Characterizing magnetoencephalographic spike sources in children with tuberous sclerosis complex

PURPOSE: Tuberous sclerosis complex (TSC) often causes medically intractable seizures. Magnetoencephalography (MEG) localizes epileptiform discharges. To evaluate the use of MEG spike sources (MEGSSs) for localizing epileptic zones in TSC patients, we characterized MEGSSs and correlated them to EEG and magnetic resonance imaging (MRI) results. METHODS: We analyzed data from seven children who underwent prolonged video-EEG, MEG, and MRI. We classified MEGSSs as clusters (six or more spike sources, 1 cm between sources regardless of number of sources). RESULTS: A single, unilateral cluster with additional scatters occurred in two patients; these predominantly lateralized dipoles correlated to prominent tubers on MRI and ictal/interictal EEG zones. Bilateral clusters with scatters existed in two patients; cluster locations partly overlapped multiple prominent tubers. These patients also had bilateral or diffuse interictal discharges, bilateral or generalized seizures, and changing seizure types and EEG findings. Only bilateral scatters occurred in three patients; scatters partly overlapped EEG interictal/ictal-onset regions; one patient had coexisting generalized seizures. In one patient with equally bilateral scatters, scatters overlapped a prominent tuber and interictal/ictal-onset zones in the right frontal region. CONCLUSIONS: MEG contributes to information from EEG and MRI for localizing epileptogenic zones in children with TSC. A single cluster with scatters in a unilateral hemisphere predicts a primary epileptogenic zone or hemisphere; bilateral or multiple clusters indicate bilateral primary or potential epileptogenic zones; and bilateral scatters without clusters may indicate epileptogenic zones that are hidden within extensive areas of scattered MEGSSs.     

Magnetoencephalography using total intravenous anesthesia in pediatric patients with intractable epilepsy: lesional vs nonlesional epilepsy

Purpose: Magnetoencephalography (MEG) provides source localization of interictal spikes. We use total intravenous anesthesia (TIVA) with propofol to immobilize uncooperative children. We evaluate the effect of TIVA on interictal spikes in children who have intractable epilepsy with or without MRI lesions. Methods: We studied 28 children (3–14 years; mean, 6.6). We intravenously administered propofol (30–60 μg/kg/min) to record MEG with simultaneous EEG. We evaluated MEG spike sources (MEGSSs). We compared spikes on simultaneous EEG under TIVA with those on scalp video-EEG without TIVA. Results: There was a significant decrease in frequent spikes (10 patients, 36%) on simultaneous EEG under TIVA compared to those (22 patients, 79%) on scalp video-EEG without TIVA (P < 0.01). MEGSSs were present in 21 (75%) of 28 patients. Clustered MEGSSs occurred in 15 (83%) of 18 lesional patients but in 3 (30%) of 10 nonlesional patients (P < 0.05). MEGSSs were more frequently absent in nonlesional (6 patients, 60%) than lesional (one patient, 5%) patients (P < 0.01). Thirteen patients with MRI and/or histopathologically confirmed neuronal migration disorder most frequently showed clustered MEGSSs (11 patients, 85%) compared to those of other lesional and nonlesional patients. Conclusion: Propofol-based TIVA reduced interictal spikes on simultaneous EEG. TIVA for MEG still had utility in identifying spike sources in a subset of pediatric patients with intractable epilepsy who were uncooperative and surgical candidates. In lesional patients, MEG under TIVA frequently localized the clustered MEGSSs. Neuronal migration disorders were intrinsically epileptogenic and produced clustered MEGSSs under TIVA. Nonlesional patients often had no MEGSS under TIVA.     

Utility of magnetoencephalography in the evaluation of recurrent seizures after epilepsy surgery

