Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of Finland.

The genetics of autosomal recessive intellectual disability (ARID) has mainly been studied in consanguineous families, however, founder populations may also be of interest to study intellectual disability (ID) and the contribution of ARID. Here, we used a genotype-driven approach to study the genetic landscape of ID in the founder population of Finland. A total of 39 families with syndromic and non-syndromic ID were analyzed using exome sequencing, which revealed a variant in a known ID gene in 27 families. Notably, 75% of these variants in known ID genes were de novo or suspected de novo (64% autosomal dominant; 11% X-linked) and 25% were inherited (14% autosomal recessive; 7% X-linked; and 4% autosomal dominant). A dual molecular diagnosis was suggested in two families (5%). Via additional analysis and molecular testing, we identified three cases with an abnormal molecular karyotype, including chr21q22.12q22.2 uniparental disomy with a mosaic interstitial 2.7 Mb deletion covering DYRK1A and KCNJ6. Overall, a pathogenic or likely pathogenic variant was identified in 64% (25/39) of the families. Last, we report an alternate inheritance model for 3 known ID genes (UBA7, DDX47, DHX58) and discuss potential candidate genes for ID, including SYPL1 and ERGIC3 with homozygous founder variants and de novo variants in POLR2F and DNAH3. In summary, similar to other European populations, de novo variants were the most common variants underlying ID in the studied Finnish population, with limited contribution of ARID to ID etiology, though mainly driven by founder and potential founder variation in the latter case.

Heterogeneous genetic patterns in bilateral perisylvian polymicrogyria: insights from a Finnish family cohort.

Bilateral perisylvian polymicrogyria is the most common form of regional polymicrogyria within malformations of cortical development, constituting 20% of all malformations of cortical development. Bilateral perisylvian polymicrogyria is characterized by an excessive folding of the cerebral cortex and abnormal cortical layering. Notable clinical features include upper motoneuron dysfunction, dysarthria and asymmetric quadriparesis. Cognitive impairment and epilepsy are frequently observed. To identify genetic variants underlying bilateral perisylvian polymicrogyria in Finland, we examined 21 families using standard exome sequencing, complemented by optical genome mapping and/or deep exome sequencing. Pathogenic or likely pathogenic variants were identified in 5/21 (24%) of families, of which all were confirmed as de novo. These variants were identified in five genes, i.e. DDX23, NUS1, SCN3A, TUBA1A and TUBB2B, with NUS1 and DDX23 being associated with bilateral perisylvian polymicrogyria for the first time. In conclusion, our results confirm the previously reported genetic heterogeneity of bilateral perisylvian polymicrogyria and underscore the necessity of more advanced methods to elucidate the genetic background of bilateral perisylvian polymicrogyria.

Optical genome mapping unveils hidden structural variants in neurodevelopmental disorders.

While short-read sequencing currently dominates genetic research and diagnostics, it frequently falls short of capturing certain structural variants (SVs), which are often implicated in the etiology of neurodevelopmental disorders (NDDs). Optical genome mapping (OGM) is an innovative technique capable of capturing SVs that are undetectable or challenging-to-detect via short-read methods. This study aimed to investigate NDDs using OGM, specifically focusing on cases that remained unsolved after standard exome sequencing. OGM was performed in 47 families using ultra-high molecular weight DNA. Single-molecule maps were assembled de novo, followed by SV and copy number variant calling. We identified 7 variants of interest, of which 5 (10.6%) were classified as likely pathogenic or pathogenic, located in BCL11A, OPHN1, PHF8, SON, and NFIA. We also identified an inversion disrupting NAALADL2, a gene which previously was found to harbor complex rearrangements in two NDD cases. Variants in known NDD genes or candidate variants of interest missed by exome sequencing mainly consisted of larger insertions (> 1kbp), inversions, and deletions/duplications of a low number of exons (1-4 exons). In conclusion, in addition to improving molecular diagnosis in NDDs, this technique may also reveal novel NDD genes which may harbor complex SVs often missed by standard sequencing techniques.

Sensitivity and specificity of seizure-onset zone estimation by ictal magnetoencephalography.

