Intellectual and language findings and their relationship to EEG characteristics in benign childhood epilepsy with centrotemporal spikes

Recent research has revealed that benign childhood epilepsy with centrotemporal spikes (BECTS) causes deficient performance in various neuropsychological areas, without arriving at a definition of a uniform profile. The purpose of this study was to examine intelligence and certain language functions in 24 children with an active centrotemporal focus, comparing them with a group of 16 controls matched for age and schooling. Test results were correlated with several EEG characteristics, including focal versus multifocal presentation of interictal epileptiform activity, lateralization, spike maximum on midtemporal or extratemporal electrodes, and rate of interictal activity when awake and during non-REM sleep. Our study demonstrated that children with BECTS have mild language defects, revealed by tests measuring phonemic fluency, verbal re-elaboration of semantic knowledge, and lexical comprehension. Interictal EEG discharges demonstrated that a high rate of occurrence while awake, multifocal location, and temporal prominence seem to impair the efficiency of some of the neuropsychological functions investigated. However, because the last EEG was obtained within the last 2 months (on average) before the assessment, and because BECTS is a form of epilepsy with signs of cortical hyperexcitability that vary over time in terms of rate, side, and location, the pattern of neuropsychological deficiencies could have changed (at least to some degree) by the time of the test, with respect to the EEG variables considered.     

Atypical hemispheric asymmetries for the processing of phonological features in children with rolandic epilepsy

We assessed language lateralization in 177 healthy 4- to 11-year-old children and adults and atypical asymmetries associated with unilateral epileptic foci in 18 children with benign epilepsy with centrotemporal spikes (BECTS). Dichotic listening results revealed two indices of immature functional asymmetry when the focus was left-sided (BECTS-L). First, children with BECTS-L did not show left hemisphere dominance for the processing of place of articulation, which was recorded in children with BECTS-R and control children. On the contrary, healthy children exhibited a gradual increase in left hemisphere dominance for place processing during childhood, which is consistent with the shift from global to finer-grained acoustic analysis predicted by the Developmental Weighting Shift model. Second, children with BECTS-L showed atypical left hemisphere involvement in the processing of the voiced value (+V), associated with a long acoustic event in French stop consonants, whereas right hemisphere dominance increased with age for +V processing in healthy children. BECTS-L, therefore, interferes with the development of left hemisphere dominance for specific phonological mechanisms.     

Left Hemispheric Dominance of Epileptiform Discharges

Summary: Purpose: We reviewed 1,360 EEG reports for all patients studied in two different neurophysiology laboratories during 1 calendar year to determine whether epileptiform discharges have a hemispheric dominance.
Methods: Both inpatients and outpatients, with or without epilepsy, were included.
Results: Ninety-four records (6.9%) demonstrated generalized epileptiform activity. Of 95 EEG reports indicating spikes solely from one hemisphere, spikes arose from the left in 61 and from the right in 34. Among 50 other records with bilateral independent spikes with lateralization, 40 were left hemisphere'dominant and 10 were right hemisphere dominant.
Conclusions: These findings raise the possibility that the left cerebral hemisphere may generate focal epilepsy more frequently than the right.     

Neuropsychological and functional MRI studies provide converging evidence of anterior language dysfunction in BECTS

Purpose:   Benign childhood epilepsy with centrotemporal spikes (BECTS) is the most common epilepsy syndrome of childhood and can be associated with language difficulties. The exact profile of these difficulties and their neurofunctional underpinnings, however, are not yet clear.
Methods:   To further understand the impact of the BECTS syndrome on language, we assessed language performance using standard neuropsychological measures, and patterns of language lateralization using functional magnetic resonance imaging (fMRI) in children with typical BECTS (n = 20) and healthy controls (n = 20).
Results:   The fMRI analyses revealed that language-related activation was less lateralized to the left hemisphere in anterior brain regions in the patients relative to the control group. This finding was consistent with decreased performance in the BECTS group compared to the control group on the neuropsychological measure most dependent on the integrity of anterior aspects of the language axis, namely, sentence production.
Discussion:   The converging lines of evidence from the neuropsychological and activation methodologies support the view that BECTS is associated with language difficulties that are regional, and anterior, in nature.     