PURPOSE: To study the role of magnetoencephalography (MEG) in the surgical evaluation of children with recurrent seizures after epilepsy surgery. METHODS: We studied 17 children with recurrent seizures after epilepsy surgery using interictal and ictal scalp EEG, intracranial video EEG (IVEEG), MRI, and MEG. We analyzed the location and distribution of MEG spike sources (MEGSSs) and the relationship of MEGSSs to the margins of previous resections and surgical outcome. RESULTS: Clustered MEGSSs occurred at the margins of previous resections within two contiguous gyri in 10 patients (group A), extended spatially from a margin by < or =3 cm in three patients (group B), and were remote from a resection margin by >3 cm in six patients (group C). Two patients had concomitant group A and C clusters. Thirteen patients underwent second surgeries. IVEEG was used in four patients. Six of seven patients with group A MEGSS clusters did not require IVEEG for second surgeries. Follow-up periods ranged from 0.6 to 4.3 years (mean: 2.6 years). Eleven children, including eight who became seizure-free, achieved Engel class I or II. CONCLUSION: Our data demonstrate the utility of MEG for evaluating patients with recurrent seizures after epilepsy surgery. Specific MEGSS cluster patterns delineate epileptogenic zones. Removing cluster regions adjacent to the margins of previous resections, in addition to removing recurrent lesions, achieves favorable surgical outcome. Cluster location and extent identify which patients require IVEEG, potentially eliminating IVEEG for some. Patients with remotely located clusters require IVEEG for accurate assessment and localization of the entire epileptogenic zone.     

MEG predicts outcome following surgery for intractable epilepsy in children with normal or nonfocal MRI findings

PURPOSE: To identify the predictors of postsurgical seizure freedom in children with refractory epilepsy and normal or nonfocal MRI findings. METHODS: We analyzed 22 children with normal or subtle and nonfocal MRI findings, who underwent surgery for intractable epilepsy following extraoperative intracranial EEG. We compared clinical profiles, neurophysiological data (scalp EEG, magnetoencephalography (MEG) and intracranial EEG), completeness of surgical resection and pathology to postoperative seizure outcomes. RESULTS: Seventeen children (77%) had a good postsurgical outcome (defined as Engel class IIIA or better), which included eight (36%) seizure-free children. All children with postsurgical seizure freedom had an MEG cluster in the final resection area. Postsurgical seizure freedom was obtained in none of the children who had bilateral MEG dipole clusters (3) or only scattered dipoles (1). All five children in whom ictal onset zones were confined to < or = 5 adjacent intracranial electrodes achieved seizure freedom compared to three of 17 children with ictal onset zones that extended over >5 electrodes (p = 0.002). None of six children with more than one type of seizure became seizure-free, compared to eight of 16 children with a single seizure type (p = 0.04). Complete resection of the preoperatively localized epileptogenic zone resulted in seizure remission in 63% (5/8) and incomplete resections, in 21% (3/14) (p = 0.06). Age of onset, duration of epilepsy, number of lobes involved in resection, and pathology failed to correlate with seizure freedom. CONCLUSIONS: Surgery for intractable epilepsy in children with normal MRI findings provided good postsurgical outcomes in the majority of our patients. As well, restricted ictal onset zone predicted postoperative seizure freedom. Postoperative seizure freedom was less likely to occur in children with bilateral MEG dipole clusters or only scattered dipoles, multiple seizure types and incomplete resection of the proposed epileptogenic zone. Seizure freedom was most likely to occur when there was concordance between EEG and MEG localization and least likely to occur when these results were divergent.     

Advanced dynamic statistical parametric mapping with MEG in localizing epileptogenicity of the bottom of sulcus dysplasia

Objective

To investigate whether advanced dynamic statistical parametric mapping (AdSPM) using magnetoencephalography (MEG) can better localize focal cortical dysplasia at bottom of sulcus (FCDB).

Atonic variant of benign childhood epilepsy with centrotemporal spikes (atonic-BECTS): a distinct electro-clinical syndrome

Purpose

To describe the clinical and electroencephalographic features, treatment strategies and outcome in a series of children with the atonic variant of benign childhood epilepsy with centrotemporal spikes (atonic-BECTS).

Material and methods

Out of the 148 patients with BECTS reviewed from January 2005 to June 2010 in our Institute, there were seven (5%) with atonic-BECTS. All underwent video EEG, high-resolution magnetic resonance imaging (MRI), neuropsychological evaluation and language assessment. Their progress was followed. In addition to sodium valproate, three were treated with steroids, followed by intravenous immunoglobulin (IVIG) when the seizures relapsed while tapering or after stopping the steroids.

Results

All of the children had earlier onset (mean = 2.4 years), increased frequency and increased duration of focal seizures compared to typical BECTS. Head drop and truncal sway due to axial or axiorhizomelic atonia occurring several times per day or week was the key manifestation. The atonic seizures worsened with carbamazepine in three, clonazepam in two and clobazam in one. When the atypical seizures commenced, some children developed one or more of the following problems: hyperactivity, attention deficit, clumsy gait, and mild cognitive or language dysfunction. Three children became seizure free, one on steroids and the other two on IVIG.