PURPOSE: Ictal video-electroencephalography (EEG) is commonly used to establish ictal onset-zone location. Recently software development has enabled systematic studies of ictal magnetoencephalography (MEG). In this article, we evaluate the ability of ictal MEG signals to localize the seizure-onset zone. METHODS: Twenty-six patients underwent ictal MEG and epilepsy surgery. Prediction of seizure-onset zone by ictal and interictal MEG was retrospectively compared with ictal-onset area found by intracranial EEG in 12 patients. The specificity and sensitivity of the prediction were calculated at hemisphere-lobe (HL) and at hemisphere-lobe-surface (HLS) levels. KEY FINDINGS: The sensitivity of ictal MEG source localization was 0.958 on HL and 0.706 on HLS levels, and its specificity was 0.900 on HL and 0.731 on HLS levels. The interictal MEG dipole cluster, defined as >10 dipoles on one lobar surface, had sensitivity of 0.400 and specificity of 0.769. Ictal MEG was equally sensitive and specific on dorsolateral and nondorsolateral neocortical surfaces up to a depth of 4 cm from the scalp. SIGNIFICANCE: Sources of ictal-onset MEG signals and interictal dipole clusters are essentially equally specific in estimation of the ictal-onset zone on lobar surface resolution, but ictal MEG is more sensitive. On the lobe resolution, ictal MEG estimates ictal-onset zone with high sensitivity and specificity.

The effect of surgery in encephalopathy with electrical status epilepticus during sleep.

PURPOSE: We analyzed clinical and electroencephalography (EEG) outcomes of 13 patients with pharmacoresistant encephalopathy with electrical status epilepticus during sleep (ESES) following epilepsy surgery. METHODS: All patients had symptomatic etiology of ESES and preoperative neuropsychological deterioration. Ten patients had daily atypical absences. Clinical outcome was assessed at 6 months and at 2 years after surgery. Clinical and EEG data were reviewed retrospectively. The spike propagation pattern and area and source strength in source montage were analyzed from preoperative and postoperative EEG studies. KEY FINDINGS: Preoperative sleep EEG showed electrical status epilepticus during sleep (SES) with one-way interhemispheric propagation in nine patients and with two-way interhemispheric propagation in four. The age of the patients at the time of surgery ranged from 3.6-9.9 years. Focal resection (two patients) or hemispherotomy (one patient with postoperative EEG) either terminated SES or restricted the discharge to one region. Either reduced SES propagation area or source strength was found in four of eight callosotomy patients with postoperative EEG. Of patients who had seizures preoperatively, Engel class I-II seizure outcome was observed in two of three children after focal resection or hemispherotomy and in two of eight children after callosotomy. None of these patients with Engel class I-II outcome had SES with two-way interhemispheric propagation on preoperative EEG. Cognitive deterioration was halted postoperatively in all except one patient. Cognitive catch-up of more than 10 IQ points was seen in three patients, all of whom had shown a first measured IQ of >75. SIGNIFICANCE: Patients with pharmacoresistant ESES based on symptomatic etiology may benefit from resective surgery or corpus callosotomy regarding both seizure outcome and cognitive prognosis.

Neural correlates of late positivities associated with infrequent visual events and response errors.

The P3 response has been one of the most extensively studied event-related potential (ERP) components. Still, the exact functional role and cortical basis of P3 has remained unsettled. To explore the cortical processes underlying the generation of late positivities, we recorded the activation evoked by frequent Go and infrequent NoGo stimuli and correct versus erroneous responses using combined magnetoencephalography (MEG) and ERP measurements during a visual Go/NoGo task. The stimulus-locked signals in the ERP channels revealed an enhanced negative N2 and a prominent late positive component (LPC) after the complex NoGo stimuli associated with successfully withheld responses. The response-locked ERP signals revealed error-related negativity (ERN) and positivity (Pe) after erroneous responses. The positive LPC and Pe components were coupled with functionally and temporally comparable MEG signals. This MEG activation detected during the positive components was localized bilaterally in the posterior temporal cortex. In the response-locked averages, the temporal activity was enhanced around 200 ms after a commission of an error. In the stimulus-locked averages, the activation was also enhanced after infrequent NoGo stimuli around 500 ms after stimulus onset and delayed about 80 ms for the initially miscategorized NoGo stimuli accompanied by erroneous response. The results suggest that the cortical correlates of Pe are not specifically related to commission of an error, but both the LPC and Pe components, and bilateral temporal cortices, are more generally involved in stimulus-driven attentional processing evoked by unexpected stimuli. The negative ERP components evoked by NoGo stimuli (N2) and erroneous responses (ERN) were found to be associated with partly non-overlapping neural sources.