Left hemisphere dysfunction affects dichotic listening in patients with temporal lobe epilepsy

This study evaluated the relative effect of left hemisphere dysfunction and side of seizure onset on dichotic listening performance in patients with temporal lobe epilepsy and left hemisphere speech dominance. Seventeen patients were divided into groups based on side of seizure onset and based on scores on a composite measure revealing left hemisphere dysfunction. The group with left hemisphere dysfunction had more correct responses from the left ear, and a left ear advantage, on dichotic listening. The group with normal left hemisphere function showed the expected right ear advantage. Side of seizure onset did not affect dichotic listening performance significantly.     

Neuropsychological development in children belonging to BECTS spectrum: Long-term effect of epileptiform activity

Benign epilepsy with centrotemporal spikes (BECTS) is an idiopathic focal epileptic syndrome in childhood. It is called “benign” because the seizure and cognitive outcomes are usually favorable, but a significant number of children with BECTS present heterogeneous cognitive deficits correlated to NREM sleep epileptiform discharges. The atypical evolutions of BECTS form a spectrum of conditions suggesting that slow sleep nocturnal interictal epileptiform discharges (IEDs) specifically determine the neuropsychological deficit.Few follow-up studies of neuropsychological outcome in BECTS are available, and very often, slow sleep has not been recorded throughout night sleep. The present study analyzed the long-term effects of IEDs during NREM sleep on neuropsychological development in children with rolandic spikes. Thirty-three children with a diagnosis of BECTS were monitored for at least two years. Results show that these children are at higher risk for residual verbal difficulties, and the abnormal neuropsychological development is significantly correlated with a greater frequency of NREM sleep discharges, school-age epilepsy onset, and a higher number of antiepileptic drugs (AEDs). The findings are discussed in terms of how slow sleep IEDs affect the consolidation of verbal skills during critical epochs of neuropsychological development.     

Dipole Reversal: An Ictal Feature of Benign Partial Epilepsy with Centrotemporal Spikes

Benign epilepsy with centrotemporal spikes (BECTS) is characterized by brief stereotypical partial seizures with motor and/or sensory symptoms with frequent secondarily generalized seizures. The interictal EEG shows slow, disphasic, high-voltage spikes in the centrotemporal areas. The few published examples of ictal tracings depict focal rhythmic sharp waves and spikes without significant postictal slowing. We report an ictal event in BECTS that is unusual in the evolution and polarity of the ictal discharges. In this subclinical seizure, ictal multiple spike and wave discharges appear as a dipole: they are electropositive in T3-C3 and negative in F3. These surface positive epileptic discharges are unique and require explanation. We postulate that the seizure discharge arises in the depths of the sylvian fissure involving folded cortical areas. This occurs in such a way that the negative component of the discharges is concealed from the scalp electrodes. Thus, a relative positivity is recorded on the surface. This represents a dipole reversal relative to the interictal discharges (characteristic of BECTS). This geometrical explanation allows us to avoid postulating an unusual mechanism of generation of this seizure.     

Magnetoencephalographic analysis of bilaterally synchronous discharges in benign rolandic epilepsy of childhood.

