illustrates the usefulness of MMII to enhance SEEG electrode trajectory planning, assist non-invasive/invasive data interpretation, plan resection strategy, and re-evaluate surgical failures. Information presented by MMII is essential to the understanding of the anatomo-functional-electro-clinical correlations in individual cases, which leads to the ultimate success of presurgical evaluation of patients with medically intractable focal epilepsies.

The Wisdom and Vision From the ACMEGS Inaugural Decade.

Concise history of fascinating magnetoencephalography (MEG) technology and catalog of very selected milestone preclinical and clinical MEG studies are provided as the background. The focus is the societal context defining a journey of MEG to and through clinical practice and formation of the American Clinical MEG Society (ACMEGS). We aspired to provide an objective historic perspective and document contributions of many professionals while focusing on the role of ACMEGS in the growth and maturation of clinical MEG field. The ACMEGS was born (2006) out of inevitability to address two vital issues-fair reimbursement and proper clinical acceptance. A beacon of accountable MEG practice and utilization is now an expanding professional organization with the highest level of competence in practice of clinical MEG and clinical credibility. The ACMEGS facilitated a favorable disposition of insurances toward MEG in the United States by combining the national replication of the grassroots efforts and teaming up with the strategic partners-particularly the American Academy of Neurology (AAN), published two Position Statements (2009 and 2017), the world's only set of MEG Clinical Practice Guidelines (CPGs; 2011) and surveys of clinical MEG practice (2011 and 2020) and use (2020). In addition to the annual ACMEGS Course (2012), we directly engaged MEG practitioners through an Invitational Summit (2019). The Society remains focused on the improvements and expansion of clinical practice, education, clinical training, and constructive engagement of vendors in these issues and pivotal studies toward additional MEG indications. The ACMEGS not only had the critical role in the progress of Clinical MEG in the United States and beyond since 2006 but positioned itself as the field leader in the future.

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.

Normal Variants in Magnetoencephalography.

Normal variants, although not occurring frequently, may appear similar to epileptic activity. Misinterpretation may lead to false diagnoses. In the context of presurgical evaluation, normal variants may lead to mislocalizations with severe impact on the viability and success of surgical therapy. While the different variants are well known in EEG, little has been published in regard to their appearance in magnetoencephalography. Furthermore, there are some magnetoencephalography normal variants that have no counterparts in EEG. This article reviews benign epileptiform variants and provides examples in EEG and magnetoencephalography. In addition, the potential of oscillatory configurations in different frequency bands to appear as epileptic activity is discussed.

Recognizing and Correcting MEG Artifacts.

Noise sources in magnetoencephalography (MEG) include: (1) interference from outside the shielded room, (2) other people and devices inside the shielded room, (3) physiologic or nonphysiologic sources inside the patient, (4) activity from inside the head that is unrelated to the signal of interest, (5) intrinsic sensor and recording electronics noise, and (6) artifacts from other apparatus used during recording such as evoked response stimulators. There are other factors which corrupt MEG recording and interpretation and should also be considered "artifacts": (7) inadequate positioning of the patient, (8) changes in the head position during the recording, (9) incorrect co-registration, (10) spurious signals introduced during postprocessing, and (11) errors in fitting. The major means whereby magnetic interference can be reduced or eliminated are by recording inside a magnetically shielded room, using gradiometers that measure differential magnetic fields, real-time active compensation using reference sensors, and postprocessing with advanced spatio-temporal filters. Many of the artifacts that plague MEG are also seen in EEG, so an experienced electroencephalographer will have the advantage of being able to transfer his knowledge about artifacts to MEG. However, many of the procedures and software used during acquisition and analysis may themselves contribute artifact or distortion that must be recognized or prevented. In summary, MEG artifacts are not worse than EEG artifacts, but many are different, and-as with EEG-must be attended to.

MEG Reporting.