Long-term outcome of 32 children with encephalopathy with status epilepticus during sleep, or ESES syndrome.

PURPOSE: To prospectively evaluate the efficacy of drug treatment and long-term cognitive outcome in children with encephalopathy with status epilepticus during sleep (ESESS). METHODS: Thirty-two children were diagnosed and prospectively followed up for at least 3 years at our unit between 1991 and 2007. Twenty-seven children were included in the prospective treatment study with valproate (VPA) and 17 with VPA combined with ethosuximide (ESM). Treatment response of disappearance of electrical status epilepticus during sleep (SES) was documented with overnight EEG recordings. Neuropsychological follow up for at least 5 years was available in 18 patients. RESULTS: Six children had atypical rolandic (AR) epilepsy, nine Landau-Kleffner syndrome (LKS), and 17 symptomatic epilepsy. Before ESESS, 20 children were cognitively normal. Prospective treatment with VPA and ESM was effective in 3 of the 17 children (18%) treated. Abolition of SES with drug treatment was observed in 16 patients. In all, 10 children (31%), 4 with AR (67%), 3 with LKS (33%), and 3 with symptomatic etiology (19%), including 9 with treatment response regained the pre-ESESS cognitive level. Unfavorable cognitive outcome was predicted by younger age at ESESS diagnosis, lower IQ at the time of the diagnosis, and no response to drug treatment when compared with those with favorable cognitive outcome. Eight of the 16 nonresponders underwent epilepsy surgery. DISCUSSION: Treatment response with VPA combined with ESM was observed more often than with other drug combinations. Most children with ESESS experienced permanent cognitive impairment. Cognitive outcome depends on treatment response on electroencephalography (EEG) and seizures, and on underlying etiology.

Neural processing of spoken words in specific language impairment and dyslexia.

Young adults with a history of specific language impairment (SLI) differ from reading-impaired (dyslexic) individuals in terms of limited vocabulary and poor verbal short-term memory. Phonological short-term memory has been shown to play a significant role in learning new words. We investigated the neural signatures of auditory word recognition and word repetition in young adults with SLI, dyslexia and normal language development using magnetoencephalography. The stimuli were 7-8 letter spoken real words and pseudo-words. They evoked a transient peak at 100 ms (N100m) followed by longer-lasting activation peaking around 400 ms (N400m) in the left and right superior temporal cortex. Both word repetition (first vs. immediately following second presentation) and lexicality (words vs. pseudowords) modulated the N400m response. An effect of lexicality was detected about 400 ms onwards as activation culminated for words but continued for pseudo-words. This effect was more pronounced in the left than right hemisphere in the control subjects. The left hemisphere lexicality effect was also present in the dyslexic adults, but it was non-significant in the subjects with SLI, possibly reflecting their limited vocabulary. The N400m activation between 200 and 700 ms was attenuated by the immediate repetition of words and pseudo-words in both hemispheres. In SLI adults the repetition effect evaluated at 200-400 ms was abnormally weak. This finding suggests impaired short-term maintenance of linguistic activation that underlies word recognition. Furthermore, the size of the repetition effect decreased from control subjects through dyslexics to SLIs, i.e. when advancing from milder to more severe language impairment. The unusually rapid decay of speech-evoked activation could have a detrimental role on vocabulary growth in children with SLI.

Interictal magnetoencephalography in parietal lobe epilepsy - Comparison of equivalent current dipole and beamformer (SAMepi) analysis.