The purpose of this study was to examine the spatial and temporal relationship between bilateral foci of bilaterally synchronous discharges in benign rolandic epilepsy of childhood (BREC) using a whole-scalp neuromagnetometer. We simultaneously recorded interictal magnetoencephalographic (MEG) and electroencephalographic (EEG) signals in six children with BREC. Interictal spikes were classified into three groups: bilaterally synchronous discharges (BSDs), unilateral discharges on right side (UD-R), and unilateral discharges on left side (UD-L). We used equivalent current dipole (ECD) modelling to analyse the cortical sources of interictal spikes. Both BSDs and UDs were found in Patients 1-4, whereas only UDs were identified in Patients 5 and 6. The ECDs of interictal spikes were located in rolandic regions, 10-20mm anterior and lateral to hand somatosensory cortices. Multi-dipole analysis of BSDs showed two ECDs in homotopic motor areas of the hemispheres. During BSDs, the right-sided activation preceded the left-sided activation by 15-21 milliseconds in Patients 1 and 2. In Patients 3 and 4, the activation occurred 17-20 milliseconds earlier in the left than the right hemisphere. Within the same hemisphere, the sources of BSDs and UDs were located in similar areas. In conclusion, our results imply the cortical epileptogenicity in bilateral perirolandic areas in BREC. The sequential activation during BSDs in both hemispheres suggest the existence of synaptic connections, possibly via the corpus callosum, between bilateral irritative foci.     

LEFT HEMISPHERE DYSFUNCTION AFFECTS DICHOTIC LISTENING IN PATIENTS WITH TEMPORAL LOBE EPILEPSY

This study evaluated the relative effect of left hemisphere dysfunction and side of seizure onset on dichotic listening performance in patients with temporal lobe epilepsy and left hemisphere speech dominance. Seventeen patients were divided into groups based on side of seizure onset and based on scores on a composite measure revealing left hemisphere dysfunction. The group with left hemisphere dysfunction had more correct responses from the left ear, and a left ear advantage, on dichotic listening. The group with normal left hemisphere function showed the expected right ear advantage. Side of seizure onset did not affect dichotic listening performance significantly.­­     

Disengagement and inhibition of visual-spatial attention are differently impaired in children with rolandic epilepsy and Panayiotopoulos syndrome

We assessed voluntary orientation and reorientation of visuospatial attention in 313 healthy 6- to 22-year-old participants, 30 children suffering from benign epilepsy with centrotemporal spikes (BECTS) and 13 children with Panayiotopoulos syndrome (PS). The developmental section highlights the late development of reorienting skills. Only children with BECTS-R showed a strong tendency toward a rightward bias in attentional orientation. Additionally, a unilateral deficit of disengagement characterizes the patients with BECTS-R and comorbid ADHD. Right rolandic spikes seem to aggravate subclinical reorienting difficulties. Finally, children with PS failed to diffuse inhibition, except in the nearest area outside the attentional focus. This deficit could be attributed to the typical occipital-to-frontal spreading of the spikes in PS. By showing distinct attentional deficiencies according to the epileptic syndrome and the epileptic focus lateralization in BECTS, the results provide new evidence for alterations of attentional mechanisms by interictal epileptic activity, which probably contribute to learning difficulties.     

Voices behind the left shoulder: two patients with right-sided temporal lobe epilepsy

Auditory vocal hallucinations are sometimes observed in temporal-lobe epilepsy, but are a frequent sign of psychosis and may rarely be mistaken for the latter. Here we report two patients who suffered from auditory vocal hallucinations, described as unintelligible human voices perceived at their left side during epileptic seizures. MEG revealed interictal epileptic discharges within the anterior partition of the right superior temporal gyrus; signal-to-noise ratio of these discharges was overall poor in EEG. The findings suggest that auditory vocal hallucinations without verbal content can evolve in the right hemisphere and are probably independent of language lateralization. This is in accordance with evidence from functional imaging, whereas most previous reports of seizures with auditory vocal hallucinations were confined to the left hemisphere.     

Impact of frequency and lateralization of interictal discharges on neuropsychological and fine motor status in children with benign epilepsy with centrotemporal spikes

Despite a positive prognosis for seizure remission, children with benign epilepsy with centrotemporal spikes (BECTS) have been reported to exhibit subtle neuropsychological difficulties. We examined the relationship between patterns of centrotemporal spikes (the typical electroencephalography [EEG] finding in BECTS) and neuropsychological and motor outcomes in children with new‐onset BECTS. Thirty‐four patients with new‐onset BECTS (not taking antiepileptic medication) and 48 typically developing children participated in the study. In BECTS patients, centrotemporal spikes (CTS) were evaluated in the first hour awake and first 2 h of sleep in a 24‐h EEG recording and left or right‐sided origin was noted. General intellectual function, language, visuospatial skill, processing speed, and fine motor skill were assessed in all participants. We found no significant difference between BECTS patients and controls on measures of general intellectual function, or visuospatial or language testing. There were significant differences in processing speed index and nondominant hand fine motor scores between groups. Significant negative relationships were observed between rates of left‐sided CTS and right hand fine motor scores. This suggests that psychomotor and fine motor speed are affected in BECTS, but the extent of affected domains may be more limited than previously suggested, especially in untreated patients early in the course of their epilepsy.     