Conclusions

BECTS in children with an early age of onset and frequent and prolonged seizures is more likely to evolve into atonic-BECTS. Carbamazepine and some benzodiazepines may worsen these seizures. Three children became seizure free with immunomodulatory therapy, one on steroids and the other two on IVIG, and had complete resolution of the transient motor and cognitive impairment. Atonic-BECTS needs to be differentiated from Lennox–Gastaut syndrome since it is potentially treatable and children recover with no sequel. Although all the children in this series continued to be on treatment with sodium valproate it is currently undetermined whether they would have required to do so if followed up for an extended period of time.     

Somatomotor mu rhythm amplitude correlates with rigidity during deep brain stimulation in Parkinsonian patients

Objective

Parkinsonian patients have abnormal oscillatory activity within the basal ganglia-thalamocortical circuitry. Particularly, excessive beta band oscillations are thought to be associated with akinesia. We studied whether cortical spontaneous activity is modified by deep brain stimulation (DBS) in advanced Parkinson’s disease and if the modifications are related to the clinical symptoms.

Methods

We studied the effects of bilateral electrical stimulation of subthalamic nucleus (STN) on cortical spontaneous activity by magnetoencephalography (MEG) in 11 Parkinsonian patients. The artifacts produced by DBS were suppressed by tSSS algorithm.

Results

During DBS, UPDRS (Unified Parkinson’s Disease Rating Scale) rigidity scores correlated with 6-10 Hz and 12-20 Hz somatomotor source strengths when eyes were open. When DBS was off UPDRS action tremor scores correlated with pericentral 6-10 Hz and 21-30 Hz and occipital alpha source strengths when eyes open.Occipital alpha strength decreased during DBS when eyes closed. The peak frequency of occipital alpha rhythm correlated negatively with total UPDRS motor scores and with rigidity subscores, when eyes closed.

Conclusion

STN DBS modulates brain oscillations both in alpha and beta bands and these oscillations reflect the clinical condition during DBS.

Significance

MEG combined with an appropriate artifact rejection method enables studies of DBS effects in Parkinson’s disease and presumably also in the other emerging DBS indications.     

Benefit of magnetic source localization in challenging refractory epilepsies

Background

About 23 million people worldwide suffer from medically refractory epilepsy. Surgery might be the best treatment option with a reasonable chance of seizure freedom. Surgical success depends on the exact definition of the epileptogenic zone (EZ). Magnetoencephalography (MEG) is one of the newer additions to the noninvasive presurgical work-up.

Objectives

This study gives an overview of the impact of MEG on the management of epilepsy patients, focusing on (1) the influence on presurgical evaluation, (2) the identification of patients with the greatest benefit, and (3) possible surgical outcome predictors.

Methods

An extensive Medline literature search was conducted for studies published from 1990.

Results

MEG is in clinical use in the presurgical evaluation of epilepsies for the identification of the EZ and outcome prediction. In cases of failed surgery, it serves as a means to locate the remaining epileptogenic cortex. The usefulness of MEG has been reported for a wide range of localizations including challenging areas like the insula. In cases of multiple possible culprit lesions, MEG can mark the epileptogenic lesion, whereas in cases of nonlesional magnetic resonance imaging (MRI) findings, MEG can pinpoint a lesional or nonlesional epileptogenic cortex area. The role of MEG in the presurgical evaluation of epilepsy was shown with rates of modified approaches in 20–35% of cases. This holds true especially for cases with extratemporal epilepsy.

Discussion

The value of MEG source localization is highest in extratemporal epilepsy, in MRI-negative or multilesional cases, if other modalities yield contradictory or inconclusive results, or in cases of suspected multifocal epilepsy. There is clear evidence that MEG yields nonredundant information and influences the therapeutic course of patients. Various patient groups likely to benefit from MEG were identified. Considering the poor chances of seizure freedom with continued medical treatment, these patients should not be denied source localization, which could result in surgery with favorable outcomes.

     

Reduced percentage of neurocysticercosis cases among patients with late-onset epilepsy in the new millennium

Objective

To determine if the number of neurocysticercosis cases among patients with late-onset epilepsy has decreased over the past two decades.