OBJECTIVE: To evaluate a novel analysis method (SAMepi) in the localization of interictal epileptiform magnetoencephalographic (MEG) activity in parietal lobe epilepsy (PLE) patients in comparison with equivalent current dipole (ECD) analysis. METHODS: We analyzed the preoperative interictal MEG of 17 operated PLE patients utilizing visual analysis and: (1) ECD with a spherical conductor model; (2) ECD with a boundary element method (BEM) conductor model; and (3) SAMepi - a kurtosis beamformer method. Localization results were compared between the three methods, to the location of the resection and to the clinical outcome. RESULTS: Fourteen patients had an epileptiform finding in the visual analysis; SAMepi detected spikes in 11 of them. A unifocal finding in both the ECD and in the SAMepi analysis was associated with a better chance of seizure-freedom (p = 0.02). There was no significant difference in the distances from the unifocal MEG localizations to the nearest border of the resection between the different analysis methods. CONCLUSIONS: Localizations of unifocal interictal spikes detected by SAMepi did not significantly differ from the conventional ECD localizations. SIGNIFICANCE: SAMepi - a novel semiautomatic analysis method - is useful in localizing interictal epileptiform MEG activity in the presurgical evaluation of parietal lobe epilepsy patients.

Magnetoencephalography in Landau-Kleffner syndrome.

Magnetoencephalography (MEG) detects weak magnetic fields outside the head. Spikes generated on the perisylvian convexity are detected only by electroencephalography (EEG), whereas spikes with intrasylvian generators are selectively seen by MEG. Generators of MEG and EEG spikes are determined using equivalent current dipoles (ECDs) that represent local cortical activity in parallel pyramidal neurons. MEG localizes cortical spike generators with a 1-2-cm spatial accuracy, and with a millisecond time resolution. This allows tracking of neural activity over successive synaptic connections in the cortical network. Both EEG and MEG are necessary for comprehensive spatial and temporal description of perisylvian epileptic networks in the Landau-Kleffner syndrome (LKS). MEG studies suggest that in more than 80% of LKS patients, the bilateral epileptic discharges are generated in the auditory- and language-related perisylvian cortex. Approximately 20% of children with LKS children have a unilateral perisylvian pacemaker that triggers secondary bilateral synchrony of spikes. This 20% may regain considerable language skills after multiple subpial transections (MSTs) of the pacemaker area. Outcome data of a few surgery patients suggest an indispensable role of MEG when planning the most efficient therapy for patients with LKS.

Fine tuning the correlation limit of spatio-temporal signal space separation for magnetoencephalography.

Head, jaw and tongue movements contribute to speech artifacts in magnetoencephalography (MEG). Their sources lay close to MEG sensors, therefore, the spatio-temporal signal space separation method (tSSS), specifically suppressing nearby artifacts, can be used for speech artifact suppression. After data reconstruction by signal space separation (referred as SSS), tSSS identifies artifacts by their correlated temporal behavior inside and outside the sensor helmet. The artifacts to be eliminated are thresholded by the quantitative level of this correlation determined by correlation limit (CL). Unnecessarily high CL value may result in suboptimal interference suppression. We evaluated the performance of tSSS with different CLs on MEG data containing speech artifacts. MEG was recorded with 204 planar gradiometers and 102 magnetometers in two subjects counting aloud. The recorded data were processed by tSSS using CLs 0.98, 0.8 and 0.6, and traces were compared. The speech artifact was increasingly suppressed with decreasing CL, but sufficient suppression was achieved at different CL in each subject. Alpha rhythm was not suppressed with CL 0.98 or 0.8; some amplitude reduction with CL 0.6 occurred in one subject. The tSSS is a robust tool suppressing MEG artifacts. It can be fine tuned for challenging artifacts which, after insufficient rejection might resemble brain signals.

A simple magnetoencephalographic auditory paradigm may aid in confirming left-hemispheric language dominance in epilepsy patients.