Neuromagnetic functional coupling during dichotic listening of speech sounds

The present magnetoencephalography (MEG) study tested the hypothesis of a phase synchronization (functional coupling) of cortical alpha rhythms (about 6-12 Hz) within a "speech" cortical neural network comprising bilateral primary auditory cortex and Wernicke's areas, during dichotic listening (DL) of consonant-vowel (CV) syllables. Dichotic stimulation was done with the CV-syllable pairs /da/-/ba/ (true DL, yielded by stimuli having high spectral overlap) and /da/-/ka/ (sham DL, obtained with stimuli having poor spectral overlap). Whole-head MEG activity (165 sensors) was recorded from 10 healthy right-handed non-musicians showing right ear advantage in a speech DL task. Functional coupling of alpha rhythms was defined as the spectral coherence at the following bands: alpha 1 (about 6-8 Hz), alpha 2 (about 8-10 Hz), and alpha 3 (about 10-12) with respect to the peak of individual alpha frequency. Results showed an inverse pattern of functional coupling: during DL of speech sounds, spectral coherence of the high-band alpha rhythms increased between left auditory and Wernicke's areas with respect to sham DL, whereas it decreased between left and right auditory areas. The increase of functional coupling within the left hemisphere would underlie the processing of the syllable presented to the right ear, which arrives to the left auditory cortex without the interference of the other syllable presented to the left ear. Conversely, the decrease of inter-hemispherical coupling of the high-band alpha might be due to the fact that the two auditory cortices do not receive the same information from the ears during DL. These results suggest that functional coupling of alpha rhythms can constitute a neural substrate for the lateralization of auditory stimuli during DL.     

Evidence for a neurophysiologic auditory deficit in children with benign epilepsy with centro-temporal spikes

Summary. Benign focal epilepsy in childhood with centro-temporal spikes (BECTS) is one of the most common forms of epilepsy. Recent studies have questioned the benign nature of BECTS, as they have revealed neuropsychological deficits in many domains including language. The aim of this study was to investigate whether the epileptic discharges during the night have long-term effects on auditory processing, as reflected on electrophysiological measures, during the day, which could underline the language deficits. In order to address these questions we recorded base line electroencephalograms (EEG), sleep EEG and auditory event related potentials in 12 children with BECTS and in age- and gender-matched controls. In the children with BECTS, 5 had unilateral and 3 had bilateral spikes. In the 5 patients with unilateral spikes present during sleep, an asymmetry of the auditory event related component (P85-120) was observed contralateral to the side of epileptiform activity compared to the normal symmetrical vertex distribution that was noted in all controls and in 3 the children with bilateral spikes. In all patients the peak to peak amplitude of this event related potential component was statistically greater compared to the controls. Analysis of subtraction waveforms (deviant – standard) revealed no evidence of a mismatch negativity component in any of the children with BECTS. We propose that the abnormality of P85-120 and the absence of mismatch negativity during wake recordings in this group may arise in response to the long-term effects of spikes occurring during sleep, resulting in disruption of the evolution and maintenance of echoic memory traces. These results may indicate that patients with BECTS have abnormal processing of auditory information at a sensory level ipsilateral to the hemisphere evoking spikes during sleep.     