Design

Retrospective cohort study of 431 consecutive patients with recurrent seizures starting after the age of 20 years evaluated at our Institution from 1990 to 2009.

Methods

Patients were classified according to the year in which they were first seen. Group I included 129 patients evaluated between 1990 and 1994, Group II included 108 patients evaluated between 1995 and 1999, Group III included 106 patients evaluated between 2000 and 2004, and Group IV included 88 patients evaluated between 2005 and 2009. We correlated the percentage of persons with cryptogenic and symptomatic epilepsy between the groups to determine if there was any change in the causes of late-onset epilepsy.

Results

One hundred seventy-one patients had cryptogenic and 260 had symptomatic epilepsy. Common causes of symptomatic epilepsy were neurocysticercosis in 120 cases, cerebrovascular disease in 68, and brain tumors in 40. We found a reduction in the number of patients with symptomatic epilepsy (p = 0.0007) as well as a reduction in the number of neurocysticercosis cases (p = 0.0004) over the study years. There was a reduction in the weight of neurocysticercosis as an etiological factor for symptomatic late-onset epilepsy related to a drop in the number of patients with this condition evaluated between 2005 and 2009 (p = 0.0045).

Conclusion

The number of neurocysticercosis cases among patients with late-onset epilepsy has changed over the years. This parasitic disease is no longer the most common cause of symptomatic late-onset epilepsy in our population.     

Magnetoencephalography localizing spike sources of atypical benign partial epilepsy

Rationale: Atypical benign partial epilepsy (ABPE) is characterized by centro-temporal electroencephalography (EEG) spikes, continuous spike and waves during sleep (CSWS), and multiple seizure types including epileptic negative myoclonus (ENM), but not tonic seizures. This study evaluated the localization of magnetoencephalography (MEG) spike sources (MEGSSs) to investigate the clinical features and mechanism underlying ABPE. Methods: We retrospectively analyzed seizure profiles, scalp video EEG (VEEG) and MEG in ABPE patients. Results: Eighteen ABPE patients were identified (nine girls and nine boys). Seizure onset ranged from 1.3 to 8.8 years (median, 2.9 years). Initial seizures consisted of focal motor seizures (15 patients) and absences/atypical absences (3). Seventeen patients had multiple seizure types including drop attacks (16), focal motor seizures (16), ENM (14), absences/atypical absences (11) and focal myoclonic seizures (10). VEEG showed centro-temporal spikes and CSWS in all patients. Magnetic resonance imaging (MRI) was reported as normal in all patients. MEGSSs were localized over the following regions: both Rolandic and sylvian (8), peri-sylvian (5), peri-Rolandic (4), parieto-occipital (1), bilateral (10) and unilateral (8). All patients were on more than two antiepileptic medications. ENM and absences/atypical absences were controlled in 14 patients treated with adjunctive ethosuximide. Conclusion: MEG localized the source of centro-temporal spikes and CSWS in the Rolandic-sylvian regions. Centro-temporal spikes, Rolandic-sylvian spike sources and focal motor seizures are evidence that ABPE presents with Rolandic-sylvian onset seizures. ABPE is therefore a unique, age-related and localization-related epilepsy with a Rolandic-sylvian epileptic focus plus possible thalamo-cortical epileptic networks in the developing brain of children.     

Evaluation of the GABAergic nervous system in autistic brain: (123)I-iomazenil SPECT study

Purpose

To evaluate the GABA_A receptor in the autistic brain, we performed ¹²³I-IMZ SPECT in patients with ASD. We compared ¹²³I-IMZ SPECT abnormalities in patients who showed intellectual disturbance or focal epileptic discharge on EEG to those in patients without such findings.

Subjects and methods

The subjects consisted of 24 patients with ASD (mean age, 7.3 ± 3.5 years), including 9 with autistic disorder (mean age, 7.0 ± 3.7 years) and 15 with Asperger’s disorder (mean age, 7.5 ± 3.2 years). We used 10 non-symptomatic partial epilepsy patients (mean age, 7.8 ± 3.6 years) without intellectual delay as a control group.For an objective evaluation of the ¹²³I-IMZ SPECT results, we performed an SEE (Stereotactic Extraction Estimation) analysis to describe the decrease in accumulation in each brain lobule numerically.