The report generated by the magnetoencephalographer's interpretation of the patient's magnetoencephalography examination is the magnetoencephalography laboratory's most important product and is a representation of the quality of the laboratory and the clinical acumen of the personnel. A magnetoencephalography report is not meant to enumerate all the technical details that went into the test nor to fulfill some imagined requirements of the electronic health record. It is meant to clearly and concisely answer the clinical question posed by the referring doctor and to convey the key findings that may inform the next step in the patient's care. The graphical component of a magnetoencephalography report is ordinarily the most welcomed by the referring doctor. Much of the text of the report may be glossed over, so the illustrations must be sufficiently annotated to provide clear and unambiguous findings. The particular images chosen for the report will be a function of the analysis software but should be selected and edited for maximum clarity. There should be a composite pictorial summary slide at the beginning or at the end of the report, which accurately conveys the gist of the report. Along with representative source localizations, reports should contain examples of the simultaneously recorded EEG that enable the referring physician to determine whether epileptic discharges occurred and whether they are consistent with the patient's previously recorded spikes. Information and images (e.g., statistics, magnetic field patterns) that provide convincing evidence of the validity of the source location should also be included.

Clinical Magnetoencephalography Practice in the United States Ten Years Later: A Survey-Based Reappraisal.

PURPOSE: Broader utilization of magnetoencephalography (MEG) and optimization of clinical practice remain strategic goals of the American Clinical Magnetoencephalography Society. Despite the implementation of the first MEG Clinical Practice Guidelines, clinical adoption has been less than expected, prompting a reassessment. METHODS: Twenty-five clinical MEG centers were invited to participate anonymously in a survey of clinical practice. RESULTS: Centers (N = 18) mostly operated within an academic medical center (10/18), were owned by the "hospital" (10/18), associated with a level 4 National Association of Epilepsy center (15/18), and directed by neurologists (10/18). A total of 873 (median 59) epilepsy studies, 1,179 evoked fields (of all types), and 1,607 (median 30) research MEG studies were reported. Fourteen of 17 centers serve children (median 35%), but only 5 of 14 sedate children for MEG. All (N = 14) centers record EEG simultaneous with MEG, and 57% used dipole source localization. The median reporting time for epilepsy studies was 12 and 10 days for presurgical mapping studies. Most (12/14) were favorable toward the Clinical Practice Guidelines and "formalized certification" but were against mandating the latter. CONCLUSIONS: A plateau in MEG volumes suggests that MEG has not become a part of the standard of care, and correspondingly, the Clinical Practice Guidelines appeared to have had little impact on clinical practice. The American Clinical Magnetoencephalography Society must continue to engage magnetoencephalographers, potential referrers, and vendors.

Utilization of MEG Among the US Epilepsy Centers: A Survey-Based Appraisal.

PURPOSE: The purported underutilization of magnetoencephalography (MEG) among the USA epilepsy centers has never been studied, and any evidence-based understanding of its magnitude is lacking. METHODS: Two hundred twenty-five National Association of Epilepsy Centers centers (2016) were invited to participate anonymously in a 13-question web-based survey of clinical practice focused on MEG use. RESULTS: On average, centers (N = 70; 61 of which were level 4) reported <6 epileptologists, >7 dedicated epilepsy monitoring unit beds, 206 phase 1 studies, 15 phase 2 studies, 10 direct resections, and 9 indirect resections; 27% owned MEG. On average, 11.2 MEGs per year were ordered for epilepsy localization and 7.6 for any presurgical mapping modalities. Wada test aka the intracarotid sodium amobarbital procedure (ISAP) (43%) and functional MRI (29%) were preferred over MEG (4%) for language mapping. The number of epileptologists and the number of epilepsy monitoring unit beds correlated positively with the most clinical volumes. The centers who own a MEG had surgical volumes significantly higher than those without. The number and complexity of patients as well as the proximity of a MEG were perceived as significant contributors/obstacles to increased MEG use. CONCLUSIONS: Only the centers with larger surgical volumes incorporate MEG regularly in presurgical evaluation of patients with drug-resistant epilepsy. A reversal of the pervasive underutilization of epilepsy surgery can benefit from MEG, but this requires a sustained concerted promotion by the epilepsy and MEG communities.

MEG for Greater Sensitivity and More Precise Localization in Epilepsy.

Magnetoencephalography is the noninvasive measurement of miniscule magnetic fields produced by brain electrical currents, and is used most fruitfully to evaluate epilepsy patients. While other modalities infer brain function indirectly by measuring changes in blood flow, metabolism, and oxygenation, magnetoencephalography measures neuronal and synaptic function directly with submillisecond temporal resolution. The brain's magnetic field is recorded by neuromagnetometers surrounding the head in a helmet-shaped sensor array. Because magnetic signals are not distorted by anatomy, magnetoencephalography allows for a more accurate measurement and localization of brain activities than electroencephalography. Magnetoencephalography has become an indispensable part of the armamentarium at epilepsy centers.