Hemispheric lateralization of microstructural white matter abnormalities in children with active benign childhood epilepsy with centrotemporal spikes (BECTS): A preliminary DTI study

PurposeThe deficit of white matter is reported to be involved during the disease progression in patients with benign childhood epilepsy with centrotemporal spikes (BECTS). The aim of this study is to investigate patterns of white matter damage in children with BECTS with left- or right-hemispheric focus by using diffusion tensor imaging (DTI), and its relationship with the cofactors such duration, seizure frequency and handedness.MethodsDiffusion tensor imaging (DTI) was performed in twenty-eight children with BECTS and eighteen healthy controls. The data were analyzed using both tract-based spatial statistics (TBSS) and region of interest (ROI) analyses. Correlations were investigated between the fractional anisotropy (FA) values of the identified altered regions and clinical features such as age, age of onset and seizure frequency.ResultsThe TBSS analysis revealed that white matter impairment in children with rolandic spikes on the ipsilateral hemisphere was much wider. The FA value was significantly lower in the body of the corpus callosum and forceps minor in BECTS patients with spikes on the ipsilateral hemisphere. The seizure frequency correlated positively with the FA values of body of corpus callosum (CC), bilateral cingulate gyrus and left uncinate fasciculi (UA).ConclusionThe impaired WM integrity in patients with BECTS was greater in patients with spikes on the dominant hemisphere, possibly due to the greater vulnerability of the left hemisphere and excitotoxic effects of seizures.     

Idiopathic rolandic epilepsy with "interictal" facial myoclonia and oromotor deficit: a longitudinal EEG and PET study.

PURPOSE: The prognosis of benign epilepsy with centrotemporal spikes (BECTS) is always favorable as far as the epilepsy is concerned. However, some data suggest that affected children may be at risk for minor cognitive impairment. We report here the longitudinal study of a young girl demonstrating that BECTS also may be associated with severe motor disturbances. METHODS: BECTS (rare left oromotor seizures, right rolandic spike-waves activated during sleep) started at the age of 3 years 6 months in a girl with normal initial psychomotor development. Her clinical, neuropsychological, and EEG status was assessed every 3-6 months. Regional cerebral glucose metabolism was measured by using the [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) method. RESULTS: Between the age of 5 and 6 years, the girl had (a) increased seizure frequency; (b) brief perioral and palpebral myoclonic jerks, concomitant with the spike component of interictal spike-waves, and (c) persistent but fluctuating oromotor deficits (drooling, dysarthria, dysphagia). The EEG showed a marked increase in abundance and amplitude of wake and sleep interictal abnormalities, which became bilateral. Awake FDG-PET revealed a bilateral increase of glucose metabolism in opercular regions. A complete and definitive EEG and clinical remission occurred at age 5 years 11 months and has persisted since (present age, 7 years 9 months). CONCLUSIONS: This case confirms that during BECTS, epileptiform dysfunctions within rolandic areas may induce "interictal" positive or negative oromotor symptoms, independent of classic seizures.     

Speech lateralization and attention/executive functions in a Finnish family with specific language impairment (SLI)

Hemisphere lateralization for speech perception was investigated in a Finnish family with specific language impairment. We used dichotic presentations of consonant-vowel (CV) syllables, consisting of the six stop-consonants paired with the vowel /a/, under three different attentional instructions. The dichotic listening technique means that two different speech stimuli are presented simultaneously, one in each ear. Left hemisphere dominance for speech perception is assessed from a preference for the right ear stimulus. Response accuracy was compared in five members, over three generations, of a family with SLI with 5 healthy control subjects. The dichotic listening task was performed under three different instructions, to attend only to the right ear stimulus, to attend only to the left ear stimulus, or with no instruction about attention. The subjects indicated orally which of the six CV-syllables they heard on each trial. There were 36 dichotic presentations of the CV-syllables for each instruction. The CV-syllables were played from a CD with digitized stimuli. The results showed no difference between the groups during the no instruction condition, indicating normal speech lateralization in the SLI group. However, the SLI group was deficient in modifying the ear advantage through focused attention to the left ear, thus indicating an attentional/executive deficit in addition to a deficit in left hemisphere lateralization. It is concluded that individuals with specific language impairment may have a cognitive deficit related to attention in addition to a language processing deficit related to left hemisphere function.     