OBJECTIVE: The intracarotid amobarbital procedure (IAP) is the current "gold standard" in the preoperative assessment of language lateralization in epilepsy surgery candidates. It is, however, invasive and has several limitations. Here we tested a simple noninvasive language lateralization test performed with magnetoencephalography (MEG). METHODS: We recorded auditory MEG responses to pairs of vowels and pure tones in 16 epilepsy surgery candidates who had undergone IAP. For each individual, we selected the pair of planar gradiometer sensors with the strongest N100m response to vowels in each hemisphere and-from the vector sum of signals of this gradiometer pair-calculated the vowel/tone amplitude ratio in the left (L) and right (R) hemisphere and, subsequently, the laterality index: LI = (L-R)/(L+R). In addition to the analysis using a single sensor pair, an alternative analysis was performed using averaged responses over 18 temporal sensor pairs in both hemispheres. RESULTS: The laterality index did not correlate significantly with the lateralization data obtained from the IAP. However, an MEG pattern of stronger responses to vowels than tones in the left hemisphere and stronger responses to tones than vowels in the right hemisphere was associated with left-hemispheric language dominance in the IAP in all the six patients who showed this pattern. This results in a specificity of 100% and a sensitivity of 67% of this MEG pattern in predicting left-hemispheric language dominance (p = 0.01, Fisher's exact test). In the analysis using averaged responses over temporal channels, one additional patient who was left-dominant in IAP showed this particular MEG pattern, increasing the sensitivity to 78% (p = 0.003). SIGNIFICANCE: This simple MEG paradigm shows promise in feasibly and noninvasively confirming left-hemispheric language dominance in epilepsy surgery candidates. It may aid in reducing the need for the IAP, if the results are confirmed in larger patient samples.

Sodium Channel SCN3A (NaV1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development.

Channelopathies are disorders caused by abnormal ion channel function in differentiated excitable tissues. We discovered a unique neurodevelopmental channelopathy resulting from pathogenic variants in SCN3A, a gene encoding the voltage-gated sodium channel NaV1.3. Pathogenic NaV1.3 channels showed altered biophysical properties including increased persistent current. Remarkably, affected individuals showed disrupted folding (polymicrogyria) of the perisylvian cortex of the brain but did not typically exhibit epilepsy; they presented with prominent speech and oral motor dysfunction, implicating SCN3A in prenatal development of human cortical language areas. The development of this disorder parallels SCN3A expression, which we observed to be highest early in fetal cortical development in progenitor cells of the outer subventricular zone and cortical plate neurons and decreased postnatally, when SCN1A (NaV1.1) expression increased. Disrupted cerebral cortical folding and neuronal migration were recapitulated in ferrets expressing the mutant channel, underscoring the unexpected role of SCN3A in progenitor cells and migrating neurons.

Current clinical magnetoencephalography practice across Europe: Are we closer to use MEG as an established clinical tool?

PURPOSE: This comprehensive survey aims at characterizing the current clinical use of magnetoencephalography (MEG) across European MEG centres. METHODS: Forty-four MEG centres across Europe were contacted in May 2015 via personalized e-mail to contribute to survey. The web-based survey was available on-line for 1 month and the MEG centres that did not respond were further contacted to maximize participation. RESULTS: Among the 57% of responders, 12 centres from 10 different countries reported to use MEG for clinical applications. A total of 524 MEG investigations were performed in 2014 for the pre-surgical evaluation of epilepsy, while in the same period 244 MEG investigations were performed for pre-surgical functional brain mapping. Seven MEG centres located in different European countries performed ≥50 MEG investigations for epilepsy mapping in 2014, both in children and adults. In those centres, time from patient preparation to MEG data reporting tends to be lower than those investigating a lower annual number of patients. CONCLUSION: This survey demonstrates that there is in Europe an increasing and widespread expertise in the field of clinical MEG. These findings should serve as a basis to harmonize clinical MEG procedures and promote the clinical added value of MEG across Europe. MEG should now be considered in Europe as a mature clinical neurophysiological technique that should be used routinely in two specific clinical indications, i.e, the pre-surgical evaluation of refractory focal epilepsy and functional brain mapping.

MEG versus EEG: influence of background activity on interictal spike detection.