Results

In the comparison of the ASD group and the control group, there was a dramatic decrease in the accumulation of ¹²³I-IMZ in the superior and medial frontal cortex. In the group with intellectual impairment and focal epileptic discharge on EEG, the decrease in accumulation in the superior and medial frontal cortex was greater than that in the group without these findings.

Conclusion

The present results suggest that disturbance of the GABAergic nervous system may contribute to the pathophysiology and aggravation of ASD, since the accumulation of ¹²³I-IMZ was decreased in the superior and medial frontal cortex, which is considered to be associated with inference of the thoughts, feelings, and intentions of others (Theory of Mind).     

Frequency-domain EEG source analysis for acute tonic cold pain perception

Objective

To investigate electrocortical responses to tonic cold pain by frequency-domain electroencephalogram (EEG) source analysis, and to identify potential electrocortical indices of acute tonic pain.

Methods

Scalp EEG data were recorded from 26 healthy subjects under tonic cold pain (CP) and no-pain control (NP) conditions. EEG power spectra and the standardized low-resolution brain electromagnetic tomography (sLORETA) localized EEG cortical sources were compared between the two conditions in five frequency bands: 1–4 Hz, 4–8 Hz, 8–12 Hz, 12–18 Hz and 18–30 Hz.

Results

In line with the EEG power spectral results, the source power significantly differed between the CP and NP conditions in 8–12 Hz (CP < NP) and 18–30 Hz (CP > NP) in extensive brain regions. Besides, there were also significantly different 4–8 Hz and 12–18 Hz source activities between the two conditions. Among the significant source activities, the left medial frontal and left superior frontal 4–8 Hz activities, the anterior cingulate 8–12 Hz activity and the posterior cingulate 12–18 Hz activity showed significant negative correlations with subjective pain ratings.

Conclusions

The brain’s perception of tonic cold pain was characterized by cortical source power changes across different frequency bands in multiple brain regions. Oscillatory activities that significantly correlated with subjective pain ratings were found in the prefrontal and cingulate regions.

Significance

These findings may offer useful measures for objective pain assessment and provide a basis for pain treatment by modulation of neural oscillations at specific frequencies in specific brain regions.     

Does photoparoxysmal response in children represent provoked seizure? Evidence from simultaneous motor task during EEG

Objectives

Acute cognitive changes during epileptiform discharges have been studied using computer assisted cognitive tasks. We aimed to demonstrate acute behavioral change (using a simple motor response task MRT) during photoparoxysmal response (PPR) in children below 18 years.

Methods

Children performed a simple repetitive motor task during intermittent photic stimulation (IPS). All episodes of PPR not associated with obvious clinical change (as observed by the technologist or reported by the patient) were analyzed for this study. The average time interval between two successive motor responses across a PPR (test time) was compared to the average time interval between two successive motor responses during IPS not associated with PPR (control time) using Wilcoxon signed ranks test.

Results

21 children who had PPR successfully completed the MRT. The difference between the mean durations was 0.894 s (p = 0.002). More than 50% increase compared to the control time was considered a delay in MRT during PPR. 10 children showed slowing of MRT during PPR.

Conclusion

By definition, acute behavioral change during generalized epileptiform discharges represent provoked seizures. Detecting subclinical seizures can have important safety implications in children (skiing, skating and driving) with PPR on EEG, but no clinical seizures. We recommend MRT during IPS.     

Topography of maturational changes in EEG burst spectral power of the preterm infant with a normal follow-up at 2years of age

Objective

To quantify the electroencephalography (EEG) burst frequency spectrum of preterm infants by automated analysis and to describe the topography of maturational change in spectral parameters.

Methods

Eighteen preterm infants <32 weeks gestation and normal neurological follow-up at 2 years underwent weekly 4-h EEG recordings (10–20 system). The recordings (n = 77) represent a large variability in postmenstrual age (PMA, 28–36 weeks). We applied an automated burst detection algorithm and performed spectral analysis. The frequency spectrum was divided into δ1 (0.5–1 Hz), δ2 (1–4 Hz), θ (4–8 Hz), α (8–13 Hz) and β (13–30 Hz) bands. Spectral parameters were evaluated as a function of PMA by regression analysis. Results were interpolated and topographically visualised.

Results

The majority of spectral parameters show significant change with PMA. Highest correlation is found for δ and θ band. Absolute band powers decrease with increasing PMA, while relative α and β powers increase. Maturational change is largest in frontal and temporal region.