Laterality and deep brain stimulation of the subthalamic nucleus: applying a dichotic listening task to patients treated for Parkinson’s disease

Ear advantage during a dichotic listening task tends to mirror speech lateralization. Previous studies in stroke patients have shown that lesions in the dominant hemisphere often seem to produce changes in ear advantage. In this study six Parkinson’s disease (PD) patients treated for motor symptoms with deep brain stimulation (DBS) of the left subthalamic nucleus (STN) were tested preoperatively and at approximately 6 and 18 months postoperatively with a dichotic listening task. Results show a significant decline of the right ear advantage over time. In three of the patients a right ear advantage preoperativley changed to a left ear advantage 18 months postoperatively. This suggests the possibility that additional longitudinal studies of this phenomenon could serve as a model for understanding changes in indirect measures of speech lateralization in stroke patients.     

Lateralized interictal epileptiform discharges during rapid eye movement sleep correlate with epileptogenic hemisphere in children with intractable epilepsy secondary to tuberous sclerosis complex

Purpose: We assessed lateralization of interictal epileptiform discharges (IEDs) in children with intractable epilepsy secondary to tuberous sclerosis complexes (TSCs) during rapid eye movement sleep (R), compared with non–rapid eye movement sleep (NR) and wakefulness (W), to determine epileptogenicity of R‐IEDs. Methods: We retrospectively studied 23 children with TSC, who underwent prolonged scalp video–electroencephalography (EEG) and magnetic resonance imaging (MRI). We determined the lateralization of ictal EEG, clinical semiology, and the largest tuber on MRI. We analyzed a minimum of 100 IEDs during R, NR, and W to classify right/left/generalized spikes to compare the lateralization with ictal EEG, clinical semiology, and MRI. Key Findings: R‐IEDs were lateralized in 22 patients (96%), W‐IEDs in 19 (83%), and NR‐IEDs in 16 (70%). Ictal EEGs were lateralized in 15 patients (65%) and clinical semiology in 5 (22%). Ictal EEG lateralization was concordant to R‐IEDs in 14 patients (93%), W‐IEDs in 11 (73%), and NR‐IEDs in 10 (67%). The lateralization of clinical semiology was concordant with R‐IEDs in 4 (80%), W‐IEDs in 3 (60%), and NR‐IEDs in 2 (40%). MRI lateralization of the largest tuber was concordant with R‐IEDs in 16 (70%), W‐IEDs in 12 (52%), and NR‐IEDs in 11 (48%). Thirteen patients (57%) underwent resective surgery, the hemisphere of which was concordant with R‐IEDs in 13 (100%), W‐IEDs in 8 (62%), and NR‐IEDs in 8 (62%). Nine (69%) of them achieved good seizure control after surgery. Significance: R provoked the most lateralized IEDs compared to NR and W in children with TSC. Lateralization of R‐IEDs corresponded with the hemisphere of ictal EEG and largest tuber, and can be used to identify surgical candidacy in TSC children with intractable epilepsy.     

Dichotic listening in 126 left-handed children: ear advantages, familial sinistrality and sex differences

In the present study we report data on dichotic listening (DL) performance in 126 left-handed children. Four specific questions were addressed: (1) What is the percentage of left-handers in a large sample of children in Sweden? (2) What is the distribution of children showing a right ear (REA), left ear (LEA), and no ear (NEA) advantage in DL? (3) What is the relationship between ear advantage and familial sinistrality in children? (4) Are there sex differences among left-handed children, and if so, are these differences also reflected in DL performance? The results showed that the left-handers constituted 8.1% of the total sample of the screened subjects. The DL results showed 65.0% REA, 25.4% LEA, and 9.6% NEA. Of the subjects, 45.2% had left-handed relatives. Overall, there were more boys than girls in the sample (65.1% vs 34.9%). It is concluded that the present data match the sodium-Amytal data on left-handed adults with about 2/3 of a left-handed population with left hemisphere language dominance.