Magnetoencephalography for localizing and characterizing the epileptic focus.

Magnetoencephalography (MEG) is the noninvasive measurement of the miniscule magnetic fields produced by electrical currents flowing in the brain-the same neuroelectric activity that produces the EEG. MEG is one of several diagnostic tests employed in the evaluation of patients with epilepsy, but without the need to expose the patient to any potentially harmful agents. MEG is especially important in those being considered for epilepsy surgery, in whom accurate localization of the epileptic focus is paramount. While other modalities infer brain function indirectly by measuring changes in blood flow, metabolism, oxygenation, etc., MEG, as well as EEG, measures neuronal and synaptic function directly and, like EEG, MEG enjoys submillisecond temporal resolution. The measurement of magnetic fields provides information not only about the amplitude of the current but also its orientation. MEG picks up the magnetic field from neuromagnetometers surrounding the head in a helmet-shaped array of sensors. Clinical whole-head systems currently have 200-300 magnetic sensors, thereby offering very high resolution. The magnetic signals are not distorted by anatomy, because magnetic susceptibility is the same for all tissues, including the skull. Hence, MEG allows for a more accurate measurement and localization of brain activities than does EEG. Because one of its primary strengths is the ability to precisely localize electromagnetic activity within brain areas, MEG results are always coregistered to the patient's MRI. When combined in this way with structural imaging, it has been called magnetic source imaging (MSI), but MEG is properly understood as a clinical neurophysiologic diagnostic test. Signal processing and clinical interpretation in magnetoencephalography require sophisticated noise reduction and computerized mathematical modeling. Technological advances in these areas have brought MEG to the point where it is now part of routine clinical practice. MEG has become an indispensable part of the armamentarium at epilepsy centers where MEG laboratories are located, especially when patients are MRI-negative or where results of other structural and functional tests are not entirely concordant.

Filtering of neurophysiologic signals.

Clinical neurophysiologic signals cover a broad range of frequencies. Filters help to emphasize waveforms that are of clinical or research interest and to mold their frequency characteristics to suit the purpose of the investigation. Some frequency content is obvious and well known, such as the alpha rhythm (8-11Hz) or spindles (12-14Hz) in the EEG. Other frequencies are not initially discriminable from background activity and require filtering in order to examine them, such as high-frequency oscillations (80-500Hz) in EEG and brainstem auditory evoked potentials (100-3000Hz). Often used to mitigate the effects of background noise or artifact, filters can be used specifically to attenuate unwanted frequencies, such as mains interference (50 or 60Hz) and electrode offset potential (<0.1Hz). For digital instrumentation, an antialiasing filter (below Nyquist) is always needed prior to sampling by the analog-to-digital converter. Once the signals are in the digital realm, sophisticated filtering operations can be carried out post hoc; but in order not to be misled, the neurophysiologist must always bear in mind the effect of filtering on the physiological waveform.

Electrical safety.

Since the purpose of clinical neurophysiology testing is to record the electrical activity of the nervous system, and often to electrically stimulate the peripheral or central nervous system (for evoked potentials, nerve conduction studies, etc.), these tests by their very nature demand an excellent electrical connection to the patient. This direct electrical connection by definition puts the patient at increased risk of electrical shock. When patients suffer from other nonneurological disorders that also require equipment to be attached to or inserted into their body, the additional and more direct electrical pathways to the heart make them even more vulnerable, especially when undergoing monitoring in the operating room or intensive care unit. Although we depend on the hospital's construction and utilities to follow appropriate regulations (the National Electrical Code in the United States) and on the vendors to sell only safe equipment (approved by the Food and Drug Administration in the United States), there may exist combinations of equipment and connections that put the patient at risk of injurious or fatal electrical shock. Regular testing and safe practices, informed by a scientific understanding of the risks, are the responsibilities of the healthcare providers in order to protect the patient from harm from electricity.

Multimodal noninvasive evaluation in MRI-negative operculoinsular epilepsy.

