The Utility of Magnetoencephalography in the Evaluation of Secondary Bilateral Synchrony: A Case Report

Distinguishing primary bilateral synchrony from secondary bilateral synchrony remains a challenge with traditional scalp EEG (1). Children with continuous spike and wave in sleep (CSWS) present such a challenge. Many of these children develop severe cognitive and language deterioration that is unresponsive to medical treatment as the disease progresses (2). In some of these children, the seemingly generalized epileptiform abnormality represents true secondary bilateral synchrony; that is, rapid bilateral spread from a limited cortical area of electrical abnormality (3,4). Tukel and Jasper first described secondary bilateral synchrony in EEG of patients with parasaggital lesions (5). This concept was further elucidated in Penfield and Jasper's pivotal text “Epilepsy and the Functional Anatomy of the Human Brain” (6). Secondary bilateral synchrony must be distinguished from true primary bilateral synchrony, which is seen in the genetic epilepsies, such as absence and juvenile myoclonic epilepsies. In addition, apparent secondary bilateral synchrony may arise from multifocal epilepsies such as Lennox-Gastaut syndrome and other degenerative syndromes of childhood. In secondary bilateral synchrony, corticocortical connections via the corpus callosum allow synchronization to occur (7). The most common location for a lesion to produce secondary bilateral synchrony is in the frontocentral region, followed by the temporal neocortex and parietal cortex (1,7,8). Cases of temporal bilateral synchrony may use the anterior commisure as well as the corpus callosum for synchronization (8). Gotman measured a fixed and constant hemispheric time difference at the onset of a synchronous discharge, which characterizes the syndrome of secondary bilateral synchrony. These fixed time lags were associated with other evidence, such as cortical lesions, in determining the predominant focus (9). In a case of true bilateral synchrony, no time lag was consistently present (9,10). In patients with multifocal epilepsies and secondary bilateral synchrony, distinct foci and spread with fixed time intervals occasionally can be distinguished from secondary bilateral synchrony from a single epileptic foci. Pharmacologic challenge with intravenous barbiturates, especially methohexital, during recording of EEG may help distinguish multifocal epilepsy with secondary bilateral synchrony from unifocal epilepsy with bilateral synchrony (2,4). Methohexital, when given at intravenous infusion at rates of 100 mg/min, has been used to highlight the primary focus by its differential effects on the primary and secondary foci (2–4). More recently, magnetoencephalogram (MEG) has been used to evaluate secondary bilateral synchrony in children with continuous spike and wave and language and/or behavioral dysfunction (11,12). Magnetoencephalography, with up to 148 channels, has been more useful in dipole localization and evaluating transcallosal spread than traditional EEG, given the limited channels in the 10-20 system (1). A 5-year-old ambidextrous male presented with a 2-year history of language deterioration. His past medical history revealed that he was the product of a 5-week premature delivery by Caesarean section. His APGARS were normal. His motor development was normal. He was sitting by 4 months, crawling at 8 months, and walking between 12 and 13 months of age. Initially, his language development was somewhat delayed. He spoke his first words at 20 months. By 30 months, he was using two- to three-word sentences. By 36 months, he had progressed to four-word sentences. A few weeks after his third birthday, his parents noted regression of language, with babbling and nonsensical words intermixed with normal language. His parents also noticed that he did not seem to understand much of what was said to him. Over the next 6 weeks, he became mute and displayed marked difficulty in comprehension of even simple commands. He was diagnosed with possible autistic regression. He was referred for neurological evaluation and a prolonged EEG was performed. The EEG recordings during slow wave sleep revealed continuous spike and wave. A diagnosis of Landau-Kleffner syndrome (LKS) was made (Fig. 1). In careful questioning of the parents, they noted episodes of eye fluttering lasting up to 15 s over the past month, during which he did not immediately respond to them. EEG tracing taken during sleep in this patient demonstrates continuous spike and wave pattern which may occupy up to 80% of slow wave sleep. Electrode designations are those of the standard 10-20 International System. Further workup included an MRI that was normal and a PET scan that showed hypometabolism of the right temporal area. A neuropsychological evaluation revealed nonverbal cognitive function normal for his age. However, his verbal cognitive function was severely affected. Medication trials followed. Lamotrigine, prednisone, and oxcarbamazepine trials had no effect on language function, but did eliminate episodes of eye fluttering. Using a Valium protocol (1 mg/kg), followed by slow taper, the EEG improved by 90% but the effect was transient. A magnetoencephalogram was obtained and the patient was referred for surgical treatment (Figs. 2 and 3). He was taken to surgery, where a right craniotomy was performed. Electrocorticography confirmed that the origin of the bilateral continuous spike and wave was on the superior surface of the superior temporal gyrus in the region of the planum temporale. A multiple subpial transection procedure was performed within the sylvian fissure and on the perisylvian cortex, with resolution of 90% of the abnormal epileptic activity. At discharge, neurologic exam other than language testing was normal. His language, both expressive and comprehensive, slowly improved with speech therapy. One year postoperatively, while language remains abnormal, there has been substantial and continuing improvement. MRI in this patient superimposed source localization of the equivalent current dipole of sample epileptiform discharges from a 148 channel magnetoencephalogram. Magnetoencephalography from 148 channel whole brain array demonstrates that the right temporal discharge precedes the left temporal discharge by approximately 17 miliseconds, proving secondary bilateral synchrony. This case presentation demonstrates the utility of MEG in evaluating patients with suspected secondary bilateral synchrony. The recording of a magnetic signal generated by intraneuronal current has advantages over the recording of EEG in that the magnetic signal is not as attenuated and potentially distorted as it passes through brain, bone, and scalp as is the electrical signal (13). With the use of whole head arrays, which have up to 148 channels, MEG has superior spatial resolution in dipole localization, as compared to EEG, which has standard 10-20 electrodes number and placement. Both techniques use the same dipole localization software and, therefore, have the same limitations in that they use mathematical models with certain assumptions for calculating the equivalent current dipole (14). However, better spatial resolution is possible with MEG because of the large number of channels the whole brain arrays employ. There have been a number of MEG studies that confirm that the MEG source localization of interictal spike is excellent when compared to electrocorticography and intracranial electrode recordings (14–16). The temporal resolution of a digitally recorded signal allows one to see the propagation of interictal epileptiform activity either within a hemisphere or across the corpus callosum, proving that what appears to be a generalized discharge actually represents secondary bilateral synchrony with one source and rapid propagation. There have been case reports about the use of MEG in patients with LKS (2,3). Magnetoencephalography has added valuable data in presurgical planning in determining the location of the dominant focus along and within the sylvian fissure during the secondary bilateral discharge seen in CSWS. Magnetoencephalography has also been found useful in separating children with LKS from those with autistic regression disorder with loss of language function. At times, this distinction is clinically difficult. Lewine and co-workers (12) looked at a group of 6 patients with LKS and 50 with autistic regression disorder. In all patients with LKS, epileptiform activity was confined to the perisylvian area with secondary propagation to frontal and parietal cortex. However, in 75% of the patients with autistic regression disorder, independent epileptiform activity was seen outside of the perisylvian cortex. Thus, the MEG demonstrates multifocal independent epileptiform foci in the autistic regression group, allowing clear distinction from the LKS group. While surgery, multiple subpial transection, has been shown to be helpful in improving language function in LKS, the results in autistic regression disorder have not been encouraging. Magnetoencephalography is an important part of the presurgical evaluation of children with language deterioration and suspected LKS. It is quite useful in evaluating patients with secondary bilateral synchrony.