Conclusions

Topographic distribution of maturational changes in spectral parameters corresponds with studies showing ongoing gyration and postnatal white matter maturation in frontal and temporal lobes.

Significance

Computer analysis of EEG may allow objective and reproducible analysis for long-term prognosis and/or stratification of clinical treatment.     

Source localization in magnetoencephalography to identify epileptogenic foci

Rationale

Magnetoencephalography (MEG) is useful to localize epileptic foci in epilepsy as MEG has higher spatio-temporal resolution than conventional diagnostic imaging studies; positron emission computed tomography, single photon emission computed tomography and magnetic resonance imaging (MRI).

Methods

We use 204-channel helmet-shaped MEG with a sampling rate of 600 Hz. A single dipole method calculates equivalent current dipoles to localize epileptic sources. The equivalent current dipoles are superimposed onto MRI as magnetic source imaging (MSI). Ictal MEG data are analyzed using time-frequency analysis. The power spectrum density is calculated using short-time Fourier transform and superimposed onto MRI results.

Results

Clustered equivalent current dipoles represent epileptogenic zones in patients with localization-related epilepsy. The surgical plan is reliably developed from source localizations of dipoles and power spectrum of interictal spike discharges, and ictal frequency.

Conclusion

MEG is indispensable in diagnosis and surgical resection for epilepsy to accurately localize the epileptogenic zone.     

Diffusion tensor and dynamic susceptibility contrast MRI in glioblastoma

Objective

We prospectively investigated the correlation between diffusion tensor (DTI), dynamic susceptibility contrast (DSC) perfusion MRI metrics and Ki-67 labelling index in glioblastomas.

Methods

We studied seventeen patients who were operated on for glioblastoma. DTI and DSC MRI were performed within a week prior to surgical excision. Lesion/normal ratios were calculated for the apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and relative mean transit time (rMTT) ratio. In the excised tumour specimens Ki-67 antigen expression was evaluated by the MIB-1 immunostaining method.

Results

A significant correlation was observed between Ki-67 index and ADC ratio (r = −0.528, p = 0.029) and FA ratio (r = 0.589, p = 0.012). rCBV and rMTT presented a trend towards significant correlation with Ki-67 index (r = 0.628, p = 0.07 and r = 0.644, p = 0.06 respectively). There was a trend towards better survival for patients with gross total tumour excision and FA values lower than 0.48 (p = 0.1 and p = 0.09 respectively). No significant correlation was found between ADC ratio, rCBV, rCBF, rMTT and overall survival.

Conclusion

ADC ratio, FA ratio, rCBV and rMTT tumour/normal tissue ratios may represent indicators of glioma proliferation. FA values may hold promise for predicting survival in patients with glioblastoma.     

Interferon, azathioprine and corticosteroids in multiple sclerosis: 6-year follow-up of the ASA cohort

Objective

To evaluate long-term effects of 2-year treatment with interferon beta combined with low-dose azathioprine and prednisone in multiple sclerosis.

Methods

In the original 2-year ASA study, 181 patients with early relapsing–remitting multiple sclerosis were randomised into 3 treatment arms: those treated with interferon beta (n = 60), with interferon beta and low-dose azathioprine (n = 58), and interferon beta, azathioprine and low-dose prednisone (n = 63). Of these, 172 were included in this 4-year non-study extension. Three monthly clinical controls and annual MRI scans were carried out. The primary endpoint was annual relapse activity. The secondary endpoints were disability and quantitative MRI parameters.

Results

Nine patients were lost to follow-up and 172 were included in the analyses. None of relapse activity, disability accumulation or MRI parameters differed significantly between the groups over 6 years. Only 5.5% and 0.6% of patients were free from disease activity at year 2 and year 6 of the treatment initiation.

Conclusion

The tested combined therapeutic regimen does not improve long-term outcomes in patients with multiple sclerosis. Furthermore, interferon is not able to completely abolish disease activity.     