OBJECTIVE: Presurgical evaluation of patients with operculoinsular epilepsy and negative MRI presents major challenges. Here the authors examined the yield of noninvasive modalities such as voxel-based morphometric MRI postprocessing, FDG-PET, subtraction ictal SPECT coregistered to MRI (SISCOM), and magnetoencephalography (MEG) in a cohort of patients with operculoinsular epilepsy and negative MRI. METHODS: Twenty-two MRI-negative patients were included who had focal ictal onset from the operculoinsular cortex on intracranial EEG, and underwent focal resection limited to the operculoinsular cortex. MRI postprocessing was applied to presurgical T1-weighted volumetric MRI using a morphometric analysis program (MAP). Individual and combined localization yields of MAP, FDG-PET, MEG, and SISCOM were compared with the ictal onset location on intracranial EEG. Seizure outcomes were reported at 1 year and 2 years (when available) using the Engel classification. RESULTS: Ten patients (45.5%, 10/22) had operculoinsular abnormalities on MAP; 5 (23.8%, 5/21) had operculoinsular hypometabolism on FDG-PET; 4 (26.7%, 4/15) had operculoinsular hyperperfusion on SISCOM; and 6 (30.0%, 6/20) had an MEG cluster (3 tight, 3 loose) within the operculoinsular cortex. The highest yield of a 2-test combination was 59.1%, seen with MAP and SISCOM, followed by 54.5% with MAP and FDG-PET, and also 54.5% with MAP and MEG. The highest yield of a 3-test combination was 68.2%, seen with MAP, MEG, and SISCOM. The yield of the 4-test combination remained at 68.2%. When all other tests were negative or nonlocalizing, unique information was provided by MAP in 5, MEG in 1, SISCOM in 2, and FDG-PET in none of the patients. One-year follow-up was available in all patients, and showed 11 Engel class IA, 4 class IB, 4 class II, and 3 class III/IV. Two-year follow-up was available in 19 patients, and showed 9 class IA, 3 class IB, 1 class ID, 3 class II, and 3 class III/IV. CONCLUSIONS: This study highlights the individual and combined values of multiple noninvasive modalities for the evaluation of nonlesional operculoinsular epilepsy. The 3-test combination of MAP, MEG, and SISCOM represented structural, interictal, and ictal localization information, and constituted the highest yield. MAP showed the highest yield of unique information when other tests were negative or nonlocalizing.

Assessment of the Utility of Ictal Magnetoencephalography in the Localization of the Epileptic Seizure Onset Zone.

Importance: Literature on ictal magnetoencephalography (MEG) in clinical practice and the relationship to other modalities is limited because of the brevity of routine studies. Objective: To investigate the utility and reliability of ictal MEG in the localization of the epileptogenic zone. Design, Setting, and Participants: A retrospective medical record review and prospective analysis of a novel ictal rhythm analysis method was conducted at a tertiary epilepsy center with a wide base of referrals for epilepsy surgery evaluation and included consecutive cases of patients who experienced epileptic seizures during routine MEG studies from March 2008 to February 2012. A total of 377 studies screened. Data were analyzed from November 2011 to October 2015. Main Outcomes and Measures: Presurgical workup and interictal and ictal MEG data were reviewed. The localizing value of using extended-source localization of a narrow band identified visually at onset was analyzed. Results: Of the 44 included patients, the mean (SD) age at the time of recording was 19.3 (14.9) years, and 25 (57%) were male. The mean duration of recording was 51.2 minutes. Seizures were provoked by known triggers in 3 patients and were spontaneous otherwise. Twenty-five patients (57%) had 1 seizure, 6 (14%) had 2, and 13 (30%) had 3 or more. Magnetoencephalography single equivalent current dipole analysis was possible in 29 patients (66%), of whom 8 (28%) had no clear interictal discharges. Sublobar concordance between ictal and interictal dipoles was seen in 18 of 21 patients (86%). Three patients (7%) showed clear ictal MEG patterns without electroencephalography changes. Ictal MEG dipoles correlated with the lobe of onset in 7 of 8 patients (88%) who underwent intracranial electroencephalography evaluations. Reasons for failure to identify ictal dipoles included diffuse or poor dipolar ictal patterns, no MEG changes, and movement artifact. Resection of areas containing a minimum-norm estimate of a narrow band at onset, not single equivalent current dipole, was associated with sustained seizure freedom. Conclusions and Significance: Ictal MEG data can provide reliable localization, including in cases that are difficult to localize by other modalities. These findings support the use of extended-source localization for seizures recorded during MEG.