The comparative sensitivity of EEG and magnetoencephalography (MEG) in the visual detection of focal epileptiform activity in simultaneous interictal sleep recordings were investigated. The authors examined 14 patients aged 3.5 to 17 years with localization-related epilepsy. Simultaneous 122-channel whole-head MEG and 33-channel EEG were recorded for 20 to 40 minutes during spontaneous sleep. The EEG and MEG data were separated and four blinded independent reviewers marked the presence and timing of epileptic discharges (ED) in the 28 data segments. EEG and MEG data were matched and spikes identified by at least three reviewers were classified in three categories according to the following criteria: type 1 MEG > EEG, type 2 EEG > MEG (type 1/2: difference of three or more raters), and type 3 EEG = MEG (three or more raters each). The presence of simultaneous sleep changes was visually determined for every single EEG-segment. Spikes with high spatiotemporal correlation were averaged and subjected to single dipole analysis of peak activity in EEG. Out of 4704 marked patterns, 1387 spikes fulfilled the above criteria. In fact, more spikes were unique to MEG (689) than to EEG (136) and to the combination of both modalities (562). ED were detected predominantly by MEG in eight patients and by EEG in two patients. The presence of vertex waves and spindles lead to a significantly higher number of spikes identified only in MEG. Averaging of type 1 spikes produced clear spike activity in EEG in 9 of 12 cases. On the contrary, only 2 of 10 type 2 spikes were visible in MEG after averaging. Dipoles of spikes visible in MEG showed a more tangential orientation compared with more radial dipoles of type 2 spikes. Spike characteristics, e.g., dipole orientation, are a key factor for a sole EEG representation. Exclusive MEG detection is more likely influenced by overlapping background activity in EEG. Because MEG is indifferent to radial activity, i.e., sleep changes, a higher ratio of spikes unique to MEG compared with EEG is detected in the case of overlapping sleep changes.

Virtual MEG Helmet: Computer Simulation of an Approach to Neuromagnetic Field Sampling.

Head movements during an MEG recording are commonly considered an obstacle. In this computer simulation study, we introduce an approach, the virtual MEG helmet (VMH), which employs the head movements for data quality improvement. With a VMH, a denser MEG helmet is constructed by adding new sensors corresponding to different head positions. Based on the Shannon's theory of communication, we calculated the total information as a figure of merit for comparing the actual 306-sensor Elekta Neuromag helmet to several types of the VMH. As source models, we used simulated randomly distributed source current (RDSC), simulated auditory and somatosensory evoked fields. Using the RDSC model with the simulation of 360 recorded events, the total information (bits/sample) was 989 for the most informative single head position and up to 1272 for the VMH (addition of 28.6%). Using simulated AEFs, the additional contribution of a VMH was 12.6% and using simulated SEF only 1.1%. For the distributed and bilateral sources, a VMH can provide a more informative sampling of the neuromagnetic field during the same recording time than measuring the MEG from one head position. VMH can, in some situations, improve source localization of the neuromagnetic fields related to the normal and pathological brain activity. This should be investigated further employing real MEG recordings.

Two-year follow-up of intelligence after pediatric epilepsy surgery.

Research findings concerning cognitive effects of pediatric epilepsy surgery form an important basis for decisions about surgery. However, most follow-up studies have been of limited duration. In this study, a 2-year follow-up of intelligence was undertaken. Risk factors were analyzed. Included were 38 patients aged 3 to 17 years. Surgery was left in 19 patients and right in 19 patients. Types of surgery included temporal lobe resection (n = 23), extratemporal or multilobar resection (n = 8), and hemispherectomy (n = 7). The Wechsler Scales of Intelligence were administered presurgically, 6 months postsurgically, and 2 years postsurgically. No significant change in verbal or performance intelligence quotient (IQ) was demonstrated on a group level. Lateralization, type of surgery, age at surgery, sex, and presurgical IQ did not affect outcome. Across assessments, IQ scores of left-hemisphere patients were lower than those of right-hemisphere patients. Scores of patients in the hemispherectomy group were lower than those of the extratemporal or multilobar resection group, which were lower than the temporal lobe resection group. Scores improved significantly in six patients and deteriorated in seven. In conclusion, epilepsy surgery in children and adolescents does not, in general, have a significant impact on cognitive development in a 2-year perspective. In individual patients, poor seizure control and extensive surgery for Rasmussen's encephalitis were related to a deterioration of IQ.