Epileptic spasms in older pediatric patients: MEG and ictal high-frequency oscillations suggest focal-onset seizures in a subset of epileptic spasms

OBJECTIVES: To elucidate the pathophysiology of intractable epileptic spasms in older children by describing the interictal magnetoencephalography spike sources (MEGSSs), intracranial EEG ictal-onset zones (IOZs) and their ictal high-frequency oscillations (HFOs) and surgical outcomes. METHODS: We studied five patients (4.5-14 years) who underwent surgery following intracranial video-EEG (VEEG) monitoring. We analyzed clinical profiles, MRIs, scalp and intracranial VEEGs, and MEGSSs. We localized ictal HFOs using a sampling rate of 1000 Hz and multiple band frequency analysis (MBFA). RESULTS: Seizure onset ranged from 0.4 to 8 years. Three patients presented with asymmetrical spasms. Interictal scalp VEEG recorded predominantly unilateral epileptiform discharges in four; generalized and multifocal in one. Ictal scalp VEEG showed generalized high-amplitude slow waves with superimposed fast waves in four patients; hemispheric electrodecremental episodes in one. MRI findings were normal in three, hemispheric polymicrogyria and periventricular heterotopia in one each. All patients had unilateral MEGSS clusters. Ictal HFOs, ranging from 150 to 250 Hz, localized over Rolandic and frontal regions in four, with one also having extensive temporo-occipital HFOs. After cortical resection, three patients were seizure free; one had >90% reduction in seizure frequency. One patient experienced residual seizures after resection of the hemispheric ictal HFO region. CONCLUSION: Unilateral clusters of MEGSSs overlapped regional IOZs in older patients with epileptic spasms. High spatio-temporal MBFA before and during spasms revealed the regional ictal HFOs. Seizure-free outcomes following resection of zone with MEGSS clusters and ictal HFOs suggested that a subset of epileptic spasms was focal-onset seizures.     

Feasibility of cerebral magnetic resonance imaging in patients with externalised spinal cord stimulator

Object

Spinal cord stimulation (SCS) is a well-known treatment option for intractable neuropathic pain after spinal surgery, but its pathophysiological mechanisms are poorly stated. The goal of this study is to analyse the feasibility of using brain MRI, functional MRI (fMRI) and Magnetic Resonance Spectroscopy (MRS) as tools to analyse these mechanisms in patients with externalised neurostimulators during trial period.

Methods

The authors conducted in an in vitro and in vivo study analysing safety issues when performing brain MRI, fMRI and MRS investigations in human subjects with externalised SCS. Temperature measurements in vitro were performed simulating SCS during MRI sequences using head transmit-receive coils in 1.5 and 3 T MRI systems. 40 Patients with externalised SCS were included in the in vivo study. 20 patients underwent brain MRI, fMRI and another 20 patients underwent brain MRI and MRS.

Results

A maximal temperature increase of 0.2 °C was measured and neither electrode displacements nor hardware failures were observed. None of the patients undergoing the MRS sequences at the 1.5 or 3 T MRI scanners described any discomfort or unusual sensations.

Conclusion

We can conclude that brain MRI, fMRI and MRS studies performed in patients with externalised SCS can be safely executed.     

Reduced parietal activation in cervical dystonia after parietal TMS interleaved with fMRI

Objective

Clinically normal hand movement with altered cerebral activation patterns in cervical dystonia (CD) may imply cerebral adaptation. Since impaired sensorimotor integration appears to play a role in dystonia, left superior parietal cortex modulation with repetitive transcranial magnetic stimulation (TMS) was employed to further challenge adaptation mechanisms reflected by changes in cerebral activation.

Methods

Seven CD patients and ten healthy controls were scanned on a 3T magnetic resonance imaging (MRI) scanner with 1 Hz inhibitory interleaved TMS. They executed and imagined right wrist flexion/extension movements. Each task was preceded by a 10-s period with or without TMS.

Results

The activations of both tasks after TMS in controls showed a similar pattern as found in CD without TMS, i.e. activation increases in bilateral prefrontal and posterior parietal regions during both tasks and decreases in right anterior parietal cortex during imagery (P < 0.001). the activations of both tasks after TMS in CD were weaker but with a similar trend in activation changes. Only in the right angular gyrus, TMS significantly failed to induce an activation increase in CD as was seen in the controls (P < 0.001).

Conclusion

The similarity between TMS effects on the distribution of cerebral activations in controls and the pattern seen in CD may support the concept that CD make use of compensatory circuitry enabling clinically normal hand movement. The fact that a similar but weaker TMS effect occurred in CD could suggest that the capacity of compensation is reduced. Particularly for the right angular gyrus, this reduction was statistically significant.