Magnetoencephalography (MEG) and other neurophysiological investigations.

Cortical generators of epileptic and certain physiological activity can be localized noninvasively by magnetoencephalography (MEG). MEG detects weak magnetic fields produced by the postsynaptic currents of pyramidal cortical cells in sulcal walls. Unlike EEG, MEG signals are not distorted by edema or bone defects, and unlike fMRI, abnormal hemodynamics do not alter the MEG. The patient's head is centered inside a helmet housing over a hundred magnetic field sensors. Cortical generators of MEG signals are determined with a useful spatial resolution and an excellent time resolution, which enable tracking of brain activity in successive points of, for example, an epileptic network. MEG sources can be co-registered and visualized on magnetic resonance images (MRI). MEG is highly sensitive for the detection of interictal epileptic discharges, and present techniques allow some degree of head movements enabling ictal recordings also. MEG is also useful for localizing the somatosensory, visual, and language areas before tailored surgery in the vicinity of eloquent cortex. In conjunction with other noninvasive modalities MEG provides nonredundant data in one-third of epilepsy surgery patients. Clinical MEG utilization is mainly focused on presurgical localization of the epileptogenic zone and eloquent cortex in epilepsy surgery candidates, including patients with Landau-Kleffner syndrome. However, MEG is also an excellent noninvasive tool to study the source distribution in childhood epilepsy syndromes and epileptic encephalopathies.

Quantifying the contribution of video in combined video-magnetoencephalographic ictal recordings of epilepsy patients.

INTRODUCTION: Magnetoencephalography (MEG) measures magnetic fields generated by neuronal currents. MEG is complementary to EEG. Considerable body of evidence indicates that ictal MEG recordings can provide useful information for pre-surgical evaluation of epilepsy patients alongside the more established long-term ictal video-EEG. Ictal MEG is recorded in some epilepsy surgery centers. However, a wider adoption of ictal MEG is hampered by lack of tools for synchronized video-MEG recording similar to those of video-EEG. METHODS: We have augmented MEG with a synchronized behavioral video-recording system. To estimate its additional value in ictal recordings, we retrospectively analyzed recordings of 10 epilepsy patients with and without the video. RESULTS: In six patients out of ten, adding the video substantially changed the resulting interpretations. In all six cases the effect was considerable: the number of detected seizures changed by more than 50%. CONCLUSIONS: Synchronized video and audio recording capabilities are important for effective ictal MEG recordings of epilepsy patients.

Functional plasticity of the motor cortical structures demonstrated by navigated TMS in two patients with epilepsy.

BACKGROUND: Recently, navigated transcranial magnetic stimulation (nTMS) has been suggested to be useful in preoperative functional localization of motor cortex in patients having tumors close to the somatomotor cortex. Resection of tumors in anatomically predicted eloquent areas without adverse effects have emphasized functional plasticity elicited by intracranial pathology. OBJECTIVE: To describe functional plasticity of motor cortex indicated by nTMS in two patients with epilepsy. METHODS: nTMS, functional MRI (fMRI), diffusion-tensor (DT)-tractography and magnetoencephalography (MEG) were utilized to preoperatively localize motor cortical areas in the workup for epilepsy surgery. The localizations were compared with each other, with the cortical anatomical landmarks, and in one patient with invasive electrical cortical stimulation (ECS). RESULTS: In two out of 19 studied patients, nTMS identified motor cortical sites that differed from those indicated by anatomical landmarks. In one patient, nTMS activated preferentially premotor cortex rather than pathways originating from the precentral gyrus. MEG and fMRI localizations conformed with nTMS whereas ECS localized finger motor function into the precentral gyrus. Resection of the area producing motor responses in biphasic nTMS did not produce a motor deficit. In the other patient, nTMS indicated abnormal ipsilateral hand motor cortex localization and confirmed the functionality of aberrant motor cortical representations of the left foot also indicated by fMRI and DT-tractography. CONCLUSION: nTMS may reveal the functional plasticity and shifts of motor cortical function. Epileptic foci may modify cortical inhibition and the nTMS results. Therefore, in some patients with epilepsy, the nTMS results need to be interpreted with caution with regard to surgical planning.